Influence of sleep stages on determining positional dependency in patients with obstructive sleep apnea.

Objective: Supine sleep position and rapid eye movement (REM) stage are widely known to aggravate the severity of obstructive sleep apnea (OSA). In general, position-dependent OSA is defined as an apnea-hypopnea index (AHI) at least twice as high in the supine position as in other sleep positions, but it can be misdiagnosed if a certain sleep stage, REM or NREM, is dominant in a specific sleep position. In this study, we investigated the influences of the sleep stages on positional dependency. Methods: The polysomnographic data from 111 OSA patients aged ≥ 18 years (AHI > five events/hour) who slept in both supine and non-supine positions (each ≥ 5% of the total sleep time) were retrospectively analyzed. The overall ratio of non-supine AHI/supine AHI (NS/S AHI ratio) during the entire sleep was compared between specific sleep stages, i.e., REM or NREM sleep. Additionally, the weighted NS/S AHI ratio reflecting the proportion of each sleep time was created and compared with the original NS/S AHI ratio. Results: The mean value of the NS/S AHI ratio did not differ between the entire sleep and the specific sleep stages. However, those ratios in the individual patients showed poor agreement of the NS/S AHI ratios between the entire sleep and the specific sleep stages. The weighted NS/S AHI ratio also demonstrated poor agreement with the original NS/S AHI ratio, mainly due to the discrepancy in mild to moderate OSA patients. Conclusion: The weighted NS/S AHI ratio might help assess precise positional dependency.

Sleeping and waking-state oral behaviors in TMD patients: their correlates with jaw functional limitation and psychological distress.

OBJECTIVES: This study investigated oral behaviors in various temporomandibular disorder (TMD) subtypes, assessing their frequency, extent, and associations with both jaw functional status and psychological distress. MATERIALS AND METHODS: Anonymized data from consecutive "initial-visit" TMD patients at a university-affiliated oral medicine clinic were obtained. Alongside demographic information, patients completed various questionnaires including the Diagnostic Criteria for TMD (DC/TMD) Symptom Questionnaire, Oral Behavior Checklist (OBC), Jaw Functional Limitation Scale-20 (JFLS-20), Patient Health Questionnaire-9 (PHQ-9), and General Anxiety Disorder Scale-7 (GAD-7). Patients underwent a protocolized clinical examination and received diagnoses of pain-related (PT), intra-articular (IT), or combined (CT) TMD using the DC/TMD diagnostic algorithms. Data were evaluated with Chi-square/non-parametric tests and logistic regression analyses (α = 0.05). RESULTS: The study comprised 700 patients (mean age 37.4 ± 15.7 years), with 12.6%, 15.1%, and 72.3% diagnosed with PT, IT, and CT, respectively. For all TMD subtypes, oral activities during sleep were more prevalent than those during wakefulness. While variations in total/subscale OBC scores were insignificant, substantial differences were observed in global/subscale JFLS (PT, CT > IT), depression (PT, CT > IT), and anxiety (CT > IT) scores. Near-moderate correlations (rs = 0,36-0.39) were discerned between overall/waking-state non-functional oral behaviors and depression/anxiety. Multivariate analysis indicated that the odds of different TMD subtypes were influenced by sex, age, and jaw functional status. CONCLUSIONS: For all TMD patients, sleep-related oral activities were more commonly reported than waking-state activities. Factors such as sex, age, and jaw functional limitation are associated with the likelihood of different TMD subtypes. STATEMENT OF CLINICAL RELEVANCE: Oral behaviors, in themselves, do not predict distinct TMD subtypes, in contrast to factors such as sex, age, and jaw functional status.

Age distribution of East Asian TMD patients and age-related differences in DC/TMD axis I findings.

OBJECTIVES: The pattern of age distribution in East Asian temporomandibular disorder (TMD) patients and age-related differences in DC/TMD diagnostic subtypes/categories were evaluated. SUBJECTS AND METHODS: TMD patients from two University-based centers in China and South Korea were enrolled. Axis I physical diagnoses were rendered according to DC/TMD. Patients were categorized into six age groups (15-24, 25-34, 35-44, 45-54, 55-64, and 65-84 years; Groups A-F respectively). RESULTS: Youths/young adults (Groups A-C) formed 74.1% of TMD patients. TMJ disc displacements (74.9%), arthralgia (49.2%), and degenerative joint disease [DJD] (36.8%) were the most common TMD subtypes. The majority had combined (54.0%) and chronic (58.5%) TMDs. Youths/young adults and middle-aged/old adults had substantially lower frequencies of merely pain-related (6.2-14.5%) and intra-articular (13.8-16.8%) TMDs correspondingly. "Being female" increased the prospects of pain-related/combined TMDs by 96%/49%, respectively. CONCLUSIONS: East Asian TMD patients comprised mostly of youths/young adults who had an alarmingly high prevalence of TMJ DJD.

Correlates of jaw functional limitation, somatization and psychological distress among different temporomandibular disorder diagnostic subtypes.

OBJECTIVES: This study investigated the jaw functional status and severity of somatic/psychological symptoms in different Diagnostic Criteria for temporomandibular disorders (DC/TMD) diagnostic subtypes and established the correlates between jaw functional limitation, somatization, depression and anxiety. METHODS: Data were accrued from consecutive 'first-visit' patients seeking TMD treatment at a university-based oral medicine/diagnosis clinic. Axis I physical TMD diagnoses were derived using the DC/TMD methodology and patients were categorized into pain-related (PT), intra-articular (IT) and combined (CT) TMD groups. Axis II measures were also administered and included the Jaw Functional Limitation Scale-20 (JFLS-20), Patient Health Questionnaire-15 and 9 (PHQ-15 and PHQ-9) and General Anxiety Disorder Scale-7 (GAD-7). Chi-square/Kruskal-Wallis tests and Spearman's correlation were employed for statistical evaluations (α = .05). RESULTS: The final dataset consisted of 772 TMD patients (mean age of 37.7 ± 15.9 years; 70.2% females). The prevalence of PT, IT and CT was 11.9%, 15.7% and 72.4%, respectively. Significant differences in functional jaw limitations, somatization, depression (CT, PT > IT) and anxiety (CT > PT, IT) were observed. Moderate-to-severe somatization, depression and anxiety were detected in 12.6%-15.7% of patients. For all three TMD groups, JFLS global scale/subscale scores were weakly associated with somatization, depression and anxiety scores (rs < 0.4). Moderate-to-strong correlations were noted between somatization, depression and anxiety (rs = 0.50-0.74). CONCLUSIONS: Functional jaw limitations were associated with painful TMDs but appear to be unrelated to somatization and psychological distress. Somatization and depression/anxiety were moderately correlated, underscoring the importance of somatic symptom screening when managing TMD patients.

DC/TMD axis I subtyping: generational and gender variations among East Asian TMD patients.

OBJECTIVES: This study examined the generational-gender distinctions in Diagnostic Criteria for Temporomandibular disorders (DC/TMD) subtypes among East Asian patients. METHODS: Consecutive "first-visit" TMD patients presenting at two university-based TMD/orofacial pain clinics in China and South Korea were enlisted. Demographic information along with symptom history was gathered and clinical examinations were performed according to the DC/TMD methodology. Axis I physical diagnoses were rendered with the DC/TMD algorithms and categorized into painful and non-painful TMDs. Patients were categorized into three birth cohorts, specifically Gen X, Y, and Z (born 1965-1980, 1981-1999, and 2000-2012 respectively) and the two genders. Data were evaluated using Chi-square/Kruskal-Wallis plus post-hoc tests and logistic regression analyses (α = 0.05). RESULTS: Gen X, Y, and Z formed 17.2%, 62.1%, and 20.7% of the 1717 eligible patients examined (mean age 29.7 ± 10.6 years; 75.7% women). Significant differences in prevalences of arthralgia, myalgia, headache (Gen X ≥ Y > Z), and disc displacements (Gen Z > Y > X) were observed among the three generations. Gen Z had substantially fewer pain-related and more intra-articular conditions than the other generations. Women presented a significantly greater frequency of degenerative joint disease and number of intra-articular conditions than men. After controlling for generation-gender interactions, multivariate analyses showed that "being Gen X" and female increased the risk of painful TMDs (OR = 2.20) and reduced the odds of non-painful TMDs (OR = 0.46). CONCLUSIONS: Generational-gender diversities in DC/TMD subtypes exist and are important for guiding TMD care and future research endeavors.

Biodegradation Potential of Polyethylene Terephthalate by the Two Insect Gut Symbionts Xanthomonas sp. HY-74 and Bacillus sp. HY-75.

Polyethylene terephthalate (PET) is a plastic material that is widely used in beverage bottles, food packaging, and other consumer products, which is highly resistant to biodegradation. In this study, we investigated the effects of two insect gut symbionts, Xanthomonas sp. HY-74 and Bacillus sp. HY-75, during PET biodegradation. Both strains degraded PET-containing agar plates, and the sole nutrition source assay showed that HY-74 had different degradation rates depending on the presence of specific carbon and nitrogen sources, whereas HY-75 exhibited comparable degradation across all tested conditions. The two strains biodegraded the PET film with 1.57 ± 0.21% and 1.42 ± 0.46% weight loss after 6 weeks, respectively. Changes in the morphology and structure of the PET films, such as erosion, scratching, and surface roughening, were determined using scanning electron microscopy (SEM). Further, the two strains biodegraded PET powder, broke it into its degradation products, and changed the surface functional groups. This is the first study to investigate the biodegradation of PET by Hymenoptera gut-derived microbes and offers promising insights into the potential applications of insect gut symbionts in PET waste management.

Assessment of nematicidal and plant growth-promoting effects of Burkholderia sp. JB-2 in root-knot nematode-infested soil.

Root-knot nematodes (RKN), Meloidogyne spp., are plant-parasitic nematodes that are responsible for considerable economic losses worldwide, because of the damage they cause to numerous plant species and the inadequate biological agents available to combat them. Therefore, developing novel and eco-friendly nematicides is necessary. In the present study, Burkholderia sp. JB-2, isolated from RKN-infested rhizosphere soil in South Korea, was evaluated to determine its nematicidal and plant growth-promoting effects under in vitro and in vivo conditions. Cell-free filtrates of the JB-2 strain showed high levels of nematicidal activity against second-stage juveniles (J2) of M. incognita, with 87.5% mortality following two days of treatment. In addition, the assessment of the activity against other six plant parasitic nematodes (M. javanica, M. hapla, M. arenaria, Ditylenchus destructor, Aphelenchoides subtenuis, and Heterodera trifolii) showed that the cell-free filtrates have a broad nematicidal spectrum. The three defense-responsive (MiMIF-2, MiDaf16-like1, and MiSkn1-like1) genes were activated, while Mi-cm-3 was downregulated when treated with cell-free filtrates of JB-2 cultures on J2. The greenhouse experiments suggested that the cell-free filtrates of the JB-2 strain efficiently controlled the nematode population in soil and egg mass formations of M. incognita in tomato (Solanum lycopersicum L., cv. Rutgers). An improvement in the host plant growth was observed, in which the shoot length and fresh weights of shoots and roots increased. The treatment with 10% of JB-2 cell-free filtrates significantly upregulated the expression levels of plant defenses (SlPR1, SlPR5, and SlPAL) and growth-promoting (ACO1, Exp18, and SlIAA1) genes compared with the corresponding parameters of the control group. Therefore, JB-2 could be a promising candidate for the sustainable management of RKN.

DC/TMD Axis I diagnostic subtypes in TMD patients from Confucian heritage cultures: a stratified reporting framework.

OBJECTIVES: This study proposed a conceptual framework for reporting Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) Axis I conditions and investigated the prevalence of TMD subtypes/categories in patients from Confucian heritage cultures. Variances in gender, age, and TMD chronicity between Chinese (CN) and Korean (KR) patients were also explored. MATERIALS AND METHODS: Subjects were recruited from consecutive patients seeking care at two University-based centers in Beijing and Seoul. Eligible patients completed a demographic survey as well as the DC/TMD Symptom Questionnaire and were clinically examined according to the DC/TMD methodology. Axis I diagnoses were subsequently rendered with the DC/TMD algorithms and documented using the stratified reporting framework. Statistical evaluations were performed with chi-square, Mann-Whitney U tests, and logistic regression analysis (α = 0.05). RESULTS: Data of 2008 TMD patients (mean age 34.8 ± 16.2 years) were appraised. Substantial differences in female-to-male ratio (CN > KR), age (KR > CN), and TMD duration (KR > CN) were observed. Ranked frequencies of the most common Axis I diagnoses were: CN - disc displacements (69.7%) > arthralgia (39.9%) > degenerative joint disease (36.7%); KR - disc displacements (81.0%) > myalgia (60.2%) > arthralgia (56.1%). Concerning TMD categories, notable differences in the prevalence of intra-articular (CN 55.1% > KR 15.4%) and combined (KR 71.8% > CN 33.4%) TMDs were discerned. CONCLUSIONS: Though culturally similar, the two countries require disparate TMD care planning/prioritization. While TMJ disorders in children/adolescents and young adults should be emphasized in China, the focus in Korea would be on TMD pain in young and middle-aged adults. CLINICAL RELEVANCE: Besides culture, other variables including socioeconomic, environmental, and psychosocial factors can influence the clinical presentation of TMDs. Chinese and Korean TMD patients exhibited significantly more intra-articular and combined TMDs respectively.

The influence of the COVID-19 pandemic, sex, and age on temporomandibular disorders subtypes in East Asian patients: a retrospective observational study.

BACKGROUND: Despite its major existential, societal, and health impacts, research concerning the COVID-19 pandemic and Temporomandibular disorders (TMDs) is still limited. This study examined the effect of the pandemic on TMD subtypes and elucidated the influence of the pandemic, sex, and age on the prospect of pain-related (PT) and/or intra-articular (IT) TMDs in East Asian patients. METHODS: Data were accrued from consecutive new patients attending two university-based TMD/orofacial pain clinics in China and South Korea, 12 months before (BC; Mar 2019-Feb 2020) and during (DC; Mar 2020-Feb 2021) the COVID-19 pandemic. TMD diagnoses were derived from pertinent symptoms, signs, and radiographic findings according to the Diagnostic Criteria for TMDs (DC/TMD) methodology. Patients were subsequently categorized into those with PT, IT, and combined TMDs (CT) and also stratified by attendance period, sex, and age groups (adolescents/young adults [AY] and middle-aged/older adults [MO]) for statistical analyses using Chi-square/Mann-Whitney U tests and logistic regression analyses (α = 0.05). RESULTS: The BC and DC groups comprised 367 (75.2% females; 82.8% AY) and 471 (74.3% females; 78.3% AY) patients correspondingly. No significant differences in sex and age group distributions were observed. The DC group had significantly more PT/IT conditions with higher prevalence of myalgia, headache, and degenerative joint disease than the BC group. Univariate analyses showed that PT/CT was associated with sex and age, whereas IT was related to the pandemic and age. However, multivariate analyses indicated that the odds of PT were affected by sex (OR = 2.52) and age (OR = 1.04) while the odds of IT (OR = 0.95) and CT (OR = 1.02) were influenced by age only. CONCLUSIONS: The COVID-19 pandemic, as an impact event, did not influence the prospect of PT and/or IT. Sex and age appeared to play more crucial roles in the development of PT and IT/CT respectively.

Comparative analysis of the oral microbiome of burning mouth syndrome patients.

Burning mouth syndrome (BMS) is a chronic pain condition accompanied by unpleasant burning sensations of the oral mucosa. While multiple factors were proposed for the etiology, evidence suggested a neuropathic pain origin while others suspected the use of antibiotics as the underlying cause. Interestingly, several reports demonstrated the intimate interaction of the nervous system and the microbiome. The current study aims to elucidate the correlation of the oral microbiome with the pathophysiology of the primary BMS. Microbiome samples obtained from the unstimulated whole saliva of 19 primary BMS patients and 22 healthy controls were sequenced and analyzed of the V3-V4 region of 16S rRNA gene. There was a distinct difference in the microbial composition between the BMS and the control groups at all taxonomic levels. Alpha diversity indexes of the oral microbiome were significantly lower in the BMS group. The samples were readily distinguished by multidimensional scaling analysis and linear discriminant analysis effect size. Streptococcus, Rothia, Bergeyella, and Granulicatella genus were dominant in the BMS group, while Prevotella, Haemophilus, Fusobacterium, Campylobacter, and Allorevotella genus were more abundant in the healthy group. Distinct microbiome signatures of BMS patients suggested a diagnostic value and a potential role in the pathogenesis of BMS.

Dissolving Microneedles for Rapid and Painless Local Anesthesia.

Microneedles are emerging drug delivery methods for painless treatment. The current study tested dissolving microneedles containing lidocaine (Li-DMN) for use in local anesthesia. An Li-DMN patch was fabricated by centrifugal lithography with carboxymethyl cellulose as a structural polymer and assessed for physical properties by optical microscopy and a fracture force analyzer. The biocompatibility was evaluated by a histology section in vitro and by ear thickness in vivo. The efficacy of the Li-DMN patch was assessed by electrophysiological recordings in primary cultured sensory neurons in vitro and a von Frey test on rats' hind paws in vivo. The physical properties of the microneedle showed enough rigidity for transdermal penetration. The maximal capacity of lidocaine-HCl in the Li-DMN patch was 331.20 ± 6.30 µg. The cytotoxicity of the dissolving microneedle to neuronal cells was negligible under an effective dose of lidocaine for 18 h. Electrophysiological recordings verified the inhibitory effect of the voltage-gated sodium channel current by the Li-DMN patch in vitro. A skin reaction to the edema test and histologic analysis of the rats' ears after application of the Li-DMN patch were negligible. Also, the application of the Li-DMN patch reduced the nocifensive behavior of the rats almost immediately. In conclusion, the dissolving microneedle patch with carboxymethyl cellulose is a promising candidate method for the painless delivery of lidocaine-HCl.

Usefulness of computed tomography in predicting ethmoidal arterial bleeding in refractory epistaxis.

PURPOSE: Epistaxis that is refractory to conservative management can be treated with endoscopic sphenopalatine artery ligation (ESPAL). Although rare, ethmoidal artery (EA) bleeding can be a cause of rebleeding after successful ESPAL. EA bleeding is diagnosed by angiography and can also be identified during surgical exploration. However, since the angiographic embolization of the EA is contraindicated, surgical hemostasis is mandatory. This study investigated whether paranasal sinus (PNS) CT could provide information for predicting EA bleeding without angiography in patients with refractory epistaxis requiring ESPAL. METHODS: Forty-seven patients, who were surgically treated [with ESPAL or EA ligation (EAL)] for refractory epistaxis from March 2010 to June 2019, were retrospectively analyzed. A positive PNS CT finding for EA bleeding was defined as the presence of soft tissue densities having continuity with the EA pathway, accompanied by a partially deficient surrounding bony canal. These findings as well as soft tissue densities in each paranasal sinus were compared between the ESPAL and EAL groups. RESULTS: All patients in the EAL group had positive CT findings of EA bleeding, compared to only 12.2% in the ESPAL group (P < 0.001). The rate of soft tissue densities within the frontal and sphenoid sinuses were noted in 26.8% and 17.1% of patients in the ESPAL group, compared to 83.3% and 83.3% of patients in the EAL group (P = 0.013 and P = 0.003, respectively). CONCLUSION: PNS CT might be useful for predicting EA bleeding in patients with refractory epistaxis requiring surgical hemostasis.

Dexmedetomidine modulates transient receptor potential vanilloid subtype 1.

Dexmedetomidine, a highly selective alpha-2 adrenergic receptor agonist and novel sedative drug with minimal respiratory suppression, have shown anti-nociceptive activity in various pain models by poorly understood mechanisms. Because alpha-2 adrenergic receptor is co-localized with TRPV1 polymodal nociceptive receptor in dorsal root ganglion neurons and up-regulated in neuropathic pain animal models, the analgesic activity might be mediated through inhibition of TRPV1 in the peripheral nervous system. In an effort to elucidate whether modulatory effect of dexmedetomidine on TRPV1 activity could be the potential peripheral mechanism underlying the antinociceptive effect of dexmedetomidine, intracellular calcium concentration after capsaicin application was investigated in mice dorsal root ganglion (DRG) neurons, with and without pretreatment of dexmedetomidine. Dexmedetomidine (10 µM) reduced capsaicin-induced calcium responses by 29.7 ± 7.39% (n = 34, p < 0.0001), in dose-dependent manner. Higher level of inhibition was observed with increased dose of dexmedetomidine (50 µM, 45.1 ± 8.58%, n = 15, p = 0.0002), and lower inhibition by decreased dose (1 µM, 18.8 ± 1.48%, n = 148, p = 0.004). RT-PCR analysis revealed expression of TRPV1 and alpha-2A, alpha-2B and alpha-2C subtypes of adrenergic receptor in mice DRG neurons, and immunocytochemical analysis revealed co-expression of TRPV1 and alpha-2A receptors in primary cultured DRG neurons. In summary, these results suggested the inhibition of TRPV1 expressed in the primary sensory neurons as a potential mechanism that contributes to the anti-nociceptive action of dexmedetomidine.

Ion Channels Involved in Tooth Pain.

The tooth has an unusual sensory system that converts external stimuli predominantly into pain, yet its sensory afferents in teeth demonstrate cytochemical properties of non-nociceptive neurons. This review summarizes the recent knowledge underlying this paradoxical nociception, with a focus on the ion channels involved in tooth pain. The expression of temperature-sensitive ion channels has been extensively investigated because thermal stimulation often evokes tooth pain. However, temperature-sensitive ion channels cannot explain the sudden intense tooth pain evoked by innocuous temperatures or light air puffs, leading to the hydrodynamic theory emphasizing the microfluidic movement within the dentinal tubules for detection by mechanosensitive ion channels. Several mechanosensitive ion channels expressed in dental sensory systems have been suggested as key players in the hydrodynamic theory, and TRPM7, which is abundant in the odontoblasts, and recently discovered PIEZO receptors are promising candidates. Several ligand-gated ion channels and voltage-gated ion channels expressed in dental primary afferent neurons have been discussed in relation to their potential contribution to tooth pain. In addition, in recent years, there has been growing interest in the potential sensory role of odontoblasts; thus, the expression of ion channels in odontoblasts and their potential relation to tooth pain is also reviewed.

Critical Role of ATP-P2X7 Axis in UV-Induced Melanogenesis.

Purinergic signaling participates in skin physiology and pathology, such as hair growth, wound healing, inflammation, pain, and skin cancer. However, few studies have investigated the involvement of purinergic signaling in skin pigmentation. This study demonstrated that extracellular adenosine 5'-triphosphate (ATP) released from keratinocytes by UVB radiation promotes melanin production in primary human epidermal melanocytes and ex vivo skin cultures. Intracellular calcium ion and protein kinase C/CREB signaling contributed to ATP-mediated melanogenesis. Also, P2X7 receptor was proven to play a pivotal role in ATP-mediated melanogenesis because P2X7 receptor blockade abrogated ATP-induced melanin production. In addition, MNT1 cells with P2X7 receptor knockout using CRISPR/Cas9 system did not show any increase in MITF expression when co-cultured with UV-irradiated keratinocytes compared to MNT1 cells with intact P2X7 receptor, which showed increased expression of MITF. In conclusion, our results indicate that the extracellular ATP-P2X7 signaling axis is an adjunctive mechanism in UV-induced melanogenesis. Furthermore, ATP-induced purinergic signaling in melanocytes may alter skin pigmentation.