Browsing by Author "Moss, Kevin"

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    Clonal hematopoiesis driven by mutated DNMT3A promotes inflammatory bone loss
    (Elsevier, 2024) Wang, Hui; Divaris, Kimon; Pan, Bohu; Li, Xiaofei; Lim, Jong-Hyung; Saha, Gundappa; Barovic, Marko; Giannakou, Danai; Korostoff, Jonathan M.; Bing, Yu; Sen, Souvik; Moss, Kevin; Wu, Di; Beck, James D.; Ballantyne, Christie M.; Natarajan, Pradeep; North, Kari E.; Netea, Mihai G.; Chavakis, Triantafyllos; Hajishengallis, George; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
    Clonal hematopoiesis of indeterminate potential (CHIP) arises from aging-associated acquired mutations in hematopoietic progenitors, which display clonal expansion and produce phenotypically altered leukocytes. We associated CHIP-DNMT3A mutations with a higher prevalence of periodontitis and gingival inflammation among 4,946 community-dwelling adults. To model DNMT3A-driven CHIP, we used mice with the heterozygous loss-of-function mutation R878H, equivalent to the human hotspot mutation R882H. Partial transplantation with Dnmt3aR878H/+ bone marrow (BM) cells resulted in clonal expansion of mutant cells into both myeloid and lymphoid lineages and an elevated abundance of osteoclast precursors in the BM and osteoclastogenic macrophages in the periphery. DNMT3A-driven clonal hematopoiesis in recipient mice promoted naturally occurring periodontitis and aggravated experimentally induced periodontitis and arthritis, associated with enhanced osteoclastogenesis, IL-17-dependent inflammation and neutrophil responses, and impaired regulatory T cell immunosuppressive activity. DNMT3A-driven clonal hematopoiesis and, subsequently, periodontitis were suppressed by rapamycin treatment. DNMT3A-driven CHIP represents a treatable state of maladaptive hematopoiesis promoting inflammatory bone loss.
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    Impacts of Skeletal Anterior Open Bite Malocclusion on Speech
    (Sage, 2022) Keyser, Mary Morgan Bitler; Lathrop, Hillary; Jhingree, Samantha; Giduz, Natalie; Bocklage, Clare; Couldwell, Sandrine; Oliver, Steven; Moss, Kevin; Frazier-Bowers, Sylvia; Phillips, Ceib; Turvey, Timothy; Blakey, George; White, Ray; White, Raymond P., Jr.; McMichael, Dalton L.; Zajac, David; Mielke, Jeff; Jacox, Laura Anne; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
    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.
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    Orthognathic speech pathology: impacts of Class III malocclusion on speech
    (Oxford University Press, 2022) Lathrop-Marshall, Hillary; Keyser, Mary Morgan B.; Jhingree, Samantha; Giduz, Natalie; Bocklage, Clare; Couldwell, Sandrine; Edwards, Haley; Glesener, Tim; Moss, Kevin; Frazier-Bowers, Sylvia; Phillips, Ceib; Turvey, Timothy; Blakey, George; White, Ray; Mielke, Jeff; Zajac, David; Jacox, Laura A.; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
    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.