A novel lncRNA-mediated epigenetic regulatory mechanism in periodontitis.

Periodontitis is a highly prevalent chronic inflammatory disease with an exaggerated host immune response, resulting in periodontal tissue destruction and potential tooth loss. The long non-coding RNA, LncR-ANRIL, located on human chromosome 9p21, is recognized as a genetic risk factor for various conditions, including atherosclerosis, periodontitis, diabetes, and cancer. LncR-APDC is an ortholog of ANRIL located on mouse genome chr4. This study aims to comprehend the regulatory role of lncR-APDC in periodontitis progression. Our experimental findings, obtained from lncR-APDC gene knockout (KO) mice with induced experimental periodontitis (EP), revealed exacerbated bone loss and disrupted pro-inflammatory cytokine regulation. Downregulation of osteogenic differentiation occurred in bone marrow stem cells harvested from lncR-APDC-KO mice. Furthermore, single-cell RNA sequencing of periodontitis gingival tissue revealed alterations in the proportion and function of immune cells, including T and B cells, macrophages, and neutrophils, due to lncR-APDC silencing. Our findings also unveiled a previously unidentified epithelial cell subset that is distinctively presenting in the lncR-APDC-KO group. This epithelial subset, characterized by the positive expression of Krt8 and Krt18, engages in interactions with immune cells through a variety of ligand-receptor pairs. The expression of Tff2, now recognized for its role in chronic inflammatory conditions, exhibited a notable increase across various tissue and cell types in lncR-APDC deficient mice. Additionally, our investigation revealed the potential for a direct binding interaction between lncR-APDC and Tff2. Intra-gingival administration of AAV9-lncR-APDC was shown to have therapeutic effects in the EP model. In conclusion, our results suggest that lncR-APDC plays a critical role in the progression of periodontal disease and holds therapeutic potential for periodontitis. Furthermore, the presence of the distinctive epithelial subpopulation and significantly elevated Tff2 levels in the lncR-APDC-silenced EP model offer new perspectives on the epigenetic regulation of periodontitis pathogenesis.

Impacts of Skeletal Anterior Open Bite Malocclusion on Speech.

Introduction: Articulation problems are seen in 80-90% of dentofacial deformity (DFD) subjects compared with 5% of the general population, impacting communication and quality of life, but the causal link is unclear. We hypothesize there are both qualitative (perceptual) and quantitative (spectral) differences in properties of stop (/t/ or /k/), fricative (/s/ or /∫/), and affricate (/t∫/) consonant sounds and that severity of anterior open bite (AOB) jaw disharmonies correlates with degree of speech abnormality. Methods: To test our hypotheses, surgical orthodontic records and audio recordings were collected from DFD patients (n=39 AOB, 62 controls). A speech pathologist evaluated subjects and recordings were analyzed using spectral moment analysis (SMA) to measure sound frequency distortions. Results: Perceptually, there is a higher prevalence of auditory and visual speech distortions in AOB DFD patients when compared to controls. Quantitatively, a significant (p<0.01) increase in the centroid frequency (M1) was seen in the /k/, /t/, /t∫/, and /s/ sounds of AOB subjects compared to the controls. Using linear regression, correlations between AOB skeletal severity and spectral distortion were found for /k/ and /t/ sounds. Conclusions: A higher prevalence of qualitative distortion and significant quantitative spectral distortions in consonant sounds were seen in AOB patients compared to controls. Additionally, severity of skeletal AOB is correlated with degree of distortion for consonant sounds. These findings provide insight into how the surgical and/or orthodontic treatment of AOB may impact speech.

Surgical Reduction of Chronic Bilateral Traumatic Dislocation of the Mandibular Condyles With Erosion of the Middle Fossa Floor: Case Report With Surgical Video.

BACKGROUND: Dislocation of the mandibular condyle (MC) is not a common condition, but when a traumatic case involves erosion of the middle fossa floor, it becomes a much more complicated and even rarer pathology. OBJECTIVE: To describe the management of traumatic dislocation of the MCs with erosion of the middle fossa floor. We provide a step-by-step surgical video demonstrating reestablishment of the condylar position and occlusion. METHODS: A 65-yr-old woman with rheumatoid arthritis presented after a ground-level fall. She was admitted to the intensive care unit with simultaneous complex medical conditions, intubated, and medically treated for over a month. She was seen in outpatient follow-up 2 mo later and noted to have an anterior open bite and bilateral temporomandibular joint pain. Computed tomography of the face showed bilateral dislocation of the MCs with erosion of the middle fossa floor. RESULTS: Open surgical treatment with bilateral eminectomies was performed to obtain adequate reduction, involving a multidisciplinary team including neurosurgery, oral-maxillofacial surgery, and otolaryngological surgery. She did well postoperatively. CONCLUSION: Multiple factors predispose a patient to MC dislocation, but we believe the catalyst in this case was significant manipulation of the jaw during endotracheal intubation. A chronic postoperative open bite can lead to much more difficult treatment, given bony erosion and fibrotic tissue formation. This case highlights the challenges of diagnosis and treatment of a bilateral traumatic dislocation and provides a surgical video reference description of repair and resolution.

Orthognathic speech pathology: impacts of Class III malocclusion on speech.

INTRODUCTION: Patients with dentofacial disharmonies (DFDs) seek orthodontic care and orthognathic surgery to address issues with mastication, esthetics, and speech. Speech distortions are seen 18 times more frequently in Class III DFD patients than the general population, with unclear causality. We hypothesize there are significant differences in spectral properties of stop (/t/ or /k/), fricative (/s/ or /ʃ/), and affricate (/tʃ/) consonants and that severity of Class III disharmony correlates with the degree of speech abnormality. METHODS: To understand how jaw disharmonies influence speech, orthodontic records and audio recordings were collected from Class III surgical candidates and reference subjects (n = 102 Class III, 62 controls). A speech pathologist evaluated subjects and recordings were quantitatively analysed by Spectral Moment Analysis for frequency distortions. RESULTS: A majority of Class III subjects exhibit speech distortions. A significant increase in the centroid frequency (M1) and spectral spread (M2) was seen in several consonants of Class III subjects compared to controls. Using regression analysis, correlations between Class III skeletal severity (assessed by cephalometric measures) and spectral distortion were found for /t/ and /k/ phones. CONCLUSIONS: Class III DFD patients have a higher prevalence of articulation errors and significant spectral distortions in consonants relative to controls. This is the first demonstration that severity of malocclusion is quantitatively correlated with the degree of speech distortion for consonants, suggesting causation. These findings offer insight into the complex relationship between craniofacial structures and speech distortions.

Effects of a High Fat Diet and Voluntary Wheel Running Exercise on Cidea and Cidec Expression in Liver and Adipose Tissue of Mice.

Cidea and Cidec play an important role in regulating triglyceride storage in liver and adipose tissue. It is not known if the Cidea and Cidec genes respond to a high fat diet (HFD) or exercise training, two interventions that alter lipid storage. The purpose of the present study was to determine the effect of a HFD and voluntary wheel running (WR) on Cidea and Cidec mRNA and protein expression in adipose tissue and liver of mice. A HFD promoted a significant increase in Cidea and Cidec mRNA levels in adipose tissue and liver. The increase in Cidea and Cidec mRNAs in adipose tissue and liver in response to a HFD was prevented by WR. Similar to the changes in Cidea mRNA, Cidea protein levels in adipose tissue significantly increased in response to a HFD, a process that was, again, prevented by WR. However, in adipose tissue the changes in Cidec mRNA did not correspond to the changes in Cidec protein levels, as a HFD decreased Cidec protein abundance. Interestingly, in adipose tissue Cidea protein expression was significantly related to body weight (R=.725), epididymal adipose tissue (EWAT) mass (R=.475) and insulin resistance (R=.706), whereas Cidec protein expression was inversely related to body weight (R=-.787), EWAT mass (R=-.706), and insulin resistance (R=-.679). Similar to adipose tissue, Cidea protein expression in liver was significantly related to body weight (R=.660), EWAT mass (R=.468), and insulin resistance (R=.599); however, unlike adipose tissue, Cidec protein levels in liver were not related to body weight or EWAT mass and only moderately associated with insulin resistance (R=-.422, P=0.051). Overall, our findings indicate that Cidea is highly associated with adiposity and insulin resistance, whereas Cidec is related to insulin sensitivity. The present study suggests that Cide proteins might play an important functional role in the development of obesity, hepatic steatosis, as well as the pathogenesis of type 2 diabetes.

Intermittent induction of HIF-1α produces lasting effects on malignant progression independent of its continued expression.

Dysregulation of hypoxia-inducible transcription factors HIF-1α and HIF-2α correlates with poor prognosis in human cancers; yet, divergent and sometimes opposing activities of these factors in cancer biology have been observed. Adding to this complexity is that HIF-1α apparently possesses tumor-suppressing activities, as indicated by the loss-of-function mutations or even homozygous deletion of HIF1A in certain human cancers. As a step towards understanding this complexity, we employed 8-week intermittent induction of a stable HIF-1α variant, HIF1α(PP), in various cancer cell lines and examined the effects on malignant progression in xenografts of immunocompromised mice in comparison to those of HIF2α(PP). Although 8-week treatment led to eventual loss of HIF1α(PP) expression, treated osteosarcoma U-2 OS cells acquired tumorigenicity in the subcutaneous tissue. Furthermore, the prior treatment resulted in widespread invasion of malignant glioma U-87 MG cells in the mouse brain and sustained growth of U-118 MG glioma cells. The lasting effects of HIF-1α on malignant progression are specific because neither HIF2α(PP) nor ß-galactosidase yielded similar effects. By contrast, transient expression of HIF1α(PP) in U-87 MG cells or constitutive expression of HIF1α(PP) but not HIF2α(PP) in a patient-derived glioma sphere culture inhibited tumor growth and spread. Our results indicate that intermittent induction of HIF-1α produces lasting effects on malignant progression even at its own expense.

Regression of cerebral arteriovenous malformation in the puerperium.

Spontaneous regression of a cerebral arteriovenous malformation (AVM) is a rare occurrence. The authors describe a patient presenting with a ruptured AVM with a feeding artery aneurysm during second trimester of pregnancy. The feeding artery with aneurysm was clipped and the hematoma removed. The AVM subsequently spontaneously regressed by serial angiography during the postpartum period. The authors believe this is the first reported case of spontaneous regression of cerebral AVM early after pregnancy. The dramatic regression noted in the postpartum period in this case suggests the particular significance of hormonal factors in the dynamics of growth and rupture of an AVM.