Quality of life, chronic pain, insomnia, and jaw malfunction in patients after alloplastic temporomandibular joint replacement: a questionnaire-based pilot study.

Studies of patients undergoing alloplastic total temporomandibular joint replacement seldom report on quality of life (QoL) and sleep. The aim of this pilot study was to assess these factors in such a patient cohort using validated psychometric questionnaires. Data were collected via online surveys comprising the following six questionnaires: Short Form-12 Health Survey (SF-12), Patient Health Questionnaire-15, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, Insomnia Severity Index, Graded Chronic Pain Scale, and Jaw Disability List. Pain intensity, limitation in nutrition, and treatment satisfaction were assessed using numerical rating scales. Mouth opening was measured at follow-up. The SF-12 Physical Composite Score was markedly lower than that of the age-matched general population, whereas the Mental Composite Score did not differ significantly. Participants indicated a low somatization level and low level of disability due to pain, but reduced QoL. Clinically relevant insomnia was reported by 36% of participants. In conclusion, the results of this pilot study indicate that QoL and sleep in patients with a total temporomandibular joint replacement differ from those in the general population, indicating the need for a comprehensive outcome assessment utilizing validated psychometric tools in accordance with the current biopsychosocial model of chronic disorders.

Effect of Sustained Joint Loading on TMJ Disc Nutrient Environment.

The temporomandibular joint (TMJ) disc nutrient environment profoundly affects cell energy metabolism, proliferation, and biosynthesis. Due to technical challenges of in vivo measurements, the human TMJ disc extracellular nutrient environment under load, which depends on metabolic rates, solute diffusion, and disc morphometry, remains unknown. Therefore, the study objective was to predict the TMJ disc nutrient environment under loading conditions using combined experimental and computational modeling approaches. Specifically, glucose consumption and lactate production rates of porcine TMJ discs were measured under varying tissue culture conditions (n = 40 discs), and mechanical strain-dependent glucose and lactate diffusivities were measured using a custom diffusion chamber (n = 6 discs). TMJ anatomy and loading area were obtained from magnetic resonance imaging of healthy human volunteers (n = 11, male, 30 ± 9 y). Using experimentally determined nutrient metabolic rates, solute diffusivities, TMJ anatomy, and loading areas, subject-specific finite element (FE) models were developed to predict the 3-dimensional nutrient profiles in unloaded and loaded TMJ discs (unloaded, 0% strain, 20% strain). From the FE models, glucose, lactate, and oxygen concentration ranges for unloaded healthy human TMJ discs were 0.6 to 4.0 mM, 0.9 to 5.0 mM, and 0% to 6%, respectively, with steep gradients in the anterior and posterior bands. Sustained mechanical loading significantly reduced nutrient levels (P < 0.001), with a critical zone in which cells may die representing approximately 13.5% of the total disc volume. In conclusion, this study experimentally determined TMJ disc metabolic rates, solute diffusivities, and disc morphometry, and through subject-specific FE modeling, revealed critical interactions between mechanical loading and nutrient supply and metabolism for the in vivo human TMJ disc. The results suggest that TMJ disc homeostasis may be vulnerable to pathological loading (e.g., clenching, bruxism), which impedes nutrient supply. Given difficulties associated with direct in vivo measurements, this study provides a new approach to systematically investigate homeostatic and degenerative mechanisms associated with the TMJ disc.

Alterations of mandibular movement patterns after total joint replacement: a case series of long-term outcomes in patients with total alloplastic temporomandibular joint reconstructions.

According to recognized guidelines, a total alloplastic replacement may be indicated to resolve temporomandibular pain and functional limitations in cases where conservative and less aggressive surgical management strategies have failed. It is broadly believed that, as a result of the surgical procedure, the function of the lateral pterygoid muscle is lost and so are the laterotrusive and protrusive jaw movements. Furthermore, the joint prosthesis design may not be conducive to lateral and protrusive movements. Using a dynamic stereometry technique, it was possible to perform a quantitative analysis of kinematics in TJR patients. The cases of four patients who showed preserved lateral and/or protrusive motion are presented here. During mouth opening, prosthetic condyle translation ranged from 3.18mm to 10.09mm and it was also possible to observe this clinically. It has been suggested that changes in prosthesis design may have improved postoperative jaw kinematics. Considering the large diversity in treatment outcomes, it is recommended that the individual prognosis should always be discussed with the patient prior to surgery.

Mechanobehavior and Ontogenesis of the Temporomandibular Joint.

Craniofacial secondary cartilages of the mandibular condyle and temporomandibular joint (TMJ) eminence grow in response to the local mechanical environment. The intervening TMJ disc distributes normal loads over the cartilage surfaces and provides lubrication. A better understanding of the mechanical environment and its effects on growth, development, and degeneration of the TMJ may improve treatments aimed at modifying jaw growth and preventing or reversing degenerative joint disease (DJD). This review highlights data recorded in human subjects and from computer modeling that elucidate the role of mechanics in TMJ ontogeny. Presented data provide an approximation of the age-related changes in jaw-loading behaviors and TMJ contact mechanics. The cells of the mandibular condyle, eminence, and disc respond to the mechanical environment associated with behaviors and ultimately determine the TMJ components' mature morphologies and susceptibility to precocious development of DJD compared to postcranial joints. The TMJ disc may be especially prone to degenerative change due to its avascularity and steep oxygen and glucose gradients consequent to high cell density and rate of nutrient consumption, as well as low solute diffusivities. The combined effects of strain-related hypoxia and limited glucose concentrations dramatically affect synthesis of the extracellular matrix (ECM), which limit repair capabilities. Magnitude and frequency of jaw loading influence this localized in situ environment, including stem and fibrocartilage cell chemistry, as well as the rate of ECM mechanical fatigue. Key in vivo measurements to characterize the mechanical environment include the concentration of work input to articulating tissues, known as energy density, and the percentage of time that muscles are used to load the jaws out of a total recording time, known as duty factor. Combining these measurements into a mechanobehavioral score and linking these to results of computer models of strain-regulated biochemical events may elucidate the mechanisms responsible for growth, maintenance, and deterioration of TMJ tissues.

Jaw closing movement and sex differences in temporomandibular joint energy densities.

Energy densities (ED, mJ/mm3 ) quantify mechanical work imposed on articular cartilages during function. This cross-sectional study examined differences in temporomandibular joint (TMJ) ED during asymmetric versus symmetric jaw closing in healthy females versus males. ED component variables were tested for differences between and within sexes for two types of jaw closing. Seventeen female and 17 male subjects gave informed consent to participate. Diagnostic criteria for temporomandibular disorders and images (magnetic resonance (MR), computed tomography) were used to confirm healthy TMJ status. Numerical modelling predicted TMJ loads (Fnormal ) consequent to unilateral canine biting. Dynamic stereometry combined MR imaging and jaw-tracking data to measure ED component variables during 10 trials of each type of jaw closing in each subject's TMJs. These data were then used to calculate TMJ ED during jaw closing asymmetrically and symmetrically. Paired and Student's t tests assessed ED between jaw closing movements and sexes, respectively. Multivariate data analyses assessed ED component variable differences between jaw closing movements and sexes (α = 0.05). Contralateral TMJ ED were 3.6-fold and significantly larger (P < .0001) during asymmetric versus symmetric jaw closing, due to significantly larger (P ≤ .001) distances of TMJ stress-field translation in asymmetric versus symmetric movement. During asymmetric jaw closing, contralateral TMJ ED were twofold and significantly larger (P = .036) in females versus males, due to 1.5-fold and significantly smaller (P ≤ .010) TMJ disc cartilage volumes under stress fields in females versus males. These results suggest that in healthy individuals, asymmetric compared to symmetric jaw closure in females compared to males has higher TMJ mechanical fatigue liabilities.

Mechanobehavioral Scores in Women with and without TMJ Disc Displacement.

Cartilage fatigue may be a factor in the precocious development of degenerative changes in the temporomandibular joint (TMJ). This cross-sectional study estimated potential for cartilage fatigue via TMJ energy densities (ED) and jaw muscle duty factors (DF), which were combined to calculate mechanobehavioral scores (MBS) in women with (+) and without (-) bilateral TMJ disc displacement (DD). All subjects gave informed consent to participate and were examined using Diagnostic Criteria (DC) for Temporomandibular Disorders (TMD) and magnetic resonance (MR) and computed tomography (CT) images. Forty-seven subjects were categorized into +DD ( n = 29) and -DD ( n = 18) groups. Dynamic stereometry (MR images combined with jaw-tracking data) characterized individual-specific data of TMJ stress-field mechanics to determine ED (ED = W/ Q mJ/mm3, where W = work done, Q = volume of cartilage) during 10 symmetrical jaw-closing cycles with a 20-N mandibular right canine load. Subjects were trained to record masseter and temporalis electromyography over 3 days and 3 nights. Root mean square electromyography/bite-force calibrations determined subject-specific masseter and temporalis muscle activities per 20-N bite-force (T20 N, µV), which defined thresholds. Muscle DF (DF = % duration of muscle activity/total recording time) were determined for a range of thresholds, and MBS (ED2 × DF) were calculated. Intergroup differences in ED, DF, and MBS were assessed via analyses of variance with Bonferroni and Tukey honest significant difference post hoc tests. Average ED for contralateral TMJs was significantly larger ( P = 0.012) by 1.4-fold in +DD compared to -DD subjects. Average DF were significantly larger (all P < 0.01) for +DD compared to -DD subjects by 1.7-, 2.5-, and 1.9-fold for day, night, and overall, respectively. Daytime MBS were significantly larger (all P < 0.04) by up to 8.5-fold in +DD compared to -DD subjects. Significantly larger ED, DF, and MBS were shown in women with compared to women without bilateral TMJ DD.

TMJ energy densities in healthy men and women.

OBJECTIVE: Cartilage fatigue, due to mechanical work, may account for the early development of degenerative joint disease (DJD) in the temporomandibular joint (TMJ), and why women are three times more likely to be afflicted. This study tested for gender differences in mechanical energy densities in women and men with healthy TMJs. DESIGN: Eighteen women and eighteen men gave informed consent. Research diagnostic criteria including imaging were used to ensure that subjects' TMJs were normal, without disc displacement or signs of DJD. Numerical modeling determined TMJ loads (Fnormal). Jaw tracking and three-dimensional dynamic stereometry characterized individual-specific data of stress-field dynamic mechanics during 10 symmetrical jaw closing cycles. These data were used to estimate tractional forces (Ftraction). Energy densities were then calculated, where: Energy Density = W/Q (W = work done or mechanical energy input = Ftraction*distance of stress-field translation, Q = volume of cartilage). Two-way analysis of variance (ANOVA) and follow-up two-group comparisons tested mean energy densities for ipsilateral and contralateral TMJs in women vs men. RESULTS: Mean energy densities ± standard deviations in ipsilateral and contralateral TMJs in women were 9.0 ± 9.7 and 8.4 ± 5.5 mJ/mm3, respectively, and were significantly larger (P = 0.004 and 0.001, respectively) compared to ipsilateral and contralateral TMJs in men, which were 5.6 ± 4.2 and 6.3 ± 4.2 mJ/mm3, respectively. CONCLUSIONS: Energy densities were significantly larger in healthy TMJs of women than men. Larger TMJ energy densities during normal jaw functions could predispose earlier mechanical fatigue of the TMJ disc.

Alloplastic total temporomandibular joint replacements: do they perform like natural joints? Prospective cohort study with a historical control.

The aim of this study was to qualitatively and quantitatively describe the biomechanics of existing total alloplastic reconstructions of temporomandibular joints (TMJ). Fifteen patients with unilateral or bilateral TMJ total joint replacements and 15 healthy controls were evaluated via dynamic stereometry technology. This non-invasive method combines three-dimensional imaging of the subject's anatomy with jaw tracking. It provides an insight into the patient's jaw joint movements in real time and provides a quantitative evaluation. The patients were also evaluated clinically for jaw opening, protrusive and laterotrusive movements, pain, interference with eating, and satisfaction with the joint replacements. The qualitative assessment revealed that condyles of bilateral total joint replacements displayed similar basic motion patterns to those of unilateral prostheses. Quantitatively, mandibular movements of artificial joints during opening, protrusion, and laterotrusion were all significantly shorter than those of controls. A significantly restricted mandibular range of motion in replaced joints was also observed clinically. Fifty-three percent of patients suffered from chronic pain at rest and 67% reported reduced chewing function. Nonetheless, patients declared a high level of satisfaction with the replacement. This study shows that in order to gain a comprehensive understanding of complex therapeutic measures, a multidisciplinary approach is needed.

A pilot study of ambulatory masticatory muscle activities in temporomandibular joint disorders diagnostic groups.

OBJECTIVE: To determine differences in masticatory muscle usage between temporomandibular joint disorders diagnostic groups. SETTING AND SAMPLE POPULATION: Seventy-one informed and consented subjects (27 men; 44 women) participated at the University at Buffalo. MATERIAL AND METHODS: Research diagnostic criteria and imaging data were used to categorize subjects according to the presence/absence +/- of TMJ disc placement (DD) and chronic pain (P) (+DD+P, n=18; +DD-P, n=14; -DD-P, n=39). Electromyographic (EMG)/bite-force calibrations determined subject-specific masseter and temporalis muscle activities per 20 N bite-force (T20N , µV). Over 3 days and nights, subjects collected EMG recordings. Duty factors (DFs, % of recording time) were determined based on threshold intervals (5-9, 10-24, 25-49, 50-79, ≥80% T20N ). anova and Tukey-Kramer post hoc tests identified 1) diagnostic group differences in T20N and 2) the effects of diagnostic group, gender, time and interval on muscle DFs. RESULTS: Mean (±SE) temporalis T20N in +DD+P subjects was significantly higher (71.4±8.8 µV) than masseter T20N in these subjects (19.6±8.8 µV; p=0.001) and in -DD-P subjects (25.3±6.0 µV, p=0.0007). Masseter DFs at 5-9% T20N were significantly higher in +DD-P women (3.48%) than +DD-P men (0.85%) and women and men in both other diagnostic groups (all p<0.03), and in +DD+P women (2.00%) compared to -DD-P men (0.83%; p=0.029). Night-time DFs at 5-9% T20N in +DD-P women (1.97%) were significantly higher than in -DD-P men (0.47%) and women (0.24%; all p<0.01). CONCLUSIONS: Between-group differences were found in masticatory muscle activities in both laboratory and natural environmental settings.

Diagnostic group differences in temporomandibular joint energy densities.

OBJECTIVES: Cartilage fatigue, due to mechanical work, may account for precocious development of degenerative joint disease in the temporomandibular joint (TMJ). This study compared energy densities (mJ/mm³) in TMJs of three diagnostic groups. SETTING AND SAMPLE POPULATION: Sixty-eight subjects (44 women, 24 men) gave informed consent. Diagnostic criteria for temporomandibular disorders (DC/TMD) and imaging were used to group subjects according to presence of jaw muscle or joint pain (+P) and bilateral disk displacement (+DD). MATERIAL AND METHODS: Subjects (+P+DD, n=16; -P+DD, n=16; and -P-DD, n=36) provided cone-beam computed tomography and magnetic resonance images, and jaw-tracking data. Numerical modeling was used to determine TMJ loads (Fnormal). Dynamic stereometry was used to characterize individual-specific data of stress-field dynamics during 10 symmetrical jaw-closing cycles. These data were used to estimate tractional forces (Ftraction). Energy densities were then calculated as W/Q (W=work done or mechanical energy input=tractional force×distance of stress-field translation, Q=volume of cartilage). anova and Tukey-Kramer post hoc analyses tested for intergroup differences. RESULTS: Mean±standard error energy density for the +P+DD group was 12.7±1.5 mJ/mm³ and significantly greater (all adjusted p<0.04) when compared to -P+DD (7.4±1.4 mJ/mm³) and -P-DD (5.8±0.9 mJ/mm³) groups. Energy densities in -P+DD and -P-DD groups were not significantly different. CONCLUSION: Diagnostic group differences in energy densities suggest that mechanical work may be a unique mechanism, which contributes to cartilage fatigue in subjects with pain and disk displacement.

Neck and shoulder muscle activity of orthodontists in natural environments.

Work related musculoskeletal disorders (WMSDs) are common among dentists and possibly caused by prolonged static load. The aim of this study was to assess the contraction pattern of neck and shoulder muscles of orthodontists in natural environments. Electromyographic (EMG) activity of right sternocleidomastoid and trapezius muscles were recorded by means of portable recorders in eight orthodontists during working conditions, and both active and resting non-working conditions. Recordings were analysed in terms of contraction episode (CE) count, amplitude, and duration. The sternocleidomastoid and trapezius muscles contracted about 40-70times per hour in the natural environment. Their EMG activity pattern mainly consisted of short-lasting, low-amplitude CEs. The counts and amplitude of sternocleidomastoid CEs did not differ across vocational and non-vocational conditions. The number and amplitude of trapezius CEs were slightly but significantly higher during the vocational condition. There were highly significant (p<0.001) differences in duration of CEs across conditions, with two to threefold increase in the average duration of trapezius muscle contractions found in the vocational setting. During orthodontic work, operators commonly hold muscular contractions for significantly longer periods than are encountered in non-vocational settings. This behaviour may be associated causally with the increases seen in WMSDs through proposed pathophysiological mechanisms occurring at the motor unit level. Our findings may also be valid for other occupations characterised by seated static postures with precision hand and wrist movements.

Quantitative sensory testing of intraoral open wounds.

Wound healing is an important aspect of oral and maxillofacial surgery. Positive sensory signs (allodynia, hyperalgesia) and negative sensory signs (hypoesthesia, hypoalgesia) may be encountered. Quantitative sensory testing (QST) has moved from bench to bedside for the detection, therapy selection and monitoring the recovery of individuals with sensory disturbances. Tracking somatosensory changes during normal and abnormal wound healing has not previously been reported. This report presents data obtained by a novel, automated, non-contact psychophysical method for assessment of wound sensitivity after standardized oral mucosal biopsy. By directing graded air puffs towards palatal biopsy wounds, thresholds for sensory detection, pain detection and pain tolerance were repeatedly assessed across 19 days, demonstrating high reliability. Participants recorded daily spontaneous and chewing-evoked maximum pains. Pain detection and tolerance thresholds increased linearly across time. Comparison between air puff evoked pain detection threshold and chewing-evoked pain demonstrated a strong correlation. Thus, for the first time, this study tracked the time course of somatosensory sensitivity of wounds induced by oral biopsies. The psychophysical data on wound healing obtained by this automated, contact-free stimulation method can be utilized as a surrogate marker for clinical pain improvements and standardized assessment of intraoral pain sensitivity, for example in oral mucositis.

Novel approach to the study of jaw kinematics in an alloplastic TMJ reconstruction.

Total alloplastic temporomandibular joint (TMJ) reconstruction is a reliable treatment modality in patients with severely diseased TMJ with good clinical behaviour. TMJ mandibular function after alloplastic reconstruction has scarcely been analysed as a biomechanical parameter and investigation has generally been limited to interincisal measurements without deeper insight into joint kinematics. Dynamic stereometry to assess condylar movements relative to the fossa was performed at the 5 year follow-up of a patient who underwent condylar resection of the right TMJ followed by total alloplastic joint reconstruction to treat pigmented villonodular synovitis. The patient could achieve wide mouth opening, but overall mandibular kinematics showed a strong deviation towards the prosthetic side due to the lack of mandibular translation caused by the absence of the lateral pterygoid attachment. Possible overloading of the joint contralateral to the TMJ prosthesis might be prevented by optimizing replacement joint design.

Time-frequency analysis of chewing activity in the natural environment.

UNLABELLED: The aim of this observational study was to investigate the features of the chewing activity and the variability of the human chewing pace, as assessed in the natural environment. It was hypothesized that the chewing pace is relatively constant within individuals across different days but is variable across individuals. Electromyographic surface activity was recorded unilaterally from the masseter in 21 participants for 3 hours over 3 recording days, in the natural environment, by means of portable recorders. The time-frequency properties of chewing activity were assessed with a previously validated algorithm. Repeated-measurements ANOVA was used for statistical analysis. Chewing activity mainly occurred in the range of 0.94 Hz (5(th) percentile) and 2.17 Hz (95(th) percentile). Mean and median chewing frequencies were 1.57 Hz and 1.58 Hz, respectively (95% confidence intervals: 1.45-1.68 Hz). The mean duration of chewing episodes was 13.0 sec, the 5(th) and 95(th) percentiles being 2.7 sec and 34.9 sec, respectively. Variability of the mean chewing frequency between individuals was much greater than that within individuals (F = 29.8; p < 0.001). The individual chewing paces were stable across different days (intraclass correlation coefficient = 0.88; 95% confidence intervals = 0.79-0.94). Our findings provide evidence that each individual, in the natural environment, chews with a consistent pace across different days. ABBREVIATIONS: ANOVA, analysis of variance; CPG, central pattern generator; EMG, electromyography; ICC, Intra-class Correlation coefficient; SD, standard deviation.

Association of Toll-like receptor 10 and susceptibility to Crohn's disease independent of NOD2.

Impaired innate inflammatory response has a key role in the Crohn's disease (CD) pathogenesis. The aim of this study was to investigate the possible role of the TLR10-TLR1-TLR6 gene cluster in CD susceptibility. A total of 508 CD patients (284, cohort 1 and 224, cohort 2) and 576 controls were included. TLR10-TLR1-TLR6 cluster single-nucleotide polymorphisms genotyping, NOD2 mutations and TLR10 mRNA quantification were performed using TaqMan assays. Nucleotide-binding oligomerization domain containing 2 (NOD2) and Toll-like receptor (TLR) loci interaction was analyzed by logistic regression and multifactor-dimensionality reduction (MDR). Entropy-based analysis was used to interpret combination effects. One TLR10 haplotype (TLR10(GGGG)) was found associated with CD susceptibility in both cohorts, individuals with two copies had approximately twofold more risk of CD susceptibility than individuals having no copies (odds ratio=1.89, P-value=0.0002). No differences in the mRNA levels were observed among the genotypes. The strongest model for predicting CD risk according to the MDR analysis was a two-locus model including NOD2 mutations and TLR10(GGGG) haplotype (P(c)<0.0001). The interaction gain attributed to the combination of both genes was negative (IG=-2.36%), indicating redundancy or independent effects. Our results support association of the TLR10 gene with CD susceptibility. The effect of TLR10 would be independent of NOD2, suggesting different signaling pathways for both genes.

Firing duration of masseter motor units during prolonged low-level contractions.

OBJECTIVE: The study aimed to determine whether motor units (MUs) of the masseter muscle can be continuously active during a prolonged low-level sustained contraction. METHODS: Intramuscular fine-wire EMG activity was recorded unilaterally from the masseter muscles of 13 pain-free volunteers (mean age ± SD = 26.7 ± 7.7 years), during low-level biting tasks performed for 30 min. The stored intramuscular EMG signals were decomposed into individual MU action-potential trains using long-term decomposition software. Depending on relative duration of the MU activity, MUs were classified as sporadically (<50% of the time), intermittently (50% ≤ time ≤ 95%), or continuously active (>95% of the time). RESULTS: The overall number of MUs identified during the low-level biting task was 203. Of these, nine continuously active MUs (4.4%) were found in six of the 13 subjects investigated, whereas 50 intermittent MUs (24.6%) were found in 12 subjects. The remaining MUs (71.0%) were sporadically active and were found in all of the subjects investigated. CONCLUSION: The majority of masseter MUs is sporadically or intermittently active during prolonged low-level contractions, but some of them can also be continuously active. SIGNIFICANCE: Sustained clenching efforts may be accompanied by continuous activity of a few selected muscle fibres.

Analysis of the influence of PTPN22 gene polymorphisms in systemic sclerosis.

OBJECTIVE: Two functional single nucleotide polymorphisms (SNP) in the PTPN22 gene (rs24746601 and rs33996649) have been associated with autoimmunity. The aim of this study was to investigate the role of the R263Q SNP for the first time and to re-evaluate the role of the R620W SNP in the genetic predisposition to systemic sclerosis (SSc) susceptibility and clinical phenotypes. METHODS: 3422 SSc patients (2020 with limited cutaneous SSc and 1208 with diffuse cutaneous SSc) and 3638 healthy controls of Caucasian ancestry from an initial case--control set of Spain and seven additional independent replication cohorts were included in our study. Both rs33996649 and rs2476601 PTPN22 polymorphisms were genotyped by TaqMan allelic discrimination assay. A meta-analysis was performed to test the overall effect of these PTPN22 polymorphisms in SSc. RESULTS: The meta-analysis revealed evidence of association of the rs2476601 T allele with SSc susceptibility (p(FDRcorrected)=0.03 pooled, OR 1.15, 95% CI 1.03 to 1.28). In addition, the rs2476601 T allele was significantly associated with anticentromere-positive status (p(FDRcorrected)=0.02 pooled, OR 1.22, 95% CI 1.05 to 1.42). Although the rs33996649 A allele was significantly associated with SSc in the Spanish population (p(FDRcorrected)=0.04, OR 0.58, 95% CI 0.36 to 0.92), this association was not confirmed in the meta-analysis (p=0.36 pooled, OR 0.89, 95% CI 0.72 to 1.1). CONCLUSION: The study suggests that the PTPN22 R620W polymorphism influences SSc genetic susceptibility but the novel R263Q genetic variant does not. These data strengthen evidence that the R620W mutation is a common risk factor in autoimmune diseases.

Bcl-2 antagonist killer 1 (BAK1) polymorphisms influence the risk of developing autoimmune rheumatic diseases in women.

OBJECTIVE: Bcl-2 antagonist killer 1 (BAK1) is a Bcl-2 family proapoptotic member suggested as a candidate gene for autoimmune diseases. The influence of BAK1 polymorphisms on the risk of developing autoimmune rheumatic diseases (AIRDs) in women was investigated. METHODS: A total of 719 Colombian women were included in the present study: 209 had systemic lupus erythematosus, 99 primary Sjögren syndrome, 159 rheumatoid arthritis and 252 were healthy matched controls. Tag single nucleotide polymorphisms (SNPs) and potentially functional variants were typed by TaqMan allele discrimination assays. HLA-DRB1 and HLA-DQB1 typing was performed by reverse dot-blot hybridisation and linkage disequilibrium (LD) with BAK1 SNPs was assessed. RESULTS: SNPs rs513349 (odds ratio (OR) 0.57, 95% CI 0.46 to 0.72, p = <0.001) and rs5745582 (OR 1.61, 95% CI 1.26 to 2.04, p = <0.001) were associated with the AIRDs included in this study. There was a significant increase of the rs513349G-rs561276C-rs5745582A (GCA) haplotype in each patient cohort as compared to controls (OR 1.95, 95% CI 1.50 to 2.54, p = <0.001). These SNPs were not in LD with HLA-DRB1 or HLA-DQB1 genes. CONCLUSIONS: The results indicate that the BAK1 polymorphisms influence the risk of acquiring AIRDs in the population studied and are consistent with the paradigm that autoimmune diseases are likely to share common susceptibility variants.

Interindividual differences in the perception of dental stimulation and related brain activity.

For identical diagnoses in the trigeminal innervation territory, individual differences have been clinically observed among the symptoms reported, such as dysesthesia and pain. Different subjective perceptions of unpleasantness and pain intensity may have different cortical substrates. The aim of this study was to identify brain areas in which activation depends on the subjective perception (intensity and unpleasantness) of electric dental stimulation. Electrical stimuli of increasing intensity were applied to maxillary canines in 14 healthy volunteers. Ratings for stimulus intensity and unpleasantness perceived across the stimulation session were reported postscan on 11-point numerical scales. The rating values were then included as covariates in the functional magnetic resonance imaging (fMRI) group analysis. Interindividual differences of intensity ratings were reflected in differential activity of the following brain areas: superior parietal lobule, superior temporal gyrus/anterior insula, inferior and middle temporal gyrus, lingual gyrus, anterior cingulate, and caudate nucleus. Differences related to unpleasantness ratings were reflected in the lingual gyrus. In conclusion, differences of perceived intensity between individuals are reflected in the differential activity of a set of brain areas distinct from those regions, reflecting rating differences of unpleasantness.

Synergist coactivation and substitution pattern of the human masseter and temporalis muscles during sustained static contractions.

OBJECTIVE: Previous reports indicated that between-muscle substitution of active motor unit pools can be found in a variety of synergist muscles, including shoulder and leg muscles, but little information is available for the masticatory muscles. We hypothesized that, during a prolonged clenching effort performed at low- to moderate-bite force levels, a substitution pattern of activity can be found also in the masseter and anterior temporal muscles. METHODS: Ten healthy volunteers were recruited and were asked to clench unilaterally on a force transducer for 10min at 10%, 15%, and 20% of the maximum bite force. During each session, bite force, perceived muscle pain and electromyographic activity were continuously assessed. Data analyses were performed by means of cross-correlation and periodogram analyses. RESULTS: During sustained static contractions, different contraction patterns of jaw elevator muscles could be identified. These included a coactivation pattern, a substitution pattern, and several intermediate situations between coactivation and substitution. CONCLUSIONS: The findings support the concept that the masticatory muscles are functionally heterogeneous and provide evidence that the neuromuscular strategies used by the masticatory system to perform sustained static contractions differ between individuals. SIGNIFICANCE: Individual neuromuscular strategies might play a role in the development of masticatory muscle pain conditions.