Prognostic factors for thyroid-stimulating immunoglobulin normalization in moderate-to-severe Graves' orbitopathy: a 36-month longitudinal study.

PURPOSE: The primary objective of this study was to identify predictive factors linked to the normalization of thyroid-stimulating immunoglobulin (TSI) levels in patients diagnosed with active, moderate-to-severe Graves' orbitopathy (GO). The study also tracked the longitudinal changes in TSI levels over a 36-month period following treatment. METHODS: The study population consisted of individuals who were recently diagnosed with active, moderate-to-severe GO and received a 12-week course of intravenous methylprednisolone (IVMP) treatment. A subgroup of patients who did not respond to the initial treatment received an additional 20 Gy of radiation therapy (RTx). TSI levels were monitored at the time of diagnosis, after treatment, and subsequently every 6 months for 36 months. Normalization was defined as a TSI level below 140%. Patients were divdied into two groups with success and failure group depending on whether TSI became normal or not. RESULTS: Out of 83 patients, 36 (43.4%) achieved normalized TSI levels within two years post-IVMP treatment. Lower initial TSI levels (< 425%), absence of additional RTx, and early treatment initiation were associated with a higher likelihood of TSI normalization (P = 0.035, P = 0.028, P < 0.001, respectively). Notably, significant differences in TSI level reduction were observed from 18 months post-treatment between the two groups (P = 0.031). A TSI cutoff value of 413% was identified as predictive for normalization at 24 months (P = 0.002). CONCLUSION: This study is the first to identify key factors that influence normalization of TSI levels in moderate-to-severe Graves' Orbitopathy. It highlights the importance of early treatment decisions, particularly for patients with initial TSI levels above 425%. Despite the treatment, less than half of the patients achieved TSI normalization within 24 months, underscoring the need for additional research to explore the relationship between TSI levels and the clinical manifestations of chronic GO.

Erratum: Correction of Tables in the Article "Reference Respiratory Muscle Strength Values and a Prediction Equation Using Physical Functions for Pulmonary Rehabilitation in Korea".

This corrects the article on p. e325 in vol. 38, PMID: 37846788.

Ultrathin Bronchoscopy for the Diagnosis of Peripheral Pulmonary Lesions: A Meta-Analysis.

BACKGROUND: Ultrathin bronchoscopy (external diameter, ≤3.5 mm) is useful for the diagnosis of peripheral pulmonary lesions because of its good accessibility. OBJECTIVES: We performed a meta-analysis to investigate the diagnostic yield of ultrathin bronchoscopy for peripheral pulmonary lesions. METHODS: We performed a systematic search of MEDLINE and EMBASE (from inception to May 2021), and meta-analysis was performed using R software. The diagnostic yield was evaluated by dividing the number of successful diagnoses by the total number of lesions, and subgroup analysis was performed to identify related factors. RESULTS: Nineteen studies with a total of 1,977 peripheral pulmonary lesions were included. The pooled diagnostic yield of ultrathin bronchoscopy was 0.65 (95% confidence interval, 0.60-0.70). Significant heterogeneity was observed among studies (χ2, 87.75; p < 0.01; I2, 79.5%). In a subgroup analysis, ultrathin bronchoscopy with 1.2 mm channel size showed a diagnostic yield of 0.61 (95% confidence interval, 0.53-0.68), whereas ultrathin bronchoscopy with 1.7 mm channel size showed 0.70 (95% confidence interval, 0.66-0.74) (χ2, 5.35; p = 0.02). In addition, there was a significant difference in diagnostic yield based on lesion size, histologic diagnosis (malignant vs. benign), bronchus sign, and lesion location from the hilum, whereas no significant difference was found based on lobar location. The overall complication rate of ultrathin bronchoscopy was 2.7% (pneumothorax, 1.1%). CONCLUSIONS: Ultrathin bronchoscopy is an excellent tool for peripheral pulmonary lesion diagnosis with a low complication rate. The diagnostic yield of ultrathin bronchoscopy was significantly higher with larger channel size, which might be attributed to the availability of radial endobronchial ultrasound.

Changing trends in the incidence and spectrum of cancers between 1990 and 2021 among HIV-infected patients in Busan, Korea.

BACKGROUND: Long-term follow-up data on cancer incidence and spectrum among human immunodeficiency virus (HIV)-infected individuals in Korea have been scarce. MATERIAL AND METHODS: This retrospective cohort study included HIV-infected individuals visiting a tertiary care hospital in Busan, South Korea between 1990 and 2021. The observation was divided into 4 periods. The incidence rate was calculated using direct standardization on age and sex, stratified by calendar period. RESULTS: Of the 1,297 patients, 92 patients (7.1%) were diagnosed with 97 cancers. Excluding 37 patients with prevalent cancer, 1,260 patients were followed for a total of 8,803.7 person-years (PYs), and 55 patients developed 60 incident cancers including 5 second primary incident cancers. In men, the AIDS-defining cancer (ADC) incidence decreased from 294.7 per 100,000 PYs in 1990-1997 to 124.8 per 100,000 PYs in 2014-2021, while the non-AIDS-defining cancer (NADC) incidence increased from 0 per 100,000 PYs to 316.5 per 100,000 PYs during the same period. The proportion of virus-unrelated NADCs (VU-NADCs) increased from 33.3% in 1998-2005 to 49% in 2014-2021. The proportion of human papillomavirus-associated cancers (HPVACs) has recently increased in both ADCs and NADCs. The median time from HIV diagnosis to their first cancer was 1.48 years for ADCs, 6.11 years for VR-NADCs, 8.3 years for VU-NADCs, and 11.5 years for HPVACs. CONCLUSION: The incidence of NADCs is increasing with the aging of HIV-infected patients, and thus, it is necessary to promote cancer screening and prevention programs.

Comparison of the Intrableb Characteristics of Anterior Segment Optical Coherence Tomography Imaging in Trabeculectomy according to Amniotic Membrane Transplantation.

INTRODUCTION: The purpose of this study was to compare the characteristics of filtering bleb with anterior segment optical coherence tomography (AS-OCT) according to amniotic membrane transplantation (AMT). METHODS: One hundred and sixteen eyes of 103 glaucoma patients who underwent trabeculectomy with (AMT group; 85 eyes) or without AMT (control group; 31 eyes) were included. Intrableb parameters were evaluated with AS-OCT. Surgical success was defined as an intraocular pressure (IOP) ≤18 mm Hg and IOP reduction ≥20% without medication at the time of AS-OCT examination. Logistic regression analyses were performed to determine factors associated with IOP control. RESULTS: In the eyes with successful IOP control, the fluid-filled space area, score, and height were greater for the AMT group than the control group (all ps < 0.001), while stripping layer thickness was greater and bleb wall reflectivity was lower for the control group than the AMT group (all ps < 0.001). Surgical success in the AMT group was associated with greater fluid-filled space score, lower bleb wall reflectivity, and microcyst formation (odds ratio [OR] = 8.016, 0.913, and 16.202, respectively, all ps ≤ 0.041). Lower bleb wall reflectivity alone was associated with surgical success in the control group (OR = 0.815, p = 0.019). CONCLUSION: The extent of the fluid-filled space was associated with successful IOP control after trabeculectomy with AMT. Hyporeflective bleb wall was associated with successful IOP control in AMT and control groups.

Reference Respiratory Muscle Strength Values and a Prediction Equation Using Physical Functions for Pulmonary Rehabilitation in Korea.

BACKGROUND: In Korea, tests for evaluating respiratory muscle strength are based on other countries' clinical experience or standards, which can lead to subjective evaluations. When evaluating respiratory function based on the standards of other countries, several variables, such as the race and cultures of different countries, make it difficult to apply these standards. The purpose of this study was to propose objective respiratory muscle strength standards and predicted values for healthy Korean adults based on age, height, weight, and muscle strength, by measuring maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and peak cough flow (PCF). METHODS: This cross-sectional study analyzed MIP, MEP, and PCF in 360 people, each group comprising 30 adult men and women aged 20-70, diagnosed as healthy after undergoing medical check-ups at a general hospital. Hand grip strength (HGS) and the five times sit-to-stand test (FTSST) results were also recorded. Correlations among respiratory muscle strength, participant demographics, and overall muscle strength were evaluated using Pearson's correlation analysis. The predicted values of respiratory muscle strength were calculated using multiple regression analysis. RESULTS: Respiratory muscle strength differed from the values reported in studies from other countries. In the entire samples, both MIP and MEP had the highest correlations with peak HGS (r = 0.643, r = 0.693; P < 0.05), while PCF had the highest correlation with forced expiratory volume in 1 s (r = 0.753; P < 0.05). Age, body mass index, peak HGS, and FTSST results were independent variables affecting respiratory muscle strength. A predictive equation for respiratory muscle strength was developed using the multiple regression equation developed in this study. CONCLUSION: Respiratory muscle strength index may differ by country. For more accurate diagnoses, standard values for each country are required. This study presents reference values for Korea, and a formula for estimation is proposed when no respiratory muscle strength measurement equipment is available. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0006778.

Effect of Observer's Sex and Chin Prominences on the Perception of the Lower Lip-Chin Prominence Angle.

ABSTRACT: This study aimed to identify the preferred range of lower lip-chin prominence angles in the Korean population and evaluate the effect of the individual lower lip-chin prominence angle on perceptions of esthetic chin profile.Chin prominence silhouettes were used to assess the lower lip-chin prominence preference. The observers randomly categorized each image as (1) normal, (2) slightly abnormal but not requiring surgical correction, and (3) abnormal and requiring surgery. Individual lower-chin prominence angles of all observers were analyzed using standardized clinical photographs.The normal range of lower lip-chin prominence angle is 0° to 25°; socially acceptable range is 0° to -10°, 25° to 40°; range needing surgery is -10° to -30° and 40° to 45°. Women are more tolerant to chin protrusion. A protrusive chin is more acceptable in observers with retrusive chin profile.Skeletal Class II profile is more acceptable than skeletal Class III in the Korean population. The individual lower-chin prominence angle could affect perception of desired surgery. These findings indicate that patient-specific treatment planning is important in achieving satisfaction in chin surgery.

CaBir1 functions as an inhibitor-of-apoptosis and affects caspase-like activitiy in Candida albicans.

CaMca1 is the only metacaspase in Candida albicans, which shows structural homology to the mammalian caspases. CaMca1 consists of the caspase domain, the P20 and P10 regions, and the conserved catalytic histidine-cysteine dyad that is required for executing apoptosis in C. albicans. However, little is known about the proteolytic processing of CaMca1 or its activation under apoptosis-inducing conditions. To understand the regulation of this process, we characterized CaBir1 which is the single IAP (inhibitor-of-apoptosis protein) in C. albicans. IAPs are a family of proteins whose members all harbor a BIR (baculovirus IAP repeat) domain and negatively regulate apoptosis by inhibiting caspases. We found that the Cabir1/Cabir1 deletion mutant exhibited increased apoptotic phenotypes, such as ROS accumulation, nuclear segmentation, and cell survival, under apoptosis-inducing conditions. Examination of CaMca1 cleavage patterns in response to various apoptotic stresses revealed that these cleavages were stress-specific and dependent on the catalytic histidine-cysteine residues of CaMca1. The Cabir1/Cabir1 mutation was not associated with altered CaMca1 processing with or without apoptotic stimuli, but the Cabir1/Cabir1 mutant exhibited significantly increased caspase-like activities. These results suggest that CaBir1 acts as an apoptosis inhibitor by regulating caspase-like activity, but not CaMca1 processing.

Association between Irritable Bowel Syndrome and Risk of Osteoporosis in Korean Premenopausal Women.

OBJECTIVE: The objective of this study is to evaluate irritable bowel syndrome (IBS) as a risk factor for osteoporosis and osteoporotic fracture in Korean women after controlling for basic confounding factors and considering detailed demographic and clinical information. SUBJECTS AND METHODS: We performed a nationwide population-based retrospective cohort analysis and matched every IBS case with a non-IBS case at a 1:4 frequency ratio based on age. The population consisted of female patients with data in the Health Insurance Review and Assessment (HIRA) database from 2002 to 2010. To determine the risk of osteoporosis and osteoporotic fracture in IBS and non-IBS patients, hazard ratios (HRs) with 95% confidence intervals (CI) were estimated using Cox proportional hazards regression models, adjusting for confounding variables, such as the area of residence, health insurance type, and economic status. RESULTS: We identified 1,017,468 patients in the HIRA database with data from 2002 to 2010 who could potentially be included in the cohort. Among these, we identified 1,545 (11.4%) women (age >19 years) with newly diagnosed IBS (IBS group). Additionally, 6,180 patients without IBS and age-matched to the IBS group were selected. Cox modeling revealed that the crude HRs for osteoporosis and osteoporotic fractures in patients with IBS were 1.476 (95% CI, 1.241-1.754) and 1.427 (95% CI, 1.086-1.876), respectively. CONCLUSION: Our data showed an increased incidence of osteoporosis and osteoporotic fractures in women with IBS compared with age-matched controls.

Arterial stiffness is an independent predictor for risk of mortality in patients with type 2 diabetes mellitus: the REBOUND study.

BACKGROUND: This study aimed to evaluate the benefit of brachial-ankle pulse wave velocity (baPWV) as a noninvasive marker of arterial stiffness for the prediction of all-cause and cause-specific mortality in patients with type 2 diabetes. METHODS: This multicenter prospective observational study analyzed 2308 patients with type 2 diabetes between 2008 and 2018. The patients were categorized according to the quartiles of baPWV. Cause of mortality was determined using death certificates and patient clinical records. We estimated proportional mortality rates from all causes, cardiovascular, cancer, and other causes among adults with diabetic status according to their baPWV. Cox regression models were used to estimate hazard ratios (HRs). RESULTS: There were 199 deaths (8.6%) in the study population during a median follow-up duration of 8.6 years. When baPWV was assessed as quartiles, a significantly higher risk of all-cause mortality (HR = 5.39, P < 0.001), cardiovascular-mortality (HR = 14.89, P < 0.001), cancer-mortality (HR = 5.42, P < 0.001), and other-cause mortality (HR = 4.12, P < 0.001) was found in quartile 4 (Q4, ≥ 1830 cm/s) than in quartiles 1-3 (Q1-3). Adding baPWV to baseline model containing conventional risk factors such as age, sex, diabetes duration, body mass index, glycated hemoglobin, systolic blood pressure, glomerular filtration rate, smoking, and insulin improved the risk prediction for all-cause (net reclassification index (NRI) = 49%, P < 0.001) and cause-specific (cardiovascular NRI = 28%, P = 0.030; cancer NRI = 55%, P < 0.001; other-cause NRI 51%, P < 0.001) mortality. CONCLUSION: This long-term, large-scale, multicenter prospective observational cohort study provide evidence that increased arterial stiffness, as measured by baPWV, predicts the risk of all-cause and cause-specific mortality in type 2 diabetes, supporting the prognostic utility of baPWV. Trial registration Clinical Research Information Service (CRIS), KCT 0005010. Retrospectively Registered May 12, 2020. https://cris.nih.go.kr/cris/search/search_result_st01.jsp?seq=16677.

The effectiveness and safety of lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma in real-world clinical practice: a study of the Korean Multiple Myeloma Working Party (KMMWP-151 study).

Although lenalidomide plus dexamethasone (RD) is a therapeutic option for relapsed/refractory multiple myeloma (RRMM), limited real-world clinical data exist. The purpose of this study was to estimate efficacy and safety of RD in RRMM patients of the clinical practice. Data from patients at 25 university hospitals in South Korea between October 2009 and December 2016 were collected retrospectively. We report the effectiveness and safety of RD in 546 RRMM patients in routine clinical practice in South Korea. Patients (median age, 65 years) typically received median 7 cycles of RD, and 184 (33.7%) patients were treated with 10 or more cycles of RD. Patients with renal impairment (CLCr < 40 mL/min; 10.4%), comorbid conditions (≥ 2; 12.0%), and poor performance status (≥ 2; 25.1%) were included. The overall response rate was 64.2%: complete response (13.1%), very good partial response (VGPR 19.9%). With median follow-up duration of 18.6 months, median PFS and OS were 11.2 months and 25.2 months, respectively. In multivariate analysis, less than 2 comorbid conditions, normal LDH, failed one chemotherapy prior to RD, and ≥ 10 cycles of RD therapy had significantly prolonged PFS (P = 0.007, P = 0.011, P = 0.007, and P < 0.001, respectively). Adverse events were acceptable. RD is effective and safe in real-life clinical practice, including patients with comorbidities. RD is an effective and safe treatment in a real clinical setting which includes patients with comorbidities. Early and continual use of RD treatment may improve RRMM survival outcomes.

Effects of Traction on Interpretation of Lumbar Bone Mineral Density in Patients with Duchenne Muscular Dystrophy: A New Measurement Method and Diagnostic Criteria Based on Comparison of Dual-Energy X-Ray Absorptiometry and Quantitative Computed Tomography.

INTRODUCTION: This study aimed to compare the performance of dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) in evaluating bone mineral density (BMD) of patients with Duchenne muscular dystrophy and scoliosis. METHODOLOGY: Twenty-nine participants (mean age 19.72 ± 6.13 years) underwent whole spine radiography, DXA before and after traction, and QCT alone without traction. Scoliosis and vertebral rotation angles obtained before and after traction were compared, and BMD values from DXA were compared to those obtained via QCT. The scoliosis angle, presented as Cobb's angle of L1-L4, was measured. RESULTS: Cobb's angle significantly decreased from 30.38° ± 24.83° before traction to 22.78° ± 20.41° after traction (p < 0.0001) and the Z-score decreased from -1.88 ± 1.59 to -2.86 ± 2.16 (p < 0.0001). Changes in rotation angle, BMD, and bone mineral content were not significant. Post-traction BMD values and Z-scores showed a higher correlation with QCT measurements than pretraction. Moreover, pre and post-traction Z-scores (≤-1.1 and -1.36, respectively) were more accurate in identifying patients with osteoporosis according to QCT scans compared with the preexisting Z-score of -2 or less. CONCLUSION: Lumbar BMD measured via DXA and scoliosis allowed a more accurate diagnosis of osteoporosis when traction was applied.

Prediction of visual field from swept-source optical coherence tomography using deep learning algorithms.

PURPOSE: To develop a deep learning method to predict visual field (VF) from wide-angle swept-source optical coherence tomography (SS-OCT) and compare the performance of three Google Inception architectures. METHODS: Three deep learning models (with Inception-ResNet-v2, Inception-v3, and Inception-v4) were trained to predict 24-2 VF from the macular ganglion cell-inner plexiform layer and the peripapillary retinal nerve fibre layer map obtained by SS-OCT. The prediction performance of the three models was evaluated by using the root mean square error (RMSE) between the actual and predicted VF. The performance was also compared among different glaucoma severities and Garway-Heath sectorizations. RESULTS: The training dataset comprised images of 2220 eyes from 1120 subjects, and the test dataset was obtained from another 305 subjects (305 eyes). In all subjects, the global prediction errors (RMSEs) were 4.44 ± 2.09 dB, 4.78 ± 2.38 dB, and 4.85 ± 2.66 dB for the Inception-ResNet-v2, Inception-v3, and Inception-v4 architectures, respectively, and the prediction error of Inception-ResNet-v2 was significantly lower than the other two (P < 0.001). As glaucoma progressed, the prediction error of all three architectures significantly worsened to 6.59 dB, 7.33 dB, and 7.79 dB, respectively. In the analysis of sectors, the nasal sector had the lowest prediction error, followed by the superotemporal sector. CONCLUSIONS: Inception-ResNet-v2 achieved the best performance, and the global prediction error (RMSE) was 4.44 dB. As glaucoma progressed, the prediction error became larger. This method may help clinicians determine VF, particularly for patients who are unable to undergo a physical VF test.

The Analysis of Electroencephalography Changes Before and After a Single Neurofeedback Alpha/Theta Training Session in University Students.

The underlying mechanisms of alpha/theta neurofeedback training have not been fully determined. Therefore, this study aimed to test the changes in the brain state feedback during the alpha/theta training. Twenty-seven healthy participants were trained during a single session of the alpha/theta protocol, and the resting quantitative electroencephalography (QEEG) was assessed before and after training. QEEG was recorded at eight scalp locations (F3, F4, C3, C4, T3, T4, O1, and O2), and the absolute power, relative power, ratio of sensory-motor rhythm beta (SMR) to theta (RST), ratio of SMR-mid beta to theta (RSMT), ratio of mid beta to theta (RMT), ratio of alpha to high beta (RAHB), and scaling exponent of detrended fluctuation analysis by each band were measured. The results indicated a significant increase of absolute alpha power, especially the slow alpha band, at all electrodes except T3 and T4. Moreover, the relative alpha power, especially the slow alpha band, showed a significant increase at all electrodes. The relative theta power showed a significant decrease at all electrodes, except T3. A significant decrease in relative beta power, relative lower beta power and relative mid beta power was observed at O1. RST (at C4, O1, and O2), RSMT and RMT (at F4, C4, O1 and O2), and RAHB (at all electrodes) showed significant increase. Scaling exponents at all electrodes except T3 showed a significant decrease. These findings indicate that a one-time session of alpha/theta training might have the possibility to enhance both vigilance and concentration, thus stabilizing the overall brain function.

Salivary glutamate is elevated in individuals with chronic migraine.

Background Glutamate has been implicated in migraine pathogenesis, and is elevated in the plasma, cerebrospinal fluid, and saliva in migraineurs. However, no comparison of glutamate levels among chronic migraine, episodic migraine and controls has been reported. The aim is to compare salivary glutamate levels of individuals with chronic migraine with those of individuals with episodic migraine and healthy controls. Methods We investigated salivary glutamate level of 46 women with chronic migraine, 50 women with episodic migraine, and 19 healthy controls via enzyme linked immunosorbent assay. Results The salivary glutamate level of the chronic migraine group (median and interquartile range, 20.47 [15.27-30.15] pmol/mg total protein) was significantly higher than those of the episodic migraine (16.17 [12.81-20.15] pmol/mg total protein, p = 0.008) and control (12.18 [9.40-16.24] pmol/mg total protein, p = 0.001) groups. The salivary glutamate level of the episodic migraine group was marginally elevated from that of the control group (post hoc p = 0.016). Thresholds of 16.58 and 17.94 pmol/mg total protein optimize the sensitivity and specificity to differentiate chronic migraine participants from healthy controls and episodic migraine participants, respectively. Conclusions Salivary glutamate level was elevated in chronic migraine participants. These data suggest that salivary glutamate level could be an indicator of CM.

Prevalence and incidence of clinically significant patulous Eustachian tube: A population-based study using the Korean National Health Insurance Claims Database.

OBJECTIVES: The aim of this study is to estimate the entire population-based prevalence and incidence of Patulous Eustachian tube (PET) using the Korean National Health Insurance (NHI) claims database. The annual trends of prevalence and incidence of PET were also investigated. METHODS: Retrospective analysis of PET patients was performed between 2010 and 2016, from the NHI claims database. PET patients were defined as those who had at least one service claim with a primary diagnosis under an ICD-10-based PET code (H69.0). RESULTS: During the study period, there were 20,533 new PET patients in Korea. In 2016 there were 4482 incident cases, and the standardized annual incidence rate was 8.8 per 100,000 persons. The standardized annual prevalence rate increased significantly from 7.2 per 100,000 persons in 2010 to 10.3 per 100,000 persons in 2016. The prevalence increased significantly on annual basis, whereas the incidence rate fluctuated over time. Interestingly, the incidence and prevalence of PET in women was almost twice as high as that in men, and peaked in their 20s. CONCLUSIONS: This study demonstrated the substantial annual increase of the NHI claims with PET code (H69.0) in Korea from 2010 to 2016. Statistical results based on the NHI claims, we confirmed the high prevalence and incidence rates of clinically significant PET in women than in men. This study only covered patient using the medical service for PET and missed PET sufferers not seeking medical service. However, this study can provide basic epidemiological information on clinically significant PET.

Mutational analysis of metacaspase CaMca1 and decapping activator Edc3 in the pathogenicity of Candida albicans.

Candida albicans, an opportunistic fungal pathogen, displays apoptotic cell death in response to various stresses and a wide range of antifungal treatments. CaMca1, which is the only metacaspase in C. albicans, has been described as a key player in apoptotic cell death. Edc3 is an mRNA decapping activator and a scaffold protein of processing bodies. Edc3 was previously shown to regulate CaMCA1 expression and oxidative stress-induced apoptosis. In this study, we analyzed the contribution of the catalytic residues of the CaMca1 to the oxidative stress-induced apoptosis and pathogenicity of C. albicans. The CaMCA1C292A mutation decreased caspase activity to a level similar to that observed in the Camca1/Camca1 deletion strain and over-expression of CaMCA1C292A failed to suppress the oxidative-stress phenotypes of the edc3/edc3 mutant strain. The edc3/edc3, Camca1/Camca1, and CaMCA1C292A mutant strains were not virulent in a murine candidiasis model. Filamentation defects were observed in the Camca1/Camca1 mutant cells, whereas this defect was only partial in CaMCA1C292A mutant cells. These results suggest that CaMca1 and Edc3 play essential roles in the oxidative stress-induced apoptosis and virulence of C. albicans, and also support the notion that Edc3 is a key regulator of CaMca1 expression.

Areca nut exposure increases secretion of tumor-promoting cytokines in gingival fibroblasts that trigger DNA damage in oral keratinocytes.

Molecular crosstalk between cancer cells and fibroblasts has been an emerging hot issue in understanding carcinogenesis. As oral submucous fibrosis (OSF) is an inflammatory fibrotic disease that can potentially transform into squamous cell carcinoma, OSF has been considered to be an appropriate model for studying the role of fibroblasts during early stage carcinogenesis. In this sense, this study aims at investigating whether areca nut (AN)-exposed fibroblasts cause DNA damage of epithelial cells. For this study, immortalized hNOF (hTERT-hNOF) was used. We found that the levels of GRO-α, IL-6 and IL-8 increased in AN-exposed fibroblasts. Cytokine secretion was reduced by antioxidants in AN-exposed fibroblasts. Increase in DNA double strand breaks (DSB) and 8-oxoG FITC-conjugate was observed in immortalized human oral keratinocytes (IHOK) after the treatment of cytokines or a conditioned medium derived from AN-exposed fibroblasts. Cytokine expression and DNA damage were also detected in OSF tissues. The DNA damage was reduced by neutralizing cytokines or antioxidant treatment. Generation of reactive oxygen species (ROS) and DNA damage response, triggered by cytokines, were abolished when NADPH oxidase (NOX) 1 and 4 were silenced in IHOK, indicating that cytokine-triggered DNA damage was caused by ROS generation through NOX1 and NOX4. Taken together, this study provided strong evidence that blocking ROS generation might be a rewarding approach for cancer prevention and intervention in OSF.

Optic Nerve Head Curvature Flattening Is Associated with Central Visual Field Scotoma.

This study aimed to develop a new index, the average curvature ratio (ACR), to represent the optic nerve head (ONH) tilting and investigate its clinical relevance. Myopic eyes were included and divided into two subgroups: flat ONH (ACR < 1.0) and convex ONH (ACR ≥ 1.0). The occurrences of central and peripheral visual field (VF) defects were compared between the two groups. A total of 375 myopic eyes were recruited, and 231 and 144 eyes were included in the flat and convex ONH groups, respectively. Central scotoma occurred more frequently in the flat ONH group. According to the Patella-Anderson criteria, the number of eyes with central scotoma was 103 (44.6%) in the flat and 44 (30.6%) in the convex ONH groups (p = 0.009). According to Kook's criteria, the number of eyes with central scotoma was 122 (52.8%) in the flat and 50 (34.7%) in the convex ONH groups (p < 0.001). Peripheral scotoma was not significantly different between the groups. In the correlation analysis, the ACR was positively correlated with spherical equivalence, but not with axial length or central corneal thickness. The ACR reflects the degree of the ONH tilt and is a good index for estimating central VF damage in myopic eyes.