Gene expression-based prediction of myeloma cell sensitivity to histone deacetylase inhibitors.

BACKGROUND: Multiple myeloma (MM) is still a fatal plasma cell cancer. Novel compounds are currently clinically tested as a single agent in relapsing patients, but in best cases with partial response of a fraction of patients, emphasising the need to design tools predicting drug efficacy. Histone deacetylase inhibitors (HDACi) are anticancer agents targeting epigenetic regulation of gene expression and are in clinical development in MM. METHODS: To create a score predicting HDACi efficacy, five MM cell lines were treated with trichostatin A (TSA) and gene expression profiles were determined. RESULTS: The expression of 95 genes was found to be upregulated by TSA, using paired supervised analysis with Significance Analysis of Microarrays software. Thirty-seven of these 95 genes had prognostic value for overall survival in a cohort of 206 newly diagnosed MM patients and their prognostic information was summed up in a histone acetylation score (HA Score); patients with the highest HA Score had the shorter overall survival. It is worth noting that MM cell lines or patients' primary MM cells with a high HA Score had a significant higher sensitivity to TSA, valproic acid, panobinostat or vorinostat. CONCLUSION: In conclusion, the HA Score allows identification of MM patients with poor survival, who could benefit from HDACi treatment.

Changes in mastication after an immediate loading implantation with complete fixed rehabilitation.

OBJECTIVE: This study aimed to measure modifications of mastication after immediate loading full-arch prosthesis (ILFAP) rehabilitation. MATERIALS AND METHOD: Fourteen patients were observed before and 6 months after ILFAP rehabilitation when masticating two natural, standardized foods (peanut and carrot) and three model foods with increasing hardness. The granulometry of the expectorated boluses from carrot and peanuts was characterized by median particle size (D50), determined at the natural point of swallowing. Chewing time (CT), number of chewing cycles (CC), and chewing frequency (CF) were video recorded. A self-assessment questionnaire for oral health-related quality of life [Geriatric Oral Health Assessment Index (GOHAI)] was also used. RESULTS: After ILFAP rehabilitation, the mean D50 values for carrot and peanuts were smaller [Repeated Model Procedures (RMP), F = 41, p < 0.001]. Mean CT and CC values recorded with the three model foods decreased, while CF increased regardless of the model food hardness (RMP, F = 14, F = 10, and F = 11, respectively, p < 0.001). The GOHAI score increased from 43 ± 9 to 56 ± 3 (t test, p < 0.001). CONCLUSION: ILFAP rehabilitation improves the ability to reduce the bolus particle size and the ability to discriminate between different food hardnesses in the 6 months post-surgery period. CLINICAL RELEVANCE: This study encourages the clinical development of immediate loading implantation with a fixed full-arch prosthesis protocol.

Survival Rate of CAD-CAM Endocrowns Performed by Undergraduate Students.

OBJECTIVES: This study aimed to evaluate the success of computer-aided design-computer-aided manufacturing (CAD-CAM) endocrown restorations of endodontically treated teeth (ETT) performed by supervised undergraduate students. The study also intended to identify possible factors that may lead to failures. METHODS AND MATERIALS: This observational open cohort study was based on clinical data from endocrown restorations performed by residents and undergraduate students in their 4th, 5th, and 6th year from July 2011 to May 2018. The presence of a tooth with an endocrown on the arch was the main criteria used to calculate the survival rate of restored teeth. The quality of the remaining endocrowns was evaluated referring to the FDI criteria. The cases of failure were categorized into either favorable or unfavorable. RESULTS: A total of 343 ETT were restored with endocrowns in 315 patients. Among them, 199 patients encompassing 225 endocrowns were followed during a 56 ± 26 month period. The survival rate of restored teeth was found to be 81.8%, the estimated Kaplan-Meier survival rate being 71.8% at 9 years. Among the 41 failed cases, 32 were favorable (debonding and/or ceramic fractures) and 9 were unfavorable. CONCLUSION: Endocrown restorations of posterior ETT using CAD-CAM technologies could be carried out by undergraduates with a low risk of failure. Teacher supervision could be reinforced, covering all steps of each endocrown procedure in order to avoid failures due to insufficient thickness or loss of retention.

Impact of morbid obesity on chewing ability.

BACKGROUND: This study compared the chewing parameters in a group of obese adult patients scheduled for gastric bypass surgery with those of a control group. METHODS: Chewing parameters were measured in two groups of subjects, one of 44 obese patients scheduled for gastric bypass surgery (body mass index [BMI] = 49.1 +/- 7.2) and the other of 30 non-obese control subjects (BMI = 20.9 +/- 2.1). In both groups, the subjects' dental status was characterized by the number of functional dental units. Kinematic parameters, namely chewing time (CT), number of chewing cycles (CC), and chewing frequency (CF), were video recorded during the mastication of five natural standardized foods (banana, apple, sweet jelly, peanut, and carrot). The particle size distribution of the expectorated bolus from carrot and peanuts was characterized by the 50th percentile (D (50)). Analysis was carried out to detect any effect of the fixed factors "dental status," "type of food," and "subject group" on the variations of the dependent factors CT, CC, CF, and D (50). RESULTS: In obese subjects, CT, CC, and D (50) were variables depending on both dental status and food. For fully dentate subjects, the group of patients with obesity showed higher values for CT and CC and lower values for D (50) for both carrot and peanuts than the control group. CONCLUSION: The chewing parameters were affected in fully dentate patients with morbid obesity compared with controls, emphasizing the need for a systematic evaluation of both dental status and chewing ability in patients scheduled for bariatric surgery.

Masticatory dysfunction in persons with Down's syndrome. Part 1: aetiology and incidence.

The functional and anatomical characteristics of Down's syndrome have direct repercussions on oral health. Orofacial dysfunction is on account of poor neuromotor control, muscle weakness, dental anomalies, dysmorphology and intercurrent illness. In particular, feeding and swallowing are impaired. The aim of this first article was to summarize the orofacial difficulties encountered by persons with Down's syndrome at all stages of life and to explain their aetiology. Indicators are proposed for the identification of masticatory problems within this population and reduced masticatory efficiency is discussed in relation to repercussions on oral and general health and on the social integration of persons with Down's syndrome. A second article will describe techniques for preventing, treating and compensating for masticatory dysfunction in this population.

Masticatory dysfunction in persons with Down's syndrome. Part 2: management.

The functional and anatomical characteristics of Down's syndrome have direct repercussions on oral health; orofacial dysfunction results and feeding and swallowing are impaired. These problems have been described in an earlier article. Different techniques are proposed for the prevention of the development of orofacial dysfunction in Down's syndrome. In particular, early myofunctional therapy coupled with appliance wear has been shown to be successful over the long term when multidisciplinary management is possible. Functional or conventional orthodontic treatment may be successful for older children when performed concurrently with the use of appropriate behaviour management techniques. More recently, techniques for the compensation of masticatory dysfunction in adults have been proposed, although further research is necessary to confirm their efficacy. The aim of this second article was to review techniques for the prevention, treatment and compensation of orofacial dysfunction in persons with Down's syndrome from birth to adulthood.

[Obesity and oral health: risk factors of obese patients in dental practice]. / Obésité et santé bucco-dentaire: spécificités du patient obèse au cabinet dentaire.

For 20 years, on a worldwide scale, the prevalence of obesity has always progressed as well in child as in adult. Obesity is frequently associated with other pathologies: cardiovascular, oncologic, systemic (diabetes) or oral. In this situation, the follow-up of obesity and its co morbidity needs a multidisciplinary approach. Obesity and oral health pathologies have risk factors in common, particularly dietary one. Indeed, it is established that food affects oral health. In the same way, an unbalanced diet raises the risk of overweight or obesity. Thereby, owing to these inter relations, the World Health Organization advocates to insert oral health in the Program for Global Health. First, this study presents the factors of risks that obesity and oral health diseases have in common. After, the risks and the specificity of the care of obese patients are outlined. Consecutively, a program of prevention and education of oral health is proposed.

Mastication of model products in complete denture wearers.

OBJECTIVE: The aim of this study was to define the characteristics of muscular activity in complete denture wearers and in dentate subjects during mastication of model foods differing in hardness but similar in terms of rheologically properties. MATERIAL AND METHODS: The foodstuffs used in this study were laboratory-developed gumdrops demonstrating viscoelastic properties. The test foods cover a range of four hardness levels. The group of complete denture wearers included 15 subjects, while the control group included 9 subjects with normal dentition. Electromyograph (EMG) recordings were taken from the masseter and temporal muscles during mastication of the test foods. The results were evaluated by one-way and two-way ANOVA followed by means comparisons using a Student-Newman-Keuls post hoc test (alpha=0.05). RESULTS: Preparing the same food bolus for swallowing required a greater number of masticatory cycles and a longer duration of mastication for complete denture wearers than for dentate subjects. In addition, complete denture wearers failed to increase EMG activity per cycle in response to hardness of the food. CONCLUSION: Denture wearers experienced difficulties during mastication, as indicated by a decreased masticatory rate and the observed failure to increase EMG activity per cycle in response to increased food hardness. The increases in number of cycle and masticatory duration appear to be a response to this impaired masticatory function.

Localisation of a reporter transcript by the c-myc 3'-UTR is linked to translation.

The 3'-untranslated region of c-myc mRNA contains a perinuclear localisation signal which is sufficient to target beta-globin coding sequences. The link between perinuclear mRNA localisation and translation has been investigated using cells transfected with chimeric gene constructs in which globin reporter sequences were linked to the c-myc 3'-untranslated region and the iron-responsive element from ferritin mRNA. Iron supplementation of the medium promoted translation of the chimeric mRNA as assessed by its presence in polysomes; in situ hybridisation showed that the mRNA was localised around the nucleus. Treatment with the iron chelator desferrioxamine for 16 h prevented both translation and mRNA localisation. In controls where the expressed mRNA lacked the iron-responsive element desferrioxamine had no effect upon localisation. In contrast, arrest of on-going global translation by puromycin treatment had no effect on mRNA localisation. The data suggest that if initiation of translation of a mRNA containing the c-myc localisation signal is prevented in some way then localisation does not occur, whereas once the mRNA has been localised further translation is not required to maintain mRNA localisation.

Stabilization of mandibular complete dentures by four mini implants: Impact on masticatory function.

OBJECTIVES: The frequent instability of mandibular removable complete dentures causes an alteration of mastication. An innovative therapeutic strategy involves placing four symphyseal mini implants. This study aimed at assessing the development of masticatory parameters and the impact on quality of life in subjects that underwent this procedure. METHODS: Eleven edentulous subjects (mean age 72±11 years) with unstable mandibular complete dentures were followed-up before (T0) and two - three months after (T1) mini implant setting. Physiological parameters (number of cycles, duration of sequence and frequency of mastication) during the mastication of food models and the bolus median particle size (d50) of carrot were evaluated at each time. Quality of life was assessed at T0 and T1 using the Global Oral Health Assessment Index (GOHAI). Parametric tests were used to test relationships between mastication, quality of life variations and mini implant setting, and to compare each parameter mean value at times T0 and T1. RESULTS: More subjects were able to chew carrot after setting the mini implants (8 subjects compared to 4 at T0). This improvement was accompanied by changes in kinematic parameters when chewing carrots, soft and hard model food, and by an improvement of their quality of life. However, the particle size values observed in the bolus remained higher than for normal dentate subjects (9.2±2.8mm). CONCLUSIONS: These results indicated that the placement of mini implants as retentive elements for mandibular full dentures had a positive impact on patients' masticatory function and quality of life. CLINICAL SIGNIFICANCE: The placement of mini implants has a positive impact on the masticatory function and oral health quality of life. The results suggest that this alternative procedure can be used as a treatment option for patients unable to receive conventional implants.

c-fos mRNA instability determinants present within both the coding and the 3' non coding region link the degradation of this mRNA to its translation.

The instability of oncogenic mRNA such as c-fos mRNA is controlled in cis by sequences present in both the coding and the 3' untranslated regions (3'UTR). The latter contains AU-rich elements (ARE) which, depending on the cellular context, mediate either their rapid degradation or inhibit their translation. These observations, along with the known increase of the life spans of many unstable mRNA promoted by inhibitors of protein synthesis, raise the possibility that both processes are linked. To investigate further the putative involvement of translation in both coding region and ARE-mediated rapid decay of c-fos mRNA, we designed an expression vector based on the use of the ferritin mRNA iron regulatory element (IRE). The latter structure links translation to intracellular iron concentration when inserted at the proper location within the 5'UTR. Rapid degradation of a beta-globin/c-fos 3'UTR construct was prevented by Desferrioxamine, an iron chelator, and facilitated by ferric ammonium citrate or hemin, while stability of other mRNAs not containing the IRE or the ARE were unchanged. The same conclusion was reached when the stability of a c-fos mRNA devoid of ARE was assessed in function of iron availability.

Clinical evaluation of mastication: validation of video versus electromyography.

BACKGROUNDS AND AIMS: The ability to evaluate masticatory function in people with neurological disabilities is important as this function is often compromised in these groups. However, current standard techniques are often impossible in such groups due to cognitive difficulties. This study is a validation of several variables read from standardised video recordings of mastication as indicators of masticatory function. METHODS: Fifteen healthy, fully dentate male subjects were recorded using EMG and by video simultaneously. An evaluation was undertaken of the video parameters (i) to compare their validity against the electromyographic parameters, (ii) to test intra-rater and inter-rater reliability and (iii) to test the ability to discriminate between four model foods differing in hardness. RESULTS: Masticatory time and the number of masticatory cycles counted on video were found to be valid and reliable indicators. In addition, the number of active chewing cycles performed with an open mouth and identification of the chewing side, were found to have reasonable validity and reliability. The former may allow discrimination between food types. CONCLUSION: As an alternative to the complex evaluation of masticatory function, observation of certain parameters from video recording could be an alternative for use in uncooperative patients.

[Removable prosthesis: masticatory efficiency]. / Prothese adjointe: efficacite masticatoire.

The late consultation in odontology often leads to tooth extraction. This negligence, in a long term, will cause complete toothlessness. This state of invalidity will be compensated by prosthesis. The removable prosthesis is often indicated because of the cost price. It is the result of a successful therapeutics, only if it fits aesthetically and functionally, within a chewing efficiency. In a first part, we will define masticatory efficiency, as different from masticatory capacity and capability. Then, in a second part, through some experimentation, we will show how fundamental research can guide the practitioner in his prosthetics choices and assessments.

Efficient transduction of healthy and malignant plasma cells by lentiviral vectors pseudotyped with measles virus glycoproteins.

A lot of genes deregulated in malignant plasma cells (PCs) involved in multiple myeloma have been reported these last years. The expression of some of these genes is associated with poor survival. A critical step is to elucidate the biological mechanisms triggered by these gene products. Such studies are hampered by the difficulty to obtain malignant PCs and to genetically modify them. Usual lentiviral vectors (LVs) pseudotyped with vesicular stomatitis virus envelope glycoprotein poorly transduced healthy and malignant PCs. Here, we report that LVs pseudotyped with the hemagglutinin and fusion glycoproteins from the measles Edmonston strain (H/F-LVs) can efficiently and stably transduce healthy and primary malignant PCs, without modifying their main phenotypic characteristics. Both LV pseudotypes efficiently transduced human myeloma cell lines. Importantly, both healthy and malignant PCs expressed CD46 and SLAMF1/CD150 membrane proteins, which are critical receptors for binding and productive genetic modification by H/F-LVs. The ability to efficiently introduce and express a given gene into PCs opens the possibility to study in detail PC biology.

The masticatory normative indicator.

There is no established quantitative, objective method to differentiate individuals with good masticatory function from those lacking this attribute. The aim of this study was to specify a normal range of median particle size values for masticated raw carrots collected just before being swallowed. The masticatory normative indicator (MNI) value thus obtained was based on seven studies carried out by different investigators using different methods for measuring particle size in carrot boluses. A simple mathematical transformation of variables and the choice of an interval of +/-1.96 times the standard deviation gave 4.0 mm as the upper limit of normal median particle size for carrots in a population of young persons with good oral health. This value identifies boluses that may be considered as resulting from impaired mastication, as illustrated in healthy individuals with experimentally hampered mastication, denture wearers, and individuals presenting with obesity or Down syndrome.

Validation of video versus electromyography for chewing evaluation of the elderly wearing a complete denture.

Chewing efficiency may affect nutritional status in the elderly. Many elderly patients are complete denture wearers, and often present cognitive problems. Those two factors make evaluation of mastication difficult with experimental methods. Analysis of video recording may be a simple way to routinely assess chewing parameters. This study aimed at validating several parameters of video evaluation versus electromyography (EMG), which is considered the 'gold standard'. The design was a prospective randomized study, carried out at the Faculty of Dentistry, University of Auvergne, Clermont-Ferrand, France. Twelve complete denture wearers chewed four model foods differing in hardness. Sessions were videotaped and EMG recordings were registered. Mastication time, number of masticatory cycles and cleaning time were recorded simultaneously by video and EMG. Two investigators independently analyzed the videos twice, in random order. Evaluation of criterion validity: a positive video/EMG correlation was found for the parameters 'chewing time' (0.89, Pearson) and 'number of masticatory cycles' (0.94, Spearman), whereas no statistical difference was found between these two EMG and video variables (t-test). Inter and intra-rater reliability gave a positive intraclass coefficient (ICC) for duration of mastication (0.86-0.98), number of masticatory cycles (0.90-0.97) and cleaning time (0.90-0.98). Discriminatory ability was studied using anova (P = 0.01): variation was significant in masticatory duration (F = 10), number of masticatory cycles (F = 10) and cleaning time (F = 4). Video may be a useful assessment tool in prosthetic rehabilitation and can be applied to help choose the type of food (solid, semi-liquid or liquid) to administer to dependent persons, particularly those suffering from dementia.

Impact of new prostheses on the oral health related quality of life of edentulous patients.

OBJECTIVE: A study was conducted to evaluate the impact of the placement of complete dentures by using the Global Oral Health Assessment Index (GOHAI). BACKGROUND: Oral health quality of life indicators can be used to evaluate the effects of dental treatments. MATERIAL AND METHODS: The 26 participants were treated in a French University Clinic during 2002. They were randomly divided into two groups. Each group received new prostheses, but evaluation of the quality of life was made at different periods [baseline, denture placement (group 1), 6 and 12 weeks (group 2) after placement]. A questionnaire was used to collect information on patient's satisfaction with the previous and new prostheses. Nonparametric tests were used to test the relationships between patients' satisfaction or baseline data and GOHAI variations with time as well as to compare mean values of GOHAI within each group. RESULTS: At baseline, the impact of oral health problems was apparent; the mean GOHAI-Add score was 45.8 (10.2). Six weeks after placement of the new denture, there was no difference in GOHAI scores compared with the initial assessment. An improvement in GOHAI score was observed 12 weeks after the participants received their new dentures (p < 0.05). Change in GOHAI-Add scores was negatively correlated with the initial GOHAI-Add score. Patients who preferred the new prosthesis enjoyed a positive change in GOHAI scores (p < 0.001). There was a relationship between participants' satisfaction with the new dentures and change in GOHAI scores (p < 0.05). CONCLUSION: The GOHAI can be used to evaluate needs for and effect of the making of new complete dentures.

Complete denture wearers: electromyography of mastication and texture perception whilst eating meat.

This study was undertaken to evaluate the sensitivity of denture wearers to different food textures and to follow masticatory pattern adaptation with variation in texture using electromyography (EMG) recordings. Nine patients with complete dentures and 9 dentate control patients without any oro-dental pathology were studied. Six different samples of beef were obtained from the same muscle by altering the state of the muscle fibres and by variation of the cooking temperature. The variations in texture were mechanically controlled. Electromyographic activity was recorded during chewing. The patients' subjective appreciation of texture was reported using a 10-cm non-structured analogue scale. The following parameters were analysed: muscle work, number of masticatory cycles, number of rejected samples, initial tenderness, overall tenderness, juiciness, and duration of chewing for each sample in the mouth. Muscle activity was less for the edentulous group, particularly that of the masseter muscles. The masticatory pattern of complete denture wearers was less adapted to each sample texture than was that of the control group. Both groups perceived differences in texture of the samples. It was concluded that although texture perception is little altered, muscular adaptation to the bolus is reduced in patients with complete dentures.

Development of a synthetic bolus using silicone elastomer for the study of masticatory efficiency.

STATEMENT OF PROBLEM: Masticatory efficiency has been proposed as an outcome measure for prosthetic rehabilitation. However, no standardized method is available for this type of assessment. PURPOSE: This study developed a normalized synthetic test food with reproducible physical and rheologic properties. MATERIAL AND METHODS: Two silicone putties of different hardness were studied. The texture of each putty varied by the addition of silicone oil. Rheologic characteristics of 7 samples were compared with the same properties of 5 natural food substances. RESULTS: Seven varieties of synthetic bolus were produced, each of which were of a different hardness, modulus of elasticity, and tensile strength. The natural food substances demonstrated great rheologic variability. The synthetic bolus samples exhibited a texture profile approaching that of natural foods. The principal difference between the 2 groups tested was that of the homogeneity of the silicone samples. CONCLUSION: None of the samples reproduced all the rheologic properties of the natural food substances; however, the results showed that their characteristics were sufficiently similar for the silicone samples to be suggested as a reproducible alternative for the testing of masticatory efficiency.