Impacts of Skeletal Anterior Open Bite Malocclusion on Speech

Introduction: Articulation problems are seen in 80% to 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 /ʃ/), and affricate (/tʃ/) 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 < .01) increase in the centroid frequency (M1) was seen in the /k/, /t/, /tʃ/, 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 distortions 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

Intermittent Induction of HIF-1α Produces Lasting Effects on Malignant Progression Independent of Its Continued Expression

<div><p>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 <i>HIF1A</i> 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 β-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.</p></div

Intermittent induction resulted in loss of of HIF1α(PP) expression.

<p>(A) Intermittent induction involves the administration of tetracycline into cell culture each week on day 1 and removal on day 4 each week for a total of 8 weeks. Afterwards, cells were allowed to expand for further analyses and injections. (B) After intermittent induction (8W), different types of cells as indicated were induced again with tetracycline for 2 days and analyzed by Western blotting in reference to those without intermittent induction (0W). (C) Cell proliferation was determined by cell counting after intermittent induction. ***, <i>p</i>-value < 0.001.</p

U-2 OS cells acquired tumorigenicity after intermittent induction of HIF1α(PP).

<p>(A) Tumor incidence is shown in 6 NSG mice after bilateral, subcutaneous injections of the 8-week HIF1α(PP) and HIF2α(PP) cells. (B) Only injections of the HIF1α(PP) cells produced tumors, as indicated by arrowheads. Scale bar, 1 cm. (C) Tumor volume was calculated based on measurements and plotted as a function of time. ***, <i>p</i>-value < 0.001. (D) Hematoxylin and eosin staining of the tumor specimens reveals invasion of the dermal layer (<i>a</i>), numerous mitoses (arrowheads) (<i>b</i>), necrosis (N) (<i>c</i>), and invasion into the striated muscle layer (<i>d</i>). Scale bar, 100 μm.</p

CIDE protein expression in adipose tissue and liver from CON-SED, CON-WR, HFD-SED, and HFD-WR mice is related to measures of adiposity and insulin resistance.

<p>*Significant Pearson product-moment correlation coefficient, P value is ≤.05.</p><p>Tissues from 20 mice were used for the analysis.</p><p>CIDE protein expression in adipose tissue and liver from CON-SED, CON-WR, HFD-SED, and HFD-WR mice is related to measures of adiposity and insulin resistance.</p

The effects of a high fat diet and voluntary wheel running on insulin-assisted glucose tolerance.

<p>Mice received a simultaneous injection of glucose (2 mg/Kg) and insulin (2 U/Kg), and glucose was measured in blood collected from the tail vein at 0, 20, 40, and 60 minutes following the injection (Panel A). The area under the insulin-assisted glucose tolerance curve (AUC) was calculated from blood glucose values during the IAGTT (Panel B).*Denotes statistically significant difference from all other groups by Fisher’s LSD post-hoc test. The number of mice per group is 6–9.</p

Tetracycline regulation of HIF1α(PP) and HIF2α(PP) expression and transcriptional activity.

<p>(A) Tetracycline regulation is diagrammed where the addition of tetracycline (tet) results in dissociation of tetracycline repressor (TetR) from the tetracycline operon (TetO) and, in turn, gene activation. (B) Western blot analysis of transduced cell types, as indicated, for the expression of HIF1α(PP) and HIF2α(PP) after 2-day treatment with tetracycline. (C) Transcriptional activities of HIF1α(PP) and HIF2α(PP) were tested in a reporter assay in reference to β-galactosidase (β-gal). ***, <i>p</i>-value < 0.001. (D, E) The expression of HIF target genes (<i>PGK1</i>, <i>CA9</i>, <i>VEGFA</i>, and <i>LOX</i>) was analyzed in specified cell lines by using real-time PCR after 2-day treatment with tetracycline.</p