A 16-year-old Korean male patient presented with macrodactyly, hemihypertrophy of the face and extremities, plantar cerebriform hyperplasia, a subcutaneous mass of the left chest, macrocephaly and verrucous epidermal nevi. These findings are consistent with Proteus Syndrome. The clinical features, etiology, management, natural course and differential diagnosis of this case are discussed.
Adolescent ; Case Report ; Disease Progression ; Human ; Male ; Proteus Syndrome/diagnosis/etiology/*physiopathology/therapy

Rhinorrhea in allergic rhinitis (AR) is characterized by the secretion of electrolytes in the nasal discharge. The secretion of Cl– and HCO3 – is mainly regulated by cystic fibrosis transmembrane conductance regulator (CFTR) or via the calciumactivated Cl– channel anoctamin-1 (ANO1) in nasal gland serous cells. Interleukin-4 (IL-4), which is crucial in the development of allergic inflammation, increases the expression and activity of ANO1 by stimulating histamine receptors. In this study, we investigated ANO1 as a potential therapeutic target for rhinorrhea in AR using an ANO1 inhibitor derived from a natural herb. Ethanolic extracts (30%) of Spirodela polyrhiza (SPEtOH) and its five major flavonoids constituents were prepared. To elucidate whether the activity of human ANO1 (hANO1) was modulated by SPEtOH and its chemical constituents, a patch clamp experiment was performed in hANO1-HEK293T cells. Luteolin, one of the major chemical constituents in SPEtOH, significantly inhibited hANO1 activity in hANO1-HEK293T cells. Further, SPEtOH and luteolin specifically inhibited the calcium-activated chloride current, but not CFTR current in human airway epithelial Calu-3 cells. Calu-3 cells were cultured to confluency on transwell inserts in the presence of IL-4 to measure the electrolyte transport by Ussing chamber. Luteolin also significantly inhibited the ATP-induced increase in electrolyte transport, which was increased in IL-4 sensitized Calu-3 cells. Our findings indicate that SPEtOH and luteolin may be suitable candidates for the prevention and treatment of allergic rhinitis. SPEtOH- and luteolin-mediated ANO1 regulation provides a basis for the development of novel approaches for the treatment of allergic rhinitis-induced rhinorrhea.

Rhinorrhea in allergic rhinitis (AR) is characterized by the secretion of electrolytes in the nasal discharge. The secretion of Cl– and HCO3 – is mainly regulated by cystic fibrosis transmembrane conductance regulator (CFTR) or via the calciumactivated Cl– channel anoctamin-1 (ANO1) in nasal gland serous cells. Interleukin-4 (IL-4), which is crucial in the development of allergic inflammation, increases the expression and activity of ANO1 by stimulating histamine receptors. In this study, we investigated ANO1 as a potential therapeutic target for rhinorrhea in AR using an ANO1 inhibitor derived from a natural herb. Ethanolic extracts (30%) of Spirodela polyrhiza (SPEtOH) and its five major flavonoids constituents were prepared. To elucidate whether the activity of human ANO1 (hANO1) was modulated by SPEtOH and its chemical constituents, a patch clamp experiment was performed in hANO1-HEK293T cells. Luteolin, one of the major chemical constituents in SPEtOH, significantly inhibited hANO1 activity in hANO1-HEK293T cells. Further, SPEtOH and luteolin specifically inhibited the calcium-activated chloride current, but not CFTR current in human airway epithelial Calu-3 cells. Calu-3 cells were cultured to confluency on transwell inserts in the presence of IL-4 to measure the electrolyte transport by Ussing chamber. Luteolin also significantly inhibited the ATP-induced increase in electrolyte transport, which was increased in IL-4 sensitized Calu-3 cells. Our findings indicate that SPEtOH and luteolin may be suitable candidates for the prevention and treatment of allergic rhinitis. SPEtOH- and luteolin-mediated ANO1 regulation provides a basis for the development of novel approaches for the treatment of allergic rhinitis-induced rhinorrhea.

Target cells differentiation techniques from stem cells are developed rapidly. Recently, direct conversion techniques are introduced in various categories. Unlike pluripotent stem cells, this technique enables direct differentiation into the other cell types such as neurons, cardiomyocytes, insulin-producing cells, and hepatocytes without going through the pluripotent stage. However, the function of these converted cells reserve an immature phenotype. Therefore, we modified the culture conditions of mouse direct converted hepatocytes (miHeps) to mature fetal characteristics, such as higher AFP and lower albumin (ALB) expression than primary hepatocytes. First, we generate miHeps from mouse embryonic fibroblasts (MEFs) with two transcription factors HNF4α and Foxa3. These cells indicate typical epithelial morphology and express hepatic proteins. To mature hepatic function, DMSO is treated during culture time for more than 7 days. After maturation, miHeps showed features of maturation such as exhibiting typical hepatocyte-like morphology, increased up-regulated ALB and CYP enzyme gene expression, down-regulated AFP expressions, and acquired hepatic function over time. Thus, our data provides a simple method to mature direct converted hepatocytes functionally and these cells enable them to move closer to generating functional hepatocytes.
Animals ; Dimethyl Sulfoxide ; Fibroblasts* ; Gene Expression ; Hepatocytes* ; Methods ; Mice ; Myocytes, Cardiac ; Neurons ; Phenotype ; Pluripotent Stem Cells ; Stem Cells ; Transcription Factors

Purpose: The aim of this study was to evaluate the accuracy of prostate volume estimates calculated from the ellipsoid formula using the anteroposterior (AP) diameter measured on axial and sagittal images obtained through ultrasonography (US) and magnetic resonance imaging (MRI). Methods: This retrospective study included 456 patients with transrectal US and MRI from two university hospitals. Two radiologists independently measured the prostate gland diameters on US and MRI: AP diameters on axial and sagittal images, transverse, and longitudinal diameters on midsagittal images. The volume estimates, volumeax and volumesag, were calculated from the ellipsoid formula by using the AP diameter on axial and sagittal images, respectively. The prostate volume extracted from MRI-based whole-gland segmentation was considered the gold standard. The intraclass correlation coefficient (ICC) was used to evaluate the inter-method agreement between volumeax and volumesag, and agreement with the gold standard. The Wilcoxon signedrank test was used to analyze the differences between the volume estimates and the gold standard. Results: The prostate gland volume estimates showed excellent inter-method agreement, and excellent agreement with the gold standard (ICCs >0.9). Compared with the gold standard, the volume estimates were significantly larger on MRI and significantly smaller on US (P<0.001). The volume difference (segmented volume–volume estimate) was greater in patients with larger prostate glands, especially on US. Conclusion Volumeax and volumesag showed excellent inter-method agreement and excellent agreement with the gold standard on both US and MRI. However, prostate volume was overestimated on MRI and underestimated on US.

Pilocarpine-induced rat epilepsy model is an established animal model that mimics medial temporal lobe epilepsy in humans. The purpose of this study was to investigate neuroimaging abnormalities in various stages of epileptogenesis and to correlate them with seizure severity in pilocarpine-induced rat epilepsy model. Fifty male Sprague-Dawley rats were subject to continuous video and electroencephalographic monitoring after inducing status epilepticus (SE) and seizure severity was estimated by frequency and total durations of class 3 to 5 spontaneous recurrent seizures (SRS) by modified Racine's classification. The 7.0 Tesla magnetic resonance imaging (MRI) with high resolution flurodeoxyglucose positron emission tomography (FDG-PET) was performed at 3 hours, 1, 3, 7 days and 4 weeks after the initial insult. The initial SRS was observed 9.7±1.3 days after the pilocarpine injection. MRI revealed an abnormal T2 signal change with swelling in both hippocampi and amygdala in acute (day 1 after injection) and latent phases (days 3 and 7), in association with PET hypometabolism in these areas. Interestingly, the mean frequency of class 3 to 5 SRS was positively correlated with abnormal T2 signals in hippocampal area at 3 days. SRS duration became longer with more decreased glucose metabolism in both hippocampi and amygdala at 7 days after pilocarpine injection. This study indicates that development and severity of SRS at chronic phase could be closely related with structural and functional changes in hippocampus during the latent period, a pre-epileptic stage.
Amygdala ; Animals ; Classification ; Epilepsy* ; Epilepsy, Temporal Lobe ; Glucose ; Hippocampus ; Humans ; Magnetic Resonance Imaging ; Male ; Metabolism ; Models, Animal ; Neuroimaging ; Pilocarpine ; Positron-Emission Tomography ; Rats ; Rats, Sprague-Dawley ; Seizures ; Status Epilepticus

Background: Exercise capacity is known to be an independent predictor of cardiovascular events and mortality. However, most previous studies were based on Western populations.Further study is warranted for Asian patients according to ethnic or national standards. We aimed to compare prognostic values of Korean and Western nomograms for exercise capacity in Korean patients with cardiovascular disease (CVD). Methods: In this retrospective cohort study, we enrolled 1,178 patients (62 ± 11 years;78% male) between June 2015 and May 2020, who were referred for cardiopulmonary exercise testing in our cardiac rehabilitation program. The median follow-up period was 1.6 years. Exercise capacity was measured in metabolic equivalents by direct gas exchange method during the treadmill test. The nomogram for exercise capacity from healthy Korean individuals and a previous landmark Western study was used to determine the percentage of predicted exercise capacity. The primary endpoint was the composite of major adverse cardiovascular events (MACE; all-cause death, myocardial infarction, repeat revascularization, stroke and hospitalization for heart failure). Results: A multivariate analysis showed that the risk of primary endpoint was more than double (hazard ratio [HR], 2.20; 95% confidence interval [CI], 1.10–4.40) in the patients with lower exercise capacity (< 85% of predicted) by Korean nomogram. The lower exercise capacity was one of the strong independent predictors along with left ventricular ejection fraction, age, and level of hemoglobin. However, the lower exercise capacity by Western nomogram could not predict the primary endpoint (HR, 1.33; 95% CI, 0.85–2.10). Conclusion Korean patients with CVD with lower exercise capacity have higher risk of MACE.Considering inter-ethnic differences in cardiorespiratory fitness, the Korean nomogram provides more suitable reference values than the Western nomogram to determine lower exercise capacity and predict cardiovascular events in Korean patients with CVD.

OBJECTIVE: The aim of this study was to demonstrate changes of subjective medication satisfaction and clinical benefit after once-daily paliperidone extended release (ER) in treatment of schizophrenia. METHODS: In an open-label, observational, and multicenter study, 374 patients with schizophrenia who switched to paliperidone ER due to any reason were recruited. Medication Satisfaction Questionnaire (MSQ), Clinical Global Impression-Severity (CGI-S), Clinical Global Impression-Improvement and visual analogue scale for sleep (VAS) were assessed at baseline, 4 weeks and 8 weeks after treatment. We also examined the type, frequency, and severity of adverse events newly formed. RESULTS: Among 374 patients, 320 patients (76.5%) were included in the intent-to-treat analysis set. The mean dose of paliperidone ER was 5.33+/-2.31 mg/day at the initiation. At the endpoint, the mean dose of paliperidone ER was 6.68+/-3.13 mg/day. The percentages of patients satisfied with medication were changed from 40.9% at baseline to 67.8% at endpoint (p<0.001). Both CGI-S scores and VAS for daytime drowsiness were significantly decreased after 8 weeks (both p<0.0001) and mean scores of MSQ and VAS for sleep quality were improved after 8 weeks (both p<0.0001). CONCLUSION: After switching to paliperidone ER, 67.8% of patients with schizophrenia who had any reason to switch medication showed subjective satisfaction for medication and clinical improvement without significant adverse events. Regarding that medication satisfaction was associated with changes of clinical states, medication satisfaction can be used for measures for clinical scales in the treatment of schizophrenia.
Humans ; Isoxazoles ; Prospective Studies ; Pyrimidines ; Surveys and Questionnaires ; Schizophrenia ; Sleep Stages ; Weights and Measures