Transition Substitution of Desired Bases in Human Pluripotent Stem Cells with Base Editors: A Step-by-Step Guide

The recent advances in human pluripotent stem cells (hPSCs) enable to precisely edit the desired bases in hPSCs to be used for the establishment of isogenic disease models and autologous ex vivo cell therapy. The knock-in approach based on the homologous directed repair with Cas9 endonuclease, causing DNA double-strand breaks (DSBs), produces not only insertion and deletion (indel) mutations but also deleterious large deletions. On the contrary, due to the lack of Cas9 endonuclease activity, base editors (BEs) such as adenine base editor (ABE) and cytosine base editor (CBE) allow precise base substitution by conjugated deaminase activity, free from DSB formation. Despite the limitation of BEs in transition substitution, precise base editing by BEs with no massive off-targets is suggested to be a prospective alternative in hPSCs for clinical applications. Considering the unique cellular characteristics of hPSCs, a few points should be considered. Herein, we describe an updated and optimized protocol for base editing in hPSCs. We also describe an improved methodology for CBE-based C to T substitutions, which are generally lower than A to G substitutions in hPSCs.

Prevalence and Public Awareness of Sleep Apnea Syndrome in South Korea

Objectives@#In South Korea, a significant number of patients with obstructive sleep apnea have benefited from the insured continuous positive pressure for sleep apnea as of 2018. However, there is limited information on public awareness of sleep apnea syndrome in the country. A nationwide survey was conducted to evaluate the current status of public awareness on the diagnosis and treatment of sleep apnea. @*Methods@#We conducted an online survey using structured questionnaires on symptoms and knowledge of diagnosis and treatment modalities for sleep apnea. A total of 4,000 participants aged 21 to 69 were proportionally allocated according to the residential area, gender, and age group. @*Results@#The STOP questionnaire, a screening tool for sleep apnea, revealed that 1,044 (21.6%) scored ≥2 points, 327 (8.1%) scored ≥3 points, and 64 (1.6%) scored 4 points. However, only 19 of the 1,044 patients were being treated for sleep apnea, and 13 had been using continuous positive airway pressure. For the diagnosis of sleep apnea, 1,318 participants (33.0%) responded that polysomnography was necessary. For sleep apnea treatment, 1,954 (48.9%) participants responded that lifestyle modification was the treatment of choice, while 1,036 (25.9%) chose continuous positive pressure. @*Conclusions@#Although one-fifth were at high risk for sleep apnea, this disorder is still underestimated. Therefore, publicity and support are needed to improve public awareness of sleep apnea.

Alterations of Functional Connectivity in Patients With Restless Legs Syndrome

Restless legs syndrome (RLS) is a common neurological illness marked by a strong desire to move one’s legs, usually in association with uncomfortable sensations. Recent studies have investigated brain networks and connectivity in RLS. The advent of network analysis has greatly improved our understanding of the brain and various neurological disorders. A few studies have investigated alterations in functional connectivity in patients with RLS. This article reviews functional connectivity studies of patients with RLS, which have identified significant alterations relative to healthy controls in several brain networks including thalamic, salience, default-mode, and small-world networks. In addition, network changes related to RLS treatment have been found, including to repetitive transcranial magnetic stimulation, transcutaneous spinal cord direct-current stimulation, and dopaminergic drugs. These findings suggest that the underlying pathogenesis of RLS includes alterations in the functional connectivity in the brain and that RLS is a network disorder.

Consideration for Coronavirus Disease 2019 Drug Treatment in Patients with Epilepsy on Antiepileptic Drugs

Several medications are approved to treat coronavirus disease 2019 (COVID-19) in Korea including nirmatrelvir/ritonavir, remdesivir, and regdanvimab. There is potential drug-drug interaction between antiepileptic drugs (AEDs) and the medications used to treat COVID-19. Several AEDs such as phenytoin, carbamazepine, phenobarbital, and primidone are strong cytochrome P450 inducers and can inhibit the drugs used for COVID-19. Particularly, these drugs are contraindicated with nirmatrelvir/ritonavir (Paxlovid®). There is a weaker drug-drug interaction between the AEDs and remdesivir. No significant interaction has been reported between the AEDs and molnupiravir. Pharmacokinetic interactions of the AEDs are important in effective management of COVID-19 in patients with epilepsy.

Garcinia Cambogia-Induced Refractory Status Epilepticus

Garcinia cambogia (G.cambogia) is a herbal dietary supplement for managing obesity. Several adverse effects of G.cambogia have been reported including serotonin syndrome and mania. We report a patient with refractory status epilepticus after taking G.cambogia. A 24-year-old woman was admitted with continuing seizures. Based on electroencephalography and neuroimaging findings, she was diagnosed as refractory status epilepticus attributed to G.cambogia-related encephalopathy. After cessation of the G.cambogia with administrating antiepileptic drugs, she fully recovered without seizure recurrence and neurological sequelae.

The Etiologies of Altered Level of Consciousness in the Emergency Department: Before versus after Coronavirus Disease-19

Background@#Altered level of consciousness (ALC) is a challenging condition in the emergency department (ED). We evaluated the clinical characteristics, causes, and prognosis of adult patients presenting with ALC at an ED of a university hospital. @*Methods@#The medical records of patients with ALC who visited the ED of a university hospital from February 2019 to November 2020 were reviewed to compare before and after the outbreak of coronavirus disease-19 (COVID-19) in Daegu, South Korea. The cause of ALC, its classification, the patients’ destinations, and prognosis were carefully decided and compared. @*Results@#A total of 1,851 patients with ALC in ED consisted of 1,068 before COVID-19 (BC; to February 17th, 2020) and 783 after COVID-19 (AC; from February 18th, 2020) were investigated. The all-time leading cause of ALC in ED was systemic infection (29.2% in BC, 25.0% in AC), followed by metabolic cause (21.0%) in BC and stroke (18.4%) in AC. Extra-cerebral etiologies of ALC were 1,206 (65.1%). The overall mortality of ALC in ED was 12.3%, consisting of 11.0% in BC and 14.2% in AC. During the daytime (07:00 to 18:59), patients in overall 1,179 patients (63.7%) with ALC visited ED, consisted of 665 (62.3%) in BC and 514 (65.5%) in AC. @*Conclusions@#This study demonstrated the extra-cerebral etiologies as the major causes of ALC in the ED. And there have been shifts in the etiology of ALC in ED.

The Emblems of Sleep Societies in Asia and the Republic of Korea

An emblem is a symbolic representational image that stands for a certain organization, concept, team, or society. This study investigated the emblems of the sleep societies in South Korea and the international sleep societies in which they were registered as members. Three South Korean sleep societies were found by searching for the keyword ‘sleep’ in the Korea Citation Index. Subsequently, we identified three international societies in which the three South Korean conferences participate. The emblems can be classified according to their composition. Taegeuk patterns represent yin and yang, electroencephalography that stands for the objective indicator of sleep, and the acronym or abbreviation indicating the name of the society. All emblems in this study were combinations of pictorial images and letters. The pictorial image of the Korean Sleep Research Society is the only emblem representing an inset with Hangeul. The emblem is a medium that conveys diverse meanings beyond representation. The societies have attempted to embody the identity as well as their directions.

Hospital Selection Factors of Sleep Disorder: Sleep Apnea Versus Other Sleep Disorders

Objectives@#The hospital selection factor is the criterion based on the judgment of the patients’ decision process. We investigated the hospital selection factors of patients with sleep disorders and compared that for patients with sleep apnea and other sleep disorders. @*Methods@#This is a questionnaire-based cross-sectional study that evaluated patients with a sleep disorder at the sleep unit of a tertiary referral center. We investigated the patients’ demographic information, occupational status, diagnosis of sleep disorders, and hospital-related and patient-related factors associated with hospital selection. @*Results@#A total of 138 patients with a sleep disorder were analyzed. Internet information was the primary data source for sleep apnea patients to select a hospital, while it was acquaintances for patients with other sleep disorders. None with sleep apnea gathered information from broadcast or print media. Patients gave the highest score for the least waiting time and recency of the hospital’s facility. Unlike patients with other sleep disorders, those with sleep apnea valued the hospital’s popularity, accessibility, availability of appointments at desired dates, and medical expense benefits. @*Conclusions@#This is the first study to analyze the hospital selection factors of patients with sleep disorders in South Korea. This study might improve the sleep medication as well as the medical system by revealing the medical use behavior of patients with sleep disorders.

Antiepileptic Drug Therapy for Status Epilepticus

Status epilepticus (SE) is one of the most serious neurologic emergencies. SE is a condition that encompasses a broad range of semiologic subtypes and heterogeneous etiologies. The treatment of SE primarily involves the management of the underlying etiology and the use of antiepileptic drug therapy to rapidly terminate seizure activities. The Drug Committee of the Korean Epilepsy Society performed a review of existing guidelines and literature with the aim of providing practical recommendations for antiepileptic drug therapy. This article is one of a series of review articles by the Drug Committee and it summarizes staged antiepileptic drug therapy for SE. While evidence of good quality supports the use of benzodiazepines as the first-line treatment of SE, such evidence informing the administration of second- or third-line treatments is lacking; hence, the recommendations presented herein concerning the treatment of established and refractory SE are based on case series and expert opinions. The choice of antiepileptic drugs in each stage should consider the characteristics and circumstances of each patient, as well as their estimated benefit and risk to them. In tandem with the antiepileptic drug therapy, careful searching for and treatment of the underlying etiology are required.

Treatments for Convulsive and Nonconvulsive Status Epilepticus in Adults: An Expert Opinion Survey in South Korea

Background@#and Purpose The aim of this study was to survey the expert opinions on treatments for convulsive status epilepticus (CSE) and nonconvulsive status epilepticus (NCSE) in adults. @*Methods@#Forty-two South Korean epileptologists participated in this survey. They completed an online questionnaire regarding various patient scenarios and evaluated the appropriateness of medications used to treat CSE and NCSE. @*Results@#Initial treatment with a benzodiazepine (BZD) followed by either a second BZD or an antiepileptic drug (AED) monotherapy was the preferred treatment strategy. More than two-thirds of the experts used a second BZD when the first one failed, and consensus was reached for 84.8% of the survey items. The preferred BZD was intravenous (IV) lorazepam for the initial treatment of status epilepticus. IV fosphenytoin and IV levetiracetam were chosen for AED monotherapy after the failure of BZD. The treatments for NCSE were similar to those for CSE. Continuous IV midazolam infusion was the treatment of choice for iatrogenic coma in refractory CSE, but other AEDs were preferred over iatrogenic coma in refractory NCSE. @*Conclusions@#The results of this survey are consistent with previous guidelines, and can be cautiously applied in clinical practice when treating patients with CSE or NCSE.

The Fever in the Emergency Department: before Versus after COVID-19 / 계명의대학술지

A high body temperature, i.e. fever, is a crucial vital sign, and suggests the patient’s infection or inflammation. COVID-19 has changed the lifestyle, and led to the changes in medical use behavior of febrile patients. We investigated the change in etiologies of fever in the emergency department (ED) before and after COVID-19. The medical records of patients with fever who visited the ED of a university hospital before and after the outbreak of COVID-19 in Daegu metropolitan city, South Korea. The cause of fever and its classification were carefully decided and established by agreement through a discussion among board-certified clinicians in emergency medicine, neurology, general surgery, and internal medicine. The etiology of fever and its prevalence in ED were compared between before and after COVID-19. A total of 3,041 patients with fever (> 37.7°C) in the ED were investigated, with 1,400 men (46.0%). Their mean age was 55.88 ± 20.59, and the average number of patients with fever in ED was 8.16 ± 3.94 per a day. The most common etiology before COVID-19 was respiratory system infection (n = 535, 30.5%), followed by gastrointestinal (n = 313, 17.8%) and urinary tract infection (n = 209, 11.9%). However, after COVID-19, gastrointestinal cause became the most common (n = 247, 27.3%), followed by respiratory system (n = 126, 13.9%) and urinary tract infection (n = 102, 11.3%). There has been paradigm-shifting in fever etiology in the emergency department. It is necessary to cope with the changed fever etiology in the COVID-19 era.

The Etiologies of Altered Level of Consciousness in the Emergency Department: Before versus after Coronavirus Disease-19

Background@#Altered level of consciousness (ALC) is a challenging condition in the emergency department (ED). We evaluated the clinical characteristics, causes, and prognosis of adult patients presenting with ALC at an ED of a university hospital. @*Methods@#The medical records of patients with ALC who visited the ED of a university hospital from February 2019 to November 2020 were reviewed to compare before and after the outbreak of coronavirus disease-19 (COVID-19) in Daegu, South Korea. The cause of ALC, its classification, the patients’ destinations, and prognosis were carefully decided and compared. @*Results@#A total of 1,851 patients with ALC in ED consisted of 1,068 before COVID-19 (BC; to February 17th, 2020) and 783 after COVID-19 (AC; from February 18th, 2020) were investigated. The all-time leading cause of ALC in ED was systemic infection (29.2% in BC, 25.0% in AC), followed by metabolic cause (21.0%) in BC and stroke (18.4%) in AC. Extra-cerebral etiologies of ALC were 1,206 (65.1%). The overall mortality of ALC in ED was 12.3%, consisting of 11.0% in BC and 14.2% in AC. During the daytime (07:00 to 18:59), patients in overall 1,179 patients (63.7%) with ALC visited ED, consisted of 665 (62.3%) in BC and 514 (65.5%) in AC. @*Conclusions@#This study demonstrated the extra-cerebral etiologies as the major causes of ALC in the ED. And there have been shifts in the etiology of ALC in ED.

The Emblems of Sleep Societies in Asia and the Republic of Korea

An emblem is a symbolic representational image that stands for a certain organization, concept, team, or society. This study investigated the emblems of the sleep societies in South Korea and the international sleep societies in which they were registered as members. Three South Korean sleep societies were found by searching for the keyword ‘sleep’ in the Korea Citation Index. Subsequently, we identified three international societies in which the three South Korean conferences participate. The emblems can be classified according to their composition. Taegeuk patterns represent yin and yang, electroencephalography that stands for the objective indicator of sleep, and the acronym or abbreviation indicating the name of the society. All emblems in this study were combinations of pictorial images and letters. The pictorial image of the Korean Sleep Research Society is the only emblem representing an inset with Hangeul. The emblem is a medium that conveys diverse meanings beyond representation. The societies have attempted to embody the identity as well as their directions.

Hospital Selection Factors of Sleep Disorder: Sleep Apnea Versus Other Sleep Disorders

Objectives@#The hospital selection factor is the criterion based on the judgment of the patients’ decision process. We investigated the hospital selection factors of patients with sleep disorders and compared that for patients with sleep apnea and other sleep disorders. @*Methods@#This is a questionnaire-based cross-sectional study that evaluated patients with a sleep disorder at the sleep unit of a tertiary referral center. We investigated the patients’ demographic information, occupational status, diagnosis of sleep disorders, and hospital-related and patient-related factors associated with hospital selection. @*Results@#A total of 138 patients with a sleep disorder were analyzed. Internet information was the primary data source for sleep apnea patients to select a hospital, while it was acquaintances for patients with other sleep disorders. None with sleep apnea gathered information from broadcast or print media. Patients gave the highest score for the least waiting time and recency of the hospital’s facility. Unlike patients with other sleep disorders, those with sleep apnea valued the hospital’s popularity, accessibility, availability of appointments at desired dates, and medical expense benefits. @*Conclusions@#This is the first study to analyze the hospital selection factors of patients with sleep disorders in South Korea. This study might improve the sleep medication as well as the medical system by revealing the medical use behavior of patients with sleep disorders.

Clinical Approach to Autoimmune Epilepsy

Autoimmune epilepsy is a newly emerging area of epilepsy. The concept of “autoimmune” as an etiology has recently been revisited thanks to advances in autoimmune encephalitis and precision medicine with immunotherapies. Autoimmune epilepsy presents with specific clinical manifestations, and various diagnostic approaches including cerebrospinal fluid analysis, neuroimaging, and autoantibody tests are essential for its differential diagnosis. The diagnosis is often indeterminate despite performing a thorough evaluation, and therefore empirical immunotherapy may be applied according to the judgment of the clinician. Autoimmune epilepsy often manifests as new-onset refractory status epilepticus (NORSE). A patient classified as NORSE should receive empirical immunotherapy as soon as possible. On the other hand, a morecautious, stepwise approach is recommended for autoimmune epilepsy that presents with episodic events. The type of autoimmune epilepsy is also an important factor to consider when choosing from among various immunotherapy options. Clinicians should additionally take the characteristics of antiepileptic drugs into account when using them as an adjuvant therapy. This expert opinion discusses the diagnostic and treatment approaches for autoimmune epilepsy from a practical point of view.

Antiepileptic Drug Selection According to Seizure Type in Adult Patients with Epilepsy

Epilepsy is a common neurological disorder that is mainly treated using antiepileptic drugs.Several antiepileptic drugs such as phenobarbital, phenytoin, primidone, and ethosuximide were developed in the early 20th century. More than 10 types of antiepileptic drugs have been developed since the 1990s, and there are now more than 20 antiepileptic drugs in active clinical use. The choice of antiepileptic drugs is based on the clinical features of the seizure types, electroencephalogram findings, epileptic syndrome, and drug stability. Currently there are 19 antiepileptic drugs approved by the Korean Food and Drug Administration, 18 of which (with the exclusion of brivaracetam) are covered by the National Health Insurance Service in Korea. We reviewed the selection of antiepileptic drugs according to the classification of epileptic seizures.

Pharmacological Treatment of Epilepsy in Elderly Patients

The incidence and prevalence of epilepsy are highest in elderly people, and the etiologies of epilepsy in the elderly differ from those in other age groups. Moreover, diagnosing and treating epilepsy in elderly people may be challenging due to differences in clinical characteristics and physiological changes associated with aging. This review focuses on the pharmacological treatment of epilepsy in elderly patients.

Refining General Principles of Antiepileptic Drug Treatments for Epilepsy

Antiepileptic drugs (AEDs) are the primary treatment strategy for epilepsy. As the use of AEDs has become more widespread and diverse over the past century, it has become necessary to refine the associated prescription strategies. This prompted the Drug Committee of the Korean Epilepsy Society to perform a systemic review of both international and domestic guidelines as well as literature related to medical treatment of epilepsy, and prepared a series of reviews to provide practical guidelines for clinicians to follow. This article is the first in a series on AED treatments for epilepsy in South Korea.

Pregnancy and Epilepsy: a Korean Tertiary Epilepsy Center Review

Background@#Pregnancy in women with epilepsy (WWE) is known to have a higher risk for fetal development complications, which may include congenital malformations. Unfortunately, information pertaining to pregnancy in WWE is difficult to obtain because there are considerable ethical issues preventing these studies from being conducted on pregnant women. Therefore, this study investigated the pregnancies of Korean WWE in a tertiary epilepsy center to observe data resulting from the outcome of the pregnancies. @*Methods@#This was a retrospective study of 48 pregnant WWE who were treated at the regional tertiary epilepsy center. All records of hospital visits before and after the period of pregnancy were analyzed to obtain information about the seizures as well as pregnancy-related outcomes, including the status of the newborns' conditions. @*Results@#The subject group consisted of 31 (63.3%) with partial epilepsy, 6 (12.5%) with generalized epilepsy, and 11 (22.9%) with unclassified epilepsy. There were 27 subjects who took one antiepileptic drug (AED), and 12 who took two AEDs. The most commonly used drug was lamotrigine (29.8%). Of the 48 WWE involved in the study, 31 underwent caesarian sections and 17 opted for natural birth. Thirty-nine (81.3%) delivered at full-term, but 9 (18.7%) delivered at preterm. Compared to full-term infants, pre-mature infants showed lower birth weight, smaller head circumference, shorter height, and lower 1-minute Apgar scores, but seizure frequencies of the mothers did not differ. @*Conclusion@#In WWE, epilepsy classification, number of AEDs taken, and frequency of seizures are not significantly correlated with delivery and fetal condition. This data could be used as a clinical reference for physicians to provide useful information to WWE if they are concerned about their pregnancies.

The Mental Health and Sleep Quality of the Medical Staff at a Hub-Hospital against COVID-19 in South Korea

Objectives@#Now, coronavirus disease (COVID-19) is worldwide threatening. Medical staff’s efforts and sacrifices against COVID-19 are still ongoing. The purpose of this study was to investigate the mental health of the medical staff who have fought against the COVID-19 in hub hospitals. @*Methods@#The medical staff underwent an evaluation of psychiatric and sleep status between March 23rd and April 3rd, 2020. Based on the evaluation, we retrospectively analyzed depression, anxiety, and sleep quality of the medical staff, who worked more than 7 days for fighting against the COVID-19. @*Results@#This study included a total of 101 medical staff. Approximately 1/4 of the medical staff showed depressive mood and low quality of sleep, and more than 1/3 reported anxiety. The nurses reported more severe psychiatric symptoms and poorer sleep quality. @*Conclusions@#This study demonstrated the mental and sleep status of the medical staff against COVID-19. Medical and social support should be considered for them.