Cytotoxic Peptaibols from Trichoderma guizhouense, a Fungus Isolated from an Urban Soil Sample.

Soil sustains human life by nourishing crops, storing food sources, and housing microbes, which may affect the nutrition and biosynthesis of secondary metabolites, some of which are used as drugs. To identify lead compounds for a new class of drugs, we collected soil-derived fungal strains from various environments, including urban areas. As various human pathogens are assumed to influence the biosynthetic pathways of metabolites in soil fungi, leading to the production of novel scaffolds, we focused our work on densely populated urban areas and tourist attractions. A soil-derived fungal extract library was screened against MDA-MB-231 cells to derive their cytotoxic activity. Notably, 10 µg/mL of the extract of Trichoderma guizhouense (DS9-1) was found to exhibit an inhibitory effect of 71%. Fractionation, isolation, and structure elucidation efforts led to the identification of nine new peptaibols, trichoguizaibols A-I (1-9), comprising 14 amino acid residues (14-AA peptaibols), and three new peptaibols, trichoguizaibols J-L (10-12), comprising 18 amino acid residues (18-AA peptaibols). The chemical structures of 1-12 were determined based on their 1D and 2D NMR spectra, HRESIMS, electronic circular dichroism data, and results of the advanced Marfey's method. The 18-AA peptaibols were found to exhibit cytotoxicity against MDA-MB-231, SK-Hep1, SKOV3, DU145, and HCT116 cells greater than that of the 14-AA peptaibols. Among these compounds, 10-12 exhibited potent sub-micromolar IC50 values. These results are expected to shed light on a new direction for developing novel scaffolds as anticancer agents.

Comparative effectiveness of hypoglossal nerve stimulation and alternative treatments for obstructive sleep apnea: a systematic review and meta-analysis.

Continuous positive airway pressure (CPAP) is the primary therapeutic modality for obstructive sleep apnea (OSA) management. However, despite efforts to encourage patients to comply with CPAP usage, long-term adherence remains low. Consequently, surgical intervention for OSA is considered a secondary option for patients who exhibit non-compliance with CPAP. Therefore, we conducted systematic review and meta-analysis assessed the relative effectiveness of hypoglossal nerve stimulation (HNS) treatment and alternative surgical interventions for managing OSA. Five databases were searched. Studies were included if they measured polysomnography parameters and assessed sleep apnea-related quality of life (Epworth Sleepiness Scale [ESS]) both before and after HNS, and compared these outcomes with control, CPAP, or airway surgery (uvulopalatopharyngoplasty, expansion sphincter pharyngoplasty, or tongue base surgery) groups. A total of 10 studies (2209 patients) met the inclusion criteria. Compared to other airway surgeries, the rates of post-treatment apnea-hypopnea index (AHI) < 10 and < 15 events/h were significantly lower in the HNS group (odds ratio [OR] 5.33, 95% confidence interval [CI] 1.21-23.42; and 2.73, 95% CI 1.30-5.71, respectively). Additionally, postoperative AHI was significantly lower in the HNS group than in all other airway surgery groups (AHI: mean difference [MD] -8.00, 95% CI -12.03 to-3.97 events/h). However, there were no significant differences in the rate of post-treatment AHI < 5 events/h (OR 1.93, 95% CI 0.74-5.06) or postoperative ESS score (MD 0.40, 95% CI-1.52 to 2.32) between the two groups. HNS is an effective option for selected patients with moderate-to-severe OSA and CPAP intolerance.

Are statins effective in preventing chronic rhinosinusitis? A systematic review and meta-analysis.

OBJECTIVES: To evaluate the association between statin use and chronic rhinosinusitis (CRS). DESIGN AND SETTING: Systematic review and meta-analysis. The methodological quality of studies was assessed using the Newcastle-Ottawa scale. PARTICIPANTS: Patients with CRS. MAIN OUTCOME MEASURES: Pooled odds ratios (ORs) with 95% confidence interval (CIs) in analyses of studies that compared the prevalence of CRS, nasal polyp, difference of Lund-Kennedy endoscopic score, Lund-Mackay CT score and Sino-nasal Outcome Test-22. RESULTS: The analysis included eight studies and 445 465 patients. Patients who used statins were at lower risk for CRS than those who did not (OR = 0.7457, 95% CI = 0.6629-0.8388, p < 0.0001, I2 = 0.0%). Patients with hyperlipidaemia were at higher risk for CRS than those with normal serum levels of lipid (OR = 1.3590, 95% CI = 1.2831-1.4394, p < 0.0001, I2 = 33.3%). However, there were no significant differences in the risk for nasal polyps between CRS patients using statins or not (OR = 1.0931, 95% CI = 0.7860-1.5202, p = 0.5968, I2 = 0.0%). Additionally, statin use was not related to Lund-Kennedy endoscopic scores, Lund-Mackay CT scores or sino-nasal outcome test-22 scores in CRS patients. CONCLUSION: The risk for CRS is lower in patients who use statins and those without hyperlipidaemia.

The Prognostic Utilities of Various Risk Factors for Laryngeal Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

Objective: To assess the prognostic utilities of various risk factors for laryngeal squamous cell carcinoma. Methods: Six databases were searched to January 2022. Hazard ratios for overall survival and disease-free survival were collected and study characteristics were recorded. The risk of bias was evaluated using the Newcastle-Ottawa scale. Results: Twenty-eight studies involving 32,128 patients were finally included. In terms of overall survival, older age, a history of alcohol consumption, a high Charlson comorbidity index score, a high TNM stage (III and IV), a high tumor stage (III and IV), nodal involvement, poor pathological differentiation, primary chemoradiotherapy and radiotherapy were associated with increased risks of death. In terms of disease-free survival, older age (≥60 years), TNM stages III and IV, tumor stages III and IV, supraglottic tumors, and nodal involvement all increased the risk of death. Conclusions: The TNM stage importantly predicts overall survival, and tumor location predicts the disease-free survival of patients with laryngeal squamous cell carcinoma. Of patients with risk factors, the Charlson comorbidity index usefully predicts overall survival.

High-Resolution Computed Tomography as an Initial Diagnostic and Localization Tool in Patients with Cerebrospinal Fluid Rhinorrhea: A Meta-Analysis.

Background and Objectives: This study was performed to investigate the utility of high-resolution computed tomography (HRCT) for the initial localization of cerebrospinal fluid rhinorrhea. Methods: HRCT data regarding the point of cerebrospinal fluid leakage (as confirmed in the operating room), collected up to December 2022, were extracted from five databases. The risk of bias of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Results: The search revealed eight relevant studies with a total of 254 patients. The diagnostic odds ratio of the imaging studies was 10.0729 (95% confidence interval [CI]: 2.4486; 41.4376; I2 = 54.1%). The area under the summary receiver operating characteristic curve was 0.8. Sensitivity, specificity, the negative predictive value, and the positive predictive value were 0.7550 (95% CI: 0.6163; 0.8553; I2 = 69.8%), 0.8502 (95% CI: 0.5986; 0.9557, I2 = 49.3%), 0.4106 (95% CI: 0.2418; 0.6035; I2 = 59.0%), and 0.9575 (95% CI: 0.8955; 0.9834; I2 = 27.7%), respectively. Conclusions: HRCT can be used to accurately localize cerebrospinal fluid rhinorrhea because it shows bony defects in high detail. However, it has limited utility for the evaluation of active leakage, and localization is difficult in the presence of coexisting lesions.

Fall risk related to subtype-specific alpha-antagonists for benign prostatic hyperplasia: a nationwide Korean population-based cohort study.

BACKGROUND: Subtype-specific alpha-antagonists are medications commonly prescribed for lower urinary-tract symptoms, benign prostatic hyperplasia in older populations. Our study aims to investigate the association between subtype-specific alpha-antagonists and fall risk. METHODS: A total of 4,202,739 men aged 60-75 years eligible for Korean Health Insurance Review and Assessment Service (HIRA) during 2017-2018 were enrolled retrospectively. After propensity score matching, 53,303 people in the exposed and unexposed groups were considered in the final study analysis. RESULTS: The subtype-specific alpha-antagonists significantly increased the risk of fall in the exposed cohort compared to the unexposed cohort (odds ratio [OR] 1.80; 95% confidence interval [CI] 1.62-2.00). Low income increased the fall risk only in the unexposed cohort (OR 1.34; 95% CI 1.04-1.73). A seasonal difference appeared only in the exposed cohort, with a significantly higher risk of fall in summer (OR 1.23; 95% CI 1.03-1.47). A total of 968 events occurred in the exposed group, and 455 of these falls occurred on the first day of medication (47%). CONCLUSIONS: Subtype-specific alpha-antagonists significantly increased the risk of falls, especially on the first day of drug initiation and during the summer season. Education on orthostatic hypotension and fall prevention should be implemented when prescribing subtype-specific alpha-antagonists.

Diterpenoids and Diacetylenes from the Roots of Aralia cordata with Inhibitory Effects on Nitric Oxide Production.

Bioactivity-guided isolation of a MeOH extract of Aralia cordata led to the isolation of four new ent-pimarane diterpenoids (1-4) and a diacetylene (5) together with 21 known compounds (6-26). Their structures were established based on the interpretation of one- and two-dimensional NMR and HRESIMS data. The absolute configurations of the new isolates were determined by electronic circular dichroism data analysis, single crystal X-ray diffraction, and Mosher's esterification method. All compounds exhibited inhibitory effects on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages with IC50 values ranging from 1.1 to 69.4 µM.

Sesquiterpenoids from Chrysanthemum indicum with Inhibitory Effects on NO Production.

Three new guaianolide lactones (1-3) and four new 9-oxonerolidol glucosides (5-8) together with 20 known compounds were isolated from the MeOH extract of the flowers of Chrysanthemum indicum. Their structures were elucidated based on the interpretation of NMR, HRESIMS, and electronic circular dichroism (ECD) data along with acid hydrolysis. Of the isolates, sesquiterpenoids 1-4 and 15 and flavones 17 and 18 exhibited inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide production in RAW 264.7 cells with IC50 values in the range 0.2-27.0 µM.

Pentacyclic triterpenes with nitric oxide inhibitory activity from Potentilla chinensis.

Three new ursane-type triterpenes (1-3) and twenty-one known triterpenoids (4-24) were isolated from the methanolic extract of the whole plants of Potentilla chinensis. Their structures were elucidated by extensive spectroscopic analysis of 1D and 2D NMR (HSQC, HMBC, COSY and ROESY) and HRESIMS data. The bioassay screening revealed the inhibitory effects on nitric oxide production of compounds 2, 5, 7, 9, 10, and 13-24 in LPS-induced RAW264.7 macrophages.

Effect of middle ear gelfoam on hearing and healing process after tympanoplasty: A prospective randomized case-control study.

PURPOSE: This prospective randomized case-control study was performed to compare the surgical outcomes of our swing-door overlay tympanoplasty with or without absorbable gelatine sponge (AGS, gelfoam) packing in the middle ear cavity, according to the surgical procedure. METHODS: Fifty-seven patients who underwent swing-door overlay tympanoplasty by a single surgeon were enrolled in the study. The data of 30 patients of the gelfoam-packing group (GPG) and 27 patients of the non-gelfoam-packing group (NGPG) were prospectively collected and compared. RESULTS: Closure of the tympanic membrane was found to be successful in all patients at postoperative 3 months evaluation. NGPG showed a statistically better healing process compared to GPG; earlier epithelialization and less fascia edema in NGPG than in GPG (P < 0.05). The air-bone gap (ABG) measured at postoperative 1 and 2 months was smaller in NGPG than GPG, although there were no statistical differences. CONCLUSION: This study revealed earlier healing process and faster recovery of ABG in NGPG, thereby indicating that the gelfoam in the middle ear may interfere with both hearing recovery and the healing process of neodrum.

The Long-Term Stability of Fat-Graft Myringoplasty in the Closure of Tympanic Membrane Perforations and Hearing Restoration.

BACKGROUND/AIMS: This study was conducted to evaluate the long-term stability of fat-graft myringoplasty (FGM) for chronic tympanic membrane perforations, analyzing the perforation closure rate and re-gained hearing outcome with respect to the size and location of the perforations. METHODS: Between August 2007 and June 2018, a total of 193 patients who underwent FGM due to chronic tympanic membrane perforation at a tertiary referral center were enrolled and analyzed. RESULTS: The mean follow-up was 14.6 months (range 6-39). The complete perforation closure rate after FGM was 89.6%, with no statistical difference among the perforation size groups. The mean postoperative air-bone gap (ABG) was 11.0 dB and mean ABG improvement was 4.9 dB. CONCLUSION: Our FGM technique had a favorable tympanic closure rate for small to large perforations, and yielded relatively good hearing improvement in the mid-size perforation cases over long-term follow-up periods. According to the topographic evaluation of FGM, this procedure resulted in a reliable perforation closure rate and audiological results regardless of the perforation site.

Dianthiamides A-E, Proline-Containing Orbitides from Dianthus chinensis.

Orbitides are plant-derived small cyclic peptides with a wide range of biological activities. Phytochemical investigation of the whole plants of Dianthus chinensis was performed with the aim to discover new bioactive orbitides. Five undescribed proline-containing orbitides, dianthiamides A-E (1-5), were isolated from a methanolic extract of Dianthus chinensis. Their structures were elucidated by extensive analysis of 1D and 2D NMR and HRESI-TOF-MS as well as ESI-MS/MS fragmentation data. The absolute configuration of the amino acid residues of compounds 1-5 was determined by Marfey's method. All compounds were tested for their cytotoxic activity, and dianthiamide A (1) exhibited weak activity against A549 cell line with IC50 value of 47.9 µM.

Clinical efficacy of standard simple elliptical incision following drain-less and subcutaneous suture technique in preauricular sinus surgery.

BACKGROUND: The purpose of this study was to review our surgical strategy and outcomes of drain-less, subcutaneous suture technique in standard simple elliptical incision on preauricular sinus (PAS) cases. METHODS: The clinical records of 198 patients (247 ears) with PASs who were operated via standard simple elliptical incision with drain-less, subcutaneous suture technique by a single surgeon (K.H.P.) between January 2008 and December 2018 were reviewed for analysis. Patients' demographics, location of PASs, previous incision and drainage (I&D) history, previous surgical excision history, duration of follow-up, postoperative infection after surgery, and recurrence after surgery were analysed. RESULTS: Out of 247 PASs, 18 (7.3%) cases had postoperative infections and 11 (4.5%) cases showed recurrence. Postoperative infection rate were higher in previous I&D groups (PIDGs, 9.8%) and previous fistulectomy groups (PFGs, 10%), and also recurrence rates of PFGs (10%) was higher than those of fresh cases. However, there were no statistically significant differences between these groups. In addition, PAS patients with postoperative complications such as infection and recurrence were more common in male patients. CONCLUSION: We report a method of drain-less standard simple elliptical incision for the surgical removal of PAS and the outcomes of the surgery. Our method showed a low recurrence rate and low chance of wound infection postoperatively not only in fresh cases but also in pre-operative I&D cases and even previous fistulectomy cases. In conclusion, our method is proposed as an effective and safe method in all kind of patient groups, without presenting post-operative discomfort to patients.

Vitamin D Deficiency as a Risk Factor of Tinnitus: An Epidemiological Study.

OBJECTIVES: Vitamin D deficiency as a risk factor of tinnitus has not been well known. We tried to evaluate the association between the serum 25-(OH) vitamin D levels and tinnitus among the Korean population to propose the possible role of serum vitamin D in patients with tinnitus. METHODS: This cross-sectional study investigated the potential risk factors of tinnitus in relation to serum 25(OH)D levels within the Korean population. It encompassed a health interview, nutrition assessment, and a health examination. Data was sourced from the KNHANES V (2010-2012), conducted by the Division of Health and Nutritional Survey under the Korean Centers for Disease Control and Prevention (KCDCP). Participants were chosen from various sampling units categorized by geography, gender, and age group. The selection was facilitated through household registries using a stratified, multistage, clustered probability sampling approach. RESULTS: Data of 16 408 subjects were collected in this study. There were significant differences in gender, economic status, educational level, and sun exposure duration between the tinnitus and non-tinnitus groups. Serum 25(OH) vitamin D level between hearing loss and normal hearing was also significantly different. The logistic regression models with serum 25(OH) vitamin D quartile and tinnitus as the dependent variable, which were controlled for age, sex, smoking status, BMI, diabetes, hypertension, sun exposure, regular exercise, income, and education, eventually demonstrated that serum vitamin D deficiency and low sun exposure duration significantly increased the risk of tinnitus development. CONCLUSION: This study demonstrated a significant association between serum vitamin D levels and tinnitus, driven by large epidemiological data. The results of our study provide baseline data for further research to investigate the role of vitamin D in the pathogenesis and management of tinnitus.

The biphasic impact of apolipoprotein E ε4 allele on age-related hearing loss.

Both the ε4 variant of the apolipoprotein E (APOE) gene and hearing loss are well-known risk factors for Alzheimer's disease. However, previous studies have produced inconsistent findings regarding the association between APOE genotypes and hearing levels, necessitating further investigation. The aim of this study was to investigate the relationship between APOE genotypes and hearing levels. This retrospective study analyzed clinical data from a clinical data warehouse of seven affiliated Catholic Medical Center hospitals. The study included 1,162 participants with records of APOE genotypes, audiometric tests, and cognitive function tests. In Generalized linear mixed model analysis, ε4 carriers exhibited lower pure tone audiometry thresholds with an estimate of -0.353 (SE = 0.126, p = 0.005). However, the interaction term for age and APOE ε4 had a coefficient of 0.577 (SE = 0.214 p = 0.006), suggesting that the APOE ε4 gene may accelerate hearing deterioration with age. Subgroup analysis based on an age cut-off of 75 revealed that ε4 carriers had better hearing at younger ages, but showed no significant difference at older ages. These results indicate that the ε4 allele may have a biphasic effect on hearing levels depending on age.

Hearing Rehabilitation With a Chat-Based Mobile Auditory Training Program in Experienced Hearing Aid Users: Prospective Randomized Controlled Study.

Background: Hearing rehabilitation with auditory training (AT) is necessary to improve speech perception ability in patients with hearing loss. However, face-to-face AT has not been widely implemented due to its high cost and personnel requirements. Therefore, there is a need for the development of a patient-friendly, mobile-based AT program. Objective: In this study, we evaluated the effectiveness of hearing rehabilitation with our chat-based mobile AT (CMAT) program for speech perception performance among experienced hearing aid (HA) users. Methods: A total of 42 adult patients with hearing loss who had worn bilateral HAs for more than 3 months were enrolled and randomly allocated to the AT or control group. In the AT group, CMAT was performed for 30 minutes a day for 2 months, while no intervention was provided in the control group. During the study, 2 patients from the AT group and 1 patient from the control group dropped out. At 0-, 1- and 2-month visits, results of hearing tests and speech perception tests, compliance, and questionnaires were prospectively collected and compared in the 2 groups. Results: The AT group (n=19) showed better improvement in word and sentence perception tests compared to the control group (n=20; P=.04 and P=.03, respectively), while no significant difference was observed in phoneme and consonant perception tests (both P>.05). All participants were able to use CMAT without any difficulties, and 85% (17/20) of the AT group completed required training sessions. There were no changes in time or completion rate between the first and the second month of AT. No significant difference was observed between the 2 groups in questionnaire surveys. Conclusions: After using the CMAT program, word and sentence perception performance was significantly improved in experienced HA users. In addition, CMAT showed high compliance and adherence over the 2-month study period. Further investigations are needed to validate long-term efficacy in a larger population. TRIAL REGISTRATION: Clinical Research Information Service (CRiS) KCT0006509; https://cris.nih.go.kr/cris/search/detailSearch.do?seq=22110&search_page=L.

Computed tomography Scan Size Analysis of stapedius and tensor tympani muscles in middle ear myoclonic tinnitus.

Objectives: To analyze the sizes of the stapedius and tensor tympani (TT) muscles using a temporal bone CT (TBCT) scan in patients with middle ear myoclonic tinnitus (MEMT) and investigate their value for the diagnosis of this rare cause of tinnitus. Methods: Medical records and TBCT of patients with MEMT or vascular tinnitus (VT) at Seoul St. Mary's Hospital from January 2012 to December 2022 were reviewed. The stapedius and TT muscles were analyzed. Results: Thirty-eight patients with unilateral MEMT and 39 patients with VT were included. More males were in the MEMT group compared to the VT group (MEMT: n = 24, VT: n = 8, p = .001). The mean age of the MEMT group was younger compared to the VT group (MEMT: 35 ± 12 years, VT: 44 ± 14.3 years, p = .005). The mean BMI for the MEMT group was less than the VT group (MEMT: 22.3 ± 2.5, VT: 24.8 ± 4.36, p = .010). The mean length and width of the stapedius in the MEMT group were larger than those of the VT group (Length MEMT: 1.47 ± 0.60 mm, VT: 0.98 ± 0.24 mm, p = .001; Width MEMT: 0.89 ± 0.32 mm, VT: 0.72 ± 0.19 mm, p = .009). The mean length and width of the TT in the MEMT group were larger than that of the VT group (Length MEMT: 3.10 ± 0.50 mm, VT: 2.27 ± 0.42, p = .001; Width MEMT: 2.02 ± 0.36, VT: 1.75 ± 0.26 p = .001). Conclusion: The mean length and width of the stapedius and TT muscles measured in the MEMT group were longer and wider than the VT group. This suggests the use TBCT scan as a diagnostic tool for MEMT. Further studies with a larger study group to validate the results of this study are recommended.Level of Evidence: 4.

Targeted isolation of dimeric sesquiterpene lactones and sesquiterpene derivatives from the roots of Inula helenium.

LC-HRMS/MS-based molecular networking was applied to investigate the bioactive sesquiterpene lactones and their analogs contained in Inula helenium, enabling the isolation of four undescribed eudesmane-eudesmane sesquiterpene dimers (1-4), a sesquiterpene-amino acid adduct (5), and 17 known sesquiterpenes (6-22). The structures were determined based on 1D, 2D NMR, and HRESIMS data analysis, as well as DP4+ probability analyses and ECD calculations. The biosynthetic pathway of the sesquiterpene dimers is postulated to proceed via the Diels-Alder reaction as the key step. The inhibitory activity of all isolates on LPS-induced nitric oxide (NO) production in RAW 264.7 macrophages was evaluated. Compounds 4, 17, and 20 exhibited significant inhibitory activity against NO production, with IC50 values of 8.4, 5.5, and 9.1 µM, respectively.

Hypoglossal Nerve Stimulation Effects on Obstructive Sleep Apnea Over Time: A Systematic Review and Meta-analysis.

OBJECTIVES: This study aimed to determine the efficacy of hypoglossal nerve stimulation (HGS) in the treatment of obstructive sleep apnea. DATA SOURCES: PubMed, Cochrane database, Embase, Web of Science, SCOPUS, and Google Scholar. REVIEW METHODS: Five databases were reviewed to identify relevant studies that measured polysomnography parameters such as the apnea-hypopnea index (AHI) and oxygen desaturation index, as well as quality of life and functional outcomes of sleep questionnaire scores, before and after HGS. RESULTS: In total, 44 studies involving 8670 patients met the inclusion criteria. At 12 months after treatment, approximately 47%, 72%, and 82% of patients achieved AHI values of <5, < 10, and <15, respectively. The reported clinical success rates according to Sher criteria were 80% within 12 months and 73% between 12 and 36 months. While the favorable effects exhibited a gradual reduction up to 12 months postimplantation, they generally maintained a consistent level between the 12th and 36th months, as assessed by AHI < 5, <15, and success rate according to Sher criteria. CONCLUSION: HGS can enhance quality of life scores and polysomnography outcomes in obstructive sleep apnea patients. Although the positive effects gradually decreased until 12 months after implantation, they generally remained consistent between 12 and 36 months.