Transcriptional Signature of Valproic Acid-Induced Neural Tube Defects in Human Spinal Cord Organoids

In vertebrates, the entire central nervous system is derived from the neural tube, which is formed through a conserved early developmental morphogenetic process called neurulation. Although the perturbations in neurulation caused by genetic or environmental factors lead to neural tube defects (NTDs), the most common congenital malformation and the precise molecular pathological cascades mediating NTDs are not well understood. Recently, we have developed human spinal cord organoids (hSCOs) that recapitulate some aspects of human neurulation and observed that valproic acid (VPA) could cause neurulation defects in an organoid model. In this study, we identified and verified the significant changes in cell–cell junctional genes/proteins in VPA-treated organoids using transcriptomic and immunostaining analysis. Furthermore, VPA-treated mouse embryos exhibited impaired gene expression and NTD phenotypes, similar to those observed in the hSCO model. Collectively, our data demonstrate that hSCOs provide a valuable biological resource for dissecting the molecular pathways underlying the currently unknown human neurulation process using destructive biological analysis tools.

Alterations in Structural and Functional Connectivities in Patients with End-Stage Renal Disease

Background@#and Purpose: The aim of this study was to evaluate the structural and functional connectivities of brain network using graph theoretical analysis in neurologically asymptomatic patients with end-stage renal disease (ESRD). We further investigated the prevalence of cognitive impairment (CI) in ESRD patients and analyzed the association between network measures of brain connectivity and cognitive function. @*Methods@#We prospectively enrolled 40 neurologically asymptomatic ESRD patients, 40 healthy controls, and 20 disease controls. All of the subjects underwent diffusion-tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rs-fMRI). We calculated measures of structural and functional connectivities based on DTI and rs-fMRI, respectively, and investigated differences therein between the ESRD patients and the healthy controls. We assessed cognitive function in the ESRD patients using the Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery. @*Results@#The ESRD patients exhibited decreased global structural and functional brain connectivities, as well as alterations of network hubs compared to the healthy controls and disease controls. About 70% of the ESRD patients had CI. Moreover, ESRD patients without CI exhibited decreased global connectivity and alterations of network hubs. Furthermore, there was a significant positive association between measures of brain connectivity and cognitive function. @*Conclusions@#We found that ESRD patients exhibited decreased structural and functional brain connectivities, and that there was a significant association between brain connectivity and cognitive function. These alterations in the brain network may contribute to the pathophysiological mechanism of CI in ESRD patients.

Headache attributed to acute pyelonephritis

Objective: This study identified the incidence and risk factors for headache attributed to acute pyelonephritis. Methods: The inclusion criteria were patients who were admitted with acute pyelonephritis at our hospital and ≥ 18 years of age. The following exclusion criteria were used: 1) patients who could not express their headache because of mental deterioration, 2) the presence of meningitis or meningoencephalitis, or 3) structural lesions on brain computed tomography or magnetic resonance images that could cause headache. The primary outcome was headache attributed to acute pyelonephritis as a dependent variable. The differences were analyzed using demographic and laboratory profiles as independent variables. Additionally, correlation analysis was performedbetweenseverity of headache using VAS score and demographic and laboratory profiles including age, WBC, and CRP. Results: A total of 479 patients met the inclusion criteria for this study, and 97 patients developed headache attributed to acute pyelonephritis. Patients with headache were younger and more likely to be female, and had a lower incidence of diabetes than those without headache. However, laboratory profiles that reflected the severity of acute pyelonephritis were not predictive factors for headache. Multiple logistic regression analysis demonstrated that young age and non-diabetes were independently significant variables for the prediction of headache attributed to acute pyelonephritis. In addition, the VAS score was found to be negative correlated with age, whereas it was not correlated with WBC and CRP. Conclusions: We determined that headache attributed to acute pyelonephritis was relatively common, and it was related to demographic characteristics but not acute pyelonephritis severity.

Has Snoring Significance for Predicting Obstructive Sleep Apnea Severity? / 대한임상신경생리학회지

BACKGROUND: The aim of this study was to investigate the predictive value of snoring frequency in the diagnosis and severity of obstructive sleep apnea. METHODS: Patients who underwent polysomnography with one or more of the following characteristics were included: 1) sleepiness, non-restorative sleep, fatigue, or insomnia symptoms; 2) arousal due to cessation of breathing or the occurrence of gasping or choking when waking up; and 3) habitual snoring, breathing interruptions, or both, noted by a bed partner or other observer. We analyzed the differences in clinical and polysomnographic variables between patients with and without obstructive sleep apnea and investigated the associations of those variables with obstructive sleep apnea severity. RESULTS: One hundred ninety-three patients met the inclusion criteria, and 145 of the 193 patients were diagnosed with obstructive sleep apnea. Multiple logistic regression analysis showed that large neck circumference (p = 0.0054) and high snoring index (p = 0.0119) were independent predictors for obstructive sleep apnea. Moreover, between the obstructive sleep apnea severity groups, there was a strong tendency of difference in body mass index (p = 0.0441) and neck circumference (p = 0.0846). However, there was no significant difference in snoring frequency according to obstructive sleep apnea severity (p = 0.4914). CONCLUSIONS: We confirmed that snoring frequency is a predictor of obstructive sleep apnea. In addition, we showed for the first time that snoring frequency is not associated with obstructive sleep apnea severity, thus it is not a valuable marker for predicting obstructive sleep apnea severity.

Predictors for Presence and Severity of Obstructive Sleep Apnea in Snoring Patients: Significance of Neck Circumference

OBJECTIVES: Documented risk factors for obstructive sleep apnea include advanced age, male gender, hypertension, large neck circumference, and obesity; but some controversy remains regarding the risk factors, especially in Asians. In this study, we evaluated the risk factors for obstructive sleep apnea in snoring patients, and also analyzed the risk factors that could predict the severity of obstructive sleep apnea. METHODS: The inclusion criteria were patients 1) who visited our hospital with a chief complaint of snoring as witnessed by a sleep partner and 2) who underwent overnight polysomnography. The primary endpoint was the presence of obstructive sleep apnea as a dependent variable. RESULTS: One hundred forty-seven patients met the inclusion criteria. Of the 147 patients, 109 patients were diagnosed with obstructive sleep apnea. Multivariate analysis showed that old age and large neck circumference were significant independent variables for predicting the presence of obstructive sleep apnea, whereas hypertension and large neck circumference were independent variables for predicting the severity of obstructive sleep apnea. CONCLUSIONS: We demonstrated that neck circumference can be used to predict the presence as well as the severity of obstructive sleep apnea in snoring Asian patients.

Hemolytic Uremic Syndrome with Clopidogrel after Coronary Angioplasty / 대한내과학회지

Thienopyridines are antiplatelet agents used in post-percutaneous coronary angioplasty patients and patients with acute coronary syndrome, stroke, and peripheral arterial disease. Ticlopidine has been shown to reduce the incidence of stent thrombosis, but it may also cause serious hematological side effects. Among the thienopyridines, clopidogrel is considered to be a safe alternative to ticlopidine because of its decreased incidence of hematological adverse effects. However, some hematological side effects can occur and may be fatal. In this case, a 47-year-old man complained of dyspnea and generalized edema. He had been taking clopidogrel after coronary angioplasty. His laboratory findings showed acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia, which were consistent with hemolytic uremic syndrome (HUS). After discontinuing clopidogrel and undergoing plasma exchange, he recovered fully. To our knowledge, this is the first reported case of clopidogrel-induced HUS in Korea.

A Case of a Right Atrial and Inferior Vena Caval Thrombus Resembling a Right Atrial Myxoma

A right atrial and inferior vena caval thrombus in a structurally normal heart is a very rare condition. We report a case of such a thrombus in a 66-year-old woman. She was admitted to our hospital with recent onset dyspnea. Based on echocardiography, we suspected that she had myxoma. We performed an excision of a mass, which was found, by pathologic examination, to be an organized mural thrombus.

Papillary Fibroelastoma Presenting as a Left Ventricular Mass

Cardiac papillary fibroelastoma (CPF) is a benign cardiac tumor that usually affects cardiac valves. It is usually discovered incidentally on routine echocardiography. However, left ventricular CPF is rare. This report describes the case of a 73-year-old female, referred to a cardiology department for evaluation of a mass of the left ventricle. The mass was found routine echocardiography. The transthoracic echocardiography revealed a 2.2x1.3 cm highly oscillating mass, attached by stalk on the inferior wall of the left ventricle. Cardiac magnetic resonance imaging demonstrated a non-enhanced, 1.8x1.0 cm mass on the inferior wall of the left ventricle. The patient underwent surgical resection of the mass, histopathologic examination of the mass confirmed the diagnosis of a CPF.

A Case of Functioning Paraganglioma in Posterior Mediastinum / 대한내분비학회지

Paraganglioma is an extraadrenal pheochromocytoma originating from chromaffin cells distributed in the sympathetic nervous systems. Functioning extraadrenal paragangliomas represent more than 10% of all pheochromocytomas, and seems to be highly malignant tumor in comparison to intraadrenal pheochromocytomas. Recently, we experienced a case of a paraganglioma in the posterior mediastinum. A 32-year-old woman was admitted to hospital due to dyspnea on exertion, and intractable hypertension. A chest X-ray showed a well-defined mass density on the right cardiac border, and biochemical studies showed characteristic findings of pheochromocytoma. A solitary pheochromocytoma was located in the posterior mediastinum using 131I-MIBG scintigraphy. The clinical manifestations, including hypertension and dyspnea were improved after operation.