Oxidative stress due to hyperglycemia damages the functions of retinal pigment epithelial (RPE) cells and is a major risk factor for diabetic retinopathy (DR). Paeoniflorin is a monoterpenoid glycoside found in the roots of Paeonia lactiflora Pall and has been reported to have a variety of health benefits. However, the mechanisms underlying its therapeutic effects on high glucose (HG)-induced oxidative damage in RPE cells are not fully understood. In this study, we investigated the protective effect of paeoniflorin against HG-induced oxidative damage in cultured human RPE ARPE-19 cells, an in vitro model of hyperglycemia. Pretreatment with paeoniflorin markedly reduced HG-induced cytotoxicity and DNA damage. Paeoniflorin inhibited HG-induced apoptosis by suppressing activation of the caspase cascade, and this suppression was associated with the blockade of cytochrome c release to cytoplasm by maintaining mitochondrial membrane stability. In addition, paeoniflorin suppressed the HG-induced production of reactive oxygen species (ROS), increased the phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2), a key redox regulator, and the expression of its downstream factor heme oxygenase-1 (HO-1). On the other hand, zinc protoporphyrin (ZnPP), an inhibitor of HO-1, abolished the protective effect of paeoniflorin against ROS production in HG-treated cells. Furthermore, ZnPP reversed the protective effects of paeoniflorin against HG-induced cellular damage and induced mitochondrial damage, DNA injury, and apoptosis in paeoniflorin-treated cells. These results suggest that paeoniflorin protects RPE cells from HG-mediated oxidative stress-induced cytotoxicity by activating Nrf2/HO-1 signaling and highlight the potential therapeutic use of paeoniflorin to improve the symptoms of DR.

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.

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.

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.

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.