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Summary Objective Vocal process granuloma (VPG) has a varied treatment success rate and may frustrate patients and physicians due to poor outcomes. There is still a lack of standard protocols to manage VPG. This study aimed to review the efficiency of a standardized low-dose laryngeal electromyographic (LEMG)-guided botulinum toxin A (BTA) injection in intractable vocal granulomas. Methods Twenty-four patients with intractable VPG were recruited. All patients underwent percutaneous LEMG-guided BTA injection on the thyroarytenoid-lateral cricoarytenoid muscle complex in an office setting. The injecting dose was standardized to 1 U in 0.1 mL normal saline at a time. We evaluated the treatment effect by measuring the lesion size with serial laryngoscope evaluations. Results The postinjection follow-up time varied from 3 to 23 months. Twenty-one patients (87.5%) experienced complete regression of the granuloma over 1–7 months (median 3 months). No major adverse effects were noted during the follow-up period. Conclusion For recalcitrant VPG, LEMG-guided low-dose BTA injection has the potential to be a safe, efficient, and effective treatment.

Objective Tracheal granulation is one of the common long term complications in patients after tracheostomy. Hypertrophic tracheal granulation may cause airway obstruction and further operation may be required to recreate an airway. Distal tracheal granulation is clinically challenging because of its position and surgical field limitation. This retrospective case review study evaluated the outcomes of PEAK PlasmaBlade-assisted tracheal surgery in patients with distal tracheal granulation. Methods This study retrospectively reviewed patients with distal tracheal granulation following long-term tracheostomy. All patients received PEAK PlasmaBlade assistance tracheal surgery (PATS) between February 2013 and December 2019. The surgery was performed using the PEAK PlasmaBlade with TnA type tip, powered by a PULSAR Generator, and guided by a 45 ° rigid endoscope. Patients were regularly followed up for a minimum of 12 months. Results A total 21 patients had completed PATS. None of the patients experience immediate life-threatening complications during or after the procedure. All the 21 patients were free of recurrent obstructive granulation within 12 months after operation. Conclusion PATS is practical, effective, and safe for distal tracheal granulation and can be performed by single surgeon. Furthermore, it is technically less demanding than other surgical approaches and it has a rapid learning curve.

Background Domiciliary oxygen therapy (DOT) is a complex intervention and has significant impact on patients’ daily activities, quality of life, and mental well-being. Suitable education is pertinent in improving patients’ understanding and use of DOT, because those receiving appropriate education have a better knowledge of their prescription, clearer expectations, and improved adherence to DOT. Research Question Do currently available online patient resources on DOT provide high-quality information for patients? Study Design And Methods We evaluated the first 100 results of three major search engines (Google, Yahoo, and Bing) using the terms home oxygen therapy and information or education. Website content was assessed based on Thoracic Society of Australia and New Zealand and British Thoracic Society domiciliary oxygen guidelines. Validated tools were used to evaluate resource quality (DISCERN instrument), suitability (Suitability Assessment of Materials [SAM]), reliability (Journal of the American Medical Association [JAMA] benchmarks and the Health on the Net [HON] code], and readability (Flesch Reading Ease and Flesch-Kincaid Grade Level). Results Thirty-six websites met study inclusion criteria. Websites from foundation or advocacy organizations scored the highest in quality and suitability, with a median DISCERN total score of 48.0 (interquartile range [IQR], 43.5-60.0), or fair, and a median SAM suitability score of 70% (IQR, 53.0%-71.0%), or superior. Industry or for-profit websites had the best content score of 7.8 (IQR, 5.0-8.6). The HON accreditation seal was present on 14% of the websites, and only five websites met the four JAMA benchmarks. The median readability scores exceeded the recommended reading grades of sixth to eighth level for consumer health-related educational resources. Interpretation The overall quality, suitability, reliability, and content of online health resources for DOT are of a low to moderate standard, with the reading grade at an unsuitable level for the general population. Health professionals should be aware of the limitations of currently available online DOT patient resources.

Chin-Kuo Chen,1,2 Shih Chieh Shen,1– 3 Li-Ang Lee,1,2 Ming-Hui Sun,2,4 Ning-Hung Chen,2,5 Li-Pang Chuang,2,5 Hsueh-Yu Li1,2 1Department of Otolaryngology-Head and Neck Surgery, Sleep Center, Chang Gung Memorial Hospital (Linkou), Taoyuan City, Taiwan; 2College of Medicine, Chang Gung University, Taoyuan City, Taiwan; 3Department of Otolaryngology-Head and Neck Surgery, New Taipei Municipal Tucheng Hospital, New Taipei City, Taiwan; 4Department of Ophthalmology, Chang Gung Memorial Hospital (Linkou), Taoyuan City, Taiwan; 5Department of Pulmonary and Critical Care Medicine, Sleep Center, Chang Gung Memorial Hospital (Linkou), Taoyuan City, TaiwanCorrespondence: Hsueh-Yu Li; Shih Chieh ShenDepartment of Otolaryngology-Head and Neck Surgery, Sleep Center, Chang Gung Memorial Hospital (Linkou), 33, No. 5, Fushing Street, Gueishan Shiang, Taoyuan City, TaiwanTel +886-3-3281200 ext.3966Fax +886-3-3979361Email hyli38@cgmh.org.tw; b9102083@cgmh.org.twPurpose: Obstructive sleep apnea (OSA) is characterized by recurring hypoxic-apneic events during sleep, and labyrinthine vascular compromise is a pathophysiologic hallmark of idiopathic sudden sensorineural hearing loss (ISSNHL). Some reports have discussed the relationship between OSA and hearing impairment; however, few have examined hearing prognosis in OSA and patients without OSA with ISSNHL. We aimed to investigate clinical manifestations of ISSNHL in patients with OSA, including severity of hearing loss and response to treatment.Patients and Methods: A case-control study was conducted by extracting data from the sleep center and cochlea center databases of the Chang Gung Memorial Hospital. A retrospective chart review was performed to include confirmed adult OSA patients diagnosed with unilateral ISSNHL. Age and sex-matched patients without OSA with ISSNHL were enrolled as controls. Pure-tone average (PTA) thresholds were measured at specific frequencies. Changes in PTA before and after standard treatment with oral prednisolone (1mg/kg/day for 5 days, then tapered) and between participants with OSA and without OSA were compared. Standard treatment was given to all ISSNHL patients.Results: Twenty-eight out of 8500 (0.33%) OSA patients experienced subsequent ISSNHL in 9 years. Patients with OSA (n=28) had poorer high-frequency perception in the unaffected ear than the patients without OSA (n=120), although the difference was not significant. Hearing in the affected ear among patients with OSA was comparable to that patients without OSA at individual frequencies and average, suggesting no difference in hearing loss in the affected ear between the two groups. In terms of high-frequencies (4000 and 8000 Hz) perception, patients with OSA had significantly poorer responses to steroid treatment than patients without OSA.Conclusion: ISSNHL may be one of the auditory complications associated with OSA. Patients with OSA had poorer prednisolone related hearing improvement in high frequencies than patients without OSA. Despite study limitations, OSA-related hypoxia and snoring noise is hazardous to hearing and standard treatments with CPAP is suggested in OSA patients for both holistic and auditory health.Keywords: obstructive sleep apnea, idiopathic sudden sensorineural hearing loss, high-frequency, hypoxemia, pure-tone average, frequencies

Methods We sought to compare the prognostic impact of tumor differentiation with respect to adverse risk factors (RFs) identified by the National Comprehensive Cancer Network (NCCN) guidelines––including extranodal extension (ENE), positive/close margins, perineural invasion, lymphatic invasion, and vascular invasion––in patients with locally advanced oral cavity squamous cell carcinoma (OCSCC). Results Between 1996 and 2018, 1179 consecutive patients with first primary pT3–4 OCSCC were included. A three‐level grading system was adopted––in which the final classification was assigned according to the most prevalent tumor grade. We identified 382/669/128 patients with well/moderately/poorly differentiated tumors, respectively. Compared with well/moderately differentiated tumors, poorly differentiated OCSCC had a higher prevalence of the following variables: female sex (4%/6%/11%), ENE, (14%/36%/61%), positive margins (0.5%/2%/4%), close margins (10%/14%/22%), perineural invasion (22%/50%/63%), lymphatic invasion (2%/9%/17%), vascular invasion (1%/4%/10%), and adjuvant therapy (64%/80%/87%). The 5‐year rates of patients with well/moderately/poorly differentiated OCSCC were as follows: local control (LC, 85%/82%/84%, p = 0.439), neck control (NC, 91%/83%/70%, p, Final tumor grading of oral cavity squamous cell carcinoma (OCSCC) is assigned according to the most prevalent grade. Relapses of poorly differentiated OCSCC tended to occur regionally and distantly. Poor tumor differentiation was the second most relevant adverse risk factor after extranodal extension. The NCCN guidelines should include poor differentiation as an adverse risk factor.

Background We compared the clinical outcomes of patients with oral cavity squamous cell carcinoma (OCSCC) with cN+pN0 versus cN0pN0 disease. Methods A total of 1309 OCSCC patients with pN0 disease were included. Of them, 1019 and 290 cases had cN0pN0 and cN+pN0 disease, respectively. For comparison purposes, we also examined 799 patients with pN+disease (cN0pN+/cN+pN+, n = 239/560). Subgroup analysis was performed in a propensity score‐matched cohort with cN0pN0 and cN+pN0 disease (n = 284 each). Results Compared with cN0pN0, patients with cN+pN0 had a higher prevalence of the following variables: betel chewing, pT3−4, depth ≥10 mm, perineural invasion, and treatment with surgery and adjuvant therapy. The prognosis of patients with cN+pN0 (mean: 52 nodes) and cN0pN0 (mean: 39 nodes) disease was similar both in the original cohort and after propensity score matching. However, the 5‐year outcomes were more favorable for cN+pN0/cN0pN0 compared with cN0pN+/cN+pN+ (local control, 88%/88%/83%/81%; neck control, 94%/93%/82%/76%; distant metastases, 4%/3%/13%/31%; disease‐free survival, 84%/83%/68%/52%; disease‐specific survival, 92%/92%/77%/57%; overall survival, 81%/82%/59%/42%; all p values 0.05). cN+pN0 disease (vs. cN0pN0) was not significantly associated with local control, neck control, distant metastases, and survivals either in univariable or multivariable analyses. Conclusions Despite a higher risk factor burden, the prognosis of patients with cN+pN0 disease did not differ from that of cases with cN0pN0. The higher nodal yield and the more frequent use of adjuvant therapy in cN+pN0 disease may explain the lack of significant differences in terms of neck control compared with cN0pN0 disease., Patients with oral cavity squamous cell carcinoma and cN+pN0 disease are characterized by a higher prevalence of adverse risk factors. However, this was not found to translate into a less favorable prognosis; therefore, the presence of cN+pN0 disease should not be considered as an adverse prognostic factor

Zika virus (ZIKV) infection during pregnancy can cause microcephaly in newborns, yet the underlying mechanisms remain largely unexplored. Here, we reveal extensive and large-scale metabolic reprogramming events in ZIKV-infected mouse brains by performing a multi-omics study comprising transcriptomics, proteomics, phosphoproteomics and metabolomics approaches. Our proteomics and metabolomics analyses uncover dramatic alteration of nicotinamide adenine dinucleotide (NAD+)-related metabolic pathways, including oxidative phosphorylation, TCA cycle and tryptophan metabolism. Phosphoproteomics analysis indicates that MAPK and cyclic GMP-protein kinase G signaling may be associated with ZIKV-induced microcephaly. Notably, we demonstrate the utility of our rich multi-omics datasets with follow-up in vivo experiments, which confirm that boosting NAD+ by NAD+ or nicotinamide riboside supplementation alleviates cell death and increases cortex thickness in ZIKV-infected mouse brains. Nicotinamide riboside supplementation increases the brain and body weight as well as improves the survival in ZIKV-infected mice. Our study provides a comprehensive resource of biological data to support future investigations of ZIKV-induced microcephaly and demonstrates that metabolic alterations can be potentially exploited for developing therapeutic strategies.

Hai-Hua Chuang,1– 3 Chi-Hung Liu,4 Chao-Yung Wang,5 Yu-Lun Lo,6 Guo-She Lee,7,8 Yi-Ping Chao,4,9 Hsueh-Yu Li,10 Terry BJ Kuo,11 Cheryl CH Yang,11 Liang-Yu Shyu,12 Li-Ang Lee10,11 1Department of Family Medicine, Chang Gung Memorial Hospital, Taipei Branch and Linkou Main Branch, Chang Gung University, Taoyuan, Taiwan; 2Department of Industrial Engineering and Management, National Taipei University of Technology, Taipei, Taiwan; 3Genomic Medicine Institute & Obesity Institute, Geisinger Medical, Danville, PA, USA; 4Department of Neurology, Chang Gung Memorial Hospital, Linkou Main Branch, Chang Gung University, Taoyuan, Taiwan; 5Department of Cardiology, Chang Gung Memorial Hospital, Linkou Main Branch, Chang Gung University, Taoyuan, Taiwan; 6Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Linkou Main Branch, Chang Gung University, Taoyuan, Taiwan; 7Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan; 8Department of Otolaryngology, Taipei City Hospital, Ren-Ai Branch, Taipei, Taiwan; 9Department of Computer Science and Information Engineering, Chang Gung University, Taoyuan, Taiwan; 10Department of Otorhinolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Linkou Main Branch, Chang Gung University, Taoyuan, Taiwan; 11Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan; 12Department of Biomedical Engineering, Chung Yuan Christian University, Taoyuan, TaiwanCorrespondence: Li-Ang LeeDepartments of Otorhinolaryngology-Head and Neck Surgery, Sleep Center, Chang Gung Memorial Hospital, Linkou Main Branch, No. 5, Fu-Hsing Street, Guishan District, Taoyuan, 33305, TaiwanTel +886 33281200 ext. 3972Fax +886 33979361Email 5738@cgmh.org.twBackground: Obstructive sleep apnea (OSA) and snoring have been reported to be modifiable risk factors for thick carotid intima-media thickness (CIMT) and carotid atherosclerosis, which are closely linked to cardiovascular disease.Methods: This cross-sectional study prospectively recruited 70 participants with OSA and without a history of carotid artery disorder, who primarily sought surgical Intervention. OSA and snoring were assessed with the Epworth Sleepiness Scale, Snore Outcomes Survey, polysomnography, and snoring sound recording. The carotid arteries were evaluated with ultrasonography and divided into three types of carotid artery profiles (normal carotid artery, thick CIMT, or significant carotid atherosclerosis). Multivariate linear/logistic/categorical regressions were performed with the forward selection approaches/logistic least absolute shrinkage and selection operator, as appropriate.Results: Normalized snoring sound energy (301– 850 Hz) was independently associated with the carotid intima-media thickness (regression coefficient [β] = 0.01, standard error [SE] = 0.004, P = 0.03; R2 = 0.067) and type of carotid profile (β = 0.40, SE = 0.09, P < 0.001; R2 = 0.156). Normalized snoring sound energy (4– 300 Hz) (β = − 0.10, SE = 0.04, P = 0.01) and female sex (β = 1.90, SE = 0.94, P = 0.04) were independently related to the presence of carotid stenosis (R2 = 0.159). The optimal regression model of the type of carotid artery profile included normalized snoring sound energy (301– 850 Hz) (β = 0.33, SE = 0.14, P = 0.03), snoring time (β = 0.26, SE = 0.13, P = 0.047), female sex (β = 0.26, SE = 0.13, P = 0.047), and increased age (β = 0.20, SE = 0.10, P = 0.04) under the control of the Snore Outcomes Survey score, 3% oxygen desaturation index, snoring sound energy (4– 1500 Hz), normalized snoring sound energy (851– 1500 Hz), cigarette smoking, and hyperlipidemia (R2 = 0.427).Conclusion: Our findings suggested that snoring sound characteristics are associated with carotid artery profiles among early OSA patients who cannot be noticed by ultrasound because organic changes of the carotid artery have not yet started. Future studies are warranted to verify the clinical significance of the results.Keywords: atherosclerosis, common carotid artery, categorical regression, obstructive sleep apnea, snoring, ultrasound

SummaryTo enhance the developmental competency of murine ovarian follicles cultured in vitro, C-type natriuretic peptide (CNP) was supplemented in the culture system. Although the mechanism is not fully elucidated, it was reported that the effect of CNP supplementation was mediated by increased cyclic guanosine monophosphate (cGMP). In the present study, cGMP levels in media for murine preantral follicle culture were compared both between a control group without CNP supplementation and an experimental group with CNP supplementation and between days in each group. In addition, follicle growth patterns and oocyte maturity were assessed and compared between the two groups. Results demonstrated that along with in vitro culture, cGMP levels increased (P < 0.05) both in the control group and the experimental group, whereas cGMP levels were not significantly different between the two groups on the same day of in vitro culture (P > 0.05). The oocyte’s maturity was superior in the experimental group compared with the control group (P < 0.05). As ovarian follicles grew three-dimensionally in the experimental group but were flattened in the control group, CNP might improve oocyte maturity through maintaining the three-dimensional architecture of the ovarian follicle because of increased transzonal projections (TZP) and functional gap junctions between oocyte and surrounding granulosa cells.

BReast tumor Kinase (BRK, also known as PTK6) is a non-receptor tyrosine kinase that is highly expressed in breast carcinomas while having low expression in the normal mammary gland, which hints at the oncogenic nature of this kinase in breast cancer. In the past twenty-six years since the discovery of BRK, an increasing number of studies have strived to understand the cellular roles of BRK in breast cancer. Since then, BRK has been found both in vitro and in vivo to activate a multitude of oncoproteins to promote cell proliferation, metastasis, and cancer development. The compelling evidence concerning the oncogenic roles of BRK has also led, since then, to the rapid and exponential development of inhibitors against BRK. This review highlights recent advances in BRK biology in contributing to the “hallmarks of cancer”, as well as BRK's therapeutic significance. Importantly, this review consolidates all known inhibitors of BRK activity and highlights the connection between drug action and BRK-mediated effects. Despite the volume of inhibitors designed against BRK, none have progressed into clinical phase. Understanding the successes and challenges of these inhibitor developments are crucial for the future improvements of new inhibitors that can be clinically relevant.

SummaryThe present study investigated the effects of c-type natriuretic peptide (CNP) on the development of murine preantral follicles during in vitro growth (IVG). Preantral follicles isolated from ovaries of Kunming mice were cultured in vitro. In the culture system, CNP was supplemented in the experimental groups and omitted in the control groups. In Experiment 1, CNP was only supplemented at the early stage and follicle development was evaluated. In Experiments 2 and 3, CNP was supplemented during the whole period of in vitro culture. In Experiment 2, follicle development and oocyte maturity were evaluated. In Experiment 3, follicle development and embryo cleavage after in vitro fertilization (IVF) were assessed. The results showed that in the control groups in all three experiments, granulosa cells migrated from within the follicle and the follicles could not reach the antral stage. In the experimental groups in all three experiments, no migration of granulosa cells was observed and follicle development was assessed as attaining the antral stage, which was significantly superior to that of the control group (P < 0.0001). Oocyte meiotic arrest was effectively maintained, hence giving good developmental competence. In conclusion, CNP supplementation in the culture system during IVG benefited the development of murine preantral follicles.

The aims of this study are to examine the changes of tongue thickness and distance of two lingual arteries through drug-induced sleep ultrasound, and explore the relationship between sonographic measurements and clinical data.A total of 26 confirmed obstructive sleep apnea patients were recruited in this one-year study. All patients received ultrasound examination twice (wakefulness and drug-induced sleep) in sleep center under level 1 polysomnographic monitor. Drug-induced sleep was performed by administration of one Stilnox (Zolpidem, 2 mg/tablet) and ultrasound procedure commenced once stage 2 sleep shown in polysomnography. Ultrasound imaging was implemented via submental approach with transducer position at the sagittal midline of the submental area (sagittal view) to measure thickness of the tongue. Transducer was then moved at a transverse midpoint between the inferior border of the mandible and the hyoid bone (transverse view) to measure the distance between 2 lingual arteries.The distance between 2 lingual arteries elongated significantly (p .001) and thickness of tongue muscle became thinner during drug-induced sleep. The distance between 2 lingual arteries (sleep) had positive correlation with apnea/hypopnea index (AHI, r = 0.51, p = .008) and body mass index (BMI, r = 0.46, p = .018).Drug-induced sleep ultrasound is feasible to measure changes of tongue in OSA patients. Ultrasound imaging showed that tongue muscle became thinner in conjunction with significant widening in distance between two lingual arteries during hypnotic-induced sleep and that was positively correlated with AHI and BMI. Drug-induced sleep ultrasound may be helpful to enhance safety in tongue surgery for OSA patients.

Background There has been ongoing research impetus to uncover novel blood-based diagnostic and prognostic biomarkers for Alzheimer’s disease (AD), vascular dementia (VaD), and related cerebrovascular disease (CEVD)-associated conditions within the spectrum of vascular cognitive impairment (VCI). Sphingosine-1-phosphates (S1Ps) are signaling lipids which act on the S1PR family of cognate G-protein-coupled receptors and have been shown to modulate neuroinflammation, a process known to be involved in both neurodegenerative and cerebrovascular diseases. However, the status of peripheral S1P in AD and VCI is at present unclear. Methods We obtained baseline bloods from individuals recruited into an ongoing longitudinal cohort study who had normal cognition (N = 80); cognitive impairment, no dementia (N = 160); AD (N = 113); or VaD (N = 31), along with neuroimaging assessments of cerebrovascular diseases. Plasma samples were processed for the measurements of major S1P species: d16:1, d17:1, d18:0, and d18:1, along with pro-inflammatory cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF). Furthermore, in vitro effects of S1Ps on cytokine expression were also studied in an astrocytoma cell line and in rodent primary astrocytes. Results Of the S1Ps species measured, only d16:1 S1P was significantly reduced in the plasma of VaD, but not AD, patients, while the d18:1 to d16:1 ratios were increased in all cognitive subgroups (CIND, AD, and VaD). Furthermore, d18:1 to d16:1 ratios correlated with levels of IL-6, IL-8, and TNF. In both primary astrocytes and an astroglial cell line, treatment with d16:1 or d18:1 S1P resulted in the upregulation of mRNA transcripts of pro-inflammatory cytokines, with d18:1 showing a stronger effect than d16:1. Interestingly, co-treatment assays showed that the addition of d16:1 reduced the extent of d18:1-mediated gene expression, indicating that d16:1 may function to “fine-tune” the pro-inflammatory effects of d18:1. Conclusion Taken together, our data suggest that plasma d16:1 S1P may be useful as a diagnostic marker for VCI, while the d18:1 to d16:1 S1P ratio is an index of dysregulated S1P-mediated immunomodulation leading to chronic inflammation-associated neurodegeneration and cerebrovascular damage.

Background/Purpose: To examine whether the prevalence rate of human papillomavirus (HPV) infection in Taiwanese patients with primary laryngeal squamous cell carcinoma (LSCC) is different from that in those with a vocal polyp (VP) or vocal fold leukoplakia (VFL). Methods: This prospective cohort study recruited 41 consecutive patients with primary LSCC and 27 and 20 patients with VP and VFL, respectively. The HPV L1 gene in surgical specimens was detected using polymerase chain reaction. High-risk HPV DNA in tissue microarray specimens was detected using in situ hybridization. Expression of p16INK4a in tissue microarray specimens was determined through immunohistochemistry. Results: The prevalence of HPV L1 DNA in the LSCC group was equivalent to that in the VP and VFL groups (7.3% vs. 7.4% vs. 10.0%; P = 0.929; effect size = 0.20). High-risk HPV DNA detected using in situ hybridization was relatively rare in all groups (2.6% vs. 5.3% vs. 0.0%; P = 0.636; effect size = 0.81). The prevalence of p16INK4a positivity was significantly lower in the LSCC group than in the VP and VFL groups (5.1% vs. 58.8% vs. 14.3%; P

This study was designed to determine the effect of phytase extracted from Aspergillus niger (Natuphos® E) on growth performance, bone mineralization, phosphorous excretion, and meat quality parameters in broilers fed available phosphorous (aP)-deficient diet. In total, 810 one-day-old Indian River broilers were randomly allotted into one of three dietary treatments, with six replicates per treatment. The three dietary treatments were 1) control group (CON: basal diet with sufficient aP), 2) low phytase (LPY: available phosphorus-deficient diet supplemented with 0.01% phytase), and 3) high phytase (HPY: available phosphorus-deficient diet supplemented with 0.02% phytase). Average daily gain and, feed intake, and feed conversion ratio were measured for 35 days. Excreta were collected from each pen on day 35. One broiler from each cage was euthanized to collect visceral organs and tibia samples. Broiler chickens fed LPY and HPY showed improved (P

I-Chun Kuo,1,2 Li-Jen Hsin,1,2 Li-Ang Lee,1,2 Tuan-Jen Fang,1,2 Ming-Shao Tsai,2,3 Yi-Chan Lee,2,4 Shih-Chieh Shen,2,5 Hsueh-Yu Li1,2 1Departments of Otolaryngology-Head & Neck Surgery, Chang Gung Memorial Hospital, Linkou Main Branch, Tao-yuan City, Taiwan; 2College of Medicine, Chang Gung University, Tao-Yuan, Taiwan; 3Departments of Otolaryngology-Head & Neck Surgery, Chang Gung Memorial Hospital, Chiayi Branch, Chiayi City, Taiwan; 4Departments of Otolaryngology-Head & Neck Surgery, Chang Gung Memorial Hospital, Keelung Branch, Keelung City, Taiwan; 5Departments of Otolaryngology-Head & Neck Surgery, New Taipei City Municipal Tucheng Hospital, New Taipei City, TaiwanCorrespondence: Hsueh-Yu LiDepartments of Otolaryngology-Head & Neck Surgery, Chang Gung Memorial Hospital, Linkou Main Branch, Tao-yuan City, TaiwanTel +886-3-328-1200 ext.3966Fax +886-3-397-9361Email hily38@cgmh.org.twObjective: This study aims to explore the factors that contribute to epiglottic collapse (EC) in patients with obstructive sleep apnea (OSA).Methods: This study enrolled 35 patients (34 males; median age, 39 years; median apnea–hypopnea index (AHI), 55.4 events/h; median body mass index (BMI), 26.9 kg/m2). EC (epiglottis attaching onto the posterior pharyngeal wall) was diagnosed by drug-induced sleep computed tomography (DI-SCT). Three dimensions were assessed for comparison between the EC and non-EC (NEC) groups that included anatomical measurement: epiglottic length and angle, endoscopic classification of epiglottis obstructing the glottis (Type I, none; Type II, partial; and Type III, total), and dynamic hyoid movement during DI-SCT (Δ hyoid = √(x2 + y2), maximal displacement of hyoid in x and y axes during sleep breathing cycle).Results: EC was found in 12 patients (34%). No difference in age, gender, AHI, and BMI between the two groups was noted. The anatomical measurement revealed that epiglottis length was significantly different between the EC and NEC groups (21.2 vs 15.8 mm; p < 0.001), with a cutoff value of 16.6 mm (sensitivity, 100%; specificity, 65.2%). The EC group patients showed larger hyoid movement than the NEC group patients (Δ hyoid, 4.8 vs 3.0 mm; p = 0.027). By contrast, epiglottic angle and endoscopic classification revealed an insignificant difference between the two groups.Conclusion: Epiglottis is a potential collapse site among multilevel obstruction in moderate to severe OSA patients. Epiglottic length is highly sensitive in predicting EC, with the cutoff value of 16.6 mm. Hyoid movement plays a role in contributing to EC in OSA patients.Keywords: obstructive sleep apnea, epiglottic collapse, drug-induced sleep computed tomography, epiglottic length, hyoid bone movement

Pancreatic cancer (PC) is one of the leading causes of death and is the fourth most malignant tumor in men. The epigenetic and genetic alterations appear to be responsible for development of PC. Small interfering RNA (siRNA) is a powerful genetic tool that can bind to its target and reduce expression level of a specific gene. The various critical genes involved in PC progression can be effectively targeted using diverse siRNAs. Moreover, siRNAs can enhance efficacy of chemotherapy and radiotherapy in inhibiting PC progression. However, siRNAs suffer from different off target effects and their degradation by enzymes in serum can diminish their potential in gene silencing. Loading siRNAs on nanoparticles can effectively protect them against degradation and can inhibit off target actions by facilitating targeted delivery. This can lead to enhanced efficacy of siRNAs in PC therapy. Moreover, different kinds of nanoparticles such as polymeric nanoparticles, lipid nanoparticles and metal nanostructures have been applied for optimal delivery of siRNAs that are discussed in this article. This review also reveals that how naked siRNAs and their delivery systems can be exploited in treatment of PC and as siRNAs are currently being applied in clinical trials, significant progress can be made by translating the current findings into the clinical settings.

Background: Early injection laryngoplasty (EIL) using hyaluronic acid (HA) is an effective treatment for glottic insufficiency in patients with acute unilateral vocal fold paralysis (UVFP). Most patients benefit by showing improvement in voice and quality of life and implied reduced need for permanent laryngoplasty. However, injected HA might resolve within a short period, so its long-term outcomes and the need for secondary procedures need to be clarified. Methods: Patients who underwent EIL with HA for acute UVFP from January 2015 to December 2018 were included. The factors that may associate with the prognosis including voice performance and laryngeal configuration at presentation, the cause of UVFP, and the type of HA for EIL were analyzed. Results: Ninety-four patients were included for analysis, with a mean follow-up period of 25.1 months (95% CI: 22.8–27.4 months). After primary HA injection, 22 patients (23.4%) underwent secondary procedures (rate: 13.1% per person-year), and most (63.6%) of the events occurred after one year from the first injection. The rate of secondary procedures within the first 12 months was 9.0% (14.1% and 4.3% for low-concentrated HA (LHA) and high-concentrated HA (HHA), respectively). The incidence of the secondary procedures was higher in the LHA group (18.2%) (p = 0.026) than in the HHA group (7.5%). Conclusions: The rate of secondary procedures was lower than the prediction based on the resorption time of HA, a finding that could be partly accounted for by both natural nerve recovery and a long-lasting effect of EIL. EIL with HHA had a lower rate of re-treatment than that with LHA, suggesting a better clinical utility for acute UVFP.

Older age, obesity, and obstructive sleep apnea syndrome (OSAS) are known to increase the risk of hypertension in adults. However, data for children are scarce. This study aimed to investigate the relationships between hypertension, age, weight status, and disease severity in 396 children with OSAS. The prevalence rates of hypertension, obesity, and severe OSAS (apnea-hypopnea index ≥10) were 27.0%, 28.0%, and 42.9%, respectively. Weight z-score and apnea-hypopnea index were independently correlated with systolic blood pressure z-score, and minimal blood oxygen saturation (SpO2) was independently associated with diastolic blood pressure z-score. Overall, late childhood/adolescence (odds ratio (OR) = 1.72, 95% CI = 1.05–2.81), obesity (OR, 2.58, 95% CI = 1.58–4.22), and severe OSAS (OR = 2.38, 95% CI = 1.48–3.81) were independent predictors of pediatric hypertension. Furthermore, late childhood/adolescence (OR = 2.50, 95% CI = 1.10–5.71) and abnormal SpO2 (mean SpO2 &lt, 95%, OR = 4.91, 95% CI = 1.81–13.27) independently predicted hypertension in obese children, and severe OSAS (OR = 2.28, 95% CI = 1.27–4.10) independently predicted hypertension in non-obese children. In conclusion, obesity, OSAS severity, and abnormal SpO2 are potentially modifiable targets to improve hypertension while treating children with OSAS.

Emerging evidence has revealed that cricothyroid (CT) muscle dysfunction in unilateral vocal fold paralysis (UVFP) further impairs patients' voices. Given that CT muscle dysfunction does not influence vocal fold position, the mechanism of voice dysfunction induced by dysfunction of CT muscle in UVFP patients remains controversial. This study compares aerodynamics between UVFP patients with and without CT muscle involvement.This cross-sectional study recruited patients with UVFP manifesting dysphonia, and UVFP was confirmed with videolaryngoscopy and laryngeal electromyography (LEMG). Voice analysis and aerodynamic tests were further performed. Patients with (CT+ group) and without (CT- group) CT muscle involvement were compared.A total of 175 patients (40 in the CT+ group and 135 in the CT- group) with UVFP were analyzed. The CT+ group showed lower maximal sound pressure level (SPL) (P=0.039), mean SPL (P=0.042), peak air pressure (P0.001), mean peak air pressure (P0.001) and aerodynamic power (P=0.004) than the CT- group.The decrease in SPL, peak air pressure, and aerodynamic power in UVFP patients with CT muscle dysfunction suggests that the effect of CT muscle dysfunction is mediated by a change in aerodynamics.

Sandblasting is a relatively common surface treatment for zirconia all-ceramic crown. However, the effect of sandblasting on the bond strength of veneering porcelain and crown is controversial in literatures. A meta-analysis can provide systematic analysis on the results of different studies. In this paper, meta-analysis was used to study the effect of sandblasting on the bond strength between the veneering porcelain and zirconia crown. First, the Medline database was adopted for literature retrieval, and then the quality of the literature was assessed, as well as screening and exclusion of the literature manually. Finally, 24 papers were included in the study after the data extraction and Review Manager software was adopted for data analysis. After the analysis, it was showed that the results of study in literatures were not biased, but there was significant heterogeneity. Then further removing the literature with large differences in data, the data were analyzed again, and the result still had high heterogeneity. Therefore, according to the current results, the sandblasting treatment could not increase the bond strength between the veneering porcelain and zirconia crown.

According to the AJCC third to seventh edition staging manuals (1988-2010), the presence of through cortex and/or skin invasion in oral cavity squamous cell carcinoma (OCSCC) identifies T4a tumors. The AJCC eighth edition (2018) introduced a depth of invasion (DOI) 20 mm as a criterion for pT4a. Subsequently, a revision maintained that tumors 4 cm with a DOI 10 mm should be classified as pT4a. We sought to analyze the prognostic impact of the three distinct criteria identifying pT4a disease.We examined 667 consecutive patients with pT3-4 buccal/gum/hard palate/retromolar SCC who underwent surgery between 1996 and 2016. pT1/pT2 (n = 108/359) disease were included for comparison purposes.The 5-year outcomes of patients with pT1/pT2/without (n = 406)/with tumor 4 cm/DOI 10 mm (n = 261), pT1/pT2/DOI ≤ 20 mm (n = 510)/ 20 mm (n = 157), and pT1/pT2/without (n = 305)/with through cortex/skin invasion (n = 362) were as follows: disease-specific survival (DSS), 98%/89%/79%/65%, p 0.001, 98%/89%/78%/59%, p 0.001, and 98%/89%79%/69%, p 0.001; overall survival (OS), 90%/79%/63%/51%, p 0.001, 90%/79%/63%/42%, p 0.001, and 90%/79%/65%/52%, p 0.001. In pT3-4 disease, a tumor 4 cm/DOI 10 mm was an independent adverse prognosticator for 5-year DSS rate, DOI 20 mm was an independent adverse prognosticator for 5-year DSS and OS rates, whereas through cortex/skin invasion independently predicted 5-year OS rates.All of the three criteria (tumor 4 cm/DOI 10 mm, DOI 20 mm, and through cortex/skin invasion) identify high-risk patients, which should be reflected in further revisions of pT4a classification in OCSCC.

Objective To elucidate potential role of cephalometric measurements to predict tongue base obstruction as observed on drug Induced Sleep Computed Tomography (DIS-CT). Methods Study included 35 patients with moderate to severe sleep apnea who underwent DIS-CT & cephalometric examination to assess tongue base obstruction. Results Statistically significant difference was noted for SNA angle & Mandibular posterior airway space (PAS) among groups with total tongue obstruction versus Non-total tongue obstruction identified on DIS-CT. Conclusion Lateral cephalogram can be used as a standard screening tool with commonly used skeletal and soft tissue parameters to predict the possibility of tongue collapse/obstruction during sleep in patient with moderate to severe OSAS.

The role of microRNA (miRNA) in influenza A virus (IAV) host species specificity is not well understood as yet. Here, we show that a host miRNA, miR-1290, is induced through the extracellular signal-regulated kinase (ERK) pathway upon IAV infection and is associated with increased viral titers in human cells and ferret animal models. miR-1290 was observed to target and reduce expression of the host vimentin gene. Vimentin binds with the PB2 subunit of influenza A virus ribonucleoprotein (vRNP), and knockdown of vimentin expression significantly increased vRNP nuclear retention and viral polymerase activity. Interestingly, miR-1290 was not detected in either chicken cells or mouse animal models, and the 3′ UTR of the chicken vimentin gene contains no binding site for miR-1290. These findings point to a host species-specific mechanism by which IAV upregulates miR-1290 to disrupt vimentin expression and retain vRNP in the nucleus, thereby enhancing viral polymerase activity and viral replication., Graphical Abstract

Obstructive sleep apnea (OSA) is a common disease in adults, which influences human relations, quality of life and associates with major complications. Continuous positive airway pressure (CPAP) is the gold standard treatment modality in OSA patients. For patients incompliant or unwilling to CPAP therapy, surgery is an alternative treatment. Sleep surgery for OSA include intrapharyngeal surgery, extrapharyngeal surgery and bariatric surgery addressing upper airway soft tissue, maxillofacial bone, and obesity, respectively. Among sleep surgeries, intrapharyngeal surgery (soft tissue surgery) is widespread used and serves overwhelming majority in OSA surgical patients. Despite the popularity of intrapharyngeal surgery, its outcomes can be influenced by multiple factors and consequently need conjunctive remedy to enhance at the short-term and sustain in the long-term. In this article, we introduce updated indications for treating OSA, practical principle in decision-making between CPAP and surgery, hybrid procedures in treating obstruction at the nose, palate, tongue and epiglottis, and postoperative integrated treatment including oropharyngeal myofunctional therapy (local), positional therapy (regional), and body weight reduction (systemic), and circadian rhythm (central). In summary, intrapharyngeal surgery is a target-oriented procedure that needs to be performed precisely and combines with integrated treatment as a holistic care for OSA patients. Keywords: Obstructive sleep apnea, Intrapharyngeal surgery, Mini-invasive septoturbinoplasty, Suspension palatoplasty, Hybrid treatment

The tonsil microbiome is associated with chronic tonsillitis and obstructive sleep apnea (OSA) in children, and the gut microbiome is associated with host weight status. In this study, we hypothesized that weight status may be associated with clinical profiles and the tonsil microbiome in children with OSA. We prospectively enrolled 33 non-healthy-weight (cases) and 33 healthy-weight (controls) pediatric OSA patients matched by the proportion of chronic tonsillitis. Differences in the tonsil microbiome between the non-healthy-weight and healthy-weight subgroups and relationships between the tonsil microbiome and clinical variables were investigated. Non-healthy weight was associated with significant intermittent hypoxemia (oxygen desaturation index, mean blood saturation (SpO2), and minimal SpO2) and higher systolic blood pressure percentile, but was not related to the tonsil microbiome. However, chronic tonsillitis was related to Acidobacteria in the non-healthy-weight subgroup, and oxygen desaturation index was associated with Bacteroidetes in the healthy-weight subgroup. In post hoc analysis, the children with mean SpO2 ≤ 97% had reduced α and β diversities and a higher abundance of Bacteroidetes than those with mean SpO2 &gt, 97%. These preliminary findings are novel and provide insights into future research to understand the pathogenesis of the disease and develop personalized treatments for pediatric OSA.

Helicobacter pylori (H. pylori) infection involves the development of gastric cancer and may be associated with laryngeal cancer. However, laryngeal H. pylori infection in Taiwanese patients with newly diagnosed laryngeal cancer has not been reported. This study was aimed to investigate the possible association between laryngeal H. pylori infection and laryngeal cancer in Taiwan and perform a systematic review of previous reports in other countries. An analysis of 105 patients with laryngeal lesions found the positive rates of H. pylori DNA (determined by polymerase chain reaction) and antigen (determined by immunohistochemistry) of the laryngeal lesions were relatively low (vocal polyps: 3% and 3%, vocal fold leukoplakia: 0% and 0%, laryngeal cancers: 0% and 2%). Furthermore, H. pylori-associated laryngopharyngeal reflux and the expression of E-cadherin and CD1d (determined by immunohistochemistry) were comparable among the three subgroups. Fifteen studies were involved in the systematic review of the digital literature database, distributed to February 2021. The data of patients with laryngeal cancer and controls showed that the laryngeal H. pylori infection rates were 29.4% and 16.7%, respectively. Although current evidence supported that laryngeal H. pylori infection was associated with laryngeal cancer globally, it might not play a role in the development of laryngeal cancer in Taiwan.

pStage IVB oral cavity squamous cell carcinoma (OCSCC) is defined as either pT4b or pN3 disease. We sought to devise an improved prognostic stratification of this patient group.Between December 2003 and January 2018, we retrospectively reviewed the clinical records of 1331 consecutive patients with OCSCC who received tumor excision and neck dissection. The number of patients with pT4a/pT4b, pT1N3b/pT2N3b/pT3N3b/pT4N3b, and pStage IVA/IVB was 370/83, 3/49/42/142, and 332/295, respectively.The 5-year rates of disease-free survival (DFS) and disease-specific survival (DSS) for patients with pT4a/pT4b disease were 64%/63% (p = 0.973) and 72%/69% (p = 0.672), respectively. The 5-year DFS and DSS rates for patients with pT1N3b/pT2N3b/pT3N3b/pT4N3b disease were 67%/65%/40%/42% (p 0.001; pT1-2N3b versus pT3-4N3b, p = 0.002) and 100%/68%/45%/49% (p 0.001; pT1-2N3b versus pT3-4N3b, p = 0.002), respectively. We devised a new definition for pStage IV by considering patients with pT4bN0-2 and pT1-2N3b diseases as pStage-IVA. The number of patients with pStage IVA/IVB (pT3-4N3b) was 443/184. The 5-year rates of AJCC pStage IVA/IVB and the newly proposed pStage IVA/IVB (pT3-4N3b) were as follows: DFS, 74%/52% and 72%/42%; DSS, 83%/58% and 81%/47%; respectively, all p value 0.001.The clinical outcomes of pT4b and pT4a OCSCC are similar. However, patients with pT3-4N3b disease have a less favorable 5-year prognosis compared with cases with pT1-2N3b. In light of the unfavorable outcomes, pT3-4N3b disease should continue to be classified as pStage IVB. Conversely, pT4bN0-2 and pT1-2N3b diseases portend a less adverse prognosis and should therefore be downstaged to pStage IVA.

(1) Background: Sleep apnea may be a risk factor for deep neck infection (DNI). The objective of this study was to investigate the effects of sleep apnea on DNI. (2) Methods: In this first nationwide retrospective cohort study on the sleep apnea–DNI correlation, we obtained data from the Longitudinal Health Insurance Database 2005, a subset of the Taiwan National Health Insurance Research Database. Patients who were newly diagnosed with sleep apnea between 1997 and 2012 were identified, and patients without sleep apnea were matched at a 1:4 ratio in age, sex, socioeconomic status, and urbanization level. The primary outcome of this study was DNI occurrence. The treatment modalities for sleep apnea and the comorbidities that occurred during the study period were also analyzed. (3) Results: Our sleep apnea and comparison (non-sleep apnea) cohorts comprised 6114 and 24,456 patients, respectively. We compared the cumulative incidence of DNI between these cohorts and found a greater incidence of DNI in the sleep apnea cohort (p &lt, 0.001). A strong sleep apnea–DNI association was found following analysis via the adjusted Cox proportional-hazards model (full model hazard ratio, 1.71, 95% confidence interval, 1.28–2.28, p &lt, 0.001). In the subgroup analysis, sleep apnea increased DNI risk in men, in those aged &lt, 50 years, and in those without diabetes mellitus, end-stage renal disease, liver cirrhosis, autoimmune disease, obesity, tonsillectomy, or adenotonsillectomy. (4) Conclusions: Our results confirmed sleep apnea to be an independent risk factor for DNI. Physicians should be aware of the potential occurrence of DNI in patients with sleep apnea.

Allergic rhinitis (AR) is correlated with diseases including allergic laryngitis, chronic obstructive pulmonary disease (COPD), asthma, and chronic rhinosinusitis (CRS). The unified airway model suggests that inflammation can spread in both lower and upper respiratory tracts. Moreover, some voice problems&mdash, laryngeal edema, dysphonia, and vocal nodules&mdash, have been associated with AR. We examined the association between AR and laryngeal pathology. We investigated 51,618 patients with AR between 1 January 1997 and 31 December 2013, along with 206,472 patients without AR matched based on age, gender, urbanization level, and socioeconomic status at a 1:4 ratio. We followed patients up to the end of 2013 or their death. The occurrence of laryngeal pathology was the primary outcome. Individuals with AR had a 2.43 times higher risk of laryngeal pathology than the comparison cohort group (adjusted HR: 2.43, 95% CI: 2.36&ndash, 2.50, p &lt, 0.001). Patients diagnosed as having AR exhibited higher comorbidity rates, including of asthma, COPD, CRS, gastroesophageal reflux disease, and nasal septum deviation, than those of the comparison cohort. Our results strongly indicate that AR is an independent risk factor for laryngeal pathology. Therefore, when treating AR and voice problems, physicians should be attuned to possible laryngeal pathology.

(1) Background: Medialization laryngoplasty with autologous thyroid cartilage (MLATC) is a surgical treatment for glottal closure insufficiency (GCI) resulted from unilateral vocal fold paralysis/paresis (UVFP) and vocal fold atrophy. We aimed to survey the influence of patient-related factors on the outcomes after MLATC. (2) Methods: The study enrolled 35 patients with GCI who underwent MLATC. Patient voice data were recorded before and after MLATC by using multiple acoustic parameters and subjective assessment in a computerized speech laboratory. GCI patients were characterized into subgroups based on three factors: age, &ge, 60 vs. &lt, 60 years, sex, men vs. women, and BMI, &ge, 24 vs. &lt, 24. (3) Results: When the subgroups were compared, men did not have better results after surgery than women. Patients ages &lt, 60 years did not exhibit any significantly different outcome compared with those aged &ge, 60 years. Patients with BMI &ge, 24 did not have any significantly different outcome compared with those with BMI &lt, 24. The subgroups of age, sex, and BMI had no significant difference in cumulative voice recovery and summation of GRBAS (G = grade, R = roughness, B = breathiness, A = asthenia, and S = strain). (4) Conclusions: MLATC is a good alternative surgery with long-term improvement in GCI patients. There is no evidence that age, sex, or BMI affect the functional outcome.

Background: Systemic inflammation and tonsil microbiome have been linked to chronic intermittent hypoxia during sleep in children with obstructive sleep apnea (OSA). However, their relationships have not been comprehensively studied. Here, we investigated the associations between systemic inflammation, tonsil microbiome, OSA severity, and surgical outcome in pediatric OSA patients regarding different weight status. Methods: We recruited 33 children with OSA and non-healthy-weight (cases) and 33 children with OSA and healthy-weight (controls) were prospectively recruited and matched by the proportion of chronic tonsillitis. Each patient underwent adenotonsillectomy and received at least 3-month follow-ups. Systemic inflammatory biomarkers (interleukin [IL]-6, IL-10) were detected in the blood sampled in the morning. Tonsil microbiome was identified with 16S ribosomal RNA gene sequencing. OSA severity was assessed by standard whole-night polysomnography. Results: Differences in systemic inflammatory biomarkers, tonsil phyla, and apnea-hypopnea index were not statistically significant between both groups. After adenotonsillectomy, all OSA severity variables significantly improved; however, apnea-hypopnea index was significantly higher in the non-healthy-weight group and serum level of IL-6 significantly reduced in the healthy-weight group. The percentage changes in IL-6 and minimal pulse oxygen saturation were respectively associated with Deinococcus-Thermus and Eremiobacteraeota in the non-healthy-weight group, whereas the percentage change in IL-6 was associated with Patescibacteria and Cloacimonetes in the healthy-weight group. Furthermore, chronic tonsillitis was related to Chloroflexi, Acidobacteria, Euryarchaeota, Thermotogae, Hydrogenedentes, and Rokubacteria in the non-healthy-weight group. Conclusion: These preliminary findings are novel and provide insight for future research to understand the pathogenesis of the disease and to develop personalized treatments.

Introduction: Efficacious screening of severe obstructive sleep apnea (OSA) is important for children with sleep-disordered breathing before time-consuming nocturnal polysomnography. However, the predictive performance of clinical variables, nocturnal unattended pulse oximetry, and snoring sound analysis to screen for severe pediatric OSA has not been comprehensively investigated. Methods: Forty-two consecutive children (11 [26%] girls and 31 [74%] boys; median age, 9 years; median body-mass index of 19.0 kg/m2) with loud snoring were prospectively recruited to undergo standard polysomnography, nocturnal pulse oximetry, and snoring sound analysis. Results: Binary logistic regression models showed that oxygen desaturation index ≥ 3% (> 5.9 events/h), adenoidal‐nasopharyngeal ratio (> 0.782), snoring sound energy of 801-1000 Hz (> 22.1 dB), and tonsil size (> 3) significantly predicted severe OSA, in descending order of odds ratio. Multivariate analysis showed that oxygen desaturation index ≥ 3%, adenoidal‐nasopharyngeal ratio, and tonsil size independently predicted severe OSA, and that their combination best predicted severe OSA (sensitivity = 91%; specificity = 84%; area under the curve = 0.92; p < 0.001). Conclusions: Our results suggested that pulse oximetry is better than snoring sound analysis to screen for severe OSA in children with loud snoring. A combination of oxygen desaturation index ≥ 3%, adenoidal‐nasopharyngeal ratio, and tonsil size can be used to efficiently screen for severe pediatric OSA.

Body composition (BC) parameters are associated with cardiometabolic diseases in children, however, the importance of BC parameters for predicting pediatric hypertension is inconclusive. This cross-sectional study aimed to compare the difference in predictive values of BC parameters and conventional anthropometric measures for pediatric hypertension in school-aged children. A total of 340 children (177 girls and 163 boys) with a mean age of 8.8 &plusmn, 1.7 years and mean body mass index (BMI) z-score of 0.50 &plusmn, 1.24 were enrolled (102 hypertensive children and 238 normotensive children). Significantly higher values of anthropometric measures (BMI, BMI z-score, BMI percentile, waist-to-height ratio) and BC parameters (body-fat percentage, muscle weight, fat mass, fat-free mass) were observed among the hypertensive subgroup compared to their normotensive counterparts. A prediction model combining fat mass &ge, 3.65 kg and fat-free mass &ge, 34.65 kg (area under the receiver operating characteristic curve = 0.688, sensitivity = 66.7%, specificity = 89.9%) performed better than BMI alone (area under the receiver operating characteristic curve = 0.649, sensitivity = 55.9%, specificity = 73.9%) in predicting hypertension. In conclusion, BC parameters are better than anthropometric measures in predicting pediatric hypertension. BC measuring is a reasonable approach for risk stratification in pediatric hypertension.

Cancer is one of the life-threatening disorders that, in spite of excellent advances in medicine and technology, there is no effective cure for. Surgery, chemotherapy, and radiotherapy are extensively applied in cancer therapy, but their efficacy in eradication of cancer cells, suppressing metastasis, and improving overall survival of patients is low. This is due to uncontrolled proliferation of cancer cells and their high migratory ability. Finding molecular pathways involved in malignant behavior of cancer cells can pave the road to effective cancer therapy. In the present review, we focus on phosphatase and tensin homolog (PTEN) signaling as a tumor-suppressor molecular pathway in gastric cancer (GC). PTEN inhibits the PI3K/Akt pathway from interfering with the migration and growth of GC cells. Its activation leads to better survival of patients with GC. Different upstream mediators of PTEN in GC have been identified that can regulate PTEN in suppressing growth and invasion of GC cells, such as microRNAs, long non-coding RNAs, and circular RNAs. It seems that antitumor agents enhance the expression of PTEN in overcoming GC. This review focuses on aforementioned topics to provide a new insight into involvement of PTEN and its downstream and upstream mediators in GC. This will direct further studies for evaluation of novel signaling networks and their targeting for suppressing GC progression.

Pediatric obstructive sleep apnea (OSA) is associated with adverse health outcomes, however, little is known about the diversity of this population. This retrospective study aims to investigate age-related differences in the anthropometric and clinical features of this population. A total of 253 Taiwanese children (70 (27.7%) girls and 183 (72.3%) boys) with OSA were reviewed. Their median age, body mass index (BMI) z-score, and apnea-hypopnea index were 6.9 years, 0.87, and 9.5 events/h, respectively. The cohort was divided into three subgroups: &lsquo, preschoolers&rsquo, (&ge, 2 and &lt, 6 years), &lsquo, school-age children&rsquo, 6 and &lt, 10 years), and &lsquo, adolescents (&ge, 10 and &lt, 18 years)&rsquo, The percentage of the male sex, BMI z-score, neck circumference, systolic blood pressure z-score, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio tended to increase with age. Adenoid grades tended to decrease with age. Overall, disease severity was independently correlated with neck circumference, tonsil size, and adenoid grade. Increased neck circumference and tonsillar hypertrophy were the most influential factors for younger children, whereas adenoidal hypertrophy became more important at an older age. In conclusion, gender prevalence ratio, anthropometric measures, and clinical features varied with age, and the pathogenic drivers were not necessarily the same as the aggravating ones.

The spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has taken on pandemic proportions, affecting over 100 countries in a matter of weeks. The goal of this study was to assess the diagnostic values of different methods of detecting and estimating the SARS-CoV-2 infection, and the auxiliary diagnostic potential of antibody assays. By retrospectively analyzing the data of viral RNAs and serum immunoglobulin M-immunoglobulin G antibodies against SARS-CoV-2 from 38 cases with confirmed coronavirus disease 2019 in the Second People's Hospital of Fuyang, we found that, in the early phase of the illness, the viral RNA was most abundant in the sputum specimens, followed by that in the throat swabs, while the antibody assays identified fewer positive cases at this stage. However, the sensitivity of the antibody assays overtook that of RNA test from the eighth day of disease onset. Simultaneous use of antibody assay and reverse transcription-quantitative real-time polymerase chain reaction improved the sensitivity of the diagnoses. Moreover, we found that most of these cases with no detectable viral RNA load during the early stages were able to be seropositive after 7 days. Our findings indicate that the antibody detection could be used as an effective supplementary indicator of SARS-CoV-2 infection in suspected cases with no detectable viral RNA, and in conjunction with nucleic acid detection in confirming the infection.

BackgroundThe spread of an novel coronavirus (SARS-CoV-2, previously named 2019-nCoV) has already taken on pandemic proportions, affecting over 100 countries in a matter of weeks. Elucidating the diagnostic value of different methods, especially the auxiliary diagnosis value of antibodies assays for SARS-CoV-2 infection is helpful for improving the sensitivities of pathogenic-diagnosis, providing timely treatment, and differentiating the infected cases from the healthy, thus preventing further epidemics.MethodsMedical records from 38 patients with confirmed SARS-CoV-2 infection in the Second People’s Hospital of Fuyang from January 22, 2020 to February 28, 2020 were collected and retrospectively analyzed. Specimens including throat swabs, sputum and serum were collected during the hospitalization period, viral RNAs and serum IgM-IgG antibodies to SARS-CoV-2 were measured respectively. The detectability of different methods as well as the auxiliary diagnosis value of antibodies test for SARS-CoV-2 infection were analyzed.ResultsAmong 38 patients, the total seropositive rate for IgM and IgG was 50.0% and 92.1%, respectively. Two patients remained seronegative throughout the course of illness. In the early phase of illness, the RNA test for sputum specimens possessed the highest detectability(92.3%), followed by the the RNA test for throat swabs (69.2%), and the antibodies assays presented lower positive rates(IgM, 23.0%, IgG, 53.8%). While, the sensitivity of antibodies assays overtook that of RNA test since day 8 after onset (IgM, 50.0%; IgG, 87.5%). Of note, the positive rate of throat swabs was only 13.0% for cases in later phase(≥15 d.a.o), and the sensitivities of IgM and IgG rose to 52.2% and 91.3%, respectively. Combined use of antibodies assay and qRT-PCR at the same time was able to improve the sensitivities of pathogenic-diagnosis, especially for the throat swabs group at the later stage of illness. Moreover, most of these cases with undetectable viral RNA in throat swabs specimens at the early stage of illness were able to be IgM/IgG seropositive after 7 days.ConclusionsThe antibodies detection against SARS-CoV-2 offers vital clinical information for physicians, and could be used as an effective supplementary indicator for suspected cases of negative viral nucleic acid detection or in conjunction with nucleic acid detection in the diagnosis of suspected cases.

Both obstructive sleep apnea (OSA) and obesity are major health issues that contribute to increased systemic inflammation in children. To date, adenotonsillectomy (AT) is still the first-line treatment for childhood OSA. However, the relationships among and predictive values of obesity, inflammation, and OSA severity have not been comprehensively investigated. This prospective study investigated body mass index (BMI), serum inflammatory markers, and OSA severity before and after AT in 60 pediatric patients with OSA. At baseline, differences in levels of interleukin-6, interleukin-9, basic fibroblast growth factor, platelet-derived growth factor-BB, as well as regulated on activation, normal T cell expressed and secreted (RANTES) were significant among the various weight status and OSA severity subgroups. After 3 months postoperatively, the differences in these inflammatory markers diminished along with a decrease in OSA severity while obesity persisted. The rate of surgical cure (defined as postoperative obstructive apnea-hypopnea index &lt, 2.0 and obstructive apnea index &lt, 1.0) was 62%. Multivariate analysis revealed that age, BMI z-score, granulocyte-macrophage colony-stimulating factor, monocyte chemotactic protein-1, and RANTES independently predicted surgical cure. Despite the significant reductions in inflammatory markers and OSA severity after AT, an inter-dependent relationship between obesity and OSA persisted. In addition to age and BMI, several inflammatory markers helped to precisely predict surgical cure.

Objective Patients with snoring and obstructive sleep apnea frequently have nasal and palatal obstruction. The objective of this study was to investigate the safety and feasibility of a palatal septal cartilage implant (SCI) for snoring and obstructive sleep apnea. Methods This was a preliminary study of 10 consecutive patients who were enrolled retrospectively from electronic charts. The patients had undergone a single-stage operation including septoturbinoplasty and palatal SCI at a tertiary referral hospital. After nasal surgery, the harvested cartilage was prepared and trimmed into strips for palatal implantation. Key procedures of palatal SCI include vertical tunneling of the midline and paramedian soft palate, insertion of the septal cartilage strips, and fixation suture of the implants. The primary outcome measures were adverse events, including implant extrusion, infection, bleeding, velopharyngeal insufficiency and globus symptoms, assessed by the Glasgow–Edinburgh Throat Scale (GETS) questionnaire (10-item, 8-grade [0–7] Likert scale). Secondary outcomes were subjective snoring loudness (visual analogue scale, VAS), excessive daytime sleepiness (Epworth sleepiness scale, ESS) and objective apnea-hypopnea index. All patients were followed up for at least 1 year. Results None of the aforementioned adverse events were noted during the one-year follow-up. Among the ten items of the GETS, the median score of nine items was 0, and the median score of the total GETS was 2.0, which was classified as “asymptomatic”. The snoring loudness improved significantly from 8.0 points (IQR 8.0–9.0) preoperation to 4.0 points (IQR 2.5–6.0) at 3 months postoperation and 4.5 points (IQR 3.3–6.0) at 1 year postoperation (P = 0.002 and P = 0.002, respectively). The ESS score improved significantly from 11.5 points (IQR 8.3–18.5) preoperation to 8.0 points (IQR 6.3–10.8) at 3 months postoperation and 8.5 points (IQR 6.3–10.8) at 1 year postoperation (P = 0.004 and P = 0.004, respectively). The apnea-hypopnea index significantly decreased from 54.7 (IQR 23.4–62.8) to 20.5 (IQR 14.7–45.6) (P = 0.047) in patients with a lower tongue position (modified Mallampati class ≤ II; n = 7). Conclusion Palatal SCI is a safe and feasible procedure. The advantages include providing implants of tailor-made length, biocompatible autologous cartilage and no need for extra-payment for the implant material. By using the SCI procedure, both nasal obstruction and sleep-disordered breathing can be managed in a single-stage operation. The long-term effectiveness of SCI deserves further research.

Apolipophorin-III (ApoLp-III) is an abundant hemolymph protein mainly involved in lipid transport and innate immunity in insects. In the present study, the gene Samia cynthia ricini ApoLp-III (ScApoLp-III) was identified from a transcriptome database, and contained 790 nucleotides with a putative open reading frame (ORF) of 561 bp encoding 186 amino acid residues. Phylogenetic analysis revealed that ScApoLp-III had significant homology with ApoLp-III protein from Antheraea pernyi. Higher ScApoLp-III expression levels were found in the fat body and silk gland by reverse transcription quantitative PCR (RT-qPCR). Injection of Staphylococcus aureus induced up-regulation of ScApoLp-III in the midgut, fat body and hemocytes. However, ScApoLp-III was down-regulated in the midgut and fat body after Pseudomonas aeruginosa injection, indicating that ScApoLp-III may contribute to the host’s defense against invading pathogens. Additionally, recombinant ScApoLp-III was found to bind different bacteria, including E. coli, P. aeruginosa, S. aureus and B. subtilis. Bactericidal tests showed that recombinant ScApoLp-III strongly inhibited Gram-negative bacteria, including Escherichia coli and P. aeruginosa. However, it had no obvious influence on Gram-positive bacteria. Taken together, our results suggest that the ScApoLp-III might play an important role in the innate immunity of S. c. ricini.

Objective To investigate the relationship between baseline snoring sound energy (SSE) and disease severity, changes in SSE after adenotonsillectomy, and the predictors of surgical success in children with obstructive sleep apnoea (OSA). Design Prospective cohort study. Setting Tertiary referral medical centre. Participants Thirty-two children with OSA whose apnoea-hypopnoea index ≥5 or apnoea-hypopnoea index ≥1.5 with OSA comorbidities were recruited. Patients with complicated OSA were excluded. All participants underwent snoring sound analysis, polysomnography, and adenotonsillectomy. Main outcome measures Snoring sound energy and apnoea-hypopnoea index were assessed at baseline and 6 months after adenotonsillectomy. Surgical success was defined as a postoperative apnoea-hypopnoea index Results The median age, body mass index, and apnoea-hypopnoea index was 9 years, 19.0 kg/m2 , and 13.2 events/h, respectively. Multivariate logistic regression showed that a baseline tonsil size of IV (odds ratio 15.7 [95% CI: 1.5-166.3]) and SSE of 801-1000 Hz > 21.9 dB (odds ratio 32.3 [95% CI: 2.6-396.6]) were significantly related to severe OSA. Following adenotonsillectomy, apnoea-hypopnoea index decreased significantly (P Conclusions Our findings suggest the potential utility of SSE of 801-1000 Hz to screen for severe OSA, predict surgical success and assess therapeutic outcomes. Specific baseline SSE may represent a potential biomarker for childhood OSA.

A surgical response to upper airway (UA) surgery for obstructive sleep apnea (OSA) depends on adequate correction of collapsible sites in the UA. This pilot study aimed to examine the surgical response to UA surgery directed by drug-induced sleep computed tomography (DI-SCT) for OSA.Prospective case series.Tertiary referral center.This study recruited 29 OSA patients (median age, 41 years; median body mass index, 26.9 kg/mDI-SCT showed that 28 (97%) patients had collapses at multiple sites, all of whom underwent multilevel UA surgery accordingly. The apnea-hypopnea index decreased from 53.6 to 26.8 ( P.001). There were 18 (62%) nonresponders and 11 (38%) responders. Multiple-site collapses could not predict surgical response ( P.99). The nonresponders had significant improvements in velopharyngeal, oropharyngeal lateral wall, and tongue collapses (all P.05), whereas the responders had significant improvements in velopharyngeal and oropharyngeal lateral wall collapses (both P ≤ .05).Despite multilevel OSA surgery, residual UA obstruction in nonresponders likely occurs due to multiple mechanisms. DI-SCT may help to elucidate the reasons for a nonresponse.

// Chung-Guei Huang 1, 2, 3, * , Li-Ang Lee 4, 5, * , Yi-Cheng Wu 5, 6 , Mei-Jen Hsiao 1, 3 , Jim-Tong Horng 1, 7 , Rei-Lin Kuo 1, 2 , Chih-Heng Huang 1, 8 , Ya-Chu Lin 3 , Kuo-Chien Tsao 1, 3 , Min-Chi Chen 5, 9 , Tse-Ching Chen 5, 10 and Shin-Ru Shih 1, 2, 3 1 Research Center for Emerging Viral Infections, Chang Gung University, Taoyuan 33302, Taiwan, ROC 2 Graduate Institute of Biomedical Sciences, Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan, ROC 3 Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan, ROC 4 Department of Otorhinolaryngology - Head and Neck Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan, ROC 5 Faculty of Medicine, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan, ROC 6 Department of Surgery, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 33305, Taiwan, ROC 7 Graduate Institute of Biomedical Sciences, Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan, ROC 8 Institute of Preventive Medicine, National Defense Medical Center, Taipei 11490, Taiwan, ROC 9 Department of Public Health and Biostatistics Consulting Center, Chang Gung University, Taoyuan 33302, Taiwan, ROC 10 Department of Pathology, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 33305, Taiwan, ROC * These authors have contributed equally to this work Correspondence to: Shin-Ru Shih, email: srshih@mail.cgu.edu.tw Tse-Ching Chen, email: ctc323@cgmh.org.tw Keywords: avian influenza A(H7N9) virus; primary epithelial cells; tropism; cytokine; patient-related characteristics Received: September 01, 2017 Accepted: February 10, 2018 Epub: February 20, 2018 Published: March 06, 2018 ABSTRACT Avian influenza A(H7N9) virus infections frequently lead to acute respiratory distress syndrome and death in humans. We aimed to investigate whether primary cultures of human respiratory tract epithelial cells are helpful to understand H7N9 virus pathogenesis and tissue tropism, and to evaluate how patient-related characteristics can affect the host’s response to infection. Normal human bronchial epithelial cells (isolated from two different donors) and primary epithelial cells (harvested from 27 patients undergoing airway surgery) were experimentally infected with H7N9 and/or H1N1pdm for 72 h. After virus infection, the culture media were collected for viral RNA quantitation and cytokine detection. Both H7N9 and H1N1pdm viruses replicated and induced a cytokine response differently for each donor in the normal human bronchial epithelial model. H7N9 replicated equivalently in epithelial cells harvested from the inferior turbinate and paranasal sinus, and those from the larynx and bronchus, at 72 h post-infection. Viral RNA quantity at 72 h was significantly higher in patients aged 21–64 years than in patients aged ≥ 65 years; however, no effects of sex, medical comorbidities, and obesity were noted. H7N9-infected cultured cells released multiple cytokines within 72 h. Levels of interleukin-1β, interleukin-6, interleukin-8, interferon-γ, and tumor necrosis factor-α were associated differently with patient-related characteristics (such as age, sex, obesity, and medical comorbidities). In the era of precision medicine, these findings illustrate the potential utility of this primary culture approach to predict a host’s response to H7N9 infection or to future infection by newly emerging viral infections, and to dissect viral pathogenesis.

The prognosis of pN3b oral cavity squamous cell carcinoma (OCSCC) remains heterogeneous. We sought to improve the prognostic stratification of patients with pN3b OCSCC through a combined analysis of FDG-PET parameters and clinicopathological risk factors (RFs).From 2001 to 2019, complete data on maximum standardized uptake values derived from FDG-PET of neck metastatic nodes (SUV-nodal-max) and clinicopathological RFs were available for 257 patients with pN3b disease.Using the 5-year disease-free survival (DFS) as the outcome of interest, the optimal cutoff points for SUV-nodal-max and lymph node ratio (LNR) were 15.9 and 0.17, respectively. The 5-year DFS rates/(number of cases) for patients with pN3b disease were as follows: SUV-nodal-max 15.9 versus ≥ 15.9, 49%(226)/21%(31), p = 0.000003; LNR 0.17 versus ≥ 0.17, 49%(230)/17%(27), p = 0.000117; absence versus presence of neck level IV/V metastases, 49%(230)/15%(27), p = 0.000004. Multivariable analyses revealed that SUV-nodal-max ≥ 15.9, LNR ≥ 0.17, and level IV/V metastases were independent prognosticators for 5-year distant metastases (DM), DFS, disease-specific survival (DSS), and overall survival (OS) rates. Based on these variables, we devised a scoring system that identified three distinct prognostic subgroups at low (score 0, n = 190), intermediate (score 1, n = 51), and high (scores 2-3, n = 16) risk. The 5-year rates of patients with pN3b disease deemed to be at low/intermediate/high risk were as follows: DM, 31%/52%/89%; DFS, 54%/26%/0%; DSS, 59%/36%/8%; OS, 42%/31%/6%, respectively; all p 0.001.A scoring system based on SUV-nodal-max, LNR, and level IV/V metastases improves the prognostic stratification of OCSCC patients with pN3b disease.