Endobronchial valves for emphysema and persistent air-leak: 10-year experience in an Asian country.

BACKGROUND: Endobronchial valve (EBV) therapy, a validated method for bronchoscopic lung volume reduction (BLVR) in severe emphysema, has been explored for persistent air-leak (PAL) management. However, its effectiveness and safety in the Asian population require further real-world evaluation. In this study, we assessed the outcomes of treatment with EBV within this demographic. METHODS: We conducted a retrospective analysis of medical records from 11 Korean centers. For the emphysema cohort, inclusion criteria were patients diagnosed with emphysema who underwent bronchoscopy intended for BLVR. We assessed these patients for clinical outcomes of chronic obstructive pulmonary disease. All patients with PAL who underwent treatment with EBV were included. We identified the underlying causes of PAL and evaluated clinical outcomes after the procedure. RESULTS: The severe emphysema cohort comprised 192 patients with an average age of 70.3 years, and 95.8% of them were men. Ultimately, 137 underwent treatment with EBV. Three months after the procedure, the BLVR group demonstrated a significant improvement in forced expiratory volume in 1 s (+160 mL vs. +30 mL; P = 0.009). Radiographic evidence of lung volume reduction 6 months after BLVR was significantly associated with improved survival (adjusted hazard ratio 0.020; 95% confidence interval 0.038-0.650; P = 0.010). Although pneumothorax was more common in the BLVR group (18.9% vs. 3.8%; P = 0.018), death was higher in the no-BLVR group (38.5% vs. 54.5%, P = 0.001), whereas other adverse events were comparable between the groups. Within the subset of 18 patients with PAL, the predominant causes of air-leak included spontaneous secondary pneumothorax (44.0%), parapneumonic effusion/empyema (22.2%), and post-lung resection surgery (16.7%). Following the treatment, the majority (77.8%) successfully had their chest tubes removed. Post-procedural complications were minimal, with two incidences of hemoptysis and one of empyema, all of which were effectively managed. CONCLUSIONS: Treatment with EBV provides substantial clinical benefits in the management of emphysema and PAL in the Asian population, suggesting a favorable outcome for this therapeutic approach.

Shortened telomere length in peripheral blood leukocytes is associated with cumulative radioactive iodine doses in patients with differentiated thyroid carcinoma.

BACKGROUND: Telomere length is associated with cancer risk and cancer aggressiveness. Radioactive iodine (RAI) therapy for thyroid cancer has raised concerns for second primary malignancy (SPM) in patients with high cumulative doses. The association between RAI dose and peripheral blood leukocyte telomere length was examined. METHODS: A total of 425 patients were included who underwent total thyroidectomy and were followed up for at least 1 year with or without RAI treatment. The relative telomere length (RTL) of the patients was assessed via a quantitative polymerase chain reaction amplification method. RAI doses were divided into five groups on the basis of cumulative dose, and a comparison was made among these groups. RESULTS: The number of patients with RAI treatment was 287 (67.5%), and the cumulative RAI dose was 3.33 GBq (range, 1.11-131.35 GBq). The mean RTL was significantly shorter in the highest RAI group (>22.2 GBq) compared to both the no-RAI and lower dose groups. The association between RAI dose and RTL was positive in the lower RAI group (1.1-3.7 GBq) and negative in the highest RAI group in both univariate and multivariate analyses. We observed 59 (13.9%) SPMs and 20 (4.7%) mortalities, and RTL did not show a significant risk effect for all-cause, thyroid cancer-specific, or SPM-specific mortality. CONCLUSIONS: In patients with thyroid cancer who underwent total thyroidectomy, peripheral blood leukocyte telomere length exhibited a significant association with cumulative RAI dose higher than 22.2 GBq. These results suggest the possibility of telomere length shortening in patients who undergo high-dose RAI treatment.

Integrative Multi-omics Analysis Reveals Different Metabolic Phenotypes Based on Molecular Characteristics in Thyroid Cancer.

PURPOSE: Thyroid cancer metabolic characteristics vary depending on the molecular subtype determined by mutational status. We aimed to investigate the molecular subtype-specific metabolic characteristics of thyroid cancers. EXPERIMENTAL DESIGN: An integrative multi-omics analysis was conducted, incorporating transcriptomics, metabolomics, and proteomics data obtained from human tissues representing distinct molecular characteristics of thyroid cancers: BRAF-like (papillary thyroid cancer with BRAFV600E mutation; PTC-B), RAS-like (follicular thyroid cancer with RAS mutation; FTC-R), and ATC-like (anaplastic thyroid cancer with BRAFV600E or RAS mutation; ATC-B or ATC-R). To validate our findings, we employed tissue microarray of human thyroid cancer tissues and performed in vitro analyses of cancer cell phenotypes and metabolomic assays after inducing genetic knockdown. RESULTS: Metabolic properties differed between differentiated thyroid cancers of PTC-B and FTC-R, but were similar in dedifferentiated thyroid cancers of ATC-B/R, regardless of their mutational status. Tricarboxylic acid (TCA) intermediates and branched-chain amino acids (BCAA) were enriched with the activation of TCA cycle only in FTC-R, whereas one-carbon metabolism and pyrimidine metabolism increased in both PTC-B and FTC-R and to a great extent in ATC-B/R. However, the protein expression levels of the BCAA transporter (SLC7A5) and a key enzyme in one-carbon metabolism (SHMT2) increased in all thyroid cancers and were particularly high in ATC-B/R. Knockdown of SLC7A5 or SHMT2 inhibited the migration and proliferation of thyroid cancer cell lines differently, depending on the mutational status. CONCLUSIONS: These findings define the metabolic properties of each molecular subtype of thyroid cancers and identify metabolic vulnerabilities, providing a rationale for therapies targeting its altered metabolic pathways in advanced thyroid cancer.

Effects of aging on accompanying intermittent hypoxia in a bleomycin-induced pulmonary fibrosis mouse model.

BACKGROUND/AIMS: Obstructive sleep apnea (OSA) is prevalent in older patients with idiopathic pulmonary fibrosis (IPF); however, it is underrecognized. OSA is characterized by intermittent hypoxia (IH) and sleep fragmentation. In this study, we evaluated the effects of IH in an older mouse model of bleomycin-induced lung fibrosis. METHODS: Bleomycin-induced mice (C57BL/6, female) were randomly divided into four groups of young vs. old and room air (RA)-exposed vs. IH-exposed. Mice were exposed to RA or IH (20 cycles/h, FiO2 nadir 7 ± 0.5%, 8 h/day) for four weeks. The mice were sacrificed on day 28, and blood, bronchoalveolar lavage (BAL) fluid, and lung tissue samples were obtained. RESULTS: The bleomycin-induced IH-exposed (EBI) older group showed more severe inflammation, fibrosis, and oxidative stress than the other groups. The levels of inflammatory cytokines in the serum and BAL fluid increased in the EBI group. Hydroxyproline levels in the lung tissue increased markedly in the EBI group. CONCLUSION: This study demonstrates the possible harmful impact of OSA in an elderly mouse model of lung fibrosis. This study further suggests that older patients with IPF and OSA may be more of a concern than younger patients with IPF. Further research is required in this area.

Trends and an Online Survey on the Use of Rigid Bronchoscopy in Korea.

BACKGROUND: Although almost all interventional pulmonologists agree that rigid bronchoscopy is irreplaceable in the field of interventional pulmonology, less is known about the types of diseases that the procedure is used for and what difficulties the operators face during the procedure. The purpose of this study is to evaluate what diseases rigid bronchoscopy is used for, whether it is widely used, and what challenges the operators face in Korea. METHODS: We enrolled 14 hospitals in this retrospective cohort of patients who underwent rigid bronchoscopy between 2003 and 2020. An online survey was conducted with 14 operators to investigate the difficulties associated with the procedure. RESULTS: While the number of new patients at Samsung Medical Center (SMC) increased from 189 in 2003-2005 to 468 in 2018-2020, that of other institutions increased from 0 to 238. The proportion of SMC patients in the total started at 100% and steadily decreased to 59.2%. The proportion of malignancy as the indication for the procedure steadily increased from 29.1% to 43.0%, whereas post-tuberculous stenosis (25.4% to 12.9%) and post-intubation stenosis (19.0% to 10.9%) steadily decreased (all P for trends < 0.001). In the online survey, half of the respondents stated that over the past year they performed less than one procedure per month. The fewer the procedures performed within the last year, the more likely collaboration with other departments was viewed as a recent obstacle (Spearman correlation coefficient, rs = -0.740, P = 0.003) and recent administrative difficulties were encountered (rs = -0.616, P = 0.019). CONCLUSION: This study demonstrated that the number of patients undergoing rigid bronchoscopy has been increasing, especially among cancer patients. For this procedure to be used more widely, it will be important for beginners to systematically learn about the procedure itself as well as to achieve multidisciplinary consultation.

Associations among sleep-disordered breathing, sleep quality, and lung cancer in Korean patients.

PURPOSE: Intermittent hypoxia and sleep fragmentation, two main features of sleep-disordered breathing (SDB), have been shown to increase the aggressiveness of lung cancer, mainly in animal and in vitro studies. However, the association between SDB and lung cancer has not been well described in human studies. In this study, we investigated the associations among SDB, sleep quality, and lung cancer in Korean patients. METHODS: Patients with histologically diagnosed lung cancer performed a home sleep apnea test. Sleep questionnaires including the Epworth Sleepiness Scale (ESS), Insomnia Severity Index, and Pittsburgh Sleep Quality Index were also administered. Clinical information related to lung cancer was collected during the study. RESULTS: Sixty-nine patients were enrolled, 31 of whom were poor sleepers. The overall prevalence of SDB was 57% and that of moderate to severe SDB was 27%. Underlying chronic obstructive pulmonary disease (COPD) and smoking history were significantly more frequent in patients with moderate to severe SDB compared to patients without or with mild SDB. No significant differences were observed in the apnea-hypopnea index (AHI), oxygen desaturation index (ODI), or time with oxygen saturation < 90% (T90) according to cancer cell types, mutations, stages, and survival. However, small-cell lung cancer patients showed a trend toward higher AHI, ODI, and T90 values. CONCLUSION: The prevalence of SDB and proportion of poor sleepers were high in Korean patients with lung cancer. Paying more attention to sleep status may be helpful for patients with COPD, a smoking history, and small-cell lung cancer.

Effects of Assistive Technology Application in Dementia Intervention for People with Mild Cognitive Impairment & Mild Alzheimer Type Dementia and Caregiver.

Background: Dementia, a degenerative disease, requires alternative treatment to maintain function, but previous studies suggest only the therapeutic effect of a temporary program. Primary Study Objective: The current study aimed to examine the effects of assistive technologies on cognitive function, daily living ability, and psychosocial symptoms in elderlies with mild cognitive impairment, elderlies with mild dementia and their caregivers. Design: The research team designed an experimental study that used application as the intervention. Setting: To recruit participants living in the local community, research participation was supported through local public health centers, welfare centers, and social welfare organizations. Evaluation and intervention were conducted by visiting the participant's home. Participant: The study participants were 29 Mild Cognitive Impairment (MCI) and 16 mild Alzheimer type dementia (AD) patients over the age of 75 with a total of 45 patients, 10 MCI caregivers and 11 AD caregivers with a total of 21 caregivers. Intervention: The assistive technologies used for intervention are 3 area (8 daily living assistive devices, 7 safety assistive technologies, and 7 cognitive assistive technologies). Up to 5 assistive technologies were provided to one subject, and they were instructed to use them every day for 8 weeks. Outcome measure: Participants were evaluated at baseline and postintervention using specific scales appropriate to an area: cognitive function, activities of daily living, depression, anxiety, quality of life, satisfaction. Results: Cognitive function showed statistically significant changes in the MCI group. Basic activities of daily living, depression, anxiety, quality of life, satisfaction showed statistically significant positive effects in both MCI and AD groups. Instrumental activities of daily living did not show any statistically significant differences. Conclusion: As an alternative to dementia care in the future, the application and management of assistive technologies for each area should be provided at the government level.

Simple Saliva Sample Collection for the Detection of SARS-CoV-2 Variants Compared With Nasopharyngeal Swab Sample.

CONTEXT.­: The use of saliva samples for diagnosis of SARS-CoV-2 infection offers several advantages, including ease of sample collection, feasibility of self-collection, and minimization of medical staff exposure to infection. The emergence of new SARS-CoV-2 variants has had an impact on the viral load of specimens and the results of real-time reverse transcription-polymerase chain reaction (rRT-PCR). OBJECTIVE.­: To compare nasopharyngeal swab and saliva samples for the diagnosis of SARS-CoV-2 using rRT-PCR. DESIGN.­: In this study, participants were recruited prospectively, and paired nasopharyngeal swab and saliva samples were collected simultaneously from each participant. After adding universal transport medium, RNA was extracted in an identical manner for both sample types, and samples were tested using rRT-PCR. In addition, samples with positive results were tested for SARS-CoV-2 variants. RESULTS.­: Of the 338 paired samples, 100 nasopharyngeal swab and 101 saliva samples tested positive for SARS-CoV-2. The rRT-PCR results of the saliva and nasopharyngeal swab samples showed a positive percent agreement of 95.0% (95% CI, 88.7%-98.4%), a negative percent agreement of 97.9% (95% CI, 95.2%-99.3%), and an overall percent agreement of 96.8% (95% CI, 94.3%-98.4%). SARS-CoV-2 was detected in the saliva samples of 6 participants with negative nasopharyngeal sample results. In addition, the sensitivity of saliva samples was similar to that of nasopharyngeal samples for detecting various SARS-CoV-2 variants, including the Omicron variant. CONCLUSIONS.­: Saliva samples can be used as an alternative to nasopharyngeal samples for convenient and effective detection of various SARS-CoV-2 variants.

Impacts of the COVID-19 pandemic on sleep center operations and sleep apnea treatment in Korea: A multicenter survey.

ABSTRACT: The coronavirus disease-2019 (COVID-19) pandemic has not only changed the lives of people around the world but also affected all areas of the healthcare system, including sleep medicine. However, no studies in Korea have investigated the status of domestic sleep centers and their challenges during the pandemic.An online survey was performed from December 2020 to January 2021. Hospitals that belonged to sleep-related academic societies and were considered well managed were included in this survey. The questionnaire focused on changes in sleep center operations, infection control policies, and patient treatment since the start of the COVID-19 pandemic. Telemedicine and future directions for sleep medicine services were also investigated.Of the 20 sleep centers that responded, 80% were at university hospitals with more than 500 inpatient beds. During the third wave of the COVID-19 pandemic in Korea (November-December 2020), the routine operating schedule of the sleep study room was reduced in 30% of the sleep centers compared to November-December 2019 (before COVID-19). The number of type 1 polysomnographies performed decreased in 85% of the sleep centers. In contrast, in-lab positive airway pressure (PAP) titrations decreased in 40%, remained unchanged in 35%, and increased in 25%. With respect to prescriptions, 30% of the sleep centers increased the number of prescriptions for auto-titrating continuous PAP. However, 60% of the sleep centers reported no change in the rate of fixed continuous PAP and auto-titrating continuous PAP prescriptions. All sleep centers that participated in this survey agreed that the need for documented infection control regulations will continue after the COVID-19 pandemic. Since the beginning of the pandemic, 30% of the centers have tried telemedicine. However, respondents expressed concern about telemedicine, citing a number of practical issues.Compared to countries where the COVID-19 pandemic was severe, Korea had less impact of COVID-19 on the sleep center operations and sleep apnea treatment. Infection and quality control in the sleep study room are important and inevitable issues, and regulation within each institution is necessary. Further research and discussion are needed regarding telemedicine and home sleep apnea test in Korea.

DEHP Down-Regulates Tshr Gene Expression in Rat Thyroid Tissues and FRTL-5 Rat Thyrocytes: A Potential Mechanism of Thyroid Disruption.

BACKGROUND: Di-2-ethylhexyl phthalate (DEHP) is known to disrupt thyroid hormonal status. However, the underlying molecular mechanism of this disruption is unclear. Therefore, we investigated the direct effects of DEHP on the thyroid gland. METHODS: DEHP (vehicle, 50 mg/kg, and 500 mg/kg) was administered to Sprague-Dawley rats for 2 weeks. The expression of the thyroid hormone synthesis pathway in rat thyroid tissues was analyzed through RNA sequencing analysis, quantitative reverse transcription-polymerase chain reaction (RT-PCR), and immunohistochemical (IHC) staining. DEHP was treated to FRTL-5 rat thyroid cells, and an RT-PCR analysis was performed. A reporter gene assay containing the promoter of thyroid stimulating hormone receptor (TSHR) in Nthy-ori 3-1 human thyroid cells was constructed, and luciferase activity was determined. RESULTS: After DEHP treatment, the free thyroxine (T4) and total T4 levels in rats significantly decreased. RNA sequencing analysis of rat thyroid tissues showed little difference between vehicle and DEHP groups. In the RT-PCR analysis, Tshr expression was significantly lower in both DEHP groups (50 and 500 mg/kg) compared to that in the vehicle group, and IHC staining showed that TSHR expression in the 50 mg/kg DEHP group significantly decreased. DEHP treatment to FRTL-5 cells significantly down-regulated Tshr expression. DEHP treatment also reduced luciferase activity in a reporter gene assay for TSHR. CONCLUSION: Although overall genetic changes in the thyroid hormone synthesis pathway are not clear, DEHP exposure could significantly down-regulate Tshr expression in thyroid glands. Down-regulation of Tshr gene appears to be one of potential mechanisms of thyroid disruption by DEHP exposure.

Effects of chewing exercises on the occlusal force and masseter muscle thickness in community-dwelling Koreans aged 65 years and older: A randomised assessor-blind trial.

Chewing exercises have been applied in clinical settings to improve the occlusal force and function of the masseter muscle in elderly individuals. However, the clinical relevance and effects of chewing exercises are unclear. This study aimed to investigate the effects of bilateral chewing exercises on the occlusal force and masseter muscle thickness in community-dwelling Koreans aged 65 years. Forty community-dwelling healthy elderly individuals were enrolled in this study. They were assigned to the experimental or the control group. The experimental group performed chewing exercises using medical equipment developed to facilitate such exercises. The chewing exercises were divided into isometric and isotonic types and were performed for 20 min/d, 5 days/wk, for 6 weeks. The control group did not perform any chewing exercises. The outcome measures were occlusal force and masseter muscle thickness, which were evaluated using an occlusometer and ultrasound device, respectively. A paired t test and an independent t test were used to evaluate the training effects. Within-group comparisons showed that occlusal force and masseter muscle thickness improved significantly in the experimental group (P < .001 for both), while the control group showed no significant improvements (P = .098 and .130). Between-group comparisons showed that the experimental group had a greater increase in occlusal force and masseter muscle thickness (P < .05 for both) compared to the control group. These results suggest that chewing exercises are effective in improving occlusal force and masseter muscle thickness in healthy elderly individuals.

A Novel Method Using Kinesiology Taping for the Activation of Suprahyoid Muscles in Healthy Adults: A Preliminary Research.

The suprahyoid muscles play a major role in safe swallowing in the pharyngeal phase. Therefore, it is clinically important to design a therapeutic approach for strengthening the suprahyoid muscles for safe and normal swallowing. This study aimed to investigate the activation of suprahyoid muscles by resistance training using kinesiology taping (KT). We enrolled 23 healthy adults. All participants performed saliva swallowing five times at 5 s intervals in three conditions (without KT, 50% stretch with KT, and 80% stretch with KT). KT in the I and reverse V shapes was pulled vertically from the hyolaryngeal complex to the sternum and medially from the superior surface of the clavicle, respectively. Another KT horizontally covered the hyolaryngeal complex to enhance the movement restriction of the hyolaryngeal complex during swallowing. Activation of the suprahyoid muscles during swallowing in the two conditions was measured using surface electromyography. In addition, a 0-10 numerical rating self-report scale was used to evaluate the required effort and the resistance felt during swallowing. Both KT 50% and 80% were significantly higher in surface electromyography (sEMG) mean value, peak value, required effort, and resistance felt during swallowing compared to normal swallowing (p < 0.05). In addition, KT 80% was significantly higher in sEMG value, peak value, required effort, and resistance felt during swallowing than KT 50% (p < 0.05). This study demonstrated that KT applied to the area under the hyolaryngeal complex improves activation of the suprahyoid muscle during swallowing. Therefore, KT applied as resistance during swallowing is considered to have therapeutic potential in dysphagia rehabilitation.

Effect of neuromuscular electrical stimulation combined with effortful swallowing using electromyographic biofeedback on oropharyngeal swallowing function in stroke patients with dysphagia: A pilot study.

BACKGROUND: Electromyographic biofeedback (EMG-BF) is known to be an effective therapy for stroke rehabilitation. However, because few studies have investigated the therapy in patients with dysphagia, its effectiveness is not yet clear. This study aimed to investigate the effect of neuromuscular electrical stimulation (NMES) using EMG-BF on swallowing function in stroke patients with oropharyngeal dysphagia. METHODS: In this study, 10 patients with dysphagia were recruited. The 1-group, pre-post study design was adopted. All subjects received NMES combined with EMG-BF in the suprahyoid area. Electrical stimulation was provided as a reward when the electrical signal generated by effortful swallowing reached a preset threshold. The intervention was provided for 30 minutes a day, 5 times a week for 4 weeks. The videofluoroscopic dysphagia scale (VDS) and penetration-aspiration scale (PAS) based on the videofluoroscopic swallowing study were used to evaluate the swallowing function. RESULTS: Pre-intervention showed no significant differences in all items of VDS (P > .05). However, there was a statistically significant change in VDS from 13.36 ±â€Š5.94 to 9.36 ±â€Š5.14 (P = .015) in the oral phase, and from 38.36 ±â€Š7.42 to 20.71 ±â€Š14.61 (P = .016) in the pharyngeal phase. The PAS scores showed significant change from 5.14 ±â€Š2.27 to 3.00 ±â€Š1.00 (P = .031). CONCLUSION: This study demonstrated that the use of NMES combined with EMG-BF had the potential to improve oropharyngeal swallowing in stroke patients with dysphagia.

Tongue stretching exercises improve tongue motility and oromotor function in patients with dysphagia after stroke: A preliminary randomized controlled trial.

OBJECTIVES: This study investigated the effect of tongue stretching exercises (TSE) on tongue motility and oromotor function in patients with dysphagia after stroke. DESIGN: This study was designed as a 4-week, double-blind, two-group, block randomized controlled trial. A total of 25 patients were randomly allocated into either the experimental (n = 13) or the control group (n = 12). The experimental group received TSE from an occupational therapist. TSE were divided into dynamic and static passive stretching exercises (20 repetitions each). The intervention was performed five times a week for four weeks. Tongue motility was measured before and after the intervention as the distance from the lower lip to the tip of tongue during maximum protrusion of the tongue. Measurements were performed twice each time and the mean value recorded. Oromotor function was assessed using the oral phase events of the videofluoroscopic dysphagia scale (VDS) based on a videofluoroscopic swallowing study. RESULTS: The experimental group showed significant differences in tongue motility, bolus formation, tongue to palate contact, premature bolus loss, and oral transit time in the oral phase of VDS (p < 0.05 for all) before and after the intervention, whereas the control group showed a significant difference only in lip closure (p < 0.05). CONCLUSION: This study demonstrated that TSE have a positive effect on tongue motility and oromotor function in patients with dysphagia after stroke. Therefore, we recommend TSE as an effective treatment for dysphagia.

Efficacy of modified chin tuck against resistance exercise using hand-free device for dysphagia in stroke survivors: A randomised controlled trial.

BACKGROUND: Chin tuck against resistance exercise was recently reported as a novel method for improving the swallowing function of patients with post-stroke dysphagia. However, as this exercise involves holding and fixing the device using the hand, physically weak patients may find it difficult to perform it. OBJECTIVES: This study aimed to investigate the effect of modified chin tuck against resistance (mCTAR) exercise on patients with post-stroke dysphagia. METHODS: In total, 30 patients with dysphagia were recruited in this study. They were randomly assigned to either the experimental or control group. The experimental group performed mCTAR exercise and received traditional dysphagia treatment, whereas the control group received only traditional dysphagia treatment. mCTAR exercise involved isometric and isotonic exercises. Aspiration and oral diet were evaluated using penetration-aspiration scale (PAS) and functional oral intake scale (FOIS), respectively. Moreover, the rate of nasogastric tube removal was analysed. RESULTS: Compared with the control group, the experimental group showed statistically significant improvement in PAS and FOIS (P < 0.001, both). The rates of nasogastric tube removal were 25% and 15% in the experimental and control groups, respectively. CONCLUSION: This study demonstrated that mCTAR exercise can reduce aspiration and improve dietary levels in patients with post-stroke dysphagia. Therefore, mCTAR exercise is expected to be beneficial for physically vulnerable patients with dysphagia who have limited hand strength and range of motion.

Effects of lingual strength training on oropharyngeal muscles in South Korean adults.

BACKGROUND: Lingual strength training (LST) has been reported to positively affect the activation of submental muscles, as well as to increase lingual muscle strength. However, there is little evidence to support its effectiveness. OBJECTIVES: This study aimed to investigate the effect of LST on the strength and thickness of oropharyngeal muscles in healthy adults. METHODS: The study included 30 subjects who were assigned to the experimental (n = 15) and the control groups (n = 15). The experimental group performed LST based on tongue-to-palate resistance exercise method. LST was categorised as isometric and isotonic exercise. The intervention was performed five times a week for 6 weeks. The control group did not receive any intervention. The lingual strength was measured using the Iowa Oral Performance Instrument. Changes in the thickness of the mylohyoid and the digastric muscles and the lingual were assessed ultrasonographically. RESULTS: After the intervention, the thickness of the mylohyoid and the digastric muscles in the experimental group was significantly greater than that in the control group (P = 0.037 and 0.042). CONCLUSION: This study demonstrated that LST increases the thickness and the strength of oropharyngeal muscles. Therefore, LST is a useful option in patients with dysphagia or in elderly patients prone to swallowing dysfunction.

Integrative analysis of genomic and transcriptomic characteristics associated with progression of aggressive thyroid cancer.

Anaplastic thyroid cancer (ATC) and advanced differentiated thyroid cancers (DTCs) show fatal outcomes, unlike DTCs. Here, we demonstrate mutational landscape of 27 ATCs and 86 advanced DTCs by massively-parallel DNA sequencing, and transcriptome of 13 ATCs and 12 advanced DTCs were profiled by RNA sequencing. TERT, AKT1, PIK3CA, and EIF1AX were frequently co-mutated with driver genes (BRAFV600E and RAS) in advanced DTCs as well as ATC, but tumor suppressors (e.g., TP53 and CDKN2A) were predominantly altered in ATC. CDKN2A loss was significantly associated with poor disease-specific survival in patients with ATC or advanced DTCs, and up-regulation of CD274 (PD-L1) and PDCD1LG2 (PD-L2). Transcriptome analysis revealed a fourth molecular subtype of thyroid cancer (TC), ATC-like, which hardly reflects the molecular signatures in DTC. Furthermore, the activation of JAK-STAT signaling pathway could be a potential druggable target in RAS-positive ATC. Our findings provide insights for precision medicine in patients with advanced TCs.

Interaction of BRAF-induced ETS factors with mutant TERT promoter in papillary thyroid cancer.

Synergistic effects of BRAFV600E and TERT promoter mutations on the poor clinical outcomes in papillary thyroid cancer (PTC) have been demonstrated. The potential mechanism of this phenomenon has been proposed: MAPK pathway activation by the BRAFV600E mutation may upregulate E-twenty six (ETS) transcription factors, increasing TERT expression by binding to the ETS-binding site generated by the TERT promoter mutation; however, it has not yet been fully proven. This article provides transcriptomic insights into the interaction between BRAFV600E and TERT promoter mutations mediated by ETS factors in PTC. RNA sequencing data on 266 PTCs from The Cancer Genome Atlas and 65 PTCs from our institute were analyzed for gene expression changes and related molecular pathways, and the results of transcriptomic analyses were validated by in vitro experiments. TERT mRNA expression was increased by the coexistence of BRAFV600E and TERT promoter mutations (fold change, 16.17; q-value = 7.35 × 10-12 vs no mutation). In the ETS family of transcription factors, ETV1, ETV4 and ETV5 were upregulated by the BRAFV600E/MAPK pathway activation. These BRAFV600E-induced ETS factors selectively bound to the mutant TERT promoter. The molecular pathways activated by BRAFV600E were further augmented by adding the TERT promoter mutation, and the pathways related to immune responses or adhesion molecules were upregulated by TERT expression. The mechanism of the synergistic effect between BRAFV600E and TERT promoter mutations on cancer invasiveness and progression in PTC may be explained by increased TERT expression, which may result from the BRAF-induced upregulation of several ETS transcription factors.

Aberrant Thyroid-Stimulating Hormone Receptor Signaling Increases VEGF-A and CXCL8 Secretion of Thyroid Cancer Cells, Contributing to Angiogenesis and Tumor Growth.

PURPOSE: Thyroid-stimulating hormone (TSH) suppression is widely used to treat well-differentiated thyroid cancer, whereas its role in poorly differentiated thyroid cancer (PDTC) is undetermined. Besides thyrocytes, TSH also binds to stromal cells, comprising tumor microenvironments. This study aimed to investigate the effects of TSH on tumor microenvironments in PDTC. EXPERIMENTAL DESIGN: An ectopic tumor model using PDTC cells (BHP10-3SCp and FRO), which exhibit TSH/cAMP-independent cell growth, was treated with TSH. IHC was performed using tissue microarrays from 13 PDTCs. RESULTS: TSH treatment significantly enhanced tumor growth of PDTCs with increased vascularity but not that of breast cancer cells, suggesting this effect is unique to thyroid cancer cells, not stromal cells. TSH significantly upregulated VEGF-A and CXCL8 expressions in BHP10-3SCp cells via AKT and ERK signaling, resulting in higher concentrations of VEGF-A and CXCL8 in conditioned medium of TSH-treated BHP10-3SCp cells (TSH-CM) compared with controls. TSH-CM treatment enhanced tube formation potentials of endothelial cells, and blocking VEGF and/or CXCL8 reduced them. Blocking VEGF and/or CXCL8 also reduced TSH-dependent tumor growth with reduced tumor vasculature in vivo. TSH-treated tumors showed increased macrophage densities, and macrophage inhibition reduced TSH-dependent tumor growth in vivo. In human PDTCs, preoperative TSH levels were positively associated with VEGF-A and tumor size, and the expression of VEGF-A was positively correlated with CD31, CD163, and CXCL8, and their clinical poor prognosis. CONCLUSIONS: Aberrant TSH receptor signaling modulates tumor angiogenesis by stimulating VEGF-A and CXCL8 secretion from PDTC cells and enhances tumor growth; thus, TSH suppression is beneficial for treating PDTCs.

Effects of Pioglitazone on Nonalcoholic Fatty Liver Disease in the Absence of Constitutive Androstane Receptor Expression.

Nonalcoholic fatty liver disease or steatohepatitis (NAFLD/NASH) is a fatty liver disease that is closely related to obesity, diabetes, and dyslipidemia. Pioglitazone, which was developed as an antidiabetic drug, is known to improve NALFD. Pioglitazone is metabolized by multiple cytochrome P450 (CYP) enzymes, which are regulated by the xenobiotic receptor constitutive androstane receptor (CAR). In this study, we investigated the effects of pioglitazone on NAFLD by absence of CAR activity under high-fat (HF)-fed conditions. CAR-/- mice showed significant improvement in NALFD after 12 weeks of pioglitazone treatment compared to wild-type mice. This improvement in NAFLD persisted in CAR-/- mice regardless of blood pioglitazone concentration. The expression of lipogenesis genes in the liver, sterol-regulatory element binding protein-1c (SREBP-1c), and stearoyl-CoA desaturase (SCD)-1 was decreased after pioglitazone treatment in HF-fed CAR-/- mice. In addition, the expression of peroxisome proliferator-activated receptor gamma 2 (PPARγ2) was decreased by pioglitazone in HF-fed CAR-/- mice. Changes in SREBP-1c and PPAR γ2 remained constant over short-term (6 h) pioglitazone and lipid injection. Our results showed that NAFLD was improved significantly by pioglitazone in a CAR deletion state. These results might be valuable because they suggest that interaction with CAR and pioglitazone/PPARγ2 may be important in regulating gene expression associated with NAFLD.