Contribution of inwardly rectifying potassium channel 4.1 in orofacial neuropathic pain: Regulation of pannexin 3 via the reactive oxygen species-activated P38 MAPK signal pathway.

The involvement of inwardly rectifying potassium channel 4.1 (Kir4.1) in neuropathic pain has been established. However, there is limited understanding of the downstream mechanism through which Kir4.1 contributes to orofacial neuropathic pain. The objective of this study was to examine the regulation of Kir4.1 on the expression of pannexin 3 (Panx3) in the trigeminal ganglion (TG) and the underlying mechanism in the context of orofacial neuropathic pain caused by chronic constriction injury of the infraorbital nerve (CCI-ION). The study observed a significant increase in Panx3 expression in the TG of mice with CCI-ION. Inhibition of Panx3 in the TG of CCI-ION mice resulted in alleviation of orofacial mechanical allodynia. Furthermore, conditional knockdown (CKD) of Kir4.1 in the TG of both male and female mice led to mechanical allodynia and upregulation of Panx3 expression. Conversely, overexpression of Kir4.1 decreased Panx3 levels in the TG and relieved mechanical allodynia in CCI-ION mice. In addition, silencing Kir4.1 in satellite glial cells (SGCs) decreased Panx3 expression and increased the phosphorylation of P38 MAPK. Moreover, silencing Kir4.1 in SGCs increased the levels of reactive oxygen species (ROS). The elevated phosphorylation of P38 MAPK resulting from Kir4.1 silencing was inhibited by using a superoxide scavenger known as the tempol. Silencing Panx3 in the TG in vivo attenuated the mechanical allodynia caused by Kir4.1 CKD. In conclusion, these findings suggest that the reduction of Kir4.1 promotes the expression of Panx3 by activating the ROS-P38 MAPK signalling pathway, thus contributing to the development of orofacial neuropathic pain.

N-methyl-D-aspartate Receptor Subunits 2A and 2B Mediate Connexins and Pannexins in the Trigeminal Ganglion Involved in Orofacial Inflammatory Allodynia during Temporomandibular Joint Inflammation.

Temporomandibular joint osteoarthritis (TMJOA) is a severe form of temporomandibular joint disorders (TMD), and orofacial inflammatory allodynia is one of its common symptoms which lacks effective treatment. N-methyl-D-aspartate receptor (NMDAR), particularly its subtypes GluN2A and GluN2B, along with gap junctions (GJs), are key players in the mediation of inflammatory pain. However, the precise regulatory mechanisms of GluN2A, GluN2B, and GJs in orofacial inflammatory allodynia during TMJ inflammation still remain unclear. Here, we established the TMJ inflammation model by injecting Complete Freund's adjuvant (CFA) into the TMJ and used Cre/loxp site-specific recombination system to conditionally knock out (CKO) GluN2A and GluN2B in the trigeminal ganglion (TG). Von-frey test results indicated that CFA-induced mechanical allodynia in the TMJ region was relieved in GluN2A and GluN2B deficient mice. In vivo, CFA significantly up-regulated the expression of GluN2A and GluN2B, Gjb1, Gjb2, Gjc2 and Panx3 in the TG, and GluN2A and GluN2B CKO played different roles in mediating the expression of Gjb1, Gjb2, Gjc2 and Panx3. In vitro, NMDA up-regulated the expression of Gjb1, Gjb2, Gjc2 and Panx3 in satellite glial cells (SGCs) as well as promoted the intercellular communication between SGCs, and GluN2A and GluN2B knocking down (KD) altered the expression and function differently. NMDAR regulated Gjb1 and Panx3 through ERK1/2 pathway, and mediated Gjb2 and Gjc2 through MAPK, PKA, and PKC intracellular signaling pathways. These findings shed light on the distinct functions of GluN2A and GluN2B in mediating peripheral sensitization induced by TMJ inflammation in the TG, offering potential therapeutic targets for managing orofacial inflammatory allodynia.

Clinical benefit of botulinum toxin for treatment of persistent TMD-related myofascial pain: A randomized, placebo-controlled, cross-over trial.

BACKGROUND: Injections of botulinum toxin type A (BoNT-A) have been proposed as an additional treatment modality for patients suffering chronic temporomandibular disorder (TMD)-related myofascial pain (MFP). BoNT-A impairs muscle function, along with its analgesic effect, and a minimal effective dose should be used. The objective of this randomized placebo-controlled crossover study was to evaluate the clinical benefit of a moderate dose (50 U) of BoNT-A. METHODS: Sixty-six subjects were randomized into two groups, one which received BoNT-A first and a second which received a saline solution (SS) first. Follow-ups were performed 2, 11, and 16 weeks after the injections. Diagnostic criteria for temporomandibular disorders (DC/TMD) diagnostic algorithms were used to evaluate characteristic pain intensity (CPI) and pain-related disability based on the Graded Chronic Pain Scale (GCPS). Electromyographic and bite force were also evaluated. RESULTS: The within-group analysis showed a significant improvement in pain intensity and pain-related disability after BoNT-A (p < 0.001, p = 0.005, p = 0.011) and SS (p = 0.003, p = 0.005, p = 0.046) injections up to week 16. The between-group analysis of pain-related variables revealed no differences between groups at any time. Nonetheless, BoNT-A, but not SS, caused a significant decline in muscle performance. The number needed to treat (NNT) regarding a clinically significant pain reduction (≥30%) was 6.3, 57.0, and 19.0 at 2, 11, and 16-week follow-ups favoring BoNT-A. CONCLUSIONS: Injections of 50 U of BoNT-A might improve MFP symptoms, but the specific effect of the drug on pain compared to the placebo is not obvious.

Theta-burst stimulation over primary somatosensory cortex modulates tactile acuity of tongue.

Background: Emerging studies in humans have established the modulatory effects of repetitive transcranial magnetic stimulation (rTMS) over primary somatosensory cortex (S1) on somatosensory cortex activity and perception. However, to date, research in this area has primarily focused on the hand and fingers, leaving a gap in our understanding of the modulatory effects of rTMS on somatosensory perception of the orofacial system and speech articulators. Objective: The present study aimed to examine the effects of different types of theta-burst stimulation-continuous TBS (cTBS), intermittent TBS (iTBS), or sham-over the tongue representation of left S1 on tactile acuity of the tongue. Methods: In a repeated-measures design, fifteen volunteers participated in four separate sessions, where cTBS, iTBS, sham, or no stimulation was applied over the tongue representation of left S1. Effects of TBS were measured on both temporal and spatial perceptual acuity of tongue using a custom vibrotactile stimulator. Results: CTBS significantly impaired spatial amplitude threshold at the time window of 16-30 minutes after stimulation, while iTBS improved it at the same time window. The effect of iTBS, however, was smaller than cTBS. In contrast, neither cTBS nor iTBS had any effect on the temporal discrimination threshold. Conclusions: The current study establishes the validity of using TBS to modulate somatosensory perception of the orofacial system. Directly modifying somatosensation in the orofacial system has the potential to benefit clinical populations with abnormal tactile acuity, improve our understanding of the role of sensory systems in speech production, and enhance speech motor learning and rehabilitation.

The reliability and minimal detectable change of common tests and measures for temporomandibular disorders.

BACKGROUND: Temporomandibular disorders are a source of orofacial pain. Understanding clinimetric properties of evaluation procedures is necessary for assessing impairments and determining response to interventions. PURPOSE: Reliability, minimal detectable change (MDC95), and 95% limits of agreement of TMJ examination procedures were investigated. METHODS: Occlusion (central incisor alignment, overjet, overbite), mandibular dynamics (maximal incisor opening, laterotrusion, protrusion active range of motion (AROM)), auscultation, tenderness, and joint play were measured on 50 asymptomatic adults (30 females), mean age 24.8. The inter-rater reliability assessment used an intra-session design. Participants returned 24-48 h later for intra-rater assessments. Intraclass correlation coefficients (ICC) and Kappa values were used to determine reproducibility. RESULTS: Intra-rater reliability for occlusion and AROM was ICC 3,1 ≥ 0.75, whereas interrater reliability was ICC 2,1 ≥ 0.68. Kappa values for inter-rater agreement of joint mobility was K = .18, whereas auscultation and palpation were K ≥ 0.48. Intra-rater Kappa values were ≥ 0.24, with lateral pterygoid region palpation having poor agreement. The MDC95 for occlusion was 1 mm, whereas AROM ranged from 3 to 6 mm. Mean AROM differences between raters were -1.16, -0.42, -0.18, and -0.8 mm for maximal incisor opening, left and right laterotrusion, and protrusion, respectively. CONCLUSION: AROM and occlusion measurements may be used with confidence; however, poor agreement for joint mobility measurements and lateral pterygoid region palpation must be recognized. When re-assessing measurements, a 3-6 and 1-mm change in AROM and occlusion, respectively, is required to be 95% certain change is not due to error. Future symptomatic population research is needed (250/250).

Pyogenic granuloma of the hard palate leading to alveolar cleft: a case report.

This case report describes a rare occurrence of pyogenic granuloma (PG) in the hard palate deviating from its typical gingival location that led to the formation of an alveolar cleft. The aggressive growth pattern of the lesion, with atypical progression from a pedunculated nodule to an alveolar cleft, raised concern. The diagnosis was based on magnetic resonance imaging and computed tomography findings, which revealed a tadpole-shaped lesion originating from the midline hard palate. The differential diagnosis included a minor salivary gland tumor. Surgical excision was performed under general anesthesia and resulted in a mucosal defect without nasolabial fistula formation or bone exposure. The palatal defect was packed with oxidized regenerated cellulose and closed with Vicryl Rapide sutures, both of which contributed to the patient's successful outcomes. Our comprehensive approach, extending across the stages of surgical planning, execution, and postoperative care, demonstrated the advantages of a multidisciplinary strategy for the accurate diagnosis and effective treatment of palatal PGs. This report makes a meaningful contribution to the existing literature on common oral lesions by emphasizing the importance of a broad differential diagnosis and a systematic approach to oral pathologies. It also raises clinical awareness of PGs with atypical presentations and the diagnostic challenge that they pose.

Neurexin 3 Regulates Synaptic Connections Between Central Amygdala Neurons and Excitable Cells of the Lateral Parabrachial Nucleus in Rats with Varicella Zoster Induced Orofacial Pain.

Introduction: Herpes Zoster in humans is the result of varicella zoster virus (VZV) infection. Injecting rats with varicella zoster virus produces pain similar to herpes zoster "shingles" pain in humans. . In a previous study, orofacial pain was induced by injecting the whisker pad of male rats with VZV and the pain response increased after attenuating neurexin 3 (Nrxn3) expression in the central amygdala. Neurons descend from the central amygdala to the lateral parabrachial nucleus and orofacial pain signals ascend to the lateral parabrachial nucleus. GABAergic neurons within the central amygdala regulate pain by inhibiting activity within the lateral parabrachial nucleus. Attenuating Nrxn3 expression in the central amygdala increased GABA release in the lateral parabrachial nucleus suggesting Nrxn3 controls pain by regulating GABA release. Nrxn3 can also control synaptic connections between neurons, and we hypothesized that Nrxn3 knockdown in the central amygdala would reduce the number of GABAergic synaptic connections in the lateral parabrachial nucleus and increase VZV associated pain. Methods: To test this idea, the number of synaptic connections between GABAergic cells of the central amygdala and excitatory or dynorphin positive neurons within the lateral parabrachial nucleus were quantitated after infusion of a virus expressing synaptophysin. Synaptophysin is a synaptic vesicle protein that labels neuronal synaptic connections. These connections were measured in rats with and without whisker pad injection of VZV and knockdown of Nrxn3 within the central amygdala. Orofacial pain was measured using a place escape avoidance paradigm. Results: GABAergic synaptic connections were reduced in the lateral parabrachial nucleus after Nrxn3 knockdown. Rats with a reduction in the number of connections had an increase in VZV associated orofacial pain. Immunostaining with the pain marker prodynorphin indicated that the reduction in GABAergic connections was primarily associated with prodynorphin positive neurons. Discussion: The results suggest Nrxn3 reduces VZV associated orofacial pain, in part, by enhancing synaptic connections between GABA cells of the central amygdala and pain neurons within the lateral parabrachial nucleus.

MicroRNA-6954-3p down-regulation contributes to orofacial neuropathic pain in mice via targeting voltage-gated sodium channel ß2 subunit protein.

The voltage-gated sodium channel ß2 subunit protein (SCN2B) plays a crucial role in neuropathic pain. However, the role and mechanisms of SCN2B in orofacial neuropathic pain are still unclear. This study aimed to investigate the upstream regulatory mechanisms of SCN2B in the trigeminal ganglion (TG) underlying orofacial neuropathic pain. Chronic constriction injury of the infraorbital nerve (CCI-ION) of mice was performed to establish the model of orofacial neuropathic pain. Von-Frey filament test was performed to detect the head withdrawal threshold (HWT) of mice. RT-qPCR, WB, FISH, and IF were used to detect the expression and distribution of SCN2B and miR-6954-3p in the TG of mice. A luciferase activity assay was carried out to prove the binding between SCN2B mRNA and miR-6954-3p. After the CCI-ION surgery, the levels of Scn2b mRNA and protein significantly increased and miR-6954-3p decreased in the TG of mice with decreasing HWT. IF staining revealed that SCN2B was expressed specifically in the TG neurons. Silencing SCN2B in the TG of CCI-ION mice significantly increased the HWT. Importantly, the 3' untranslated region (UTR) of Scn2b mRNA was proved to bind with miR-6954-3p. FISH and IF staining demonstrated that miR-6954-3p was expressed in TG neurons and co-expressed with SCN2B. Furthermore, intra-ganglionic injection of miR-6954-3p agomir into the TG of CCI-ION mice resulted in the down-regulation of SCN2B and increased the HWT. These findings suggest that the down-regulation of miR-6954-3p in the TG promotes orofacial neuropathic pain by promoting SCN2B expression following trigeminal nerve injury. PERSPECTIVE: This study points to the important role of SCN2B in orofacial neuropathic pain. Furthermore, miR-6954-3p is proven to regulate the expression of SCN2B by binding to the 3' UTR of Scn2b mRNA. These findings indicate that SCN2B and miR-6954-3p are potential therapeutic targets for the treatment of orofacial neuropathic pain.

Temporomandibular joint rehabilitative approaches for children and adolescents affected by juvenile idiopathic arthritis: A systematic review.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease of childhood, and temporomandibular joints (TMJs) are involved in 39%-78% of patients. AIM: The aim of this systematic review was to assess the effectiveness of conservative approaches in improving TMJ arthritis in children and adolescents affected by JIA. DESIGN: PubMed, Scopus, and Web of Science were systematically searched from the inception until February 25, 2024, to identify observational studies presenting participants with a diagnosis of JIA affecting the TMJ, rehabilitative approaches for TMJ arthritis as interventions, and clinical or radiological assessment of TMJ arthritis as outcome. RESULTS: Of 478 papers suitable for title/abstract screening, 13 studies were included. The studies evaluated the effectiveness of intra-articular (IA) corticosteroid (CS) injections, IA infliximab injections, arthrocentesis alone or in combination with IACS injections, occlusal splint, functional appliance, and physiotherapy. The effectiveness of IACS injections was shown in eight studies. IA infliximab injections did not appear to significantly improve TMJ arthritis. CONCLUSION: Results of this systematic review suggested that conservative treatments, especially IACS injections, might be effective in improving TMJ arthritis in patients affected by JIA. Further studies with a higher level of evidence and more representative samples should be conducted.

The test of masticating and swallowing solids (ToMaSS): An investigation of applicability and clinical utility in children with orofacial myofunctional disorders.

BACKGROUND: Orofacial myofunctional disorders (OMD) are often associated with limitations of oral ingestion of solid food. The Test of Masticating and Swallowing Solids (ToMaSS) is a simple diagnostic tool to assess and quantify oropharyngeal efficiency while eating a standardised cracker. OBJECTIVES: The objective of this study was to investigate the applicability and clinical utility of the ToMaSS in children with OMD. METHODS: In this case-control study, data were collected from 18 children between 4 and 11 years with confirmed OMD. Inter-rater reliability and age effects on the ToMaSS parameters were investigated and the specific performance profile of the OMD children was identified. RESULTS: Inter-rater reliability was excellent for the ToMaSS parameters 'bites' (ICC = .999), 'masticatory cycles' (ICC = .961), 'time'(ICC≧ .999) and good for 'number of swallows' (ICC = .810). 'Masticatory cycles' and 'time' decreased as a function of age with a significant difference in the 'number of masticatory cycles' between the youngest (4-6 years) and oldest (10-14 years) participants (p = .006, Z = -2.739). Deviations from normative data in at least one of the four ToMaSS parameters were found in 90% of the OMD children with 'bites', and 'masticatory cycles' predominantly corresponding to the performances expected in typically-developing children in younger age groups. CONCLUSIONS: The ToMaSS is a reliable diagnostic instrument and clinically useful to detect limited efficiency of oral solid bolus intake and specific impairments in chewing function and duration of food intake in children with OMD. Our data suggest that OMD is associated with delayed development of efficient solid bolus preparation.

Preliminary Assessment of an Ambulatory Device Dedicated to Upper Airway Muscle Training in Patients With Sleep Apnea: Proof-of-Concept Study.

BACKGROUND: Obstructive sleep apnea/hypopnea syndrome (OSAHS) is a prevalent condition affecting a substantial portion of the global population, with its prevalence increasing over the past 2 decades. OSAHS is characterized by recurrent upper airway (UA) closure during sleep, leading to significant impacts on quality of life and heightened cardiovascular and metabolic morbidity. Despite continuous positive airway pressure (CPAP) being the gold standard treatment, patient adherence remains suboptimal due to various factors, such as discomfort, side effects, and treatment unacceptability. OBJECTIVE: Considering the challenges associated with CPAP adherence, an alternative approach targeting the UA muscles through myofunctional therapy was explored. This noninvasive intervention involves exercises of the lips, tongue, or both to improve oropharyngeal functions and mitigate the severity of OSAHS. With the goal of developing a portable device for home-based myofunctional therapy with continuous monitoring of exercise performance and adherence, the primary outcome of this study was the degree of completion and adherence to a 4-week training session. METHODS: This proof-of-concept study focused on a portable device that was designed to facilitate tongue and lip myofunctional therapy and enable precise monitoring of exercise performance and adherence. A clinical study was conducted to assess the effectiveness of this program in improving sleep-disordered breathing. Participants were instructed to perform tongue protrusion, lip pressure, and controlled breathing as part of various tasks 6 times a week for 4 weeks, with each session lasting approximately 35 minutes. RESULTS: Ten participants were enrolled in the study (n=8 male; mean age 48, SD 22 years; mean BMI 29.3, SD 3.5 kg/m2; mean apnea-hypopnea index [AHI] 20.7, SD 17.8/hour). Among the 8 participants who completed the 4-week program, the overall compliance rate was 91% (175/192 sessions). For the tongue exercise, the success rate increased from 66% (211/320 exercises; SD 18%) on the first day to 85% (272/320 exercises; SD 17%) on the last day (P=.05). AHI did not change significantly after completion of training but a noteworthy correlation between successful lip exercise improvement and AHI reduction in the supine position was observed (Rs=-0.76; P=.03). These findings demonstrate the potential of the device for accurately monitoring participants' performance in lip and tongue pressure exercises during myofunctional therapy. The diversity of the training program (it mixed exercises mixed training games), its ability to provide direct feedback for each exercise to the participants, and the easy measurement of treatment adherence are major strengths of our training program. CONCLUSIONS: The study's portable device for home-based myofunctional therapy shows promise as a noninvasive alternative for reducing the severity of OSAHS, with a notable correlation between successful lip exercise improvement and AHI reduction, warranting further development and investigation.

The feasibility of visualizing and quantifying muscle changes in postoperative oral cancer patients using Quantitative Muscle Ultrasound (QMUS).

PURPOSE: Quantitative muscle ultrasound (QMUS) is a patient friendly tool for examining orofacial muscles. Resection of tissue can have an effect on the architecture and function of these muscles. The aim of this study is to investigate the feasibility of visualizing and quantifying muscle changes in postoperative oral cancer patients and to relate the findings to tumor and patient characteristics. METHODS: Adult patients with a resected first primary pT1 or T2 oral squamous cell carcinoma, at least one year post operatively, where included. Ultrasound data were collected of the geniohyoid muscle, digastric muscles, masseter muscle, transverse muscle and genioglossus muscle. Ultrasound images were labeled as clearly visible, questionable or unclear. Of the clear muscles, echogenicity and muscle thickness were measured. RESULTS: 37 patients were included. The masseter muscle was clearly visible in all ultrasound images, both intrinsic tongue muscles had the lowest visibility (45.9%). There was a significant correlation between visibility and tumor localization for the genioglossus (p = 0.029). Age correlated with the visibility of the genioglossus muscle, BMI with the genioglossus and transverse muscles. Echogenicity and muscle thickness of the clearly identified muscles did not differ from normative values. CONCLUSION: QMUS of orofacial muscles is feasible in postoperative oral cancer patients with relatively small tumor sizes. Tongue resections negatively affected the visibility of the two intrinsic tongue muscles. These preliminary results for particular muscles indicate that the use of ultrasound might be promising in oral cancer patients to help determine targeted goals in post-operative rehabilitation.

Assessment of sleep quality in patients with orofacial pain and headache complaints: A polysomnographic study.

BACKGROUND: Sleep is a physiological function essential for survival, recovery, tissue repair, memory consolidation, and brain function. Pain is also an indispensable aspect of human life. The coexistence of sleep disorders and pain is often described in the literature, yet it is critical to define sleep not only subjectively but also using objective instrumental methods, such as polysomnography, that provide data on sleep quality. OBJECTIVES: The aim of the study was to determine the relationship between orofacial pain (OFP), headache (HA) and sleep quality using subjective and objective sleep quality assessment methods. Additionally, we aimed to explore whether poor sleep quality was related to OFP and HA alone or was influenced by the coexistence of psycho-emotional factors such as depression, anxiety and stress. MATERIAL AND METHODS: A single-night video-polysomnography was performed on patients from the Outpatient Clinic for Temporomandibular Disorders at Wroclaw Medical University, Poland, who had been diagnosed with OFP and HA. Additionally, questionnaires were employed to assess sleep quality, pain, HA, and the psycho-emotional state. RESULTS: There was no statistically significant relationship between the severity of OFP and HA and polysomnographic sleep quality parameters. On the other hand, the quality of sleep as determined by questionnaire studies correlated markedly with the severity of experienced pain. The severity of pain was found to be significantly correlated with depression, anxiety and perceived stress scores. CONCLUSIONS: The psycho-emotional aspects are of critical importance in the perception of OFP and HA. They can be associated with worsened subjective sleep quality, insomnia or daytime sleepiness. Therefore, the treatment of such patients must be preceded by a comprehensive assessment of their psychoemotional state, as anxiety, stress and depression can significantly influence the course of the disease and the response to treatment procedures.

Kinesio Taping as an alternative therapy for limited mandibular mobility with pain in female patients with temporomandibular disorders: A randomized controlled trial.

BACKGROUND: Kinesio Taping (KT) is a non-invasive therapy commonly used in physiotherapy (PT). However, the available data on its effectiveness in patients with symptomatic temporomandibular disorders (TMD) remains scarce and contradictory. OBJECTIVES: The aim of the study was to evaluate the analgesic and myorelaxant effects of KT in TMD patients with limited mandibular mobility. MATERIAL AND METHODS: A single-blind randomized controlled trial was conducted among female patients aged 20-45 years with Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) group Ib, using a parallel group design and equal randomization (1:1). All patients underwent surface electromyography (sEMG) of the masseter muscle (MAS), pain intensity was assessed using a Numeric Rating Scale (NRS), and temporomandibular joint mobility was measured before and after 6 and 12 days of treatment. The Perceived Stress Scale (PSS-10) questionnaire was administered on the first and last days of treatment. Statistical analysis was performed using analysis of variance (ANOVA). Mauchly's sphericity test determined changes over time and between groups for variables with a normal distribution. Bonferroni's correction was used for post hoc multiple comparisons. Variables with a non-normal distribution were analyzed using the nparLD package and multiple comparison post hoc test, while correlations were assessed using Spearman's coefficient. RESULTS: Each treatment had a significant effect on the bioelectrical sEMG parameters (p = 0.05). Kinesio Taping had a superior analgesic effect compared to the controls (p < 0.001). The combination of KT with therapeutic exercise (TE) proved to be a more effective therapy for improving the maximal mouth opening (MMO) and reducing perceived stress than monotherapy (p < 0.001). Minimally significant clinical differences were observed for sEMG, MMO and PSS-10 parameters after both therapies. CONCLUSIONS: Kinesio Taping combined with TE may be considered an effective complementary noninvasive treatment modality for TMD, either as a stand-alone or as part of the therapeutic process in patients experiencing pain and limited mandibular ROM. Additionally, the use of KT and TE was found to have a beneficial effect on perceived stress levels.

Photobiomodulation Therapy in the Management of Late Complications After Facial Filling.

The aim of the present study is to report a clinical case of a patient diagnosed with a late adverse reaction to the injection of filler material - persistent and intermittent delayed swelling (PIDS) - in which photobiomodulation therapy (PBMT) with low-power laser was used for edema reduction. This is an observational, descriptive, and retrospective work of a case report. The female patient, aged 73 years old, had undergone dermal filler six years before and complained of increased volume in the face region (glabellar region, labiomental sulcus, and nasolabial folds) and was submitted to ultrasound and anatomopathological analysis. PBMT using a low-power laser (660 nm and 808 nm, simultaneous irradiation, in contact, 2 J/point, 100 mW) proved to be effective for the non-invasive approach of late adverse reaction to dermal filler, such as PIDS, a common complication related to the use of dermal fillers.

Clinician and patient experiences of managing and living with oral and dental manifestations of scleroderma: A scoping review.

Oral and dental manifestations of scleroderma are extremely common, yet they are often overlooked within rheumatology and poorly understood within dentistry. Previous research has indicated the need to understand the oral and dental experiences of people living with scleroderma and those involved in their care. This scoping review aims, for the first time, to comprehensively map what is known regarding the identification and management of oral and dental manifestations of scleroderma, how these are experienced by people living with scleroderma, and to explore key characteristics of barriers and enablers to good oral and dental care in scleroderma. A scoping review was conducted using six databases (Embase, PubMed, PsychINFO, ASSIA, Scopus and SSCI), according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses - extension for Scoping Review. Grey literature was also included. Studies were eligible for inclusion if the full text and abstract were available in English, published between 2002 and 2022, and focused on the concept of oral and dental care in adults with scleroderma, either relating to identification and management, enablers and barriers to best practice, or patient experiences and well-being. Qualitative research which seeks to understand patients' lived experiences was a notable gap in the literature. Similarly, there was a significant lack of focus on the oral and dental manifestations of scleroderma in rheumatology. Three key features were identified which would facilitate best practice in research and clinical contexts: the necessity of multidisciplinary care; the necessity of centralising patient experience; and the necessity of mitigating barriers to dental care. We conclude that increased awareness of scleroderma within dentistry and streamlining referral procedures between the disciplines of dentistry and rheumatology, to enable the early identification and management of scleroderma, are crucial.

Prevalence of Temporomandibular Disorders (TMD) in Dental Patients at a Specialized Regional Medical Center in Italy.

BACKGROUND AND AIM: This study aimed to evaluate the prevalence of temporomandibular disorders (TMDs) in a sample of general dental patients seeking dental treatments in a northeastern Italian university clinic. MATERIALS AND METHODS: Records of all patients presented for the first time to the dental division of Maggiore Hospital, Italy, between January 1, 2016, and December 31, 2017, were collected. Patients comprised those presenting to the dental clinics for non-TMD complaints, who, upon general examination, were found to have TMD signs and were referred for TMD evaluation. Data were extracted and analyzed, retrospectively. The prevalence of TMDs, age, gender, signs, and symptoms were evaluated. RESULTS: Out of the 18,774 patients studied, 284 had signs of TMD. Women predominance was evident (73%), and patients aged 45-50 were the most frequent sub-population within the TMD population. Clicking was the most commonly present symptom (26.8%), and arthralgia was most commonly diagnosed among this sample (30.7%). A considerable number of patients suffered from muscular disease (myalgia and myofascial pain with 10.1% and 20.7% of the patients, respectively). Significant associations were found among those with myofascial pain on the one hand and degenerative disease and disc displacement with reduction, on the other hand. Furthermore, disc displacement with reduction on one side was associated with displacement without reduction on the other side. CONCLUSION: A considerable number of patients presenting with dental complaints may have asymptomatic TMDs. This highlights the importance of systematic screening of dental patients for TMDs as part of general assessment.

A novel IRF6 gene mutation impacting the regulation of TGFß2-AS1 in the TGFß pathway: A mechanism in the development of Van der Woude syndrome.

Several mutations in the IRF6 gene have been identified as a causative link to VWS. In this investigation, whole-exome sequencing (WES) and Sanger sequencing of a three-generation pedigree with an autosomal-dominant inheritance pattern affected by VWS identified a unique stop-gain mutation-c.748C>T:p.R250X-in the IRF6 gene that co-segregated exclusively with the disease phenotype. Immunofluorescence analysis revealed that the IRF6-p.R250X mutation predominantly shifted its localization from the nucleus to the cytoplasm. WES and protein interaction analyses were conducted to understand this mutation's role in the pathogenesis of VWS. Using LC-MS/MS, we found that this mutation led to a reduction in the binding of IRF6 to histone modification-associated proteins (NAA10, SNRPN, NAP1L1). Furthermore, RNA-seq results show that the mutation resulted in a downregulation of TGFß2-AS1 expression. The findings highlight the mutation's influence on TGFß2-AS1 and its subsequent effects on the phosphorylation of SMAD2/3, which are critical in maxillofacial development, particularly the palate. These insights contribute to a deeper understanding of VWS's molecular underpinnings and might inform future therapeutic strategies.

COVID-19 vaccine and non-syndromic orofacial clefts in five arab countries. A case-control study.

OBJECTIVES: Risk factors for non-syndromic orofacial cleft (NSOFCs) include genetic profile and environmental exposure to medication and illnesses during pregnancy. We assessed the association between the COVID-19 vaccination and the incidence of NSOFC across five Middle Eastern countries. MATERIALS AND METHODS: This multi-country, hospital-based, case-control study included infants with NSOFCs whose first 3 intrauterine months coincided with the time when pregnant women were allowed to receive COVID-19 vaccination in the countries participating in the study. Newborns with NSOFCs were examined for cleft type and their parents were interviewed for maternal exposures and COVID-19 vaccination. Controls were newborns matched to cases in gender and setting. RESULTS: The study recruited 977 (348 children with NSOFCs and 629 controls). Maternal use of nicotine (Adjusted Odds Ratio (AOR): 2.437; P = 0.044) and family history of NSOFC (AOR: 11.059; P < 0.001) increased significantly the AOR of having a child with NSOFC. On the other hand, COVID-19 vaccine administration to pregnant mothers have significantly decreased the AOR of having a child with NSOFC (AOR: 0.337; P = 0.006). CONCLUSION: This study suggests that COVID-19 vaccination is not related to NSOFC and might protect against having a child affected with such a congenital anomaly. CLINICAL RELEVANCE: The finding of this study is important for healthcare providers for considering COVID-19 vaccination for pregnant woman. Clear communication and education about the potential risks and benefits would be crucial for informed decision-making. The study's results would directly impact pregnant individuals, as they would need accurate information to make informed decisions about their health and the health of their infants.

Rare variants analyses suggest novel cleft genes in the African population.

Non-syndromic orofacial clefts (NSOFCs) are common birth defects with a complex etiology. While over 60 common risk loci have been identified, they explain only a small proportion of the heritability for NSOFCs. Rare variants have been implicated in the missing heritability. Thus, our study aimed to identify genes enriched with nonsynonymous rare coding variants associated with NSOFCs. Our sample included 814 non-syndromic cleft lip with or without palate (NSCL/P), 205 non-syndromic cleft palate only (NSCPO), and 2150 unrelated control children from Nigeria, Ghana, and Ethiopia. We conducted a gene-based analysis separately for each phenotype using three rare-variants collapsing models: (1) protein-altering (PA), (2) missense variants only (MO); and (3) loss of function variants only (LOFO). Subsequently, we utilized relevant transcriptomics data to evaluate associated gene expression and examined their mutation constraint using the gnomeAD database. In total, 13 genes showed suggestive associations (p = E-04). Among them, eight genes (ABCB1, ALKBH8, CENPF, CSAD, EXPH5, PDZD8, SLC16A9, and TTC28) were consistently expressed in relevant mouse and human craniofacial tissues during the formation of the face, and three genes (ABCB1, TTC28, and PDZD8) showed statistically significant mutation constraint. These findings underscore the role of rare variants in identifying candidate genes for NSOFCs.