Sensorineural hearing loss (SNHL) is the most common sensory disorder, with a high Mendelian genetic contribution. Considering the genotypic and phenotypic heterogeneity of SNHL, the advent of next-generation sequencing technologies has revolutionized knowledge on its genomic architecture. Nonetheless, the conventional application of panel and exome sequencing in real-world practice is being challenged by the emerging need to explore the diagnostic capability of whole-genome sequencing, which enables the detection of both noncoding and structural variations. Small molecules and gene therapies represent good examples of how breakthroughs in genetic understanding can be translated into targeted therapies for SNHL. For example, targeted small molecules have been used to ameliorate autoinflammatory hearing loss caused by gain-of-function variants of NLRP3 and inner ear proteinopathy with OSBPL2 variants underlying dysfunctional autophagy. Strikingly, the successful outcomes of the first-in-human trial of OTOF gene therapy highlighted its potential in the treatment of various forms of genetic hearing loss. clustered regularly interspaced short palindromic repeats (CRISPR)-based technologies are currently being developed for site-specific genome editing to treat human genetic disorders. These advancements have led to an era of genotype- and mechanism-based precision medicine in SNHL practice.

OBJECTIVE: Low cholesterol is associated with depression among western countries. The objective of this study was to examine the relationship between cholesterol and depression in Korean population with low levels of serum cholesterol. METHODS: The data of about 740,000 individuals, aged 30-64 years at entry in the Korean Cancer Prevention Study, were used. Total cholesterol levels were measured in 1992. Depression was measured using the modified DSM-IV (Diagnostic Criteria of Major Depressive Episode in Diagnostic and Statistical Manual of Mental Disorders-IV) scale. Total cholesterol was classified into four groups (quartile). Odds Ratios of low level of cholesterol were evaluated using multi-variable logistic models. RESULTS: The prevalence of major depression was 7.7% in men and 10.4% in women. After adjustment for various confounding variables, an inverse association was detected between cholesterol levels and depression intensity among men and women. The odds ratio (95% confidence interval) of the lowest quartile of cholesterol was 1.16 (1.13-1.20) on major depression compared with the highest quartile of cholesterol in men. The corresponding odds ratio among women was 1.09 (1.04-1.15). The strongest association among 9 items of depression was found at "decreased appetite and lost weight" in both men (OR=1.68) and women (OR=1.43). CONCLUSION: Low cholesterol is associated with major depression in men and women. Further studies are necessary to evaluate the cross-validation, to explore the biological mechanism, and to identify the clinical implication.
Appetite ; Cholesterol ; Confounding Factors (Epidemiology) ; Depression* ; Diagnostic and Statistical Manual of Mental Disorders ; Epidemiology ; Female ; Humans ; Logistic Models ; Male ; Odds Ratio ; Prevalence

Drug-induced liver injury (DILI) is the serious and fatal drug-associated adverse effect, but its incidence is very low and individual variation in severity is substantial. Acetaminophen (APAP)-induced liver injury accounts for >50% of reported DILI cases but little is known for the cause of individual variations in the severity. Intrinsic genetic variation is considered a key element but the identity of the genes was not well-established. Here, pre-biopsy method and microarray technique was applied to uncover the key genes for APAP-induced liver injury in mice, and a cause and effect experiment employing quantitative real-time PCR was conducted to confirm the correlation between the uncovered genes and APAP-induced hepatotoxicity. We identified the innately and differentially expressed genes of mice susceptible to APAP-induced hepatotoxicity in the pre-biopsied liver tissue before APAP treatment through microarray analysis of the global gene expression profiles (Affymetrix GeneChip® Mouse Gene 1.0 ST for 28,853 genes). Expression of 16 genes including Gdap10, Lpl, Gabra3 and Ccrn4l were significantly different (t-test: FDR <10%) more than 1.5 fold in the susceptible animals than resistant. To confirm the association with the susceptibility to APAP-induced hepatotoxicity, another set of animals were measured for the expression level of selected 4 genes (higher two and lower two genes) in the liver pre-biopsy and their sensitivity to APAP-induced hepatotoxicity was evaluated by post hoc. Notably, the expressions of Gabra3 and Lpl were significantly correlated with the severity of liver injury (p<0.05) demonstrating that these genes may be linked to the susceptibility to APAP-induced hepatotoxicity.
Acetaminophen ; Animals ; Drug-Induced Liver Injury ; Genetic Variation ; Incidence ; Lipoprotein Lipase* ; Lipoproteins* ; Liver ; Methods ; Mice ; Microarray Analysis ; Real-Time Polymerase Chain Reaction ; Receptors, GABA-A* ; Toxicogenetics ; Transcriptome

Gerstmann's syndrome, assigned to a lesion of the dominant parietal lobe, is a neurological disorder characterized by acalculia, agraphia, right-left disorientation and finger agnosia. Some studies report that these symptoms are also shown in other brain lesions. We report two patients who presented with this tetrad of symptoms in initial assessment. Their Brain MRI images both showed lesion of left frontal lobe. Over time, these symptoms became better but some still remained in last assessment. Accordingly, we suggest that a left frontal lesion cause Gerstmann's syndrome.
Agnosia ; Agraphia ; Brain ; Dyscalculia ; Frontal Lobe* ; Gerstmann Syndrome* ; Humans ; Magnetic Resonance Imaging ; Nervous System Diseases ; Parietal Lobe

Neuroblastoma is the most common pediatric extracranial solid tumor derived from primitive neural crest cells of the sympathetic nervous system. Although one-fifths of all neuroblastomas occurs within the thorax, thoracic neuroblastomas detected in fetus have been rarely reported. We report a case of fetal thoracic neuroblastoma with massive pleural effusion detected with prenatal ultrasonography. A 34-year-old Korean second-gravida was referred to our hospital at 30 weeks of gestation for evaluation, after the right lung mass found in the fetus. Approximately 3 cm, well-defined, hyperechoic mass was found in the right thorax with right pleural effusion, with the initial suspicion of teratoma. However, as mass continued to grow with deteriorating pleural effusion and fetal hydrops, the mass was considered malignant after 3 weeks. After a cesarean delivery, an approximately 4 cm mass with peripheral calcification and hemothorax was found on neonatal ultrasonography. Neuroblastoma was diagnosed on excision biopsy.
Adult ; Biopsy ; Fetus ; Hemothorax ; Humans ; Hydrops Fetalis ; Lung ; Mediastinum ; Neural Crest ; Neuroblastoma* ; Pleural Effusion ; Pregnancy ; Sympathetic Nervous System ; Teratoma ; Thorax ; Ultrasonography ; Ultrasonography, Prenatal

Background: Basiliximab is used as an alternative to tacrolimus in patients with decreased renal function. However, studies on basiliximab as a maintenance immunosuppressant, particularly in patients with lung transplantation, are limited. Therefore, here, we investigated the efficacy and safety of basiliximab in patients with lung transplantation. Methods: Adult patients with acute kidney injury (AKI) who received lung transplantation at a single general hospital between July 1, 2014 and June 30, 2018, were selected and classified in tacrolimus and basiliximab groups. Both groups received a triple-drug regimen (tacrolimus, mycophenolate mofetil, and steroids). However, tacrolimus was discontinued in the basiliximab group when AKI occurred, and two or more repeat basiliximab doses were administered within 3 months after transplantation. The electronic medical records were analyzed retrospectively. Results: Of the 85 patients who met the selection criteria, 61 and 24 were assigned to the tacrolimus and basiliximab groups, respectively. Significant improvement in renal function was observed in the basiliximab group (p <0.001).However, there were no differences in acute and chronic rejection rates in both the groups. No difference was observed in the incidence rate of complications between the groups, except for chronic kidney disease, which showed higher incidence in the basiliximab group (25.0% vs. 4.9%; p =0.013). Conclusions We suggest the use of basiliximab as an immunosuppressant alternative to tacrolimus in patients with acute renal failure after lung transplantation. Basiliximab demonstrated effectiveness as an immunosuppressant and improved renal function. Therefore, basiliximab can be used in patients with decreased renal function.

Background: Basiliximab is used as an alternative to tacrolimus in patients with decreased renal function. However, studies on basiliximab as a maintenance immunosuppressant, particularly in patients with lung transplantation, are limited. Therefore, here, we investigated the efficacy and safety of basiliximab in patients with lung transplantation. Methods: Adult patients with acute kidney injury (AKI) who received lung transplantation at a single general hospital between July 1, 2014 and June 30, 2018, were selected and classified in tacrolimus and basiliximab groups. Both groups received a triple-drug regimen (tacrolimus, mycophenolate mofetil, and steroids). However, tacrolimus was discontinued in the basiliximab group when AKI occurred, and two or more repeat basiliximab doses were administered within 3 months after transplantation. The electronic medical records were analyzed retrospectively. Results: Of the 85 patients who met the selection criteria, 61 and 24 were assigned to the tacrolimus and basiliximab groups, respectively. Significant improvement in renal function was observed in the basiliximab group (p <0.001).However, there were no differences in acute and chronic rejection rates in both the groups. No difference was observed in the incidence rate of complications between the groups, except for chronic kidney disease, which showed higher incidence in the basiliximab group (25.0% vs. 4.9%; p =0.013). Conclusions We suggest the use of basiliximab as an immunosuppressant alternative to tacrolimus in patients with acute renal failure after lung transplantation. Basiliximab demonstrated effectiveness as an immunosuppressant and improved renal function. Therefore, basiliximab can be used in patients with decreased renal function.

BACKGROUND: A considerable amount of research has shown that knowledge and appropriate awareness are essential for encouraging positive behaviors and promoting health. In Korea, the roles that behavioral changes play in the prevention of cancer have been an important issue since the introduction of the 10 codes for cancer prevention in 2006. Thus, the present study investigated the associations of tobacco-related knowledge with awareness and attitudes towards positive smoking-cessation behaviors. METHODS: The present study analyzed data from the 2010 national questionnaire survey (n = 1,006). This study evaluated sociodemographic characteristics, smoking status, self-rated health status, health-related interests, and the accuracy of 12 tobacco-related statements to determine knowledge level and to investigate its impact on awareness and behaviors related to smoking. These parameters were examined and staged using the Precaution Adoption Process Model. RESULTS: A higher level of tobacco-related knowledge was significantly associated with a positive attitude towards smoking cessation (5–8 correct answers: odds ratio [OR], 2.53; 95% confidence interval [CI], 1.57–4.08; ≥ 9 correct answers: OR, 3.90; 95% CI, 2.22–6.82; reference: ≤ 4 correct answers). Interestingly, among current smokers, only those who correctly responded to ≥ 9 of 12 tobacco-related statements were significantly associated with a positive attitude towards smoking cessation. CONCLUSION: This study found that having a higher level of tobacco-related knowledge had a significant impact on positive attitudes towards smoking cessation. This suggests that there is a need to disseminate appropriate knowledge to the general population to encourage positive attitudes and promote healthful behaviors in terms of smoking.
Korea ; Odds Ratio ; Smoke* ; Smoking Cessation ; Smoking*

OBJECTIVE: In this study, we evaluated the prevalence of allergic disease in offsprings delivered via the delivery modes of vaginal delivery vs. planned Cesarean section vs. Cesarean section with labor. METHODS: This study included 175 mother-neonate pairs from Severance Hospital who were enrolled in the Cohort for Childhood Origin of Asthma and allergic diseases study. Information regarding prenatal environmental factors, delivery, and diagnosis of allergic diseases was obtained from a questionnaire and medical record review. Patients with at least 3 years of follow-up data were included in this study. Results were adjusted for sex, birth weight, gestational age at birth, season of birth, neonatal intensive care unit admission, parity, breastfeeding, and maternal factors. RESULTS: A total of 175 offsprings were eligible for analysis. Among the subjects, 52.0% were delivered by vaginal delivery, 34.3% by planned Cesarean section, and 16.6% by Cesarean section with labor. Fifty-nine offsprings (33.7%) were diagnosed with allergic disease at a median age of 1 year (range 0.5–3 years). The prevalence of allergic disease was not associated with delivery mode after adjusting for confounding variables. Time period from membrane rupture to delivery, duration of the active phase, and the beginning of the pelvic division prior to Cesarean section were not associated with allergic disease development in offsprings. CONCLUSION: Cesarean section, irrespective of the occurrence of labor before surgery, did not increase the prevalence of allergic disease in infants up to 3 years of age.
Asthma ; Birth Weight ; Breast Feeding ; Cesarean Section* ; Cohort Studies ; Confounding Factors (Epidemiology) ; Diagnosis ; Female ; Follow-Up Studies ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Intensive Care, Neonatal ; Medical Records ; Membranes ; Parity ; Parturition ; Pregnancy ; Prevalence* ; Rupture ; Seasons

Background: The aim of this study was to capture multifaceted clinical characteristics of congenital cytomegalovirus (CMV) infection from diagnosis to treatment using a multidisciplinary approach including obstetrics, pediatrics, pathology, and otorhinolaryngology-head and neck surgery. Methods: This is a retrospective study including 30 consecutive cases of congenital CMV infection that were diagnosed at a single tertiary hospital located in Seoul, Korea from January 2009 to December 2020. Congenital CMV infection was defined as a positive result by polymerase chain reaction from urine, saliva or cerebrospinal fluid or positive CMV IgM from neonatal blood sampled within 3 weeks after birth. All cases were analyzed with respect to whole clinical characteristics from diagnosis to treatment of congenital CMV by a multidisciplinary approach including prenatal sonographic findings, maternal immune status regarding CMV infection, detailed placental pathology, neonatal clinical manifestation, auditory brainstem response test, and antiviral treatment (ganciclovir or valganciclovir). Long-term outcomes including developmental delay and hearing loss were also investigated. Results: The total number of births during the study period in our institution was 19,385, with the prevalence of congenital infection estimated to be 0.15%. Among 30 cases of congenital CMV, the median gestational age at delivery was 32.2 weeks [range, 22.6–40.0] and 66.7% of these infants were delivered preterm at less than 37 weeks. Suspected fetal growth restriction was the most common prenatal ultrasound finding (50%) followed by ventriculomegaly (17.9%) and abnormal placenta (17.9%), defined as thick placenta with calcification. No abnormal findings on ultrasound examination were observed in one-third of births. Maternal CMV serology tests were conducted in only 8 cases, and one case each of positive and equivocal IgM were found. The most common placental pathologic findings were chronic villitis (66.7%) and calcification (63.0%), whereas viral inclusions were identified in only 22.2%. The most common neonatal manifestations were jaundice (58.6%) followed by elevation of aspartate aminotransferase (55.2%) and thrombocytopenia (51.7%). After excluding cases for which long-term outcomes were unavailable due to death (n = 4) or subsequent follow up loss (n = 3), developmental delay was confirmed in 43.5% of infants (10/23), and hearing loss was confirmed in 42.9% (9/21) during the follow-up period. In our cohort, 56.7% (17/30) of neonates were treated for congenital CMV with ganciclovir or valganciclovir. Conclusion Our data show that prenatal findings including maternal serologic tests and ultrasound have limited ability to detect congenital CMV in Korea. Given that CMV is associated with high rates of developmental delay and hearing loss in infants, there is an urgent need to develop specific strategies for the definite diagnosis of congenital CMV infection during the perinatal period by a multidisciplinary approach to decrease the risks of neurologic impairment and hearing loss through early antiviral treatment.