Search

Purpose We sought to assess mortality trends in chest-abdominal trauma patients, before and after the implementation of the Project Supporting Establishment of Trauma Centers (PSETC) in the Republic of Korea. Methods Data from the National Health Insurance Service claims database between 2009 to 2017 were analyzed. Patients with chest-abdominal trauma were defined as those with relevant main diagnosis codes and claims for emergency medical management fees. Mortality and cumulative data were analyzed for each year to compare mortality before and after the establishment of regional trauma centers across Korea (2014). Results In total, 29,127 patients were included in the analysis. While the annual incidence of trauma-related chest-abdominal injuries increased, mortalities decreased. In particular, the trauma incidence rate among patients over 50 years increased during the study period. Mortalities at trauma centers did not change year by year after the PSETC. Before and after 2014, when trauma centers operated under the PSETC, mortalities decreased [trauma cases before the PSETC; n = 14,321 (mortality 5.61), after the PSETC; n = 14,806 (mortality 4.96)]. Conclusion The number of patients treated for chest-abdominal injuries increased from 2009 to 2017 in Korea, whereas mortalities decreased over the same period.

Background: Ocular involvement is relatively common in granulomatosis with polyangiitis (GPA); however, choroidal involvement is rare. We present a case of serous retinal detachment resulting from choroidal involvement in GPA. Case presentation: A 55-year-old male presented to our clinic with bilateral eye redness and pain. Ocular examination revealed bilateral conjunctival injection, and dilation of the episcleral and scleral vessels. Slit-lamp examination revealed anterior chamber cells. Optical coherence tomography (OCT) confirmed serous retinal detachment (SRD) in the left eye. The patient had recently been diagnosed with GPA following a lung biopsy and had received immunosuppressive therapy, including systemic steroids, cyclosporine, mycophenolate mofetil, and rituximab. Five weeks after treatment, the clinical symptoms of the patient, including SRD, improved with alleviation of systemic symptoms. However, tapering systemic steroids and immunosuppressants and discontinuing rituximab led to disease reactivation. OCT demonstrated a recurrence of subretinal fluid, which had previously resolved, and slit-lamp examination showed mild bilateral engorged scleral vessels. Conclusions: Choroidal involvement can present as SRD and may indicate disease activity in patients with GPA.

Abstract Purpose To evaluate the long-term prognosis of polypoidal choroidal vasculopathy (PCV) treated with anti-vascular endothelial growth factor (anti-VEGF) combined with verteporfin photodynamic therapy (PDT), according to polypoidal lesion regression. Methods This study retrospectively reviewed the data of 33 naïve eyes with PCV treated with anti-VEGF combined with verteporfin PDT and followed-up for at least 7 years. The collected data included demographic profile, best-corrected visual acuity (BCVA), central foveal thickness (CFT), PED volume, and presence of submacular hemorrhage. Regression of polypoidal lesion was determined using indocyanine green angiography and optical coherence tomography. All eyes were divided into regression or persistent groups, based on the polypoidal lesion regression one year after the initial combined treatment. Results BCVA improvement was maintained for 3 years in the regression (p = 0.001) and 1 year in the persistent (p = 0.006) groups, respectively. The mean BCVA of the regression group was better than that of the persistent group over 7 years, but the difference was significant only at 1 year (p = 0.037). The number of eyes which maintained BCVA less than or equal to 0.3 logMAR at 7 years was 11 eyes (64.7%) in regression group and 4 eyes (25.0%) in persistent group (p = 0.022). Conclusions Regression of the polypoidal lesion at 1 year after the initial combination treatment was associated with favorable long-term visual prognosis, particularly in terms of maintaining good visual acuity.

Abstract Purpose To evaluate the correlations between swept-source optical coherence tomography angiography (SS-OCTA) parameters and clinical outcomes in eyes with neovascular age-related macular degeneration (nAMD) administered a bimonthly intravitreal aflibercept regimen. Methods This prospective, single-arm, interventional study enrolled 33 patients with treatment-naïve nAMD. The eyes received three monthly aflibercept injections followed by five bi-monthly regimens (total 50 weeks). The structural parameters including central subfield thickness (CST) and 5 mm pigment epithelial detachment (PED) volume and microvascular parameters including macular neovascularization (MNV) area, vessel density (VD), and vessel length density (VLD) were recorded every before and 1 week after treatment. Results Patients who gained > 5 letters of best-corrected visual acuity (BCVA) from the baseline showed greater decreases in VD and VLD during the loading phase. Patients without recurrent or persistent fluid during the maintenance phase showed greater decreases in CST and 5 mm PED volume after the first injection. The decrease in mean VD during the loading phase was significantly correlated with the final BCVA (r = -0.820, p = 0.004). Moreover, the decrease in mean VLD during the loading phase was significantly correlated with the improvement in the final BCVA (r = -0.726, p = 0.017). Conclusions The decrease in mean VD during the loading phase was significantly negatively correlated with the final BCVA at the last visit. The decrease in mean VLD during the loading phase, mean CST during the loading phase, and the improvement in final BCVA showed significant correlations. Therefore, early changes in OCTA microvascular and OCT structural parameters could help predict clinical outcomes in nAMD. Trial Registration The trial was registered with the Clinical Research Information Service (CRIS), which joined the WHO International Clinical Trials Registry Platform (ICTRP) (Registration number: KCT0007375, Date of first trial registration: 10/06/2022).

Abstract RNA-binding proteins (RBPs) containing low-sequence complexity domains mediate the formation of cellular condensates and membrane-less organelles with biological functions via liquid‒liquid phase separation (LLPS). However, the abnormal phase transition of these proteins induces the formation of insoluble aggregates. Aggregates are pathological hallmarks of neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS). The molecular mechanisms underlying aggregate formation by ALS-associated RPBs remain largely unknown. This review highlights emerging studies on various posttranslational modifications (PTMs) related to protein aggregation. We begin with the introduction of several ALS-associated RBPs that form aggregates induced by phase separation. In addition, we highlight our recent discovery of a new PTM involved in the phase transition during the pathogenesis of fused-in-sarcoma (FUS)-associated ALS. We suggest a molecular mechanism through which LLPS mediates glutathionylation in FUS-linked ALS. This review aims to provide a detailed overview of the key molecular mechanisms of LLPS-mediated aggregate formation by PTMs, which will help further the understanding of the pathogenesis and development of ALS therapeutics.

Background: Platinum-based combination chemotherapy, including cisplatin and carboplatin, are important cytotoxic anti-cancer agents that are widely used to treat various solid tumors. Carboplatin has a similar effect on survival in small cell lung cancer, but generally has a milder toxicity profile when compared with cisplatin. Both may cause moderate or severe neurotoxicity, but ocular neurotoxicity from carboplatin is rarely reported. Case presentation: A 79-year-old man underwent intravenous polychemotherapy (atezolizumab, etoposide, and carboplatin) for small cell lung cancer. One week after the second cycle of chemotherapy, he reported bilateral visual loss as hand motion in both eyes. Dilated fundus examination showed retinal arterial narrowing without hemorrhage, and diffuse choroidal and retinal thinning was observed in an optical coherence tomography scan. Fluorescein angiography revealed significantly delayed circulation without evidence of obstructive lesions. 30-Flicker electroretinogram testing showed a complete absence of cone response in both eyes. The patient’s visual acuity aggravated to no light perception in both eyes, even after the cessation of chemotherapy. Conclusions: Carboplatin combination chemotherapy administered at therapeutic doses can result in irreversible visual loss, a side effect that is not widely acknowledged. When using carboplatin, physicians should be aware of its potential ocular toxicity.

(1) Background: Although Candida albicans accounts for the majority of fungal infections, therapeutic options are limited and require alternative antifungal agents with new targets; (2) Methods: A biofilm formation assay with RPMI1640 medium was performed with Liriope muscari extract. A combination antifungal assay, dimorphic transition assay, and adhesion assay were performed under the biofilm formation condition to determine the anti-biofilm formation effect. qRT-PCR analysis was accomplished to confirm changes in gene expression; (3) Results: L. muscari extract significantly reduces biofilm formation by 51.65% at 1.56 μg/mL use and therefore increases susceptibility to miconazole. L. muscari extract also inhibited the dimorphic transition of Candida; nearly 50% of the transition was inhibited when 1.56 μg/mL of the extract was treated. The extract of L. muscari inhibited the expression of genes related to hyphal development and extracellular matrix of 34.4% and 36.0%, respectively, as well as genes within the Ras1-cAMP-PKA, Cph2-Tec1, and MAP kinase signaling pathways of 25.58%, 7.1% and 15.8%, respectively, at 1.56 μg/mL of L. muscari extract treatment; (4) Conclusions: L. muscari extract significantly reduced Candida biofilm formation, which lead to induced antifungal susceptibility to miconazole. It suggests that L. muscari extract is a promising anti-biofilm candidate of Candida albicans since the biofilm formation of Candida albicans is an excellent target for candidiasis regulation.

Abstract Purpose To evaluate the peripapillary microvasculature changes in patients with epiretinal membrane (ERM) following pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling using swept-source optical coherence tomography angiography (SS-OCTA). Method Medical records and multimodal imaging data of 33 eyes after PPV for ERM were retrospectively reviewed. Peripapillary SS-OCTA images of 6×6 mm2 were recorded at at pre- and post-operatively every 6 months for 1 year. A semi-automated method was used to analyzed SS-OCTA images, excluding the optic disc area, using the MATLAB software. The peripapillary vessel density (pVD) of superficial capillary plexus (SCP) and deep capillary plexus (DCP) was quantified in four quadrants (superior, inferior, nasal and temporal). Result The mean pVD in SCP and DCP decreased at 6- and 12-months follow-up. In sectoral analysis, superior, inferior, and temporal quadrants pVD in SCP and DCP were significantly reduced at 1 year after vitrectomy (all p < 0.05). Meanwhile, inferior quadrants pVD in SCP and DCP showed the earliest significant reduction at 6-months (p = 0.022 and 0.048, respectively). A reduction of post-operative mean pVD in DCP was significantly greater in patients with diabetic retinopathy (p = 0.043). Conclusion Peripapillary capillary density significantly decreased after surgical removal of ERM. Vitrectomy with ILM peeling can cause peripapillary microvascular damage starting in inferior sector.

Abstract TATA-binding protein associated factor 15 (TAF15) is involved in the pathology of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Although TAF15 accumulates as cytoplasmic aggregates in neurons and the clearance of aggregates may be a therapeutic strategy for ALS, the underlying mechanisms of TAF15 in ALS remain poorly understood. Recently, we found that glutathione transferase omega 2 (GstO2) expression level is significantly reduced in the brain tissue of TAF15-expressing flies. In this study, we demonstrated that GstO2 overexpression in TAF15-induced flies rescues the locomotive activity and neuromuscular junctional defects. Furthermore, TAF15 levels in both cytoplasm and nuclear fractions significantly decreased in the heads of GstO2 co-expressing flies. GstO2-co-overexpression in neurons caused a marked decrease in intracellular reactive oxygen species generation in TAF15-induced flies. Our findings demonstrated that GstO2 was a pathogenic regulator of TAF15-associated proteinopathies. They help expand our understanding of TAF15-associated ALS pathogenesis.

Objective This study aimed to evaluate the preference for antivascular endothelial growth factor (anti-VEGF) versus laser ablation therapy as primary and additional treatment in aggressive retinopathy of prematurity (ROP) and type 1 ROP.Methods This multicentre retrospective study was conducted at nine medical centres across South Korea. A total of 94 preterm infants with ROP who underwent primary treatment between January 2020 and December 2021 were enrolled. All eyes were classified as having type 1 ROP or aggressive ROP. Data on the zone, primary treatment chosen, injection dose, presence of reactivation and additional treatment were collected and analysed.Results Seventy infants (131 eyes) with type 1 ROP and 24 infants (45 eyes) with aggressive ROP were included. Anti-VEGF injection was selected as the primary treatment in 74.05% of the infants with type 1 ROP and 88.89% with aggressive ROP. Anti-VEGF injection was selected as the ROP was located in zone I or posterior zone II, and laser ablation was selected when it was located in zone II. The anti-VEGF injection doses varied and tended to be higher in the aggressive ROP group. Infants with aggressive ROP were 2.08 times more likely to require additional treatment than those with type 1 ROP. When ROP reactivation occurred, laser therapy was preferred as an additional treatment.Conclusion In Korea, the preference for anti-VEGF therapy or laser therapy differed according to ROP subtype, zone and primary or secondary treatment. These findings suggest that ROP treatment are considered according to ROP subtype, location and reactivation.

Central serous chorioretinopathy (CSC) is a pachychoroid spectrum disease characterized by serous detachment of the neurosensory retina with subretinal fluid in young and middle-aged adults. The pathogenesis of CSC is not yet fully understood. However, it is considered a multifactorial disease that is strongly associated with choroidal dysfunction or vascular engorgement. Although there is no consensus on the treatment of CSC, photodynamic therapy has been effectively used to manage serous retinal detachment (SRD) in CSC. Moreover, micropulse diode laser photocoagulation and focal laser treatment have also been used. Recently, oral medications, including mineralocorticoid receptor antagonists, have been proposed for the management of CSC. Multimodal imaging plays a significant role in the diagnosis and treatment of CSC. Optical coherence tomography angiography (OCTA) has the advantage of detecting vascular flow in the retina and choroid layer, allowing for a better understanding of the pathology, severity, prognosis, and chronicity of CSC. In addition, early detection of choroidal neovascularization in CSC is possible using OCTA. This review article aims to provide a comprehensive and updated understanding of CSC, focusing on treatment.

A 28-year-old male patient presented to the outpatient department with visual disturbance in both eyes. The patient had a history of stage IV lupus nephritis that was diagnosed at the age of 14 years and had undergone hemodialysis at the age of 23 years. After he started hemodialysis, the systemic condition was well controlled, and systemic steroids were not used. His best-corrected visual acuity (BCVA) was 20/200 in the right eye and 20/100 in the left eye. Funduscopic examination revealed shallow subretinal fluid (SRF) and serous retinal detachment in both eyes. The first impression of this patient was central serous chorioretinopathy. However, the late phase of fluorescein angiography (FA) demonstrated multiple subretinal leakages, and the late phase of indocyanine green angiography showed choroidal vascular engorgement and multiple hyperfluorescent plaques in both eyes. Systemic lupus erythematosus showed moderate activity according to the results of the systemic evaluation. Based on the clinical examination, lupus choroidopathy was suspected in both eyes. Half-fluence photodynamic therapy (PDT) was administered to both eyes rather than systemic steroids because the patient was systemically stable. Three months after PDT, no SRF was observed in either eye. In addition, multiple subretinal leakages on FA were reduced compared to those before treatment. There was no recurrence of SRF for 4 years after PDT, and the final BCVA was 20/70 in the right eye and 20/40 in the left eye. During this time, numerous hypoautofluorescence spots appeared adjacent to the major retinal vessels in fundus autofluorescence.

Pumped-storage hydroelectricity (PSH) is a facility that stores energy in the form of the gravitational potential energy of water by pumping water from a lower to a higher elevation reservoir in a hydroelectric power plant. The operation of PSH can be divided into two states: the turbine state, during which electric energy is generated, and the pump state, during which this generated electric energy is stored as potential energy. Additionally, the condition monitoring of PSH is generally challenging because the hydropower turbine, which is one of the primary components of PSH, is immersed in water and continuously rotates. This study presents a method that automatically detects new abnormal conditions in target structures without the intervention of experts. The proposed method automatically updates and optimizes existing abnormal condition classification models to accommodate new abnormal conditions. The performance of the proposed method was evaluated with sensor data obtained from on-site PSH. The test results show that the proposed method detects new abnormal PSH conditions with an 85.89% accuracy using fewer than three datapoints and classifies each condition with a 99.73% accuracy on average.

Abstract To investigate the pathophysiologic characteristics of diabetic complications, we identified differences in plasma metabolites in subjects with type 2 diabetes (T2DM) with or without diabetic macular edema (DME) and a disease duration > 15 years. An cohort of older T2DM patients with prolonged disease duration was established, and clinical information and biospecimens were collected following the guidelines of the National Biobank of Korea. DME phenotypes were identified by ophthalmologic specialists. For metabolomics studies, propensity matched case and control samples were selected. To discover multi-biomarkers in plasma, non-targeted metabolite profiling and oxylipin profiling in the discovery cohort were validated in an extended cohort. From metabolomic studies, 5 amino acids (asparagine, aspartic acid, glutamic acid, cysteine, and lysine), 2 organic compounds (citric acid and uric acid) and 4 oxylipins (12-oxoETE, 15-oxoETE, 9-oxoODE, 20-carboxy leukotriene B4) were identified as candidate multi-biomarkers which can guide DME diagnosis among non-DME subjects. Receiver operating characteristic curves revealed high diagnostic value of the combined 5 amino acids and 2 organic compounds (AUC = 0.918), and of the 4 combined oxylipins (AUC = 0.957). Our study suggests that multi-biomarkers may be useful for predicting DME in older T2DM patients.

With the rapid development of computer vision, vision cameras have been used as noncontact sensors for structural displacement measurements. However, vision-based techniques are limited to short-term displacement measurements because of their degraded performance under varying illumination and inability to operate at night. To overcome these limitations, this study developed a continuous structural displacement estimation technique by combining measurements from an accelerometer with vision and infrared (IR) cameras collocated at the displacement estimation point of a target structure. The proposed technique enables continuous displacement estimation for both day and night, automatic optimization of the temperature range of an infrared camera to ensure a region of interest (ROI) with good matching features, and adaptive updating of the reference frame to achieve robust illumination–displacement estimation from vision/IR measurements. The performance of the proposed method was verified through lab-scale tests on a single-story building model. The displacements were estimated with a root-mean-square error of less than 2 mm compared with the laser-based ground truth. In addition, the applicability of the IR camera for displacement estimation under field conditions was validated using a pedestrian bridge test. The proposed technique eliminates the need for a stationary sensor installation location by the on-site installation of sensors and is therefore attractive for long-term continuous monitoring. However, it only estimates displacement at the sensor installation location, and cannot simultaneously estimate multi-point displacements which can be achieved by installing cameras off-site.

Abstract This study evaluated quantitative changes in microvascular parameters after panretinal photocoagulation (PRP) in diabetic retinopathy (DR), using swept-source OCT Angiography (SS-OCTA). A total of 27 treatment-naïve eyes were subjected to PRP and followed-up for > 12 months after the procedure. Foveal avascular zone (FAZ) area, macular perfusion density (PD), and vessel length density (VLD) were calculated on a 3 × 3 mm en face OCTA image and nonperfusion area (NPA) was obtained on a 12 × 12 mm en face OCTA image. One month after PRP, PD and VLD of superficial and deep capillary plexus decreased and subsequently, increased progressively across the next 12 months, with statistically significant differences (P = 0.015 and 0.02). Continuous decreasing trends in total NPA values was observed across 12 months after PRP (P = 0.125). A difference in PD of the superficial capillary plexus between baseline and 6 months post PRP, was significantly associated with the progression of DR, 12 months after PRP (OR 0.528; P = 0.025). We found significant longitudinal retinal microvascular changes after PRP in DR. Overall macular perfusion status was impaired and progressively recovered across the next 12 months, compared to the baseline. Additionally, the early treatment responses in PD can predict the long-term outcomes of PDR after PRP.

AbstractDistributed consensus requires the consent of more than half of the congress to produce irreversible results, and the performance of the consensus algorithm deteriorates with the increase in the number of nodes. This problem can be addressed by delegating the agreement to a few selected nodes. Since the selected nodes must comply with the Byzantine node ratio criteria required by the algorithm, the result selected by any decentralized node cannot be trusted. However, some trusted nodes monopolize the consensus node selection process, thereby breaking decentralization and causing a trilemma. Therefore, a consensus node selection algorithm is required that can construct a congress that can withstand Byzantine faults with the decentralized method. In this paper, an algorithm based on the Byzantine agreement among decentralized agents to facilitate agreement between decentralization nodes is proposed. It selects a group of random consensus nodes per block by applying the proposed proof of nonce algorithm. By controlling the percentage of Byzantine included in the selected nodes, it solves the trilemma when an arbitrary node selects the consensus nodes.

Abstract Background Cytoplasmic inclusions of transactive response DNA binding protein of 43 kDa (TDP-43) in neurons and astrocytes are a feature of some neurodegenerative diseases, such as frontotemporal lobar degeneration with TDP-43 (FTLD-TDP) and amyotrophic lateral sclerosis (ALS). However, the role of TDP-43 in astrocyte pathology remains largely unknown. Methods To investigate whether TDP-43 overexpression in primary astrocytes could induce inflammation, we transfected primary astrocytes with plasmids encoding Gfp or TDP-43-Gfp. The inflammatory response and upregulation of PTP1B in transfected cells were examined using quantitative RT-PCR and immunoblot analysis. Neurotoxicity was analysed in a transwell coculture system of primary cortical neurons with astrocytes and cultured neurons treated with astrocyte-conditioned medium (ACM). We also examined the lifespan, performed climbing assays and analysed immunohistochemical data in pan-glial TDP-43-expressing flies in the presence or absence of a Ptp61f RNAi transgene. Results PTP1B inhibition suppressed TDP-43-induced secretion of inflammatory cytokines (interleukin 1 beta (IL-1β), interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α)) in primary astrocytes. Using a neuron-astrocyte coculture system and astrocyte-conditioned media treatment, we demonstrated that PTP1B inhibition attenuated neuronal death and mitochondrial dysfunction caused by overexpression of TDP-43 in astrocytes. In addition, neuromuscular junction (NMJ) defects, a shortened lifespan, inflammation and climbing defects caused by pan-glial overexpression of TDP-43 were significantly rescued by downregulation of ptp61f (the Drosophila homologue of PTP1B) in flies. Conclusions These results indicate that PTP1B inhibition mitigates the neuronal toxicity caused by TDP-43-induced inflammation in mammalian astrocytes and Drosophila glial cells.

The differential effects of two seawater (SW) transfer regimes on the hypoosmoregulation, hormonal response, feed efficiency, and growth performance of 50 g juvenile steelhead trout (Oncorhynchus mykiss) were determined to better understand the chronic responses to two salinity increase regimes. The fish reared in freshwater (FW) were exposed to either FW (control) or SW (32 ppt) via two regimes. In the first regime, the fish were exposed to a daily increase in salinity of 11 ppt and transferred to 32 ppt on the 3rd day (3DSW), and in the second regime, the fish were exposed to 20 ppt on the 1st day, which was followed by a daily 2 ppt increase, and transferred to 32 ppt on the 7th day (7DSW). Subsequently, an 8-week growth trial was conducted. At the end of the trial, the body weight of the control fish was higher than that of the 3DSW and 7DSW while the specific growth rate of the control was higher than that of the 3DSW but not significantly different from that of the 7DSW. Similarly, the feed efficiencies of the control were not different from that of the 7DSW but were higher than that of the 3DSW. The results on the plasma Na+ and Cl levels, osmolality, and gill Na+/K+ ATPase activity indicated that steelhead in the 3DSW and 7DSW developed high hypoosmoregulatory ability at weeks 4 and 8. Kidney Na+/K+-ATPase activity increased in the 7DSW and 3DSW groups at week 4. Circulating growth hormone and insulin-like growth factor I levels in the 7DSW group were elevated at week 4, whereas the cortisol level was not changed. Our results suggest that the 7DSW but not the 3DSW alleviated the chronic effect of osmotic stress on the growth rate and feed efficiency of 50 g steelhead trout following SW transfer.

The mechanisms that sense alterations in total body sodium content to facilitate sodium homeostasis in response to an acute sodium challenge that does not increase blood pressure have not been fully elucidated. We hypothesized that the renal sympathetic nerves are critical to mediate natriuresis via α1- or β-adrenoceptors signal transduction pathways to maintain sodium balance in the face of acute increases in total body sodium content that do not activate the pressure-natriuresis mechanism. To address this hypothesis, we used acute bilateral renal denervation (RDNX), an anteroventral third ventricle (AV3V) lesion and α1- or β-antagonism during an acute 1M NaCl sodium challenge in conscious male Sprague Dawley rats. An acute 1M NaCl infusion did not alter blood pressure and evoked profound natriuresis and sympathoinhibition. Acute bilateral RDNX attenuated the natriuretic and sympathoinhibitory responses evoked by a 1M NaCl infusion [peak natriuresis (μeq/min) sham 14.5 ± 1.3 vs. acute RDNX: 9.2 ± 1.4, p < 0.05; plasma NE (nmol/L) sham control: 44 ± 4 vs. sham 1M NaCl infusion 11 ± 2, p < 0.05; acute RDNX control: 42 ± 6 vs. acute RDNX 1M NaCl infusion 25 ± 3, p < 0.05]. In contrast, an AV3V lesion did not impact the cardiovascular, renal excretory or sympathoinhibitory responses to an acute 1M NaCl infusion. Acute i.v. α1-adrenoceptor antagonism with terazosin evoked a significant drop in baseline blood pressure and significantly attenuated the natriuretic response to a 1M NaCl load [peak natriuresis (μeq/min) saline 17.2 ± 1.4 vs. i.v. terazosin 7.8 ± 2.5, p < 0.05]. In contrast, acute β-adrenoceptor antagonism with i.v. propranolol infusion did not impact the cardiovascular or renal excretory responses to an acute 1M NaCl infusion. Critically, the natriuretic response to an acute 1M NaCl infusion was significantly blunted in rats receiving a s.c. infusion of the α1-adrenoceptor antagonist terazosin at a dose that did not lower baseline blood pressure [peak natriuresis (μeq/min) sc saline: 18 ± 1 vs. sc terazosin 7 ± 2, p < 0.05]. Additionally, a s.c. infusion of the α1-adrenoceptor antagonist terazosin further attenuated the natriuretic response to a 1M NaCl infusion in acutely RDNX animals. Collectively these data indicate a specific role of a blood pressure-independent renal sympathetic nerve-dependent α1-adrenoceptor-mediated pathway in the natriuretic and sympathoinhibitory responses evoked by acute increases in total body sodium.

In this paper, we investigate a motion-tracking system for robotic computer-assisted implant surgery. Failure of the accurate implant positioning may result in significant problems, thus an accurate real-time motion-tracking system is crucial for avoiding these issues in computer-assisted implant surgery. Essential features of the motion-tracking system are analyzed and classified into four categories: workspace, sampling rate, accuracy, and back-drivability. Based on this analysis, requirements for each category have been derived to ensure that the motion-tracking system meets the desired performance criteria. A novel 6-DOF motion-tracking system is proposed which demonstrates high accuracy and back-drivability, making it suitable for use in computer-assisted implant surgery. The results of the experiments confirm the effectiveness of the proposed system in achieving the essential features required for a motion-tracking system in robotic computer-assisted implant surgery.

The purpose of the critical evaluation of the spent fuel pool (SFP) is to verify that the maximum effective multiplication factor (Keff) is less than the critical safety limit at 100% stored condition of the spent fuel with the maximum reactivity. At nuclear power plants, the storage standard of spent fuel, ie, the loading curve, is established to prevent criticality from being generated in SFP. Here, the loading curve refers to a graph showing the minimum discharged burnup versus the initial enrichment of spent fuel. Recently, US NRC proposed the new critical safety assessment guideline (DSS-ISG-2010-01, Revision 0) of PWR SFPs and most of utilities in US is following it. Of course, the licensed criterion of the maximum effective multiplication factor of SFP remains unchanged and it should be less than 0.95 from the 95% probability and the 95% confidence level. However, the new guideline is including the new evaluation methodologies like the application of the axial burnup profile, the validation of depletion and criticality code, and trend analysis. Among the new evaluation methodologies, the most important factor that affects Keff is the axial burnup profile of spent fuel. US NRC recommends to consider the axial burnup profiles presented in NUREG-6801 in criticality analysis. In this paper, criticality effect was evaluated considering three profiles, respectively: i) Axial burnup profiles presented in NUREG-6801. ii) Representative PWR axial burnup profile. iii) Uniform axial burnup profile. As the result, the case applying the axial burnup profiles presented in NUREG-6801 showed the highest Keff among three cases. Therefore, we need to introduce a new methodology because it can be issued if the axial burnup profiles presented in NUREG/CR-6801 are applied to the domestic nuclear power plants without any other consideration. Keywords: Criticality, Axial burnup profile, Uniform burnup profile, Spent fuel, Burnup credit, Spent fuel pool, Rack, Neutron absorber

Dry storage systems are one of the storage methods for spent nuclear fuel used in many countries that operate nuclear power plants. To ensure the safe storage of spent nuclear fuel, dry storage systems are designed to maintain radiation shielding, thermal management, and subcritical and mechanical integrity. In addition, these systems must be able to withstand earthquakes, tornadoes, floods, extreme temperatures, and other operating and design-based accident conditions. In order to develop a model with safety and economic feasibility by analyzing various dry storage systems, a vertically dry storage module was proposed, and evaluations were performed on safety evaluation along with design requirements. As a result of the evaluation, all of the safety design requirements were met. This evaluation’s results can be used as basic data for the detailed design of the dry storage module to proceed with further research, including the preparation of a safety analysis report and experimental verification for licensing applications.

Transactive response DNA-binding protein 43 (TDP-43)-induced neurotoxicity is currently well recognized as a contributor to the pathology of amyotrophic lateral sclerosis (ALS), and the deposition of TDP-43 has been linked to other neurodegenerative diseases, such as frontotemporal lobar degeneration (FTLD) and Alzheimer’s disease (AD). Recent studies also suggest that TDP-43-induced neurotoxicity is associated with ubiquitin-proteasome system (UPS) impairment. Histone deacetylase 6 (HDAC6) is a well-known cytosolic deacetylase enzyme that suppresses the toxicity of UPS impairment. However, the role of HDAC6 in TDP-43-induced neurodegeneration is largely unknown. In this study, we found that HDAC6 overexpression decreased the levels of insoluble and cytosolic TDP-43 protein in TDP-43-overexpressing N2a cells. In addition, TDP-43 overexpression upregulated HDAC6 protein and mRNA levels, and knockdown of Hdac6 elevated the total protein level of TDP-43. We further found that HDAC6 modulates TDP-43-induced UPS impairment via the autophagy-lysosome pathway (ALP). We also showed that TDP-43 promoted a short lifespan in flies and that the accumulation of ubiquitin aggregates and climbing defects were significantly rescued by overexpression of HDAC6 in flies. Taken together, these findings suggest that HDAC6 overexpression can mitigate neuronal toxicity caused by TDP-43-induced UPS impairment, which may represent a novel therapeutic approach for ALS.

Purpose. To evaluate the clinical characteristics and long-term prognosis of pachychoroid neovasculopathy (PCN) when compared with type 1 neovascular age-related macular degeneration (nAMD). Methods. We retrospectively analyzed 30 and 60 patients whose eyes were diagnosed as treatment-naïve PCN or type 1 nAMD, respectively. All subjects were followed up for 5 years. Baseline angiographic characteristics and long-term clinical outcomes were compared between the two groups. Results. PCN group consisted of patients of younger age and represented more choroidal vascular hyperpermeability, polypoidal lesion, and history of central serous chorioretinopathy (CSC) at the time of diagnosis (all p

Edaravone, the first known free radical scavenger, has demonstrated cellular protective properties in animals and humans. Owing to its antioxidant activity, edaravone modulates oxidative damage in various diseases, especially neurodegenerative diseases. In 2015, edaravone was approved in Japan to treat amyotrophic lateral sclerosis. The distinguishing pathogenic features of neurodegenerative diseases include high reactive oxygen species levels and mitochondrial dysfunction. However, the correlation between mitochondria and edaravone has not been elucidated. This review highlights recent studies on novel therapeutic perspectives of edaravone in terms of its effect on oxidative stress and mitochondrial function.

High-density spent fuel (SF) storage racks have been installed to increase SF pool capacity. In these SF racks, neutron absorber materials were placed between fuel assemblies allowing the storage of fuel assemblies in close proximity to one another. The purpose of the neutron absorber materials is to preclude neutronic coupling between adjacent fuel assemblies and to maintain the fuel in a subcritical storage condition. METAMIC neutron absorber has been used in high-density storage racks. But, neutron absorber materials can be subject to severe conditions including long-term exposure to gamma radiation and neutron radiation. Recently, some of them have experienced degradation, such as white spots on the surface. Under these conditions, the material must continue to serve its intended function of absorbing neutrons. For the first time in Korea, this article uses a neutron attenuation test to examine the performance of METAMIC surveillance coupons. Also, scanning electron microscope analysis was carried out to verify the white spots that were detected on the surface of METAMIC. In the neutron attenuation test, there was no significant sign of boron loss in most of the METAMIC coupons, but the coupon with white spots had relatively less B-10 content than the others. In the scanning electron microscope analysis, corrosion material was detected in all METAMIC coupons. Especially, it was confirmed that the coupon with white spots contains much more corrosion material than the others. Keywords: Blister, Criticality, METAMIC, Neutron Absorber, Neutron Attenuation Test, Scanning Electron Microscope

TAR DNA-binding protein 43 (TDP-43) is a member of an evolutionarily conserved family of heterogeneous nuclear ribonucleoproteins that modulate multiple steps in RNA metabolic processes. Cytoplasmic aggregation of TDP-43 in affected neurons is a pathological hallmark of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer’s disease (AD), and limbic predominant age-related TDP-43 encephalopathy (LATE). Mislocalized and accumulated TDP-43 in the cytoplasm induces mitochondrial dysfunction and reactive oxidative species (ROS) production. Here, we show that TDP-43- and rotenone-induced neurotoxicity in the human neuronal cell line SH-SY5Y were attenuated by hydroxocobalamin (Hb, vitamin B12 analog) treatment. Although Hb did not affect the cytoplasmic accumulation of TDP-43, Hb attenuated TDP-43-induced toxicity by reducing oxidative stress and mitochondrial dysfunction. Moreover, a shortened lifespan and motility defects in TDP-43-expressing Drosophila were significantly mitigated by dietary treatment with hydroxocobalamin. Taken together, these findings suggest that oral intake of hydroxocobalamin may be a potential therapeutic intervention for TDP-43-associated proteinopathies.

Neuroretinitis is a rare clinical entity, characterized by optic nerve edema and star-shape hard exudate around fovea. The clinical features include acute unilateral visual loss, dyschromatopsia, relative afferent pupillary defect and visual field abnormalities. Increased vascular permeability of the optic disc is the main pathophysiology. As it is a not fully known clinical entity, diagnosis is challenging. In this case, we use multimodal imaging to reveal pathophysiology and anatomical change of early mild neuroretinitis. Case presentation: A 28-year-old healthy woman presented to the clinic with mild blurred vision in her left eye. After complete ophthalmic examination, outer retinal thickening of the temporal peripapillary area and optic disc edema were observed. Two days after diagnosis, the retinal edema and visual symptoms were aggravated. A hard exudate, maybe a part of macular star, was observed. Multimodal imaging including optical coherence tomography (OCT), swept-source OCT angiography (SS-OCTA), fluorescein angiography, and indocyanine green angiography visualized choroidal thinning and insufficient circulation beneath the outer retinal edema. Following steroid pulse therapy, the retinal edema and blurred vision were completely resolved. Conclusions: Multimodal imaging suggested that unilateral optic disc edema and early macular star help the diagnosis of neuroretinitis. In SS-OCTA, we found focal choroidal insufficiency. The focal insufficient choroidal circulation might be a contribution factor for idiopathic neuroretinitis. Multimodal imaging including SS-OCTA may be a valuable tool for detecting and monitoring disease progression.

BackgroundThis is part of a prospective study carried out as a national project to secure standardized public resources for type 2 diabetes mellitus (T2DM) patients in Korea. We compared various characteristics of long-standing T2DM patients with diabetic retinopathy (DR) and macular edema (ME).MethodsFrom September 2014 to July 2015, T2DM patients with disease duration of at least 15 years were recruited at a single university hospital. Clinical data and samples were collected according to the common data elements and standards of procedure developed by the Korean Diabetes Association Research Council. Each participant was assessed by ophthalmologists for DR and ME.ResultsAmong 220 registered patients, 183 completed the ophthalmologic assessment. DR was associated with longer disease duration (odds ratio [OR], 1.071; 95% confidence interval [CI], 1.001 to 1.147 for non-proliferative diabetic retinopathy [NPDR]) (OR, 1.142; 95% CI, 1.051 to 1.242 for proliferative diabetic retinopathy [PDR]) and the use of long-acting insulin (OR, 4.559; 95% CI, 1.672 to 12.427 for NPDR) (OR, 4.783; 95% CI, 1.581 to 14.474 for PDR), but a lower prevalence of a family history of cancer (OR, 0.310; 95% CI, 0.119 to 0.809 for NPDR) (OR, 0.206; 95% CI, 0.063 to 0.673 for PDR). ME was associated with higher glycosylated hemoglobin levels (OR, 1.380; 95% CI, 1.032 to 1.845) and the use of rapid-acting insulin (OR, 5.211; 95% CI, 1.445 to 18.794).ConclusionVarious clinical features were associated with DR and ME. Additional epidemiological and biorepository-based studies using this cohort are being conducted to deepen our understanding of diabetic complications in Korea.

Amyotrophic lateral sclerosis (ALS) is a rare neurological disorder that affects the motor neurons responsible for regulating muscle movement. However, the molecular pathogenic mechanisms of ALS remain poorly understood. A deficiency in the antioxidant tripeptide glutathione (GSH) in the nervous system appears to be involved in several neurodegenerative diseases characterized by the loss of neuronal cells. Impaired antioxidant defense systems, and the accumulation of oxidative damage due to increased dysfunction in GSH homeostasis are known to be involved in the development and progression of ALS. Aberrant GSH metabolism and redox status following oxidative damage are also associated with various cellular organelles, including the mitochondria and nucleus, and are crucial factors in neuronal toxicity induced by ALS. In this review, we provide an overview of the implications of imbalanced GSH homeostasis and its molecular characteristics in various experimental models of ALS.

Transfemoral cerebral angiography (TFCA) has been increasingly used as diagnostic method for the evaluation of cerebral vessels. Ophthalmologic complication after TFCA has rarely been reported, and most complications are associated with an intraoperative thrombo-embolic event. We reported a patient who developed a superior altitudinal visual field defect one day after diagnostic TFCA. The ophthalmic exam revealed a prominent inferior optic disc edema, and the fluorescein angiographic showed the non-perfusion of the corresponding inferior sectoral optic disc. Diffusion-weighted MRI on the day following cerebral angiography revealed multiple focal scattered acute infarctions. Even one month after steroid pulse therapy, the superior nasal field defect remained with minimal improvement. We believe this case was consistent with an acute anterior ischemic optic neuropathy (AION) due to thrombo-embolism after TFCA. Ophthalmic examinations and a visual field test should be performed before and immediately after the TFCA, particularly in the case with a high risk of thromboembolic events.

Diabetic nephropathy (DN) is the most serious complication of diabetes and a leading cause of kidney failure and mortality in patients with diabetes. However, the exact pathogenic mechanisms involved are poorly understood. Impaired mitochondrial function and accumulation of damaged mitochondria due to increased imbalance in mitochondrial dynamics are known to be involved in the development and progression of DN. Accumulating evidence suggests that aberrant mitochondrial fission is involved in the progression of DN. Conversely, studies linking excessively enlarged mitochondria to DN pathogenesis are emerging. In this review, we summarize the current concepts of imbalanced mitochondrial dynamics and their molecular aspects in various experimental models of DN. We discuss the recent evidence of enlarged mitochondria in the kidneys of DN and examine the possibility of a therapeutic application targeting mitochondrial dynamics in DN.

Many leading companies in the automotive industry have been putting tremendous effort into developing new powertrains and technologies to make their products more energy efficient. Evaluating the fuel economy benefit of a new technology in specific powertrain systems is straightforward; and, in an early concept phase, obtaining a projection of energy efficiency benefits from new technologies is extremely useful. However, when carmakers consider new technology or powertrain configurations, they must deal with a trade-off problem involving factors such as energy efficiency and performance, because of the complexities of sizing a vehicle’s powertrain components, which directly affect its energy efficiency and dynamic performance. As powertrains of modern vehicles become more complicated, even more effort is required to design the size of each component. This study presents a component-sizing process based on the forward-looking vehicle simulator “Autonomie” and the optimization algorithm “POUNDERS”; the supervisory control strategy based on Pontryagin’s Minimum Principle (PMP) assures sufficient computational system efficiency. We tested the process by applying it to a single power-split hybrid electric vehicle to determine optimal values of gear ratios and each component size, where we defined the optimization problem as minimizing energy consumption when the vehicle’s dynamic performance is given as a performance constraint. The suggested sizing process will be helpful in determining optimal component sizes for vehicle powertrain to maximize fuel efficiency while dynamic performance is satisfied. Indeed, this process does not require the engineer’s intuition or rules based on heuristics required in the rule-based process.

Although mitochondrial dysfunction is associated with the development and progression of diabetic nephropathy (DN), its mechanisms are poorly understood, and it remains debatable whether mitochondrial morphological change is a cause of DN. In this study, a Drosophila DN model was established by treating a chronic high-sucrose diet that exhibits similar phenotypes in animals. Results showed that flies fed a chronic high-sucrose diet exhibited a reduction in lifespan, as well as increased lipid droplets in fat body tissue. Furthermore, the chronic high-sucrose diet effectively induced the morphological abnormalities of nephrocytes in Drosophila. High-sucrose diet induced mitochondria fusion in nephrocytes by increasing Opa1 and Marf expression. These findings establish Drosophila as a useful model for studying novel regulators and molecular mechanisms for imbalanced mitochondrial dynamics in the pathogenesis of DN. Furthermore, understanding the pathology of mitochondrial dysfunction regarding morphological changes in DN would facilitate the development of novel therapeutics.

Amyotrophic lateral sclerosis (ALS) is a common neurodegenerative disease characterized by progressive motor neuron degeneration. Although several studies on genes involved in ALS have substantially expanded and improved our understanding of ALS pathogenesis, the exact molecular mechanisms underlying this disease remain poorly understood. Glycogen synthase kinase 3 (GSK3) is a multifunctional serine/threonine-protein kinase that plays a critical role in the regulation of various cellular signaling pathways. Dysregulation of GSK3β activity in neuronal cells has been implicated in the pathogenesis of neurodegenerative diseases. Previous research indicates that GSK3β inactivation plays a neuroprotective role in ALS pathogenesis. GSK3β activity shows an increase in various ALS models and patients. Furthermore, GSK3β inhibition can suppress the defective phenotypes caused by SOD, TDP-43, and FUS expression in various models. This review focuses on the most recent studies related to the therapeutic effect of GSK3β in ALS and provides an overview of how the dysfunction of GSK3β activity contributes to ALS pathogenesis.

In this paper, we propose a dynamic displacement estimation method for large-scale civil infrastructures based on a two-stage Kalman filter and modified heuristic drift reduction method. When measuring displacement at large-scale infrastructures, a non-contact displacement sensor is placed on a limited number of spots such as foundations of the structures, and the sensor must have a very long measurement distance (typically longer than 100 m). RTK-GNSS, therefore, has been widely used in displacement measurement on civil infrastructures. However, RTK-GNSS has a low sampling frequency of 10–20 Hz and often suffers from its low stability due to the number of satellites and the surrounding environment. The proposed method combines data from an RTK-GNSS receiver and an accelerometer to estimate the dynamic displacement of the structure with higher precision and accuracy than those of RTK-GNSS and 100 Hz sampling frequency. In the proposed method, a heuristic drift reduction method estimates displacement with better accuracy employing a low-pass-filtered acceleration measurement by an accelerometer and a displacement measurement by an RTK-GNSS receiver. Then, the displacement estimated by the heuristic drift reduction method, the velocity measured by a single GNSS receiver, and the acceleration measured by the accelerometer are combined in a two-stage Kalman filter to estimate the dynamic displacement. The effectiveness of the proposed dynamic displacement estimation method was validated through three field application tests at Yeongjong Grand Bridge in Korea, San Francisco–Oakland Bay Bridge in California, and Qingfeng Bridge in China. In the field tests, the root-mean-square error of RTK-GNSS displacement measurement reduces by 55–78 percent after applying the proposed method.

Transactive response DNA-binding protein-43 (TDP-43) is involved in the pathology of familial and sporadic amyotrophic lateral sclerosis (ALS). TDP-43-mediated ALS models in mice, Drosophila melanogaster, and zebrafish exhibit dysfunction of locomotor function, defective neuromuscular junctions, and motor neuron defects. There is currently no effective cure for ALS, and the underlying mechanisms of TDP-43 in ALS remain poorly understood. In this study, a genetic screen was performed to identify modifiers of human TDP-43 (hTDP-43) in a Drosophila model, and glutathione S-transferase omega 2 (GstO2) was found to be involved in hTDP-43 neurotoxicity. GstO2 overexpressed on recovered defective phenotypes resulting from hTDP-43, including defective neuromuscular junction (NMJ) boutons, degenerated motor neuronal axons, and reduced larvae and adult fly locomotive activity, without modulating the levels of hTDP-43 protein expression. GstO2 modulated neurotoxicity by regulating reactive oxygen species (ROS) produced by hTDP-43 in the Drosophila model of ALS. Our results demonstrated that GstO2 was a key regulator in hTDP-43-related ALS pathogenesis and indicated its potential as a therapeutic target for ALS.

A displacement measurement system fusing a low cost real-time kinematic global positioning system (RTK-GPS) receiver and a force feedback accelerometer is proposed for infrastructure monitoring. The proposed system is composed of a sensor module, a base module and a computation module. The sensor module consists of a RTK-GPS rover and a force feedback accelerometer, and is installed on a target structure like conventional RTK-GPS sensors. The base module is placed on a rigid ground away from the target structure similar to conventional RTK-GPS bases, and transmits observation messages to the sensor module. Then, the initial acceleration, velocity and displacement responses measured by the sensor module are transmitted to the computation module located at a central monitoring facility. Finally, high precision and high sampling rate displacement, velocity, and acceleration are estimated by fusing the acceleration from the accelerometer, the velocity from the GPS rover, and the displacement from RTK-GPS. Note that the proposed displacement measurement system can measure 3-axis acceleration, velocity as well as displacement in real time. In terms of displacement, the proposed measurement system can estimate dynamic and pseudo-static displacement with a root-mean-square error of 2 mm and a sampling rate of up to 100 Hz. The performance of the proposed system is validated under sinusoidal, random and steady-state vibrations. Field tests were performed on the Yeongjong Grand Bridge and Yi Sun-sin Bridge in Korea, and the Xihoumen Bridge in China to compare the performance of the proposed system with a commercial RTK-GPS sensor and other data fusion techniques.

Direct numerical simulations are performed to investigate the characteristics of a turbulent core-annular flow with water-lubricated high viscosity oil in a horizontal pipe. Six different superficial velocity ratios (jw/jo = 0.057-0.41) are examined by changing the water superficial velocity jw for a fixed oil superficial velocity jo. The pressure drops in the pipe and the shapes of the phase interface agree well with those from previous experiments. The oil core flow is almost a plug flow, and the gaps between the phase interface and pipe wall are narrow and wide near the upper and lower surfaces of the pipe, respectively, due to the buoyancy. Within a narrow gap, water is confined mostly in a valley region of the wavy phase interface and hardly goes through its crest. On the other hand, water near the phase interface at a wide gap convects downstream almost at the core speed and the flow near the wall is similar to that of single-phase wall-bounded turbulent flow. The annular flow is characterized by three different regimes depending on the clearance Reynolds number (Rec) based on the core velocity and local gap size: laminar Couette flow driven by the core for Rec = 600, transitional flow for 600 < Rec < 2500 and turbulent flow for Rec = 2500. The minimum pressure drop occurs at jw/jo = 0.11 in the early transition regime. For all jw/jo considered, the negative lift force acting on the core comes from the pressure force which balances the buoyancy. [ABSTRACT FROM AUTHOR]