Impact of national health insurance and socioeconomic disparities on newborn hearing screening performance in South Korea: A nationwide population-based evaluation.

OBJECTIVES: This study aimed to assess the impact of national health insurance coverage on newborn hearing screening (NHS) outcomes by analyzing hearing questionnaires from the National Infant Health Check-up Program (NIHCP) in South Korea. METHODS: This study evaluated the performance and referral rates of NHS using nationwide data from 814,875 infants enrolled in the 4-month NIHCP from January 2017 to December 2019. This period encompasses the periods before and after the National Health Insurance in South Korea began covering NHS expenses in October 2018. The study also investigated household income levels to determine their relationship with participation in the NIHCP and NHS outcomes. RESULTS: The performance of NIHCP increased year-on-year, with NHS performance rates increasing from 88.5 % in 2017 to 91.5 % in 2019. Analysis by household income level revealed that the medical benefit recipients' group had the lowest NHS performance rate of 81.9 % in 2019, whereas that of the higher income level group exceeded 90 %. The NHS referral rate remained consistent at 0.9 % nationally during the study period. CONCLUSION: The inclusion of NHS in national insurance coverage positively influenced its performance rates across South Korea. Nevertheless, the data indicate the need for more focused and customized support for low-income families to enhance early hearing detection and interventions in newborns and infants.

Pediatric Benign Paroxysmal Positional Vertigo: Degree of Nystagmus and Concurrent Dizziness Differs from Adult BPPV.

Background: Benign paroxysmal positional vertigo (BPPV) is characterized by brief, intense episodes of vertigo triggered by abrupt changes in head position. It is generally accepted as being most common in adults, while it is regarded as rare in children. It is necessary to compare the disease between pediatric and adult patients for a better understanding of the disease's characteristics and its natural history. This study aimed to identify the clinical characteristics of BPPV in children and compare them with those of adult BPPV patients. Methods: All children ≤ 18 years old who were diagnosed with BPPV were selected by searching the electronic database of our hospital. Clinical features were identified by medical record review. For adult patients, we collected data from patients > 19 years of age. Results: A total of 30 pediatric (13.65 ± 4.15 years old) and 264 adult patients (60.86 ± 13.74 years old) were included in the study. Among pediatric patients, the lateral canals were involved in 80% and the posterior canals in 16.67%. In adult patients, the lateral and posterior canals were involved similarly (p = 0.007). The degree of nystagmus in pediatric patients was 6.82 ± 12.09, while in adults it was 15.58 ± 20.90 (p < 0.001). The concurrent dizziness disorder was higher in the pediatric group and recurrence was higher in the adult group. In the regression analysis, it was found that adult patients had a stronger nystagmus with a value of 6.206 deg/sec, and the risk of concurrent dizziness disorder was found to be 5.413 times higher in the pediatric group (p < 0.05). Conclusions: BPPV occurs in pediatric patients with lower prevalence, but it cannot be overlooked. In the pediatric group, a relatively high proportion of patients demonstrated lateral canal involvement, weaker nystagmus, and additional dizziness disorder.

Amphiregulin normalizes altered circuit connectivity for social dominance of the CRTC3 knockout mouse.

Social hierarchy has a profound impact on social behavior, reward processing, and mental health. Moreover, lower social rank can lead to chronic stress and often more serious problems such as bullying victims of abuse, suicide, or attack to society. However, its underlying mechanisms, particularly their association with glial factors, are largely unknown. In this study, we report that astrocyte-derived amphiregulin plays a critical role in the determination of hierarchical ranks. We found that astrocytes-secreted amphiregulin is directly regulated by cAMP response element-binding (CREB)-regulated transcription coactivator 3 (CRTC3) and CREB. Mice with systemic and astrocyte-specific CRTC3 deficiency exhibited a lower social rank with reduced functional connectivity between the prefrontal cortex, a major social hierarchy center, and the parietal cortex. However, this effect was reversed by astrocyte-specific induction of amphiregulin expression, and the epidermal growth factor domain was critical for this action of amphiregulin. These results provide evidence of the involvement of novel glial factors in the regulation of social dominance and may shed light on the clinical application of amphiregulin in the treatment of various psychiatric disorders.

Hearing loss in neonates and infants.

Hearing in neonates and infants is crucial for their development of language and communication skills. Unless hearing loss is appropriately managed early, it can cause a significant socioeconomic burden considering its detrimental impact on the child's development and its common nature. It is also the most common congenital sensory deficit, with an approximate incidence of 1.5 per 1,000 newborns. Its etiologies are heterogeneous: genetic causes are reportedly involved in up to 80% of cases, while congenital cytomegalovirus infection is the leading environmental factor contributing to congenital hearing loss. The introduction of newborn hearing screening using automated auditory brainstem response and/or automated otoacoustic emission in many developed countries has helped detect and manage hearing loss early. Current auditory rehabilitation options such as cochlear implantation implementing cutting-edge technologies can treat almost all degrees of hearing loss, emphasizing the importance of early hearing detection and intervention. Rapidly developing genetic diagnostic technologies and future cutting-edge treatment options, including gene therapy, will shed light on the future management of hearing loss in neonates and infants.

Status of the Newborn Hearing Screening in the 4-Months Age National Infant Health Checkup in Korea: A Nationwide Population-Based Study.

BACKGROUND: The aims of this study are to review data on 4-months age National Health Screening Program for Infants and Children (NHSPIC) using a National Health Insurance Service (NHIS) database, and to analyze the newborn hearing screening (NHS) results and related characteristics of the 4-months NHSPIC for 7 years in South Korea. METHODS: We analyzed a NHIS database of infants who had participated in the 4-month age NHSPIC from 2010 to 2016. According to the results of hearing questionnaires and physical examination, we analyzed the outcomes of NHS and related infantile and socioeconomic factors. RESULTS: Among 3,128,924 of total eligible infants in Korea between the year 2010 and 2016, 69.2% (2,164,621 infants) conducted 4-months age NHSPIC, and 94.4% (2,042,577 infants) of which performed hearing questionnaires regarding NHS. Among the total hearing examinees, premature infants accounted for 3.6%, infants who were hospitalized in the neonatal intensive care unit (NICU) for more than 5 days accounted for 5.6%, and infants with head and neck abnormalities were 0.6%. The NHS performing rate was 79.1% for total hearing examinees in 2010, but gradually increased to 88.9% in 2016. The NHS performing rate in 2016 was 93.4% for premature infants, 91.7% for NICU hospitalized babies. The mean referral rate was 0.6% for total hearing examinees, 1.4% for premature infants, and 2.3% for NICU hospitalized babies. When we analyzed the NHS performing rate and the referral rate according to the household income level, the NHS performing rate of infants in Medical Aid programs was the lowest as 65.6%, and the NHS performing rates in other five levels of NHIS was higher ranging between 85.1% to 86.0%. The referral rate of infants in the Medical Aid program (3.8%) was significantly higher than those of infants in other classes (1.10-1.25%). CONCLUSION: The estimated overall NHS performing rate in Korea gradually increased and was 88.9% in 2016. The overall referral rate was low as 0.6%, and it was significantly different depending on the infant's health condition and household income levels. We assume that our finding would help to establish policies managing hearing impaired children, and to develop the customized hearing care service programs considering the household economic levels.

Analysis of Newborn Hearing Screening Results in South Korea after National Health Insurance Coverage: A Nationwide Population-Based Study.

Newborn hearing screening (NHS) has been covered by national health insurance since October 2018 in Korea. However, the results of the NHS are not reported due to the absence of a follow-up tracking system. This study analyzed the status and the predicted referral rates of NHS after the Korean national health insurance coverage by analyzing the National Health Insurance Service database in 2019 and 2020. The NHS coverage was 91.7% of total birth in 2019 and 92.1% in 2020. The predicted referral rate of NHS calculated by the duplicated NHS cases was 1.05% in 2019 and 0.99% in 2020. However, another predicted referral rate calculated by the number of diagnostic auditory brainstem responses (ABRs) performed was 1.44% in 2019 and 1.43% in 2020. The first NHS was performed within one day of birth for 96.5% of the babies and within three days of birth for 97%. However, diagnostic ABR was adequately performed within three months of birth for only 4.3%, while 82.3% performed the test after six months which delays appropriate intervention for hearing loss. National support such as national coordinators, follow-up tracking, and data management systems are needed for early hearing detection and intervention of newborns and infants in Korea.

Effect of Endoscopic Sinus Surgery on Eustachian Tube Function in Adult Sinusitis Patients: A Prospective Case-Control Study.

The eustachian tube (E-tube) function is known to be related with sinusitis; however, the effect of endoscopic sinus surgery (ESS) on E-tube function is not clearly documented. This study aimed to prospectively evaluate the function of the E-tube by using both subjective and objective tests in adult chronic sinusitis patients undergoing ESS, and to compare with those of the patients without sinusitis. Thirty adult patients who underwent ESS for treatment of chronic sinusitis and another thirty patients without sinusitis who underwent other nasal surgeries (septoplasty, rhinoplasty, or closed reduction) were evaluated and compared for E-tube function before and after three months of their surgeries. The E-tube function tests included the seven-item eustachian tube dysfunction questionnaire (ETDQ-7), Valsalva test, and inflation-deflation test that were compared preoperatively and postoperatively in both groups. Compared with the group without sinusitis, the ESS group showed significant improvement of E-tube function after surgery in the ETDQ-7 (p = 0.002), right Valsalva test (p = 0.015), right deflation test (p = 0.005), and left deflation test (p = 0.006). A binary logistic regression analysis revealed that ESS significantly improved E-tube function in the right Valsalva test in a univariate (p = 0.021) and multivariate analysis (p = 0.008), and E-tube function in the left deflation test in a univariate (p = 0.021) and multivariate analysis (p = 0.039). These findings indicate that E-tube function is significantly improved after ESS in adult sinusitis patients, and that the presence of sinusitis and implementation of ESS should be considered (if sinusitis is present) in managing patients with ear diseases that are affected by E-tube function.

Analysis of the Referral Rates of Newborn Hearing Screening Test According to Childbirth Delivery Methods in Neonatal Care Units.

It is known that neonates born by cesarean delivery (CD) may have higher referral rates than those born by vaginal delivery (VD) for newborn hearing screening (NHS). False-positive NHS results can increase costs and parental anxiety. This study analyzed the differences in NHS referral rates according to delivery methods in Level I, II, and III neonatal care units. A retrospective chart review was done for 2322 infants (4644 ears) with delivery records who underwent NHS between 2004 and 2017. The first NHS was performed immediately before discharge when the infant was in good condition via the automated auditory brainstem response (AABR) or automated otoacoustic emissions (AOAE). There were 98 neonates (196 ears) who underwent both AABR and AOAE simultaneously as the first NHS, 30 of which failed. We used a total of 4810 ears in this analysis. Of all enrolled ears, 2075 ears were of neonates born by CD, and 2735 ears were of neonates born by VD. A total of 2460 ears were from patients in Level III neonatal intensive care units (NICU) and 2350 ears were from Level I and II neonatal care units. The overall referral rate was higher in infants born via CD (4.5%) than VD (3.2%). In Level I and II neonatal intensive care units, the referral rate was significantly higher in those born via CD (3.0%) than via VD (1.4%). Further, based on the screening method, AABR (75.8%) was more frequently used than AOAE (24.2%), thereby revealing AABR's higher referral rate in CD (2.9%) than in VD (1.2%). The referral rate of infants who underwent the NHS within three days of birth was higher in the CD group (3.0%) than in the VD group (1.3%). There was no significant difference in the referral rate depending on the delivery method when infants were hospitalized for more than four days or hospitalized in the NICU. The referral rate according to the delivery methods was significantly higher when the NHS test was performed for healthy newborns in the Level I and II neonatal care units born by CD within 72 h using AABR. Therefore, we recommend that the hearing screening test for newborns delivered by cesarean section be performed after 72 h of age. The results of this study may reduce the false-positive NHS results, unnecessary further tests, and parental anxiety.

Transcriptomic analysis of tobacco-flavored E-cigarette and menthol-flavored E-cigarette exposure in the human middle ear.

Electronic cigarettes (e-cigarettes) are the most widely used electronic nicotine delivery systems and are designed to imitate smoking and aid in smoking cessation. Although the number of e-cigarette users is increasing rapidly, especially among young adults and adolescents, the potential health impacts and biologic effects of e-cigarettes still need to be elucidated. Our previous study demonstrated the cytotoxic effects of electronic liquids (e-liquids) in a human middle ear epithelial cell (HMEEC-1) line, which were affected by the manufacturer and flavoring agents regardless of the presence of nicotine. In this study, we aimed to evaluate the gene expression profile and identify potential molecular modulator genes and pathways in HMEEC-1 exposed to two different e-liquids (tobacco- and menthol-flavored). HMEEC-1 was exposed to e-liquids, and RNA sequencing, functional analysis, and pathway analysis were conducted to identify the resultant transcriptomic changes. A total of 843 genes were differentially expressed following exposure to the tobacco-flavored e-liquid, among which 262 genes were upregulated and 581 were downregulated. Upon exposure to the menthol-flavored e-liquid, a total of 589 genes were differentially expressed, among which 228 genes were upregulated and 361 were downregulated. Among the signaling pathways associated with the differentially expressed genes mediated by tobacco-flavored e-liquid exposure, several key molecular genes were identified, including IL6 (interleukin 6), PTGS2 (prostaglandin-endoperoxide synthase 2), CXCL8 (C-X-C motif chemokine ligand 8), JUN (Jun proto-oncogene), FOS (Fos proto-oncogene), and TP53 (tumor protein 53). Under menthol-flavored e-liquid treatment, MMP9 (matrix metallopeptidase 9), PTGS2 (prostaglandin-endoperoxide synthase 2), MYC (MYC proto-oncogene, bHLH transcription factor), HMOX1 (heme oxygenase 1), NOS3 (nitric oxide synthase 3), and CAV1 (caveolin 1) were predicted as key genes. In addition, we identified related cellular processes, including inflammatory responses, oxidative stress and carcinogenesis, under exposure to tobacco- and menthol-flavored e-liquids. We identified differentially expressed genes and related cellular processes and gene signaling pathways after e-cigarette exposure in human middle ear cells. These findings may provide useful evidence for understanding the effect of e-cigarette exposure.

Analysis of the Risk Factors Associated with Hearing Loss of Infants Admitted to a Neonatal Intensive Care Unit: A 13-Year Experience in a University Hospital in Korea.

Early detection of hearing loss in neonates is important for normal language development, especially for infants admitted to the neonatal intensive care unit (NICU) because the infants in NICU have a higher incidence of hearing loss than healthy infants. However, the risk factors of hearing loss in infants admitted to the NICU have not been fully acknowledged, especially in Korea, although they may vary according to the circumstances of each country and hospital. In this study, the risk factors of hearing loss in NICU infants were analyzed by using the newborn hearing screening (NHS) and the diagnostic auditory brainstem response (ABR) test results from a 13-year period. A retrospective chart review was performed using a list of NICU infants who had performed NHS from 2004 to 2017 (n = 2404) in a university hospital in Korea. For the hearing loss group, the hearing threshold was defined as 35 dB nHL or more in the ABR test performed in infants with a 'refer' result in the NHS. A four multiple number of infants who had passed the NHS test and matched the age and gender of the hearing loss group were taken as the control group. Various patient factors and treatment factors were taken as hearing loss related variables and were analyzed and compared. From the 2404 infants involved, the prevalence of hearing loss was 1.8% (n = 43). A comparison between the hearing loss group (n = 43) and the control group (n = 172) revealed that history of sepsis, peak total bilirubin, duration of vancomycin use, days of phototherapy, and exposure to loop-inhibiting diuretics were significantly different, and can be verified as significant risk factors for hearing loss in NICU infants.

Status of early hearing detection and intervention in South Korea: a nationwide population-based study of national infant health checkup.

The aim of this study was to evaluate the status of early hearing detection and intervention after newborn hearing screening (NHS) in South Korea. A retrospective review of Korean national health insurance service data of all infants receiving the 4-month old national infant health checkup between 2010 and 2016 from a nationwide population-based database was conducted. Based on the results of the NHS-administered hearing questionnaires as part of the national infant health checkup, individuals were classified into "pass" (1,730,615 infants) or "refer" (10,941 infants) groups. Next, an analysis was conducted of age and the frequencies of tracking audiologic tests and surgeries of the middle ear (ME) and cochlear implants (CI). Diagnostic auditory brainstem response and audiometry, and surgeries of ME and CI were significantly performed more and earlier in the refer group compared with the pass group. For infants in the pass group who were presumed to have delayed or acquired hearing loss, the time of the first audiology tests and CI surgery was significantly delayed compared to those in the refer group; the average ages for first CI were 37 and 52 months in the refer group and pass group, respectively. Therefore, for early detection of delayed-onset hearing loss, regular hearing screening programs should be considered throughout the preschool ages.

Analysis of the effectiveness of coupon-mediated newborn hearing screening program through comparison of two government-funded pilot projects in South Korea.

OBJECTIVE: The aims of this study are to compare the results of two government-funded newborn hearing screening (NHS) pilot programs and evaluate the feasibility and the effectiveness of the coupon-mediated NHS program in Korea. METHODS: We retrospectively analyzed the database of the NHS center of the Ministry of Health and Welfare (MHW) from 2007 to 2013. Before the NHS was covered by national health insurance in 2018, the MHW conducted two types of NHS pilot programs. For the first pilot program, the MHW initiated an area based universal newborn hearing screening (UNHS) program which initially included 16 in 2007 and then spreading to 32 administrative areas in 2008 for all newborns in the pilot areas regardless of income level. The second pilot program was an offshoot of the continuing expansion of the first pilot program, which was a nationwide coupon-mediated NHS program for low-income families from 2009. The hearing loss (HL) was defined as a threshold of 40 dB nHL or worse on the auditory brainstem response (ABR) test. In both NHS pilot programs, the government financially supported the cost of the first NHS test and one ABR test for an infant who did not pass NHS test. RESULTS: During the 1st NHS pilot program, 29.8% of the target neonates were screened which was 3.9% of total births; during the 2nd NHS pilot program 81.1% of the target neonates were screened which was 8.8% of total births. Documented diagnostic ABR tests were performed in 12.4% of referred infants in the 1st program and 33.5% in the 2nd program. The prevalence of HL was 0.11% in the 1st program and 0.15% in the 2nd program. In the 2nd NHS coupon-mediated program, the NHS was performed on average 5.4 ± 8.7 days after birth, and the diagnostic ABR test in the referred infants were performed on 61.3 ± 45.0 days after birth. There was no comparable recorded data in the 1st NHS pilot program. CONCLUSIONS: This study suggests that the coupon-mediated NHS pilot program may be a worthwhile government-led NHS project for the proper tracking and accurate statistics. This program helped formulate UNHS national health insurance policies. However, to become a successful UNHS program, the governmental supports for both timely interventions and the inauguration of a web tracking system are mandatory.

Comparison of newborn hearing screening results between well babies and neonates admitted to the neonatal intensive care unit for more than 5 days: Analysis based on the national database in Korea for 9 years.

OBJECTIVE: The purpose of this cohort study is to compare newborn hearing screening (NHS) results between healthy newborns and neonates who were admitted to the neonate intensive care unit (NICU) for more than 5 days based on the national database for 9 years. Ultimately, we've tried to analyze the associated factors necessary to manage the national NHS program according to the group, which would help to establish policy to effectively detect and support hearing impaired children and which would help to control qualities. METHODS: The Ministry of Health and Welfare (MHW) introduced a nationwide coupon-mediated program for the low-income class since 2009. The coupon consisted of two parts, the screening part and the confirming parts with the same unique number, and the MHW supported the cost of one screening test and one diagnostic auditory brainstem response (ABR) test for infants who did not pass from the screening test. We have analyzed the screening test performing rate, the referral rate according to the screening methods or institutions, the prevalence of hearing loss, and the average age of hearing loss diagnosis. Hearing loss was defined as any hearing impairment either unilateral or bilateral with the hearing threshold ≥ 40 dB nHL on the diagnostic ABR test, irrespective of its etiology. RESULTS: A total of 524,371 newborns were enrolled in the study, and 506,634 (96.6%) neonates were in the "well-baby group (WBG)", while 17,737 (3.4%) were in the "high-risk group (HRG)". The referral rate of the screening test was 1.5% in average, 1.3% in the WBG, and 7.5% in the HRG. The referral rates varied according to the screening methods and screening institutions. The adjusted prevalence of HL was 5.6/1,000 in average, 4.6/1,000 in the WBC, and 28.8/1,000 in the HRG. The screening tests were performed 4.3 ± 6.7 days after birth and the diagnostic tests were done 62.7 ± 37.5 days after birth in WBG. In HRG, dates were 17.7 ± 19.3 days and 97.6 ± 51.4 days, respectively. CONCLUSIONS: The prevalence of hearing loss in infants who were hospitalized in NICU for more than 5 days was about seven times higher than that in healthy newborns. However, different referral rates were noted depending on both institutions and the screening methods. These differences need to be addressed in order to improve our program and ensure that all neonates with hearing loss, especially neonates with high risk factor, are detected and appropriately referred for the treatment.

Clinically Relevant Extended-Spectrum ß-Lactamase-Producing Escherichia coli Isolates From Food Animals in South Korea.

Extended-spectrum ß-lactam antimicrobials have been broadly used in food animals and humans to control infectious diseases. However, the emergence and rapid spread of extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae, mainly Escherichia coli, have seriously threatened global health in recent decades. In this study, we determined the prevalence, antimicrobial susceptibility, and genetic properties of ESBL-producing E. coli (ESBL-EC) strains isolated from food animals in South Korea. A total of 150 fecal samples from healthy chickens (n = 34), pigs (n = 59), and cattle (n = 57) were screened from January to July 2018. Among these, 77 non-duplicate cefotaxime-resistant ESBL-EC strains were isolated from 32 chicken, 41 pig, and 4 cattle samples, with the corresponding occurrence rates of 94.1, 69.5, and 7.0%, respectively. All the isolates showed multidrug resistance (MDR) and produced at least one type of ß-lactamase, including CTX-M (98.7%) and TEM (40.3%). CTX-M-14 (53.1%), CTX-M-55 (53.7%), and CTX-M-65 (50.0%) were the predominant genotypes in the chicken, pig, and cattle samples, respectively. Multilocus sequence typing revealed 46 different sequence types (STs), including the human-associated extraintestinal pathogenic E. coli ST131 (n = 2), ST10 (n = 5), ST38 (n = 1), ST410 (n = 4), ST354 (n = 2), ST58 (n = 3), ST117 (n = 1), and ST457 (n = 1). To the best of our knowledge, this is the first report of pandemic E. coli ST131 in non-human isolates in South Korea. Our results demonstrate the high prevalence and diversity of MDR-ESBL-EC in food animals and highlight them as potential pathogenic ESBL-EC reservoirs that may pose a high risk to human health.

Development of a dried blood spot sampling method towards therapeutic monitoring of radotinib in the treatment of chronic myeloid leukaemia.

WHAT IS KNOWN AND OBJECTIVE: Dried blood spot (DBS) sampling is a minimally invasive method of blood sampling that enables monitoring of drug concentrations to be more convenient. This study aimed at developing a DBS sampling method for an accurate and precise prediction of radotinib plasma concentrations (Cp ) in patients with chronic myeloid leukaemia (CML). METHODS: Dried blood spot and venous blood samples were simultaneously collected from fifty CML patients who had been receiving radotinib for at least a week. Radotinib concentrations were measured using a high-performance liquid chromatographic method with tandem mass spectrometric detection. Unmeasured Cp was predicted directly based on a Deming regression between DBS concentrations (CDBS ) and Cp . Unmeasured Cp was also predicted from CDBS corrected by each patient's haematocrit (Hct). Both prediction methods were evaluated for their accuracy and precision using Deming regression and Bland-Altman analysis. RESULTS AND DISCUSSION: The Deming regression equation between CDBS and Cp was obtained as follows: Cp  = 1.34∙CDBS  + 4.26 (r2  = .97). Cp was directly predictable using Cp,pred1  = 1.34∙CDBS  + 4.26. With Hct correction, Cp was alternatively predictable using Cp,pred2  = CDBS / (1-Hct + Hct2 ). The slopes of Deming regression line between predicted and measured Cp were 0.99 and 1.02 for the direct and Hct-corrected method, respectively. The mean biases (accuracy) were -0.44% and 1.6% with the 95% limits of agreement (precision) of -22.4% to 21.5% and -20.5% to 23.7%, respectively. More than 93% of predicted and measured Cp pairs had their differences within 20% of the mean of each pair in both methods. WHAT IS NEW AND CONCLUSIONS: Radotinib CDBS are highly correlated with radotinib Cp. Radotinib Cp can be accurately and precisely predicted from CDBS using direct or Hct-corrected prediction methods. Both appear to be appropriate for the therapeutic monitoring of radotinib in patients with CML.

3-Benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H)-one suppresses FcεRI-mediated mast cell degranulation via the inhibition of mTORC2-Akt signaling.

Mast cells express high-affinity IgE receptor (FcεRI) on their surface, cross-linking of which leads to the immediate release of proinflammatory mediators such as histamine but also late-phase cytokine secretion, which are central to the pathogenesis of allergic diseases. Despite the growing evidences that mammalian target of rapamycin (mTOR) plays important roles in the immune system, it is still unclear how mTOR signaling regulates mast cell function. In this study, we investigated the effects of 3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H)-one (3BDO) as an mTOR agonist on FcεRI-mediated allergic responses of mast cells. Our data showed that administration of 3BDO decreased ß-hexosaminidase, interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) release in murine bone marrow-derived mast cells (BMMCs) after FcεRI cross-linking, which was associated with an increase in mTOR complex 1 (mTORC1) signaling but a decrease in activation of Erk1/2, Jnk, and mTORC2-Akt. In addition, we found that a specific Akt agonist, SC79, is able to fully restore the decrease of ß-hexosaminidase release in 3BDO-treated BMMCs but has no effect on IL-6 release in these cells, suggesting that 3BDO negatively regulates FcεRI-mediated degranulation and cytokine release through differential mechanisms in mast cells. The present data demonstrate that proper activation of mTORC1 is crucial for mast cell effector function, suggesting the applicability of the mTORC1 activator as a useful therapeutic agent in mast cell-related diseases.

Pregnancy Does Not Increase the Risk of Bell's Palsy: A National Cohort Study.

OBJECTIVES: The objective of this study was to compare the incidence of Bell's palsy between women during pregnancy or postpartum periods and non-pregnant/non-postpartum women (controls). METHODS: Using the national cohort from the Korean Health Insurance Review and Assessment Service, pregnant/postpartum participants (63,264) and control participants (126,528) were matched in a 1:2 ratio based on age, income, region of residence, and medical history. The incidence of Bell's palsy in both groups was measured from pregnancy to 1 year postpartum. RESULTS: Among the 63,264 pregnant/postpartum participants, 20 were diagnosed with or treated for Bell's palsy during pregnancy, and 38 during postpartum periods. The annual incidence of Bell's palsy per 100,000 women during pregnancy was 43.4 in the patient group and 80.2 in the control group (p < 0.05), and that during postpartum periods was 60.1 the patient group and 50.6 in the control group (p > 0.05). CONCLUSION: The annual incidence of Bell's palsy was not increased in pregnant women relative to that in the control.

Referral rates for newborn hearing screening based on the test time.

OBJECTIVES: To suggest the optimal timing for newborn hearing screening to obtain an ideal and stable referral rate in well babies and in babies in neonatal intensive care units (NICU). METHODS: This study analyzed nationwide hearing screening data of 71,596 newborns in the low-income families who received support from the government in 2017. The referral rate for neonatal hearing screening, based on the period from birth to screening, was compared in well babies (n = 68,206) who were born healthy or hospitalized in the NICU for < 5 days and moved to a well-baby nursery and babies (n = 3,390) who were in the NICU for ≥ 5 days. RESULTS: In well babies, most screenings (73.1%) were performed in the first three days of life. Most babies (74%) in the NICU underwent screening within the first 20 days after birth. The referral rates for babies at 32-60 days after birth differed from those of other screening days, except for the rates at 21-31 days after birth. Referral rates for NHS at > 60 days after birth were significantly higher than those for other periods in babies overall. However, the incidence of hearing loss according to age did not differ significantly within or between groups. CONCLUSIONS: Referral rates based on the period from birth to screening were significantly different between well babies and NICU babies. To reduce and ensure stable referral rates, we recommend that the hearing screening be performed between 2 and 20 days after birth for well babies and between 5 and 31 days after birth for NICU babies.

Auditory Cortical Plasticity and Reorganization in Rats With Single-Sided Deafness During Early Developmental Period.

OBJECTIVE: We aimed to examine the serial change of sound-specific auditory cortical activation patterns in age-matched normal hearing (NH) and young single-sided deafness (YSSD) rats to understand the critical period that influences a benefit of a binaural hearing. METHOD: Experiments were performed on the age-matched 64 Sprague-Dawley rats; NH group = 45 rats, and YSSD group = 19 rats. NH rats were evaluated the multi-unit neural activities from the age of post-14 days (P14ds) to P73ds by week interval. For YSSD group, left-side cochlear ablations were done at the age of P10ds, and multineural recordings were implemented at the post-deafening (PD) 2 weeks (W), PD4W, PD6W, and PD8W, with age matching. After craniotomy, tungsten wire-based 16-channel microelectrode array was inserted to the surface of the auditory cortex. Gaussian white sound stimulation was introduced to the right ear every 500 ms, and analyses were performed of the Peri-stimulus time histogram. The parameters, including peak latency, peak amplitude, total responsive area, and index of contralaterality, were evaluated. RESULTS: In NH group, larger peak amplitude and total responsive area and shorter peak latency of the contralateral hemisphere to sound stimulation were observed in all ages. Interestingly, YSSD group demonstrated that total reactive area in the contralateral side was significantly smaller than that in the ipsilateral side at PD2W and PD4W, indicating the disappearance of contralateral dominance within PD4W. Subsequently, monaural stimulation from the hearing ear exclusively activated the contralateral hemisphere at PD6W and PD8W. CONCLUSION: Early onset of unilateral deafening leads to the alternation of contralateral dominance in the early period, replaced by faster and massive reorganization toward the ipsilateral cortex. But, gradual adaptation in the contralateral side was exclusively observed. Given the short critical period in the young SSD model, early intervention may be crucial for the development of binaural hearing if SSD occurs early in life.

A Mobile Videoconference-Based Intervention on Stress Reduction and Resilience Enhancement in Employees: Randomized Controlled Trial.

BACKGROUND: Videoconferencing-based treatments have shown great potential in increasing engagement and compliance by decreasing the barriers of time and distance. In general, employees tend to experience a lot of stress, but find it difficult to visit a clinic during office hours. OBJECTIVE: The purpose of this study was to investigate the effectiveness of a mobile videoconference-based intervention for stress reduction and resilience enhancement in employees. METHODS: In total, 81 participants were randomly allocated to one of the three conditions: mobile videoconferencing, in-person, and self-care; of these, 72 completed the study. All participants underwent assessment via self-reported questionnaires before, immediately after, and 1 month after the intervention. Intervention lasted for 4 weeks and consisted of elements of cognitive behavioral therapy, positive psychology, and meditation. Changes in clinical variables regarding stress and resilience across time were compared between treatment conditions. RESULTS: There were significant condition × time effects on variables measuring perceived stress, resilience, emotional labor, and sleep, demonstrating significantly differential effects across time according to treatment condition. Moreover, there were significant effects of condition on perceived stress and occupational stress. There were no significant differences in any variable between the mobile videoconferencing and in-person conditions at 1 month after the intervention. CONCLUSIONS: Results indicate that both mobile videoconferencing and in-person interventions were comparably effective in decreasing stress and enhancing resilience. Further studies with a larger sample size and a longer follow-up period are warranted to investigate the long-term effect of mobile videoconferencing interventions. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03256682; https://clinicaltrials.gov/ct2/show/NCT03256682 (Archived by WebCite at http://www.webcitation.org/71W77bwnR).