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Objectives Posterior benign paroxysmal positional vertigo (p-BPPV) is the most common type of BPPV, and canalith-repositioning procedure (CRP) is frequently applied for treatment. Supine to prolonged lateral position (SPLP), a simple home-based maneuver, can be performed for treatment of p-BPPV. The purpose of this study was to investigate whether combination of CRP and SPLP could be more effective in symptom alleviation compared with CRP alone and reduce times of repeated CRP for patients with p-BBPV. Methods A retrospective chart review enrolled 96 patients diagnosed with primary p-BPPV. Of these patients, 64 patients were included in the CRP group and 32 patients, in the CRP+SPLP group. The outcome was determined according to days required to reach negative result in Dix-Hallpike test, duration of vertigo and dizziness following the first repositioning procedure, and times of CRP performed to reach resolution of p-BPPV. Results Of patients in the CRP and CRP+SPLP groups, 38% and 16% received CRP at least twice to reach resolution, respectively (P = 0.034). Patients in the CRP group and CRP+SPLP group spent an average of 9.8 ± 6.1 days and 7.9 ± 3.4 days, respectively reaching a negative result in Dix-Hallpike test (P = 0.050). In terms of duration for relieving vertigo and dizziness, the CRP+SPLP group achieved symptom relief with shorter duration (P = 0.036 and P = 0.025, respectively). Conclusion Compared with CRP alone, combination of CRP and SPLP improved the therapeutic effectiveness and shortened the duration of suffering from vertigo and dizziness in patients with p-BPPV.

Objective To evaluate the correlation of neonatal parameters with late-onset sensorineural hearing loss (SNHL) and vestibular dysfunction in individuals with congenital cytomegalovirus (cCMV) infection using the National Health Insurance Research Database (NHIRD) in Taiwan. Design Retrospective cohort study. Setting The whole Taiwanese population. Participants Patients with related diagnostic codes and examinations in their records were regarded as having cCMV infection. Each subject in that group was matched to 10 control individuals with noncongenital CMV infection on the basis of several neonatal parameters, including low gestational age, low birth weight, low Apgar score, maternal history of CMV infection and prolonged cCMV infection. A total of 5893 and 58 930 participants were enrolled in the study and control groups, respectively. Main outcome measures The main outcomes were the development of SNHL and the development of vestibular dysfunction within one year after birth as reflected by diagnostic codes and specific examinations. Cox proportional hazard regression was used to calculate the adjusted hazard ratio (HR) and 95% confidence interval (CI) of each primary outcome between the two groups. Results Overall, 109 and 397 episodes of SNHL developed in the study group and the control group, respectively, and the study group demonstrated a significantly higher incidence of SNHL (adjusted HR: 2.56; 95% CI: 2.07-3.18). In addition, similar incidence rates of vestibular dysfunction were found in the study group and the control group, with 7 and 90 events, respectively (adjusted HR: 0.77; 95% CI: 0.36-1.67). In subgroup analyses, a higher incidence of SNHL was correlated with lower gestational age (GA) (adjusted HR: 2.09; 95% CI: 1.29-3.39), lower birth weight (BW) (adjusted HR: 2.05; 95% CI: 1.28-3.30) and prolonged cCMV infection (adjusted HR: 3.92; 95% CI: 1.95-7.88). Conclusions Low GA, low BW and a long disease course are significantly correlated with late-onset SNHL in cCMV infection.

In this paper, we theoretically propose and demonstrate a non-unitary beam-splitter (BS) by introducing coupling losses at the interface of the plasmonic waveguide and multimode dielectric waveguide (DW). The coupling losses enable us to modify the reflection and transmission factors, which can result in arbitrary shift of interference curves of two outputs. Specially, the lossy non-unitary BS can tune the amplitudes and phases of two outputs, even making them change synchronously, regardless of input phase differences. After a $$\pi /2$$ phase delay in one arm, these two outputs are fed into another multimode DW. This DW is a normal unitary BS, working like the Michelson interferometer, where anti-synchronous interference can take place. At last, the whole device outputs an invariant zero energy state in one port, exhibiting a phase-insensitive performance. Our study provides a versatile design platform to realize non-unitary/unitary BS and construct more multi-functional devices.

The purposes of the study were (1) to assess the physical activity (PA) status, muscle strength (MS), and flexibility of survivors of head and neck cancer (HNC) and compare these findings with normative data from national labor fitness measures; (2) to examine the differences among PA subgroups, as categorized using Godin’s scores; and (3) to examine the association between stretching exercises and cervical range of motion (CROM). A cross-sectional study with consecutive sampling was used to recruit HNC survivors from a medical center in Northern Taiwan who had completed either radiation therapy (RT) or multimodality treatments including RT within the current 5 years. The level of PA, daily function, fatigue, quality of life (QOL), MS (handgrip and hip flexor), BMI, and flexibility (CROM and fingertip-to-floor tests) of the participants were assessed. A total of 108 participants completed the assessments from 135 eligible patients (80% response rate). Although 60.2% reported engaging in PA, only 16.7% met WHO guidelines. Compared to subjects in the normative data, the survivors of HNC in this study had poorer handgrip strength, BMI, and CROM, but better forward flexion. The participants who were consistent with WHO PA guidelines reported less fatigue, better right hip flexor MS, and better QOL than those who did not engage in any PA. Lack of sufficient PA and generally poorer fitness were found in study subjects. Longitudinal research to explore changes in fitness and barriers to PA compliance is strongly suggested to better enhance HNC patients’ PA and fitness.

S Our previous study first investigated feasibility of applying ultrasound (US) and microbubbles (MBs) via external auditory canal to facilitate drug delivery into inner ear. However, most drugs are in aqueous formulae and eliminated via Eustachian tubes after drug application. In this study, feasibility of sustained release of thermosensitive poloxamer 407 (P407)-based MB gel for US mediation-enhanced inner ear drug (dexamethasone, DEX) delivery was investigated. The sol-to-gel transition temperature showed that mixture of DEX and only 10% and 12.5% P407 in MBs can be used for in vitro and in vivo drug delivery experiments. In in vitro Franz diffusion experiments, the release rates of 12.5% P407-MBs + US groups in the model using DEX as the delivered reagent at 3 h resulted in values 1.52 times greater than those of 12.5% P407-MBs groups. In guinea pigs, by filling tympanic bulla with DEX in 12.5% P407-MBs (DEX-P407-MBs), USMB applied at post-treatment days 1 and 7 induced 109.13% and 66.67% increases in DEX delivery efficiencies, respectively, compared to the group without US. On the 28th day after US-mediated P407-MB treatment, the safety assessment showed no significant changes in the hearing thresholds and no damage to the integrity of cochlea or middle ear. These are the first results to demonstrate feasibility of US-modified liquid form DEX-P407-MB cavitation for enhancing permeability of round window membrane. Then, a gel form of DEX-P407-MBs was generated and thus prolonged the release of DEX in middle ear to maintain the therapeutic DEX level in inner ear for at least 7 days.

Background The study aims are to evaluate the associations between nasopharyngeal carcinoma (NPC) risk and cigarette smoking and to explore the effects of cigarette smoking on Epstein‐Barr virus (EBV) infection for NPC risk. Methods 1235 male NPC cases and 1262 hospital‐based male controls matched to cases were recruited across six collaborative hospitals between 2010 and 2014. Using a standardized questionnaire, information on cigarette smoking and other potential risk factors for NPC was obtained. Blood was collected and used for anti‐EBV VCA IgA and anti‐EBV EA‐EBNA1 IgA testing using standard methods. Unconditional logistic regression analysis was used to estimate odds ratio (OR) with 95% confidence interval (CI) for each risk factor after adjusting for confounders. Results 63.6% of cases and 44.0% of controls reported ever smoking cigarettes. After full adjustment, current smokers had a significant 1.60‐fold (95% CI = 1.30‐1.97) and former smokers a borderline significant 1.27‐fold (95% CI = 1.00‐1.60) increased NPC risk compared to never smokers. NPC risk increased with increasing duration, intensity, and pack‐years of cigarette smoking but not with age at smoking initiation. Among controls, anti‐EBV VCA IgA seropositivity rate was higher in current smokers than never smokers (14.0% vs 8.4%; OR = 1.82; 95% CI = 1.19‐2.79). Mediation analyses showed that more than 90% of the cigarette smoking effect on NPC risk is mediated through anti‐EBV VCA IgA. Conclusion This study confirms the association between long‐term cigarette smoking and NPC and demonstrates that current smoking is associated with seropositivity of anti‐EBV VCA IgA antibodies., Smoking duration and intensity but not age at initiation are NPC risk factors, and anti‐EBV VCA IgA seropositivity rate was higher in current than never smokers among controls. Mediation analyses show that NPC and EBV association may be explained by the interplay between smoking and EBV antibodies serostatus.

Ultrasound (US) has been found to rejuvenate and invigorate the hair follicles, increase the size of hair shafts, and promote new hair growth. Our present study found that dual-frequency US-mediated microbubble (MB) cavitation significantly enhanced minoxidil (Mx) delivery in both in vitro and in vivo models, while increasing the hair growth efficacy compared to single-frequency US sonication. The in vitro experiments showed that cavitation activity was enhanced more significantly during dual-frequency sonication than single-frequency sonication in higher concentration of MBs. The pigskin penetration depth in the group in which dual-frequency US was combined with MBs was 1.54 and 2.86 times greater than for single-frequency US combined with MBs and in the control group, respectively; the corresponding increases in the release rate of Mx at 18 hours in in vitro Franz-diffusion-cell experiments were 24.9% and 43.7%. During 21 days of treatment in C57BL/6J mice experiments, the growth rate at day 11 in the group in which dual-frequency US was combined with MBs increased by 2.07 times compared to single-frequency US combined with MBs. These results indicate that dual-frequency US-mediated MB cavitation can significantly increase both skin permeability and transdermal drug delivery. At the same US power density, hair growth was greater in the group with dual-frequency US plus MBs than in the group with single-frequency US plus MBs, without damaging the skin in mice.

Background: There are still oral cancer patients without surgery. To improve the survival, it is necessary to know the causes of the oral cancer patients without surgery. Methods: 23,217 patients with a newly-diagnosed oral cancer in Taiwan Cancer Registry (TCR) database between 2011 and 2015 were enrolled. Data from TCR database named “Reason for No Surgery of Primary Site” were extracted for analysis of the causes of those without surgery. Overall survival plots were presented using the Kaplan–Meier method with log-rank test. Results: 3263 (14%) patients did not received surgery. Among them, there were 720 patients (group 3) without surgery although surgery was advised, 154 patients (group 2) because of poor condition or death before surgery, and 2389 patients (group 1) because of other causes. Twenty-four percent of the patients with surgery were treated one month and more after diagnosis. The 5-year overall survival rates were 68.7%, 25.2%, 9.1% and 17.3% for surgery group, group 3, 2 and 1, respectively (p

Aim: Treatment of lymphoma differs from head and neck carcinomas. The aim of this study was to provide a comprehensive of review lymphomas arising in head and neck region. Methods: Patients between 2003 and 2015 with lymphomas in head and neck region were retrospectively reviewed with pathology subtype, age, gender, location, and diagnostic procedure. Results: One hundred and fifty-one lymphoma patients were enrolled. Diffuse large B-cell lymphoma accounted for 56.3% of all patients, followed by follicular lymphoma (6.0%) and NK/T-cell lymphoma (6.0%). Nearly 38.4% of patients manifested as enlarged cervical node while another 61.6% presented as extranodal lymphoma with tonsils (21.8%) the most commonly affected site, followed by parotid gland and tongue base. Open surgery or excisional biopsy had the highest sensitivity of 95.8% for a confirmed diagnosis, followed by punch biopsy (74.7%), core biopsy (51.0%), and fine-needle aspiration (2.2%). Conclusions: Lymphoma is frequently encountered in head and neck region. Early diagnosis was made possible by detailed examinations and adequate diagnostic procedure with consideration of both procedure sensitivity and risks.

Surface plasmon-polaritons (SPPs)-based waveguides, especially hybrid plasmonic nanowires, which have attracted extensive interests due to easy fabrication, high transmittance, subwavelength mode confinement and long propagation distance, are appropriate platforms for enhancing the interaction with graphene. Considering that graphene is a two-dimensional (2D) material with surface conductivity, it is important to enhance the in-plane electrical components parallel to graphene. Here, we propose a tunable graphene optical modulator based on arrayed hybrid plasmonic nanowires, utilizing strong subwavelength confinement of gap-surface plasmonic modes (GSPMs) and near-field coupling in the periodic metasurface structure to enhance effective light-matter interactions. The modulator has a typical modulation depth (MD) of 4.7 dB/μm, insertion loss (IL) of 0.045 dB/μm, and a broadband response. The modulation performance can be further optimized, achieving MD of 16.7 dB/μm and IL of 0.17 dB/μm. Moreover, with the optimized modulator, the 3 dB bandwidth can reach 200 GHz. The energy consumption of modulator is about 0.86 fJ/bit. Our design exhibits fascinating modulation performance, fabrication compatibility and integration potential. It may inspire the schematic designs of graphene-based plasmonic modulator and pave a way to the application of 2D materials-involved optoelectronic devices.

BACKGROUND The survival outcomes of different salvage treatments for patients with recurrent oral cancer remain unclear. METHODS A total of 556 patients with recurrent oral cancer between 2010 and 2015 were reviewed. Clinical/pathological risk factors and different salvage treatments were analyzed. RESULTS The 2-year disease-free survival rates after recurrence in patients not receiving salvage operation (305 patients), receiving salvage operation with (121 patients), and without (130 patients) major pathological risk factors (margin or extranodal extension) were 5.3%, 32.4%, and 77.2%, respectively (p

The aim of this study was to investigate the time dependent effects of tetramethylpyrazine (TMP, main activity compound of Ligusticum chuanxiong Hort) on two neurological disorders and their neuropsychiatric comorbidities. 6 Hz corneal rapid kindling was used to induce epileptogenesis and the inflammatory pain was induced by intra-articular Complete Freund’s adjuvant (CFA) injection. The mechanical pain thresholds were measured using von Frey hair (D4, D11, D18, D25 after CFA first injection), and the vertical rearings of the mice was observed. To test the neuropsychiatric comorbidities, anxiety-like behaviors of mice were examined by open field and elevated plus maze tests. Two behavioral despair models, tail suspension test and forced swimming test were also used to evaluate the depressive like behaviors. The results showed that TMP administered from the initial day (D1-D35 in kindling model, D0-D14 and D0-D28 in CFA model) of modeling retarded both the developments of 6 Hz corneal rapid kindling epileptogenesis and the CFA induced inflammatory pain. In comparison, late periods administration of TMP (D21-D35 in kindling and D14-D28 in CFA model) showed no effect on the epileptogenesis and the generalized seizures (GS) of kindling, but alleviated maintenance of CFA induced inflammatory pain. Furthermore, we also found all TMP treatments from the initial day of modeling alleviated the co-morbid depressive and anxiety-like behaviors in both models; however, late periods treatments did not, either in kindling or the CFA induced inflammatory pain. BDNF/ERK signaling impairment was also tested by western blot, and the results showed that TMP administered from the initial day of modeling increased the hippocampal BDNF/ERK expression, whereas late period administration showed no effects. Overall, our findings reveal the inconsistent time dependent effects of Tetramethylpyrazine on neurological disorders and their relative neuropsychiatric comorbidities, and provide novel insight into the early application of TMP that might enhance hippocampal BDNF/ERK signaling to alleviate neuropsychiatric comorbidities in neurological diseases.

Objectives The present study aimed to evaluate the impact of proactive swallowing rehabilitation on swallowing function and quality of life (QoL) in oral cancer patients in the first two years after definitive treatment. Materials and Methods Consecutive adult patients with locally advanced oral cancer who received radical surgery, free flap reconstruction, and adjuvant radiotherapy were recruited prospectively, to whom proactive swallowing rehabilitation was provided. Body weight (BW); fiberoptic endoscopic evaluation of swallowing (FEES), functional oral intake scale (FOIS), and diet level; 10-item eating assessment tool (EAT-10), and MD Anderson Dysphagia Inventory (MDADI); and adherence at baseline, 1, 3, 6, 12, and 24 months were evaluated. Results A total of 104 patients were included during May 2018 to July 2020. Compared to the baseline, significant deterioration in BW, FOIS, and MDADI was noted at one month. However, a trend of recovery was observed in FOIS from one month, and in BW and MDADI from three months. A total of 94% patients were free of tube feeding at 12 months but with a diet requiring special preparations or compensation. Safe swallowing could be achieved in approximately 90% of the participants after six months with diet modification or compensatory maneuvers. BW at 18 and 24 months did not differ significantly from baseline. Conclusion Proactive swallowing therapy is feasible for patients with locally advanced oral cancer receiving definitive treatments. It facilitates safe oral intake and adequate nutrition. Patients who performed swallowing exercises had a faster and better recovery in swallowing function and swallowing-related QoL.

Only a small portion of the patients with oral squamous cell carcinoma (OSCC) experience bone metastasis. This study is to evaluate the percentage of bone metastasis at diagnosis and after treatment and to discuss whether bone scan is necessary in OSCC patients. The medical records of all patients with newly diagnosed OSCC receiving bone scan or positron emission tomography (PET) at diagnosis between 2010 and 2015 were retrospectively reviewed. A total of 1049 patients were enrolled, including 458 (44%) with early stage tumor and 591 (56%) with late stage tumor. In total, 33 (3.1%) patients had bone metastasis at diagnosis (9 patients, 0.86%) and after treatment (24 patients, 2.29%) during the mean follow-up of 12 months. Among those with subsequent bone metastasis, only 5 (21%) patients had bone-only metastasis. All patients with bone metastasis before primary treatment and all but two patients with bone metastasis after treatment had locoregionally advanced OSCC. The mean survival time of the 33 patients after diagnosis of bone metastasis was 121 days. Bone metastasis is uncommon in patients with OSCC. It is not necessary to routinely use bone scan for initial staging, especially early stage OSCC, and for follow-up.

In clinical practice, it is sometimes difficult to evaluate the intra–false vocal fold lesion. Transcutaneous ultrasound can be an option to evaluate the soft tissue lesion within the right false vocal cord in a 65‐year‐old man with laryngeal Rosai‐Dorfman disease presenting with hoarseness and right false cord swelling., Transcutaneous laryngeal ultrasound could evaluate the intra–false cord soft tissue lesion with intact mucosa, which is sometimes difficult by laryngeal endoscopy, CT, or MRI.

Background Genetic and environmental factors are important determinants of nasopharyngeal carcinoma (NPC). NPC is associated with Epstein-Barr virus (EBV) infection. Studies have reported familial aggregation of NPC, but evidence has been mixed for elevated rates of cancers other than NPC. Methods The authors reassessed their previous evaluation of familial aggregation of cancer in 348 high-risk Taiwanese multiplex families with 2 or more NPC cases enrolled between 1980 and 2003. Participants were linked to the Taiwan National Cancer Registry and National Death Registry to identify cancers. Results In all, 2590 individuals contributed 37,959 person-years over an average of 15 years of follow-up; 314 incident cancers were identified. The authors computed multiple primary standardized incidence ratios (MP-SIRs) to evaluate the overall risk and the risk of infection-associated, EBV-associated, and individual cancers. The overall MP-SIR was 1.24 (95% confidence interval [CI], 1.10-1.38). The exclusion of excess NPC risk led to an overall MP-SIR of 1.11 (95% CI, 0.98-1.25). Similarly, the risk of cancers associated with infectious agents was driven by the excess in NPC, and its exclusion led to an MP-SIR of 1.22 (95% CI, 0.99-1.48) for infection-associated cancers and to an MP-SIR of 1.18 (95% CI, 0.72-1.82) for EBV-associated cancers. The authors observed a significant excess of second cancers among NPC cases (oral cancer, mouth cancer, tongue cancer, gum cancer, nasal cavity cancer, bone cancer, and non-Hodgkin lymphoma). Conclusions This reassessment of the largest NPC multiplex family study confirms the presence of NPC coaggregation within families in Taiwan but does not provide evidence for a broader familial syndrome involving NPC and other tumors. Among NPC cases, elevated rates of secondary cancers, mostly at the, head and neck and hematopoietic cancers suggest radiation treatment effects on subsequent cancer risk.

The application of insulin-like growth factor 1 (IGF-1) to the round window membrane (RWM) is an emerging treatment for inner ear diseases. RWM permeability is the key factor for efficient IGF-1 delivery. Ultrasound microbubbles (USMBs) can increase drug permeation through the RWM. In the present study, the enhancing effect of USMBs on the efficacy of IGF-1 application and the treatment effect of USMB-mediated IGF-1 delivery for noise-induced hearing loss (NIHL) were investigated. Forty-seven guinea pigs were assigned to three groups: the USM group, which received local application of recombinant human IGF-1 (rhIGF-1, 10 µg/µL) following application of USMBs to the RWM, the RWS group, which received IGF-1 application alone, and the saline-treated group. The perilymphatic concentration of rhIGF-1 in the USM group was 1.95- and 1.67- fold of that in the RWS group, 2 and 24 h after treatment, respectively. After 5 h of 118 dB SPL noise exposure, the USM group had the lowest threshold shift in auditory brainstem response, least loss of cochlear outer hair cells, and least reduction in the number of synaptic ribbons on postexposure day 28 among the three groups. The combination of USMB and IGF-1 led to a better therapeutic response to NIHL. Two hours after treatment, the USM group had significantly higher levels of Akt1 and Mapk3 gene expression than the other two groups. The most intense immunostaining for phosphor-AKT and phospho-ERK1/2 was detected in the cochlea in the USM group. These results suggested that USMB can be applied to enhance the efficacy of IGF-1 therapy in the treatment of inner ear diseases.

Objectives Dysplastic changes at the surgical margin of oral squamous cell carcinoma (OSCC) could be encountered frequently. However, the impact of a dysplastic surgical margin on patients with OSCC remains unclear. Materials and methods Retrospectively, we reviewed patients with OSCC who were diagnosed and treated at the National Taiwan University Hospital between January 2010 and December 2015. Patients were divided into four groups: clear (≥5 mm), close ( Results Of 1642 patients, 596 had clear margin, 169 had positive margin, 707 had close margin, and 170 had dysplastic margin. The mean age at diagnosis was 55 ± 11 years (range, 16-97 years). Dysplastic margins were frequently present in patients with primary T1/T2 OSCC (odds ratio [OR] = 1.7, p = 0.009), tumor without perineural invasion (OR = 1.48, p = 0.04), and tumor thickness ≤10 mm (OR = 1.94, p = 0.001). In patients with clear, close, positive, and dysplastic margins, the 5-year disease-free survival rates were 63.1%, 51%, 37.2%, and 54.7%, respectively; overall survival (OS) rates were 71.1%, 61.9%, 49%, and 72%, respectively. Disease-free and overall survival were not significantly different in patients with dysplastic and clear margins (p = 0.37 and p = 0.38, respectively). Adjuvant radiotherapy had no significant benefit for patients with dysplastic margins. Finally, a multivariate analysis showed that the presence of a dysplastic margin was not an independent risk factor for disease-free (p = 0.43) and overall survival (p = 0.71). Conclusions The survival rates of the patients with OSCC who had dysplastic margin were significantly better than those with positive margin.

Objective To investigate the risk for second primary cancer in the hypopharynx and esophagus (SPC-HE) among individuals with an initial oral/oropharyngeal cancer. Materials and methods Mass screening data from Taiwan (2004-2009) included individuals who were ≥18 years old and smoked cigarettes and/or chewed betel quid. Occurrence of SPC-HE was monitored until December 31, 2014. Results were expressed as adjusted relative risk (aRR) and 95% confidence interval (CI). Results One hundred and fifty-eight out of 4,494 subjects with oral cancer developed SPC-HE (incidence rate: 6.47 per 1,000 person-years). Relative to patients with primary cancers in the lip, the risk of an SPC-HE was higher in patients with primary cancers in oropharynx (aRR: 19.98, 95% CI: 4.72-84.55), floor of mouth (aRR: 12.13, 95% CI: 2.67-55.15), and hard palate (aRR: 7.31, 95% CI: 1.65-32.37), but not in patients with cancers in tongue (aRR: 3.67, 95% CI: 0.89-15.17) or gum (aRR: 3.99, 95% CI: 0.92-17.35). Regression analyses also showed the risk of an SPC-HE was greater in alcohol drinkers than those who did not (aRR: 1.65, 95% CI: 1.10-2.48). Conclusions Compared with the initial cancer in the lip, patients with a cancer in the oropharynx, floor of mouth, and hard palate had a higher risk for the SPC-HE.

Silicon nanowires (SiNWs) have attracted increasing attention for their enhanced light harvesting and large junction area of photovoltaic devices compared to planar silicon wafers. However, high su...

Androgen deprivation therapy (ADT) has been a mainstay of treatment for advanced prostate cancer (PCa), but limited studies have been performed to investigate the association between ADT and autoimmune diseases. We conducted a population-based nationwide cohort study of 17,168 patients newly diagnosed with PCa between 1996 and 2013 using the National Health Insurance Research Database (NHIRD) of Taiwan. Cox proportional hazards models with 1:1 propensity score-matched analysis were used to investigate the association between ADT use and the risk of autoimmune diseases. The autoimmune diseases included Graves’ disease, Crohn’s disease, psoriasis, systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis, Guillain-Barre syndrome, Sjogren’s syndrome, myasthenia gravis, pernicious anemia, hereditary hemolytic anemia, polyarteritis nodosa, Celiac disease, uveitis, polymyalgia rheumatica, dermatomyositis, Hashimoto’s thyroiditis, hypersensitivity vasculitis, Behcet’s disease, polymyositis, alopecia areata, Wegener’s granulomatosis, ulcerative colitis, autoimmune hemolytic anemia, pemphigus, multiple sclerosis, systemic sclerosis, Goodpasture syndrome, giant cell arteritis, thromboangitis obliterans, arteritis obliterans, and Kawasaki disease. The duration of ADT use as a time-dependent variable was also examined for its association with autoimmune diseases. We also performed six secondary analyses. Of the 17,168 selected PCa patients, 14,444 patients met all the inclusion and exclusion criteria. After propensity score matching, 5590 ADT users and 5590 non-ADT users were included in the study cohort. A propensity score-matched analysis (adjusted hazard ratio (aHR), 0.619, 95% confidence interval (CI), 0.51–0.75, P

Cisplatin-based chemotherapy is the foundation of treatment for major non-small cell lung cancer (NSCLC) patients. However, cisplatin resistance is still a challenging issue, and the molecular mechanisms underlying this resistance remain to be fully explored. CLEC4M, a Ca2+-dependent C-type lectin, has recently been found to correlate with tumourigenesis. This study mainly focused on whether CLEC4M impacts clinical prognosis and how CLEC4M contributes to cisplatin resistance in NSCLC. Our results found that CLEC4M was correlated with poor prognosis in patients with lung cancer. In addition, a positive association between CLEC4M expression and the IC50 values of cisplatin was found, which suggests that CLEC4M may impact cisplatin sensitivity. In vitro results from cultured A549 and H1299 cells confirmed that CLEC4M could enhance cisplatin resistance, while CLEC4M knockdown led to higher sensitivity to cisplatin in these cells. Further experiments showed that the underlying mechanisms included inhibition of cisplatin-induced cell apoptosis by CLEC4M and improved DNA repair capacity by upregulating XPA and ERCC1 expression. In addition, CLEC4M was able to promote cell migration with or without cisplatin treatment. Collectively, these findings suggest the potential clinical significance of CLEC4M inhibition in overcoming cisplatin resistance in NSCLC patients.

Background: The incidence of HPV positive oropharyngeal cancer is increasing in Taiwan. Given this, it is critical to understand the prevalence of oral HPV infection since this cancer is potentially preventable. A community-based study was conducted to evaluate the prevalence of oral HPV infection and sexual behavior changes. Methods: Between January and December 2016, 100 subjects between 20 and 70 years-old with current/ever betel nut chewing or current cigarette smoking visited the Department of Health, New Taipei City. Subjects with cancer history or known HIV/AIDS were excluded. Sexual behavior information was collected through a questionnaire. Oral rinse samples and oropharyngeal swabs were obtained for HPV genotyping using the EasyChip HPV genotyping array (King-Car, Taiwan). Results: 92 men and 8 women were recruited. The prevalence of oral HPV infection was 3%, present between 60 and 70 (11%) and between 30 and 40 years old (4%). The prevalence of the first sexual contact at younger than 20 years old were 71.4%, 53.6%, 15.4% and 44% in

OBJECTIVES/HYPOTHESIS In this study, we expanded our previous investigation by testing the efficiency of trans-round window membrane dexamethasone (DEX) delivery mediated by ultrasound (US)-aided microbubbles (MBs) and its preventive effects regarding noise exposure in animal models. STUDY DESIGN Live animal model. METHODS Forty-two pigmented male guinea pigs were divided into the following three groups: an US-MBs (USM) group, in which the tympanic bulla was filled with DEX and MBs and exposed to US; a round window soaking (RWS) group, without the US irradiation; and a control group. The above-mentioned manipulations were performed 2 hours prior to white noise exposure. The cochlear damage, including auditory threshold shifts, hair cell loss, and expression of cochlear HMGB1, was evaluated. RESULTS The enhanced DEX delivery efficiency of the USM group was approximately 2.4× to 11.2× greater than that of the RWS group. After the noise exposure, the RWS group showed significant cochlear protection compared with the control group, and more significant and dominant protective effects were demonstrated in the USM group. CONCLUSIONS The application of US-MBs provides a safe and more effective approach than spontaneous diffusion, which is commonly used in clinical practice; thus, this technique holds potential for future inner-ear drug delivery. LEVEL OF EVIDENCE NA Laryngoscope, 129:1907-1914, 2019.

STUDY OBJECTIVES: To investigate the association between non-apnea sleep disorders (NSD) and subsequent benign paroxysmal positional vertigo (BPPV) risk. METHODS: This retrospective cohort study was conducted using the Taiwan National Health Insurance Research Database from 2000 to 2013. We established an NSD group (n = 24,624) and an age-, sex- and index year-matched comparison group (n = 98,496). The primary outcome was the occurrence of BPPV. The incidence rates of BPPV in the two cohorts were compared with a 14-year follow-up. Cox proportional hazard regression analysis was used to evaluate the effects of NSD on BPPV risk. RESULTS: The incidence rate of BPPV was 43.33 per 100,000 person-years for the NSD cohort and 29.33 per 100,000 person-years for the comparison cohort. NSD significantly increased the risk of BPPV (adjusted hazard ratio [HR] = 2.487; 95% confidence interval = 1.996–3.099, P < .001). Subgroup analysis revealed that NSD increase the risk of development of BPPV by 2.357- to 3.658-fold in patients with hypertension, diabetes mellitus, chronic obstructive pulmonary disease, and hyperlipidemia. Furthermore, when comparing different types of NSD, chronic insomnia carries the highest risk of BPPV (adjusted HR = 3.563), followed by organic sleep disorders (adjusted HR = 2.763), sleep disturbance (adjusted HR = 2.506), and acute insomnia (adjusted HR = 2.237). CONCLUSIONS: We demonstrate that NSD are associated with an increased risk of BPPV. Relative to other types of NSD, patients with chronic insomnia are at the highest risk for development of BPPV. CITATION: Shih CP, Wang CH, Chung CH, Lin HC, Chen HC, Lee JC, Chien WC. Increased risk of benign paroxysmal positional vertigo in patients with non-apnea sleep disorders: a nationwide, population-based cohort study. J Clin Sleep Med. 2018;14(12):2021–2029.

Objectives To elucidate the risk of malignant transformation to invasive oral cancer by subtypes of oral potentially malignant disorders (OPMD) and to examine the independent effects of risk factors, particularly alcohol drinking, by subtype based on a nationwide oral cancer screening program targeting at general population with habits of smoking and/or betel quids chewing. Materials and methods The total of 8501 subjects diagnosed as different subtypes of OPMDs from the Taiwanese screening program between 2004 and 2009 were followed up over time to ascertain the occurrence of invasive oral cancer. The hazard ratios of malignant transformation were estimated by using Cox proportional hazards regression model. Results The overall malignant rate (per 1000 person-years) to oral cancer was 8.4 (407 incident cases with an average of 5.7 years of follow-up). The highest rate was noted in exophytic verrucous hyperplasia (33), followed by erythroplakia (11.8), erythroleukoplakia (10.7), oral submucous fibrosis (OSF) (8.6), and leukoplakia (5.4). After adjusting for confounders, exophytic verrucous hyperplasia still had a 5.69 (4.47–7.24) times risk compared with leukoplakia. The corresponding figures for erythroplakia, erythroleukoplakia, and OSF were 2.25 (1.31–3.89), 2.00 (1.13–3.53), and 1.63 (1.29–2.06), respectively. Alcohol drinking elevated the overall risk of malignant transformation by 23% (1–52% and also triggered a higher risk in OSF (aHR = 1.62 (1.06–2.47)). The higher risk attributed to betel quids chewing was noted for exophytic verrucous hyperplasia (aHR = 4.23 (1.55–11.55)). Conclusions The risk of malignant transformation to oral cancer varied with the subtypes of OPMD and was elevated in OSF and verrucous hyperplasia attributed to alcohol drinking and betel quids, respectively.

This is the first report of multifocal inflammatory pseudotumor (IPT) involving the temporal bone, orbit and paranasal sinus, and the use of rituximab as adjunctive therapy in multifocal temporal bone IPT.We describe a 46-year-old man with orbital and maxillary sinus IPT, whose disease progressed despite radiation and steroid burst. He then developed contralateral mastoid disease, otalgia, aural fullness, and hearing loss.He was initiated on rituximab and prednisone therapy. Mastoidectomy with near-total tumor removal was accomplished and histopathology confirmed IPT. A literature review was also performed.Tumor regression or recurrence.Despite disease progression after radiation and steroids, his orbital, sinus, and mastoid disease improved after surgery, steroids, and rituximab. A review of four other previously reported cases of multifocal disease involving the temporal bone suggest that multifocal disease may be a more aggressive entity with higher recurrence rate compared with solitary disease. Although surgery and steroids are typically recommended, there is currently no consensus treatment recommendation.Multifocal IPT of the temporal bone is a rare but aggressive entity for which surgery and steroid combination therapy should be first line treatment. We suggest rituximab may be an effective adjunctive treatment particularly for recurrent disease or where systemic therapy may be favored.

Objectives: Acupuncture, widely used in Chinese society, has been studied as an adjunct treatment of idiopathic sudden sensorineural hearing loss (ISSNHL). The purpose of this study is to investiga...

Background: To realize the association between stratified expression levels of ER and PgR and long-term prognosis of breast cancer patients who received adjuvant hormone therapy, this study aimed to propose better prognostic cut-off levels for estrogen receptor (ER) and progesterone receptor (PgR). Methods: Patients who received adjuvant hormone therapy after surgical intervention were selected. The ER and PgR status and their effects on breast cancer-specific survival (BCSS) and disease-free survival (DFS) over 5 and 10 years were evaluated. Next, subgroups were generated based on ER and PgR expression percentage and Allred scores. Survival curves were constructed using the Kaplan–Meier method. Results: ER and PgR expression were significantly associated with better prognosis in 5 years, whereas only PgR expression was significantly associated during the 10-year follow-up. The optimal cut-off values for better 5-year BCSS were ER &gt, 50%, ER Allred score &gt, 7, PgR ≥ 1%, or PgR Allred score ≥ 3, the corresponding values for DFS were ER &gt, 40%, 6, PgR &gt, 10%, or PgR Allred score ≥ 3. In the long-term follow-up, PgR of &gt, 50% or Allred score of &gt, 5 carriers revealed a better prognosis of both BCSS and DFS. Conclusion: Patients with a PgR expression &gt, 50% or an Allred score &gt, 5 exhibited better 10-year BCSS and DFS.

Esophageal cancer (EC) is a deadly cancer that frequently develops multiple primary cancers (MPCs). However, the risk biomarkers of MPC in EC have hardly been investigated. We retrospectively enrolled 920 subjects with primary EC and analyzed the possible risk factors as well as MPC single-nucleotide polymorphisms (SNPs) from blood DNA. A total of 184 subjects (20.0%) were confirmed to have MPC, 59 (32.8%) had synchronous MPC, and 128 (69.6%) had head and neck cancer. Elderly EC patients have an increased risk of having gastrointestinal cancer (Odds ratio, OR[95% CI]=6.70 [1.49–30.19], p=0.013) and a reduced risk of developing HNC (OR[95% CI]=0.44 [0.24–0.81], p=0.008). MPC risk was also associated with betel nut chewing (OR[95% CI]=1.63, 1.14–2.32], p=0.008), the A allele of ALDH2:rs671 (p=0.074 and 0.030 for GA and AA, respectively), the CC genotype in CISH:rs2239751 (OR[95% CI]=1.99 [1.2–3.32], p=0.008), and the G allele of ERCC5:rs17655 (p=0.001 and 0.090 for GC and CC, respectively). ADH1B:rs1229984 also correlated with MPC risk (p=0.117). Patients carrying four risk SNPs had a 40-fold risk of MPC (OR[95% CI]=40.25 [6.77–239.50], pp=0.039) compared to those without any risk SNPs. In conclusion, hereditary variations in ALDH2, CISH, ERCC5, and ADH1B have great potential in predicting the incidence of MPC in EC patients. An extensive cancer screening program during clinical follow-up would be beneficial for patients with high MPC susceptibility.

We sought to compare the clinical outcomes of Taiwanese patients with resected oral cavity squamous cell carcinoma (OCSCC) who underwent reconstruction with free versus local flaps.From 2011 to 2017, we examined 8646 patients with first primary OCSCC who received surgery either with or without adjuvant therapy. Of these patients, 7297 and 1349 received free and local flap reconstruction, respectively. Two propensity score-matched groups of patients who underwent free versus local flap (n = 1268 each) reconstructions were examined. Margin status was not included as a propensity score-matched variable.Compared with local flaps, patients who received free flaps had a higher prevalence of the following variables: male sex, age 65 years, pT3-4, pN1-3, p-Stage III-IV, depth ≥ 10 mm, margin 4 mm, extranodal extension (ENE), and adjuvant therapy (all p 0.0001). Multivariable analysis identified the reconstruction method (local vs. free flaps, only overall survival [OS]), age ≥ 65 years, pT3-4, pN1-3, p-Stage III-IV, depth ≥ 10 mm (only OS), margins ≤ 4 mm, and ENE as independent adverse prognosticators for disease-specific survival (DSS) and OS. The results of propensity score-matched analyses revealed that, compared with free flaps, patients who underwent local flap reconstruction showed less favorable 5-year DSS (hazard ratio [HR] 1.26, 82%/77%; p = 0.0100) and OS (HR 1.21, 73%/68%; p = 0.0079).After adjusting for covariates using multivariate models, and also by propensity score modeling, OCSCC patients who underwent free flap reconstruction showed a higher frequency of clear margins and a significant survival advantage compared with those who received local flaps.

Background This study aimed to translate the English version of the supportive care needs scale of head and neck cancer patients (SCNS-HNC) questionnaire into Mandarin and to test the reliability and validity of the SCNS-SF34 and SCNS-HNC module in head and neck cancer patients. Methods The Mandarin version of the Supportive Care Needs Survey Short-Form (SCNS-SF34) and SCNS-HNC scales were used to assess 206 patients with head and neck cancer in Chengdu, China. Among them, 51 patients were re-tested 2 or 3 days after the first survey. The internal consistency of the scale was evaluated by Cronbach’s alpha coefficient, the retest reliability of the scale was evaluated by retest correlation coefficient r, the structural validity of the scale was evaluated by exploratory factor analysis, and the ceiling and floor effects of the scale were evaluated. Results The Mandarin version of the SCNS-HNC had Cronbach’s alpha coefficients greater than 0.700 (0.737 ≤ 0.962) for all of the domains. Except for the psychological demand dimension (r = 0.674) of the SCNS-SF34 scale, the retest reliability of the other domains was greater than 0.8. Three common factors were extracted by exploratory factor analysis, and the cumulative variance contribution rate was 64.39%. Conclusions The Mandarin version of the SCNS-SF34 and SCNS-HNC demonstrated satisfactory reliability and validity and is able to measure the supportive care needs of Chinese patients with head and neck cancer. Trial registration ChiCTR, ChiCTR1900026635. Registered 16 October 2019- Retrospectively registered.

Objectives Recurrent idiopathic sudden sensorineural hearing loss (ISSNHL) is a rare disease. In this study, we evaluated the correlations between hearing recovery after the first and recurrent episodes of ISSNHL and characterized the clinical features of different episodes of ISSNHL. Methods This retrospective study was conducted by reviewing medical records pertaining to the period 2008–2018. A total of 30 patients (16 male, 14 female) who had experienced at least two episodes of ISSNHL were included. All patients were had received steroid therapy (including systemic and IT) and/or hyperbaric oxygen therapy within 2 weeks after the onset of disease. The SDRG's criteria was used for the grading of hearing recovery. Results The median age at the first and second episode of ISSNHL was 48 and 53.5 years, respectively; a total of 30% of patients presented with vertigo in the first episode and 40% presented with vertigo in the second episode. The hearing outcomes of both episodes showed significant improvement after treatment. The rate of complete recovery after the first and second episodes was 46.67% and 33.33%, respectively. A significant positive correlation was observed between the treatment outcomes of the first and second episodes (r = 0.721, p Conclusion In ISSNHL, hearing recovery after a recurrent episode is significantly correlated with the hearing outcome after the initial episode (p = 0.042). The treatment outcome of the first episode is a prognostic factor for the outcomes of recurrent episodes.

The aim of study is to investigate the risk of developing acquired cholesteatoma and external auditory canal (EAC) stenosis after traumatic brain injury (TBI) from the Taiwan National Health Insurance Research Database (NHIRD). Each subject was individually traced from their index date to identify those who received a diagnosis of acquired cholesteatoma and EAC stenosis. Cox regression analyses were applied to determine the risk of TBI-related acquired cholesteatoma and EAC stenosis. The follow-up data collected over 10 years were obtained from the TBI and comparison cohorts, of 455,834 and 911,668 patients, respectively. Multivariate analysis demonstrated that TBI significantly increased the risk of cholesteatoma (adjusted hazard ratio (HR), 1.777, 95% confidence interval (CI), 1.494&minus, 2.114, p &lt, 0.001) and EAC stenosis (adjusted (HR), 3.549, 95% (CI), 2.713&minus, 4.644, p &lt, 0.001). In our subgroup injury analysis, falls had the highest associated risk (4.308 times), followed by traffic injuries (66.73%, 3.718 times that of the control group). Otolaryngologists should not neglect the clinical importance and carefully investigate the possibility of subsequent cholesteatoma and EAC stenosis, which leads to hearing impairment in patients with TBI. Our research also shows the important role in preventing TBI, especially as a result of traffic injuries and falls.

Hearing impairment was observed in patients with chronic kidney disease (CKD). Our purpose was to investigate the relationship between sensorineural hearing loss (SNHL) and associated comorbidities in the CKD population. We conducted a retrospective, population-based study to examine the risk of developing SNHL in patients with CKD. Population-based data from 2000-2010 from the Longitudinal Health Insurance Database of the Taiwan National Health Insurance Research Database was used in this study. The population sample comprised 185,430 patients who were diagnosed with CKD, and 556,290 without CKD to determine SNHL risk factors. Cox proportional hazard regression analysis demonstrated the CKD group had a significantly increased risk of SNHL compared with the non-CKD group [adjusted hazard ratio (HR), 3.42; 95% confidence interval (CI), 3.01-3.90, p < 0.001]. In the CKD group, the risk of SNHL (adjusted HR, 5.92) was higher among patients undergoing hemodialysis than among those not undergoing hemodialysis (adjusted HR, 1.40). Furthermore, subgroup analysis revealed an increased risk of SNHL in patients with CKD and comorbidities, including heart failure (adjusted HR, 7.48), liver cirrhosis (adjusted HR, 4.12), type 2 diabetes mellitus (adjusted HR, 3.98), hypertension (adjusted HR, 3.67), and chronic obstructive pulmonary disease (adjusted HR, 3.45). CKD is an independent risk of developing SNHL. Additionally, hemodialysis for uremia can increase the risk of SNHL. Cardiovascular, lung, liver, and metabolic comorbidities in CKD patients may further aggravate the risk of SNHL by inter-organ crosstalk. We should pay attention to SNHL in this high-risk population.

BACKGROUND: Epstein-Barr virus (EBV) is necessary for the development of nasopharyngeal carcinoma (NPC). By adulthood, ~90% of individuals test EBV-positive, but only a fraction develop cancer. Factors that identify which individuals are most likely to develop disease, including differential antibody response to the virus, could facilitate detection at early stages when treatment is most effective. METHODS: We measured anti-EBV IgG and IgA antibody responses in 607 Taiwanese individuals. Antibodies were measured using a custom protein microarray targeting 199 sequences from 86 EBV proteins. Variation in response patterns between NPC cases and controls was used to develop an antibody-based risk score for predicting NPC. The overall accuracy (area under the curve[AUC]) of this risk score, and its performance relative to currently-used biomarkers, was evaluted in two independent Taiwanese cohorts. FINDINGS: Levels of 60 IgA and 73 IgG anti-EBV antibodies differed between Stage I/IIa NPC cases and controls (P

BACKGROUND: To compare the depiction conspicuity of three-dimensional (3D) magnetic resonance cholangiopancreatography (MRCP) based on gradient- and spin-echo (GRASE) and two-dimensional (2D) thick-slab MRCP using fast spin-echo (FSE) in different segments of hepatic and pancreatic ducts at 3T. METHODS: Both 3D GRASE and 2D thick-slab FSE MRCP, with parameters adjusted under the constraints of specific absorption rate and scan time within single breath-hold, were performed for 95 subjects (M/F =49:46; age range, 25–75) at 3T. Conspicuity of eight ductal segments was graded by two experienced raters using a 4-point score. Situations where one technique is superior or inferior to the other were recorded. RESULTS: 3D GRASE MRCP outperformed 2D thick-slab FSE MRCP in the common bile duct and common hepatic ducts (both with P

To determine the tumor genomic, immunologic expression, and risk factors of treatment outcomes for patients with double head and neck squamous cell carcinoma (HNSCC) and esophageal squamous cell carcinoma (ESCC).We reviewed patients with double HNSCC and ESCC between 1995 and 2014. The TP53 genomic mutation, CD8+ tumor infiltrating lymphocytes (TIL) and tumor programmed cell death ligand 1 (PD-L1) expression of paired HNSCC and ESCC were analyzed.A total of 116 patients (57 metachronous and 59 synchronous) were included. There were 88 (75.86%) patients with HNSCC and 80 (68.97%) with ESCC harboured TP53 disruptive mutation. Nearly 106 (91.38%) patients had different clonality of TP53 mutation in paired HNSCC and ESCC. The immunologic expression of synchronous and metachronous patients was significantly different. Compared to the metachronous patients, the synchronous patients had significantly higher HNSCC CD8+ TIL (p = 0.03), ESCC CD8+ TIL (p 0.001), HNSCC PD-L1+ tumor proportion score (TPS, p = 0.04), and ESCC PD-L1+ TPS (p = 0.04). Furthermore, among the synchronous patients, the immunologic expression between HNSCC and ESCC was significantly correlated. The CD8+ TIL and PD-L1 TPS had strongly (r = 0.63, p 0.0001) and moderately (r = 0.42, p = 0.001) positive correlations, respectively. Finally, advanced stage (III/IV) HNSCC was a significant factor for disease-free (p = 0.03) and overall survival (p = 0.005).In patients with double HNSCC and ESCC, nearly all HNSCC and ESCC were of multicentric origin. For the synchronous patients, there was more adaptive immune resistance in HNSCC and ESCC. The immunologic expression between paired HNSCC and ESCC was also significantly correlated.

High-efficiency High-Voltage Integrated Voltage Regulators (HV-IVR) will allow the next generation of data centers and servers to operate with higher efficiency while delivering more computing power. High-density embedded inductors operating at frequencies over 10 MHz allows the miniaturization of power modules enabling their integration closer to the SoC. However, single stage 48V to 1V IVR present new challenges that are not seen in low voltage converter such as 3.3V or 1.7V to 1V. In this work, a novel expandable interleaved toroidal inductor cell with vias-in-slot thru magnetic sheet is presented. In addition, we present a new metric for magnetic material and inductor technologies to describe their efficiency under different duty cycle conditions. Using the analysis of two available magnetic sheets with permeability 50 and 150 at 10MHz, we present the magnetic properties of a magnetic sheet to obtain 95% of inductor efficiency, an inductance density of 113 nH/mm3 at 10 MHz, a saturation current over 2.5A, and DC resistance around 20 mΩ. These inductor requirements are given by the possible power stage topologies that can be used to achieve 48V to 1V, where some of them use single inductor while others use coupled or tapped inductors. The efficiency conditions for the inductor presented in this work must be matched by the power stage topology, leading to a co-design between power inductor and the power stage topology. In this work we present why the duty cycle must be extended by a factor of 4 in order to obtain a 95% efficiency in the inductor. We provide a process for the fabrication of these inductors. Finally, a test inductor is fabricated that shows an inductance density of 77 nH/mm3 and correlates well with the simulation model. This allows to predict with good accuracy the inductor performance with the proposed inductor design and magnetic sheet properties.

The aim of the study is to investigate the ability of phytochemicals to overcome the multiple drug resistance (MDR) of bladder cancer. 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay was used to evaluate the cytotoxic sensitivity of T24‐GCB cells, a GCB resistant cell line, to different phytochemicals, including capsaicin, quercetin, curcumin, and resveratrol, and their combination with gemcitabine. Western blot analysis was used to detect the expression of membranous ABCC2 and metabolic proteins, DCK, TK1, and TK2 in tumor cells. Animal models were used to confirm the treatment efficacy of phytochemicals in combination with gemcitabine to bladder cancer. The observed/expected ratio of cytotoxicity analysis revealed that capsaicin has synergistic effect with gemcitabine to T24‐GCB cells in a dose‐dependent pattern. Quercetin, curcumin, and resveratrol have additive effect with gemcitabine to T24‐GCB cells. Capsaicin and quercetin alone and combination with gemcitabine decreased the expression of ABCC2 and DCK and TKs, in T24‐GCB cells. On the contrary, resveratrol and curcumin alone and combination with gemcitabine increased the expression of ABCC2 but decreased cytoplasmic kinases simultaneously. In xenografted subcutaneous tumor model on nude mice, combination treatment of capsaicin and gemcitabine demonstrated the highest tumor suppression effect when compared to capsaicin or gemcitabine treatment alone. The MDR of bladder cancer is closely related to membranous ABCC2, cytoplasmic DCK, and TKs expression. Capsaicin owns the strongest synergistic cytotoxic effect of gemcitabine to T24‐GCB cells. This combination regimen may provide as an adjunctive treatment for overcoming MDR in bladder cancer.

Background Previously, we used ultrasound (US)-mediated cisplatin (CDDP)-loaded microbubbles (CDDP-MBs) to increase intratumoral CDDP level while decreasing systemic cytotoxicity. Statins have shown antitumorigenic properties. Our study investigated the effects of atorvastatin with CDDP-MBs and US on head neck cancer. Methods Cell viability analysis with CDDP-MBs and atorvastatin combined with US in FaDu cell line were tested. Cell proliferation and glutathione level were also evaluated. Results Both CDDP and atorvastatin reduced cell's viability. Coadministration of CDDP and atorvastatin resulted in synergistic inhibitory effect. After US sonication, cell viability with atorvastatin and CDDP was significantly reduced for CDDP combined with MBs (65.98% to 49.13%) and for CDDP-MBs (86.17% to 50.15%). CDDP-MBs combined with atorvastatin and US inhibited the proliferation of cells: 19.61% for CDDP-MBs + atorvastatin + US, 36.28% for CDDP + atorvastatin, and 71.73% for atorvastatin alone. Also, CDDP-MBs + atorvastatin + US induced apoptosis by decreasing cellular level of glutathione. Conclusions Atorvastatin combined with MB-conjugated CDDP exerts synergistic inhibitory effect on head neck cancer.

Nasal septal abscess is an uncommon condition but it can cause potentially life-threatening intracranial complications and cosmetic nasal deformity. We analyzed ten years of cases to determine the optimal diagnostic and therapeutic modalities. A retrospective review of case notes from Tri-Service General Hospital archives was performed. Records of six patients diagnosed with nasal septal abscess, who were treated from September 2007 to August 2017 were retrospectively reviewed. Patients’ clinical symptoms, etiology, diagnostic methods, bacteriology, antibiotic and surgical treatment were recorded and analyzed. Out of six patients diagnosed with nasal septal abscess, three were male and three were female. Ages ranged from 19 to 75 years (mean 51 years). The most common symptoms at presentation were nasal pain and nasal obstruction. Typical etiologies were trauma or acute sinusitis, but uncontrolled diabetes mellitus was also an important etiology. In the series of six patients, four of them had positive findings of abscess and in drainage, had the following bacterial cultures: Staphylococcus aureus (two cases), methicillin-resistant S. aureus (one case), and Klebsiella pneumoniae (one case). In addition to antibiotic treatment, all patients underwent surgical drainage and had complete resolution of disease without intracranial complications during at least 1 year of follow-up. However, two out of the six patients developed saddle nose deformity. This study highlights that: 1. In view of the rapidly increasing number of diabetes mellitus cases, uncontrolled diabetes mellitus is an important etiology of nasal septal abscess. 2. Although S. aureus is the most common pathogen, we must pay attention to methicillin-resistant S. aureus (MRSA) to prevent severe complications and patients who are at increased risk for MRSA colonization should be administrated antibiotics against MRSA initially. 3. Nasal septal abscess should be managed with parenteral broad spectrum antibiotics, appropriate drainage and immediate reconstruction of the destructed septal cartilage with autologous cartilage graft, to prevent serious intracranial complications and cosmetic nasal deformity.

By using a real management cost method to re-calculate economic costs at Taiwanese banks, this article sheds light on the relationship between CAMELS (capital, asset quality, management, earnings, ...

Two-dimensional electron systems have attracted attention as thermoelectric materials, which can directly convert waste heat into electricity. It has been theoretically predicted that thermoelectric power factor can be largely enhanced when the two-dimensional electron layer is far narrower than the de Broglie wavelength. Although many studies have been made, the effectiveness has not been experimentally clarified thus far. Here we experimentally clarify that an enhanced two-dimensionality is efficient to enhance thermoelectric power factor. We fabricated superlattices of [N unit cell SrTi1−xNb x O3|11 unit cell SrTiO3]10—there are two different de Broglie wavelength in the SrTi1−xNb x O3 system. The maximum power factor of the superlattice composed of the longer de Broglie wavelength SrTi1−xNb x O3 exceeded ∼5 mW m−1 K−2, which doubles the value of optimized bulk SrTi1−xNb x O3. The present approach—use of longer de Broglie wavelength—is epoch-making and is fruitful to design good thermoelectric materials showing high power factor., 電子をギュッと閉じ込めて熱電材料の性能を倍増 --熱電材料を高性能化する理論を実証--. 京都大学プレスリリース. 2018-07-10.

To apply final as-built BIM models to facility management (FM) during the operation phase, it is important for owners to obtain an accurate, final as-built model from the general contractors (GCs) following project closeout. Confirming the accuracy of the final as-built BIM model is one of the most important works executed by owners to meet the accuracy requirement of final as-built models for FM. However, many practical problems arise relating to the management of final as-built models such as final as-built model mismatch, the lack of available final as-built models, and the entry of incorrect non-geometric information into the final as-built models. To solve these practical problems, this study develops a Final As-built BIM Model Management (FABMM) system for owners to handle final as-built BIM model inspection, modification, and confirmation (BMIMC) work beyond project closeout. The proposed approach and system can be used to manage the status and results of BMIMC management work for the final as-built BIM model to be performed. The proposed approach and system were applied in a case study in a selected building in Taiwan to verify and demonstrate its practical effectiveness. This study identifies the benefits, limitations, and conclusions of the FABMM system, and presents suggestions for its further application.

Epstein-Barr virus detection using nasopharyngeal swabs has been suggested as a potential screening test that could improve the specificity of current EBV-based serological assays. However, application requires insertion of the swab deep into the nasopharynx, a procedure not amenable to non-clinic screening. We reasoned that swabbing the more easily accessible nasal cavity might provide an appealing alternative for NPC detection. Patients > 18 years of age diagnosed with histologically confirmed NPC were recruited from the Otolaryngology Department at the National Taiwan University Hospital. ENT clinicians collected both nasal and nasopharyngeal swabs. EBV DNA and cellular beta-globulin DNA were quantified using quantitative PCR targeting a highly-conserved region of the BKRF1 gene. EBV DNA was detectable (non-zero) in all 34 nasopharyngeal swabs and above the positivity threshold of 1666 EBV copies in 30 (88.2%) patients. EBV DNA was detectable in 50% of 34 nasal swabs and above the positivity threshold in four (11.8%) patients. Average EBV DNA levels were >3-fold higher (P

Objective To investigate the latency and amplitude of auditory brainstem response (ABR) and hearing prognosis in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). Methods Patients with ISSNHL were classified into four different recovery groups. All patients' clinical and demographic features were analyzed. Two-channel ABRs were collected in response to click stimuli at 90 dB nHL. ABR amplitudes for wave I and ABR latency for waves I, III, and V were analyzed. Results One hundred and two patients (54 men and 48 women) were included in the study. Hearing recovery was observed in 72 cases (70.6%). Waves I, III, and V latencies were significantly prolonged in the affected ears compared with the unaffected ears. A smaller wave I amplitude was found in the affected ear compared with the unaffected ear in the three recovery groups. There was a significant association between wave I latency and hearing outcome (p = 0.009) with a prolonged trend from complete to slight hearing recovery group. Conclusions There was a significant correlation between wave I latency and hearing outcome in patients with ISSNHL. The finding may provide diagnostic information and serve as a potential prognostic indicator in patients with ISSNHL.

Background Margin status and lymph node metastasis are the most important prognostic factors for oral cancers. However, while adequate surgical resection is crucial for local control and prognosis, the definition of clear margins has long been a subject of debate. In this study, we analyzed data from a nationwide population-based cancer registry database and evaluated the impact of surgical margins on cancer-specific survival (CSS) and overall survival (OS) as well as the optimal cutoff of adequate surgical margins. Methods This analysis included all cases of oral cancer diagnosed from 2011 to 2017 that were reported to the Taiwan Cancer Registry database. The staging system was converted from American Joint Committee on Cancer (AJCC) version 7 to AJCC version 8. Kaplan–Meier analysis and Cox proportional-hazards regression were performed to identify covariates that were significantly associated with CSS and OS. Results Between 2011 and 2017, 15,654 of a total of 36,091 cases diagnosed with oral cancers were included in the final analyses. Advanced N stage, positive margins, and advanced T stage are the leading risk factors for poor CSS and OS. When surgical margins were subdivided into 1-mm intervals from 5 mm to positive margin, we found that surgical margins Conclusions This is the first nationwide, population-based cohort to revisit the question of the adequate surgical margins for oral cancers. We conclude that surgical margins ≥4 mm and ≥5 mm are adequate for good CSS and OS, respectively.