Environmental toxicants have been linked to aging and age-related diseases. The emerging evidence has shown that the enhancement of detoxification gene expression is a common transcriptome marker of long-lived mice, Drosophila melanogaster, and Caenorhabditis elegans. Meanwhile, the resistance to toxicants was increased in long-lived animals. Here, we show that farnesoid X receptor (FXR) agonist obeticholic acid (OCA), a marketed drug for the treatment of cholestasis, may extend the lifespan and healthspan both in C. elegans and chemical-induced early senescent mice. Furthermore, OCA increased the resistance of worms to toxicants and activated the expression of detoxification genes in both mice and C. elegans. The longevity effects of OCA were attenuated in Fxr ^-/- mice and Fxr homologous nhr-8 and daf-12 mutant C. elegans. In addition, metabolome analysis revealed that OCA increased the endogenous agonist levels of the pregnane X receptor (PXR), a major nuclear receptor for detoxification regulation, in the liver of mice. Together, our findings suggest that OCA has the potential to lengthen lifespan and healthspan by activating nuclear receptor-mediated detoxification functions, thus, targeting FXR may offer to promote longevity.

Objective: To establish the reference standard of the median nerve conduction study (NCS) in Korea. Methods: A total of 648 median motor and 602 median sensory NCSs from 349 Korean healthy volunteers were tested and analyzed prospectively. Equipment calibration, assessment of intraand inter-rater reliability, and the NCSs per se were conducted according to a predetermined protocol. A reference standard was established from uncertainty components for the following parameters: the onset and peak latencies; the baseline-to-peak and peak-to-peak amplitudes; the area and duration of the negative wave; and the nerve conduction velocity. The effects of sex, age and stimulation intensity were analyzed. Results: Each measured value of 648 median motor and 602 median sensory nerves were obtained and presented with both mean and expanded uncertainties, as well as mean and standard deviations. The cut-off values with expanded uncertainty were determined for different age and sex groups. After adjusting for anthropometric covariates, all parameters except duration were affected by age, and sex appeared to influence both duration and area. While stimulation intensity significantly affected some parameters including latencies, the effect sizes were negligible. Conclusion We propose the median NCS reference standard using the largest Korean dataset ever available. The use of the traceable and reliable reference standard is anticipated to promote more accurate and dependable diagnosis and appropriate management of median neuropathies in Korea.

Background: Tinnitus is a bothersome condition associated with various symptoms. However, the mechanisms of tinnitus are still uncertain, and a standardized assessment of the diagnostic criteria for tinnitus is required. We aimed to reach a consensus on diagnosing tinnitus with professional experts by conducting a Delphi study with systematic review of the literature. Methods: Twenty-six experts in managing tinnitus in Korea were recruited, and a two-round modified Delphi study was performed online. The experts evaluated the level of agreement of potential criteria for tinnitus using a scale of 1–9. After the survey, a consensus meeting was held to establish agreement on the results obtained from the Delphi process. Consensus was defined when over 70% of the participants scored 7–9 (agreement) and fewer than 15% scored 1–3 (disagreement). To analyze the responses of the Delphi survey, the content validity ratio and Kendall’s coefficient of concordance were evaluated. Results: Consensus was reached for 22 of the 38 statements. For the definition of tinnitus, 10 out of 17 statements reached consensus, with three statements achieving complete agreement including; 1) Tinnitus is a conscious perception of an auditory sensation in the absence of a corresponding external stimulus, 2) Tinnitus can affect one’s quality of life, and 3) Tinnitus can be associated with hearing disorders including sensorineural hearing loss, vestibular schwannoma, Meniere’s disease, otosclerosis, and others. For the classification of tinnitus, 11 out of 18 statements reached consensus. The participants highly agreed with statements such as; 1) Vascular origin is expected in pulse-synchronous tinnitus, and 2) Tinnitus can be divided into acute or chronic tinnitus. Among three statements on the diagnostic tests for tinnitus only Statement 3, “There are no reliable biomarkers for sensory or emotional factors of tinnitus.”reached consensus. All participants agreed to perform pure-tone audiometry and tinnitus questionnaires, including the Tinnitus Handicap Inventory and Tinnitus Questionnaire. Conclusion We used a modified Delphi method to establish a consensus-based definition, a classification, and diagnostic tests for tinnitus. The expert panel reached agreement for several statements, with a high level of consensus. This may provide practical information for clinicians in managing tinnitus.

Background/Aims: To identify changes in symptoms and pulmonary sequelae in patients with coronavirus disease 2019 (COVID-19). Methods: Patients with COVID-19 hospitalized at seven university hospitals in Korea between February 2020 and February 2021 were enrolled, provided they had ≥ 1 outpatient follow-up visit. Between January 11 and March 9, 2021 (study period), residual symptom investigations, chest computed tomography (CT) scans, pulmonary function tests (PFT), and neutralizing antibody tests (NAb) were performed at the outpatient visit (cross-sectional design). Additionally, data from patients who already had follow-up outpatient visits before the study period were collected retrospectively. Results: Investigation of residual symptoms, chest CT scans, PFT, and NAb were performed in 84, 35, 31, and 27 patients, respectively. After 6 months, chest discomfort and dyspnea persisted in 26.7% (4/15) and 33.3% (5/15) patients, respectively, and 40.0% (6/15) and 26.7% (4/15) patients experienced financial loss and emotional distress, respectively. When the ratio of later CT score to previous ones was calculated for each patient between three different time intervals (1–14, 15–60, and 61–365 days), the median values were 0.65 (the second interval to the first), 0.39 (the third to the second), and 0.20 (the third to the first), indicating that CT score decreases with time. In the high-severity group, the ratio was lower than in the low-severity group. Conclusions In COVID-19 survivors, chest CT score recovers over time, but recovery is slower in severely ill patients. Subjects complained of various ongoing symptoms and socioeconomic problems for several months after recovery.

Objectives: The aim of this study was to determine the most effective treatment approach by comparing the impacts of various otolith reduction techniques in patients with apogeotropic lateral semicircular canal benign paroxysmal positional vertigo (LC-BPPV). Methods: We performed a multicenter randomized prospective study from January to December 2015, involving 72 consecutive patients with apogeotropic LC-BPPV. The patients were divided into three treatment groups: therapeutic head-shaking (group A), the Gufoni-Appiani maneuver (group B), and the cupulolith repositioning maneuver (CuRM; group C). Each group underwent evaluation and treatment up to the fourth week. Treatment success was defined as the disappearance of positional vertigo and nystagmus. Results: This study included 72 patients (49 male and 23 female), with a mean (±standard deviation) age of 55.4±13.5 years. The mean duration of vertigo experienced prior to treatment was 3.9±4.4 days. The mean latency and duration of nystagmus were 2.7±3.0 seconds and 47.9±15.8 seconds, respectively. The overall treatment frequency was 2.0±0.9. The number of treatments differed significantly among the three groups (P<0.05). After 4 weeks, the success rates for groups A, B, and C were 90.5%, 92.3%, and 100%, respectively. No significant difference was observed in the success rate across treatment methods and periods (P>0.05). However, CuRM was the only method with a 100% treatment success rate. Conclusion While no clear difference was observed among the three treatments for LC-BPPV, CuRM was found to be superior to the other approaches in the long term.

Objective: To compare the biomechanical properties of the glenohumeral joint capsule between adhesive capsulitis (AC) after breast cancer surgery and idiopathic AC and demonstrate the effects of hydrodilatation (HD) with corticosteroid injection for AC after breast cancer surgery. Methods: Twenty-three prospective patients with AC after breast cancer surgery (BC group) and 44 retrospective patients with idiopathic AC without breast cancer (CON group) underwent HD with corticosteroid injection and home exercise training. We compared their biomechanical characteristics (capsular capacity, maximal pressure, and capsular stiffness). In the BC group, the passive range of motion (ROM) of the affected shoulder and a questionnaire (Shoulder Pain and Disability Index [SPADI]) were evaluated at baseline and 2 and 4 weeks after treatment. Results: The BC group showed higher biomechanical characteristics (maximal pressure and capsular stiffness) than did the CON group. The mean maximal pressure and capsular stiffness were 519.67±120.90 mmHg and 19.69±10.58 mmHg/mL in the BC group and 424.78±104.42 mmHg and 11.55±7.77 mmHg/mL in the CON group (p=0.002 and p=0.001, respectively). And, the BC group showed significant improvements in all ROMs (abduction, flexion, and external rotation) and the SPADI pain and disability sub-scores following the treatment. Conclusion The glenohumeral joint capsular stiffness was greater in the patients with AC after breast cancer surgery than in those with idiopathic AC. HD with corticosteroid injection was effective in treating AC after breast cancer surgery.

Objective: To evaluate the efficacy and safety of Daewoong botulinum toxin type A (NABOTA) after its launch in South Korea. Methods: This prospective, multicenter, open-label phase IV clinical trial included 222 patients with stroke. All patients visited the clinic at baseline and at weeks 4, 8, and 12 after injection of upto 360 units of NABOTA into the wrist, elbow, and finger flexor muscles at the first visit. The primary outcome was the change in Modified Ashworth Scale (MAS) score for the wrist flexor muscles between baseline and week 4. The secondary outcomes were the changes in MAS, Disability Assessment Scale (DAS), and Caregiver Burden Scale (CBS) scores between baseline and each visit, and the Global Assessment Scale (GAS) score at week 12. Results: There was a statistically significant decrease in the MAS score for the wrist flexors between baseline and week 4 (-0.97±0.66, p<0.001). Compared with baseline, the MAS, DAS and CBS scores improved significantly during the study period. The GAS was rated as very good or good by 86.8% of physicians and by 60.0% of patients (or caregivers). The incidence of adverse events was 14.4%, which is smaller than that in a previous trial. Conclusion NABOTA showed considerable efficacy and safety in the management of upper limb spasticity in stroke patients.

Objective: Dysregulation of gene expression through epigenetic mechanisms may have a vital role in the pathogenesis of schizophrenia (SZ). In this study, we investigated the association of altered methylation patterns with SZ symptoms and early trauma in patients and healthy controls. Methods: The present study was conducted to identify methylation changes in CpG sites in peripheral blood associated with recent-onset (RO) psychosis using methylome-wide analysis. Lifestyle factors, such as smoking, alcohol, exercise, and diet, were controlled. Results: We identified 2,912 differentially methylated CpG sites in patients with RO psychosis compared to controls. Most of the genes associated with the top 20 differentially methylated sites had not been reported in previous methylation studies and were involved in apoptosis, autophagy, axonal growth, neuroinflammation, protein folding, etc. The top 15 significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways included the oxytocin signaling pathway, long-term depression pathway, axon guidance, endometrial cancer, long-term potentiation, mitogen-activated protein kinase signaling pathway, and glutamatergic pathway, among others. In the patient group, significant associations of novel methylated genes with early trauma and psychopathology were observed. Conclusion Our results suggest an association of differential DNA methylation with the pathophysiology of psychosis and early trauma. Blood DNA methylation signatures show promise as biomarkers of future psychosis.

Background: Coronavirus disease 2019 (COVID-19) during pregnancy is associated with increased disease severity and an increased risk of perinatal complications. However, few studies of pregnant women with COVID-19 have been conducted in Korea. The purpose of this study was to describe the clinical course and pregnancy outcomes of pregnant women admitted to our hospital with COVID-19 according to the severity. Materials and Methods: This retrospective cohort study included women aged 18 years of age or older who were hospitalized in the Gachon University Gil Medical Center with COVID-19 during pregnancy between July 1, 2021 and January 31, 2022. COVID-19 severity was classified according to the “Criteria for severity classification by symptoms of COVID-19” presented by the Korea Disease Control and Prevention Agency. Severe cases were defined as those who required oxygen treatment administered via a high-flow nasal cannula or invasive mechanical ventilation or should be applied extracorporeal membrane oxygenation (ECMO) or continuous renal replacement therapy. Results: A total of 103 pregnant women were hospitalized with COVID-19 during the study period. Their mean age was 33 (± 4.14) years, and 4 (3.9%) had been vaccinated against COVID-19. At the time of diagnosis of COVID-19, 3 (2.9%), 33 (32.0%), and 67 (65.1%) patients were in the first, second, and third trimester, respectively. The most common symptoms were cough (99 patients, 96.1%) and fever (85 patients, 82.5%). There was 1 (1.0%) asymptomatic patient. Forty patients (38.8%) required supplemental oxygen and 19 patients (18.4%) had severe disease. Of the 19 severe cases, 7 were in the 2nd trimester and 12 were in the 3rd trimester. Forty-one (39.8%) patients delivered, including two twin deliveries. Of the 41 cases of delivery, 14 were premature, 4 out of 21 (19.0%) in mild, 4 out of 12 (25.0%) in moderate, and 6 out of 8 (75.0%) in severe. Severe disease was associated with an increased rate of preterm birth (P = 0.012). Four of the 43 neonates (9.1%) received oxygen treatment. Conclusion Pregnant women with COVID-19 had a high rate of severe disease and a high preterm delivery rate, especially among those with severe disease.

Background: This study aimed to describe the maternal, obstetrical, and neonatal outcomes in pregnant women with coronavirus disease 2019 (COVID-19) and identify the predictors associated with the severity of COVID-19. Methods: This multicenter observational study included consecutive pregnant women admitted because of COVID-19 confirmed using reverse transcriptase-polymerase chain reaction (RT-PCR) test at 15 hospitals in the Republic of Korea between January 2020 and December 2021. Results: A total of 257 women with COVID-19 and 62 newborns were included in this study. Most of the patients developed this disease during the third trimester. Nine patients (7.4%) developed pregnancy-related complications. All pregnant women received inpatient treatment, of whom 9 (3.5%) required intensive care, but none of them died. The gestational age at COVID-19 diagnosis (odds ratio [OR], 1.096, 95% confidence interval [CI], 1.04–1.15) and parity (OR, 1.703, 95% CI, 1.13–2.57) were identified as significant risk factors of severe diseases. Among women who delivered, 78.5% underwent cesarean section. Preterm birth (38.5%), premature rupture of membranes (7.7%), and miscarriage (4.6%) occurred, but there was no stillbirth or neonatal death. The RT-PCR test of newborns’ amniotic fluid and umbilical cord blood samples was negative for severe acute respiratory syndrome coronavirus 2. Conclusion At the time of COVID-19 diagnosis, gestational age and parity of pregnant women were the risk factors of disease severity. Vertical transmission of COVID-19 was not observed, and maternal severity did not significantly affect the neonatal prognosis.