Neurosteroids play an important role as endogenous neuromodulators that are locally produced in the central nervous system and rapidly change the excitability of neurons and the activation of microglial cells and astrocytes. Here we review the mechanisms of synthesis, metabolism, and actions of neurosteroids in the central nervous system. Neurosteroids are able to play a variety of roles in the central nervous system under physiological conditions by binding to membrane ion channels and receptors such as gamma-aminobutyric acid type A receptors, Nmethyl-D-aspartate receptors, L- and T-type calcium channels, and sigma-1 receptors. In addition, numerous neurological disorders, including persistent neuropathic pain, multiple sclerosis, and seizures, have altered the levels of neurosteroids in the central nervous system. Thus, we review how local synthesis and metabolism of neurosteroids are modulated in the central nervous system and describe the role of neurosteroids under pathological conditions. Furthermore, we discuss whether neurosteroids may play a role as a new therapeutic for the treatment of neurological disorders.

Purpose: Improvement of left ventricular (LV) diastolic dysfunction (DD) is known to be a good prognostic factor in patients with heart failure with reduced ejection fraction (EF). In the present study, we investigated the predisposing risk factors affecting the reversibility of LV diastolic filling pattern (DFP) in patients with preserved EF. Materials and Methods: A total of 600 patients with pseudonormal LVDFP and preserved EF who underwent follow-up echocardiography were enrolled between 2011 and 2020. We compared their index and follow-up echocardiography findings and determined the predisposing risk factor affecting the reversibility of LVDFP. Results: Comparing the index and follow-up echocardiography findings showed that 379 (63%) patients had improved to normal or impaired relaxation LVDFP (improved group) and 221 (37%) patients had maintained or worsened LVDFP (unimproved group).The incidence of paroxysmal atrial fibrillation (PAF) was significantly higher in the unimproved group than in the improved group (4.7% vs. 9.5%, p=0.026). After adjustment for relevant clinical risk factors of diastolic dysfunction, PAF was determined to be an independent predisposing risk factor for the unimproved LVDFP (odds ratio: 2.10, 95% confidence interval: 1.06–4.15, p=0.033).Among the parameters of diastolic dysfunction in follow-up echocardiography, the left atrial volume index, mean E/A ratio, and E/e' were significantly improved in patients without PAF but remained in patients with PAF. Conclusion We identified that PAF was an independent predisposing risk factor of the unimproved LVDFP in patients with pseudonormal LVDFP and preserved EF. Therefore, early detection and management of PAF might be required in patients with LVDD and preserved EF to prevent adverse cardiovascular events.

Background and Objectives: This study aimed to analyze postoperative performance and mapping characteristics of cochlear implants (CIs) by comparing patients with autism spectrum disorder (ASD) to those without ASD, and to suggest CI mapping solutions in patients with ASD.Subjects and Method This retrospective study enrolled 10 children with ASD and hearing disabilities, who received simultaneous bilateral CI (ASD group), and 20 children with bilateral hearing disabilities, who received simultaneous bilateral CI at the same age (control group). CI performance was analyzed using speech perception tests (categorical auditory performance score and monosyllable, bisyllable, and Ling’s 6 tests) and a sound field test. The mapping characteristics focused on variables related to stimulus intensity and fine-tuning. Results: The performance of the ASD group was significantly poorer than that of the control group in all speech perception and sound field tests. At the comfortable (C) and threshold (T) levels, the ASD group scored significantly lower than the control group. The dynamic range of ASD group was significantly narrower than the control group. The ASD group had significantly lower pulse width, sensitivity, and volume than control group. Conclusion CI mapping in the ASD group showed practical limitations. To avoid overstimulation in patients with ASD, the dynamic range should be set narrow, or the C/T level should be set lower than normal. Key control factors, such as pulse width, sensitivity, and volume, should be set lower than the control group. Although lower performance from CI is generally expected in the ASD group, CI mapping in the ASD group requires a long-term approach with dedicated efforts and patience.

Purpose: Inotuzumab ozogamicin (INO) has demonstrated a safe bridging role to allogeneic hematopoietic stem cell transplantation (HSCT) in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). How‑ ever, hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is frequently observed. This study aimed to identify significant features of INO-associated VOD/SOS. Methods: We reviewed seven cases of hepatic VOD/SOS that developed either during INO salvage or after alloge‑ neic HSCT following INO-induced complete remission (CR). Diagnosis and severity grading of VOD/SOS were based on the revised criteria from the European Society for Blood and Marrow Transplantation. Defibrotide was used to treat severe to very severe cases. Results: Four patients developed VOD/SOS during INO salvage therapy (at 21 and 36 days post-INO1, 77 days postINO3, and 21 days post-INO5), while three were diagnosed at 2, 5, and 10 days post-HSCT following INO-induced CR.Doppler ultrasonography revealed preserved portal vein flow (range 10.2–26.0 cm/sec) and normal hepatic artery resistive index (RI, range 0.56–0.74) in all but one patient (RI 0.83). Despite this, all patients presented with massive ascites and progressively elevated total bilirubin levels. All cases were classified as severe to very severe; six were treated with defibrotide and one underwent liver transplantation. Most patients ultimately died owing to VOD/SOS progression. Conclusion Post-INO VOD/SOS manifested as two different clinical settings and was characterized by preserved portal vein flow, which complicated diagnosis. Despite timely defibrotide administration, clinical outcomes were poor.These findings emphasize the need for vigilance and potential consideration of prophylactic strategies for prevention of INO-associated VOD/SOS.

Background: Strain elastography (SE) and shear wave elastography (SWE) are emerging techniques for evaluating the elasticity of soft tissue. This study aimed to determine interobserver and intraobserver reliability for elasticity measurements of different tissues and anatomic locations using SE and SWE. Methods: Ten healthy adult male individuals with 20 upper extremities participated in this study. The elasticities of the wrist extensor muscle, the common extensor tendon, and supraspinatus tendon were measured. Strain ratio and shear wave velocity were measured twice by 2 different examiners (examiner 1 with over 20 years of experience in musculoskeletal sonography and examiner 2 with 1 year of experience). Interobserver and intraobserver reliability was assessed using the intraclass correlation coefficient (ICC). Results: The 10 individuals’ age ranged from 28 to 35 years. In SE, interobserver reliabilities at the 3 anatomic locations (wrist extensor muscle, common extensor tendon, and supraspinatus tendon) showed fair to moderate agreement (ICC = 0.489, p = 0.076;ICC = 0.408, p = 0.131; and ICC = 0.296, p = 0.711, respectively). The intraobserver reliabilities of examiner 1 were moderate to substantial only at the wrist extensor muscle and the common extensor tendon (ICC = 0.563, p = 0.039 and ICC = 0.702, p = 0.006, respectively). In SWE, interobserver reliabilities for the wrist extensor muscle and the supraspinatus tendon were moderate to substantial (ICC = 0.756, p = 0.002 and ICC = 0.565, p = 0.039, respectively). The intraobserver reliabilities of examiner 1 at the 3 anatomic locations were almost perfect (ICC = 0.843, p = 0.001; ICC = 0.800, p = 0.001; and ICC = 0.825, p = 0.001, respectively).The results of examiner 2 showed almost perfect agreement at the wrist extensor muscle (ICC = 0.886, p = 0.001) and moderate to substantial agreement at the tendons of the common extensor and supraspinatus (ICC = 0.592, p = 0.029 and ICC = 0.682, p = 0.008, respectively). Conclusions SWE is a reliable method for assessing the flexibility of soft tissue, but it is affected by expertise and the specific anatomical site.

Background and Objectives: This study aimed to analyze postoperative performance and mapping characteristics of cochlear implants (CIs) by comparing patients with autism spectrum disorder (ASD) to those without ASD, and to suggest CI mapping solutions in patients with ASD.Subjects and Method This retrospective study enrolled 10 children with ASD and hearing disabilities, who received simultaneous bilateral CI (ASD group), and 20 children with bilateral hearing disabilities, who received simultaneous bilateral CI at the same age (control group). CI performance was analyzed using speech perception tests (categorical auditory performance score and monosyllable, bisyllable, and Ling’s 6 tests) and a sound field test. The mapping characteristics focused on variables related to stimulus intensity and fine-tuning. Results: The performance of the ASD group was significantly poorer than that of the control group in all speech perception and sound field tests. At the comfortable (C) and threshold (T) levels, the ASD group scored significantly lower than the control group. The dynamic range of ASD group was significantly narrower than the control group. The ASD group had significantly lower pulse width, sensitivity, and volume than control group. Conclusion CI mapping in the ASD group showed practical limitations. To avoid overstimulation in patients with ASD, the dynamic range should be set narrow, or the C/T level should be set lower than normal. Key control factors, such as pulse width, sensitivity, and volume, should be set lower than the control group. Although lower performance from CI is generally expected in the ASD group, CI mapping in the ASD group requires a long-term approach with dedicated efforts and patience.

BACKGROUND/OBJECTIVES: Particulate matter 2.5 (PM2.5) exposure can promote epithelialmesenchymal transition (EMT) in human retinal pigment epithelial (RPE) cells. The flowers of Tagetes erecta Linn, commonly known as marigold, are rich in diverse flavonoids and carotenoids and play a significant role in preventing cellular damage induced by oxidative stress, but the role of their extracts in RPE cells has not been reported. This study aimed to evaluate the influence of an ethanol extract of T. erecta Linn flower (TE) on PM2.5-induced EMT processes in RPE ARPE-19 cells.MATERIALS/METHODS: To investigate the protective effect of TE against ARPE-19 cell damage following PM2.5 treatment, cells were exposed to TE for 1 h before exposure to PM2.5 for 24 h. We investigated whether the efficacy of TE on suppressing PM2.5-induced EMT was related to antioxidant activity and the effect on the expression changes of factors involved in EMT regulation. Additionally, we further explored the role of intracellular signaling pathways associated with EMT inhibition. RESULTS: TE significantly blocked PM2.5-induced cytotoxicity while effectively preventing mitochondrial dysfunction, increased reactive oxygen species (ROS) generation, and mitochondrial membrane potential disruption. TE inhibited PM2.5-induced EMT and inflammatory response by suppressing the ROS-mediated transforming growth factor-β/ suppressor of mothers against decapentaplegic/mitogen-activated protein kinases signaling pathway. CONCLUSION Our results suggest that marigold extract is a highly effective in protection against PM2.5-induced eye damage.

Neurosteroids play an important role as endogenous neuromodulators that are locally produced in the central nervous system and rapidly change the excitability of neurons and the activation of microglial cells and astrocytes. Here we review the mechanisms of synthesis, metabolism, and actions of neurosteroids in the central nervous system. Neurosteroids are able to play a variety of roles in the central nervous system under physiological conditions by binding to membrane ion channels and receptors such as gamma-aminobutyric acid type A receptors, Nmethyl-D-aspartate receptors, L- and T-type calcium channels, and sigma-1 receptors. In addition, numerous neurological disorders, including persistent neuropathic pain, multiple sclerosis, and seizures, have altered the levels of neurosteroids in the central nervous system. Thus, we review how local synthesis and metabolism of neurosteroids are modulated in the central nervous system and describe the role of neurosteroids under pathological conditions. Furthermore, we discuss whether neurosteroids may play a role as a new therapeutic for the treatment of neurological disorders.

Purpose: Improvement of left ventricular (LV) diastolic dysfunction (DD) is known to be a good prognostic factor in patients with heart failure with reduced ejection fraction (EF). In the present study, we investigated the predisposing risk factors affecting the reversibility of LV diastolic filling pattern (DFP) in patients with preserved EF. Materials and Methods: A total of 600 patients with pseudonormal LVDFP and preserved EF who underwent follow-up echocardiography were enrolled between 2011 and 2020. We compared their index and follow-up echocardiography findings and determined the predisposing risk factor affecting the reversibility of LVDFP. Results: Comparing the index and follow-up echocardiography findings showed that 379 (63%) patients had improved to normal or impaired relaxation LVDFP (improved group) and 221 (37%) patients had maintained or worsened LVDFP (unimproved group).The incidence of paroxysmal atrial fibrillation (PAF) was significantly higher in the unimproved group than in the improved group (4.7% vs. 9.5%, p=0.026). After adjustment for relevant clinical risk factors of diastolic dysfunction, PAF was determined to be an independent predisposing risk factor for the unimproved LVDFP (odds ratio: 2.10, 95% confidence interval: 1.06–4.15, p=0.033).Among the parameters of diastolic dysfunction in follow-up echocardiography, the left atrial volume index, mean E/A ratio, and E/e' were significantly improved in patients without PAF but remained in patients with PAF. Conclusion We identified that PAF was an independent predisposing risk factor of the unimproved LVDFP in patients with pseudonormal LVDFP and preserved EF. Therefore, early detection and management of PAF might be required in patients with LVDD and preserved EF to prevent adverse cardiovascular events.