Circling mouse (C57BL/6J-cir/cir) deleted the transmembrane inner ear (Tmie) gene is an animal model for human non-syndromic recessive deafness, DFNB6. In circling mouse, hair cells in the cochlea have degenerated and hair bundles have become irregularity as time goes on. Tmie protein carries out a function of the mechanoelectrical transduction channel in cochlear hair cells. Myosin7a (MYO7A) protein has key roles in development of the cochlear hair bundles as well as in the function of cochlear hair cells. To find whether Tmie protein interacts with MYO7A proteins in the cochlea postnatal developmental stage, we investigated expression of the MYO7A proteins in the cochlear hair cells of circling mice by western blot analysis and whole mount immunofluorescence at postnatal day 5 (P5). The expression of MYO7A showed statistically significant increase in the cochlea of C57BL/6J-+/cir and C57BL/6J-cir/cir mice than that of C57BL/6J-+/+ mice. The MYO7A intensity of the cochlear hair cells also increased in C57BL/6J-+/cir and C57BL/6J-cir/cir mice compared with those of C57BL/6J-+/+ mice. Taken together, the results indicate that Tmie protein may have an important role with MYO7A protein in the development and maintenance of the stereociliary bundles during postnatal developmental stage of the cochlea.
Animals ; Blotting, Western ; Cochlea ; Deafness ; Ear, Inner ; Fluorescent Antibody Technique ; Hair ; Hair Cells, Auditory* ; Humans ; Mice* ; Models, Animal

PURPOSE: Unclassified variants (UVs) of BRCA1 and BRCA2 genes are not defined as pathogenic for breast cancer, and their clinical significance currently remains undefined. Therefore, this study was conducted to identify potentially pathogenic UVs by comparing their prevalence between breast cancer patients and controls. MATERIALS AND METHODS: A total of 328 breast cancer patients underwent BRCA1/2 genetic screening at the National Cancer Center of Korea. Genetic variants of BRCA genes that were categorized as unclassified according to the Breast Cancer Information Core database were selected based on allelic frequency, after which candidate variants were genotyped in 421 healthy controls. We also examined family members of the study participants. Finally, the effects of amino acid substitutions on protein structure and function were predicted in silico. RESULTS: Genetic tests revealed 33 UVs in BRCA1 and 47 in BRCA2. Among 15 candidates genotyped in healthy controls, c.5339T>C in BRCA1 and c.6029T>G, c.7522G>A in BRCA2 were not detected. Moreover, the c.5339T>C variant in the BRCA1 gene was detected in four patients with a family history of breast cancer. This nonsynonymous variant (Leu1780Pro) in the BRCA1 C-terminal domain was predicted to have an effect on BRCA1 protein structure/function. CONCLUSION: This study showed that comparison of genotype frequency between cases and controls could help identify UVs of BRCA genes that are potentially pathogenic. Moreover, ourfindings suggest that c.5339T>C in BRCA1 might be a pathogenic variant for patients and their families.
Amino Acid Substitution ; BRCA1 Protein ; Breast Neoplasms* ; Breast* ; Computer Simulation ; Genes, BRCA1 ; Genes, BRCA2* ; Genetic Testing ; Genotype ; Humans ; Korea ; Prevalence

Conventional denture impression techniques have limitations for edentulous patients with severe alveolar bone resorption and can cause problems from excessive border extension. Especially when a patient has movable tissue it is difficult to make accurate impression, thus might interrupt stable seating of complete denture. Fabrication of complete denture using closed mouth technique for edentulous patient with severe ridge resorption is thought to provide better stability and retention. In this case, an 86-year-old patient had both edentulous jaws with epulis fissuratum on maxillary anterior ridge and severe mandibular ridge resorption. Thus, tentative vertical dimension was determined by using Centric tray and individual tray attached with gothic arch tracer was fabricated. Complete denture was fabricated using closed mouth technique and the patient was satisfied with better stability and retention of the complete denture.
Aged, 80 and over ; Bone Resorption ; Denture, Complete* ; Dentures ; Gingival Diseases ; Humans ; Jaw, Edentulous ; Mouth* ; Vertical Dimension

PURPOSE: Digital mammography (DM) has replaced screen-film mammography (SFM). However, findings of comparisons between the performance indicators of DM and SFM for breast-cancer screening have been inconsistent. Moreover, the summarized results from studies comparing the performance of screening mammography according to device type vary over time. Therefore, this study aimed to compare the performance of DM and SFM using recently published data. METHODS: The MEDLINE, Embase, and Cochrane Library databases were searched for paired studies, cohorts, and randomized controlled trials published through 2018 that compared the performance of DM and SFM. All studies comparing the diagnostic accuracy of DM and SFM in asymptomatic, average-risk women aged 40 years and older were included. Two reviewers independently assessed the study quality and extracted the data. RESULTS: Thirteen studies were included in the meta-analysis. The pooled sensitivity (DM, 0.76 [95% confidence interval {CI}, 0.70–0.81]; SFM, 0.76 [95% CI, 0.70–0.81]), specificity (DM, 0.96 [95% CI, 0.94–0.97]; SFM, 0.97 [95% CI, 0.94–0.98]), and area under the receiver-operating characteristic curve (DM, 0.94 [95% CI, 0.92–0.96]; SFM, 0.92 [95% CI, 0.89–0.94]) were similar for both DM and SFM. The pooled screening performance indicators reinforced superior accuracy of full-field DM, which is a more advanced type of mammography, than SFM. The advantage of DM appeared greater among women aged 50 years or older. There was high heterogeneity among studies in the pooled sensitivity, specificity, and overall diagnostic accuracy estimates. Stratifying by study design (prospective or retrospective) and removing studies with a 2-year or greater follow-up period resulted in homogeneous overall diagnostic accuracy estimates. CONCLUSION: The breast-cancer screening performance of DM is similar to that of SFM. The diagnostic performance of DM depends on the study design, and, in terms of performance, full-field DM is superior to SFM, unlike computed radiography systems.
Breast Neoplasms ; Cohort Studies ; Early Detection of Cancer ; Female ; Follow-Up Studies ; Humans ; Mammography ; Mass Screening ; Population Characteristics ; Radiography ; Sensitivity and Specificity

Atrial fibrillation (AF) is a strong risk factor for embolic stroke. In patients with AF, optimal anticoagulation therapy, administered according to the stroke risk scoring system, can effectively reduce the stroke risk. However, AF episodes are frequently asymptomatic, with a significant number of them detected after a stroke event. Therefore, the early detection of subclinical AF and the subsequent administration of optimal oral anticoagulation therapy is expected to reduce the risk of stroke. However, this strategy requires more effective screening for the detection of AF in the asymptomatic stage, which accounts for the recent research interest in silent/subclinical AF. Today, the widespread use of cardiac implantable electronic devices and wearable rhythm monitors has enabled the detection of atrial high-rate episodes/subclinical AF in a substantial number of patients. The risk of stroke appears to be related to the duration of this phenomenon. Subclinical AF increases the risk of stroke, but generally not as much as clinical AF, but whether long-term anticoagulation therapy is required in patients with subclinical AF is unclear. Here we review existing data on the epidemiology, clinical significance, and suggest guidelines on management of subclinical AF and the optimal screening strategies aimed at its detection.

Atrial fibrillation (AF) is a strong risk factor for embolic stroke. In patients with AF, optimal anticoagulation therapy, administered according to the stroke risk scoring system, can effectively reduce the stroke risk. However, AF episodes are frequently asymptomatic, with a significant number of them detected after a stroke event. Therefore, the early detection of subclinical AF and the subsequent administration of optimal oral anticoagulation therapy is expected to reduce the risk of stroke. However, this strategy requires more effective screening for the detection of AF in the asymptomatic stage, which accounts for the recent research interest in silent/subclinical AF. Today, the widespread use of cardiac implantable electronic devices and wearable rhythm monitors has enabled the detection of atrial high-rate episodes/subclinical AF in a substantial number of patients. The risk of stroke appears to be related to the duration of this phenomenon. Subclinical AF increases the risk of stroke, but generally not as much as clinical AF, but whether long-term anticoagulation therapy is required in patients with subclinical AF is unclear. Here we review existing data on the epidemiology, clinical significance, and suggest guidelines on management of subclinical AF and the optimal screening strategies aimed at its detection.

This study aimed to estimate the medical cost of cancer in the first five years of diagnosis and in the final six months before death in people who developed cancer after human immunodeficiency virus (HIV) infection in Korea. The study utilized the Korea National Health Insurance Service-National Health Information Database (NHIS-NHID). Among 16,671 patients diagnosed with HIV infection from 2004 to 2020 in Korea, we identified 757 patients newly diagnosed with cancer after HIV diagnosis. The medical costs for 60 months after diagnosis and the last six months before death were calculated from 2006 to 2020. The mean annual medical cost due to cancer in HIV-infected people with cancer was higher for acquired immunodeficiency syndrome (AIDS)-defining cancers (48,242 USD) than for non-AIDS-defining cancers (24,338 USD), particularly non-Hodgkin’s lymphoma (53,007 USD), for the first year of cancer diagnosis. Approximately 25% of the cost for the first year was disbursed during the first month of cancer diagnosis. From the second year, the mean annual medical cost due to cancer was significantly reduced. The total medical cost was higher for non-AIDS-defining cancers, reflecting their higher incidence rates despite lower mean medical costs. The mean monthly total medical cost per HIV-infected person who died after cancer diagnosis increased closer to the time of death. The estimated burden of medical costs in patients with HIV in the present study may be an important index for defining healthcare policies in HIV patients in whom the cancer-related burden is expected to increase.

Background and objectives: Atrial fibrillation is a known risk factor for cryptogenic stroke and therefore requires early detection and prompt management. We investigated predictors of stroke recurrence in patients with cryptogenic stroke and concomitant non-sustained atrial tachycardia but not atrial fibrillation. Subjects and methods: We investigated 390 patients (219 men, mean age 67 ± 12 years) diagnosed with stroke and non-sustained atrial tachycardia on 24-h Holter monitoring and recorded the total number of atrial premature contractions identified by the Holter monitor. Multiple atrial premature contractions were defined as atrial premature contractions > 34 beats/day. We analyzed the rates of 5-year freedom from stroke recurrence or atrial fibrillation and investigated independent predictors of stroke recurrence and undiagnosed atrial fibrillation. Results: The mean follow-up period was 35 ± 21 months, and the overall stroke recurrence rate was 9.0%. Kaplan–Meier survival analysis revealed that the rate of freedom from stroke recurrence was significantly lower in patients with multiple atrial premature contractions. Also, the patients with multiple atrial premature contractions had higher cumulative incidence rate of new-onset AF (p = 0.019). Multivariate analysis showed that multiple atrial premature contractions (hazard ratio 2.49, 95% confidence interval 1.05–5.88, p = 0.038), cigarette smoking status (hazard ratio 2.66, 95% confidence interval 1.15–6.17, p = 0.022), and the left atrial volume index (hazard ratio 1.05, 95% confidence interval 1.01–1.09, p = 0.020) were significantly associated with stroke recurrence in patients with cryptogenic stroke. However, these factors were not statistically significant predictors of future onset of atrial fibrillation. Conclusions Multiple atrial premature contractions were significantly correlated with an increased left atrial volume index, which could predict future onset of atrial fibrillation and stroke recurrence. This study showed that multiple atrial premature contractions predict stroke recurrence in patients with cryptogenic stroke without atrial fibrillation.