Craniofacial Phenotype in Obstructive Sleep Apnea and Its Impact on Positive Airway Pressure (PAP) Adherence.

Positive airway pressure (PAP) is an important treatment tool for patients with moderate and severe obstructive sleep apnea (OSA), and adherence to PAP significantly affects treatment outcomes. Disease severity, adverse effects, and psychosocial factors are known to predict medication adherence. Cephalometric parameters have been reported to positively correlate with upper airway collapse. However, research on the correlation between these cephalometric parameters and PAP adherence remains insufficient. This study aimed to identify this relationship. This study included 185 patients with OSA who were prescribed PAP. Polysomnography (PSG) was performed to diagnose OSA, and paranasal sinus computed tomography (PNS CT) was performed to check for comorbidities of the upper airway. In addition, cephalometric parameters such as the hyoid-posterior nasal spine (H-PNS), posterior nasal spine-mandibular plane (PNS-MP), and hyoid-mandibular plane (H-MP) were measured in the midsagittal and axial CT views. Adherence was evaluated 3-12 months after the PAP prescription. A total of 136 patients were PAP-adherent, and 49 were nonadherent. There were more males in the adherent group and a higher average height in the adherent group. The PSG results showed that the apnea-hypopnea index (AHI), respiratory disturbance index (RDI), oxygen desaturation index (ODI), arousal index (AI), rapid eye movement (REM) AHI, and supine AHI were significantly higher, and the lowest oxygen saturation was lower in the adherent group. In the analysis of covariance (ANCOVA) model adjusted for sex and height, among the cephalometric parameters, H-MP was significantly longer in the adherent group (p = 0.027), and H-PNS showed a longer tendency (p = 0.074). In the logistic regression analysis model, the odds ratio (OR) and 95% confidence intervals (95% CI) of adherence and severe OSA in the third tertile compared to the first tertile of H-MP were 2.93 (1.25-6.86) and 4.00 (1.87-8.56). In the case of H-PNS, they were 2.58 (1.14-5.81) and 4.86 (2.24-10.54), respectively. This study concluded that an inferiorly placed hyoid bone in adult patients is associated with PAP adherence and disease severity.

Clinical Practice Guidelines for Oropharyngeal Dysphagia.

OBJECTIVE: Dysphagia is a common clinical condition characterized by difficulty in swallowing. It is sub-classified into oropharyngeal dysphagia, which refers to problems in the mouth and pharynx, and esophageal dysphagia, which refers to problems in the esophageal body and esophagogastric junction. Dysphagia can have a significant negative impact one's physical health and quality of life as its severity increases. Therefore, proper assessment and management of dysphagia are critical for improving swallowing function and preventing complications. Thus a guideline was developed to provide evidence-based recommendations for assessment and management in patients with dysphagia. METHODS: Nineteen key questions on dysphagia were developed. These questions dealt with various aspects of problems related to dysphagia, including assessment, management, and complications. A literature search for relevant articles was conducted using Pubmed, Embase, the Cochrane Library, and one domestic database of KoreaMed, until April 2021. The level of evidence and recommendation grade were established according to the Grading of Recommendation Assessment, Development and Evaluation methodology. RESULTS: Early screening and assessment of videofluoroscopic swallowing were recommended for assessing the presence of dysphagia. Therapeutic methods, such as tongue and pharyngeal muscle strengthening exercises and neuromuscular electrical stimulation with swallowing therapy, were effective in improving swallowing function and quality of life in patients with dysphagia. Nutritional intervention and an oral care program were also recommended. CONCLUSION: This guideline presents recommendations for the assessment and management of patients with oropharyngeal dysphagia, including rehabilitative strategies.

Oncological Outcomes after Pulmonary Metastasectomy for Head and Neck Squamous-Cell Carcinoma and Adenoid Cystic Carcinoma.

INTRODUCTION: Pulmonary metastatic head and neck cancer has a poor prognosis. Pulmonary metastasectomy has been performed but only in carefully selected patients. The aim of this study was to examine the clinical characteristics and oncological follow-up of patients who underwent pulmonary metastasectomy. METHODS: Data of 54 patients with squamous-cell carcinoma (SCC) or adenoid cystic carcinoma (ACC) who underwent metastasectomy between 2003 and 2019 at two tertiary referral centers were retrospectively reviewed. RESULTS: The 3-year and 5-year disease-free survival rates after metastasectomy were 49.9% and 39.9% for SCC and 38.9% and 32.4% for ACC, respectively. Univariate analysis revealed that a disease-free interval (DFI) less than 14 months and R1 resection (hazard ratio [HR] [95% confidence interval]: 2.95 [0.77-5.62], 4.64 [0.99-21.65], respectively) were risk factors for recurrence in SCC and that a high T stage (HR: 5.24 [1.22-22.58]) was a risk factor in ACC. In SCC, a DFI less than 14 months and R1 resection (hazard ratio: 6.35 [1.36-29.54], 12.79 [1.53-106.95], respectively) were risk factors in a multivariate analysis. CONCLUSION: Pulmonary metastasectomy had a fair effect on head and neck SCC and ACC, and the prognosis was better in SCC patients with a DFI greater than 14 months.

Optimal Airway Management in the Treatment of Descending Necrotizing Mediastinitis Secondary to Deep Neck Infection.

PURPOSE: To review our experiences of descending necrotizing mediastinitis (DNM) secondary to deep neck infection (DNI) and determine appropriate airway management for decreasing mortality and morbidity of patients with DNM. METHODS: Medical records of 20 patients (8 women and 12 men) who had been managed for DNM secondary to DNI between March 2006 and December 2019 were analyzed. Diagnosis and extent of infection were confirmed by computed tomography of the neck and chest. The upper airway was closely monitored with a fiberoptic laryngoscope. Complications were evaluated according to various types of airway management in our serial cases. RESULTS: Five (25%) out of 20 patients died as a result of septic shock and multiorgan failure. None of these patients died of accidental airway obstruction or airway management mishaps. Keeping short-term orotracheal intubation was safe and adequate after the initial surgery. Early tracheotomy was performed for 4 patients and it was significantly associated with mortality (P = .032). Three patients who underwent late tracheotomy had no mortality. Patients with tracheotomy had longer duration of overall hospital stay than those without tracheotomy. CONCLUSIONS: Well-controlled airway management might decrease mortality, hospitalization, and airway complications in patients with DNM secondary to DNI. Keeping orotracheal intubation rather than upfront tracheotomy should be first considered when managing airway along with examination of the upper airway with a fiberoptic laryngoscope.

Use of a combination of N-acetylcysteine and clonazepam to treat burning mouth syndrome.

OBJECTIVE: This study was intended to evaluate the clinical efficacy of a combination of N-acetylcysteine (NAC) and clonazepam for treatment of burning mouth syndrome (BMS). STUDY DESIGN: A total of 160 patients with BMS were divided into 3 groups: group 1 received NAC (400 mg/d), group 2 received clonazepam (0.5 mg/d), and group 3 received both NAC and clonazepam. We evaluated symptom relief after 8 weeks of treatment using a visual analog scale (VAS). To assess oral health-related quality of life, we used the validated Korean version of an oral health impact profile (OHIP-14K). RESULTS: The overall response rates of the 3 groups were 60.3%, 51.3%, and 80.0%, respectively. The mean VAS and OHIP-14K scores significantly decreased in all groups after the 8-week treatments. The VAS score changes were -12.2 ± 19.5, -10.0 ± 14.1, and -21.0 ± 24.6, respectively (P = .001), in the 3 groups and the OHIP-14K changes were -2.3 ± 9.2, -4.4 ± 6.9, and -8.7 ± 10.3, respectively (P = .020). Group 3 showed significantly larger differences in VAS and OHIP-14K scores than group 2, before and after treatment. CONCLUSIONS: In the treatment of BMS, the NAC/clonazepam combination therapy was more effective than either monotherapy.

Oncological outcomes of preoperatively unexpected malignant tumors of the parotid gland.

PURPOSE: Unexpected parotid cancers are often encountered due to inaccuracies in the preoperative evaluation. This study aimed to examine the clinical characteristics and oncological outcomes of these cancers and to propose the appropriate management strategy. METHODS: This is a multicenter case series study in which a total of 302 patients were diagnosed postoperatively with parotid cancers between 2003 and 2017. Of these, 85 cases without evidence of malignancy prior to surgery but identified as malignant on postoperative pathology were included. RESULTS: Of 85 patients, 76 and 9 underwent superficial and total parotidectomy, respectively. A positive resection margin was present in 24.7% of the cases. Postoperative radiotherapy was administered to 43.6% of patients; 4.2% had a local recurrence, and no patients died of the disease. The 5-year overall and relapse-free survival rates were 100.0% and 95.2%, respectively. Patients who underwent piecemeal resection had significantly poorer oncologic outcomes. Age, sex, histologic grade, T stage, extracapsular extension, resection margin status, and postoperative radiotherapy did not affect recurrence and survival. CONCLUSION: Preoperatively unexpected parotid cancers had excellent local control and overall survival despite positive or close resection margin, with or without postoperative radiotherapy. Therefore, patients with unexpected parotid malignancies may benefit from less aggressive postoperative management option.

Possible association between oral health and sleep duration: A cross-sectional study based on the Korean National Health and Nutrition Examination Surveys from 2010 to 2015.

ABSTRACT: This study was performed to investigate the association between oral health and sleep duration in South Korean subjects using 2010-2015 data from the Korean National Health and Nutrition Examination Survey (KNHANES).Cross-sectional data on 35,599 adults over the age of 19 years who completed KNHANES were analyzed. All participants reported subjective oral health status and their daily average sleep duration using a self-reported questionnaire. Sleep duration and oral health status were divided into 3 categories: ≤5, 6-8, ≥9 h/day and good, fair, poor, respectively.The overall prevalence of poor oral health status was 43.8%. Univariate analysis demonstrated that poor oral health status was significantly associated with age, smoking, alcohol, diabetes, education, income, depression, marital status, and sleep duration. After adjusting for covariates (age, sex, diabetes mellitus, hypertension, obesity, smoking, income, education, marital status), sleep durations of ≤5 hours (OR = 1.42; 95% CI, 1.26-1.60) and ≥9 hours (OR = 1.21; 95% CI, 1.04-1.40) were significantly associated with poor oral health, compared to a sleep duration of 6-8 hours. Short or long sleep duration was more likely to have an impact on the development of poor oral health status in men than in women. A significant relationship between sleep duration and oral health status was found in participants younger than 60 years.This is the first report that both short and long sleep durations are significantly associated with the development of poor oral health status. The effect of short or long sleep duration on poor oral health was more significant in younger subjects and in men.

Functional Voice and Swallowing Outcome Analysis After Thyroid Lobectomy: Transoral Endoscopic Vestibular Versus Open Approach.

BACKGROUND: The transoral endoscopic thyroidectomy vestibular approach (TOETVA) is a scarless remote-access thyroidectomy technique. This study compared subjective and objective voice outcomes and swallowing outcomes of patients who underwent thyroid lobectomy using the TOETVA versus conventional open thyroidectomy (OT). METHODS: In addition to questionnaires, acoustic and aerodynamic analyses were performed to compare subjective and objective voice outcomes of the two groups. Swallowing outcome analyses were conducted using Swallowing Impairment Index-6 (SIS-6) scores. Assessments were performed preoperatively and 3 and 6 months after surgery. Propensity score matching was performed to compare the outcomes of the two groups. RESULTS: One hundred and two patients were included in this study (52 TOETVA and 50 OT). Excluding two patients who had vocal cord palsy and open conversion in the TOETVA group, 100 patients completed 3-month postoperative surveys. There were no significant differences between the groups in VAS, GRBAS, or VHI-10 scores at the preoperative and 3- and 6-month assessments. For both groups, there were no significant changes in acoustic or aerodynamic parameters during the 3-6-month postoperative period. The TOETVA group had lower SIS-6 scores at the postoperative 6-month assessment, but the SIS-6 scores after 12 months were similar between groups before and after propensity score matching. CONCLUSIONS: Following TOETVA lobectomy, there were no significant changes in voice outcomes 3 and 6 months after surgery, and the outcomes were comparable with those of OT. The TOETVA group also had swallowing outcomes that were comparable with the OT group.

Feasibility of Brachial Plexus Schwannoma Enucleation With Intraoperative Neuromonitoring.

OBJECTIVES: To evaluate the feasibility of brachial plexus schwannoma enucleation under intraoperative neuromonitoring. METHODS: Five patients who were treated for brachial plexus schwannoma under intraoperative neuromonitoring from 2008 to 2018 were included in this retrospective review. Neuromonitoring was performed with a 100-µV event threshold of the neuromonitoring system (NIM-2 or 3) at the deltoid, biceps brachii, triceps brachii, and brachioradialis muscles. Patient characteristics, tumor size and location, intraoperative neuromonitoring findings, and postoperative function were evaluated. RESULTS: The intraoperative neuromonitoring findings were in accordance with the preoperative assessment of the included nerve root. Three patients had no postoperative morbidity, one patient had temporary paresthesia of the forearm for 2 months, and one patient mild loss of grip strength for 1 month. CONCLUSION: Intraoperative neuromonitoring of the arm and forearm muscles during enucleation of brachial plexus schwannoma promoted confident and successful surgery with minimal postoperative morbidity.

Changes in immune markers in tumor-free lymph node and peripheral blood of malignant head and neck cancer patients.

BACKGROUND: Immunoediting theory, which explains the balance between the host immunity and cancer cells, could suggest a new way to reduce the recurrence of cancer. This study aimed to compare changes in immune cells in tumor-free lymph node and peripheral blood according to their malignancy, disease status, and prognosis. METHODS: From October 2016 to August 2017, 26 malignant and 14 benign cases were enrolled, and the tumor-free lymph node and peripheral blood were harvested during the surgery. The proportions of cluster of differentiation 4 (CD4), CD8, CD19, CD33, CD40, and CD40 ligand (CD40L) expression and cytokine levels in the serum were compared between the malignant and benign patients. Furthermore, among the malignant group, the changes occurring due to the disease progression or recurrence were evaluated. RESULTS: In the malignant patients, a significantly decreased proportion of cells expressing CD8 and CD40 in the peripheral blood was observed compared to benign patients. In the advanced stage (stage III or IV) and in patients with extracapsular spread, significant decrease in CD33 cells in tumor-free lymph nodes could be observed. On performing a survival analysis based on the recurrence, patients with interferon-γ (IFNγ) level greater than 16 pg/mL exhibited significantly higher recurrence rate, and this higher level of IFNγ was associated with distant metastasis. CONCLUSIONS: Immune markers exhibiting clinical significance differ from each other based on the comparison between benign and malignant groups, between advanced and early cancer, and between recurrence and nonrecurrence. And this result suggests that research in the immune system is likely to have an important effect on future treatment.

Preservation of Salivary Function Following Extracapsular Dissection for Tumors of the Parotid Gland.

PURPOSE: This study evaluated salivary function after extracapsular dissection (ECD) compared with partial superficial parotidectomy (PSP) and classic superficial parotidectomy (CSP) of benign parotid gland tumors. The authors hypothesized that ECD would be superior to PSP and CSP in preserving postoperative salivary function. MATERIALS AND METHODS: Retrospective analyses were performed for 43 consecutive patients who underwent parotidectomies of benign parotid tumors performed by a single experienced surgeon. Clinical data and pre- and postoperative whole salivary flow rates were compared among the operative procedures. Pearson χ2 and Fisher exact tests were used to compare categorical variables. Kruskal-Wallis, Mann-Whitney U, and Wilcoxon signed rank tests were used to compare means. A P value less than .05 was considered significant throughout the study. RESULTS: Tumor sizes did not differ among groups. Operative times, amounts of drainage, and hospital days for ECD were markedly decreased compared with CSP and tended to be decreased compared with PSP. Resection margins were exposed in 0, 12.5, and 6.7% of patients who underwent ECD, PSP, and CSP, respectively. Postoperative complications occurred less often (but not meaningfully) after ECD. Postoperative basal salivary flow rates in the ECD, PSP, and CSP groups were 0.39, 0.32, and 0.14 mL/minute, respectively (P = .05). Stimulated salivary flow rates remained stable for the ECD and PSP groups but decreased in the CSP group. CONCLUSION: ECD is a safe and time-efficient surgical approach, offering early recovery from parotid tumors and better preservation of salivary function. ECD should be considered a surgical approach for parotid tumors, especially those in the parotid tail region, such as Warthin tumors.

Dural arteriovenous fistula masquerading as pulsatile tinnitus: radiologic assessment and clinical implications.

Pulsatile tinnitus (PT) is often an initial presenting symptom of dural arteriovenous fistula (dAVF), but it may be overlooked or diagnosed late if not suspected on initial diagnostic work-up. Here, we assess anatomical features, treatment outcomes, and clinical implications of patients with PT due to dAVF. Of 220 patients who were diagnosed with dAVF between 2003 and 2014, 30 (13.6%) presented with only PT as their initial symptom. The transverse-sigmoid sinus (70.0%) was the most common site, followed by the hypoglossal canal (10.0%) and the middle cranial fossa (6.7%) on radiologic evaluation. Regarding venous drainage patterns, sinus or meningeal venous drainage pattern was the most common type (73.3%), followed by sinus drainage with a cortical venous reflux (26.7%). PT disappeared completely in 21 (80.8%) of 26 patients who underwent therapeutic intervention with transarterial embolization of the fistula, improved markedly in 3 (11.5%), and remained the same in 2 (7.7%). In conclusion, considering that PT may be the only initial symptom in more than 10% of dAVF, not only otolaryngologists but also neurologists and neurosurgeons should meticulously evaluate patients with PT. In most cases, PT originating from dAVF can be cured with transarterial embolization regardless of location and venous drainage pattern.

Clinical Implications of Septal Deviation in Lateralized Olfaction.

OBJECTIVES: Results of butanol threshold tests (BTTs) have shown that birhinal olfaction tends to converge toward monorhinal olfaction of the dominant nostril. However, birhinal olfaction may also be worse than dominant-side monorhinal olfaction. The goal of our study was to investigate the effect of deviated nasal septum on birhinal olfaction in patients with lateralized olfaction and to examine the effect of septoplasty in these patients. METHODS: A retrospective study with planned data collection was conducted in 518 patients who underwent BTTs. Lateralized olfaction was defined as monorhinal BTT scores that differed by >2 between sides. Underestimated birhinal olfaction was defined as a birhinal BTT score >2 lower than the dominant nostril monorhinal BTT score. Patients with lateralized olfaction were divided into 2 groups: group 1, underestimated birhinal olfaction; and group 2, without underestimated birhinal olfaction. RESULTS: Among 518 patients, 112 with lateralized olfaction were enrolled in this study. Group 1 included 23 patients (20.5%) and group 2 included 89 patients (79.5%). The severity of septal deviation (ratio of the distance of narrower side to wider side) did not differ between the 2 groups. Septal deviation to the dominant nostril was more common in group 1 than group 2 (73.9% vs. 37.6%; P=0.002). Five patients with septal deviation to the dominant nostril with underestimated birhinal olfaction underwent septoplasty. Improved lateralized olfaction occurred in all 5 patients postoperatively (P=0.041). CONCLUSION: Septal deviation of the dominant nostril in patients with lateralized olfaction is associated with underestimated birhinal olfaction. Septoplasty may improve olfaction by increasing airflow in the dominant olfactory side.

Treatment outcomes and clinical relevance of the Follicular Lymphoma International Prognostic Index in Korean follicular lymphoma patients treated with chemotherapy.

BACKGROUND/AIMS: The Follicular Lymphoma International Prognostic Index (FLIPI) and FLIPI2 are well-known prognostic models for patients with follicular lymphoma (FL). However, their prognostic relevance has not been examined before in Korean patients with FL. METHODS: We reviewed clinical and laboratory information from our database of patients between 1995 and 2012. In total, 125 patients were stratified in three categories according to FLIPI or FLIPI2 scores: low-, intermediate-, and high-risk groups. We compared FLIPI and FLIPI2 in terms of progression-free survival (PFS) and overall survival (OS). RESULTS: Among the 125 patients, the prognostic value of FLIPI and FLIPI2 was evaluated in 73 patients who fulfilled the criteria of both prognostic models. Risk stratification by FLIPI and FLIPI2 showed significant differences in unfavorable parameters among each risk group, particularly between low- and intermediate-risk groups. The high-risk group b was significantly associated with poor PFS on both FLIPI and FLIPI2 (p < 0.05). However, the OS was significantly different only in the risk groups determined by FLIPI2 (p = 0.042). In a subgroup analysis of patients who received rituximab-containing chemotherapy, the risk stratification of both prognostic models showed a significant impact on PFS, especially in the low-risk group. CONCLUSIONS: FLIPI and FLIPI2 are appropriate prognostic models in Korean FL patients, especially for discriminating low-risk patients from intermediate- and high-risk groups.

Incus footplate assembly: Indication and surgical outcome.

OBJECTIVES/HYPOTHESIS: To review surgical findings and hearing outcomes of incus footplate assembly (IFA) for the patients with conductive hearing loss due to missing stapes superstructure with a mobile stapes footplate. STUDY DESIGN: Retrospective case review and survey. METHODS: Pre- and postoperative audiometric data and intraoperative findings were reviewed. Postoperative air-bone gap (ABG) and ABG closure (postoperative air-conduction threshold-preoperative bone-conduction threshold) were analyzed. RESULTS: The causes of missing stapes superstructure and conductive hearing loss were congenital ossicular anomaly (n = 5), chronic otitis media (n = 2), and congenital cholesteatoma (n = 1). The prosthesis was designed to fit between the medial side of the incus and stapes footplate and had a mean length of 3.6 ± 0.5 mm. The mean pre- and postoperative ABG were 38.3 ± 4.8 and 13.3 ± 10.0 dB, respectively. The postoperative ABG at frequencies of 0.25, 0.5, 1.0, 2.0, 3.0, and 4.0 kHz were 20.0 ± 15.4, 16.9 ± 11.9, 16.3 ± 10.3, 10.6 ± 7.3, 12.9 ± 14.0, and 23.1 ± 16.2 dB, respectively. The mean ABG closure was 9.5 dB (range, -1.3∼35.8 dB). Seven cases obtained the best results (mean ABG closure ≤10 dB). In the remaining patient, the mean ABG closure was 9.5 dB until 6 months after surgery, but was 35.8 dB 1 year after surgery. CONCLUSIONS: IFA seems to be a reasonable surgical option in patients with missing the stapes superstructure, but with a mobile footplate in which the long process of incus is preserved. LEVEL OF EVIDENCE: 4 Laryngoscope, 126:2569-2573, 2016.

High-throughput in vivo genotoxicity testing: an automated readout system for the somatic mutation and recombination test (SMART).

Genotoxicity testing is an important component of toxicity assessment. As illustrated by the European registration, evaluation, authorization, and restriction of chemicals (REACH) directive, it concerns all the chemicals used in industry. The commonly used in vivo mammalian tests appear to be ill adapted to tackle the large compound sets involved, due to throughput, cost, and ethical issues. The somatic mutation and recombination test (SMART) represents a more scalable alternative, since it uses Drosophila, which develops faster and requires less infrastructure. Despite these advantages, the manual scoring of the hairs on Drosophila wings required for the SMART limits its usage. To overcome this limitation, we have developed an automated SMART readout. It consists of automated imaging, followed by an image analysis pipeline that measures individual wing genotoxicity scores. Finally, we have developed a wing score-based dose-dependency approach that can provide genotoxicity profiles. We have validated our method using 6 compounds, obtaining profiles almost identical to those obtained from manual measures, even for low-genotoxicity compounds such as urethane. The automated SMART, with its faster and more reliable readout, fulfills the need for a high-throughput in vivo test. The flexible imaging strategy we describe and the analysis tools we provide should facilitate the optimization and dissemination of our methods.

Serendipitous discovery of 2-((phenylsulfonyl)methyl)-thieno[3,2-d]pyrimidine derivatives as novel HIV-1 replication inhibitors.

We identified a novel class of 2-((phenylsulfonyl)methyl)-thieno[3,2-d]pyrimidine compounds as potent HIV-1 replication inhibitors serendipitously during the process of evaluation of triazolothienopyrimidine (TTPM) compounds. Herein, we report synthesis and biological evaluation of 2-((phenylsulfonyl)methyl)-thieno[3,2-d]pyrimidine compounds using a cell-based full replication assay to identify thienopyrimidines 6 and 30, which could be further utilized as viable lead compounds.

Methods for studying the biological consequences of endo-siRNA deficiency in Drosophila melanogaster.

Endogenous small interfering RNAs (endo-siRNAs) are a newly emerged class of small regulatory RNAs. In Drosophila melanogaster, the production of endo-siRNAs depends on the RNase III enzyme Dicer-2 (Dcr-2). Loss of dcr-2 function reduces the resistance of adult flies to various stresses and shortens their life span. The mutants also exhibit alterations in carbohydrate and lipid metabolism. These findings suggest that the endo-siRNA pathway plays a protective role during exposure to stress and aging in D. melanogaster, possibly by regulating metabolic homeostasis. Here, we describe the methods that were used to discover the phenotypes associated with endo-siRNA deficiency by using dcr-2 null mutants.

A fluorescence-based assay for measuring the redox potential of 5-lipoxygenase inhibitors.

The activities and side effects of 5-lipoxygenase (5-LO) inhibitors can be predicted by identifying their redox mechanisms. In this study, we developed a fluorescence-based method to measure the redox potential of 5-LO inhibitors and compared it to the conventional, absorbance-based method. After the pseudo-peroxidase reaction, the amount of remaining lipid peroxide was quantified using the H2DCFDA (2',7'-dichlorodihydrofluorescein diacetate) fluorescence dye. Our method showed large signal windows and provided comparable redox potential values. Importantly, the redox mechanisms of known inhibitors were accurately measured with the fluorescence assay, whereas the conventional, absorbance-based method showed contradictory results. Our findings suggest that our developed method is a better alternative for classifying the redox potential of 5-LO inhibitors, and the fluorescence assay can be effectively used to study the mechanisms of action that are related to redox cycling.

Identification of two HIV inhibitors that also inhibit human RNaseH2.

A total of 140,000 compounds were screened in a targetfree cell-based high throughput assay against HIV-1 infection, and a subset of 81 promising compounds was identified. Secondary screening of these 81 compounds revealed two putative human RNaseH2 inhibitors, RHI001 and RHI002, with IC50 value of 6.8 µM and 16 µM, respectively. RHI002 showed selective activity against human RNaseH2 while RHI001 inhibited HIV-RNaseH, E. coli RNaseH, and human RNaseH1 with IC50 value of 28.5 µM, 7.9 µM, and 31.7 µM, respectively. Kinetic analysis revealed that both inhibitors had non-competitive inhibitor-like properties. Because RNaseH2 is involved in the etiology of Aicardi-Goutier syndrome and has been suggested as an anticancer drug target, small molecule inhibitors modulating its activity would be useful for investigating the cellular function of this molecule.