Efficacy and Safety of Escitalopram, Desvenlafaxine, and Vortioxetine in the Acute Treatment of Anxious Depression: A Randomized Rater-blinded 6-week Clinical Trial

Objective@#Anxious depression is associated with greater chronicity, higher severity of symptoms, more severe functional impairment, and poor response to drug treatment. However, evidence for first-choice antidepressants in patients with anxious depression is limited. This study aimed to compare the efficacy and safety of escitalopram, desvenlafaxine, and vortioxetine in the acute treatment of anxious depression. @*Methods@#Patients (n = 124) with major depressive disorder and high levels of anxiety were randomly assigned to an escitalopram treatment group (n = 42), desvenlafaxine treatment group (n = 40), or vortioxetine treatment group (n = 42) in a 6-week randomized rater-blinded head-to-head comparative trial. Changes in overall depressive and anxiety symptoms were assessed using the 17-item Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Rating Scale (HAMA), respectively. @*Results@#Patients demonstrated similar baseline-to-endpoint improvement in scores and similar response and remission rates for HAMD and HAMA. Analysis of the individual HAMD items revealed that desvenlafaxine significantly reduced anxiety somatic scores (p= 0.013) and hypochondriasis scores (p = 0.014) compared to escitalopram. With respect to the individual HAMA items, desvenlafaxine treatment showed significantly lower scores for respiratory symptoms (p = 0.013) than escitalopram treatment and cardiovascular symptoms (p = 0.005) than vortioxetine treatment. The treatments were well tolerated, with no significant differences. @*Conclusion@#Our results indicated no significant differences in the efficacy and tolerability of escitalopram, desvenlafaxine, and vortioxetine in this subtype of patients with anxious depression during the acute phase of treatment.

Plasminogen Activator Inhibitor-1: Potential Inflammatory Marker in Late-life Depression

Objective@#Although several previous studies have examined the association between late-life depression and blood adipokine levels, a marker of chronic inflammation, no studies have comprehensively considered the effects of metabolic syndrome, which is known to affect blood adipokine levels. This study examined blood adipokine levels in geriatric depression after adjusting for the effects of metabolic syndrome. @*Methods@#Participants were selected from the Ansan Geriatric Study (depression group [n = 76] and control group [n = 76]). Blood concentrations of four adipokines (adiponectin, resistin, neutrophil-gelatinase-associated lipocalin [NGAL], and plasminogen activator inhibitor-1 [PAI-1]) were measured using immunoassays. The effects of blood adipokine concentration on the diagnosis of depression were analyzed using multivariate logistic regression to adjust for the effects of metabolic syndrome and potential confounding factors. @*Results@#When the effects of metabolic syndrome and potential confounding factors were adjusted, only PAI-1 could explain the diagnosis of depression among all the adipokines. The depression group showed a lower blood PAI-1 level than the control group. Adiponectin, resistin, and NGAL could not explain the diagnosis of depression when the effects of metabolic syndrome and potential confounding factors were adjusted. @*Conclusion@#This study suggests the possibility that the blood PAI-1 levels in clinically pathological late-life depression may show contrasting results to those with subclinical depressive symptoms. Additionally, considering that most previous studies have been conducted with pre-geriatric populations, the study suggests the possibility that geriatric depression may show inflammatory changes with patterns that are different from those of depression in the pre-geriatric population.

Effectiveness of the COVID-19 vaccine in the Honam region of the Republic of Korea

Objectives@#In 2021, the effectiveness of the COVID-19 vaccine was analyzed among people living in the Honam region (Gwangju, Jeollanam-do, Jeollabuk-do, and Jeju) of the Republic of Korea. And we investigated changes in the dominant virus strain. @*Methods@#This study used the data provided by the Korean Ministry of the Interior and Safety for individuals ≥12 years old in the Honam region, and the Integrated Disease and Health Management System of the Korea Centers for Disease Control and Prevention for COVID-19-vaccinated individuals as of December 31, 2021. Statistical analyzes were performed using IBM SPSS ver. 23.0. The occurrence of confirmed cases by vaccination status, the relative risk, and vaccine effectiveness by vaccine type were calculated. @*Results@#In 2021, the COVID-19 vaccination rate in Honam was 88.6%. The overall vaccine effectiveness (after 2 and 3 doses) was 98.7% (p98%, and the effect among persons who received 2 doses was >90% regardless of the vaccine type. Although vaccine effectiveness decreased because of reduced antibody levels over time (as observed in breakthrough infections), receiving a booster dose restored the neutralizing antibody levels.

Surgical treatment of knee osteoarthritis focusing on the patellofemoral joint

Surgical management of the osteoarthritic knee joint consists of osteotomies such as a high tibial osteotomy (HTO), uni-compartmental knee arthroplasty (UKA), and total knee arthroplasty (TKA). These surgeries mainly treat the tibiofemoral joint but can also have an impact on the patellofemoral (PF) joint. These changes in PF joint can affect the surgical outcome.Current Concepts: PF joint problems are relative contraindications in UKA. However, recent studies have reported that these problems do not markedly affect the result of UKA. During HTO, the patella height and tracking can change, affecting the PF joint problem. The effect of the PF joint can be minimized through various methods of closing wedge HTO or modified opening wedge (OW) HTO, such as retro-tubercular biplanar OWHTO. However, this method is controversial regarding its impact on clinical outcomes. In TKA, pain caused by PF joint problems can be reduced using techniques such as patella resurfacing, patelloplasty, and denervation; however, there is no clear consensus.Discussion and Conclusion: The surgical treatment of degenerative knee osteoarthritis has an impact on the PF joint, which can affect the outcome of surgery and vice versa. However, these impacts only occasionally cause clinical difference. Conclusively, these surgeries should be done by considering the PF joint because changes in the joint can affect the surgical outcome.

Elevated BMPR2 expression amplifies osteoblast differentiation in ankylosing spondylitis

Objective@#Bone morphogenetic protein receptor type 2 (BMPR2) has been associated with radiographic changes in ankylosing spondylitis (AS), but further characterization of the cellular signaling pathway in osteoprogenitor (OP) is not clearly understood.The aim of this study was to investigate the expression of BMPR2 and bone morphogenetic protein 2 (BMP2)-mediated responsibility in AS. @*Methods@#We collected 10 healthy control (HC) and 14 AS-OPs derived from facet joints. Subsequently, we then conducted RNA sequencing with two samples per group and selected BMP-related genes. Facet joint tissues and derived primary OPs were evaluated by validation of selected RNA sequencing data, immunohistochemistry, and comparison of osteogenic differentiation potential. @*Results@#Based on RNA-sequencing analysis, we found that BMPR2 expression is higher in AS-OPs compared to in HC-OPs. We also validated the increased BMPR2 expression in facet joint tissues with AS and its derived OPs in messenger RNA and protein levels. Additionally, primary AS-OPs showed much greater response to osteogenic differentiation induced by BMP2 and a higher capacity for smad1/5/8-induced RUNX2 expression compared to HCs. @*Conclusion@#The expression of BMPR2 was found to be significantly increased in facet joint tissues of patients with AS. These findings suggest that BMPR2 may play a role in the BMP2-mediated progression of AS.

Clinical Practice Guideline: Clinical Efficacy of Nasal Surgery in the Treatment of Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is a common disorder characterized by upper airway obstruction during sleep. To reduce the morbidity of OSA, sleep specialists have explored various methods of managing the condition, including manifold positive airway pressure (PAP) techniques and surgical procedures. Nasal obstruction can cause significant discomfort during sleep, and it is likely that improving nasal obstruction would enhance the quality of life and PAP compliance of OSA patients. Many reliable studies have offered evidence to support this assumption. However, few comprehensive guidelines for managing OSA through nasal surgery encompass all this evidence. In order to address this gap, the Korean Society of Otorhinolaryngology-Head and Neck Surgery (KORL-HNS) and the Korean Society of Sleep and Breathing designated a guideline development group (GDG) to develop recommendations for nasal surgery in OSA patients. Several databases, including OVID Medline, Embase, the Cochrane Library, and KoreaMed, were searched to identify all relevant papers using a predefined search strategy. The types of nasal surgery included septoplasty, turbinate surgery, nasal valve surgery, septorhinoplasty, and endoscopic sinus surgery. When insufficient evidence was found, the GDG sought expert opinions and attempted to fill the evidence gap. Evidence-based recommendations for practice were ranked according to the American College of Physicians’ grading system. The GDG developed 10 key action statements with supporting text to support them. Three statements are ranked as strong recommendations, three are only recommendations, and four can be considered options. The GDG hopes that this clinical practice guideline will help physicians make optimal decisions when caring for OSA patients. Conversely, the statements in this guideline are not intended to limit or restrict physicians’ care based on their experience and assessment of individual patients.

The Cognitive Profiles of Partial PTSD in Vietnam War Veterans / 신경정신의학

Objectives@#This study identifies the distinct cognitive function profiles of partial posttraumatic stress disorder (PTSD). @*Methods@#Medical records of Vietnam War Korean Veterans, who visited a psychiatric clinic and underwent a Clinician-Administered PTSD scale (CAPS) and neurocognitive test on the same day, were retrospectively reviewed. Based on the CAPS interview, participants were divided into partial PTSD (n=10) and non-PTSD (n=36) groups. The neurocognitive test score profiles of both groups were compared. Analysis of covariance was performed to adjust the contribution of possible confounders to cognitive function. @*Results@#Cognitive profile analysis displayed significantly poorer performance of executive function and mental flexibility (measured by the Trail Making Test B) and concentration (measured by mini mental status exam) in the partial PTSD group. When adjusted with age, depressive symptom measure, and education level, no significant differences were obtained in the cognitive profiles between both groups. @*Conclusion@#Results of the current study revealed a deficit in executive function and concentration in partial PTSD subjects compared to non-PTSD. However, when adjusted with possible confounders such as depressive symptoms, the cognitive profiles of partial PTSD displayed no significant difference with the cognitive profiles of non-PTSD subjects.

Differences in White Matter Hyperintensity in Elderly Veterans With and Without Post-Traumatic Stress Disorder

Objective@#Exposure to stressful events is associated with the progression of white matter hyperintensity (WMH). The purpose of this study was to determine the difference in WMH depending on the presence of Post-traumatic stress disorder (PTSD). @*Methods@#The patients who underwent brain magnetic resonance imaging and clinician-administered PTSD scale (CAPS) at the Veteran Health Service Medical Center were reviewed retrospectively. WMH were evaluated using the Fazekas scale. The patients with PTSD (n=51; age 66.25±10.43 years) were compared with patients exposed to trauma without PTSD (n=67; age 69.45±10.44 years). @*Results@#The scores of Beck Depression Scale, Beck Anxiety scale, and CAPS were significantly higher in the PTSD group. The PTSD group showed a significant difference on the Fazekas scale compared to the trauma-exposed group without PTSD (periventricular white matter, p=0.001; deep white matter, p=0.008). After adjusting for age, smoking and comorbidity, WMH was higher in the PTSD group than in the trauma exposed group (periventricular white matter, p<0.001; deep white matter, p=0.006). @*Conclusion@#The results suggests that there may be an association between PTSD and WMH as well as stressful events.

Changes in Patients Who Receive Coverage for Positive Airway Pressure Therapy According to Alterations in National Health Insurance Benefit Standards for Mild Obstructive Sleep Apnea / 대한이비인후과학회지

Background and Objectives@#The aim of this study was to identify the frequency of indicators of National Health Insurance (NHI) coverage for positive airway pressure (PAP) therapy and to investigate the changes in patients receiving coverage for PAP therapy after the alterations were made in the insurance benefit standards for mild obstructive sleep apnea (OSA).Subjects and Method We divided the mild OSA patients into two groups according to altered categorization in insurance benefit standards (Mild1: 5≤AHI<10; Mild2: 10≤AHI<15). Eight indicators related to the NHI coverage were identified: four symptoms, three complications, and the minimal blood oxygen saturation during polysomnography (min SpO2) of ≤85% during polysomnography. We also investigated the change in the number of patients receiving insurance benefits under the altered insurance benefit standards. @*Results@#Of the 233 OSA patients, 66, 57, and 110 patients were diagnosed as mild, moderate and severe OSA, respectively. For all of them, the most common indicator related to NHI coverage for PAP therapy was the minimum SpO2 of less than 85% during polysomnography, and the second most common indicator was daytime sleepiness. In the mild OSA group, however, daytime sleepiness was found to be the most common indicator, found in 46 (70%) patients, followed by 38 (58%) patients with min SpO2 of less than 85%. In this group, 59 (89.4%) would have been benefited before the change in the insurance benefit standards whereas 51 patients (77.3%) would now be benefited under the changed insurance benefit standards. @*Conclusion@#Daytime sleepiness was the most commonly observed indicator in the mild OSA patients. The number of patients receiving insurance benefits for PAP therapy significantly decreased after the change was made in the NHI benefit standards for mild OSA

A Korean Child with Schaaf-Yang Syndrome Presented with Hearing Impairment: A Case Report

Schaaf-Yang syndrome (SYS) is a rare genomic imprinting disorder caused by truncating mutations in the paternally derived MAGE family member L2 (MAGEL2) allele. It is also responsible for Prader-Willi syndrome, characterized by neonatal hypotonia, developmental delay, intellectual disability, respiratory distress in early infancy, and arthrogryposis. More than 250 individuals with approximately 57 different molecular variants have been reported since 2013, but the phenotype-genotype association in SYS is not yet fully understood. Here, we describe the case of a Korean patient diagnosed with SYS harboring a mutation in the paternal allele of MAGEL2: c.2895G>A, resulting in a protein change of p.Trp965*. The patient’s phenotype included respiratory distress, arthrogryposis, hypotonia, and feeding difficulty in the early neonatal period. Mild renal dysfunction and hearing impairment were observed during infancy.

A Review on the Cause of Fever During Clozapine Treatment / 정신신체의학

Clozapine is accepted as the “gold standard” antipsychotics for treatment-resistant schizophrenia. Clozapine rarely causes extrapyramidal syndrome and tardive dyskinesia, which are common with other antipsychotics, and only a transient elevation of hyperprolactinemia has been reported. Despite such clinical usefulness, there are limitations to the use of clozapine due to adverse drug reactions (ADR). Fever is a common in adverse drug reactions associated with clozapine. At initiation of clozapine most fatal ADR such as agranulocytosis and neuroleptic malignant syndrome associated with fever, in which case clozapine should be discontinued immediately. However, as benign causes of fever are much more frequent than life-threatening ADR, clozapine should not be discontinued unconditionally in the event of fever during clozapine initiation. In addition, fever may occur at any time during the maintenance of clozapine treatment. In particular, since the risk of pneumonia does not decrease over time, and clozapine has a higher risk of pneumonia than other antipsychotic drugs, it is recommended to adjust clozapine dosage through therapeutic drug monitoring.

Cognitive Processing Therapy as a First-line Treatment for Post-Traumatic Stress Disorder / 정신신체의학

Posttraumatic stress disorder (PTSD) is well known to have a limited response to drug treatment. Many recently published clinical care guidelines recommend trauma-focused psychotherapies such as cognitive processing therapy (CPT) and prolonged exposure therapy (PE) as first-line treatment and medication such as sero-tonin reuptake inhibitors and venlafaxine as second-line treatment. Current review introduces the session composition and contents of CPT and presents various CPT studies that show therapeutic effect for civilian and veterans/military with PTSD. In order for clinicians to help effectively patients with PTSD, it is necessary to learn and actively use evidence-based trauma-focused psychotherapies including CPT and PE.

Acute Efficacy and Safety of Escitalopram Versus Desvenlafaxine and Vortioxetine in the Treatment of Depression With Cognitive Complaint: A Rater-Blinded Randomized Comparative Study

Objective@#This study aimed to compare the efficacy and safety of escitalopram, vortioxetine, and desvenlafaxine for acute treatment of major depressive disorder (MDD) with cognitive complaint (CC). @*Methods@#A total of 129 patients with MDD who also complained of CC were randomized evenly to either escitalopram, vortioxetine, or desvenlafaxine group and underwent a multi-center, six-week, rater-blinded, and head-to-head comparative trial. Differences in depressive symptoms following treatment were measured using the Hamilton Depression Rating Scale (HAMD) and the Montgomery-Åsberg Depression Rating Scale (MADRS). Subjective cognitive function and the presence of adverse events were assessed. @*Results@#The three antidepressant treatment groups did not show significant differences in the improvement of depressive symptoms as measured by HAMD and MADRS. Desvenlafaxine treatment was associated with a superior treatment response rate in depressive symptoms compared to vortioxetine or escitalopram treatment. However, no significant differences were found in the remission rate of depressive symptoms. The three antidepressant treatment groups did not show significant differences in the improvement of CC. Adverse profiles of each treatment group were tolerable, with no significant differences. @*Conclusion@#In acute antidepressant treatment for MDD with CC, escitalopram, vortioxetine, and desvenlafaxine presented similar efficacy in relief of depressive symptoms; however, desvenlafaxine was associated with a superior treatment. Further studies are needed to confirm these results by investigating the therapeutic efficacy and safety profile of long-term antidepressant treatment of MDD with CC (Clinical Trial Registry, http://cris.nih.go.kr/cris/en/: KCT0002173).

Adherence to Positive Airway Pressure therapy as Severity of Adult Obstructive Sleep Apnea / 대한이비인후과학회지

Background and Objectives@#The aim of this study was to compare adherence to positive airway pressure (PAP) therapy in patients with obstructive sleep apnea (OSA) of different severity.Subjects and Method We conducted a retrospective study including 270 adult OSA patients who used a PAP device for at least 3 months. We assessed the percentage of days on which the device was used, the percentage of days on which the device was used for ≥4 h, and the average duration of PAP device usage at 12 weeks of PAP therapy. We also evaluated adequate adherence to PAP therapy using a PAP device for ≥4 h/day and during ≥70% of nights. @*Results@#The percentage of days on which a PAP device used did not differ significantly according to OSA severity (median [Q1-Q3]; mild: 91.40% [81.25%-97.65%], moderate: 94.50% [86.90%-100%], severe: 95.90% [88.10%-100%], p=0.268). We also found that the percentage of days on which a PAP device was used during sleep for ≥4 h was not significantly different in patients with different OSA severity (median [Q1-Q3], mild: 76.20% [69.70%-89.90%], moderate: 89.30% [67.65%-95.70%], severe: 85.70% [75.85%-95.45%], p=0.097). The percentage of patients with adequate PAP adherence did not differ significantly according to OSA severity (mild: 74.2%, moderate: 72.1%, severe: 83.0%, p=0.084). Moreover, the mean duration (minutes) of PAP device usage during sleep did not differ significantly according to OSA severity in the mild, moderate, and severe OSA groups (mean±standard deviation, mild: 348.03± 47.78 min, moderate: 358.58±85.22 min, severe: 363.79±57.21 min, p=0.440). @*Conclusion@#Adherence to PAP therapy did not differ significantly according to OSA severity. Therefore, it is necessary to continuously expand and maintain the insurance for health promotion in OSA patient in South Korea.

Influence of Nasal Cavity Dimension and Sleep Posture on the Severity of Obstructive Sleep Apnea / 대한이비인후과학회지

Background and Objectives@#The aim of this study was to evaluate the effect of sleep position and nasal cavity dimension according to minimal cross-sectional area (MCA) on the severity of obstructive sleep apnea (OSA).Subjects and Method This study enrolled 528 consecutive patients who completed overnight polysomnography (PSG) and acoustic rhinometry. Positional sleep time and apnea-hypopnea index (AHI) were compared between the right and left lateral sleep positions (RLSP vs. LLSP), and between the wide and narrow lateral side sleep position (WLSP vs. NLSP) according to MCA. @*Results@#The sleep time was longer for LSP than for WLSP (20.35%±19.69% and 15.92%±16.35%, respectively) with a statistically significant difference (p=0.001). However, the AHI was not significantly different between the two groups. The sleep time was longer for RLSP than for LLSP (20.65%±19.31% and 15.39%±16.05%, respectively) with a statistically significant difference (p<0.001). In the RLSP-dominant group, there were fewer left nasal cavity narrowed patients than right nasal cavity narrowed patients (91 vs. 129, respectively). Furthermore, in the LLSP-dominant group, there were fewer right nasal cavity narrowed patients than left nasal cavity narrowed patients (60 vs. 85, respectively, p=0.001). However, we found that the AHI value was not significantly different according to sleep posture and nasal cavity dimension. @*Conclusion@#Snoring patients preferred RLSP to LLSP, and preferred to sleep on the lateral side of the narrow nasal cavity. The OSA severity was not different according to sleep position and nasal cavity dimension.

Standardization of the Korean Version of the Patient Health Questionnaire-4 (PHQ-4)

Objective@#The Patient Health Questionnaire-4 (PHQ-4) has been used for screening owing to ease of use and brevity.In this study, we developed the Korean version of the PHQ-4 and tested its validity. @*Methods@#One hundred sixteen new adult outpatients at the Department of Psychiatry of the Korea University Ansan Hospital participated in the study. We simultaneously administered other depression/anxiety scales: the Hamilton Rating Scale for Depression, the Hamilton Anxiety Scale, the Beck Depression Inventory, and the Beck Anxiety Inventory. @*Results@#The mean PHQ-4 score was 6.52 (standard deviation = 3.45). Cronbach’s α was 0.792, and the intraclass correlation coefficient of test and 2-week interval retest was 0.827 (p ＜ 0.01). The Pearson correlation coefficients between the PHQ-4 total score and other depression/anxiety scales were all over 0.6. Confirmatory factorial analysis showed acceptable convergent validity and reliability but questionable discriminant validity for some model fit values. @*Conclusion@#The Korean version of the PHQ-4 has sufficient internal consistency, test-retest reliability, and construct validity, but its two-factor structure showed incompleteness. However, we suggest that it should be used as a brief screening measure for common psychiatric distress that warrants further detailed assessment, but not to separately assess the severity of depression and anxiety symptoms.

Clinical Features of Olfactory Dysfunction in COVID-19 Patients

Background@#The aim of this study was to evaluate the subjective and objective olfactory function in coronavirus disease 2019 (COVID-19) patients and the effect of olfactory training. @*Methods@#A prospective cohort study was performed in 53 patients who recovered from COVID-19 and visited our tertiary hospital. Subjective olfactory function was evaluated using the 11-point Likert scale (0–10) and the Korean version of the Questionnaire of Olfactory Disorders (QOD). Objective olfactory function was evaluated using Cross-Cultural Smell Identification Test (CC-SIT). Confirmed patients were followed up after 2 months of olfactory training. @*Results@#The median, interquartile range (Q1–Q3) score of subjective olfactory function significantly deteriorated in patients with olfactory dysfunction (OD) than in those without OD, even after 3 months of onset (11-point Likert scale, 8, 6–9 vs. 10, 10–10; short version of QOD-negative statements, 19, 16–21 vs. 21, 21–21; QOD-visual analogue scale, 7, 1–13 vs. 0, 0–0; all P < 0.001). However, the objective olfactory function was not significantly different between the two groups (median, interquartile range; 11, 9–11 vs. 11, 9–11, P = 0.887). The percentage of patients with objective hyposmia (CC-SIT ≤ 10) was also not significantly different (47.4% vs. 40%,P = 0.762). OD in COVID-19 was normalized after 2 months of olfactory training in 70% of patients even after 3 months of olfactory impairment. @*Conclusion@#Although subjective olfactory function is significantly decreased in the OD group, the objective olfactory function was not significantly different. Moreover, olfactory training is effective in COVID-19 patients with OD.

Changes in Brain Electrical Activity According to Post-traumatic Stress Symptoms in Survivors of the Sewol Ferry Disaster: A 1-year Longitudinal Study

Objective@#The pathology of post-traumatic stress disorder (PTSD) is associated with changes in brain structure and function, especially in the amygdala, medial prefrontal cortex, hippocampus, and insula. Survivors of tragic accidents often experience psychological stress and develop post-traumatic stress symptoms (PTSS), regardless of the diagnosis of PTSD. This study aimed to evaluate electroencephalographic changes according to PTSS in victims of a single traumatic event. @*Methods@#This study enrolled 60 survivors of the Sewol ferry disaster that occurred in 2014 from Danwon High School and collected electroencephalographic data through 19 channels twice for each person in 2014 and 2015 (mean 451.88 [standard deviation 25.77] days of follow-up). PTSS was assessed using the PTSD Checklist-Civilian Version (PCL-C) and the participants were divided into two groups according to the differences in PCL-C scores between 2014 and 2015. Electroencephalographic data were converted to three-dimensional data to perform low-resolution electrical tomographic analysis. @*Results@#Significant electroencephalographic changes over time were observed. The group of participants with worsened PCL-C score showed an increased change of delta slow waves in Brodmann areas 13 and 44, with the largest difference in the insula region, compared to those with improved PCL-C scores. @*Conclusion@#Our findings suggests that the electrophysiological changes in the insula are associated with PTSS changes.

Novel Anti-Angiogenic and Anti-Tumour Activities of the N-Terminal Domain of NOEY2 via Binding to VEGFR-2 in Ovarian Cancer

The imprinted tumour suppressor NOEY2 is downregulated in various cancer types, including ovarian cancers. Recent data suggest that NOEY2 plays an essential role in regulating the cell cycle, angiogenesis and autophagy in tumorigenesis. However, its detailed molecular function and mechanisms in ovarian tumours remain unclear. In this report, we initially demonstrated the inhibitory effect of NOEY2 on tumour growth by utilising a xenograft tumour model. NOEY2 attenuated the cell growth approximately fourfold and significantly reduced tumour vascularity. NOEY2 inhibited the phosphorylation of the signalling components downstream of phosphatidylinositol-3’-kinase (PI3K), including phosphoinositide-dependent protein kinase 1 (PDK-1), tuberous sclerosis complex 2 (TSC-2) and p70 ribosomal protein S6 kinase (p70S6K), during ovarian tumour progression via direct binding to vascular endothelial growth factor receptor-2 (VEGFR-2). Particularly, the N-terminal domain of NOEY2 (NOEY2-N) had a potent anti-angiogenic activity and dramatically downregulated VEGF and hypoxia-inducible factor-1α (HIF-1α), key regulators of angiogenesis. Since no X-ray or nuclear magnetic resonance structures is available for NOEY2, we constructed the threedimensional structure of this protein via molecular modelling methods, such as homology modelling and molecular dynamic simulations. Thereby, Lys15 and Arg16 appeared as key residues in the N-terminal domain. We also found that NOEY2-N acts as a potent inhibitor of tumorigenesis and angiogenesis. These findings provide convincing evidence that NOEY2-N regulates endothelial cell function and angiogenesis by interrupting the VEGFR-2/PDK-1/GSK-3β signal transduction and thus strongly suggest that NOEY2-N might serve as a novel anti-tumour and anti-angiogenic agent against many diseases, including ovarian cancer.

Clinical Features of Olfactory Dysfunction in COVID-19 Patients

Background@#The aim of this study was to evaluate the subjective and objective olfactory function in coronavirus disease 2019 (COVID-19) patients and the effect of olfactory training. @*Methods@#A prospective cohort study was performed in 53 patients who recovered from COVID-19 and visited our tertiary hospital. Subjective olfactory function was evaluated using the 11-point Likert scale (0–10) and the Korean version of the Questionnaire of Olfactory Disorders (QOD). Objective olfactory function was evaluated using Cross-Cultural Smell Identification Test (CC-SIT). Confirmed patients were followed up after 2 months of olfactory training. @*Results@#The median, interquartile range (Q1–Q3) score of subjective olfactory function significantly deteriorated in patients with olfactory dysfunction (OD) than in those without OD, even after 3 months of onset (11-point Likert scale, 8, 6–9 vs. 10, 10–10; short version of QOD-negative statements, 19, 16–21 vs. 21, 21–21; QOD-visual analogue scale, 7, 1–13 vs. 0, 0–0; all P < 0.001). However, the objective olfactory function was not significantly different between the two groups (median, interquartile range; 11, 9–11 vs. 11, 9–11, P = 0.887). The percentage of patients with objective hyposmia (CC-SIT ≤ 10) was also not significantly different (47.4% vs. 40%,P = 0.762). OD in COVID-19 was normalized after 2 months of olfactory training in 70% of patients even after 3 months of olfactory impairment. @*Conclusion@#Although subjective olfactory function is significantly decreased in the OD group, the objective olfactory function was not significantly different. Moreover, olfactory training is effective in COVID-19 patients with OD.