Which obesity index is the most useful marker for predicting hepatic steatosis in children and adolescents with obesity? A cross-sectional study using quantitative magnetic resonance imaging.

INTRODUCTION: We aimed to evaluate the relationships between hepatic steatosis and various indices of obesity, and to identify the most useful index for the prediction of hepatic steatosis in children and adolescents with obesity. METHODS: A total of 226 children and adolescents with a mean body mass index (BMI) z-score of 2.65 and a mean age of 11.4 years were subjected to anthropometric and body composition measurements, laboratory testing, abdominal fat mass assessment, and hepatic fat accumulation by magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF). The participants were divided into quartiles according to the severity of their hepatic steatosis, and the presence of hepatic steatosis was defined using an MRI-PDFF ≥ 5%. RESULTS: The multivariate ordinal regression analysis showed that the severity of hepatic steatosis was positively associated with BMI, waist circumference, waist-to-hip ratio, waist-to-height ratio, fat mass, fat-free mass, visceral adiposity, and abdominal subcutaneous adiposity. Higher activities of liver enzymes and higher concentrations of triglyceride, C-reactive protein, fasting insulin, and leptin were associated with more severe hepatic steatosis, whereas high-density lipoprotein-cholesterol and adiponectin were negatively associated with hepatic steatosis. The indices of obesity with areas under the receiver operating characteristic curves (AUCs) > 0.8 for the prediction of hepatic steatosis were liver enzymes, visceral adipose tissue area, waist-to-hip ratio, and waist-to-height ratio. CONCLUSION: The severity of hepatic steatosis significantly correlated with various indices of obesity and cardiometabolic markers in children and adolescents with obesity. The indices of abdominal obesity would be the most useful for the prediction of hepatic steatosis.

Antioxidant and Antineuroinflammatory Mechanisms of Kaempferol-3-O-ß-d-Glucuronate on Lipopolysaccharide-Stimulated BV2 Microglial Cells through the Nrf2/HO-1 Signaling Cascade and MAPK/NF-κB Pathway.

Aglycone- and glycoside-derived forms of flavonoids exist broadly in plants and foods such as fruits, vegetables, and peanuts. However, most studies focus on the bioavailability of flavonoid aglycone rather than its glycosylated form. Kaempferol-3-O-ß-d-glucuronate (K3G) is a natural flavonoid glycoside obtained from various plants that have several biological activities, including antioxidant and anti-inflammatory effects. However, the molecular mechanism related to the antioxidant and antineuroinflammatory activity of K3G has not yet been demonstrated. The present study was designed to demonstrate the antioxidant and antineuroinflammatory effect of K3G against lipopolysaccharide (LPS)-stimulated BV2 microglial cells and to evaluate the underlying mechanism. Cell viability was determined by MTT assay. The inhibition rate of reactive oxygen species (ROS) and the production of pro-inflammatory mediators and cytokines were measured by DCF-DA assay, Griess assay, enzyme-linked immunosorbent assay (ELISA), and western blotting. K3G inhibited the LPS-induced release of nitric oxide, interleukin (IL)-6, and tumor necrosis factor-α (TNF-α) as well as the expression of prostaglandin E synthase 2. Additionally, K3G reduced the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nuclear factor-kappa B (NF-κB) related proteins. Mechanistic studies found that K3G downregulated phosphorylated mitogen-activated protein kinases (MAPKs) and upregulated the Nrf2/HO-1 signaling cascade. In this study, we demonstrated the effects of K3G on antineuroinflammation by inactivating phosphorylation of MPAKs and on antioxidants by upregulating the Nrf2/HO-1 signaling pathway through decreasing ROS in LPS-stimulated BV2 cells.

Usefulness of universal SARS-CoV-2 PCR testing for inpatients and their caregivers during the omicron era.

Background: Since January 2022, the Omicron variant has become the dominant strain in South Korea, and COVID-19 cases among hospitalized patients and their guardians or caregivers have increased. We evaluated the usefulness of universal periodic screening for SARS-CoV-2 in patients and resident caregivers in a South Korean tertiary care hospital. Methods: We evaluated the reason for testing in COVID-19 confirmed patients and resident caregivers during their hospitalization from March 3 to 31, 2022. The rate of positive PCR universal testing in hospital (or residency) (HD) on days 3 and 7 in asymptomatic patients and caregivers were evaluated. The test for SARS-CoV-2 was done by RT-PCR. Results: During the study period, 677 patients were diagnosed with COVID-19. The reasons for testing were the symptoms (226 (33%)), pre-admission test (183 (27%)), exposure to COVID-19 (124 (18%)), universal testing on HD 3 (94 (14%)), and that on HD 7 (34 (5%)). Caregivers (n = 340) were tested during their residency due to exposure to COVID-19 cases, 103 (30%); universal testing on HD 3, 90 (26%); symptom development, 46 (14%); pre-stay, 39 (11%); and universal testing on HD 7, 29 (9%). The positive test rates of inpatients and caregivers on HD 3 and HD 7 were as follows: 1.4% (93/6553) and 2.1% (55/2646) in inpatients, and 1.3% (79/5989) and 1.7% (35/2106) in caregivers, respectively. Conclusions: Universal testing, regardless of symptom or epidemiologic link, is useful for detecting pre-symptomatic and asymptomatic COVID-19 cases among hospitalized patients and caregivers and preventing a nosocomial outbreak during the Omicron era.

DNA methylome and single-cell transcriptome analyses reveal CDA as a potential druggable target for ALK inhibitor-resistant lung cancer therapy.

Acquired resistance to inhibitors of anaplastic lymphoma kinase (ALK) is a major clinical challenge for ALK fusion-positive non-small-cell lung cancer (NSCLC). In the absence of secondary ALK mutations, epigenetic reprogramming is one of the main mechanisms of drug resistance, as it leads to phenotype switching that occurs during the epithelial-to-mesenchymal transition (EMT). Although drug-induced epigenetic reprogramming is believed to alter the sensitivity of cancer cells to anticancer treatments, there is still much to learn about overcoming drug resistance. In this study, we used an in vitro model of ceritinib-resistant NSCLC and employed genome-wide DNA methylation analysis in combination with single-cell (sc) RNA-seq to identify cytidine deaminase (CDA), a pyrimidine salvage pathway enzyme, as a candidate drug target. CDA was hypomethylated and upregulated in ceritinib-resistant cells. CDA-overexpressing cells were rarely but definitively detected in the naïve cell population by scRNA-seq, and their abundance was increased in the acquired-resistance population. Knockdown of CDA had antiproliferative effects on resistant cells and reversed the EMT phenotype. Treatment with epigenome-related nucleosides such as 5-formyl-2'-deoxycytidine selectively ablated CDA-overexpressing resistant cells via accumulation of DNA damage. Collectively, our data suggest that targeting CDA metabolism using epigenome-related nucleosides represents a potential new therapeutic strategy for overcoming ALK inhibitor resistance in NSCLC.

Vascular Alterations Preceding Arterial Wall Thickening in Overweight and Obese Children.

BACKGROUND: Childhood obesity is linked to adverse cardiovascular outcomes in adulthood. This study aimed to assess the impact of childhood obesity on the vasculature and to investigate whether vascular alteration precedes arterial wall thickening in childhood. METHODS: A total of 295 overweight (body mass index [BMI] 85th to 95th percentile, n = 30) and obese (BMI ≥ 95th percentile, n = 234) children aged 7-17 years and 31 normal-weight controls with similar age and gender were prospectively recruited. We assessed anthropometric data and laboratory findings, and measured the carotid intima-media thickness (IMT), carotid artery (CA) diameter, M-mode-derived arterial stiffness indices, and velocity vector imaging parameters, including the CA area, fractional area change, circumferential strain, and circumferential strain rate (SR). RESULTS: The mean ± standard deviation age of the participants was 10.8 ± 2.1 years; 172 (58%) children were male. Regarding structural properties, there was no difference in the IMT between the three groups. The CA diameter was significantly increased in obese children, whereas the CA area showed a significant increase beginning in the overweight stage. Regarding functional properties, contrary to ß stiffness and Young's elastic modulus, which were not different between the three groups, the circumferential SR showed a significant decrease beginning in the overweight stage and was independently associated with BMI z-scores after adjusting for covariates. CONCLUSION: We have demonstrated that arterial stiffening and arterial enlargement precede arterial wall thickening, and that these vascular alterations begin at the overweight stage in middle childhood or early adolescence.

Evaluation of the Immunological Activity of Gryllus bimaculatus Water Extract.

Edible insects are commonly consumed across the world because of their size, availability, and nutritional benefits. They have also been recommended as a potential solution to food shortage because of their high nutritional value. In this study, we demonstrated the immunological effects of Gryllus bimaculatus on RAW 264.7 cells and splenocytes obtained from mouse. This is the first study to evaluate the immunological effects of G. bimaculatus water extract. Innate and adaptive immunity were evaluated and measured in RAW 264.7 cells and/or mouse splenocytes using a cell viability assay; changes in cytokine abundance, nitric oxide production, and cell surface molecule abundance were determined using flow cytometry; and western blotting analysis was performed for various immune signaling pathways. G. bimaculatus water extract showed no cytotoxicity in cells, and the results suggest that treatment with G. bimaculatus water extract can induce macrophage activation through mitogen-activated protein kinase and nuclear factor-κB signaling, induction of proinflammatory cytokines [interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α] and activation of the expression of cell surface molecules [cluster of differentiation (CD)80, CD86, major histocompatibility complex (MHC) class I, and MHC class II]. Treatment with G. bimaculatus water extract increased the production of cytokines (IL-2, IL-4, and interferon-γ) in splenocytes. The results indicate that G. bimaculatus water extract can regulate innate and adaptive immunity via modulation macrophages and splenocytes activation and can serve as an immunological agent. We inferred that G. bimaculatus is a safe and efficient natural material that enhances immunological activity.

Evaluation of Anti-Cancer Activity of Gryllus bimaculatus Water Extract on Non-Small Cancer Lung Cell via Apoptosis.

Gryllus bimaculatus, traditionally used in oriental medicine, demonstrates functional and pharmacological potential through demonstrating immunomodulatory, hepato-protective properties, anti-inflammatory, antioxidant, and neuroprotective effects. In this study, we examined the effect of G. bimaculatus on cell proliferation and apoptosis in lung cancer cells. This is the first study to examine the anti-cancer effects of G. bimaculatus extracts on non-small cell lung cancer. Frozen G. bimaculatus was obtained, homogenized, and dissolved in distilled water. Using a freeze dryer, samples were concentrated until almost all the water was removed, and extracts were diluted in solutions of phosphate buffered saline. Anti-cancer effects of extracts on human non-small cancer lung cells were estimated based on cell cytotoxicity, western blot, and flow cytometry, using lipopolysaccharides as a positive control. H460 and A549 human non-small cell cancer lung cells were treated with G. bimaculatus water extracts of various concentrations, with lipopolysaccharide used as a pos-itive control. The results showed that treatment with the extract for 24 or 48 h inhibited H460 proliferation, demonstrated by reduced cell numbers with morphological changes. Furthermore, flow cytometry analysis demonstrated that the extracts induced cell death on H460. However, extracts did not show cytotoxic effects on A549 cells. In conclusion, the extract induced apoptosis of lung cancer cells, possibly via caspase, Bcl-2 family signaling pathways. Therefore, G. bimaculatus water extracts are safe and efficient natural materials that may have great potential in the treatment of lung cancer.

EZH2 as a Potential Target for NAFLD Therapy.

Non-alcoholic fatty liver disease (NAFLD) is a complex disease that is affected by genetic predisposition and epigenetic modification. Deregulation of epigenetic pathways is now recognized as a frequent event in NAFLD, and understanding the mechanistic roles of these epigenetic factors may lead to new strategies for NAFLD treatment. Enhancer of zeste homolog 2 (EZH2) catalyzes methylation on Lys 27 of histone H3, which leads to chromatin compaction and gene silencing. EZH2 regulates embryonic development and cell lineage determination and is related to many human diseases. Recent studies show that EZH2 has critical roles in liver development, homeostasis, and regeneration. Moreover, aberrant activation of EZH2 promotes NAFLD progression. Several EZH2 inhibitors have been developed and studied both in vitro and in clinical trials. In this review, we summarize our current understanding of the role of EZH2 in NAFLD and highlight its potential as a novel therapeutic target for NAFLD treatment.

Antimicrobial and Immunomodulatory Effects of Bifidobacterium Strains: A Review.

Bifidobacterium strains can provide several health benefits, such as antimicrobial and immunomodulatory effects. Some strains inhibit growth or cell adhesion of pathogenic bacteria, including multidrug-resistant bacteria, and their antibacterial activity can be intensified when combined with certain antibiotics. In addition, some strains of bifidobacteria reduce viral infectivity, leading to less epithelial damage of intestinal tissue, lowering the virus shedding titer, and controlling the release of antiviral substances. Furthermore, bifidobacteria can modulate the immune system by increasing immunoglobulins, and inducing or reducing pro- or antiinflammatory cytokines, respectively. In particular, these anti-inflammatory effects are helpful in the treatment of patients who are already suffering from infection or inflammatory diseases. This review summarizes the antimicrobial effects and mechanisms, and immunomodulatory effects of Bifidobacterium strains, suggesting the potential of bifidobacteria as an alternative or complementary treatment option.

Factors associated with dropout in a lifestyle modification program for weight management in children and adolescents.

BACKGROUND: Significant dropout rates remain a serious concern in pediatric weight control program, but few studies have identified predictors of dropout. AIMS: The objective of the study is to identify factors associated with dropout from a pediatric lifestyle modification weight control program at different phases. METHODS: Data on overweight and obese participants (n = 242) aged 11-18 years in the Intervention for Childhood and Adolescent Obesity via Activity and Nutrition (ICAAN) study were collected at baseline, 6-months, and 24-months through self-report and a laboratory test. Logistic regression analysis was performed for those who dropped out during the first 6-months, and multivariate generalized estimating equation analysis identified longitudinal factors associated with those who dropped out after 24 months. RESULTS: Lower family functioning (OR = 2.30, 95% CI [1.18-4.46]), exercise group (OR = 0.36, 95% CI [0.15-0.86]), lower initial attendance rate (OR = 6.09, 95% CI [2.94-12.6]), and non-self -referral pathways (OR = 2.35, 95% CI [1.05-5.27]) were significantly associated with 6-month dropouts. For late dropout, lower family functioning (OR = 1.71, 95% CI [1.06-2.77]) and lower initial attendance rates (OR = 2.06, 95% CI [1.12-3.81]) remained significant. CONCLUSION: Family function and initial attendance rate were associated with lower dropout rates. Developing a supportive family environment and focusing on the early-stage factors at the intervention's outset may reduce overall dropout rates in obesity prevention intervention.

Increased Expression of Interleukin-12 in Lesional Skin of Atopic Dermatitis Patients with Psoriasiform Features on Histopathology: An Immunohistochemical Study.

BACKGROUND: Based on clinical and genetic differences, atopic dermatitis (AD) and psoriasis have been classified in two different diseases, but recently, some authors regarded them as in one spectrum. The histological similarities including epidermal hyperplasia between chronic stages of AD and psoriasis supports the presence of two diseases in one spectrum. OBJECTIVE: We investigated clinical and immunohistopathological characteristics of adult Korean patients with AD showing psoriasiform chronic dermatitis on histopathology. METHODS: In total, 59 Korean patients with chronic AD were enrolled. Clinical, laboratory, and histopathological features were compared between AD patients with psoriasiform features and those with non-psoriasiform chronic dermatitis features on histology. In addition, immunohistopathological characteristics were analyzed using antibodies for key regulatory and effector cytokines in psoriasis. RESULTS: Fifteen patients (25.4%) showed a more "psoriasiform" histological appearance. The lesions in patients with psoriasiform features often showed clearer boundaries and noticeable scaling. The interleukin (IL)-23 expression in the psoriasiform chronic dermatitis group was not different from that in the psoriasis group, but the IL-17 expression was less than that in the psoriasis group. In the case of IL-12, multiple dermal inflammatory cells with dendrites were stained in the psoriasiform chronic dermatitis group compared with the 2 other non-psoriasiform subgroups. CONCLUSION: The results suggest that IL-12 secreted from dermal inflammatory cells might be one of the important factors associated with the formation of psoriasiform features in chronic AD. However, further studies are required to better define the specific role of IL-12.

Hearing loss in Korean adolescents: The prevalence thereof and its association with leisure noise exposure.

The increasing use of personal listening devices (PLDs) has been accompanied by a rise in the prevalence of hearing loss (HL) in younger age groups. However, there have been few reports on the relationship between HL and leisure noise exposure (LNE) in adolescents. The purpose of our study was to investigate the prevalence of HL in students attending general middle and high schools and to identify factors affecting HL prevalence. A total of 2,879 nationally representative adolescents in the first years of middle and high school underwent audiometric testing and otological examinations, and completed questionnaires, from June to December 2016. A speech-frequency hearing loss (SFHL) was considered present when the pure tone averages (PTAs) at 0.5, 1, and 2 kHz were ≥ 15 dB and a high-frequency hearing loss (HFHL) was considered present when the PTAs at 3, 4, 6, and 8 kHz were ≥ 15 dB. About 17% of Korean adolescents exhibited at least slight HL. The prevalence rates of SFHL and HFHL in the poorer ear were 11.6% and 10.3%, respectively, among Korean adolescents. The use of local area network (LAN) gaming centers and an experience of being asked by others to lower earphone volume were associated with both SFHL and HFHL. It is important to avoid excessive LNE to prevent adolescent HL. Additionally, SFHL or HFHL in the poorer ear was associated with lower academic performance.

Principal Clinical Factors Predicting Therapeutic Outcomes After Surgical Drainage of Postoperative Cheek Cysts: Experience From a Single Center.

OBJECTIVES: Postoperative cheek cyst (POCC) is a late postoperative complication of radical maxillary sinus surgery including the Caldwell-Luc (C-L) operation. The present study aimed to evaluate the therapeutic outcomes of surgical treatment for POCC and to assess the clinical factors correlated to these outcomes. METHODS: This study included 57 patients (67 nostrils) diagnosed with POCC who underwent surgical drainage. The medical records of the patients were retrospectively reviewed for radiological findings, treatment modalities, residual symptoms, and recurrences. RESULTS: In total, 30 patients were male and 27 patients were female with a mean age of 55 years, and the patients were usually diagnosed with POCC 28.2 years after radical surgery. Endonasal endoscopic marsupialization was performed via inferior meatal antrostomy, and if possible, middle meatal antrostomy was performed at the same time. In patients with cysts that were difficult to reach using an endonasal endoscopic approach, additional open C-L approaches were performed. The median follow-up period was 19.4 months. Overall, adequate drainage and symptomatic relief were achieved in 91% (61/67) of the patients. The recurrence rate was significantly higher in patients who had anterolateral POCC. Failure to achieve symptomatic relief was correlated to a smaller cyst and the use of the open C-L approach for drainage. CONCLUSION: The location and size of the cyst as well as the use of the open surgical approach were important factors in predicting the therapeutic outcome of POCC. The time point of treatment and surgical approaches should be based on the above-mentioned findings.

Prediction of Obstructive Sleep Apnea Based on Respiratory Sounds Recorded Between Sleep Onset and Sleep Offset.

OBJECTIVES: To develop a simple algorithm for prescreening of obstructive sleep apnea (OSA) on the basis of respiratory sounds recorded during polysomnography during all sleep stages between sleep onset and offset. METHODS: Patients who underwent attended, in-laboratory, full-night polysomnography were included. For all patients, audio recordings were performed with an air-conduction microphone during polysomnography. Analyses included all sleep stages (i.e., N1, N2, N3, rapid eye movement, and waking). After noise reduction preprocessing, data were segmented into 5-s windows and sound features were extracted. Prediction models were established and validated with 10-fold cross-validation by using simple logistic regression. Binary classifications were separately conducted for three different threshold criteria at apnea hypopnea index (AHI) of 5, 15, or 30. Prediction model characteristics, including accuracy, sensitivity, specificity, positive predictive value (precision), negative predictive value, and area under the curve (AUC) of the receiver operating characteristic were computed. RESULTS: A total of 116 subjects were included; their mean age, body mass index, and AHI were 50.4 years, 25.5 kg/m2 , and 23.0/hr, respectively. A total of 508 sound features were extracted from respiratory sounds recorded throughout sleep. Accuracies of binary classifiers at AHIs of 5, 15, and 30 were 82.7%, 84.4%, and 85.3%, respectively. Prediction performances for the classifiers at AHIs of 5, 15, and 30 were AUC, 0.83, 0.901, and 0.91; sensitivity, 87.5%, 81.6%, and 60%; and specificity, 67.8%, 87.5%, and 94.1%. Respective precision values of the classifiers were 89.5%, 87.5%, and 78.2% for AHIs of 5, 15, and 30. CONCLUSION: This study showed that our binary classifier predicted patients with AHI of ≥15 with sensitivity and specificity of >80% by using respiratory sounds during sleep. Since our prediction model included all sleep stage data, algorithms based on respiratory sounds may have a high value for prescreening OSA with mobile devices.

Association between Physical Fitness and Cardiometabolic Risk of Children and Adolescents in Korea.

BACKGROUND: This study aimed to investigate the association between physical fitness and cardiometabolic health of Korean children and adolescents. METHODS: In total, 168 participants (89 boys and 79 girls) aged 10-16 years were recruited for the Intervention for Childhood and Adolescent Obesity via Activity and Nutrition Study in 2016. The subjects were categorized into two groups using the definition of metabolic syndrome by the International Diabetes Federation: metabolically unhealthy (with at least two of the five criteria) and healthy groups (with less than one criterion). Correlation analysis of the participants' general characteristics was performed. Odds ratios (ORs) of physical fitness for cardiometabolic risk were evaluated via logistic regression. RESULTS: Metabolically unhealthy children showed greater weight, height, and body mass index, higher Children's Depression Inventory score, and longer screen time than did the metabolically healthy children. Metabolically healthy children showed greater upper and lower extremity muscular strength than did the metabolically unhealthy children (P=0.04 and P<0.001, respectively). In the multiple logistic regression analysis, lower extremity muscle strength was inversely related to the clustered cardiometabolic risk of the children and adolescents with or without adjustment for confounders (OR, 4.32; 95% confidence interval [CI], 1.87-9.97; OR, 7.64; 95% CI, 1.55- 37.74, respectively). CONCLUSION: Physical fitness, especially lower extremity muscle strength, is significantly inversely associated with individual and clustered cardiometabolic risks in Korean children and adolescents.

Photobiomodulation of extracellular matrix enzymes in human nucleus pulposus cells as a potential treatment for intervertebral disk degeneration.

Intervertebral disc (IVD) degeneration is associated with imbalances between catabolic and anabolic responses, regulated by extracellular matrix (ECM)-modifying enzymes such as matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors of metalloproteinases (TIMPs). Potential contributing factors, such as interleukin (IL)-1ß and tumor necrosis factor (TNF)-α, derived from infiltrated, activated macrophages within IVD tissues, can trigger abnormal production of ECM-modifying enzymes and progression of IVD degeneration. Novel therapies for regulating ECM-modifying enzymes can prevent or ameliorate IVD degeneration. Photobiomodulation (PBM), known to regulate wound repair, exhibits regenerative potential by modulating biological molecules. This study examined the effects of PBM, administered at various wavelengths (630, 525, and 465 nm) and energy densities (16, 32, and 64 J/cm2), on the production of ECM-modifying enzymes in replicated degenerative IVD. Our results showed that PBM selectively inhibited the production of ECM-modifying enzymes in a dose- and wavelength-dependent manner, suggesting that it could be a novel tool for treating symptomatic IVD degeneration.

Electrical dynamic range is only weakly associated with auditory performance and speech recognition in long-term users of cochlear implants.

OBJECTIVE: The electrical dynamic range (EDR) has been suggested to be related to auditory performance in cochlear implant (CI) users. However, few reports have evaluated postlingual CI users who have used CIs for long periods in comparison with prelingual CI users. Here, we evaluated auditory perception and speech performance in terms of the EDR in long-term CI users. The EDR, and auditory and speech performances, were compared between pre- and post-lingual CI users. METHODS: We enrolled all patients who received CIs from April 2000 to December 2010 at Seoul National University Hospital, and who had ≥5 years of experience with CIs. The EDRs affording subjective responses at the threshold level (T-level) and comfortable level (C-level) were analyzed in terms of their relationships with pure tone audiometry levels, speech evaluation scores, including those on the Phonetically Balanced (PB) Word List test, vowel and consonant tests, a sentence test, and the Korean version of the Central Institute for the Deaf (K-CID) test; we also calculated Category in Auditory Performance (CAP) scores. RESULTS: We found no significant difference in the average EDR, CAP, K-CID, PB word, consonant, or vowel scores between pre- and post-lingual CI users. The EDR was weakly associated with the PB word (P = 0.003, r = 0.462) and consonant scores (P = 0.005, r = 0.438). Other speech evaluations, such as the CAP, K-CID, and vowel scores, were not significantly associated with the EDR T-level. We found no association between pure tone thresholds at 0.5, 1, or 2 kHz, and the speech evaluation scores or EDRs of low-, middle-, or high-frequency channels. CONCLUSIONS: The EDR was only weakly associated with speech performance, such as scores on consonant and PB word tests in long-term CI users, irrespective of pre- or post-lingual deafness status.

Initial Influenza Virus Replication Can Be Limited in Allergic Asthma Through Rapid Induction of Type III Interferons in Respiratory Epithelium.

Although asthmatics has been considered to be highly susceptible to respiratory viral infection and most studies have focused on exacerbation of asthma by influenza A virus (IAV) infection, few experimental evidences exist to directly demonstrate that asthmatic mice are actually resistant to IAV infection. Here, we show that asthmatic mice are not highly susceptible to IAV in the early stage of infection and type III interferon (IFN) maintains antiviral immune response in the lung of IAV-infected asthmatic mouse resulting in inhibition of initial viral spread. C57BL/6 mice with allergic asthma were infected with IAV (WS/33: H1N1) and survival rate, body weight, viral titer, histopathological findings of lung and cytokine profiles including IFNs and Th2 cytokines were measured. Notably, asthmatic mice were significantly resistant to IAV and showed lower viral load until 7 days after infection. Furthermore, IAV-infected asthmatic mice exhibited decreased Th2-related inflammation in lung tissue until 7 days. These increased antiviral resistant mechanism and reduced Th2 inflammation were attributable to rapid induction of type III IFNs and blockade of type III IFNs in asthmatic lung led to aggravated IAV infection and to enhance the production of Th2 cytokines. Asthmatic mice showed bi-phasic responses against IAV-caused lung infection such as rapid production of type III IFNs and subsequent induction of type II IFNs. Actually, IAV-infected asthmatic mice become vulnerable to IAV infection after 7 days with noticeable morbidity and severe weight loss. However, intranasal administration of type III IFNs protects completely asthmatic mice from IAV-mediated immunopathology and lung infection until 14 days after infection. Taken together, our study indicates that the rapid induction of type III IFN might be distinctive immunological findings in the respiratory tract of IAV-infected asthmatic mice at the early stage of infection and crucial for suppression of initial viral spread in vivo asthma accompanying with restriction of Th2 cytokine productions.

Phototherapy suppresses inflammation in human nucleus pulposus cells for intervertebral disc degeneration.

The etiology of intervertebral disc (IVD) degeneration accompanied by low back pain (LBP) is largely unknown, and there are no curative therapies. Painful IVD degeneration is associated with infiltrated macrophage-mediated inflammatory response of human nucleus pulposus (NP) cells. The present study aimed to address the hypothesis that pro-inflammatory cytokines derived from macrophages lead to the altered molecular phenotype of human NP cells and to investigate the effects of phototherapy (630, 525, 465 nm with 16, 32, 64 J/cm2) on pain-related cytokine interleukin (IL)-6 and chemokine IL-8 under inflammatory conditions in human NP cells. Human NP cells were treated with soluble factors derived from macrophages in an inflammatory microenvironment, similar to that found in degenerative IVD. Human NP cells were also treated with phototherapy (630, 525, 465 nm with 16, 32, 64 J/cm2), and their cytokine and chemokine levels were detected. The soluble factors caused modulated expression of IL-6, IL-8, and matrix metalloproteinases (MMPs) at the gene and protein levels, causing a shift toward matrix catabolism through the expression of MMPs and increased pain-related factors via preferential activation of the nuclear factor-kappa B (NF-κB) p50 protein. Importantly, phototherapy attenuated the protein and gene expression of pain-related factor IL-6 at all doses and wavelengths. Interestingly, phototherapy also modulated the protein and gene expression of IL-8, which is responsible for the anabolic response, at a wavelength of 465 nm at all doses, in human NP cells. These findings suggested that phototherapy, at an optimal dose and wavelength, might be a useful therapeutic tool to treat IVD degeneration.

Hepatic damage exacerbates cisplatin-induced acute kidney injury in Sprague-Dawley rats.

The objective of this study was to elucidate the effect of hepatic damage on cisplatin (CDDP)-induced acute kidney injury (AKI). Thioacetamide (TAA, 150 mg/kg), a hepatotoxicant, was intraperitoneally (i.p.) injected to male Sprague-Dawley rats for 3 d prior to CDDP (5 mg/kg, i.p.) injection. All animals were sacrificed 5 d after CDDP treatment, and urine or blood was obtained to measure various parameters. No significant changes in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity were observed after CDDP treatment. However, pretreatment with TAA significantly elevated ALT and AST activity. Serum blood urea nitrogen and creatinine levels significantly increased in CDDP-treated group compared to control. In addition, urinary excretion of novel protein-based biomarkers such as neutrophil gelatinase-associated lipocalin, vascular endothelial growth factor, kidney injury molecule-1, and tissue inhibitor of metalloproteinase-1 rose markedly in the CDDP-treated group. In particular, pretreatment with TAA markedly elevated CDDP-induced urinary excretion of protein-based nephrotoxic biomarkers compared with CDDP alone. Hematoxylin and eosin staining demonstrated that pretreatment with TAA following CDDP injection led to more severe tubular damage and apoptosis in rats compared with CDDP alone. Antioxidant status was significantly reduced in kidneys following pretreatment with TAA prior to CDDP. These findings indicate that liver injury enhanced the vulnerability of kidney to CDDP-induced AKI and this phenomenon may be associated with severe apoptotic damage.