Poorer sleep quality in patients with chronic temporomandibular disorders compared to healthy controls.

OBJECTIVES: This study aimed to investigate and compare sleep quality between patients with chronic temporomandibular disorder and healthy controls, and to analyze the association of sleep quality with disease characteristics, obstructive sleep apnea risk factors, and excessive daytime sleepiness. METHODS: Chronic temporomandibular disorder patients (n = 503, mean age: 33.10 ± 13.26 years, 333 females) and 180 age- and sex-matched healthy controls (mean age: 32.77 ± 12.95 years, 116 females) were included, who completed well-organized clinical report and answered questions on sleep quality (Pittsburgh Sleep Quality Index), sleep apnea risk factors (STOP-Bang questionnaire), and excessive daytime sleepiness (Epworth sleepiness scale). RESULTS: Mean global Pittsburgh Sleep Quality Index scores were significantly higher in the patients (6.25 ± 2.77) than in healthy controls (3.84 ± 2.29) (p <  0.001). Poor sleep was significantly more prevalent in the patient group (56.9%) than in healthy controls (22.2%) (p <  0.001). Compared with healthy controls, chronic temporomandibular disorder patients had a higher likelihood of obstructive sleep apnea (STOP-Bang total score ≥ 3; 7.2% vs. 16.1%; p <  0.01) and higher excessive daytime sleepiness (Epworth sleepiness scale score ≥ 10; 12.8% vs. 19.7%; p <  0.05). Age (odds ratio = 2.551; p <  0.001), female sex (odds ratio = 1.885; p = 0.007), total Epworth sleepiness scale score (odds ratio = 1.839; p = 0.014), and headache attributed to temporomandibular disorder (odds ratio = 1.519; p = 0.049) were the most powerful predictors of poor sleep (global Pittsburgh Sleep Quality Index score ≥ 5) in chronic temporomandibular disorder patients. CONCLUSION: Chronic temporomandibular disorder patients had markedly impaired sleep quality than healthy controls. Poorer sleep in patients with chronic temporomandibular disorder was associated with a variety of clinical factors, including a higher likelihood of excessive daytime sleepiness, older age, female gender, higher Epworth sleepiness scale scores, and the presence of headache attributed to temporomandibular disorder.

Emerging Potential of Exosomes in Regenerative Medicine for Temporomandibular Joint Osteoarthritis.

Exosomes are nanosized vesicles (30-140 nm) of endocytic origin that play important roles in regenerative medicine. They are derived from cell membranes during endocytic internalization and stabilize in biological fluids such as blood and synovia. Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative disease, which, in addition to chronic pain, is characterized by progressive cartilage breakdown, condylar bone remodeling, and synovitis. However, traditional clinical treatments have limited symptom- and structure-modifying effects to restore damaged cartilage and other TMJ tissues. This is due to the limited self-healing capacity of condylar cartilage. Recently, stem-cell-derived exosomes have been studied as an alternative therapeutic approach to tissue repair and regeneration. It is known that trophic regulation of mesenchymal stem cells (MSCs) has anti-inflammatory and immunomodulatory effects under pathological conditions, and research on MSC-derived exosomes is rapidly accumulating. MSC-derived exosomes mimic the major therapeutic effects of MSCs. They affect the activity of immune effector cells and possess multilineage differentiation potential, including chondrogenic and osteogenic differentiation. Furthermore, exosomes are capable of regenerating cartilage or osseous compartments and restoring injured tissues and can treat dysfunction and pain caused by TMJ OA. In this review, we looked at the uniqueness of TMJ, the pathogenesis of TMJ OA, and the potential role of MSC-derived exosomes for TMJ cartilage and bone regeneration.

Sex-related differences in symptoms of temporomandibular disorders and structural changes in the lateral pterygoid muscle after whiplash injury.

Whiplash injury is an initiating or aggravating factor of temporomandibular disorder (TMD). Although there are sex-related differences in the mechanism of pain perception and pain control, there is a lack of research on differences in TMD after whiplash injury. We aimed to evaluate sex-related differences in the clinical symptoms and magnetic resonance imaging (MRI) findings of patients with TMD attributed to whiplash injury. This retrospective, cross-sectional study included 100 patients (50 women; 50 men; mean age, 37.60 years) who visited our oro-facial pain clinic with symptoms of TMD after whiplash injury. All patients underwent detailed evaluations for history of trauma, and their clinical and MRI findings were comprehensively assessed. Women with TMD after whiplash injury perceived more pain and presented more tenderness upon palpation than did men with TMD. In addition, women showed higher volume (58% vs 26%) and signal changes (54% vs 20%) in the lateral pterygoid muscle (LPM) and more anterior disc displacement without reduction (ADDWoR) (40% vs 20%) than did men. The presence of ADDWoR (odds ratio, 10.58; P = 0.007) and condylar degeneration (odds ratio, 9.30; P = 0.015) predicted LPM volume; stressful conditions (beta = 1.34; P = 0.011) correlated with increased visual analogue scale scores, and sleep problem was associated with an increased palpation index (PI) (beta = 0.42; P < 0.001) and neck PI (beta = 0.49; P < 0.001) scores only in women. Our results showed sex-specific differences in pain intensity, distribution of clinical and abnormal MRI findings, and their relationships, and these differences should be considered when treating patients with TMD.

Effects of intramuscular morphine in men and women with temporomandibular disorder with myofascial pain.

OBJECTIVES: This placebo-controlled randomized double-blinded clinical study assessed the analgesic efficacy of intramuscular morphine in TMD patients with myofascial pain and sex-dependent responses of the morphine treatment. SUBJECTS AND METHODS: Men and women with TMD were treated with morphine (1.5 or 5 mg), lidocaine, or saline in the masseter muscle. VAS of pain intensity, PPT, and PPtol were compared between treatment groups and gender. An additional group was treated with morphine in the trapezius muscle to evaluate the systemic effect of morphine that may reduce pain in the masseter muscle. RESULTS: There was a significant difference in VAS scores between the morphine 5 mg group and the saline group favoring morphine, but not between the morphine 5 mg and lidocaine. Morphine 1.5 and 5 mg treatments led to consistently and significantly elevated PPT and PPtol measures in men, but not in women. Morphine administered in the trapezius muscle did not affect the outcome measures. CONCLUSION: A single dose intramuscular morphine produced analgesic effects up to 48 hr in patients with myofascial pain. Intramuscular morphine elevated mechanical pain threshold and tolerance in the masseter only in male patients, suggesting sex differences in local morphine effects. No systemic effect of intramuscular morphine was detected.

N-methyl-D-aspartate (NMDA) impairs myogenesis in C2C12 cells.

INTRODUCTION: N-methyl-d-aspartate (NMDA) is expressed in sensory neurons and plays important roles in peripheral pain mechanisms. The aim of this study was to examine the effects and molecular mechanisms of NMDA on C2C12 myoblast proliferation and differentiation. METHODS: Cytotoxicity and differentiation were examined by the MTT assay, reverse transcription-polymerase chain reaction, and immunofluorescence. RESULTS: NMDA had no cytotoxicity (10-500 µM) and inhibited myoblastic differentiation of C2C12 cells, as assessed by F-actin immunofluorescence and levels of mRNAs encoding myogenic markers such as myogenin and myosin heavy-chain 2. It inhibited phosphorylation of mammalian target of rapamycin (mTOR) by inactivating mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38. It induced reactive oxygen species production. Furthermore, NMDA-suppressed expression of F-actin was reversed by adding the antioxidant N-acetylcysteine. CONCLUSIONS: Collectively, these results indicate that NMDA impairs myogenesis or myogenic differentiation in C2C12 cells through the mTOR/MAPK signaling pathways and may lead to skeletal muscle degeneration. Muscle Nerve 56: 510-518, 2017.

Effects of sodium tri- and hexameta-phosphate in vitro osteoblastic differentiation in Periodontal Ligament and Osteoblasts, and in vivo bone regeneration.

The present study was designed to assess the effects and underlying mechanism of two poly(P) compounds, sodium triphosphate (STP, Na5P3O10) and sodium hexametaphosphate (SHMP, Na15P13O40~Na20P18O40) on osteoblastic differentiation of human periodontal ligament cells (PDLCs) and osteoblasts in vitro, and bone formation in vivo. Differentiation was assessed by alkaline phosphatase (ALP) activity, mineralization, and mRNA expression for marker genes. To examine the osteogenic potential to regenerate bone, the critical-sized mouse calvarial defect model was utilized. Incubation of PDLCs and osteoblasts with STP and SHMP resulted in a dose- and time-dependent increase in growth, alkaline phosphatase (ALP) activity, mineralization and mRNA expression for marker genes. STP and SHMP increased phosphorylation of adenosine monophosphate-activated protein kinase (AMPK), Akt, and mammalian target of rapamycin (mTOR), and mitogen-activated protein kinases (MAPK). Treatment with the mTOR inhibitor, rapamycin, attenuatted STP- and SHMP-induced osteoblastic differentiation. Micro-CT and histologic analysis showed that STP significantly increased new bone formation in calvarial defects, compared with SHMP and control group. Collectively, this is the first study to demonstrate that STP and SHMP promotes the osteoblastic differentiation in vitro, whereas STP only stimulated bone repair in vivo. Therefore, STP may be useful therapeutic approach for the regeneration of bone or periodontal tissue.

Sonic Hedgehog Promotes Cementoblastic Differentiation via Activating the BMP Pathways.

Although sonic hedgehog (SHH), an essential molecule in embryogenesis and organogenesis, stimulates proliferation of human periodontal ligament (PDL) stem cells, the effects of recombinant human SHH (rh-SHH) on osteoblastic differentiation are unclear. To reveal the role of SHH in periodontal regeneration, expression of SHH in mouse periodontal tissues and its effects on the osteoblastic/cementoblastic differentiation in human cementoblasts were investigated. SHH is immunolocalized to differentiating cementoblasts, PDL cells, and osteoblasts of the developing mouse periodontium. Addition of rh-SHH increased cell growth, ALP activity, and mineralization nodule formation, and upregulated mRNA expression of osteoblastic and cementoblastic markers. The osteoblastic/cementoblastic differentiation of rh-SHH was abolished by the SHH inhibitor cyclopamine (Cy) and the BMP antagonist noggin. rh-SHH increased the expression of BMP-2 and -4 mRNA, as well as levels of phosphorylated Akt, ERK, p38, and JNK, and of MAPK and NF-κB activation, which were reversed by noggin, Cy, and BMP-2 siRNA. Collectively, this study is the first to demonstrate that SHH can promote cell growth and cell osteoblastic/cementoblastic differentiation via BMP pathway. Thus, SHH plays important roles in the development of periodontal tissue, and might represent a new therapeutic target for periodontitis and periodontal regeneration.

Combined effects of dentin sialoprotein and bone morphogenetic protein-2 on differentiation in human cementoblasts.

The aim of this study is to determine the effects of the combination of recombinant human BMP-2 (rh-BMP-2) and dentin sialoprotein (rh-DSP) on growth and differentiation in human cementoblasts and determine the underlying signal transduction mechanism. Compared to treatment of cementoblasts with either rh-BMP-2 or rh-DSP alone, the combination of rh-BMP-2 and rh-DSP synergistically increased cell growth, ALP activity, nodule formation and expression of differentiation markers. The differentiation-promoting effect was also observed in periodontal ligament cells and an osteoblastic cell line. Likewise, combination of rh-DSP and rh-BMP-2 increased BMP-2 mRNA expression and Smad1/5/8 phosphorylation, which was blocked by the BMP antagonist noggin. The expression levels of α2ß1 integrin and RhoA, as well as the phosphorylation status of FAK and Akt, were increased by the combination of rh-BMP-2 and rh-DSP in a time-dependent manner. In addition, rh-BMP-2 and rh-DSP enhanced expression of Wnt ligands, ß-catenin activation and GSK-3ß phosphorylation, all of which were inhibited by the Wnt receptor antagonist DKK1. Furthermore, treatment with rh-DSP plus rh-BMP-2 resulted in phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 and also induced the nuclear translocation of the NF-κB p65 subunit, which was blocked by noggin. This study demonstrates for the first time that rh-DSP and rh-BMP-2 act synergistically, enhancing each other's ability to stimulate cementoblastic cell growth and differentiation in vitro via autocrine BMP, integrin, Wnt/ß-catenin, MAP kinase and NF-κB pathways. These results support the therapeutic potential of a combination strategy for aiding periodontal regeneration.

Age and sex differences in comorbidities in adult temporomandibular disorders: A cross-sectional study using Korea National Health and Nutrition Examination Survey (KNHANES).

OBJECTIVES: To investigate the relationship between Temporomandibular disorder (TMD) and associated comorbidities in groups matched according to age and sex. METHODS: Using data from the cross-sectional fifth Korea National Health and Nutrition Examination Survey (KNHANES). Of the 25,534 eligible KNHANES, 17,762 adults aged ≥19 years who responded to survey questionnaire on TMD and comorbidities. Subjects were classified into eight groups according to age and sex. Logistic regression analyses were performed to evaluate the association between TMD and comorbidities according to age and sex. RESULTS: Of the enrolled participants, 2,107 (11.86%) complained of ≥1 TMD symptoms. In all groups, odds ratios (ORs) for prevalence of TMD were >1 in those with tinnitus. Rhinitis was closely associated with TMD in 6 groups. ORs for TMD with comorbidities according to age and sex were as follows: hypertension, men aged 50-64 years (OR 0.62; CI 0.41-0.94); ischemic heart disease, men aged 35-49 years (4.38; 1.54-12.47); osteoarthritis, women aged 50-64 years (1.38; 1.03-1.86); diabetes mellitus, men aged 35-49 years (0.21; 0.05-0.88); depression, men aged 50-64 years (1.68; 1.00-2.83), women aged 35-49 years (1.39; 1.05-1.85) and women aged 65-80 years (2.01; 1.46-2.77); migraine, men aged 50-64 years (1.60; 1.14-2.25), women aged d35-49 years (1.44; 1.14-1.81) and women aged 35-49 years (1.43; 1.07-1.90); cold hypersensitivity in the hands and feet, men aged 19-34 years (1.64; 1.05-2.58), men aged 35-49 years (1.68; 1.04-2.70), men aged 65-80 years (1.74; 1.09-2.75) and women aged 35-49 years (1.45; 1.15-1.84); olfaction disorder, men aged 50-64 years (2.49; 1.39-4.43); voice disorder, men aged 50-64 years (2.25; 1.28-3.96) and women aged 65-80 years (1.69; 1.09-2.63). CONCLUSIONS: This study confirmed that the types and effects of comorbidities related to prevalence of TMD may differ according to the patient's age and sex and this result will increase the predictability of the onset of TMD.

Prediction of xerostomia in elderly based on clinical characteristics and salivary flow rate with machine learning.

Xerostomia may be accompanied by changes in salivary flow rate and the incidence increases in elderly. We aimed to use machine learning algorithms, to identify significant predictors for the presence of xerostomia. This study is the first to predict xerostomia with salivary flow rate in elderly based on artificial intelligence. In a cross-sectional study, 829 patients with oral discomfort were enrolled, and six features (sex, age, unstimulated and stimulated salivary flow rates (UFR and SFR, respectively), number of systemic diseases, and medication usage) were used in four machine learning algorithms to predict the presence of xerostomia. The incidence of xerostomia increased with age. The SFR was significantly higher than the UFR, and the UFR and SFR were significantly correlated. The UFR, but not SFR, decreased with age significantly. In patients more than 60 years of age, the UFR had a significantly higher predictive accuracy for xerostomia than the SFR. Using machine learning algorithms with tenfold cross-validation, the prediction accuracy increased significantly. In particular, the prediction accuracy of the multilayer perceptron (MLP) algorithm that combined UFR and SFR data was significantly better than either UFR or SFR individually. Moreover, when sex, age, number of systemic diseases, and number of medications were added to the MLP model, the prediction accuracy increased from 56 to 68%.

Sodium hydrogen sulfide inhibits nicotine and lipopolysaccharide-induced osteoclastic differentiation and reversed osteoblastic differentiation in human periodontal ligament cells.

Although previous studies have demonstrated that hydrogen sulfide (H(2)S) stimulated or inhibited osteoclastic differentiation, little is known about the effects of H(2)S on the differentiation of osteoblasts and osteoclasts. To determine the possible bioactivities of H(2)S on bone metabolism, we investigated the in vitro effects of H(2)S on cytotoxicity, osteoblastic, and osteoclastic differentiation as well as the underlying mechanism in lipopolysaccharide (LPS) and nicotine-stimulated human periodontal ligament cells (hPDLCs). The H(2)S donor, NaHS, protected hPDLCs from nicotine and LPS-induced cytotoxicity and recovered nicotine- and LPS-downregulated osteoblastic differentiation, such as alkaline phosphatase (ALP) activity, mRNA expression of osteoblasts, including ALP, osteopontin (OPN), and osteocalcin (OCN), and mineralized nodule formation. Concomitantly, NaHS inhibited the differentiation of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts in mouse bone marrow cells and blocked nicotine- and LPS-induced osteoclastogenesis regulatory molecules, such as RANKL, OPG, M-CSF, MMP-9, TRAP, and cathepsin K mRNA. NaHS blocked nicotine and LPS-induced activation of p38, ERK, MKP-1, PI3K, PKC, and PKC isoenzymes, and NF-κB. The effects of H(2)S on nicotine- and LPS-induced osteoblastic and osteoclastic differentiation were remarkably reversed by MKP-1 enzyme inhibitor (vanadate) and expression inhibitor (triptolide). Taken together, we report for the first time that H(2)S inhibited cytotoxicity and osteoclastic differentiation and recovered osteoblastic differentiation in a nicotine- and periodontopathogen-stimulated hPDLCs model, which has potential therapeutic value for treatment of periodontal and inflammatory bone diseases.

Growth inhibition and apoptosis-inducing effects of cudraflavone B in human oral cancer cells via MAPK, NF-κB, and SIRT1 signaling pathway.

The goal of this study was to investigate the effect and molecular mechanism of cudraflavone B, a prenylated flavonoid isolated from the root bark of Cudrania tricuspidata, against oral squamous cell carcinoma cells. We observed that cudraflavone B inhibited proliferation of these cells in a time- and dose-dependent manner. At 15 µM, cudraflavone B induced cell death via apoptosis (characterized by the appearance of nuclear morphology) and increased the accumulation of the sub-G1 peak (portion of apoptotic annexin V positive cells). Treatment with cudraflavone B triggered the mitochondrial apoptotic pathway (indicated by induction of the proapoptotic protein p53 and the p21 and p27 effector proteins), downregulation of cell cycle regulatory proteins (e.g., p-Rb, changing Bax/Bcl-2 ratios, cytochrome-c release), and caspase-3 activation. Cudraflavone B time-dependently activated NF-κB, the MAP kinases p38, and ERK, and induced the expression of SIRT1. SIRT1 activator, resveratrol, dose-dependently attenuated the growth-inhibitory and apoptosis-inducing effect of cudraflavone B and blocked cudraflavone B-induced regulatory protein expressions in the mitochondrial pathway such as p53, p21, p27, Bax, caspase-3, and cytochrome-c. Conversely, treatment with SIRT1 inhibitor sirtinol caused opposite effects. These results demonstrate for the first time that the molecular mechanism underlying the antitumor effect in oral squamous cell carcinoma cells is related to the activation of MAPK/and NF-κB as well as of the SIRT1 pathway. Therefore, cudraflavone B may be a lead for the development of a potential candidate for human oral squamous cell carcinoma cells.

Volatile sulfide compounds and oral microorganisms on the inner surface of masks in individuals with halitosis during COVID-19 pandemic.

Mask-wearing is still recommended owing to the continuing impact of the COVID-19 pandemic. Within the closed chamber created by the mask, people are increasingly self-aware of their oral malodor. In this prospective and cross-sectional study, we aimed to measure volatile sulfide compound (VSC) levels in patients with halitosis and investigate the oral microbiome profile on the inner surface of their KF94 masks. We also investigated which oral microbiota increases VSC levels and whether the oral microbiomes of oral saliva and mask are correlated. A total of 50 subjects (41 women, average age 38.12 ± 12.58 years old) were included in the study, 25 healthy subjects and 25 patients with halitosis who wore masks for more than 3 h. The dominant bacterial species, bacterial profile, and Shannon diversity index of whole unstimulated saliva and the inner surface of the mask were investigated. The bacterial 16S ribosomal RNA genes of the major oral bacterial species were analyzed using real-time PCR. Gas chromatography was used to measure hydrogen sulfide (H2S) and methyl mercaptan (CH3SH), which are representative VSCs. The total bacterial DNA copy number was significantly higher in the saliva sample than in the mask sample (p < 0.001), and the average value was 276 times greater. Shannon diversity index was also significantly higher in saliva than in the inner surface of the mask (2.62 ± 0.81 vs. 1.15 ± 1.52, p < 0.001). The most common Gram-negative and Gram-positive species in the masks were Porphyromonas gingivalis (Pg) and Lactobacillus casei (Lc), respectively. The bacterial species with significant positive correlations between saliva and mask samples were Prevotella intermedia (Pi) (r = 0.324, p = 0.022), Eikenella corrodens (r = 0.309, p = 0.029), Lc (r = 0.293, p = 0.039), and Parvimonas micra (Pm) (r = 0.366, p = 0.009). The mean value of CH3SH was significantly higher in the halitosis group than in the non-halitosis group (17.84 ± 29.00 vs. 3.84 ± 10.57 ppb, p = 0.031). In the halitosis group, the DNA copy numbers and VSC levels showed highly positive correlation coefficients in the order Pg, Treponema denticola (Td), Tannerella forsythia (Tf), Pi, and Prevotella nigrescens (Pn) (all p < 0.05). Regarding bacterial profiles of the mask, Td was strongly correlated with CH3SH (r = 0.414, p = 0.040) and total VSCs (r = 0.374, p = 0.033) only in halitosis group. Mask-wearing time was strongly correlated with total VSCs, H2S, and CH3SH (all r > 0.8, p < 0.001). Oral bacteria, whose association with halitosis has been identified, increased VSC levels in mask-wearing subjects during the COVID-19 pandemic, particularly the number of Gram-negative anaerobes such as Pg and Td. Mask-wearing time was a major factor in increasing VSC levels. The study results suggest that people with halitosis could control these Gram-negative bacteria by improving oral hygiene and regularly changing masks.

Comparison of sleep quality deterioration by subgroup of painful temporomandibular disorder based on diagnostic criteria for temporomandibular disorders.

Chronic pain conditions, including temporomandibular disorders, are closely related to poor sleep quality. This study investigated whether sleep deterioration in patients with painful temporomandibular disorder differed depending on the origin of pain, and also analyzed which clinical disease characteristics and whether psychological distress affected sleep quality. A total of 337 consecutive patients (215 women; mean age, 33.01 ± 13.01 years) with painful temporomandibular disorder (myalgia [n=120], temporomandibular joint arthralgia [n=62], mixed joint-muscle temporomandibular disorder pain [n=155]), who were assessed and classified based on the diagnostic criteria for temporomandibular disorder (DC/TMD), were enrolled. They completed a battery of standardized reports on clinical sign and symptoms, and answered questions on sleep quality, excessive daytime sleepiness, and patients' psychological status. The mean global Pittsburgh Sleep Quality Index scores were significantly higher in the mixed temporomandibular disorder pain group (6.97 ± 3.38) and myalgia group (6.40 ± 3.22) than in the arthralgia group (5.16 ± 2.94) (p=0.001). Poor sleepers were significantly more prevalent in the mixed temporomandibular disorder pain group (76.8%) and myalgia group (71.7%) than in the arthralgia group (54.8%) (p=0.006). The presence of psychological distress in the myalgia group (ß=1.236, p=0.022), global severity index of the Symptom Checklist-90-Revised in the arthralgia group (ß=1.668, p=0.008), and presence of headache (ß=1.631, p=0.002) and self-reported sleep problems (ß=2.849, p<0.001) in the mixed temporomandibular disorder pain group were associated with an increase in the Pittsburgh Sleep Quality Index score. Ultimately, as the source of pain in painful temporomandibular disorder can affect and determine sleep quality and contributing factors, and as the complex interplay between sleep and pain can vary, a comprehensive treatment approach is necessary because good sleep is required by patients.

Sleep analysis results of portable polysomnography in patients with acute and chronic temporomandibular disorder.

Objective: This study aimed to investigate portable polysomnography (PSG)-based 'sleep' and pre-diagnosis of obstructive sleep apnoea (OSA) in acute temporomandibular disorder (TMD) and patients with chronic TMD. Methods: Randomly selected 25 patients with acute TMD (mean age, 42.58 ± 18.77 years; 14 females) and 26 age-and sex-matched patients with chronic TMD (mean age, 49.24 ± 17.52 years, 19 females) were enrolled. Results: The eight psychological subscales of SCL-90R had significantly higher values in the chronic TMD group than in the acute TMD group (all p < 0.05). There was no significant group difference in the respiratory event index examined using a portable PSG. OSA was observed in 57.7% in acute TMD, and 68.0% in chronic TMD, respectively. From the multiple regression analysis, palpation index was the strongest predictor of pre-diagnosis of OSA (OR = 17.550). Among the contributing factors for TMD, psychological stress (OR = 12.226), self-reported sleep problems (OR = 10.222), and above-average value of DEP (OR = 1.443) were followed. Conclusion: Patients with chronic TMD were psychologically more vulnerable than those with acute TMD, and the existence of subjectively perceived sleep problems or objective sleep indices examined by portable PSG could affect TMD symptom severity in different ways.

Investigation of Snoring and Obstructive Sleep Apnea Using Portable Polysomnography in Patients with Temporomandibular Disorder.

Objective: To investigate snoring and obstructive sleep apnea (OSA) in patients with temporomandibular disorder (TMD) using portable polysomnography and identify sex-based differences in clinical features and sleep-related results. Methods: Seventy consecutive patients (44 female; mean age, 46.6918.18 years) with myofascial pain-associated TMD, diagnosed based on the criteria for TMD Axis I, were enrolled. Sleep quality and quantity were measured using portable polysomnography. Clinical characteristics were investigated using well-structured standardized reports on clinical signs and symptoms, questionnaires, and clinical examination by TMD specialists. Results: Among 70 TMD patients, 50.0% had OSA and 15.7% had snoring, with no sex-based differences. The mean Mallampati scores for OSA prediction (2.69±1.12 vs. 1.70±0.82, p<0.001), mean body mass index (BMI) (24.94±1.78 vs. 22.02±2.24, p<0.001), and ratio of overweight patients (57.7 vs. 11.4%) with BMI ≥25 were significantly higher in males than in females (all p<0.001). Conversely, the mixed sleep apnea index was significantly higher in females than in males (0.81±0.80 vs. 0.44±0.54, p=0.022). Female sex was associated with the absence of snoring (OR=0.146, p=0.022). Based on the area under curve (AUC) value for snoring prediction, Mallampati score was the strongest predictor (AUC>0.932, p<0.001), followed by BMI, overweight, and obstructive sleep apnea index (AUC>0.8, all p<0.001). Conclusions: Our results support the necessity of investigating sex-based differences when examining sleep problems, including snoring and OSA, in TMD patients. Mallampati scoring could be a useful tool for physical examination prior to polysomnography. Sleep and biopsychosocial factors are important for the diagnosis and treatment of TMD.

Clinical factors affecting depression in patients with painful temporomandibular disorders during the COVID-19 pandemic.

Temporomandibular disorders (TMD) are a multifactorial condition associated with both physical and psychological factors. Stress has been known to trigger or worsens TMD. We aimed to investigate whether the novel coronavirus disease-2019 (COVID-19) pandemic aggravates depression in patients with painful TMD, and the factors that affect their level of depression. We included 112 patients with painful TMD (74 females, 38 males; mean age: 35.90 ± 17.60 years; myalgia [n = 38], arthralgia [n = 43], mixed joint-muscle TMD pain [n = 31]). TMD was diagnosed based on the Diagnostic Criteria for TMD Axis I. Physical pain intensity was recorded using the visual analog scale (VAS); psycho-emotional status (depression: Beck Depression Inventory [BDI], anxiety: Beck Anxiety Inventory [BAI], and generalized stress related to COVID19: Global Assessment of Recent Stress [GARS]) was investigated twice (before [BC] and after COVID-19 [AC]). Additionally, factors affecting BDI-AC were investigated. BDI (p < 0.001), BAI (p < 0.001), GARS (p < 0.001), and VAS (p < 0.01) scores were significantly increased at AC than BC. The depression, anxiety, and stress levels were significantly positively correlated, and the AC and BC values of each factor showed a high correlation. In the mixed TMD group, BDI-AC was positively correlated with VAS-AC (p < 0.001). In the multiple regression analysis, clenching habit was the strongest predictor of an increase in the BDI scores from moderate to severe, followed by psychological distress, muscle stiffness, female sex, BAI-AC, and TMJ sounds. COVID-19 has negatively affected the psycho-emotional state of patients with painful TMD, and several clinical factors, including female sex and clenching habits, have influenced depression.

Advantages of deep learning with convolutional neural network in detecting disc displacement of the temporomandibular joint in magnetic resonance imaging.

This study investigated the usefulness of deep learning-based automatic detection of anterior disc displacement (ADD) from magnetic resonance imaging (MRI) of patients with temporomandibular joint disorder (TMD). Sagittal MRI images of 2520 TMJs were collected from 861 men and 399 women (average age 37.33 ± 18.83 years). A deep learning algorithm with a convolutional neural network was developed. Data augmentation and the Adam optimizer were applied to reduce the risk of overfitting the deep-learning model. The prediction performances were compared between the models and human experts based on areas under the curve (AUCs). The fine-tuning model showed excellent prediction performance (AUC = 0.8775) and acceptable accuracy (approximately 77%). Comparing the AUC values of the from-scratch (0.8269) and freeze models (0.5858) showed lower performances of the other models compared to the fine-tuning model. In Grad-CAM visualizations, the fine-tuning scheme focused more on the TMJ disc when judging ADD, and the sparsity was higher than that of the from-scratch scheme (84.69% vs. 55.61%, p < 0.05). The three fine-tuned ensemble models using different data augmentation techniques showed a prediction accuracy of 83%. Moreover, the AUC values of ADD were higher when patients with TMD were divided by age (0.8549-0.9275) and sex (male: 0.8483, female: 0.9276). While the accuracy of the ensemble model was higher than that of human experts, the difference was not significant (p = 0.1987-0.0671). Learning from pre-trained weights allowed the fine-tuning model to outperform the from-scratch model. Another benefit of the fine-tuning model for diagnosing ADD of TMJ in Grad-CAM analysis was the deactivation of unwanted gradient values to provide clearer visualizations compared to the from-scratch model. The Grad-CAM visualizations also agreed with the model learned through important features in the joint disc area. The accuracy was further improved by an ensemble of three fine-tuning models using diversified data. The main benefits of this model were the higher specificity compared to human experts, which may be useful for preventing true negative cases, and the maintenance of its prediction accuracy across sexes and ages, suggesting a generalized prediction.

Age group prediction with panoramic radiomorphometric parameters using machine learning algorithms.

The aim of this study is to investigate the relationship of 18 radiomorphometric parameters of panoramic radiographs based on age, and to estimate the age group of people with permanent dentition in a non-invasive, comprehensive, and accurate manner using five machine learning algorithms. For the study population (209 men and 262 women; mean age, 32.12 ± 18.71 years), 471 digital panoramic radiographs of Korean individuals were applied. The participants were divided into three groups (with a 20-year age gap) and six groups (with a 10-year age gap), and each age group was estimated using the following five machine learning models: a linear discriminant analysis, logistic regression, kernelized support vector machines, multilayer perceptron, and extreme gradient boosting. Finally, a Fisher discriminant analysis was used to visualize the data configuration. In the prediction of the three age-group classification, the areas under the curve (AUCs) obtained for classifying young ages (10-19 years) ranged from 0.85 to 0.88 for five different machine learning models. The AUC values of the older age group (50-69 years) ranged from 0.82 to 0.88, and those of adults (20-49 years) were approximately 0.73. In the six age-group classification, the best scores were also found in age groups 1 (10-19 years) and 6 (60-69 years), with mean AUCs ranging from 0.85 to 0.87 and 80 to 0.90, respectively. A feature analysis based on LDA weights showed that the L-Pulp Area was important for discriminating young ages (10-49 years), and L-Crown, U-Crown, L-Implant, U-Implant, and Periodontitis were used as predictors for discriminating older ages (50-69 years). We established acceptable linear and nonlinear machine learning models for a dental age group estimation using multiple maxillary and mandibular radiomorphometric parameters. Since certain radiomorphological characteristics of young and the elderly were linearly related to age, young and old groups could be easily distinguished from other age groups with automated machine learning models.