135 results on '"Connor NP"'
Search Results
2. Association of extraesophageal reflux disease and sinonasal symptoms: prevalence and impact on quality of life.
- Author
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Pasic TR, Palazzi-Churas KL, Connor NP, Cohen SB, and Leverson GE
- Published
- 2007
3. Discoordination of laryngeal and respiratory movements in aged rats.
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Nagai H, Ota F, Konopacki R, Connor NP, Nagai, Hiromi, Ota, Fumikazu, Konopacki, Richard, and Connor, Nadine P
- Abstract
Voice and swallowing actions require the coordination of multiple motor systems, and this coordination may be impaired with aging. Although recent work has reported impairments in age-related laryngeal kinematics in rats, the temporal relationship of laryngeal excursions to the respiratory cycle is unknown. The goal of this study was to assess laryngeal-respiratory coordination by examining temporal interrelationships between change in laryngeal aperture and chest wall movement during quiet breathing in a rat model. Glottal images were recorded, digitized, and synchronized with respiratory signals, and temporal features were measured. In the young animals, glottal opening began before the onset of inspiration, and glottal and respiratory cycles were phasic and stereotypic. In old animals, however, inspiration often began during the glottal closing phase, and both respiratory signals were asymmetric. Discoordination of laryngeal and respiratory motor actions associated with aging may be caused by a generalized decline in sensorimotor cranial functions and may contribute to age-related swallowing and communication impairment. [ABSTRACT FROM AUTHOR]
- Published
- 2005
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4. Endolymphatic sac decompression as a treatment for Meniere's disease.
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Durland WF Jr., Pyle GM, and Connor NP
- Published
- 2005
5. Therapeutic potential of growth factors for aging voice.
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Hirano S, Bless DM, del Río AM, Connor NP, Ford CN, Hirano, Shigeru, Bless, Diane M, del Río, Alejandro Muñoz, Connor, Nadine P, and Ford, Charles N
- Abstract
Objectives/hypothesis: It has been reported that in aged vocal folds, dense collagen deposition takes place and hyaluronic acid decreases in the lamina propria, which are thought to contribute to the vocal problems occurring with age (presbyphonia). To restore aged vocal folds to their younger state, it seems crucial to address these age-related lamina propria changes. Intervention that might increase hyaluronic acid and decrease collagen would appear to be a potentially useful approach. The present study examined the effects of growth factors on aged fibroblasts in terms of the production of hyaluronic acid and collagen type I.Study Design: In vitro study using animal model.Methods: Fibroblasts were harvested from young and aged rat vocal folds and cultured with or without hepatocyte growth factor and/or basic fibroblast growth factor at different concentrations. Subsequently, the production of hyaluronic acid and collagen type I was examined in the supernatant culture media using enzyme-linked immunosorbent assay.Results: Aged fibroblasts produced less hyaluronic acid than younger fibroblasts. When aged and young fibroblasts were cultured with basic fibroblast growth factor, hyaluronic acid production increased and collagen type I production decreased regardless of the concentration, whereas the effects of hepatocyte growth factor appeared to vary with concentration. The basic fibroblast growth factor also was associated with stimulation of growth of aged fibroblasts.Conclusion: The present results suggest that growth factors, especially basic fibroblast growth factor, may have therapeutic potential in restoration of aged vocal fold. [ABSTRACT FROM AUTHOR]- Published
- 2004
6. Developmental deglutition and intrinsic tongue muscle maturation phenotypes in the Ts65Dn mouse model of Down syndrome.
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Glass TJ, Chatwin BA, Fisher EH, Hang KK, Yang Q, Brutto R, Waghray R, and Connor NP
- Abstract
Introduction: Down syndrome (DS) is associated with difficulties with feeding during infancy and childhood. Weaning, or transitioning from nursing to independent deglutition, requires developmental progression in tongue function. However, little is known about whether postnatal tongue muscle maturation is impacted in DS. This study tested the hypothesis that the Ts65Dn mouse model of DS has developmental delays in deglutition, comprised of differences in eating and drinking behaviors relative to euploid controls, coinciding with atypical measures of intrinsic tongue muscle microanatomy., Methods: The Ts65Dn mouse model of DS and euploid controls were evaluated at 7 days of age (p7; nursing), p21 (weaning), and p35 (mature deglutition) (n = 13-18 mice per group). Eating behavior, drinking behavior, and body weight changes were quantified in p21 and p35 mice through the use of automated monitoring over 24 h. Intrinsic tongues of mice at all three ages were sectioned and stained to permit quantification of the sizes of the four major intrinsic tongue muscles. Transverse intrinsic tongue muscles were evaluated for myofiber size (average myofiber cross sectional area (CSA) of all fibers, MyHC2a fibers, MyHC 2b fibers, and minimum Feret fiber diameter), and percentage of MyHC isoforms (%MyHC2a + fibers, and %MyHC 2b + fibers) in anterior, middle, and posterior regions., Results: Ts65Dn showed significant differences from euploid in deglutition measures. Compared to euploid, Ts65Dn also showed differences in intrinsic tongue muscle microanatomy and biology. Specifically, Ts65Dn intrinsic tongues had smaller transverse muscle myofiber size measures than control in the anterior and middle tongue, but not in the posterior tongue., Conclusion: Differences in intrinsic tongue muscles coincide with feeding phenotypes in the Ts65Dn mouse model of DS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Glass, Chatwin, Fisher, Hang, Yang, Brutto, Waghray and Connor.)
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- 2024
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7. Cellular and transcriptomic changes by the supplementation of aged rat serum in human pluripotent stem cell-derived myogenic progenitors.
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Tey SR, Anderson RS, Yu CH, Robertson S, Kletzien H, Connor NP, Tanaka K, Ohkawa Y, and Suzuki M
- Abstract
Introduction: The changing composition of non-cell autonomous circulating factors in blood as humans age is believed to play a role in muscle mass and strength loss. The mechanisms through which these circulating factors act in age-related skeletal muscle changes is not fully understood. In this study, we used human myogenic progenitors derived from human pluripotent stem cells to study non-cell autonomous roles of circulating factors during the process of myogenic differentiation., Methods: Myogenic progenitors from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) were supplemented with serum samples from aged or young Fischer 344 × Brown Norway F1-hybrid rats. The effect of aged or young serum supplementation on myogenic progenitor proliferation, myotube formation capacity, differentiation, and early transcriptomic profiles were analyzed., Results: We found that aged rat serum supplementation significantly reduced cell proliferation and increased cell death in both ESC- and iPSC-derived myogenic progenitors. Next, we found that the supplementation of aged rat serum inhibited myotube formation and maturation during terminal differentiation from progenitors to skeletal myocytes when compared to the cells treated with young adult rat serum. Lastly, we identified that gene expression profiles were affected following serum supplementation in culture., Discussion: Together, aged serum supplementation caused cellular and transcriptomic changes in human myogenic progenitors. The current data from our in vitro model possibly simulate non-cell autonomous contributions of blood composition to age-related processes in human skeletal muscle., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Tey, Anderson, Yu, Robertson, Kletzien, Connor, Tanaka, Ohkawa and Suzuki.)
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- 2024
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8. Vocal and tongue exercise in early to mid-stage Parkinson disease using the Pink1-/- rat.
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Hoffmeister JD, Broadfoot CK, Schaen-Heacock NE, Lechner SA, Krasko MN, Nisbet AF, Russell J, Szot J, Glass TJ, Connor NP, Kelm-Nelson CA, and Ciucci MR
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- Animals, Male, Protein Kinases metabolism, Protein Kinases genetics, Rats, Physical Conditioning, Animal physiology, Physical Conditioning, Animal methods, Serotonin metabolism, Rats, Transgenic, Tongue physiopathology, Parkinson Disease physiopathology, Disease Models, Animal, Vocalization, Animal physiology
- Abstract
Vocal and swallowing deficits are common in Parkinson disease (PD). Because these impairments are resistant to dopamine replacement therapies, vocal and lingual exercise are the primary treatment, but not all individuals respond to exercise and neural mechanisms of treatment response are unclear. To explore putative mechanisms, we used the progressive Pink1-/- rat model of early to mid-stage PD and employed vocal and lingual exercises at 6- and 10-months of age in male Pink1-/- and wild type (WT) rats. We hypothesized that vocal and lingual exercise would improve vocal and tongue use dynamics and increase serotonin (5HT) immunoreactivity in related brainstem nuclei. Rats were tested at baseline and after 8 weeks of exercise or sham exercise. At early-stage PD (6 months), vocal exercise resulted in increased call complexity, but did not change intensity, while at mid-stage (10 months), vocal exercise no longer influenced vocalization complexity. Lingual exercise increased tongue force generation and reduced relative optical density of 5HT in the hypoglossal nucleus at both time points. The effects of vocal and lingual exercise at these time points are less robust than in prodromal stages observed in previous work, suggesting that early exercise interventions may yield greater benefit. Future work targeting optimization of exercise at later time points may facilitate clinical translation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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9. Altered tongue muscle contractile properties coincide with altered swallow function in the adult Ts65Dn mouse model of down syndrome.
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Glass TJ, Russell JA, Fisher EH, Ostadi M, Aori N, Yu YE, and Connor NP
- Abstract
Purpose: Down syndrome (DS) is a developmental disability associated with difficulties in deglutition. The adult Ts65Dn mouse model of DS has been previously shown to have differences in measures of swallowing compared with euploid controls. However, the putative mechanisms of these differences in swallowing function are unclear. This study tested the hypothesis that the Ts65Dn genotype is associated with atypical measures of tongue muscle contractile properties, coinciding with atypical swallow function., Methods: Adult (5-month-old) Ts65Dn ( n = 15 female, 14 male) and euploid sibling controls ( n = 16 female, 14 male) were evaluated through videofluoroscopy swallow studies (VFSS) to quantify measures of swallowing performance including swallow rate and inter-swallow interval (ISI). After VFSS, retrusive tongue muscle contractile properties, including measures of muscle fatigue, were determined using bilateral hypoglossal nerve stimulation., Results: The Ts65Dn group had significantly slower swallow rates, significantly greater ISI times, significantly slower rates of tongue force development, and significantly greater levels of tongue muscle fatigue, with lower retrusive tongue forces than controls in fatigue conditions., Conclusion: Tongue muscle contractile properties are altered in adult Ts65Dn and coincide with altered swallow function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Glass, Russell, Fisher, Ostadi, Aori, Yu and Connor.)
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- 2024
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10. Differential impact of unilateral stroke on the bihemispheric motor cortex representation of the jaw and tongue muscles in young and aged rats.
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Cullins MJ and Connor NP
- Abstract
Introduction: Dysphagia commonly occurs after stroke, yet the mechanisms of post-stroke corticobulbar plasticity are not well understood. While cortical activity associated with swallowing actions is bihemispheric, prior research has suggested that plasticity of the intact cortex may drive recovery of swallowing after unilateral stroke. Age may be an important factor as it is an independent predictor of dysphagia after stroke and neuroplasticity may be reduced with age. Based on previous clinical studies, we hypothesized that cranial muscle activating volumes may be expanded in the intact hemisphere and would contribute to swallowing function. We also hypothesized that older age would be associated with limited map expansion and reduced function. As such, our goal was to determine the impact of stroke and age on corticobulbar plasticity by examining the jaw and tongue muscle activating volumes within the bilateral sensorimotor cortices., Methods: Using the middle cerebral artery occlusion rat stroke model, intracortical microstimulation (ICMS) was used to map regions of sensorimotor cortex that activate tongue and jaw muscles in both hemispheres. Young adult (7 months) and aged (30 months) male F344 × BN rats underwent a stroke or sham-control surgery, followed by ICMS mapping 8 weeks later. Videofluoroscopy was used to assess oral-motor functions., Results: Increased activating volume of the sensorimotor cortex within the intact hemisphere was found only for jaw muscles, whereas significant stroke-related differences in tongue activating cortical volume were limited to the infarcted hemisphere. These stroke-related differences were correlated with infarct size, such that larger infarcts were associated with increased jaw representation in the intact hemisphere and decreased tongue representation in the infarcted hemisphere. We found that both age and stroke were independently associated with swallowing differences, weight loss, and increased corticomotor thresholds. Laterality of tongue and jaw representations in the sham-control group revealed variability between individuals and between muscles within individuals., Conclusion: Our findings suggest the role of the intact and infarcted hemispheres in the recovery of oral motor function may differ between the tongue and jaw muscles, which may have important implications for rehabilitation, especially hemisphere-specific neuromodulatory approaches. This study addressed the natural course of recovery after stroke; future work should expand to focus on rehabilitation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cullins and Connor.)
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- 2024
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11. Tongue and laryngeal exercises improve tongue strength and vocal function outcomes in a Pink1-/- rat model of early Parkinson disease.
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Broadfoot CK, Hoffmeister JD, Lechner SA, Krasko MN, Lambert E, Russell JA, Szot JC, Glass TJ, Connor NP, Kelm-Nelson CA, and Ciucci MR
- Subjects
- Animals, Rats, Exercise Therapy, Serotonin, Tongue, Ultrasonics, Parkinson Disease
- Abstract
Parkinson disease (PD) causes voice and swallow dysfunction even in early stages of the disease. Treatment of this dysfunction is limited, and the neuropathology underlying this dysfunction is poorly defined. Targeted exercise provides the greatest benefit for offsetting voice and swallow dysfunction, and previous data suggest the hypoglossal nucleus and noradrenergic-locus coeruleus (LC) may be involved in its early pathology. To investigate relationships between targeted exercise and neuropathology of voice and swallow dysfunction, we implemented a combined exercise paradigm that included tongue force and vocalization exercises early in the Pink1-/- rat model. We tested the hypotheses that (1) tongue and vocal exercise improves tongue force and timing behaviors and vocalization outcomes, and (2) exercise increases optical density of serotonin (5-HT) in the hypoglossal nucleus, and tyrosine hydroxylase immunoreactive (Th-ir) cell counts in the LC. At two months of age Pink1-/- rats were randomized to exercise or non-exercise treatment. Age-matched wildtype (WT) control rats were assigned to non-exercise treatment. Tongue force and timing behaviors and ultrasonic vocalizations were measured at baseline (two months) and final (four months) timepoints. Optical density of 5-HT in the hypoglossal nucleus and TH-ir cell counts in the LC were obtained. Pink1-/- rats produced greater tongue forces, faster tongue contraction, and higher-intensity vocalization following exercise. There were no differences in LC TH-ir. The non-exercised Pink1-/- group had reduced density of 5-HT in the hypoglossal nucleus compared to the WT control group. The changes to tongue function and vocalization after targeted exercise suggests exercise intervention may be beneficial in early PD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)
- Published
- 2024
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12. Early ultrasonic vocalization deficits and related thyroarytenoid muscle pathology in the transgenic TgF344-AD rat model of Alzheimer's disease.
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Rudisch DM, Krasko MN, Barnett DGS, Mueller KD, Russell JA, Connor NP, and Ciucci MR
- Abstract
Background: Alzheimer's disease (AD) is a progressive neurologic disease and the most common cause of dementia. Classic pathology in AD is characterized by inflammation, abnormal presence of tau protein, and aggregation of β-amyloid that disrupt normal neuronal function and lead to cell death. Deficits in communication also occur during disease progression and significantly reduce health, well-being, and quality of life. Because clinical diagnosis occurs in the mid-stage of the disease, characterizing the prodrome and early stages in humans is currently challenging. To overcome these challenges, we use the validated TgF344-AD (F344-Tg(Prp-APP, Prp-PS1)19/Rrrc) transgenic rat model that manifests cognitive, behavioral, and neuropathological dysfunction akin to AD in humans., Objectives: The overarching goal of our work is to test the central hypothesis that pathology and related behavioral deficits such as communication dysfunction in part manifest in the peripheral nervous system and corresponding target tissues already in the early stages. The primary aims of this study are to test the hypotheses that: (1) changes in ultrasonic vocalizations (USV) occur in the prodromal stage at 6 months of age and worsen at 9 months of age, (2) inflammation as well as AD-related pathology can be found in the thyroarytenoid muscle (TA) at 12 months of age (experimental endpoint tissue harvest), and to (3) demonstrate that the TgF344-AD rat model is an appropriate model for preclinical investigations of early AD-related vocal deficits., Methods: USVs were collected from male TgF344-AD ( N = 19) and wildtype (WT) Fischer-344 rats ( N = 19) at 6 months ( N = 38; WT: n = 19; TgF344-AD : n = 19) and 9 months of age ( N = 18; WT: n = 10; TgF344-AD : n = 8) and acoustically analyzed for duration, mean power, principal frequency, low frequency, high frequency, peak frequency, and call type. RT-qPCR was used to assay peripheral inflammation and AD-related pathology via gene expressions in the TA muscle of male TgF344-AD rats ( n = 6) and WT rats ( n = 6) at 12 months of age., Results: This study revealed a significant reduction in mean power of ultrasonic calls from 6 to 9 months of age and increased peak frequency levels over time in TgF344-AD rats compared to WT controls. Additionally, significant downregulation of AD-related genes Uqcrc2 , Bace2 , Serpina3n , and Igf2, as well as downregulation of pro-inflammatory gene Myd88 was found in the TA muscle of TgF344-AD rats at 12 months of age., Discussion: Our findings demonstrate early and progressive vocal deficits in the TgF344-AD rat model. We further provide evidence of dysregulation of AD-pathology-related genes as well as inflammatory genes in the TA muscles of TgF344-AD rats in the early stage of the disease, confirming this rat model for early-stage investigations of voice deficits and related pathology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Rudisch, Krasko, Barnett, Mueller, Russell, Connor and Ciucci.)
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- 2024
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13. Ultrasonic vocalization phenotypes in the Ts65Dn and Dp(16)1Yey mouse models of Down syndrome.
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Glass TJ, Lenell C, Fisher EH, Yang Q, and Connor NP
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- Mice, Male, Animals, Vocalization, Animal, Ultrasonics, Phenotype, Disease Models, Animal, Down Syndrome genetics
- Abstract
Down syndrome (DS) is a developmental disorder associated with a high incidence of challenges in vocal communication. DS can involve medical co-morbidities and structural social factors that may impact communication outcomes, which can present difficulties for the study of vocal communication challenges. Mouse models of DS may be used to study vocal communication differences associated with this syndrome and allow for greater control and consistency of environmental factors. Prior work has demonstrated differences in ultrasonic vocalization (USV) of the Ts65Dn mouse model of DS at a young adult age, however it is not known how USV characteristics are manifested at mature ages. Given that the aging process and age-related co-morbidities may also impact communication in DS, addressing this gap in knowledge may be of value for efforts to understand communication difficulties in DS across the lifespan. The current study hypothesized that the Ts65Dn and Dp(16)1Yey mouse models of DS would demonstrate differences in multiple measures of USV communication at a mature adult age of 5 months., Methods: Ts65Dn mice (n = 16) and euploid controls (n = 19), as well as Dp(16)1Yey mice (n = 20) and wild-type controls (n = 22), were evaluated at 5 months of age for USV production using a mating paradigm. Video footage of USV sessions were analyzed to quantify social behaviors of male mice during USV testing sessions. USV recordings were analyzed using Deepsqueak software to identify 10 vocalization types, which were quantified for 11 acoustic measures., Results: Ts65Dn, but not Dp(16)1Yey, showed significantly lower proportions of USVs classified as Step Up, Short, and Frequency Steps, and significantly higher proportions of USVs classified as Inverted U, than euploid controls. Both Ts65Dn and Dp(16)1Yey groups had significantly greater values for power and tonality for USVs than respective control groups. While Ts65Dn showed lower frequencies than controls, Dp(16)1Yey showed higher frequencies than controls. Finally, Ts65Dn showed reductions in a measure of complexity for some call types. No significant differences between genotype groups were identified in analysis of behaviors during testing sessions., Conclusion: While both Ts65Dn and Dp(16)1Yey show significant differences in USV measures at 5 months of age, of the two models, Ts65Dn shows a relatively greater numbers of differences. Characterization of communication phenotypes in mouse models of DS may be helpful in laying the foundation for future translational advances in the area of communication difficulties associated with DS., (Copyright © 2023. Published by Elsevier Inc.)
- Published
- 2023
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14. Age-related sex differences in tongue strength and muscle morphometry in a rat model.
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Rohl AH, Connor NP, and Russell JA
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- Female, Rats, Male, Animals, Rats, Inbred F344, Muscle Fibers, Skeletal, Tongue physiology, Cytoskeletal Proteins, Myosin Heavy Chains, Muscle, Skeletal physiology, Sex Characteristics, Muscle Contraction physiology
- Abstract
Objective: To investigate potential effects of sex on voluntary tongue strength, evoked twitch and tetanic tension, speed of contraction, and muscle fiber cross-sectional area in the muscles of the rat tongue. Additionally, we aimed to determine whether estrous cycle stage impacts any of the dependent variables as a pilot investigation into the use of female rats in a model of tongue exercise and aging., Design: Fischer 344-Brown Norway male and female rats in two age groups (16 middle-aged, 16 young-adult) were trained to use a tongue force operandum. Tongue muscle contraction, myosin heavy chain (MyHC) composition, and cross section area of the genioglossus and styloglossus muscles were examined. Vaginal lavage determined estrous cycle stage of the female rats daily., Results: The female group had significantly lower evoked twitch and tetanic tension, longer contraction times, and a smaller proportion of MyHC type IIa and MyHC type IIx in the styloglossus muscle. There was no significant sex effect in maximal voluntary tongue force (MVTF) despite a significant weight difference between the male and female groups. There were no significant age or sex effects in the genioglossus. Estrous cycle stage did not have a significant effect on any of the dependent variables., Conclusions: Sex and age both have a significant effect on tongue muscle structure and physiology. While the female group showed reduced contraction speed and maximal twitch and tetanic tension relative to the male group, differences in muscle morphology appeared to vary by muscle., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)
- Published
- 2023
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15. Bioenergetic Evaluation of Muscle Fatigue in Murine Tongue.
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Glass TJ, Rowe LM, Cullen J, and Connor NP
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- Humans, Rats, Mice, Animals, Muscle, Skeletal physiology, Tongue physiology, Deglutition physiology, Muscle Fatigue, Deglutition Disorders etiology
- Abstract
Muscle fatigue is the diminution of force required for a particular action over time. Fatigue may be particularly pronounced in aging muscles, including those used for swallowing actions. Because risk for swallowing impairment (dysphagia) increases with aging, the contribution of muscle fatigue to age-related dysphagia is an emerging area of interest. The use of animal models, such as mice and rats (murine models) allows experimental paradigms for studying the relationship between muscle fatigue and swallowing function with a high degree of biological precision that is not possible in human studies. The goal of this article is to review basic experimental approaches to the study of murine tongue muscle fatigue related to dysphagia. Traditionally, murine muscle fatigue has been studied in limb muscles through direct muscle stimulation and behavioral exercise paradigms. As such, physiological and bioenergetic markers of muscle fatigue that have been validated in limb muscles may be applicable in studies of cranial muscle fatigue with appropriate modifications to account for differences in muscle architecture, innervation ratio, and skeletal support. Murine exercise paradigms may be used to elicit acute fatigue in tongue muscles, thereby enabling study of putative muscular adaptations. Using these approaches, hypotheses can be developed and tested in mice and rats to allow for future focused studies in human subjects geared toward developing and optimizing treatments for age-related dysphagia., (© 2022. The Author(s).)
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- 2023
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16. Changes in ultrasonic vocalizations after unilateral cerebral ischemia in a rat stroke model.
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Cullins MJ, Lenell C, Ciucci MR, and Connor NP
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- Rats, Animals, Mice, Vocalization, Animal physiology, Quality of Life, Infarction, Middle Cerebral Artery complications, Ultrasonics, Stroke complications
- Abstract
Stroke frequently results in communication impairments that negatively impact quality of life and overall recovery, yet the biological mechanisms underlying these changes are not well understood. Ultrasonic vocalizations (USVs) in rodent models of disease and aging have been used to improve our understanding of the biological mechanisms that underlie vocal deficits and their response to interventions. Changes in USVs after middle cerebral artery occlusion (MCAO) in mice have been reported, yet rat models have significant anatomical and behavioral advantages over mice, including the ability to vocally train rats with an established paradigm. We sought to determine whether a unilateral MCAO rat stroke model provides a biologically and behaviorally relevant way to study post stroke vocalization deficits. We hypothesized that left MCAO would be associated with changes in USVs. Six weeks after MCAO or sham-control surgery, USVs were recorded in rats using an established mating paradigm. Stroke was associated with differences in USV acoustics including more frequent use of simple calls characterized by shorter durations and restricted bandwidths. These parameters were also found to correlate with post stroke lingual weakness. This is the first study to describe changes to rat USVs using a stroke model. These results suggest the unilateral MCAO rat stroke model is a biologically and behaviorally relevant model to understand how stroke affects vocal behaviors., Competing Interests: Declarations of interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)
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- 2023
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17. Predicting health-related quality of life change using natural language processing in thyroid cancer.
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Lian R, Hsiao V, Hwang J, Ou Y, Robbins SE, Connor NP, Macdonald CL, Sippel RS, Sethares WA, and Schneider DF
- Abstract
Background: Patient-reported outcomes (PRO) allow clinicians to measure health-related quality of life (HRQOL) and understand patients' treatment priorities, but obtaining PRO requires surveys which are not part of routine care. We aimed to develop a preliminary natural language processing (NLP) pipeline to extract HRQOL trajectory based on deep learning models using patient language., Materials and Methods: Our data consisted of transcribed interviews of 100 patients undergoing surgical intervention for low-risk thyroid cancer, paired with HRQOL assessments completed during the same visits. Our outcome measure was HRQOL trajectory measured by the SF-12 physical and mental component scores (PCS and MCS), and average THYCA-QoL score.We constructed an NLP pipeline based on BERT, a modern deep language model that captures context semantics, to predict HRQOL trajectory as measured by the above endpoints. We compared this to baseline models using logistic regression and support vector machines trained on bag-of-words representations of transcripts obtained using Linguistic Inquiry and Word Count (LIWC). Finally, given the modest dataset size, we implemented two data augmentation methods to improve performance: first by generating synthetic samples via GPT-2, and second by changing the representation of available data via sequence-by-sequence pairing, which is a novel approach., Results: A BERT-based deep learning model, with GPT-2 synthetic sample augmentation, demonstrated an area-under-curve of 76.3% in the classification of HRQOL accuracy as measured by PCS, compared to the baseline logistic regression and bag-of-words model, which had an AUC of 59.9%. The sequence-by-sequence pairing method for augmentation had an AUC of 71.2% when used with the BERT model., Conclusions: NLP methods show promise in extracting PRO from unstructured narrative data, and in the future may aid in assessing and forecasting patients' HRQOL in response to medical treatments. Our experiments with optimization methods suggest larger amounts of novel data would further improve performance of the classification model., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose.
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- 2023
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18. Discovering domains important to health-related quality of life in differentiated thyroid cancer.
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Hsiao V, Hanlon BM, Robbins SE, Connor NP, Macdonald CL, Sippel RS, and Schneider DF
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- Humans, Quality of Life, Surveys and Questionnaires, Adenocarcinoma, Thyroid Neoplasms surgery
- Abstract
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The 20 qualitative codes most frequently included in the ElasticNet regression model for the prediction of Average THYCA score. 8 codes were included in 100% of the 1000 runs performed. Positive coefficients indicate that the presence of the code predicted higher average THYCA; negative coefficients indicate the presence of the code predicted lower average THYCA. Note that as higher THYCA scores correspond to decreased HRQOL, positive coefficients imply features that predict a higher Average THYCA score, and thus a lower HRQOL.
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- 2022
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19. Time Heals Most Wounds - Perceptions of Thyroidectomy Scars in Patients With Thyroid Cancer.
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Bach K, Prince S, Pitt SC, Robbins S, Connor NP, Macdonald C, Sippel RS, and Long KL
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- Humans, Personal Satisfaction, Thyroid Cancer, Papillary surgery, Thyroidectomy adverse effects, Cicatrix etiology, Thyroid Neoplasms surgery
- Abstract
Background: Patients understandably have concerns about thyroidectomy scars. This study aimed to characterize patients' perceptions of their thyroidectomy scar before and up to 1-y after surgery., Methods: Patients with papillary thyroid cancer (n = 83) completed semi-structured interviews before and at 2-wks, 6-Wk, 6-mo, and 1-y post-thyroidectomy. Interviews probed about scar concerns and appearance. Content analysis was used to identify themes., Results: The majority of participants did not express concerns about scar appearance. When expressed, preoperative concerns often stemmed from previous surgery experiences or unease with neck incisions. Postoperatively, concerns about scar appearance decreased over time throughout the healing period with most patients being satisfied with their scar appearance by 6-mo after surgery., Conclusions: Patients with papillary thyroid cancer express few concerns about scar thyroidectomy appearance. Surgeons can reassure patients who have preoperative concerns that most patients are satisfied with their scar appearance by 6-mo after surgery., (Copyright © 2021. Published by Elsevier Inc.)
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- 2022
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20. Progressive Protrusive Tongue Exercise Does Not Alter Aging Effects in Retrusive Tongue Muscles.
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Glass TJ, Figueroa JE, Russell JA, Krekeler BN, and Connor NP
- Abstract
Purpose: Exercise-based treatment approaches for dysphagia may improve swallow function in part by inducing adaptive changes to muscles involved in swallowing and deglutition. We have previously shown that both aging and progressive resistance tongue exercise, in a rat model, can induce biological changes in the genioglossus (GG); a muscle that elevates and protrudes the tongue. However, the impacts of progressive resistance tongue exercise on the retrusive muscles (styloglossus, SG; hyoglossus, HG) of the tongue are unknown. The purpose of this study was to examine the impact of a progressive resistance tongue exercise regimen on the retrusive tongue musculature in the context of aging. Given that aging alters retrusive tongue muscles to more slowly contracting fiber types, we hypothesized that these biological changes may be mitigated by tongue exercise. Methods: Hyoglossus (HG) and styloglossus (SG) muscles of male Fischer 344/Brown Norway rats were assayed in age groups of young (9 months old, n = 24), middle-aged (24 months old, n = 23), and old (32 months old, n = 26), after receiving an 8-week period of either progressive resistance protrusive tongue exercise, or sham exercise conditions. Following exercise, HG and SG tongue muscle contractile properties were assessed in vivo . HG and SG muscles were then isolated and assayed to determine myosin heavy chain isoform (MyHC) composition. Results: Both retrusive tongue muscle contractile properties and MyHC profiles of the HG and SG muscles were significantly impacted by age, but were not significantly impacted by tongue exercise. Old rats had significantly longer retrusive tongue contraction times and longer decay times than young rats. Additionally, HG and SG muscles showed significant MyHC profile changes with age, in that old groups had slower MyHC profiles as compared to young groups. However, the exercise condition did not induce significant effects in any of the biological outcome measures. Conclusion: In a rat model of protrusive tongue exercise, aging induced significant changes in retrusive tongue muscles, and these age-induced changes were unaffected by the tongue exercise regimen. Collectively, results are compatible with the interpretation that protrusive tongue exercise does not induce changes to retrusive tongue muscle function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Glass, Figueroa, Russell, Krekeler and Connor.)
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- 2021
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21. Respiratory-swallow coordination in a rat model of chemoradiation.
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Rowe LM, Connor NP, and Russell JA
- Subjects
- Animals, Chemoradiotherapy adverse effects, Deglutition, Rats, Rats, Sprague-Dawley, Deglutition Disorders, Head and Neck Neoplasms
- Abstract
Background: Chemoradiation treatment (CRT) for head and neck cancer (HNC) is associated with postswallow inhale events that elevate the risk of penetration/aspiration. The purpose of this study was to assess the validity of a rat model for investigating the effect of CRT on respiratory-swallow coordination., Methods: Videofluoroscopic swallow study was performed on 10 Sprague-Dawley rats 3 months post-CRT (3 mg/kg Cisplatin, 10 fractions of 4.5 Gy/day radiotherapy to tongue base), and 10 naïve controls. We examined the effect of CRT on swallow apnea duration, diaphragm movement, and bolus kinematics., Results: CRT rats had a significant increase in postswallow inhale (p = 0.008), which was associated with significantly longer swallow apnea durations, lower diaphragm displacement at swallow onset, and faster pharyngoesophageal bolus speed., Conclusion: The rat CRT model is valid for the study of respiratory-swallow coordination due to the consistency of findings in this study with those reported in clinical CRT studies in HNC., (© 2021 Wiley Periodicals LLC.)
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- 2021
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22. Central activation deficits contribute to post stroke lingual weakness in a rat model.
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Cullins MJ, Russell JA, Booth ZE, and Connor NP
- Subjects
- Animals, Hypoglossal Nerve, Muscle Denervation, Muscle Fibers, Skeletal, Muscle, Skeletal, Rats, Tongue, Muscle Contraction, Stroke
- Abstract
Lingual weakness frequently occurs after stroke and is associated with deficits in speaking and swallowing. Chronic weakness after stroke has been attributed to both impaired central activation of target muscles and reduced force-generating capacity within muscles. How these factors contribute to lingual weakness is not known. We hypothesized that lingual weakness due to middle cerebral artery occlusion (MCAO) would manifest as reduced muscle force capacity and reduced muscle activation. Rats were randomized into MCAO or sham surgery groups. Maximum volitional tongue forces were quantified 8 wk after surgery. Hypoglossal nerve stimulation was used to assess maximum stimulated force, muscle twitch properties, and force-frequency response. The central activation ratio was determined by maximum volitional/maximum stimulated force. Genioglossus muscle fiber type properties and neuromuscular junction innervation were assessed. Maximum volitional force and the central activation ratio were significantly reduced with MCAO. Maximum stimulated force was not significantly different. No significant differences were found for muscle twitch properties, unilateral contractile properties, muscle fiber type percentages, or fiber size. However, the twitch/tetanus ratio was significantly increased in the MCAO group relative to sham. A small but significant increase in denervated neuromuscular junctions (NMJs) and fiber-type grouping occurred in the contralesional genioglossus. Results suggest that the primary cause of chronic lingual weakness after stroke is impaired muscle activation rather than a deficit of force-generating capacity in lingual muscles. Increased fiber type grouping and denervated NMJs in the contralesional genioglossus suggest that partial reinnervation of muscle fibers may have preserved force-generating capacity, but not optimal activation patterns. NEW & NOTEWORTHY Despite significant reductions in maximum volitional forces, the intrinsic force-generating capacity of the protrusive lingual muscles was not reduced with unilateral cerebral ischemia. Small yet significant increases in denervated NMJs and fiber-type grouping of the contralesional genioglossus suggest that the muscle underwent denervation and reinnervation. Together these results suggest that spontaneous neuromuscular plasticity was sufficient to prevent atrophy, yet central activation deficits remain and contribute to chronic lingual weakness after stroke.
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- 2021
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23. Patients' Reaction to Diagnosis with Thyroid Cancer or an Indeterminate Thyroid Nodule.
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Pitt SC, Saucke MC, Wendt EM, Schneider DF, Orne J, Macdonald CL, Connor NP, and Sippel RS
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- Adult, Anxiety etiology, Anxiety psychology, Biopsy, Fine-Needle, Fear, Female, Grounded Theory, Humans, Interviews as Topic, Male, Middle Aged, Neoplasm Staging, Patient Education as Topic, Predictive Value of Tests, Qualitative Research, Randomized Controlled Trials as Topic, Thyroid Cancer, Papillary pathology, Thyroid Cancer, Papillary surgery, Thyroid Neoplasms pathology, Thyroid Neoplasms surgery, Thyroid Nodule pathology, Thyroid Nodule surgery, Thyroidectomy, Tumor Burden, Waiting Lists, Health Knowledge, Attitudes, Practice, Patients psychology, Thyroid Cancer, Papillary psychology, Thyroid Neoplasms psychology, Thyroid Nodule psychology
- Abstract
Introduction: Little is known about the experiences and concerns of patients recently diagnosed with thyroid cancer or an indeterminate thyroid nodule. This study sought to explore patients' reactions to diagnosis with papillary thyroid cancer (PTC) or indeterminate cytology on fine needle aspiration. Methods: We conducted semistructured interviews with 85 patients with recently diagnosed PTC or an indeterminate thyroid nodule before undergoing thyroidectomy. We included adults with nodules ≥1 cm and Bethesda III, IV, V, and VI cytology. The analysis utilized grounded theory methodology to create a conceptual model of patient reactions. Results: After diagnosis, participants experienced shock, anxiety, fear, and a strong need to "get it out" because "it's cancer!" This response was frequently followed by a sense of urgency to "get it done," which made waiting for surgery difficult. These reactions occurred regardless of whether participants had confirmed PTC or indeterminate cytology. Participants described the wait between diagnosis and surgery as difficult, because the cancer or nodule was "still sitting there" and "could be spreading." Participants often viewed surgery and getting the cancer out as a "fix" that would resolve their fears and worries, returning them to normalcy. The need to "get it out" also led some participants to minimize the risk of complications or adverse outcomes. Education about the slow-growing nature of PTC reassured some, but not all patients. Conclusions: After diagnosis with PTC or an indeterminate thyroid nodule, many patients have strong emotional reactions and an impulse to "get it out" elicited by the word "cancer." This reaction can persist even after receiving education about the excellent prognosis. Understanding patients' response to diagnosis is critical, because their emotional reactions likely pose a barrier to implementing guidelines recommending less extensive management for PTC.
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- 2021
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24. Dysphagia Care Across the Continuum: A Multidisciplinary Dysphagia Research Society Taskforce Report of Service-Delivery During the COVID-19 Global Pandemic.
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Miles A, Connor NP, Desai RV, Jadcherla S, Allen J, Brodsky M, Garand KL, Malandraki GA, McCulloch TM, Moss M, Murray J, Pulia M, Riquelme LF, and Langmore SE
- Subjects
- COVID-19 transmission, Humans, COVID-19 epidemiology, COVID-19 prevention & control, Deglutition Disorders therapy, Infection Control organization & administration, Telemedicine organization & administration
- Abstract
At the time of writing this paper, there are over 11 million reported cases of COVID-19 worldwide. Health professionals involved in dysphagia care are impacted by the COVID-19 pandemic in their day-to-day practices. Otolaryngologists, gastroenterologists, rehabilitation specialists, and speech-language pathologists are subject to virus exposure due to their proximity to the aerodigestive tract and reliance on aerosol-generating procedures in swallow assessments and interventions. Across the globe, professional societies and specialty associations are issuing recommendations about which procedures to use, when to use them, and how to reduce the risk of COVID-19 transmission during their use. Balancing safety for self, patients, and the public while maintaining adequate evidence-based dysphagia practices has become a significant challenge. This paper provides current evidence on COVID-19 transmission during commonly used dysphagia practices and provides recommendations for protection while conducting these procedures. The paper summarizes current understanding of dysphagia in patients with COVID-19 and draws on evidence for dysphagia interventions that can be provided without in-person consults and close proximity procedures including dysphagia screening and telehealth.
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- 2021
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25. Dose in Exercise-Based Dysphagia Therapies: A Scoping Review.
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Krekeler BN, Rowe LM, and Connor NP
- Subjects
- Exercise, Exercise Therapy, Humans, Reproducibility of Results, Deglutition Disorders therapy
- Abstract
Background: Optimal exercise doses for exercise-based approaches to dysphagia treatment are unclear. To address this gap in knowledge, we performed a scoping review to provide a record of doses reported in the literature. A larger goal of this work was to promote detailed consideration of dosing parameters in dysphagia exercise treatments in intervention planning and outcome reporting., Methods: We searched PubMed, Scopus[Embase], CINAHL, and Cochrane databases from inception to July 2019, with search terms relating to dysphagia and exercises to treat swallowing impairments. Of the eligible 1906 peer-reviewed articles, 72 met inclusionary criteria by reporting, at minimum, both the frequency and duration of their exercise-based treatments., Results: Study interventions included tongue exercise (n = 16), Shaker/head lift (n = 13), respiratory muscle strength training (n = 6), combination exercise programs (n = 20), mandibular movement exercises (n = 7), lip muscle training (n = 5), and other programs that did not fit into the categories described above (n = 5). Frequency recommendations varied greatly by exercise type. Duration recommendations ranged from 4 weeks to 1 year. In articles reporting repetitions (n = 66), the range was 1 to 120 reps/day. In articles reporting intensity (n = 59), descriptions included values for force, movement duration, or descriptive verbal cues, such as "as hard as possible." Outcome measures were highly varied across and within specific exercise types., Conclusions: We recommend inclusion of at least the frequency, duration, repetition, and intensity components of exercise dose to improve reproducibility, interpretation, and comparison across studies. Further research is required to determine optimal dose ranges for the wide variety of exercise-based dysphagia interventions.
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- 2021
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26. What is the experience of our patients with transient hypoparathyroidism after total thyroidectomy?
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Doubleday AR, Robbins SE, Macdonald CL, Elfenbein DM, Connor NP, and Sippel RS
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- Adult, Aged, Calcium blood, Female, Follow-Up Studies, Humans, Hypocalcemia diagnosis, Hypocalcemia epidemiology, Hypocalcemia etiology, Hypoparathyroidism diagnosis, Hypoparathyroidism epidemiology, Hypoparathyroidism etiology, Male, Middle Aged, Parathyroid Glands injuries, Parathyroid Glands metabolism, Parathyroid Hormone blood, Parathyroid Hormone metabolism, Postoperative Complications diagnosis, Postoperative Complications epidemiology, Postoperative Complications etiology, Preoperative Period, Prospective Studies, Qualitative Research, Risk Factors, Thyroid Neoplasms blood, Young Adult, Hypocalcemia psychology, Hypoparathyroidism psychology, Postoperative Complications psychology, Quality of Life, Thyroid Neoplasms surgery, Thyroidectomy adverse effects
- Abstract
Background: We sought to better understand the experience of patients with transient hypoparathyroidism using patient interviews and quality of life surveys., Methods: This is a prospective analysis of 62 patients after total thyroidectomy at a high-volume institution. Semistructured patient interviews and quality of life surveys were conducted preoperatively and postoperatively at 2 weeks, 6 weeks, 6 months, and 1 year and compared based on postoperative parathyroid hormone levels., Results: Postoperative parathyroid hormone levels were <10 pg/mL in 32% of patients (n = 20), 10 to 20 pg/mL in 19% (n = 12), and >20 pg/mL in 48% (n = 30). Hypocalcemic symptoms at 2 weeks were reported in 28 of 55 patients (51%), but patients felt "well prepared" and reported it "wasn't a big deal." If symptoms persisted at 6 weeks, they became more bothersome. At 6 months and 1 year, patients reported calcium supplementation prevented most symptoms and did not interfere with daily activities. Quality of life as measured by the European Organization for Research and Treatment of Cancer and the 12-Item Short Form Survey demonstrated a slight improvement at 1 year postoperatively regardless of parathyroid hormone level., Conclusion: Early postoperative transient hypoparathyroidism is common but when appropriately managed did not have a substantial negative impact on the overall quality of life., (Copyright © 2020 Elsevier Inc. All rights reserved.)
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- 2021
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27. Effects of Tongue Exercise Frequency on Tongue Muscle Biology and Swallowing Physiology in a Rat Model.
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Krekeler BN, Weycker JM, and Connor NP
- Subjects
- Animals, Biology, Muscles, Rats, Rats, Inbred F344, Deglutition, Tongue
- Abstract
Age-related changes in muscle composition and function are often treated using exercise, including muscles of the tongue to treat swallowing impairments (dysphagia). Although tongue exercise is commonly prescribed, optimal tongue exercise doses have not been determined. The purpose of this study was to evaluate effects of varying tongue exercise frequency on tongue force, genioglossus muscle fiber size, composition and metabolism, and swallowing in a rat model. We randomized 41 old and 40 young adult Fischer 344/Brown Norway rats into one of four tongue exercise groups: 5 days/week; 3 days/week; 1 day/week; or sham. Tongue force was higher following all exercise conditions (vs sham); the 5 day/week group had the greatest change in tongue force (p < 0.001). There were no exercise effects on genioglossus (GG) fiber size or MyHC composition (p > 0.05). Significant main effects for age showed a greater proportion of Type I fibers in (p < 0.0001) and increased fiber size of IIa fibers (p = 0.026) in old. There were no significant effects of citrate synthase activity or PGC-1α expression. Significant differences were found in bolus speed and area (size), but findings were potentially influenced by variability. Our findings suggest that tongue force is influenced by exercise frequency; however, these changes were not reflected in characteristics of the GG muscle assayed in this study. Informed by findings of this study, future work in tongue dose optimization will be required to provide better scientific premise for clinical treatments in humans.
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- 2020
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28. Myogenic marker expression as a function of age and exercise-based therapy in the tongue.
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Kletzien H, Kelm-Nelson CA, Wang S, Suzuki M, and Connor NP
- Subjects
- Aged, Aging, Animals, Exercise Therapy, Humans, Muscle, Skeletal, Rats, Deglutition, Tongue
- Abstract
Degeneration of tongue muscles with aging may contribute to swallowing deficits observed in elderly people. However, the capacity for tongue muscle stem cells (SCs) to regenerate and repair the aged tongue and improve tongue strength following tongue exercise (a current clinical treatment) has never been examined. We found that the expression of regenerative, myogenic markers were impaired with age and may be related to increased expression of senescent marker p16
INK4a . Tongue strength increased in young adult and old rats following exercise and was related to the expression of Pax7, MyoD, myogenin, and p16INK4a . Our study also suggests that strengthening of tongue muscles via clinical rehabilitation strategies also increased the expression of SC regenerative markers in the tongue throughout the exercise duration., (Copyright © 2020 Elsevier Inc. All rights reserved.)- Published
- 2020
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29. Functional characterization of extrinsic tongue muscles in the Pink1-/- rat model of Parkinson disease.
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Glass TJ, Kelm-Nelson CA, Szot JC, Lake JM, Connor NP, and Ciucci MR
- Subjects
- Animals, Disease Models, Animal, Gene Knockout Techniques, Male, Myosin Heavy Chains metabolism, Palatal Muscles metabolism, Parkinson Disease physiopathology, Rats, Tongue metabolism, Tongue physiopathology, Palatal Muscles physiopathology, Parkinson Disease genetics, Protein Kinases genetics
- Abstract
Parkinson disease (PD) is associated with speech and swallowing difficulties likely due to pathology in widespread brain and nervous system regions. In post-mortem studies of PD, pathology has been reported in pharyngeal and laryngeal nerves and muscles. However, it is unknown whether PD is associated with neuromuscular changes in the tongue. Prior work in a rat model of PD (Pink1-/-) showed oromotor and swallowing deficits in the premanifest stage which suggested sensorimotor impairments of these functions. The present study tested the hypothesis that Pink1-/- rats show altered tongue function coinciding with neuromuscular differences within tongue muscles compared to wildtype (WT). Male Pink1-/- and WT rats underwent behavioral tongue function assays at 4 and 6 months of age (n = 7-8 rats per group), which are time points early in the disease. At 6 months, genioglossus (GG) and styloglossus (SG) muscles were analyzed for myosin heavy chain isoforms (MyHC), α-synuclein levels, myofiber size, centrally nucleated myofibers, and neuromuscular junction (NMJ) innervation. Pink1-/- showed greater tongue press force variability, and greater tongue press forces and rates as compared to WT. Additionally, Pink1-/- showed relative increases of MyHC 2a in SG, but typical MyHC profiles in GG. Western blots revealed Pink1-/- had more α-synuclein protein than WT in GG, but not in SG. There were no differences between Pink1-/- and WT in myofiber size, centrally-nucleated myofibers, or NMJ innervation. α-synuclein protein was observed in nerves, NMJ, and vessels in both genotypes. Findings at these early disease stages suggest small changes or no changes in several peripheral biological measures, and intact motor innervation of tongue muscles. Future work should evaluate these measures at later disease stages to determine when robust pathological peripheral change contributes to functional change, and what CNS deficits cause behavioral changes. Understanding how PD affects central and peripheral mechanisms will help determine therapy targets for speech and swallowing disorders., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2020
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30. A Randomized Controlled Clinical Trial: No Clear Benefit to Prophylactic Central Neck Dissection in Patients With Clinically Node Negative Papillary Thyroid Cancer.
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Sippel RS, Robbins SE, Poehls JL, Pitt SC, Chen H, Leverson G, Long KL, Schneider DF, and Connor NP
- Subjects
- Female, Humans, Laryngoscopy, Lymphatic Metastasis pathology, Male, Middle Aged, Prospective Studies, Thyroid Cancer, Papillary diagnostic imaging, Thyroid Cancer, Papillary radiotherapy, Thyroidectomy, Neck Dissection, Thyroid Cancer, Papillary pathology, Thyroid Cancer, Papillary surgery
- Abstract
Objective: The aim of this prospective randomized-controlled trial was to evaluate the risks/benefits of prophylactic central neck dissection (pCND) in patients with clinically node negative (cN0) papillary thyroid cancer (PTC)., Background: Microscopic lymph node involvement in patients with PTC is common, but the optimal management is unclear., Methods: Sixty patients with cN0 PTC were randomized to a total thyroidectomy (TT) or a TT+ pCND. All patients received postoperative laryngoscopies and standardized radioiodine treatment. Thyroglobulin (Tg) levels and/or neck ultrasounds were performed at 6 weeks, 6 months, and 1 year., Results: Tumors averaged 2.2 ± 0.2 cm and 11.9% had extra-thyroidal extension. Thirty patients underwent a pCND and 27.6% had positive nodes (all ≤6 mm). Rates of postoperative PTH < 10 (33.3% vs 24.1%, P = 0.57) and transient nerve dysfunction (13.3% vs 10.3%, P = 1.00) were not significantly different between groups. Six weeks after surgery, both TT and TT + pCND were equally likely to achieve a Tg < 0.2 (54.5% vs 66.7%, P = 0.54) and/or a stimulated Tg (sTg) <1 (59.3% vs 64.0%, P = 0.78). At 1 year, rates of Tg < 0.2 (88.9% vs 90.0%, P = 1.00) and sTg < 1 (93.8% vs 92.3%, P = 1.00) remained similar between groups. Neck ultrasounds at 1 year were equally likely to be read as normal (85.7% in TT vs 85.1% in pCND, P = 1.00)., Conclusions: cN0 PTC patients treated either with TT or TT + pCND had similar complication rates after surgery. Although microscopic nodes were discovered in 27.6% of pCND patients, oncologic outcomes were comparable at 1 year., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2020
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31. Perceived Professional and Institutional Factors Influencing Clinical Adoption of Pharyngeal High-Resolution Manometry.
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Rogus-Pulia NM, Jones CA, Forgues AL, Orne J, Macdonald CL, Connor NP, and McCulloch TM
- Subjects
- Focus Groups, Humans, Manometry, Pharynx, Deglutition Disorders diagnosis, Speech-Language Pathology
- Abstract
Purpose We assessed experienced clinicians' perceptions of benefits and drawbacks to the clinical adoption of pharyngeal high-resolution manometry (HRM). This article focuses on the professional and institutional factors that influence the clinical adoption of pharyngeal HRM by speech-language pathologists (SLPs). Method Two surveys (closed- and open-ended questions) and a series of focus groups were completed with SLP members of both the American Speech-Language-Hearing Association and the Dysphagia Research Society (DRS). Transcripts were inductively coded for emergent themes. Results Thirteen SLPs were recruited to attend focus group sessions at the American Speech-Language-Hearing Association. Eighty-seven SLPs responded to the DRS open-set response survey. Two additional focus groups of 11 SLPs were convened at the DRS meeting. Conventional content analysis revealed overall SLP enthusiasm for the clinical use of HRM, with some concerns about the technology adoption process. The following themes related to the professional and institutional factors influencing clinical adoption were identified: (a) scope of practice, (b) access, (c) clinical workflow, and (d) reimbursement. Conclusion These data serve to elucidate the most salient factors relating to the clinical adoption of pharyngeal HRM into routine speech-language pathology clinical practice. While enthusiasm exists, a variety of systems-level issues must be addressed to support this process.
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- 2020
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32. Effects of inhaled fluticasone propionate on extrinsic tongue muscles in rats.
- Author
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Setzke C, Broytman O, Russell JA, Morel N, Sonsalla M, Lamming DW, Connor NP, and Teodorescu M
- Subjects
- Animals, Facial Muscles, Fluticasone, Humans, Muscle Fibers, Skeletal, Rats, Hypoglossal Nerve, Tongue
- Abstract
Obstructive sleep apnea (OSA) is more common in patients with asthma, and inhaled corticosteroids may contribute to OSA pathogenesis in these patients. This study tested the effects of orally inhaled fluticasone propionate (FP) on extrinsic tongue muscles. Unanesthetized rats were treated with FP or placebo for 28 days. On day 29 , tongue retrusive and protrusive functions were tested via hypoglossal nerve stimulation under a state of anesthesia, followed by genioglossus (GG), styloglossus (SG) and hyoglossus (HG) muscle extraction, after euthanasia, for histology [myosin heavy chain (MHC) fibers and laminin content reflecting extracellular matrix (ECM)]. On protrusive testing, FP increased percent maximum tetanic force at 40 Hz ( P = 0.03 vs. placebo) and endurance index ( P = 0.029 vs. placebo). On retrusive testing, FP increased maximum twitch ( P = 0.026 vs. placebo) and tetanic forces ( P = 0.02 vs. placebo) with no effect on endurance index. On histology, FP increased GG cross-sectional area of MHC type IIa ( P = 0.036 vs. placebo) and tended to increase type IIb ( P = 0.057 vs. placebo) fibers and HG MHC IIx fibers ( P = 0.065). The FP group had significantly increased laminin-stained areas, of greatest magnitude in the HG muscle. FP affects tongue protrusive and retrusive functions differently, concurrent with a shift in MHC fibers and increased ECM accumulation. These differential alterations may destabilize the tongue's "muscle hydrostat" during sleep and promote collapse. NEW & NOTEWORTHY The effects of inhaled corticosteroid on upper airway may contribute to OSA pathogenesis in asthma. In this study, we tested the effects of orally inhaled fluticasone propionate on tongue protrusive and retrusive functions and on tongue extrinsic muscle fiber composition and molecular properties. We found that fluticasone treatment: 1 ) increased protrusive endurance and retrusive maximum twitch and tetanic force; and 2 ) on histology, increased cross-sectional area of myosin heavy chain (MHC) type IIa fibers and tended to increase cross-sectional area of MHC type IIb fibers in the protrusive muscle and of MHC IIx fibers in the retrusors. It also increased laminin-stained areas, across extrinsic tongue muscles, of greatest magnitude in the retrusors; and 3 ) reduced protein degradation and activated pathways associated with increased protein synthesis in the protrusor. These differential effects on the protrusors and retrusors may destabilize the tongue's "muscle hydrostat" properties during sleep and promote collapse.
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- 2020
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33. Tongue Force Training Induces Plasticity of the Lingual Motor Cortex in Young Adult and Aged Rats.
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Cullins MJ, Wenninger JM, Cullen JS, Russell JA, Kleim JA, and Connor NP
- Abstract
Tongue exercise programs are used clinically for dysphagia in aged individuals and have been shown to improve lingual strength. However, the neural mechanisms of age-related decline in swallowing function and its association with lingual strength are not well understood. Using an established rat model of aging and tongue exercise, we hypothesized that the motor cortex of aged rats would have a smaller lingual motor map area than young adult rats and would increase in size as a function of tongue exercise. Over 8 weeks, rats either underwent a progressive resistance tongue exercise program (TE), learned the task but did not exercise (trained controls, TC), or were naïve untrained controls (UC). Cortical motor map areas for tongue and jaw were determined using intracortical microstimulation (ICMS). Rats in the TE and TC groups had a significantly larger motor cortex region for the tongue than the UC group. Lingual cortical motor area was not correlated with protrusive tongue force gains and did not differ significantly with age. These results suggest that learning a novel tongue force skill was sufficient to induce plasticity of the lingual motor cortex yet increasing tongue strength with progressive resistance exercise did not significantly expand the lingual motor area beyond the gains that occurred through the skilled learning component., (Copyright © 2019 Cullins, Wenninger, Cullen, Russell, Kleim and Connor.)
- Published
- 2019
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34. A Qualitative Analysis of the Preoperative Needs of Patients With Papillary Thyroid Cancer.
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Pitt SC, Wendt E, Saucke MC, Voils CI, Orne J, Macdonald CL, Connor NP, and Sippel RS
- Subjects
- Adult, Emotions, Female, Humans, Male, Middle Aged, Surgeons, Thyroid Cancer, Papillary psychology, Thyroid Neoplasms psychology, Health Services Needs and Demand, Physician-Patient Relations, Preoperative Care, Qualitative Research, Thyroid Cancer, Papillary surgery, Thyroid Neoplasms surgery
- Abstract
Background: Thyroid cancer patients report unmet needs after diagnosis. However, little is known about their specific needs. Therefore, we sought to characterize the needs of patients with thyroid cancer before undergoing surgery., Material and Methods: We conducted semistructured interviews with 32 patients with papillary thyroid cancer after their preoperative surgical consultation. Data were analyzed using thematic content analysis., Results: The central need of patients with thyroid cancer was a strong patient-surgeon relationship characterized by informational and emotional support, and respect for the patient as a person. Patients preferred disease- and treatment-related information to be individualized and to take into account aspects of their daily life. They wanted adequate time for asking questions with thoughtful answers tailored to their case. Patients additionally desired emotional support from the surgeon characterized by empathy and validation of their cancer experience. They particularly wanted surgeons to address their fears and anxiety. Patients also highly valued the surgeons' ability to see beyond their disease and acknowledge them as a unique person with respect to their occupation, psychosocial state, and other individual characteristics. When surgeons met patients' needs, they felt reassured, comfortable with their cancer diagnosis, and prepared for treatment. Suboptimal support increased patients' anxiety particularly when they felt the surgeon minimized their concerns., Conclusions: Preoperatively, patients with thyroid cancer desire a strong patient-surgeon relationship. They rely on the surgeon to provide adequate informational and emotional support and respect them as individuals. In turn, patients feel reassured and prepared for treatment., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
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35. The Adult Ts65Dn Mouse Model of Down Syndrome Shows Altered Swallow Function.
- Author
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Glass TJ, Valmadrid LCV, and Connor NP
- Abstract
There are increased risks for deglutition disorders in people with Down syndrome (DS). Although mouse models have been used to study the biological underpinnings of DS in other areas, relatively little is known about swallowing phenotypes in these models. We hypothesized that swallowing performance would be affected in adult mouse models of DS, relative to typical control mice. Videofluoroscopic swallow studies (VFSS) were conducted on adults of two mouse models of DS: Ts65Dn and Dp(16)1Yey, and evaluated in comparison with age-matched controls. Relative to other groups, adult Ts65Dn showed significantly slower swallow rates, longer inter-swallow intervals (ISI), and greater numbers of jaw excursion cycles preceding each swallow. In contrast, adult Dp(16)1Yey mice showed swallowing performance similar to control mice. Exploratory quantitative analyses of the intrinsic tongue (transverse muscle), and extrinsic tongue muscles [genioglossus (GG), styloglossus (SG), and hyoglossus (HG)] showed no significant differences between genotype groups in myosin heavy chain isoform profiles. Collectively, these findings suggest that while swallowing is typical in adult Dp(16)1Yey, swallowing in adult Ts65Dn is atypical due to unknown causes. The finding that adult Ts65Dn may have utility as a model of dysphagia provides new opportunities to elucidate biological underpinnings of dysphagia associated with DS.
- Published
- 2019
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36. Reduced tongue force and functional swallowing changes in a rat model of post stroke dysphagia.
- Author
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Cullins MJ and Connor NP
- Subjects
- Animals, Deglutition Disorders etiology, Deglutition Disorders therapy, Disease Models, Animal, Infarction, Middle Cerebral Artery complications, Male, Rats, Rats, Sprague-Dawley, Stroke Rehabilitation methods, Tongue, Deglutition physiology, Deglutition Disorders physiopathology, Stroke physiopathology
- Abstract
Purpose: Dysphagia is a common problem after stroke that is often associated with tongue weakness. However, the physiological mechanisms of post-stroke tongue muscle weakness and optimal treatments have not been established. To advance understanding of physiological mechanisms of post stroke dysphagia, we sought to validate the unilateral transient middle cerebral artery occlusion (MCAO) rat model of ischemic stroke as a translational model of post stroke dysphagia. Our goal was to establish clinically relevant measures and chronicity of functional deficits; criteria that increase the likelihood that findings will translate to the clinic. We hypothesized that MCAO would cause tongue weakness and functional swallowing changes., Methods: Maximum voluntary tongue forces and videofluoroscopic swallowing studies were collected in 8-week old male Sprague-Dawley rats prior to receiving either a left MCAO (N = 10) or sham (N = 10) surgery. Tongue forces and VFSS were reassessed at 1 and 8 weeks post-surgery., Results: Maximum voluntary tongue force, bolus area, and bolus speed were significantly reduced in the MCAO group at the 1 and 8-week timepoints., Conclusion: Clinically relevant changes to swallowing and tongue force support the use of the MCAO rat model as a translational model of post stroke dysphagia. This model will allow for future studies to improve our understanding of the physiology contributing to these functional changes as well as the impact of therapeutic interventions on physiological targets and function., (Copyright © 2019 Elsevier B.V. All rights reserved.)
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- 2019
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37. Correlates of Early Pharyngeal High-Resolution Manometry Adoption in Expert Speech-Language Pathologists.
- Author
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Jones CA, Forgues AL, Rogus-Pulia NM, Orne J, Macdonald CL, Connor NP, and McCulloch TM
- Subjects
- Adult, Female, Humans, Male, Manometry methods, Middle Aged, Pharynx, Speech-Language Pathology methods, Manometry statistics & numerical data, Practice Patterns, Physicians' statistics & numerical data, Speech-Language Pathology statistics & numerical data
- Abstract
Pharyngeal high-resolution manometry (HRM) is at a point of entry into speech-language pathologist (SLP) clinical practice. However, the demographic characteristics of SLPs who are early adopters of HRM are unclear; perspectives of early adopters may shape how the technology is received by the field at large. We hypothesized that younger SLPs, those working in outpatient settings, those with a strong knowledge base in HRM, and those with experience in other types of instrumentation are more likely to have interest in adopting HRM. We surveyed the population of board-certified SLPs (BCS-S; n = 262) with a 33% response rate (n = 78). Firth logistic regression was used to determine differences in those expressing interest in adopting HRM into future practice (n = 28) and those who did not (n = 45) from the analytic sample of 73 respondents. The best fitting model predicted that SLPs: (1) with training in more types of instrumentation; and (2) believing they could explain the HRM procedure to a patient were more likely to plan to adopt pharyngeal HRM into regular clinical practice. Experience with a variety of instrumentation techniques may encourage SLPs to use new forms of technology. Knowledge of early adopter demographics will allow for development of targeted trainings and determination of HRM implementation barriers. Identification of a clinician sub-group more likely to adopt other new technologies in the future may also be possible.
- Published
- 2019
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38. Laryngeal muscle biology in the Pink1-/- rat model of Parkinson disease.
- Author
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Glass TJ, Kelm-Nelson CA, Russell JA, Szot JC, Lake JM, Connor NP, and Ciucci MR
- Subjects
- Animals, Disease Models, Animal, Male, Myofibrils metabolism, Myosin Heavy Chains metabolism, Rats, Rats, Long-Evans, Laryngeal Muscles metabolism, Parkinson Disease metabolism, Protein Kinases metabolism
- Abstract
Neuromuscular pathology is found in the larynx and pharynx in humans with Parkinson disease (PD); however, it is unknown when this pathology emerges. We hypothesized that pathology occurs in early (premanifest) stages. To address this, we used the Pink1-/- rat model of PD, which shows age-dependent dopaminergic neuron loss, locomotor deficits, and deficits related to laryngeal function. We report findings in the thyroarytenoid muscle (TA) in Pink1-/- rats compared with wild-type (WT) control rats at 4 and 6 mo of age. TAs were analyzed for force production, myosin heavy chain isoform (MyHC), centrally nucleated myofibers, neural cell adhesion molecule, myofiber size, and muscle section size. Compared with WT, Pink1-/- TA had reductions in force levels at 1-Hz stimulation and 20-Hz stimulation, increases in relative levels of MyHC 2L, increases in incidence of centrally nucleated myofibers in the external division of the TA, and reductions in myofiber size of the vocalis division of the TA at 6 mo of age. Alterations of laryngeal muscle biology occur in a rat model of premanifest PD. Although these alterations are statistically significant, their functional significance remains to be determined. NEW & NOTEWORTHY Pathology of peripheral nerves and muscle has been reported in the larynx and pharynx of humans diagnosed with Parkinson disease (PD); however, it is unknown whether differences of laryngeal muscle occur at premanifest stages. This study examined the thyroarytenoid muscles of the Pink1-/- rat model of PD for differences of muscle biology compared with control rats. Thyroarytenoid muscles of Pink1-/- rats at premanifest stages show differences in multiple measures of muscle biology.
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- 2019
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39. SLP-Perceived Technical and Patient-Centered Factors Associated with Pharyngeal High-Resolution Manometry.
- Author
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Jones CA, Rogus-Pulia NM, Forgues AL, Orne J, Macdonald CL, Connor NP, and McCulloch TM
- Subjects
- Adult, Deglutition, Esophagus physiopathology, Female, Focus Groups, Humans, Male, Manometry methods, Perception, Pharynx physiopathology, Pressure, Qualitative Research, Reference Values, Deglutition Disorders diagnosis, Manometry statistics & numerical data, Speech-Language Pathology methods
- Abstract
High-resolution manometry (HRM) objectively measures swallowing-related pressures in the pharynx and esophagus. It has been used in many research applications, but it is unclear how HRM is perceived amongst speech-language pathologists (SLP) as it enters into clinical practice. The purpose of this study was to explore SLP perceptions of clinical HRM use. Based on qualitative data collected at four focus groups held at two national conferences and a survey based on open-ended questions, we found broad consensus among those queried regarding how HRM's objective and targeted data could enhance diagnosis and drive treatments. However, we found less consensus among SLPs regarding which patients may and may not benefit, as well as when in the clinical process HRM would best supplement existing technologies, showing a need for further research. These findings highlight how SLPs can be motivated to adopt new clinical technologies if they see a patient-centered benefit and underscore the need for continued SLP education on pharyngeal HRM.
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- 2019
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40. Age-related alterations in swallowing biomechanics.
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Kletzien H, Cullins MJ, and Connor NP
- Subjects
- Animals, Biomechanical Phenomena physiology, Image Processing, Computer-Assisted, Models, Animal, Rats, Aging physiology, Deglutition physiology, Deglutition Disorders diagnosis, Deglutition Disorders physiopathology, Fluoroscopy methods, Mastication physiology, Video Recording methods
- Abstract
Background: Aging rodent models allow for the discovery of underlying mechanisms of cranial muscle dysfunction. Methods are needed to allow quantification of complex, multivariate biomechanical movements during swallowing. Videofluoroscopic swallow studies (VSS) are the standard of care in assessment of swallowing disorders in patients and validated quantitative, kinematic, and morphometric analysis methods have been developed. Our purpose was to adapt validated morphometric techniques to the rodent to computationally analyze swallowing dysfunction in the aging rodent., Methods: VSS, quantitative analyses (bolus area, bolus velocity, mastication rate) and a rodent specific multivariate, morphometric computational analysis of swallowing biomechanics were performed on 20 swallows from 5 young adult and 5 old Fischer 344/Brown Norway rats. Eight anatomical landmarks were used to track the relative change in position of skeletal levers (cranial base, vertebral column, mandible) and soft tissue landmarks (upper esophageal sphincter, base of tongue)., Results: Bolus area significantly increased and mastication rate significantly decreased with age. Aging accounted for 77.1% of the variance in swallow biomechanics, and 18.7% of the variance was associated with swallow phase (oral vs pharyngeal). Post hoc analyses identified age-related alterations in tongue base retraction, mastication, and head posture during the swallow., Conclusion: Geometric morphometric analysis of rodent swallows suggests that swallow biomechanics are altered with age. When used in combination with biological assays of age-related adaptations in neuromuscular systems, this multivariate analysis may increase our understanding of underlying musculoskeletal dysfunction that contributes to swallowing disorders with aging., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
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41. Early impacts of modified food consistency on oromotor outcomes in mouse models of Down syndrome.
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Glass TJ, Twadell SL, Valmadrid LC, and Connor NP
- Subjects
- Animals, Disease Models, Animal, Down Syndrome metabolism, Mice, Muscle Contraction physiology, Muscle, Skeletal physiology, Myosin Heavy Chains metabolism, Down Syndrome physiopathology, Eating physiology, Food, Mastication physiology
- Abstract
Down syndrome (DS) in humans is associated with differences of the central nervous system and oromotor development. DS also increases risks for pediatric feeding challenges, which sometimes involve the use of altered food consistencies. Therefore, experimental food consistency paradigms are of interest to oromotor investigations in mouse models of Down syndrome (DS). The present work reports impacts of an altered food consistency paradigm on the Ts65Dn and Dp(16)1Yey mouse models of DS, and sibling control mice. At weaning, Ts65Dn, Dp(16)1Yey and respective controls were assigned to receive either a hard food or a soft food (eight experimental groups, n = 8-10 per group). Two weeks later, mice were assessed for mastication speeds and then euthanized for muscle analysis. Soft food conditions were associated with significantly smaller weight gain (p = .003), significantly less volitional water intake through licking (p = .0001), and significant reductions in size of anterior digastric myofibers positive for myosin heavy chain isoform (MyHC) 2b (p = .049). Genotype was associated with significant differences in weight gain (p = .004), significant differences in mastication rate (p = .001), significant differences in a measure of anterior digastric muscle size (p = .03), and significant reductions in size of anterior digastric myofibers positive for MyHC 2a (p = .04). In multiple measures, the Ts65Dn model of DS was more affected than other genotype groups. Findings indicate a soft food consistency condition in mice is associated with significant reductions in weight gain and oromotor activity, and may impact digastric muscle. This suggests extended periods of food consistency modifications may have impacts that extend beyond their immediate roles in facilitating deglutition., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2019
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42. Comparison Between Patient-Perceived Voice Changes and Quantitative Voice Measures in the First Postoperative Year After Thyroidectomy: A Secondary Analysis of a Randomized Clinical Trial.
- Author
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Kletzien H, Macdonald CL, Orne J, Francis DO, Leverson G, Wendt E, Sippel RS, and Connor NP
- Subjects
- Adult, Female, Humans, Interviews as Topic, Male, Middle Aged, Postoperative Complications diagnosis, Voice Disorders diagnosis, Postoperative Complications etiology, Quality of Life, Thyroidectomy, Voice Disorders etiology, Voice Quality
- Abstract
Importance: Voice changes after thyroidectomy are typically attributed to recurrent laryngeal nerve injury. However, most postoperative voice changes occur in the absence of clinically evident vocal fold paralysis. To date, no study has compared the prevalence, duration, and consequences of voice-related disability from the patient perspective with use of quantitative vocal measures., Objectives: To assess the quality-of-life consequences of postthyroidectomy voice change from the perspective of patients with thyroid cancer and to compare patient-perceived voice changes with changes in quantitative vocal variables at 5 time points in the first postoperative year., Design, Setting, and Participants: This prospective mixed methods observational study within a randomized clinical trial occurred at the University of Wisconsin Hospital and Clinics. Participants were 42 patients with clinically node-negative papillary thyroid cancer without a preexisting vocal cord paralysis who were recruited and enrolled from outpatient clinics between June 6, 2014, and March 6, 2017, as part of the ongoing randomized clinical trial., Intervention: Total thyroidectomy., Main Outcomes and Measures: Semistructured interviews, symptom prevalence, and instrumental voice evaluations (laryngoscopy, phonation threshold pressure, Dysphonia Severity Index, and Voice Handicap Index) occurred at baseline (n = 42) and 2-week (n = 42), 6-week (n = 39), 6-month (n = 35), and 1-year (n = 30) postoperative time points., Results: Participants had a mean age of 48 years (interquartile range, 38-58 years; age range, 22-70 years) and were mostly female (74% [31 of 42]) and of white race/ethnicity (98% [41 of 42]). Impaired communication was the primary theme derived from patient interviews from before thyroidectomy to after thyroidectomy. Voice changes were perceived by 24 participants at 2 weeks after thyroidectomy. After surgery, voice symptoms were prevalent and persisted for 50% (21 of 42) of participants out to at least 1 year of follow-up. Quantitative vocal perturbations were detected in the Dysphonia Severity Index and Voice Handicap Index at the 2-week follow-up but returned to baseline levels by the 6-week follow-up visit., Conclusions and Relevance: Voice changes are common after surgery for papillary thyroid cancer and affect quality of life for many patients out to 1 year of follow-up. Directly querying patients about postoperative voice changes and questioning whether commonly used aerodynamic and acoustic variables detect meaningful voice changes are important in identifying patients whose quality of life has been affected by postthyroidectomy dysphonia., Trial Registration: ClinicalTrials.gov Identifier: NCT02138214.
- Published
- 2018
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43. Differential impact of tongue exercise on intrinsic lingual muscles.
- Author
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Cullins MJ, Krekeler BN, and Connor NP
- Subjects
- Aging physiology, Animals, Male, Muscle, Skeletal metabolism, Myosin Heavy Chains metabolism, Rats, Rats, Inbred F344, Tongue metabolism, Muscle, Skeletal physiology, Physical Conditioning, Animal physiology, Tongue physiology
- Abstract
Objectives/hypothesis: Aging is associated with muscle fiber hypotrophy and decreased percentages of rapidly contracting myosin heavy chain (MyHC) type IIb muscle fibers. Tongue exercise programs used to treat dysphagia target age-related decline in tongue muscle function, but the impact of exercise on the intrinsic tongue muscles is unknown. We hypothesized that exercise would induce muscle fiber hypertrophy and increase the percentage of MyHC IIa fibers in the intrinsic tongue., Study Design: Animal model., Methods: Eight old and eight young-adult rats underwent 8 weeks of tongue exercise training, and 8 animals of each age group served as controls. Longitudinal, transverse, and verticalis muscle samples from the anterior, middle, and posterior regions of the tongue were sectioned and stained to determine muscle fiber diameter and MyHC composition., Results: MyHC fiber type distribution was altered by exercise, and the effects differed by muscle and region of the tongue. In the exercise groups, as compared to the control groups, the anterior transverse and middle superior longitudinal muscles had significantly reduced percentages of MyHC IIx positive fibers and higher percentages of rapidly contracting fatigable MyHC IIb positive muscle fibers, whereas the middle transverse and posterior longitudinal muscles had increased percentages of the less rapidly contracting and more fatigue-resistant MyHC IIa fibers. The impact of exercise did not differ with age, as there was no significant interaction between age and exercise. Tongue exercise had no significant effect on muscle fiber diameter., Conclusions: The impact of exercise varied among the tongue muscles, which may indicate different functional contributions to the tongue exercise task., Level of Evidence: NA Laryngoscope, 128:2245-2251, 2018., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)
- Published
- 2018
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44. Effect of neuromuscular electrical stimulation frequency on muscles of the tongue.
- Author
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Kletzien H, Russell JA, Leverson G, and Connor NP
- Subjects
- Animals, Electric Stimulation methods, Implantable Neurostimulators, Male, Rats, Rats, Inbred BN, Rats, Inbred F344, Hypoglossal Nerve physiology, Muscle Contraction physiology, Muscle Fatigue physiology, Tongue innervation, Tongue physiology
- Abstract
Introduction: Neuromuscular electrical stimulation (NMES) for the treatment of swallowing disorders is delivered at a variety of stimulation frequencies. We examined the effects of stimulation frequency on tongue muscle plasticity in an aging rat model., Methods: Eighty-six young, middle-aged, and old rats were assigned to either bilateral hypoglossal nerve stimulation at 10 or 100 Hz (5 days/week, 8 weeks), sham, or no-implantation conditions. Muscle contractile properties and myosin heavy chain (MyHC) composition were determined for hyoglossus (HG) and styloglossus (SG) muscles., Results: Eight weeks of 100-Hz stimulation resulted in the greatest changes in muscle contractile function with significantly longer contraction and half-decay times, the greatest reduction in fatigue, and a transition toward slowly contracting, fatigue-resistant MyHC isoforms., Discussion: NMES at 100-Hz induced considerable changes in contractile and phenotypic profiles of HG and SG muscles, suggesting higher frequency NMES may yield a greater therapeutic effect. Muscle Nerve, 2018., (© 2018 Wiley Periodicals, Inc.)
- Published
- 2018
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45. Correction to: Patient Adherence to Dysphagia Recommendations: A Systematic Review.
- Author
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Krekeler BN, Broadfoot CK, Johnson S, Connor NP, and Rogus-Pulia N
- Abstract
The original version of this article unfortunately contains mistakes. The second sentence in the section "Results", under the heading "Study Design" was incorrect. It should read as: Two studies [24, 29] used a prospective cohort study design with a JAMA rating of 2. Four studies [17, 25, 27, 34] completed retrospective studies earning a JAMA score of 3. Four studies [26, 28, 30, 33] earned a JAMA quality rating score of 4 and used the following designs: case series [26, 28, 33], and pilot study [30]. In Table 1, "Study Population (n)" and "Design (JAMA quality rating)" values were incorrect for Shinn et al. (2013) [24]. The correct information is given here. HNC (n = 109) Prospective Cohort (2).
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- 2018
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46. Tongue exercise and ageing effects on morphological and biochemical properties of the posterior digastric and temporalis muscles in a Fischer 344 Brown Norway rat model.
- Author
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Krekeler BN, Leverson G, and Connor NP
- Subjects
- Animals, Immunohistochemistry, Male, Muscle Fibers, Skeletal, Myosin Heavy Chains chemistry, Neck Muscles chemistry, Protein Isoforms, Rats, Rats, Inbred F344, Temporal Muscle chemistry, Tongue chemistry, Aging physiology, Myosin Heavy Chains physiology, Neck Muscles physiology, Temporal Muscle physiology, Tongue physiology
- Abstract
Objective: This study sought to examin effects of age and tongue exercise on the posterior digastric (opener) and the temporalis (closer). We hypothesized 1) age would result in differing morphological (cross sectional area) and biochemical (myosin heavy chain isoform) components of these muscles; 2) tongue exercise would result in coactivation of these muscles inducing a decrease in age-related differences between age groups., Design: Young adult (9 months) and old (32 months) Fischer 344 Brown Norway rats were randomized into a tongue exercise or control group. Post-training, posterior digastric and temporalis muscles were harvested and analyzed using: 1) Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE) to assess percent myosin heavy chain (MyHC) content; 2) Immunohistochemical staining to determine cross sectional area (CSA)., Results: A larger proportion of slowly contracting MyHC isoforms in the posterior digastric and temporalis muscles were found in old. No significant main effects for age or exercise in fiber size were found in posterior digastric muscle. An interaction between age and exercise for temporalis cross sectional area indicated the old exercise group had smaller average cross sectional area than all other groups. CONCLUSIONS FINDINGS: suggest that: 1) Increasing age induces biochemical changes in muscles of the jaw, specifically showing an increase the proportion of slower contracting MyHC isoforms; 2) Increasing age and tongue exercise induce a reduction in muscle fiber cross sectional area in the temporalis muscle only. However, continued study of these cranial muscle systems is warranted to better understand these changes that occur with age and exercise., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Published
- 2018
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47. Patient Adherence to Dysphagia Recommendations: A Systematic Review.
- Author
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Krekeler BN, Broadfoot CK, Johnson S, Connor NP, and Rogus-Pulia N
- Subjects
- Deglutition, Head and Neck Neoplasms, Humans, Pilot Projects, Prospective Studies, Retrospective Studies, Deglutition Disorders therapy, Patient Compliance
- Abstract
Patient adherence to treatment recommendations is an important issue for healthcare providers, in a multitude of specialties, and is critical when assessing the efficacy and effectiveness of a particular treatment approach. Patients who have swallowing impairment often require complex and specific interventions requiring altered daily patterns of behavior. Patients with dysphagia who do not follow recommendations or prescribed exercises may not receive maximum benefit of an intervention. Poor adherence also makes it more difficult to evaluate efficacy of a treatment both clinically and in experimental settings. Further, swallow safety can be compromised if certain recommendations are not followed. Our purpose was to systematically review the literature to understand what is known about adherence within the field of dysphagia treatment. We systematically identified 12 studies that tracked and reported patient-specific adherence. In this review, we found that the average adherence rate from these studies ranges between 21.9 and 51.9%. Adherence to prophylactic treatment recommendations for patients with head and neck cancer was the focus in 9/12 studies. The findings of this review identify a large gap in knowledge regarding adherence to dysphagia treatment. Few studies account for adherence within their study designs. When planning dysphagia treatment studies, it is imperative that investigators include information regarding patient adherence to accurately interpret findings. Given the variable adherence rates found in this review, factors influencing patient adherence with dysphagia treatments should be identified to increase adherence in future trials.
- Published
- 2018
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- View/download PDF
48. Patient-Reported Dysphagia After Thyroidectomy: A Qualitative Study.
- Author
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Krekeler BN, Wendt E, Macdonald C, Orne J, Francis DO, Sippel R, and Connor NP
- Subjects
- Adult, Aged, Female, Humans, Male, Middle Aged, Patient Reported Outcome Measures, Postoperative Complications etiology, Prospective Studies, Young Adult, Deglutition Disorders etiology, Thyroid Neoplasms surgery, Thyroidectomy adverse effects
- Abstract
Importance: It is important that clinicians understand consequences of thyoridectomy on swallowing from the patient perspective to better care for this population., Objective: Using rigorous qualitative methodology, this study set out to characterize the effect of swallowing-related symptoms after thyroidectomy on patient quality of life and swallowing-related outcomes., Design, Setting, and Participants: Prospective, grounded theory analysis of interviews with 26 patients at 3 time points after thyroidectomy (2 weeks, 6 weeks, and 6 months). Data were collected from an ongoing clinical trial (NCT02138214), and outpatient interviews were conducted at the University of Wisconsin Hospital and Clinics. All participants were age 21 to 73 years with a diagnosis of papillary thyroid cancer without cervical or distant metastases and had undergone total thyroidectomy. Exclusion criteria were preexisting vocal fold abnormalities (eg, polyps, nodules), neurological conditions affecting the voice or swallowing ability, and/or development of new-onset vocal fold paresis or paralysis (lasting longer than 6 months) after total thyroidectomy., Interventions: Total thyroidectomy., Main Outcomes and Measures: Symptoms of dysphagia and related effects on quality of life elicited through grounded theory analysis of semistructured interviews with patients after thyroidectomy designed to foster an open-ended, patient-driven discussion., Results: Of the 26 patients included, 69% were women (n = 18); mean (SD) age, 46.4 (14.1) years; mean (SD) tumor diameter 2.2 (1.4) cm. Two weeks after thyroidectomy, 80% of participants (n = 20) reported at least 1 swallowing-related symptom when prompted by the interview cards; during the open interview, 53% of participants (n = 14) volunteered discussion of swallowing-related symptoms unprompted. However, only 8% of participants in this study (n = 2) qualified for a follow-up dysphagia evaluation, indicating that the majority of reported symptoms were subjective in nature. Six weeks and 6 months after thyroidectomy, 42% (n = 11) and 17% (n = 4) of participants, respectively, reported continued swallowing symptoms using the prompts; 12% (n = 3) discussed symptoms without prompting cards at both time points., Conclusions and Relevance: Swallowing symptoms after thyroidectomy are underreported in the literature. This study revealed that as many as 80% of patients who have thyroidectomy may experience swallowing-related symptoms after surgery, and many develop compensatory strategies to manage or reduce the burden of these symptoms. Considering the large number of individuals who may experience subjective dysphagia, preoperative counseling should include education and management of such symptoms.
- Published
- 2018
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49. A Pilot Study of Perceived Mouth Dryness, Perceived Swallowing Effort, and Saliva Substitute Effects in Healthy Adults Across the Age Range.
- Author
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Rogus-Pulia NM, Gangnon R, Kind A, Connor NP, and Asthana S
- Subjects
- Adult, Aged, Aged, 80 and over, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Perception, Pilot Projects, Saliva, Young Adult, Deglutition physiology, Saliva, Artificial therapeutic use, Xerostomia complications
- Abstract
Xerostomia, or perceived mouth dryness, increases with advancing age, but its influence on swallowing effort is unknown. This study: (1) quantified relationships among age, perceived sense of swallowing effort, and ratings of perceived mouth dryness, and (2) examined changes in swallowing effort following application of a gel-based saliva substitute in healthy participants. This was a cross-sectional observational study and data were collected from attendees of a community healthy aging fair. Forty-two healthy participants (mean age = 65 years; 20 female) were enrolled. Each participant rated perceived effort with swallowing and perceived mouth dryness on a 10-cm horizontal, undifferentiated line. After participants applied a gel-based saliva substitute (Biotene
® Oral Balance) to their tongue and oral mucosa, they rated perceived effort with swallowing again. Age was associated with greater perceived mouth dryness (r = 0.37, p < 0.03) but not with perceived swallowing effort (r = 0.16, p = 0.32). Perceived mouth dryness was associated with greater perceived swallowing effort (r = 0.62, p < 0.001). Perceived swallowing effort declined following application of the salivary substitute (mean difference = 9.39 mm, p < 0.002). Age was found to be a significant predictor of perceived mouth dryness (p < .02); and perceived mouth dryness was found to significantly predict perceived swallow effort (p < .001). Perceived mouth dryness increased with advancing age, but perceived swallowing effort did not. Regardless of age, participants with higher levels of perceived mouth dryness also reported more perceived effort with swallowing suggesting a role for adequate oral lubrication in this perception. Even in healthy participants, use of a gel-based saliva substitute lowered perceived swallowing effort.- Published
- 2018
- Full Text
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50. Age-related effect of cell death on fiber morphology and number in tongue muscle.
- Author
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Kletzien H, Hare AJ, Leverson G, and Connor NP
- Subjects
- Aging pathology, Animals, Apoptosis, Body Weight, Caspase 3 biosynthesis, Caspase 3 genetics, Cell Count, Cell Death, In Situ Nick-End Labeling, Male, Muscle, Skeletal pathology, Proto-Oncogene Proteins c-bcl-2 biosynthesis, Proto-Oncogene Proteins c-bcl-2 genetics, Rats, Rats, Inbred F344, Muscle Fibers, Skeletal pathology, Tongue pathology, Tongue Diseases pathology
- Abstract
Introduction: Multiple pathways may exist for age-related tongue muscle degeneration. Cell death is one mechanism contributing to muscle atrophy and decreased function. We hypothesized with aging, apoptosis, and apoptotic regulators would be increased, and muscle fiber size and number would be reduced in extrinsic tongue muscles., Methods: Cell death indices, expression of caspase-3 and Bcl-2, and measures of muscle morphology and number were determined in extrinsic tongue muscles of young and old rats., Results: Significant increases in cell death, caspase-3, and Bcl-2 were observed in all extrinsic tongue muscles along with reductions in muscle fiber number in old rats., Discussion: We demonstrated that apoptosis indices increase with age in lingual muscles and that alterations in apoptotic regulators may be associated with age-related degeneration in muscle fiber size and number. These observed apoptotic processes may be detrimental to muscle function, and may contribute to degradation of cranial functions with age. Muscle Nerve 57: E29-E37, 2018., (© 2017 Wiley Periodicals, Inc.)
- Published
- 2018
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- View/download PDF
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