Publications by authors named "Chia-Der Lin"

79 Publications

Cytolethal Distending Toxin C Exploits Lipid Rafts to Mitigate -Induced Pathogenesis.

Front Cell Dev Biol 2020 23;8:617419. Epub 2021 Feb 23.

Department of Microbiology and Immunology, Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan.

infection is associated with several gastrointestinal diseases, including gastritis, peptic ulcer, and gastrointestinal adenocarcinoma. Two major cytotoxins, vacuolating cytotoxin A (VacA) and cytotoxin-associated gene A (CagA), interact closely with lipid rafts, contributing to -associated disease progression. The cytolethal distending toxin consists of three subunits: CdtA, CdtB, and CdtC. Among them, CdtA and CdtC bind to membrane lipid rafts, which is crucial for CdtB entry into cells. In this study, we employed recombinant CdtC (rCdtC) to antagonize the functions of cytotoxin in cells. Our results showed that rCdtC alleviates cell vacuolation induced by VacA. Furthermore, rCdtC reduces CagA translocation, which decreases nuclear factor kappa-B activation and interleukin-8 production, resulting in the mitigation of gastric epithelial cell inflammation. These results reveal that CdtC hijacks cholesterol to compete for cytotoxin actions lipid rafts, ameliorating -induced pathogenesis.
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http://dx.doi.org/10.3389/fcell.2020.617419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940356PMC
February 2021

Metformin Increases Survival in Hypopharyngeal Cancer Patients with Diabetes Mellitus: Retrospective Cohort Study and Cell-Based Analysis.

Pharmaceuticals (Basel) 2021 Feb 26;14(3). Epub 2021 Feb 26.

Department of Life Sciences, and Ph.D. program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan.

Hypopharyngeal squamous cell carcinoma (HSCC) is usually diagnosed at an advanced stage, leading to a poor prognosis. Even after improvement of surgical techniques, chemotherapy, and radiation technology, the survival rate of HSCC remains poor. Metformin, which is commonly used for type 2 diabetes mellitus (DM), has been suggested to reduce the risk of various cancer types. However, only a few clinical studies mentioned the relationship between metformin use and HSCC. Hence, the aim of this study was to elucidate the specific effect and mechanism of action of metformin in hypopharyngeal cancer. We first assessed whether metformin use has an effect on hypopharyngeal cancer patients with DM by conducting a retrospective cohort study. Our results showed that DM hypopharyngeal cancer patients who used metformin exhibited significantly better overall survival rates than that without metformin treatment. The cell-based analysis further indicated that metformin treatment regulated p38/JNK pathway to reduce Cyclin D1 and Bcl-2 expressions. In addition, metformin activated the pathways of AMPKα and MEK/ERK to phosphorylate p27(Thr198) and reduce mTOR phosphorylation in cells. These actions direct cells toward G1 cell cycle arrest, apoptosis, and autophagy. Our results, through combining a clinical cohort analysis with an in vitro study, demonstrate that metformin can be used for drug repositioning in the treatment of DM patients with hypopharyngeal cancer.
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http://dx.doi.org/10.3390/ph14030191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996771PMC
February 2021

Fine Particulate Matter Exposure Alters Pulmonary Microbiota Composition and Aggravates Pneumococcus-Induced Lung Pathogenesis.

Front Cell Dev Biol 2020 26;8:570484. Epub 2020 Oct 26.

Department of Microbiology and Immunology, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.

Exposure to fine particulate matter (PM) with aerodynamic diameter ≤2.5 μm (PM) is closely correlated with respiratory diseases. Microbiota plays a key role in maintaining body homeostasis including regulation of host immune status and metabolism. As reported recently, PM exposure causes microbiota dysbiosis and thus promotes disease progression. However, whether PM alters pulmonary microbiota distribution and aggravates bacteria-induced pathogenesis remains unknown. In this study, we used mouse experimental models of PM exposure combined with infection. We characterized the airway microbiota of bronchoalveolar lavage fluid (BALF) by sequencing the 16S rRNA V3-V4 amplicon on the Illumina MiSeq platform, followed by a combination of bioinformatics and statistical analyses. Shannon-diversity index, observed ASVs, and Fisher's diversity index indicated that microbiota richness was significantly decreased in the mice treated with either PM or pneumococcus when compared with the control group. The genera , , , and were remarkably increased in mice exposed to PM combined with pneumococcal infection as compared to mice with pneumococcal infection alone. Histopathological examination exhibited that a more pronounced inflammation was present in lungs of mice treated with PM and pneumococcus than that in mouse groups exposed to either PM or pneumococcal infection alone. Our results demonstrate that PM alters the microbiota composition, thereby enhancing susceptibility to pneumococcal infection and exacerbating lung pathogenesis.
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http://dx.doi.org/10.3389/fcell.2020.570484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649221PMC
October 2020

Chronic rhinosinusitis and premorbid autoimmune diseases: a population-based case-control study.

Sci Rep 2020 10 29;10(1):18635. Epub 2020 Oct 29.

Department of Otorhinolaryngology, China Medical University Hospital, Taichung, 40447, Taiwan.

Evidence shows that chronic rhinosinusitis (CRS) is associated with prior presence of autoimmune diseases; however, large-scale population-based studies in the literature are limited. We conducted a population-based case-control study investigating the association between CRS and premorbid autoimmune diseases by using the National Health Insurance Research Database in Taiwan. The CRS group included adult patients newly diagnosed with CRS between 2001 and 2013. The date of diagnosis was defined as the index date. The comparison group included individuals without CRS, with 1:4 frequency matching for gender, age, and index year. Premorbid diseases were forward traced to 1996. Univariate and multivariate logistic regression was performed to estimate odds ratios (ORs) and 95% confidence intervals. The CRS group consisted of 30,611 patients, and the comparison group consisted of 122,444 individuals. Patients with CRS had a higher significant association with premorbid autoimmune diseases (adjusted OR 1.39 [1.28-1.50]). Specifically, patients with CRS had a higher significant association with ankylosing spondylitis, polymyositis, psoriasis, rheumatoid arthritis, sicca syndrome, and systemic lupus erythematosus (adjusted OR 1.49 [1.34-1.67], 3.47 [1.12-10.8], 1.22 [1.04-1.43], 1.60 [1.31-1.96], 2.10 [1.63-2.72], and 1.69 [1.26-2.25]). In subgroup analysis, CRS with and without nasal polyps demonstrated a significant association with premorbid autoimmune diseases (adjusted OR 1.34 [1.14-1.58] and 1.50 [1.38-1.62]). In addition, CRS with fungal and non-fungal infections also demonstrated a significant association with premorbid autoimmune diseases (adjusted OR 2.02 [1.72-2.49] and 1.39 [1.28-1.51]). In conclusion, a significant association between CRS and premorbid autoimmune diseases has been identified. These underlying mechanisms need further investigation.
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http://dx.doi.org/10.1038/s41598-020-75815-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596473PMC
October 2020

ACE2 localizes to the respiratory cilia and is not increased by ACE inhibitors or ARBs.

Nat Commun 2020 10 28;11(1):5453. Epub 2020 Oct 28.

Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305, USA.

The coronavirus SARS-CoV-2 is the causative agent of the ongoing severe acute respiratory disease pandemic COVID-19. Tissue and cellular tropism is one key to understanding the pathogenesis of SARS-CoV-2. We investigate the expression and subcellular localization of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), within the upper (nasal) and lower (pulmonary) respiratory tracts of human donors using a diverse panel of banked tissues. Here, we report our discovery that the ACE2 receptor protein robustly localizes within the motile cilia of airway epithelial cells, which likely represents the initial or early subcellular site of SARS-CoV-2 viral entry during host respiratory transmission. We further determine whether ciliary ACE2 expression in the upper airway is influenced by patient demographics, clinical characteristics, comorbidities, or medication use, and show the first mechanistic evidence that the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) does not increase susceptibility to SARS-CoV-2 infection through enhancing the expression of ciliary ACE2 receptor. These findings are crucial to our understanding of the transmission of SARS-CoV-2 for prevention and control of this virulent pathogen.
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http://dx.doi.org/10.1038/s41467-020-19145-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595232PMC
October 2020

Noise Induced Hearing Loss and Tinnitus-New Research Developments and Remaining Gaps in Disease Assessment, Treatment, and Prevention.

Brain Sci 2020 Oct 13;10(10). Epub 2020 Oct 13.

School of Medicine, China Medical University, Taichung City 40402, Taiwan.

Long-term noise exposure often results in noise induced hearing loss (NIHL). Tinnitus, the generation of phantom sounds, can also result from noise exposure, although understanding of its underlying mechanisms are limited. Recent studies, however, are shedding light on the neural processes involved in NIHL and tinnitus, leading to potential new and innovative treatments. This review focuses on the assessment of NIHL, available treatments, and development of new pharmacologic and non-pharmacologic treatments based on recent studies of central auditory plasticity and adaptive changes in hearing. We discuss the mechanisms and maladaptive plasticity of NIHL, neuronal aspects of tinnitus triggers, and mechanisms such as tinnitus-associated neural changes at the cochlear nucleus underlying the generation of tinnitus after noise-induced deafferentation. We include observations from recent studies, including our own studies on associated risks and emerging treatments for tinnitus. Increasing knowledge of neural plasticity and adaptive changes in the central auditory system suggest that NIHL is preventable and transient abnormalities may be reversable, although ongoing research in assessment and early detection of hearing difficulties is still urgently needed. Since no treatment can yet reverse noise-related damage completely, preventative strategies and increased awareness of hearing health are essential.
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http://dx.doi.org/10.3390/brainsci10100732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602100PMC
October 2020

Noise Induced Hearing Loss and Tinnitus-New Research Developments and Remaining Gaps in Disease Assessment, Treatment, and Prevention.

Brain Sci 2020 Oct 13;10(10). Epub 2020 Oct 13.

School of Medicine, China Medical University, Taichung City 40402, Taiwan.

Long-term noise exposure often results in noise induced hearing loss (NIHL). Tinnitus, the generation of phantom sounds, can also result from noise exposure, although understanding of its underlying mechanisms are limited. Recent studies, however, are shedding light on the neural processes involved in NIHL and tinnitus, leading to potential new and innovative treatments. This review focuses on the assessment of NIHL, available treatments, and development of new pharmacologic and non-pharmacologic treatments based on recent studies of central auditory plasticity and adaptive changes in hearing. We discuss the mechanisms and maladaptive plasticity of NIHL, neuronal aspects of tinnitus triggers, and mechanisms such as tinnitus-associated neural changes at the cochlear nucleus underlying the generation of tinnitus after noise-induced deafferentation. We include observations from recent studies, including our own studies on associated risks and emerging treatments for tinnitus. Increasing knowledge of neural plasticity and adaptive changes in the central auditory system suggest that NIHL is preventable and transient abnormalities may be reversable, although ongoing research in assessment and early detection of hearing difficulties is still urgently needed. Since no treatment can yet reverse noise-related damage completely, preventative strategies and increased awareness of hearing health are essential.
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http://dx.doi.org/10.3390/brainsci10100732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602100PMC
October 2020

Neurofibromatosis type 2 initially presenting as a preauricular mass: a case report.

J Otolaryngol Head Neck Surg 2020 Jun 26;49(1):45. Epub 2020 Jun 26.

Department of Otolaryngology Head and Neck Surgery, China Medical University Hospital, No.2, Yude Rd., North Dist., Taichung City, 404, Taiwan, Republic of China.

Neurofibromatosis type 2 (NF2) is a rare genetic disease involving multiple tumors of the central and peripheral nervous systems. Most patients with NF2 have bilateral vestibular schwannomas; nonvestibular schwannomas may also develop. While the majority of patients may present with hearing impairment, tinnitus, dizziness and balance disorders, some may present with cutaneous manifestations. We describe the case of a 20-year-old man who initially presented with a solitary subcutaneous painless nodule in the left preauricular area without any other symptoms. He received excisional biopsy for the preauricular mass and the pathologic diagnosis was schwannoma. Magnetic resonance imaging of brain and neck revealed multiple mass lesions over the bilateral cerebellopontine angle cisterns, extending to the bilateral internal auditory canals, bilateral cervical neuroforamens, cervical and upper thoracic spinal canals, and left posterior neck. The patient was diagnosed with NF2 according to the clinical criteria. He underwent gamma knife stereotactic radiosurgery for bilateral vestibular schwannomas and is now under regular monitoring. CONCLUSION: NF2 patients may present with an isolated solitary cutaneous schwannoma with no other associated clinical findings. Further assessment is thus warranted in young patients presenting with a peripheral schwannoma despite absence of other clinical findings.
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http://dx.doi.org/10.1186/s40463-020-00438-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320571PMC
June 2020

Robust ACE2 protein expression localizes to the motile cilia of the respiratory tract epithelia and is not increased by ACE inhibitors or angiotensin receptor blockers.

medRxiv 2020 May 12. Epub 2020 May 12.

Baxter Laboratory, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, California, USA.

We investigated the expression and subcellular localization of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), within the upper (nasal) and lower (pulmonary) respiratory tracts of healthy human donors. We detected ACE2 protein expression within the cilia organelle of ciliated airway epithelial cells, which likely represents the initial or early subcellular site of SARS-CoV-2 viral entry during respiratory transmission. We further determined whether ACE2 expression in the cilia of upper respiratory cells was influenced by patient demographics, clinical characteristics, co-morbidities, or medication use, and found no evidence that the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) increases ACE2 protein expression.
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http://dx.doi.org/10.1101/2020.05.08.20092866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273284PMC
May 2020

Association between Angiotensin-Converting Enzyme Inhibitors and Lung Cancer-A Nationwide, Population-Based, Propensity Score-Matched Cohort Study.

Cancers (Basel) 2020 Mar 21;12(3). Epub 2020 Mar 21.

Graduate Institute of Biomedical Sciences and School of Medicine, College of Medicine, China Medical University, Taichung 40447, Taiwan.

Background: Direct evidence of lung cancer risk in Asian users of angiotensin-converting enzyme inhibitors (ACEIs) is lacking.

Methods: The ACEI cohort comprised 22,384 patients aged ≥ 18 years with a first prescription of ACEI. The comparison angiotensin receptor blocker (ARB) cohort consisted of age-, sex- and comorbidity-matched patients at a ratio of 1:1. The primary outcome was the incidence of lung cancer, which was evaluated using a proportional hazard model.

Results: The overall incidence rates of lung cancer in the ACEI and ARB cohorts were 16.6 and 12.2 per 10,000 person-years, respectively. The ACEI cohort had a significantly higher risk of lung cancer than the ARB cohort (adjusted hazard ratio [aHR]. = 1.36; 95% confidence interval [CI]. = 1.11-1.67). Duration-response and dose-response analyses revealed that compared with patients who did not receive ACEIs, patients who received ACEIs for more than 45 days per year (aHR = 1.87; 95% CI = 1.48-2.36) and patients who received more than 540 defined daily doses of ACEIs per year (aHR =1.80; 95% CI = 1.43--2.27) had a significantly higher risk of lung cancer. The cumulative incidence of lung cancer was also significantly higher in the ACEI cohort than in the ARB cohort (log-rank test, = 0.002).

Conclusions: ACEI use is associated with an increased risk of lung cancer compared with ARB use. Patients using ARBs have a significantly lower risk of lung cancer than non-ARB users.
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http://dx.doi.org/10.3390/cancers12030747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140054PMC
March 2020

Long-Term Surveillance of Antibiotic Prescriptions and the Prevalence of Antimicrobial Resistance in Non-Fermenting Gram-Negative Bacilli.

Microorganisms 2020 Mar 12;8(3). Epub 2020 Mar 12.

School of Medicine, Department of Medical Laboratory Science and Biotechnology, Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, Taiwan.

The increasing emergence of multidrug-resistant (MDR) bacteria has been recognized as a public health threat worldwide. Hospitalized patients and outpatients are commonly infected by non-fermenting Gram-negative bacilli (NFGNB), particularly the - complex (ACB) and . Antimicrobial agents are critical for treating the nosocomial infections caused by NFGNB. The aim of this study was to assess antimicrobial resistance and the use of antimicrobial agents. The bacterial isolates of 638,152 specimens from both inpatients and outpatients, retrieved from 2001 to 2008 at a medical center in central Taiwan, were examined for their susceptibility to various antimicrobial agents, including cefepime, imipenem, ciprofloxacin, gentamicin, amikacin, meropenem, and levofloxacin. Administrated prescriptions of the monitored antibiotics were analyzed using the Taiwan National Health Insurance Research Database (NHIRD). Our results show that the defined daily doses (DDDs) for cefepime, imipenem, and ciprofloxacin increased with time, and a trend toward reduced antimicrobial sensitivities of both ACB and was noticeable. In conclusion, the antimicrobial sensitivities of ACB and were reduced with the increased use of antibiotics. Continuous surveillance of antibiotic prescriptions and the prevalence of emerging resistance in nosocomial infections is warranted.
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http://dx.doi.org/10.3390/microorganisms8030397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7142802PMC
March 2020

Low-grade albuminuria is associated with hearing loss in non-diabetic US males: A cross-sectional analysis of 1999-2004 national health and nutrition examination survey.

Medicine (Baltimore) 2020 Mar;99(11):e19284

School of Medicine, College of Medicine, China Medical University, Taichung.

High levels of albuminuria have been demonstrated to associate with hearing loss in non-diabetic people, while the clinical impact of low-grade albuminuria has attracted less attention. This cross-sectional population-based study aimed to examine whether hearing loss in non-diabetic United States (US) adults is independently associated with low-grade albuminuria or reduced estimated glomeruli filtration rate (eGFR).A total of 2518 participants aged 20 to 69 years were selected from the US National Health and Nutritional Examination Survey database. Participants with diabetes or high-grade albuminuria were excluded. Hearing loss was assessed using low-frequency pure-tone average (LFPTA) thresholds (0.5, 1.0, 2.0 kHz) and high-frequency pure-tone average (HFPTA) thresholds (3.0, 4.0, 6.0, 8.0 kHz). Logistic and linear regression analyses were used to evaluate associations between renal function indicators and hearing loss.The median age of included participants was 37.4 years, and 55% of them were female. Multivariate analysis revealed that participants with urinary albumin-to-creatinine ratio (UACR) in the highest tertile had a significantly higher risk of hearing loss (OR, 1.79; 95% CI, 1.01-3.19) and higher HFPTA thresholds (β: 2.23; SE: 0.77). Participants with eGFR <60 mL/min/1.73 m had higher LFPTA thresholds (β: 4.31; SE: 1.79). After stratification by sex, a significant risk remained only for males in the highest UACR tertile, with 2.18 times the risk of hearing loss (95% CI, 1.06-4.48).Non-diabetic US males with low-grade albuminuria are at increased risk of hearing loss, independent of eGFR.
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http://dx.doi.org/10.1097/MD.0000000000019284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220087PMC
March 2020

Medical students' resilience: a protective role on stress and quality of life in clerkship.

BMC Med Educ 2019 Dec 27;19(1):473. Epub 2019 Dec 27.

Center of Rheumatology and Immunology, China Medical University Hospital, Taichung, Taiwan, Republic of China.

Background: Resilience refers to the ability to be flexible and adaptive in response to challenges. Medical students in clerkship who are transitioning from medical studies to clinical practice face a variety of workplace demands that can lead to negative learning experiences and poor quality of life. This study explored whether medical students' resilience plays a protective role against the stresses incurred during workplace training and on their professional quality of life during clerkships.

Methods: This was a 1-year prospective web-based questionnaire study comprising one cohort of medical students in their fifth year who were working as clerks as part of their 6-year medical education programme at one medical school in Taiwan between September 2017 and July 2018. Web-based, validated, structured, self-administered questionnaires were used to measure the students' resilience at the beginning of the clerkship and their perceived training stress (i.e. physical and psychological demands) and professional quality of life (i.e. burnout and compassion satisfaction) at each specialty rotation. Ninety-three medical students who responded to our specialty rotation surveys at least three times in the clerkship were included and hierarchical regressions were performed.

Results: This study verified the negative effects of medical students' perceived training stress on burnout and compassion satisfaction. However, although the buffering (protective) effects of resilience were observed for physical demands (one key risk factor related to medical students' professional quality of life), this was not the case for psychological demands (another key risk factor). In addition, through the changes in R square (∆R) values of the hierarchical regression building, our study found that medical students' perceived training stresses played a critical role on explaining their burnout but their resilience on their compassion satisfaction.

Conclusions: Medical students' resilience demonstrated a buffering effect on the negative relationship between physical demands and professional quality of life during clerkships. Moreover, different mechanisms (predictive paths) leading to medical students' professional quality of life such as burnout and compassion satisfaction warrant additional studies.
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http://dx.doi.org/10.1186/s12909-019-1912-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935077PMC
December 2019

Immunoglobulin G4-Related Disease Presented as Recurrent Otitis Media and Mixed Hearing Loss Treated With Cyclophosphamide and Rituximab: A Case Report.

Arch Rheumatol 2019 Jun 30;34(2):233-237. Epub 2018 Nov 30.

Department Rheumatology, China Medical University Hospital, Taichung, Taiwan.

Immunoglobulin G4-related disease (IgG4-RD) is a systemic autoimmune disease; however, it rarely presents as recurrent otitis media and mixed hearing loss. In this article, we present a 43-year-old male patient who presented with recurrent otitis media and mixed hearing loss that is the 12th case of IgG4-RD with middle and inner ear involvement. We also report the clinical response of cyclophosphamide and rituximab therapy in IgG4- RD. These two drugs have never been used to treat otologic symptoms, but were used to treat other organs affected by IgG4-RD. One year later, the patient underwent mastoidectomy of the right ear and the pathological reports revealed IgG4-related disease. A rheumatologist administered immunosuppressive therapy comprising cyclophosphamide and rituximab. After therapy, patient's right-sided mixed hearing loss partially improved. We recorded all pure tone audiometry data to evaluate the clinical course and treatment effect. Finally, we concluded that pathological confirmation and further immunosuppressive therapy should be considered in a timely manner to prevent hearing impairment. We recommend cyclophosphamide and rituximab for the treatment of diseases involving the middle and inner ear.
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http://dx.doi.org/10.5606/ArchRheumatol.2019.7178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6719581PMC
June 2019

Efficacy and Safety of AM-111 in the Treatment of Acute Unilateral Sudden Deafness-A Double-blind, Randomized, Placebo-controlled Phase 3 Study.

Otol Neurotol 2019 06;40(5):584-594

Auris Medical AG, Basel, Switzerland.

Objective: To confirm the efficacy and safety of AM-111 (brimapitide), a cell-penetrating c-Jun N-terminal Kinase (JNK) inhibitor, in patients suffering from severe to profound acute unilateral idiopathic sudden sensorineural hearing loss (ISSNHL).

Study Design: Prospective, double-blind, randomized, placebo-controlled phase 3 study with follow-up visits on Days 3, 7, 28, and 91.

Setting: Fifty-one European and Asian sites (tertiary referral centers, private ENT practices).

Patients: Two hundred fifty-six patients aged 18 to 65 years presenting within 72 hours following ISSNHL onset with mean hearing loss ≥ 40 dB and mean threshold ≥ 60 dB at the 3 worst affected contiguous test frequencies.

Interventions: Single-dose intratympanic injection of AM-111 (0.4 or 0.8 mg/ml) or placebo; oral prednisolone as reserve therapy if hearing improvement < 10 dB at Day 7.

Main Outcome Measures: Hearing improvement to Day 28 was the primary efficacy endpoint; complete hearing recovery, frequency of reserve therapy used, complete tinnitus remission, improvement in word recognition were secondary endpoints. Safety was evaluated by the frequency of clinically relevant hearing deterioration and adverse events.

Results: While the primary efficacy endpoint was not met in the overall study population, post-hoc analysis showed a clinically relevant and nominally significant treatment effect for AM-111 0.4 mg/ml in patients with profound ISSNHL. The study drug and the administration procedure were well tolerated.

Conclusions: AM-111 provides effective otoprotection in case of profound ISSNHL. Activation of the JNK stress kinase, AM-111's pharmacologic target, seems to set in only following pronounced acute cochlear injury associated with large hearing threshold shifts.
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http://dx.doi.org/10.1097/MAO.0000000000002229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6553962PMC
June 2019

Pentoxifylline versus Steroid Therapy for Idiopathic Sudden Sensorineural Hearing Loss with Diabetes.

J Int Adv Otol 2018 Aug;14(2):176-180

China Medical University Hospital, Otolaryngology Head and Neck Surgery, Taichung City, Taiwan.

Objectives: To compare the efficacy of pentoxifylline with that of conventional steroid therapy in diabetic patients with idiopathic sudden sensorineural hearing loss (ISSNHL) and to compare blood sugar levels during hospitalization.

Materials And Methods: Medical charts were retrospectively reviewed for all diabetic patients admitted to one institution for ISSNHL between 2000 and 2015. We analyzed 298 cases; 50 patients received pulse steroid treatment (steroid group) and 248 received intravenous administration of pentoxifylline only (pentoxifylline group). Hearing change was evaluated by comparing the initial hearing tests with follow-up hearing tests for up to 3 months. Blood sugar levels were also compared between the 2 groups.

Results: At 3 months post-treatment, the degree of hearing recovery was similar between the 2 groups. The pure-tone average was improved from baseline by 17.9±21.2 dB in the steroid group and 18.9±20.7 dB in the pentoxifylline group (p=0.776); hearing recovery rates were also similar (40% vs 39.1%; p=0.826). During hospitalization, average fasting blood sugar levels were higher (203.9±92.0 vs 174.4±54.8 mg/dL; p=0.033) and acute hyperglycemia was more common (48.0% vs 33.1%; p=0.044) with steroid versus pentoxifylline treatment.

Conclusion: Hearing recovery rates did not significantly differ between steroid and pentoxifylline treatment in diabetic patients with ISSNHL, but pentoxifylline appeared to be associated with better blood sugar control.
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http://dx.doi.org/10.5152/iao.2018.4690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354469PMC
August 2018

Comparison of Balloon Dilation and Laser Eustachian Tuboplasty in Patients with Eustachian Tube Dysfunction: A Meta-analysis.

Otolaryngol Head Neck Surg 2018 04 20;158(4):617-626. Epub 2018 Mar 20.

1 Department of Otolaryngology-Head and Neck Surgery, China Medical University Hospital, Taichung, Taiwan.

Objective We aimed to perform a meta-analysis examining balloon dilatation and laser tuboplasty for the treatment of eustachian tube dysfunction (ETD). Data Sources PubMed, Cochrane, and Embase search up to April 18, 2016, with the following keywords: eustachian, middle-ear, eustachian tuboplasty, balloon tuboplasty, laser tuboplasty, laser dilatation, and balloon dilatation. Review Methods Randomized controlled trials and prospective, retrospective, and 1-arm studies of patients with ETD treated with balloon dilatation or laser tuboplasty were included. Outcome measures were improvement of eustachian tube score (ETS) and tympanometry and Valsalva maneuver results. Results Two retrospective and 11 prospective studies were included (1063 patients; 942 treated with balloon and 121 with laser tuboplasty). Balloon tuboplasty resulted in a significant improvement of ETS (pooled standardized mean difference [SMD], 0.94; 95% confidence interval [CI], 0.23-1.66; P = .009) and, compared with laser tuboplasty, a greater tympanometry improvement rate (pooled event rate = 73% vs 13%; P = .001). Valsalva maneuver improvement rate was not different between the group results (pooled event rate = 67% vs 50%; P = .472). The maximum number of studies that provided outcome data for any one measure was only 4, and sensitivity analysis indicated ETS results may have been overly influenced by 2 studies. No balloon tuboplasty studies reported ETS data, preventing comparison between the 2 procedures. Conclusion Both procedures can improve symptoms of ETD; however, because of the limited numbers of studies reporting data of the outcomes of interest, it remains unclear if one procedure provides greater benefits.
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http://dx.doi.org/10.1177/0194599817753609DOI Listing
April 2018

Exponential Modeling of Frequency-Following Responses in American Neonates and Adults.

J Am Acad Audiol 2018 02;29(2):125-134

Department of Otolaryngology-HNS, China Medical University Hospital, Taiwan, China.

Background: The scalp-recorded frequency-following response (FFR) has been widely accepted in assessing the brain's processing of speech stimuli for people who speak tonal and nontonal languages. Characteristics of scalp-recorded FFRs with increasing number of sweeps have been delineated through the use of an exponential curve-fitting model in Chinese adults; however, characteristics of speech processing for people who speak a nontonal language remain unclear.

Purpose: This study had two specific aims. The first was to examine the characteristics of speech processing in neonates and adults who speak a nontonal language, to evaluate the goodness of fit of an exponential model on neonatal and adult FFRs, and to determine the differences, if any, between the two groups of participants. The second aim was to assess effective recording parameters for American neonates and adults.

Research Design: This investigation employed a prospective between-subject study design.

Study Sample: A total of 12 American neonates (1-3 days old) and 12 American adults (24.1 ± 2.5 yr old) were recruited. Each neonate passed an automated hearing screening at birth and all adult participants had normal hearing and were native English speakers.

Data Collection And Analysis: The English vowel /i/ with a rising pitch contour (117-166 Hz) was used to elicit the FFR. A total of 8,000 accepted sweeps were recorded from each participant. Three objective indices (Frequency Error, Tracking Accuracy, and Pitch Strength) were computed to estimate the frequency-tracking acuity and neural phase-locking magnitude when progressively more sweeps were included in the averaged waveform. For each objective index, the FFR trends were fit to an exponential curve-fitting model that included estimates of asymptotic amplitude, noise amplitude, and a time constant.

Results: Significant differences were observed between groups for Frequency Error, Tracking Accuracy, and Pitch Strength of the FFR trends. The adult participants had significantly smaller Frequency Error (p < 0.001), better Tracking Accuracy (p = 0.001), and larger Pitch Strength (p = 0.003) values than the neonate participants. The adult participants also demonstrated a faster rate of improvement (i.e., a smaller time constant) in all three objective indices compared to the neonate participants. The smaller time constants observed in adults indicate that a larger number of sweeps will be needed to adequately assess the FFR for neonates. Furthermore, the exponential curve-fitting model provided a good fit to the FFR trends with increasing number of sweeps for American neonates (mean r = 0.89) and adults (mean r = 0.96).

Conclusions: Significant differences were noted between the neonatal and adult participants for Frequency Error, Tracking Accuracy, and Pitch Strength. These differences have important clinical implications in determining when to stop a recording and the number of sweeps needed to adequately assess the frequency-encoding acuity and neural phase-locking magnitude in neonates and adults. These findings lay an important foundation for establishing a normative database for American neonates and adults, and may prove to be useful in the development of diagnostic and therapeutic paradigms for neonates and adults who speak a nontonal language.
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http://dx.doi.org/10.3766/jaaa.16135DOI Listing
February 2018

Effect of Transcranial Direct Current Stimulation in Patients With Tinnitus: A Meta-Analysis and Systematic Review.

Ann Otol Rhinol Laryngol 2018 Feb 1;127(2):79-88. Epub 2017 Dec 1.

1 Department of Otolaryngology-Head and Neck Surgery, China Medical University Hospital, Taichung, Taiwan.

Objectives: Subjective tinnitus is a phantom sensation experienced without any external source of sound that profoundly impacts the quality of life. Some investigations have claimed that transcranial direct current stimulation (tDCS) reduces tinnitus, but studies on tDCS have demonstrated variable results. This meta-analysis aimed to examine the effect of tDCS on patients with tinnitus.

Methods: We searched for articles published through January 5, 2016, in Medline, Cochrane, EMBASE, and Google Scholar using the following keywords: tinnitus, transcranial direct current stimulation, and tDCS. The study outcomes were change in magnitude estimates of loudness (loudness), tinnitus-related distress (distress), and Tinnitus Handicap Inventory (THI).

Results: Pooled results demonstrated that tDCS did not have a beneficial effect on loudness (pooled standardized difference in means = 0.674, 95% CI, -0.089 to 1.437, P = .083). Further, the pooled results demonstrated a greater reduction in distress for the tDCS group (pooled standardized difference in means = 0.634, 95% CI, 0.021-1.247, P = .043).

Conclusions: We conclude that the pooled results demonstrated a greater reduction in distress for groups treated with tDCS as compared with those administered a sham treatment.
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http://dx.doi.org/10.1177/0003489417744317DOI Listing
February 2018

Predictors of hearing outcomes following low-dose stereotactic radiosurgery in patients with vestibular schwannomas: A retrospective cohort review.

Clin Neurol Neurosurg 2017 Nov 5;162:16-21. Epub 2017 Sep 5.

Department of Otolaryngology, China Medical University Hospital, Taichung, Taiwan; Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.

Objectives: Hearing deterioration is a major concern for hearing-preserved patients with vestibular schwannomas who are treated with stereotactic radiosurgery (SRS). Thus, determining which patients are more likely to have worse hearing outcomes following SRS may facilitate clinicians in deciding whether conservative policy should be applied in the interest of hearing preservation. This study aimed to define the predictors of hearing outcomes following SRS.

Patients And Methods: This retrospective study included 100 patients who underwent low-dose SRS (12- to 13-Gy marginal dose) for vestibular schwannomas between January 2004 and January 2014. Clinical factors and hearing outcomes following radiosurgery were reviewed.

Results: All patients had serviceable hearing at diagnosis and prior to SRS. The median follow-up period was 6.5years (range, 3-10years). The hearing preservation rate in the first, third, and fifth year after radiosurgery was 89%, 68%, and 63%, respectively. A mean cochlear dose lower than 4Gy was a favorable predictor of hearing outcome. Maximal cochlear dose, patient age, pre-treatment pure-tone average, and imaging characteristics were not associated with post-treatment hearing preservation. Our study showed an accelerated rate of deterioration of serial pure-tone average in the first 3years, followed by a more gradual decline after radiosurgery.

Conclusion: Our results suggest that cochlear dose constraint is the most crucial factor for hearing preservation. This study provides insight into the rate of hearing preservation and the pattern of hearing deterioration following radiosurgery and can help clinicians advise patients of hearing outcomes following SRS.
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http://dx.doi.org/10.1016/j.clineuro.2017.09.001DOI Listing
November 2017

Cytolethal Distending Toxin Enhances Radiosensitivity in Prostate Cancer Cells by Regulating Autophagy.

Front Cell Infect Microbiol 2017 8;7:223. Epub 2017 Jun 8.

Department of Medical Research, School of Medicine, Graduate Institute of Basic Medical Sciences, China Medical University and HospitalTaichung, Taiwan.

Cytolethal distending toxin (CDT) produced by contains three subunits: CdtA, CdtB, and CdtC. Among these three toxin subunits, CdtB is the toxic moiety of CDT with DNase I activity, resulting in DNA double-strand breaks (DSB) and, consequently, cell cycle arrest at the G2/M stage and apoptosis. Radiation therapy is an effective modality for the treatment of localized prostate cancer (PCa). However, patients often develop radioresistance. Owing to its particular biochemical properties, we previously employed CdtB as a therapeutic agent for sensitizing radioresistant PCa cells to ionizing radiation (IR). In this study, we further demonstrated that CDT suppresses the IR-induced autophagy pathway in PCa cells by attenuating c-Myc expression and therefore sensitizes PCa cells to radiation. We further showed that CDT prevents the formation of autophagosomes via decreased high-mobility group box 1 (HMGB1) expression and the inhibition of acidic vesicular organelle (AVO) formation, which are associated with enhanced radiosensitivity in PCa cells. The results of this study reveal the detailed mechanism of CDT for the treatment of radioresistant PCa.
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http://dx.doi.org/10.3389/fcimb.2017.00223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5462984PMC
February 2018

Lactoferrin interacts with SPLUNC1 to attenuate lipopolysaccharide-induced inflammation of human nasal epithelial cells via down-regulated MEK1/2-MAPK signaling.

Biochem Cell Biol 2017 06 8;95(3):394-399. Epub 2017 Feb 8.

a Department of Life Sciences, and Agricultural Biotechnology Center, National Chung Hsing University, Taichung 40227, Taiwan.

The short palate, lung, and nasal epithelium clone 1 (SPLUNC1) protein is an important innate material in the upper airway, and lactoferrin (LF) aids the innate functions in humans. In this study, a nasal epithelial model was used to investigate how LF modulates SPLUNC1 to reduce the inflammatory process mediated by lipopolysaccharide (LPS). The inflammation of human RPMI-2650 cells was induced with LPS to evaluate SPLUNC1 expression after treating the cells with bovine LF (bLF). The interaction pathway between LF and SPLUNC1 in LPS-induced inflammation was further investigated. Our study reveals that the addition of bLF results in the recovery of SPLUNC1 expression in nasal epithelial cells under LPS-induced inflammation. MAPK is involved in the main pathway for the SPLUNC1 and bLF interaction. Decreased SPLUNC1 function could be recovered by addition of bLF. The MEK1/2-MAPK signaling pathway is crucial for the SPLUNC1 and bLF interaction. Therefore, LF could support SPLUNC1 in the innate immunity recovery process.
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http://dx.doi.org/10.1139/bcb-2016-0047DOI Listing
June 2017

Training demands on clerk burnout: determining whether achievement goal motivation orientations matter.

BMC Med Educ 2016 Aug 22;16(1):214. Epub 2016 Aug 22.

School of Medicine, Medical Sociology, China Medical University, No.91, Hsueh-Shih Road, Taichung, 40402, Taiwan, Republic of China.

Background: In the education field, learning experiences are considered learners' properties and are viewed as a key determinant in explaining learners' learning processes, especially for training novices such as clerks with varying levels of commitment to the medical profession. This study explored whether clerks' achievement goal motivation orientations might buffer the negative well-being to a certain extent, considering their training demands during clinical training.

Methods: Ninety-four clerks at a tertiary medical center were longitudinally traced during their 2-year clerkship spanning from September 2013 to April 2015. Web-based, validated, structured, self-administered questionnaires were used to evaluate the clerks' properties of achievement goal motivation orientation and personal background at the beginning of the clerkship. Regular surveys were conducted to evaluate their perceptions of training demands and burnout at each specialty rotation. Overall, 2230 responses were analyzed, and linear mixed-effects models were used to examine the repeated measures of the clerks.

Results: The results revealed that higher perceived psychological and physical demands of training were related to higher perceived burnout during the 2-year clerkship. Although both the clerks' task and ego orientations were related to reduced burnout (direct effects), only task orientation was indicated to exert a buffering effect on their perception of physical demands on burnout in the 1st year of the clerkship.

Conclusions: Considering the negative effects of training demands (psychological and physical), we observed a limited effect of the task achievement motivation orientation of medical students; therefore, additional studies might focus on strategies to facilitate medical students in clerkships in addressing both the psychological and physical demands inherent in training workplaces to improve their learning experience and well-being.
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http://dx.doi.org/10.1186/s12909-016-0742-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994176PMC
August 2016

Development of Subcortical Pitch Representation in Three-Month-Old Chinese Infants.

Percept Mot Skills 2016 Feb 1;122(1):123-35. Epub 2016 Feb 1.

Department of Otolaryngology-HNS, China Medical University Hospital, Taiwan;School of Medicine, China Medical University, Taiwan.

This study investigated the development of subcortical pitch processing, as reflected by the scalp-recorded frequency-following response, during early infancy. Thirteen Chinese infants who were born and raised in Mandarin-speaking households were recruited to partake in this study. Through a prospective-longitudinal study design, infants were tested twice: at 1-3 days after birth and at three months of age. A set of four contrastive Mandarin pitch contours were used to elicit frequency-following responses. Frequency Error and Pitch Strength were derived to represent the accuracy and magnitude of the elicited responses. Paired-samples t tests were conducted and demonstrated a significant decrease in Frequency Error and a significant increase in Pitch Strength at three months of age compared to 1-3 days after birth. Results indicated the developmental trajectory of subcortical pitch processing during the first three months of life.
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http://dx.doi.org/10.1177/0031512516631054DOI Listing
February 2016

Subcortical neural representation to Mandarin pitch contours in American and Chinese newborns.

J Acoust Soc Am 2016 06;139(6):EL190

Department of Otolaryngology-HNS, China Medical University Hospital, 2 Yuh-Der Road, Taichung 404, Taiwan

Voice pitch carries important information for speech understanding. This study examines the neural representation of voice pitch at the subcortical level, as reflected by the scalp-recorded frequency-following responses from ten American and ten Chinese newborns. By utilizing a set of four distinctive Mandarin pitch contours that mimic the English vowel /yi/, the results indicate that the rising and dipping pitch contours produce significantly better tracking accuracy and larger response amplitudes than the falling pitch contour. This finding suggests a hierarchy of potential stimuli when testing neonates who are born in a tonal or non-tonal linguistic environment.
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http://dx.doi.org/10.1121/1.4953998DOI Listing
June 2016

Influence of clerks' personality on their burnout in the clinical workplace: a longitudinal observation.

BMC Med Educ 2016 Jan 28;16:30. Epub 2016 Jan 28.

Department of Education, Department of Otolaryngology, China Medical University Hospital, No.2, Yude Road, Taichung, 404, Taiwan, ROC.

Background: The clinical training of medical students in clerkship is crucial to their future practice in healthcare services. This study investigates burnout during a 2-year clerkship training period as well as the role of personality traits on burnout during training.

Methods: Ninety-four clerks at a tertiary medical centre who provided at least 10 responses to a routine survey on clinical rotation were included in this study, which spanned September 2013 to April 2015. Web-based, validated, structured, self-administered questionnaires were used to evaluate the clerks' personalities at the beginning of the first clerkship year, and regular surveys were conducted to evaluate their burnout at each clinical specialty rotation throughout the 2-year clerkship period. Overall, 2230 responses were analysed, and linear mixed-effects models were used to examine the repeated measures of the clerks.

Results: Our findings revealed that medical student burnout scores were lower in the second year than they were in the first year of clerkships. Using the Big Five personality factors, all of the propensities, namely extroversion, agreeableness, consciousness, emotional stability, and openness were related to different extents of burnout reduction in the first clerkship year (P < .05). However, only emotional stability and openness were related to clerks' reduced burnout in the second clerkship year. Furthermore, being female, older, and with accompanied living were more closely related to lower burnout compared with being male, younger, and living alone throughout the clerkship period.

Conclusions: The students in the first-year clerkship, particularly those with higher burnout levels, had tendencies in the Big Five personality characteristics, exhibiting higher levels of introversion, antagonism, lack of direction, neuroticism, and not open to new experiences. The students in the second-year clerkship who do not exhibit a high propensity for emotional stability and openness should be of particular concern. The findings can serve as a reference for clinical teachers and mentors to effectively prevent and reduce the burnout of medical students during clerkship training at clinical workplaces.
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http://dx.doi.org/10.1186/s12909-016-0553-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4730758PMC
January 2016

Interleukin-13 Inhibits Lipopolysaccharide-Induced BPIFA1 Expression in Nasal Epithelial Cells.

PLoS One 2015 8;10(12):e0143484. Epub 2015 Dec 8.

Graduate Institute of Basic Medical Science, School of Medicine, China Medical University and Hospital, Taichung, Taiwan.

Short palate, lung, and nasal epithelium clone 1 (SPLUNC1) protein is expressed in human nasopharyngeal and respiratory epithelium and has demonstrated antimicrobial activity. SPLUNC1 is now referred to as bactericidal/permeability-increasing fold containing family A, member 1 (BPIFA1). Reduced BPIFA1 expression is associated with bacterial colonization in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Interleukin 13 (IL-13), predominately secreted by T helper 2 (TH2) cells, has been found to contribute to airway allergies and suppress BPIFA1 expression in nasal epithelial cells. However, the molecular mechanism of IL-13 perturbation of bacterial infection and BPIFA1 expression in host airways remains unclear. In this study, we found that lipopolysaccharide (LPS)-induced BPIFA1 expression in nasal epithelial cells was mediated through the JNK/c-Jun signaling pathway and AP-1 activation. We further demonstrated that IL-13 downregulated the LPS-induced activation of phosphorylated JNK and c-Jun, followed by attenuation of BPIFA1 expression. Moreover, the immunohistochemical analysis showed that IL-13 prominently suppressed BPIFA1 expression in eosinophilic CRSwNP patients with bacterial infection. Taken together, these results suggest that IL-13 plays a critical role in attenuation of bacteria-induced BPIFA1 expression that may result in eosinophilic CRSwNP.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0143484PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4672888PMC
June 2016

Redesigning a clinical mentoring program for improved outcomes in the clinical training of clerks.

Med Educ Online 2015 16;20:28327. Epub 2015 Sep 16.

School of Medicine, China Medical University, Taichung, Taiwan, ROC.

Introduction: Mentorship has been noted as critical to medical students adapting to clinical training in the medical workplace. A lack of infrastructure in a mentoring program might deter relationship building between mentors and mentees. This study assessed the effect of a redesigned clinical mentoring program from the perspective of clerks. The objective was to assess the benefits of the redesigned program and identify potential improvements.

Methods: A redesigned clinical mentoring program was launched in a medical center according to previous theoretical and practical studies on clinical training workplaces, including the elements of mentor qualifications, positive and active enhancers for mentor-mentee relationship building, the timing of mentoring performance evaluation, and financial and professional incentives. A four-wave web survey was conducted, comprising one evaluation of the former mentoring program and three evaluations of the redesigned clinical mentoring program. Sixty-four fifth-year medical students in clerkships who responded to the first wave and to at least two of the three following waves were included in the study. A structured and validated questionnaire encompassing 15 items on mentor performance and the personal characteristics of the clerks was used. Mixed linear models were developed for repeated measurements and to adjust for personal characteristics.

Results: The results revealed that the redesigned mentoring program improved the mentors' performance over time for most evaluated items regarding professional development and personal support provided to the mentees.

Conclusions: Our findings serve as an improved framework for the role of the institution and demonstrate how institutional policies, programs, and structures can shape a clinical mentoring program. We recommend the adoption of mentorship schemes for other cohorts of medical students and for different learning and training stages involved in becoming a physician.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4575418PMC
http://dx.doi.org/10.3402/meo.v20.28327DOI Listing
June 2016

Pitch perception and frequency-following responses elicited by lexical-tone chimeras.

Int J Audiol 2016 25;55(1):53-63. Epub 2015 Aug 25.

b Department of Otolaryngology-HNS , China Medical University Hospital , Taichung , Taiwan.

Objective: Previous research has shown the usefulness of utilizing auditory chimeras in assessing a listener's perception of the envelope and fine structure for an acoustic stimulus. However, research comparing and contrasting behavioral and electrophysiological responses to this stimulus type is scarce.

Design: Two sets of chimeric stimuli were constructed by interchanging the envelopes and fine-structures of the rising/yi(2)/and falling/yi(4)/Mandarin pitch contours that were filtered through 1, 2, 4, 8, 16, 32, and 64 frequency banks. Behavioral pitch-perception tasks were administered through a two-alternative, forced-choice paradigm. Electrophysiological responses were measured through scalp-recorded frequency-following responses (FFRs) to the lexical-tone chimeras.

Study Sample: Twenty American and twenty Chinese adults were recruited.

Results: A two-way analysis of variance showed significance (p < 0.05) within and across the filter bank and language background factors for the behavioral measurements, while the frequency-following response demonstrated a significance only across the filter banks.

Conclusions: Perceptual importance of envelope cues increases starting from 16 filter banks, while the FFR accuracy and magnitude decreases with increasing number of filter banks. These results can be useful in assessing experience-dependent neuroplasticity and in designing speech processing strategies for cochlear-implant users who speak tonal or non-tonal languages around the globe.
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http://dx.doi.org/10.3109/14992027.2015.1072774DOI Listing
August 2016

Increased Acquired Cholesteatoma Risk in Patients with Osteoporosis: A Retrospective Cohort Study.

PLoS One 2015 14;10(7):e0132447. Epub 2015 Jul 14.

Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan; Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan.

Objective: Clinically, we found the increased incidence of acquired colesteatoma in the patients with osteoporosis. In this study, we used a retrospective cohort to examine this association and to investigate the possible mechanism.

Methods: We conducted a population-based retrospective cohort study by using the National Health Insurance Research Database (NHIRD). We identified an osteoporosis cohort comprising 37 124 patients newly diagnosed with osteoporosis aged 20 years or older. Patients in the comparison cohort had no history of osteoporosis and were frequency matched with the patients in the osteoporosis cohort according to sex, age, and index year.

Results: The acquired cholesteatoma incidence rates for the osteoporosis and comparison cohorts were 1.12 and 0.83 per 1000 person-years, respectively. After we adjusted for confounding factors, the osteoporosis cohort exhibited a 1.32-fold increased acquired cholesteatoma risk relative to the comparison cohort (hazard ratio [HR] = 1.32, 95% confidence interval [CI] = 1.11-1.57). In addition, patients with no history of otitis media (HR = 1.33, 95% CI = 1.11-1.59), cancer (HR = 1.34, 95% CI = 1.12-1.60), or COPD (HR = 1.26, 95% CI = 1.05-1.52) in the osteoporosis cohort exhibited an increased risk of subsequent acquired cholesteatoma relative to those in the comparison cohort.

Conclusions: Our cohort study indicated that patients with osteoporosis had a 1.31-fold increased acquired cholesteatoma risk relative to the comparison cohort. This risk was further increased in patients with comorbid otitis media. Hence, we recommend that otolaryngologists evaluate the condition of the middle ear of patients with osteoporosis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0132447PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4501779PMC
April 2016