Understanding the genetic basis and pathomechanisms underlying dementia arising from single-gene mutations is crucial to expand our knowledge in the field of dementia research. In this review, we comprehensively summarize the results of existing research using induced pluripotent stem cells (iPSCs) to investigate familial Alzheimer’s disease caused by mutations in the presenilin-1 (PSEN1), presenilin-2 (PSEN2), or amyloid precursor protein (APP) genes. We further review existing iPSC studies in leukodystrophies, including Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), caused by mutations in the notch receptor 3 (NOTCH3) gene; and adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), caused by mutations in the colony-stimulating factor 1 receptor (CSF1R) gene. We systematically review the advantages and necessity of using iPSCs in research to elucidate the pathogenesis of neurodegenerative diseases, particularly to facilitate disease modeling. Furthermore, we introduce applied research based on iPSC technology. Through this review, we aimed to help elucidate the mechanisms by which causative genes induce dementia symptoms in neurodegenerative diseases, which would help contribute to the development of effective treatment strategies.

Objectives: . This study investigated age-related differences in nasal morphometry and the degree of changes within an individual over at least a 10-year period by pairing previous and recent three-dimensional reconstructed computed tomography (CT) images. Methods: . Forty-eight adult Korean patients who underwent at least two CT scans of the nasal region with an interval of at least 10 years were selected. Patients were categorized into six subgroups according to sex and age (20–39 years, 40–49 years, and ≥50 years) at the time of initial imaging. Eight nasal parameters were measured on the initial and recent images, and paired comparisons between the two images were performed based on the data. The differences in the degree of change by age were also analyzed. Results: . Over an average image interval of 12 years, men exhibited an increase in the nasofrontal angle (3.2°±5.4°, P=0.041), profile nasal length (1.7±1.7 mm, P=0.002), and nasal bridge height (1.2±1.6 mm, P=0.002). Conversely, they showed a decrease in the nasofacial angle (–2.3°±2.9°, P=0.010). Women also demonstrated an increase in the nasofrontal angle (2.5°±5.2°, P=0.010), profile nasal length (1.4±1.9 mm, P<0.001), and nasal bridge height (1.3±1.6 mm, P<0.001). However, they exhibited a decrease in the nasofacial angle (–2.0°±2.1°, P<0.001), glabella angle (–9.1°±9.8°, P<0.001), and pyriform angle (–8.5°±10.1°, P<0.001). With the exception of the nasal bridge height (P=0.036) and pyriform angle (P=0.022), the degree of changes in most parameters did not show significant differences across age groups. Conclusion . Our findings indicate that the aging nose exhibits a greater nasal length with inferior angulation of the nasal tip, with an increase in the nasofrontal angle, profile nasal length, and nasal bridge height, along with a decrease in the nasofacial angle. The degree of most nasal morphologic changes demonstrated no significant differences by specific age group.

Purpose: Renal tumors account for approximately 7% of all childhood cancers. These include Wilms tumor (WT), clear cell sarcoma of the kidney (CCSK), malignant rhabdoid tumor of the kidney (MRTK), renal cell carcinoma (RCC), congenital mesoblastic nephroma (CMN) and other rare tumors. We investigated the epidemiology of pediatric renal tumors in Korea. Materials and Methods: From January 2001 to December 2015, data of pediatric patients (0–18 years) newly-diagnosed with renal tumors at 26 hospitals were retrospectively analyzed. Results: Among 439 patients (male, 240), the most common tumor was WT (n=342, 77.9%), followed by RCC (n=36, 8.2%), CCSK (n=24, 5.5%), MRTK (n=16, 3.6%), CMN (n=12, 2.7%), and others (n=9, 2.1%). Median age at diagnosis was 27.1 months (range 0-225.5) and median follow-up duration was 88.5 months (range 0-211.6). Overall, 32 patients died, of whom 17, 11, 1, and 3 died of relapse, progressive disease, second malignant neoplasm, and treatment-related mortality. Five-year overall survival and event free survival were 97.2% and 84.8% in WT, 90.6% and 82.1% in RCC, 81.1% and 63.6% in CCSK, 60.3% and 56.2% in MRTK, and 100% and 91.7% in CMN, respectively (p < 0.001). Conclusion The pediatric renal tumor types in Korea are similar to those previously reported in other countries. WT accounted for a large proportion and survival was excellent. Non-Wilms renal tumors included a variety of tumors and showed inferior outcome, especially MRTK. Further efforts are necessary to optimize the treatment and analyze the genetic characteristics of pediatric renal tumors in Korea.

Background: Obstructive sleep apnea (OSA) is closely related to maternal obesity in pregnant women, and the association increases with later pregnancy. Obesity and OSA are risk factors of pregnancy-related complications, including gestational hypertension, gestational diabetes mellitus (GDM), and fetal morbidities. We aimed to determine the prevalence of OSA and to assess the impact of OSA on pregnancy-related disorders in overweight pregnant women. Methods: Eligible participants who were overweight [body mass index (BMI) ≥ 23 kg/m 2 ] in gestational age 30 weeks or more, assessed OSA using a portable polysomnography at home.Clinical data were collected from pregnant women and their babies. Results: The average age of 51 participants was 34.5 years (27–44 years). The number of primipara was 25 (49%) and that of multipara was 26 (51%). Eight cases of GDM (15.7%) and five cases of preeclampsia (9.8%) were reported, and six patients (11.8%) experienced preterm delivery. In results of polysomnography, 14 patients (27.5%) were diagnosed as OSA. Apnea-hypopnea index moderately correlated with BMI (r = 0.515, P < 0.001). The BMI (P < 0.005) and preeclampsia rate (P < 0.017) were higher in the OSA group compared to the control group. Odds ratios (ORs) adjusting age, BMI, parity, and abortion history were calculated. The presence of OSA increased OR of preeclampsia (OR, 13.1; 95% confidence interval, 1.1–171.3). The majority of preeclampsia patients (4/5, 80%) underwent preterm delivery. Conclusion OSA is an important risk factor for preeclampsia, resulting in preterm delivery.For overweight pregnant women, an OSA evaluation should be mandatory.

Objectives: . Our previous study found that multilevel obstructive sleep apnea (OSA) surgery mitigated laryngopharyngeal reflux (LPR) symptoms in terms of the reflux symptom index (RSI), but no studies have investigated the impact of OSA surgery on laryngoscopic parameters. The aim of this study was to examine the clinical outcome of LPR improvement following OSA surgery, with a focus on both the RSI and the reflux finding score (RFS). Methods: . Prospectively collected data from 28 patients who underwent multilevel OSA surgery from 2017 to 2021 were retrospectively analyzed. Patients were asked to complete the RSI questionnaire and underwent a laryngoscopic examination to evaluate the RFS before and after surgery. Age, height, weight, body mass index (BMI), and polysomnography data before and after surgery were also reviewed. Results: . After surgery, the total RSI and RFS decreased significantly from 11.96±8.40 to 7.68±6.82 (P=0.003) and from 6.57±3.49 to 3.21±1.87 (P<0.001). The positive rates of RSI and RFS decreased from 28.6% to 17.9% and 32.1% to 0%, respectively. Significant improvements were found in the RSI subdomains of throat clearing, throat mucus, breathing difficulty, troublesome cough, and heartburn sensation, while all RFS subdomains except granuloma improved significantly. In subgroup analyses, no significant differences were found between subgroups based on age, OSA severity, or BMI. Conclusion . OSA surgery has the potential to alleviate both LPR symptoms and laryngoscopic results. Additional research integrating more objective techniques and novel treatment strategies is required to better comprehend the clinical impact of OSA surgery on LPR.

Background/Aims: The prospective Crohn’s Disease Clinical Network and Cohort Study is a nationwide multicenter cohort study of patients with Crohn’s disease (CD) in Korea, aiming to prospectively investigate the clinical features and long-term prognosis associated with CD. Methods: Patients diagnosed with CD between January 2009 and September 2019 were prospectively enrolled. They were divided into two cohorts according to the year of diagnosis: cohort 1 (diagnosed between 2009 and 2011) versus cohort 2 (between 2012 and 2019). Results: A total of 1,175 patients were included, and the median follow-up duration was 68 months (interquartile range, 39.0 to 91.0 months). The treatment-free durations for thiopurines (p<0.001) and anti-tumor necrosis factor agents (p=0.018) of cohort 2 were shorter than those of cohort 1. Among 887 patients with B1 behavior at diagnosis, 149 patients (16.8%) progressed to either B2 or B3 behavior during follow-up. Early use of thiopurine was associated with a reduced risk of behavioral progression (adjusted hazard ratio [aHR], 0.69; 95% confidence interval [CI], 0.50 to 0.90), and family history of inflammatory bowel disease was associated with an increased risk of behavioral progression (aHR, 2.29; 95% CI, 1.16 to 4.50). One hundred forty-one patients (12.0%) underwent intestinal resection, and the intestinal resection-free survival time was significantly longer in cohort 2 than in cohort 1 (p=0.003). The early use of thiopurines (aHR, 0.35;95% CI, 0.23 to 0.51) was independently associated with a reduced risk of intestinal resection. Conclusions The prognosis of CD in Korea appears to have improved over time, as evidenced by the decreasing intestinal resection rate. Early use of thiopurines was associated with an improved prognosis represented by a reduced risk of intestinal resection.

Background/Aims: Biofeedback therapy is widely used to treat patients with chronic constipation, especially those with dyssynergic defecation. Yet, the utility of high-resolution manometry with novel parameters in the prediction of biofeedback response has not been reported. Thus, we constructed a model for predicting biofeedback therapy responders by applying the concept of integrated pressurized volume in patients undergoing high-resolution anorectal manometry. Methods: Seventy-one female patients (age: 48-68 years) with dyssynergic defecation who underwent initial high-resolution anorectal manometry and subsequent biofeedback therapy were enrolled. The manometry profiles were used to calculate the 3-dimensional integrated pressurized volumes by multiplying the distance, time, and amplitude during simulated evacuation. Partial least squares regression was performed to generate a predictive model for responders to biofeedback therapy by using the integrated pressurized volume parameters. Results: Fifty-five (77.5%) patients responded to biofeedback therapy. The responders and non-responders did not show significant differences in the conventional manometric parameters. The partial least squares regression model used a linear combination of eight integrated pressurized volume parameters and generated an area under the curve of 0.84 (95% confidence interval: 0.76-0.95, P < 0.01), with 85.5% sensitivity and 62.1% specificity. Conclusions Integrated pressurized volume parameters were better than conventional parameters in predicting the responsiveness to biofeedback therapy, and the combination of these parameters and partial least squares regression was particularly promising. Integrated pressurized volume parameters can more effectively explain the physiology of the anorectal canal compared with conventional parameters.

Background: Chronic exposure to low-dose persistent organic pollutants (POPs) can induce mitochondrial dysfunction. This study evaluated the association between serum POP concentrations and oxygen consumption rate (OCR) as a marker of mitochondrial function in humans and in vitro cells. Methods: Serum concentrations of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) were measured in 323 adults. The OCRs of platelets and peripheral blood mononuclear cells (PBMCs) were assessed in 20 mL of fresh blood using a Seahorse XF analyzer. Additionally, the in vitro effects of Arochlor-1254, β-hexachlorocyclohexane, and p,p´-dichlorodiphenyltrichloroethane at concentrations of 0.1 pM to 100 nM were evaluated in human platelets, human PBMCs, and Jurkat T-cells. Results: The association between serum POP concentrations and OCR differed depending on the cell type. As serum OCP concentrations increased, basal platelet OCR levels decreased significantly; according to the OCP quintiles of summary measure, they were 8.6, 9.6, 8.2, 8.0, and 7.1 pmol/min/μg (P trend=0.005). Notably, the basal PBMC OCR levels decreased remarkably as the serum PCB concentration increased. PBMC OCR levels were 46.5, 34.3, 29.1, 16.5, and 13.1 pmol/min/μg according to the PCB quintiles of summary measure (P trend <0.001), and this inverse association was consistently observed in all subgroups stratified by age, sex, obesity, type 2 diabetes mellitus, and hypertension, respectively. In vitro experimental studies have also demonstrated that chronic exposure to low-dose POPs could decrease OCR levels. Conclusion The findings from human and in vitro studies suggest that chronic exposure to low-dose POPs can induce mitochondrial dysfunction by impairing oxidative phosphorylation.

Various invasive fungal infections can occur in immunocompromised hosts, and an acute invasive fungal infection (AIFI) can be fatal. Because of its high mortality rate, AIFI must be quickly diagnosed and treated, such as anti-fungal agents or surgical debridement. In an immunocompromised host, nasal herpes simplex infection, usually caused by herpes simplex virus (HSV) type-1, can have various clinical manifestations, some of which can mimic AIFI. However, the management of acute viral infection differs significantly from invasive fungal infections of the nose. A fast and accurate differential diagnosis is mandatory because a delay in the disease-specific treatment of acute invasive infections can lead to mortality. This report describes two immunocompromised patients with mucosal and skin lesions around the nose. We provide clinical clues when mucosal lesions of the nasal cavity and skin lesions around the nose develop in immunocompromised hosts.