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1
Hott, Morgan E. "Cartilage tissue engineering: uses of injection molding and computer aided design for the fabrication of complex geometries with high dimensional tolerances: a dissertation." eScholarship@UMMS, 2007. https://escholarship.umassmed.edu/gsbs_diss/325.
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Cartilage Tissue Engineering. Joint pain and functional impairment due to cartilage damage from osteoarthritis and other means is a major source of disability for adults the world over. Cartilage is an avascular tissue with a very limited capacity for self repair. Current medical and surgical approaches to cartilage repair also have limited efficacy, and in all cases fail to completely restore a normal, healthy cartilage phenotype. Tissue engineering is a relatively new approach to cartilage repair that seeks to fabricate a replacement tissue, indistinguishable from healthy, native tissue.
The basic idea of the tissue engineering approach is to seed tissue synthesizing cells into a shapeable, biocompatible/bioabsorbable scaffold that serves as a temporary extracellular matrix with a localized source of bioactive molecules to direct the development of new tissue. The challenge of tissue engineering is to identify cells, scaffolds, and growth conditions that will be optimal for tissue regeneration. The goal of the current studies was to evaluate one aspect of all three of the major components of cartilage tissue engineering: cell source, scaffolding material and preparation, and controlled growth factor delivery.
We evaluated the chondrogenic potential of human nasal chondrocytes grown in calcium alginate in an in vivo culture system, the potential of computer-aided design and injection molding with calcium alginate to reliably reproduce complex geometries with high dimensional tolerances, and the potential for the controlled release of TGF-β1 from calcium alginate modified by the covalent addition of a recently discovered TGF-β binding peptide.
We found that adult human nasal chondrocytes show significant chondrogenic potential when grown within an alginate scaffold. We also found that alginate is readily amenable to an injection molding process that utilizes precision made molds from computer-aided design and solid free form fabrication, allowing for the fabrication of tissue engineered constructs with very precise shape fidelity. Additionally, we found that calcium alginate could be reliably modified by the covalent addition of peptides, and that the addition of a newly discovered TGF-β binding peptide delayed the release of pre-loaded TGF-β1. Together these results show some of the encouraging prospects for cartilage tissue engineering.
`Menière’s Syndrome.Menière’s syndrome is an inner ear disorder characterized by idiopathic endolymphatic hydrops with associated periodic tinnitus, vertigo, and progressive sensorineural hearing loss. It affects approximately 0.2% of the population, for whom it can be quite devastating. In addition to progressive hearing loss people with Menière’s syndrome are prone to sudden attacks of vertigo and tinnitus that are severe enough that they can lead to falls and potentially serious injury. People subject to frequent attacks are unable to drive, with obvious consequences on standard of living.
In the current studies we evaluated the standard animal model of Menière’s syndrome by comparing cochlear turn specific hearing thresholds and the degree of hydrops in that turn. A positive correlation between these had previously been established in the study of human temporal bones from people with Menière’s syndrome, but had not been reported in the animal model.
We also evaluated the potential of aminoguanidine, a relatively specific inhibitor of the inducible isoform of nitric oxide synthase, as a neuroprotective therapeutic agent for preservation of hearing in animals with surgically induced endolymphatic hydrops.
We found, for the first time, a partial correlation between cochlear turn specific hydrops and hearing thresholds in the most commonly used animal model of Menière’s syndrome, helping to validate the utility of this animal model for future studies. We also found that aminoguanidine did indeed partially preserve hearing in animals with surgically induced Menière’s syndrome. This encouraging result appears to be the first report of a medical intervention protective against hearing loss in an animal model of Menière’s syndrome, and may help us to understand the etiology pathology seen in Menière’s syndrome.
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Fagelson, Marc A. "Introduction." Digital Commons @ East Tennessee State University, 2010. https://dc.etsu.edu/etsu-works/1605.
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Fagelson, Marc A. "Overview of Tinnitus." Digital Commons @ East Tennessee State University, 2015. https://dc.etsu.edu/etsu-works/1593.
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Excerpt: Tinnitus is the sensation of ringing, buzzing, whooshing or other sound in the ears or head without an external stimulus. You are not alone if you feel that your experience with tinnitus has changed you as a person. It can impair your ability to carry out basic activities, such as sleeping, relaxing, or enjoying a quiet peaceful location. It can influence the ability to interact with other people.
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Fagelson, Marc A., and David Baguley. "New Developments in Tinnitus Research." Digital Commons @ East Tennessee State University, 2010. https://dc.etsu.edu/etsu-works/1637.
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Fagelson, Marc A. "Overview." Digital Commons @ East Tennessee State University, 2008. https://www.amzn.com/0966182677.
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Book Summary: This book was written for more than 50 million Americans who experience tinnitus - some 2 million disabled by it. Just some of the helpful ideas and simple treatment options in this book that readers can effectively accomplish at home include altering medications or changing diets, using sound therapy such as music, learning techniques for improving concentration through use of positive imagery, and improving sleep patterns by controlling middle-of-the-night thinking. The enormous advantages of this book over other titles on this topic come from the 17 renowned scientists who have contributed to this invaluable consumer resource, one that will make a difference in the lives of readers who suffer from this unfortunate malady.
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Fagelson, Marc A. "Remote Tinnitus Counseling Session." Digital Commons @ East Tennessee State University, 2006. https://dc.etsu.edu/etsu-works/1625.
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Haas, R., Jacek Smurzynski, and Marc A. Fagelson. "The Effect of Tinnitus on Gap Detection." Digital Commons @ East Tennessee State University, 2012. https://dc.etsu.edu/etsu-works/1601.
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Fillon, S., A. Danielle Rose, L. Rost, and Marc A. Fagelson. "Measures of Tinnitus in Normal-hearing Individuals." Digital Commons @ East Tennessee State University, 2002. https://dc.etsu.edu/etsu-works/1607.
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Fagelson, Marc A. "Treating the Stressed Tinnitus Patient." Digital Commons @ East Tennessee State University, 2004. https://dc.etsu.edu/etsu-works/1616.
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Fagelson, Marc A. "Tinnitus, Hyperacusis, & Post-Traumatic Stress Disorder." Digital Commons @ East Tennessee State University, 2003. https://dc.etsu.edu/etsu-works/1610.
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Fagelson, Marc A. "Tinnitus in Military and Veteran Populations." Digital Commons @ East Tennessee State University, 2015. https://www.amzn.com/1597567213.
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Excerpt: Tinnitus: Clinical and Research Perspectives summarizes contemporary findings from basic and clinical research regarding tinnitus mechanisms, effects, and interventions. The text features a collection of international authors, active researchers, and clinicians who provide an expansive scope of material that ensures relevance for patients and professionals. Reviews and reports of contemporary research findings underscore the text s value for classroom use in audiology and otolaryngology programs. Patients and students of audiology will benefit from the text s coverage of tinnitus mechanisms, emerging practice considerations, and expectations for outcomes--for example, recent successes of cognitive behavioral therapy, neuromodulation, and hearing aid use. These and other topics, such as the effects of noise and drugs on tinnitus, are reported in a way that enhances clinicians ability to weave such strategies into their own work. The influence of tinnitus on all aspects of life is explored, from art to medicine and communication to isolation, thereby providing clinicians and patients a deeper understanding of and greater facility managing a tinnitus experience. Finally, this text includes case studies that provide a practical view of tinnitus effects and management approaches. The editors hope that the consideration of mechanisms, interventions, and outcomes resonates with patients, clinicians, and students of audiology.
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Fagelson, Marc A. "Gap Discrimination and Speech Perception in Noise." Digital Commons @ East Tennessee State University, 1999. https://dc.etsu.edu/etsu-works/1583.
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The relation between discrimination of silent gaps and speech‐in‐noise perception was measured in 20 normal‐hearing listeners using speech‐shaped noise as both the gap markers and the noise source for speech testing. In the gap discrimination experiment, subjects compared silent gaps marked by 60 dB SPL 250‐ms noise bursts to standards of either 5, 10, 20, 50, 100, or 200 ms. The gap results were most similar to those reported by Abel [S. M. Abel, J. Acoust. Soc. Am. 52, 519–524 (1972)] as ΔT/T decreased non‐monotonically with increased gap length. In a second experiment, the California Consonant Test (CCT) was administered at 50 dB HL via CD in three conditions: quiet, +10 S/N, and 0 S/N. Results from both experiments were correlated and the association between ΔT/T and CCT scores was generally negative. Listeners who discriminated the gaps with greater acuity typically had higher speech scores. The relation was strongest for the smaller gap standards at each S/N, or when performance for any gap duration was compared to the CCT results obtained in quiet.
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Fagelson, Marc A. "Forward." Digital Commons @ East Tennessee State University, 2013. https://www.amzn.com/140519989X.
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Book Summary: Tinnitus: A Multidisciplinary Approach provides a broad account of tinnitus and hyperacusis, detailing the latest research and developments in clinical management, incorporating insights from audiology, otology, psychology, psychiatry and auditory neuroscience. It promotes a collaborative approach to treatment that will benefit patients and clinicians alike.
The 2nd edition has been thoroughly updated and revised in line with the very latest developments in the field. The book contains 40% new material including two brand new chapters on neurophysiological models of tinnitus and emerging treatments; and the addition of a glossary as well as appendices detailing treatment protocols for use in an audiology and psychology context respectively.
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Fagelson, Marc A. "Taming TBI-Associated Tinnitus." Digital Commons @ East Tennessee State University, 2015. https://dc.etsu.edu/etsu-works/1594.
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Regardless of the tinnitus sound (itself), tinnitus can be especially challenging for clients when paired with traumatic brain injury and post-traumatic stress. Research offers insight into how clinicians can help clients manage this co-occurrence.
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Fagelson, Marc A. "Interactions between Tinnitus and PTSD." Digital Commons @ East Tennessee State University, 2004. https://dc.etsu.edu/etsu-works/1615.
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Fagelson, Marc A. "Addressing Patients’ Perceptions of Control in Tinnitus Treatment." Digital Commons @ East Tennessee State University, 2006. https://dc.etsu.edu/etsu-works/1624.
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Fonseca, Sonya G. "Role of WFS1 in Regulating Endoplasmic Reticulum Stress Signaling: A Dissertation." eScholarship@UMMS, 2009. https://escholarship.umassmed.edu/gsbs_diss/414.
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The endoplasmic reticulum (ER) is a multi-functional cellular compartment that functions in protein folding, lipid biosynthesis, and calcium homeostasis. Perturbations to ER function lead to the dysregulation of ER homeostasis, causing the accumulation of unfolded and misfolded proteins in the cell. This is a state of ER stress. ER stress elicits a cytoprotective, adaptive signaling cascade to mitigate stress, the Unfolded Protein Response (UPR). As long as the UPR can moderate stress, cells can produce the proper amount of proteins and maintain a state of homeostasis. If the UPR, however, is dysfunctional and fails to achieve this, cells will undergo apoptosis.
Diabetes mellitus is a group of metabolic disorders characterized by persistent high blood glucose levels. The pathogenesis of this disease involves pancreatic β-cell dysfunction: an abnormality in the primary function of the β-cell, insulin production and secretion. Activation of the UPR is critical to pancreatic β-cell survival, where a disruption in ER stress signaling can lead to cell death and consequently diabetes. There are several models of ER stress leading to diabetes. Wolcott-Rallison syndrome, for example, occurs when there is a mutation in the gene encoding one of the master regulators of the UPR, PKR-like ER kinase (PERK).
In this dissertation, we show that Wolfram Syndrome 1 (WFS1), an ER transmembrane protein, is a component of the UPR and is a downstream target of two of the master regulators of the UPR, Inositol Requiring 1 (IRE1) and PERK. WFS1 mutations lead to Wolfram syndrome, a non-autoimmune form of type 1 diabetes accompanied by optical atrophy and other neurological disorders. It has been shown that patients develop diabetes due to the selective loss of their pancreatic β-cells. Here we define the underlying molecular mechanism of β-cell loss in Wolfram syndrome, and link this cell loss to ER stress and a dysfunction in a component of the UPR, WFS1. We show that WFS1 expression is localized to the β-cell of the pancreas, it is upregulated during insulin secretion and ER stress, and its inactivation leads to chronic ER stress and apoptosis.
This dissertation also reveals the previously unknown function of WFS1 in the UPR. Positive regulation of the UPR has been extensively studied, however, the precise mechanisms of negative regulation of this signaling pathway have not. Here we report that WFS1 regulates a key transcription factor of the UPR, activating transcription factor 6 (ATF6), through the ubiquitin-proteasome pathway. WFS1 expression decreases expression levels of ATF6 target genes and represses ATF6-mediated activation of the ER stress response (ERSE) promoter. WFS1 recruits and stabilizes an E3 ubiquitin ligase, HMG-CoA reductase degradation protein 1 (HRD1), on the ER membrane. The WFS1-HRD1 complex recruits ATF6 to the proteasome and enhances its ubiquitination and proteasome-mediated degradation, leading to suppression of the UPR under non-stress conditions. In response to ER stress, ATF6 is released from WFS1 and activates the UPR to mitigate ER stress.
This body of work reveals a novel role for WFS1 in the UPR, and a novel mechanism for regulating ER stress signaling. These findings also indicate that hyperactivation of the UPR can lead to cellular dysfunction and death. This supports the notion that tight regulation of ER stress signaling is crucial to cell survival. This unanticipated role of WFS1 for a feedback loop of the UPR is relevant to diseases caused by chronic hyperactivation of ER stress signaling network such as pancreatic β-cell death in diabetes and neurodegeneration.
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McDaniel, L. M., Marc A. Fagelson, and Sherri Smith. "Changes in Scores of Tinnitus Handicap Inventory Over Time." Digital Commons @ East Tennessee State University, 2008. https://dc.etsu.edu/etsu-works/1628.
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Fagelson, Marc A. "Tinnitus in the Military and Veterans." Digital Commons @ East Tennessee State University, 2008. https://dc.etsu.edu/etsu-works/1632.
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Fagelson, Marc A. "Associations Between Tinnitus and PTSD Affect Tinnitus Management." Digital Commons @ East Tennessee State University, 2004. https://dc.etsu.edu/etsu-works/1617.
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Fagelson, Marc A. "Identification and Treatment of the Patient with Severe Tinnitus." Digital Commons @ East Tennessee State University, 2003. https://dc.etsu.edu/etsu-works/1611.
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Fagelson, Marc A., and David M. Baguley. "Tinnitus in the Future." Digital Commons @ East Tennessee State University, 2015. https://www.amzn.com/1597567213.
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Excerpt: Tinnitus: Clinical and Research Perspectives summarizes contemporary findings from basic and clinical research regarding tinnitus mechanisms, effects, and interventions. The text features a collection of international authors, active researchers, and clinicians who provide an expansive scope of material that ensures relevance for patients and professionals. Reviews and reports of contemporary research findings underscore the text s value for classroom use in audiology and otolaryngology programs. Patients and students of audiology will benefit from the text s coverage of tinnitus mechanisms, emerging practice considerations, and expectations for outcomes--for example, recent successes of cognitive behavioral therapy, neuromodulation, and hearing aid use. These and other topics, such as the effects of noise and drugs on tinnitus, are reported in a way that enhances clinicians ability to weave such strategies into their own work. The influence of tinnitus on all aspects of life is explored, from art to medicine and communication to isolation, thereby providing clinicians and patients a deeper understanding of and greater facility managing a tinnitus experience. Finally, this text includes case studies that provide a practical view of tinnitus effects and management approaches. The editors hope that the consideration of mechanisms, interventions, and outcomes resonates with patients, clinicians, and students of audiology.
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Fagelson, Marc A. "Audiological Assessment of Tinnitus Patients." Digital Commons @ East Tennessee State University, 2009. https://dc.etsu.edu/etsu-works/1634.
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Rose, A. Danielle, and Marc A. Fagelson. "Efficacy of Treatment in a VA Tinnitus Clinic." Digital Commons @ East Tennessee State University, 2004. https://dc.etsu.edu/etsu-works/1614.
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Self-assessment forms and diagnostic tests were used to assess benefits of a treatment program that addressed tinnitus and hyperacusis severity in a population of 30 veterans (29 males, 1female) between the ages of 43 and 79. Patients were enrolled in the treatment program for an average of 20.8 months (range=12-31 months). For the purposes of this study, tinnitus was defined as the subjective perception of a sound lacking an environmental correlate. Hyperacusis was defined as the over-sensitivity to an environmental sound present at a level that would not produce excessive loudness for individuals with normal hearing sensitivity. Treatment strategies included guided counseling regarding auditory and neurological mechanisms of tinnitus coupled with sound therapy designed to reduce the tinnitus disruption. Sound therapy instruments utilized by the subjects included hearing aids, cochlear implants, bedside noise generators, and near-level tinnitus maskers. The tinnitus handicap inventory (THI), self-assessment forms, and loudness discomfort level (LDL) testing were administered to assess benefit of the treatment program. Subjects were first interviewed using an interview form adapted from Jastreboff and Jastreboff, 1999. The THI was then administered in interview format to all patients. Initial sessions were approximately two hours in length. Follow-up sessions lasted approximately one hour. Most patients returned for at least three follow-up visits over the course of their treatment. The correlation between the patients hearing thresholds and the tinnitus handicap inventory (THI) score were poor, consistent with previous reports. Pre and post-testing with the THI indicated that 36.7% of the test subjects experienced significant improvement in tinnitus handicap. The total scores and all sub-scale scores on the THI showed statistically significant improvements. An analysis of the self-assessment forms revealed that 27% of the subjects experienced improvement with concentration, 27% experienced improvement with sleep, 36.7% experienced improvement with quiet recreational activities, and 23.3% experienced improvement with social activities. LDL testing was administered at the initial and post treatment sessions with twenty-two of the thirty subjects. LDL testing indicated that hyperacusis severity was reduced by 13.6% in the right ear and 4.6% in the left ear from the initial evaluation to the post treatment evaluation. Regarding test subject satisfaction with the treatment program, 93.3% expressed satisfaction, and 90% indicated they would be unhappy if asked to return their sound generating devices. Test subjects appeared to be satisfied with their overall experiences with the tinnitus treatment program. The clinical implications of these findings will be discussed.
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Fagelson, Marc A. "Clinical Findings Linking Tinnitus to Post-Traumatic Stress Disorder." Digital Commons @ East Tennessee State University, 2007. https://dc.etsu.edu/etsu-works/1626.
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Fagelson, Marc A. "Approaches to Tinnitus Management and Treatment." Digital Commons @ East Tennessee State University, 2014. https://dc.etsu.edu/etsu-works/1591.
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Tinnitus continues to challenge patients from all walks of life and clinicians from a variety of disciplines. The lack of an evidence base to support a specific treatment confounds efforts to provide consistent benefit to patients and in many instances creates in the patient the impression that nothing can be done to improve their situation. Part of the problem is that although patients rarely experience complete elimination of a tinnitus signal, they often experience relief when receiving effective counseling, specific coping strategies, and sound therapy. Although in most clinical activities the tinnitus remains (i.e., it is not cured), its influence may wane as the patient learns to manage their environment, activities, and ultimately their response to tinnitus. At the same time, several medical interventions target reduction of the tinnitus sound, an approach more consistent with what patients expect as a cure. Therefore, the majority of clinical activity directed at care for patients with tinnitus typically targets either elimination of the tinnitus sound (tinnitus treatment) or modification of the patient's response to the sound (tinnitus management). This review distinguishes and offers examples of both treatment and management programs employed clinically for patients with tinnitus.
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Fagelson, Marc A. "Tinnitus and Posttraumatic Stress Disorder." Digital Commons @ East Tennessee State University, 2009. https://dc.etsu.edu/etsu-works/1636.
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Smith, Sherri L., and Marc A. Fagelson. "Development of the Self-Efficacy for Tinnitus Management Questionnaire." Digital Commons @ East Tennessee State University, 2011. https://dc.etsu.edu/etsu-works/1589.
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Background: Self-efficacy refers to the beliefs (i.e., confidence) individuals have in their capabilities to perform skills needed to accomplish a specific goal or behavior. Research in the treatment of various health conditions such as chronic pain, balance disorders, and diabetes shows that self-efficacy beliefs play an important role in treatment outcomes and management of the condition. This article focuses on the application of self-efficacy to the management of tinnitus. The first step in formally incorporating self-efficacy in existing treatment regimens or developing a self-efficacy approach for tinnitus treatment is to have a valid and reliable measure available to assess the level of tinnitus self-efficacy.
Purpose: The objective of this study was to develop the Self-Efficacy for Tinnitus Management Questionnaire (SETMQ) and to obtain the psychometric properties of the questionnaire in a group of patients with tinnitus.
Research Design: Observational study.
Study Sample: A total of 199 patients who were enrolled in the Tinnitus Clinic at the James H. Quillen Veterans Affairs Medical Center participated in the current study.
Data Collection and Analysis: The SETMQ was mailed to patients enrolled in the Tinnitus Clinic. The participants who completed one copy of the SETMQ were mailed a second copy to complete approximately 2 weeks later. An exploratory factor analysis was conducted to identify the most coherent subscale structure of the SETMQ. The internal consistency and test‐retest reliability for each of the subscales and the questionnaire as a whole were assessed. The validity of the SETMQ also was evaluated by investigating the relations between the SETMQ and other clinical measures related to tinnitus.
Results: Five components emerged from the factor analysis that explained 75.8% of the variance related to the following areas: (1) routine tinnitus management, (2) emotional response to tinnitus, (3) internal thoughts and interaction with others, (4) tinnitus concepts, and (5) use of assistive devices. Four items failed to load on any factor and were discarded, resulting in 40 items on the final SETMQ. The internal consistency reliability of the overall questionnaire and for each subscale was good (Chronbach's α ranged from .74 to .98). Item-total correlations ranged from .47 to .86, indicating that each item on the SETMQ correlated at a moderate or marked level with the SETMQ aggregate score. Intraclass correlation coefficients were computed to determine the test‐retest reliability of the SETMQ total scale and separately for each subscale, which were all above .80, indicating good test‐retest reliability. Correlations among the SETMQ subscales and various tinnitus-related measures (e.g., Tinnitus Handicap Inventory, tinnitus loudness rating, tinnitus distress rating, etc.) were significant, albeit indicative of fair to good relations overall (range r = ‐.18 to ‐.53).
Conclusions: The results of the current study suggest that the SETMQ is a valid and reliable measure that may be an insightful instrument for clinicians and investigators who are interested in assessing tinnitus self-efficacy. Incorporating self-efficacy principles into tinnitus management would provide clinicians with another formalized treatment option. A self-efficacy approach to treating tinnitus may result in better outcomes compared with approaches not focusing on self-efficacy principles.
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Fagelson, Marc A. "Psychoacoustic Measures of Tinnitus." Digital Commons @ East Tennessee State University, 2005. https://dc.etsu.edu/etsu-works/1620.
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Fagelson, Marc A. "Tinnitus Management Affects Symptoms of PTSD." Digital Commons @ East Tennessee State University, 2008. https://dc.etsu.edu/etsu-works/1629.
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Wicker, Christina Ann. "MULTIVARIATE ANALYSIS TO IDENTIFY POTENTIAL BIOMARKERS FOR PROGNOSIS AND TREATMENT RESISTANCE IN HEAD AND NECK CANCER PATIENTS." UKnowledge, 2018. https://uknowledge.uky.edu/toxicology_etds/19.
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It is estimated that nearly 50,000 individuals in the United States will be diagnosed with head and neck cancer in 2017 (American Cancer Society www.cancer.org). Ninety percent of oral cancers are head and neck squamous cell carcinoma (HNSCC). Major obstacles in the treatment of HNSCC are recurrence and treatment resistance, which contributes to increased mortality. Therefore, there is increased need to determine genetic alterations in HNSCC that may be ideal novel drug targets, and biomarkers to improve diagnostic and prognostic testing.
Abnormal localization and overexpression of base excision repair protein and transcriptional regulator Apurinic/Apyrimidic endonuclease (APE1) has been associated with treatment resistance and poor prognosis. Therefore, we explored mechanisms for how APE1 contributes to treatment resistance and increased mortality in HNSCC.
Because oxidative stress heavily influences APE1’s expression and transcriptional regulatory activities, we examined genes involved in oxidative stress management, including SOD3 and NRF2. PPARGC1A, a NRF2 transcriptional co-activator, was also examined as our lab previously observed a link between APE1 and PPARGC1A expression. This previous work also revealed that APE1 suppressed gene expression of tumor suppressor, decorin (DCN).
To examine possible mechanisms for how APE1 regulates expression of tumor suppressors and antioxidants, digital image analysis of immunohistochemistry staining was used to identify alterations in protein expression. Nuclear and total cellular protein expression of APE1, DCN, NRF2, PPARGC1A, and SOD3 were quantified in regions of proximal benign, carcinoma in situ (CIS) and invasive HNSCC. Patient survival analysis revealed that increased APE1, DCN, and PPARGC1A protein levels were significantly associated with reduced survival in CIS, benign, and invasive tissues respectively. Using multivariate analysis of protein expression, we identified that increased APE1 protein levels in the CIS of primary tumors were associated with the presence of cancer invaded lymph nodes. Elevated DCN and SOD3 protein levels in benign tissue were associated with poorly differentiated tumors as was reduced PPARGC1A in CIS.
Most importantly, potential prognostic biomarkers for use in early cancer development were identified. Identifying poor prognosis in early cancer development allows the possibility of improved treatment strategies, which could prevent invasive cancer development, and increase patient survival.
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Milanesi, Jovana de Moura. "Caracterização da respiração oral: avaliação multidisciplinar." Universidade Federal de Santa Maria, 2016. http://repositorio.ufsm.br/handle/1/3446.
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Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorIn the presence of nasal obstruction, nasal patency may be reduced, and nasal breathing is replaced by mouth breathing (MB). Orofacial, and otorhinolaringologic changes are present in this breathing mode, as well as head posture misalignment, as a compensatory mechanism for the nasal airflow impairment. Some characteristics are typically found, but MB diagnosis is still controversial among multidisciplinary assessments. This study was conduct to identify variables associated with mouth breathing diagnosis in children, based on multidisciplinary domains, including anamnesis, speech therapy, otorhinolaryngologic, occlusal and physiotherapeutic assessments. It also aimed to compare nasal patency and otorhinolaryngologic-orofacial features and craniocervical posture in children. Six-12 year-old children, both sexes underwent muldisciplinary evaluation constituted by: anamnesis; speech therapy evaluation, according to MBGR protocol; clinical and endoscopic otorhinolaryngologic (OTRL) examination; occlusal and physical therapy assessments (nasal patency and body posture). Nasal patency was measured, by means of Peak Nasal Inspiratory Flow absolute (PNIF) values and Nasal Obstruction Symptom Evaluation (NOSE) scale. Craniocervical posture was evaluated with biophotogrametric measures (software SAPO, v.0.68), such as: Cervical Distance (CD); Head Horizontal Alignment (HHA), Flexion-Extension Head Position (FE) and Lumbar Distance (LD). Mann-Whitney, Kruskal-Wallis, Spearman Correlation Coefficient and Multiple Logistic Regression were used for data analysis. One hundred thirty three children took part in the study. Significant lower values of PNIF and %PNIF in children with restless sleep (p=0.006 and p=0.002), nasal obstruction report (p=0.027 and p=0.023) and runny nose (p=0.004 and p=0.012), unsystematic lip closure during mastication (p=0.040 and 0.026), masticatory speed reduced (p=0.006 and p= 0.008) and altered solid food swallowing (p=0.006 and p=0.001) were found. Significant lower PNIF was found in children with pale inferior turbinate (p=0.040). PNIF and %PNIF was significantly higher in children with mild everted lip (p=0.008 and p=0.000). PNIF was significantly higher in children with tongue width increased (p=0.027) and lower in children with hard palate width reduced (p=0.037). PNIF was significantly lower in children with altered speech (p=0.004). FE was significantly higher in children with nasal patency decreased (p=0.023). Negative and weak correlation between FE and %PNIF (r=-0.266; p=0.002) and positive and weak correlation between CD and PNIF (r=0.209; p=0.016) were found. NOSE scores were negatively correlated with PNIF (r= -0.179; p=0.039). It was found association of MB diagnosis in each professional domain with: nasal obstruction report (OR =5.55), time of pacifier sucking (OR=1.25), convex facial type (OR=3.78), obtuse nasal angle (OR=4.30), half-open or open lip posture (OR=4.13), tongue positioned on the mouth floor (OR=5.88), hard palate width reduced (OR=2.99), unexpected contraction of orbicularis and mentalis muscles during mastication (OR= 2.97), obstructive pharyngeal tonsills (OR=8.37), Angle Class II malocclusion (OR= 10.85) and regular gingival maintenance (OR=2.89). Nasal patency was lower in children with restless sleep, rhinitis signs and symptoms, hard palate width reduced and with changes in mastication, deglutition and speech functions. Children with decreased nasal patency presented greater head extension and, this postural deviation is prone to increase as nasal airflow decreases, indicating the relationship between craniocervical posture and nasal patency. Nasal obstruction report, time of pacifier sucking, convex facial type, obtuse nasal angle, half-open or open lip posture, tongue positioned on the mouth floor, hard palate width reduced, unexpected contraction during mastication, obstructive pharyngeal tonsils, Angle Class II malocclusion and regular gingival maintenance were associated with MB diagnosis
Na presença de uma obstrução nasal, a permeabilidade pode estar reduzida e a respiração nasal é substituída pela respiração oral (RO). Alterações orofaciais e otorrinolaringológicas são associadas a essa condição, bem como alterações na postura da cabeça, como mecanismo compensatório a redução do fluxo nasal. Algumas características são tipicamente associadas a RO, mas seu diagnóstico ainda permanece controverso. Este estudo foi conduzido para identificar variáveis associadas com o diagnóstico de respiração oral em crianças, baseado nos domínios multidisciplinares. Também se propôs a comparar a permeabilidade nasal e as características orofaciais, fonoaudiológicas e postura craniocervical em crianças. Um total de 133 crianças de seis a 12 anos de idade, de ambos os sexos, submeteram-se avaliação multidisciplinar constituída de: anamnese; avaliação fonoaudiológica, de acordo com o protocolo MBGR; exame OTRL clínico e endoscópico; avaliações oclusal e fisioterapêutica (permeabilidade nasal e postura corporal). A permeabilidade nasal foi medida por meio do Pico de Fluxo Inspiratório Nasal (PFIN) e valores da escala Nasal Obstruction Symptom Evaluation (NOSE). A postura corporal foi avaliada com medidas biofotogramétricas (Software SAPO, v.0.68) como: Distância Cervical (DC); Alinhamento Horizontal da Cabeça (AHC); Ângulo de Flexo-Extensão da Cabeça (FE) e Distância Lombar (DL). Para a análise dos dados foram utilizados os testes U de Mann-Whitney, Kruskal-Wallis, Correlação de Spearmann e Regressão Logística Múltipla. PFIN e %PFIN foram menores nas crianças com sono agitado (p=0,006 e p=0,002), relato de obstrução nasal (p=0,027 e p=0,023), rinorreia (p=0,004 e p=0,012), fechamento labial assistemático na mastigação (p=0,040 e p=0,026), velocidade mastigatória reduzida (p=0,006 e p= 0,008), com alteração na deglutição de sólidos (p=0,006 e p=0,001) e somente PFIN naquelas com largura de palato reduzida (p=0,037) e alteração da fala (p=0,004). Foram encontrados valores menores de PFIN nas crianças com palidez das conchas nasais inferiores (p=0,040). PFIN e %PFIN foram maiores nas crianças com lábio levemente evertido (p=0,008 e p=0,000) e somente o PFIN naquelas com largura aumentada da língua (p=0,027). FE foi maior nas crianças com permeabilidade nasal diminuída (p=0,023). Foi encontrada correlação negativa e fraca entre FE e %PFIN (r=-0,266; p=0,002) e positiva e fraca entre DC e PFIN (r=0,209; p=0,016). Os escores da escala NOSE foram negativamente correlacionados com PFIN (r= -0,179; p=0,039). Foi observada associação do diagnóstico de respiração com: relato de obstrução nasal (OR =5,55), tempo de uso de chupeta (OR=1,25), tipo facial convexo (OR=3,78), ângulo nasolabial obtuso (OR=4,30), postura de lábios entreabertos ou abertos (OR=4,13), postura de língua no assoalho da boca (OR=5,88), largura do palato duro reduzida (OR=2,99), contrações não esperadas dos músculos orbiculares e mentual durante a mastigação (OR= 2,97), tonsilas faríngeas obstrutivas (OR=8,37), má oclusão classe II de Angle (OR= 10,85) e conservação gengival regular (OR=2,89). A permeabilidade nasal foi menor em crianças com sono agitado, sinais e sintomas de rinite, largura reduzida do palato duro e alterações nas funções de mastigação, deglutição e fala. Crianças com permeabilidade nasal reduzida apresentaram maior extensão da cabeça e esta alteração postural tende a aumentar à medida que o fluxo nasal diminui, indicando uma relação entre a postura craniocervical e permeabilidade nasal. Foram associadas com a RO as variáveis: relato de obstrução nasal; tempo de uso de chupeta; tipo facial convexo; ângulo nasolabial obtuso; postura de lábios entreabertos ou abertos; postura de língua no assoalho da boca; largura reduzida do palato duro; contrações não esperadas na mastigação; tonsilas faríngeas obstrutivas, má oclusão classe II de Angle e conservação gengival regular.
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Fagelson, Marc A., and Sherri L. Smith. "Tinnitus Self-Efficacy and Other Tinnitus Self-Report Variables in Patients With and Without Post-Traumatic Stress Disorder." Digital Commons @ East Tennessee State University, 2016. https://dc.etsu.edu/etsu-works/1598.
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Objective: Individuals with tinnitus and co-occurring psychological conditions typically rate their tinnitus as more disturbing than individuals without such comorbidities. Little is known about how tinnitus self-efficacy, or the confidence that individuals have in their abilities to successfully manage the effects of tinnitus, is influenced by mental or psychological health (PH) status. The purpose of this study was to examine the influence of psychological state on tinnitus perceptions and tinnitus self-efficacy in individuals with chronic tinnitus.
Design: Observational study. Three groups (N = 199) were examined and included: (1) those with tinnitus without a concurrent psychological condition (tinnitus-only; n = 103), (2) those with tinnitus and concurrent PH condition other than post-traumatic stress disorder (PTSD; tinnitus + PH; n = 34), and (3) those with tinnitus and PTSD (tinnitus + PTSD; n = 62). The Self-Efficacy for Tinnitus Management Questionnaire (SETMQ) was administered. Responses on the SETMQ were compared among the groups, as well as to other indicators of tinnitus perception such as (1) the percentage of time tinnitus was audible (tinnitus awareness), (2) the percentage of time tinnitus was distressing/bothersome, (3) tinnitus loudness, (4) tinnitus handicap inventory scores, (5) subjective ratings of degree of hearing loss, and (6) subjective ratings of sound tolerance problems.
Results: The tinnitus + PTSD group reported significantly poorer tinnitus self-efficacy levels on average than the tinnitus-only group on all SETMQ subscales and poorer self-efficacy levels than the tinnitus + PH group for most subscales (except for routine management and devices). Tinnitus self-efficacy levels were similar between the tinnitus + PH and tinnitus-only groups except for the emotional response subscale in which the tinnitus-only patients reported higher self-efficacy on average than both the other groups. Group differences were not seen for tinnitus loudness ratings nor for the amount of time individuals were aware of their tinnitus. Group differences were observed for the percentage of time tinnitus was distressing/bothersome, self-reported degree of hearing loss, sound tolerance problems ratings, and responses on the tinnitus handicap inventory (THI). In general, the group differences revealed patient ratings for the tinnitus-only group were least severe, followed by the tinnitus + PH group, and the tinnitus + PTSD group rated tinnitus effects as most severe. With all patient responses, the tinnitus + PTSD group was found to be significantly more affected by tinnitus than the tinnitus-only group; in some cases, the responses were similar between the tinnitus + PTSD and tinnitus + PH group and in other cases, responses were similar between the tinnitus + PH group and the tinnitus-only group.
Conclusions: Tinnitus self-efficacy, along with other self-assessed tinnitus characteristics, varied across groups distinguished by PH diagnoses. In general, individuals with tinnitus and concurrent PTSD reported significantly poorer tinnitus self-efficacy and more handicapping tinnitus effects when compared to individuals with other psychological conditions or those with tinnitus alone. The group differences highlighted the need to consider tinnitus self-efficacy in intervention strategies, particularly for patients with tinnitus and concurrent PTSD as the results reiterated the unique ability of PTSD to interact in powerful and disturbing ways with the tinnitus experience and with patients’ coping ability.
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Fagelson, Marc A. "Post-Traumatic Stress Disorder." Digital Commons @ East Tennessee State University, 2009. https://dc.etsu.edu/etsu-works/1635.
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Rose, A. Danielle, and Marc A. Fagelson. "Treatment Outcome in a VA Tinnitus Clinic." Digital Commons @ East Tennessee State University, 2005. https://dc.etsu.edu/etsu-works/1619.
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Fagelson, Marc A. "Loudness Growth in Patients with Tinnitus and PTSD." Digital Commons @ East Tennessee State University, 2005. https://dc.etsu.edu/etsu-works/1618.
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Smith, Sherri, and Marc A. Fagelson. "Preliminary Psychometric Results of a Tinnitus Self-Efficacy Questionnaire." Digital Commons @ East Tennessee State University, 2008. https://dc.etsu.edu/etsu-works/1630.
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Eriksson, Per Olof. "Developing otitis media : experimental studies in particular regarding inflammatory changes in the tympanic membrane." Doctoral thesis, Umeå : Univ, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-180.
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Fagelson, Marc A. "Hyperacusis and PTSD in a Veteran Tinnitus Clinic." Digital Commons @ East Tennessee State University, 2009. https://dc.etsu.edu/etsu-works/1633.
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Fagelson, Marc A. "Sound Therapy Approaches: Post-traumatic Tinnitus." Digital Commons @ East Tennessee State University, 2016. https://dc.etsu.edu/etsu-works/1603.
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Fagelson, Marc A. "Post-traumatic Stress Disorder Affects Auditory Behavior of Tinnitus Patients." Digital Commons @ East Tennessee State University, 2005. https://dc.etsu.edu/etsu-works/1599.
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Fagelson, Marc A., Sherri Smith, and L. M. McDaniel. "Analysis of Self-assessed Tinnitus Handicap in Patients with Post-Traumatic Stress Disorder." Digital Commons @ East Tennessee State University, 2008. https://dc.etsu.edu/etsu-works/1631.
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Fagelson, Marc A., Colleen Noe, Owen Murnane, and Jennifer S. Blevins. "Predicted Gain and Functional Gain With Transcranial Routing of Signal Completely-in-the-Canal Hearing Aids." Digital Commons @ East Tennessee State University, 2004. https://dc.etsu.edu/etsu-works/1586.
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Transcranial routing of signal (TCROS) was accomplished using completely-in-the-canal (CIC) hearing aids in 5 profoundly unilaterally hearing-impaired individuals. The functional gain realized by the participants far exceeded the gain predicted by measuring the acoustic output and real ear aided response of the hearing aids. The difference between predicted and functional gain increased with signal frequency and was attributed at least in part to mechanical vibration of the hearing aid in the external canal. Implications for fitting unilateral hearing loss using TCROS amplifying systems are discussed.
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Fagelson, Marc A., Colleen Noe, Jennifer Blevins, and Owen Murnane. "Bone Conduction Transmission and Head‐Shadow Effects for Unilateral Hearing Losses Fit with Transcranial Cic Hearing Aids." Digital Commons @ East Tennessee State University, 2000. https://dc.etsu.edu/etsu-works/1584.
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Bone conduction transmission and head‐shadow effects were determined with transcranial completely‐in‐the‐canal (TCCIC) CROS hearing aids. Five subjects with documented profound unilateral hearing loss and experience with traditional CROS/BICROS fittings (TCROS) were tested with a CIC hearing aid placed in their poorer ear. Peak SPL was measured at the tympanic membrane and ranged from 105–115 dB SPL at 2000 Hz. Pure‐tone crossover thresholds and functional gain tested at frequencies from 250–8000 Hz varied considerably more than the SPL measures. The pure‐tone results indicated that sensitivity in the better ear was moderately associated with functional gain across frequency. Speech recognition was then tested in the sound field in two conditions: direct (noise in the poorer ear, speech in the better ear) and indirect (noise in the better ear, speech in the poorer ear) at S/Ns of −6, 0, +6, +12, and quiet. The TCCIC fittings were more effective than TCROS aids across S/Ns, particularly in the direct condition. In the indirect condition, the two fittings performed similarly. When data were pooled across conditions, the TCCIC aids provided better word recognition than the TCROS aids, particularly for those subjects with greater sensitivity in the better ear.
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Frykholm, Carina. "Clinical and Genetic Studies of Hearing Impairment." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Universitetsbiblioteket [distributör], 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-8290.
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Locke, Richard R. "Anatomy of the transmastoid endolymphatic sac decompression in the management of Ménière’s disease." Thesis, University of Glasgow, 2008. http://theses.gla.ac.uk/208/.
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Ménière’s disease affects 1 in 1000 people and produces vertigo and hearing loss (Morrison, 1981). Endolymphatic sac decompression has been advocated on the basis that endolymphatic hydrops is the underlying pathology. The endolymphatic sac is said to be the terminal dilatation of the membranous labyrinth. It has been proposed that endolymph flows from the semicircular canals and cochlea to the endolymphatic sac. Portman (1927) devised a procedure for ‘decompressing’ the endolymphatic sac by removal of the bone from the posterior cranial fossa to relieve the symptoms of Ménière’s disease. Surgery on the endolymphatic sac remains controversial. Shea (1979) and Bagger-Sjöbäck et al (1990, 1993) have studied the endolymphatic sac using different techniques. There are discrepancies in the results between the two studies. The hypothesis that the endolymphatic sac can be safely approached and decompressed by a transmastoid route was tested. A total of thirteen cadaver heads and ten isolated temporal bones were used. A series of dissections were performed to examine the endolymphatic sac, perform measurements and analyse surgical approaches to the sac. Histological and electron microscopic study were performed. The lumen of the endolymphatic sac was not always identifiable in the dura of the posterior cranial fossa or it frequently lay over the sigmoid sinus. In the dura of the posterior cranial fossa where the endolymphatic sac is located was a thickening of the dura. This thickening was present even in the absence of the endolymphatic sac. The endolymphatic sac can be safely approached by a transmastoid approach, if there is an extraosseous component to the endolymphatic sac. The proximal endolymphatic sac can be approached by posterior cranial fossa route.
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Adura, Peter. "Virus-host interactions following experimental rhinovirus infection in airways disease." Thesis, University of Southampton, 2013. https://eprints.soton.ac.uk/374747/.
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Sundstedt, Stina. "Swallowing and deep brain stimulation : swallowing function in Parkinson's disease after subthalamic nucleus and caudal zona incerta deep brain stimulation." Licentiate thesis, Umeå universitet, Öron- näs- och halssjukdomar, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-86133.
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Background Swallowing problems are common in Parkinson’s disease, and these affect morbidity and mortality largely due to aspiration-induced pneumonia. Even mild dysphagia affects patient Quality of Life. Deep Brain Stimulation (DBS), a surgical treatment for Parkinson’s disease, improves overall motor function, though the effect of DBS on swallowing function is not clear. The aim of the studies in this thesis was to improve our understanding of the effect from DBS of caudal zona incerta and subthalamic nucleus on pharyngeal swallowing function. Specific aims were to compare DBS effects over time postoperatively (6 & 12 months) for swallowing function, on and off stimulation, with a preoperative baseline assessment in order to identify possible negative swallowing effects of DBS. Methods Eight patients with DBS in caudal zona incerta and eleven patients with DBS in subthalamic nucleus were included in the two studies. The effect of DBS on swallowing function was evaluated by self-estimation on a visual analogue scale and fiberoptic endoscopic evaluation of swallowing function with a predefined swallowing protocol including Rosenbek’s Penetration/Aspiration Scale, Secretion Severity Scale,preswallow spillage, pharyngeal residue and pharyngeal clearance. The patients with caudal zona incerta DBS also answered questions regarding swallowing-related Quality of Life. All patients received L-dopa treatment during postoperative assessments. Results There was no clear effect of DBS on swallowing function in the two samples. The occurrence of aspiration, secretions, pharyngeal residue or clearance was not affected by the surgery or the stimulation. In the subthalamic nucleus DBS sample, self-estimations revealed an improvement with stimulation turned on. For the caudal zona incerta DBS patients, no effect of DBS was seen on the results from the swallowing-related QOL questions. Conclusion Subthalamic nucleus DBS and caudal zona incerta DBS did not appear to have a negative effect on swallowing function in this cohort. Patients with subthalamic nucleus DBS reported a self-perceived improvement in swallowing function after DBS. There appears to be no increased risk for aspiration or penetration due to surgery or stimulation regardless of stimulation site. Since the sample sizes in these cohorts are small, the findings need to be confirmed in larger studies.
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Fagelson, Marc A. "The Association Between Tinnitus and Posttraumatic Stress Disorder." Digital Commons @ East Tennessee State University, 2007. https://dc.etsu.edu/etsu-works/1673.
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Nwe, Thin Thin. "The management of peritonsillar abscess." Thesis, 1999. http://hdl.handle.net/10413/7661.
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Over a four month period from 1 st November 1998 to 28th February 1999 a randomised prospective study was undertaken in 75 patients with peritonsiller abscess (PTA) to determine the treatment modality that is most effective in alleviating the excruiating pain and discomfort associated with the condition. The patients were divided into three treatment groups. There were 25 patients in each group. Group A patients were treated with intravenous antibiotics and intra muscular opiates, Group B aspiration and oral antibiotics and Group C incision and drainage and oral antibiotics.
Pain relief was objectively assessed with each treatment modality by measuring the upper to lower incisor distance, 15 mins, 24 hours and 48 hours and oral intake at 2 hours, 24 hours and 48 hours after the initial treatment. The improvement of the mean upper to lower incisor distance 15 minutes after the initial treatment was 5% in Group A, 38% in Group B and 100% in Group C. Twenty four hours later the improvement was 30% in Group A, 111 % in Group B and 125% in Group C. None of the patients in Group A were able to take fluid orally at 2 hours. Only 2 patients (8%) could in Group B and 23 patients (92%) in Group C. 24 hours later, 15 patients (60%) could take fluid orally in group A, 19 (76%) in group B and 25 (100%) in group C. Treatment failures were those patients in whom the trismus, odynophagia and pyrexia failed to subside after 48 hours. There were 8 patients (30 per cent) in group A, 6 (24%) in group B and none in Group C. The 14 failures were successfully treated with incision and drainage. The conclusion derived from this study is that incision and drainage is superior to intravenous antibiotic and aspiration in alleviating the pain and discomfort associated with peritonsillar abscess.Thesis (M.Med.)-University of Natal, 1999.