Social network analysis for medical narcotics in South Korea: focusing on patients and healthcare organizations.

BACKGROUND: Medical narcotics must be administered under medical supervision because of their potential for misuse and abuse, leading to more dangerous and addictive substances. The control of medical narcotics requires close monitoring to ensure that they remain safe and effective. This study proposes a methodology that can effectively identify the overprescription of medical narcotics in hospitals and patients. METHODS: Social network analysis (SNA) was applied to prescription networks for medical narcotics. Prescription data were obtained from the Narcotics Information Management System in South Korea, which contains all data on narcotic usage nationwide. Two-mode networks comprising hospitals and patients were constructed based on prescription data from 2019 to 2021 for the three most significant narcotics: appetite suppressants, zolpidem, and propofol. Two-mode networks were then converted into one-mode networks for hospitals. Network structures and characteristics were analyzed to identify hospitals suspected of overprescribing. RESULTS: The SNA identified hospitals that overprescribed medical narcotics. Patients suspected of experiencing narcotic addiction seek treatment in such hospitals. The structure of the network was different for the three narcotics. While appetite suppressants and propofol networks had a more centralized structure, zolpidem networks showed a less centralized but more fragmented structure. During the analysis, two types of hospitals caught our attention: one with a high degree, meaning that potential abusers have frequently visited the hospital, and the other with a high weighted degree, meaning that the hospital may overprescribe. For appetite suppressants, these two types of hospitals matched 84.6%, compared with 30.0% for propofol. In all three narcotics, clinics accounted for the largest share of the network. Patients using appetite suppressants were most likely to visit multiple locations, whereas those using zolpidem and propofol tended to form communities around their neighborhoods. CONCLUSIONS: The significance of this study lies in its analysis of nationwide narcotic use reports and the differences observed across different types of narcotics. The social network structure between hospitals and patients varies depending on the composition of the medical narcotics. Therefore, these characteristics should be considered when controlling medication with narcotics. The results of this study provide guidelines for controlling narcotic use in other countries.

Orientation and stretching of supracolloidal chains of diblock copolymer micelles by spin-coating process.

Supracolloidal chains consisting of nano- or micro-scale particles exhibit anisotropic properties not observed in individual particles. The orientation of the chains is necessary to manifest such characteristics on a macroscopic scale. In this study, we demonstrate the orientation of supracolloidal chains composed of nano-scale micelles of a diblock copolymer through spin-coating. We observed separate chains coated on a substrate with electron microscopy, and analyzed the orientation and stretching of the chains quantitatively with image analysis software. In drop-casting, the chains were coated randomly with no preferred orientation, and the degree of stretching exhibited an intrinsic semi-flexible nature. In contrast, spin-coated chains were aligned in the radial direction, and the apparent persistence length of the chain increased, confirming the stretching of the chain quantitatively. Furthermore, by incorporating fluorophores into supracolloidal chains and confirming the oriented chains with confocal fluorescence microscopy, it is demonstrated that oriented chains can be utilized as a template to align functional materials.

Glioma subtype classification from histopathological images using in-domain and out-of-domain transfer learning: An experimental study.

We provide in this paper a comprehensive comparison of various transfer learning strategies and deep learning architectures for computer-aided classification of adult-type diffuse gliomas. We evaluate the generalizability of out-of-domain ImageNet representations for a target domain of histopathological images, and study the impact of in-domain adaptation using self-supervised and multi-task learning approaches for pretraining the models using the medium-to-large scale datasets of histopathological images. A semi-supervised learning approach is furthermore proposed, where the fine-tuned models are utilized to predict the labels of unannotated regions of the whole slide images (WSI). The models are subsequently retrained using the ground-truth labels and weak labels determined in the previous step, providing superior performance in comparison to standard in-domain transfer learning with balanced accuracy of 96.91% and F1-score 97.07%, and minimizing the pathologist's efforts for annotation. Finally, we provide a visualization tool working at WSI level which generates heatmaps that highlight tumor areas; thus, providing insights to pathologists concerning the most informative parts of the WSI.

Effect of Silica in the Manufacture of Autologous Serum Eye Drops on Corneal Stromal Cells.

PURPOSE: The aim of this study was to evaluate the effect of serum clot activator, silica (SiO 2 ), which may be used for making autologous serum eye drops, on human corneal fibroblasts. METHODS: Cultured human corneal fibroblasts were exposed to 10%, 20%, and 30% silica for 1, 6, and 24 hours; methyl thiazolyl tetrazolium-based colorimetric assay was performed to determine the survival rate of fibroblasts and lactate dehydrogenase leakage assay to assess the cytotoxicity. The apoptotic response was evaluated by flow cytometric analysis and fluorescence staining with Annexin V and propidium iodide. Cellular morphology was evaluated by inverted phase-contrast light microscopy and electron microscopy. RESULTS: The survival rate of human corneal fibroblasts and cytotoxicity showed both dose-dependent and time-dependent responses. The fluorescent micrograph and flow cytometry showed that as the exposure time increased, more cells underwent apoptosis or necrosis after treatment with 30% silica. When observed with light and electron microscopy, the number of corneal fibroblasts decreased and they were more detached from the dish. In addition, damaged corneal fibroblasts showed degenerative changes after exposure to 30% silica. CONCLUSIONS: Silica showed dose-dependent and time-dependent toxicity in human corneal fibroblasts. It is safer to keep the blood in tubes without a clot activator when manufacturing autologous serum eye drops to prevent possible corneal cytotoxicity.

Changes in Intraocular Pressure and Anterior Chamber Parameters Following Cataract Surgery, Vitrectomy, and Combined Surgery.

PURPOSE: The aim of this study is to investigate changes in intraocular pressure (IOP) and anterior-segment parameters before and after cataract surgery, vitrectomy, and combined surgery. METHODS: The records of patients who had undergone cataract surgery (cataract group), vitrectomy (vitrectomy group), or combined cataract surgery and vitrectomy (combined group) at our hospital were retrospectively examined. The vitrectomy group consisted of pseudophakic eyes. IOP and anterior-segment measurements, including anterior chamber depth (ACD), angle opening distance (AOD), trabecular-iris angle (TIA), and trabecular-iris space area (TISA), were measured using swept-source anterior-segment optical coherence tomography before and 6 months after surgery in 41, 15, and 40 eyes, respectively. RESULTS: In the cataract and combined groups, there was a decrease in IOP (cataract group: from 15.8 to 13.4 mmHg, p <0.001; combined group: from 15.8 to 14.2 mmHg, p = 0.002) and an increase in the central corneal thickness after surgery (p <0.001). The ACD increased in all groups, with a smaller increase in the vitrectomy group (p <0.03). Postoperative AOD, TIA, and TISA were significantly increased in the cataract and combined groups (p <0.02). Higher preoperative IOP and larger IOP reduction after surgery were correlated with smaller preoperative AOD, TISA, and TIA in cataract and combined groups (p <0.034). A small preoperative ACD was related to smaller preoperative AOD, TISA, TIA (r > 0.649, p <0.001), and postoperative IOP reduction in the cataract and combined groups (r = 0.377, p = 0.018 and r = 0.559, p = 0.001, respectively). CONCLUSIONS: Compared to the vitrectomy group, the cataract and combined groups showed reduced postoperative IOP and increased AOD, TISA, and TIA. In these two groups, patients with shallower preoperative ACDs showed greater changes in IOP after surgery. Changes in IOP after surgery are thought to be related to changes in the anterior segment caused by the removal of the crystalline lens.

Correction: The amoebicidal effect of Torreya nucifera extract on Acanthamoeba lugdunensis.

[This corrects the article DOI: 10.1371/journal.pone.0281141.].

The clinical effectiveness of fused image of single-photon emission CT and facial CT for the evaluation of degenerative change of mandibular condylar head.

BACKGROUND: The primary objective of this study was to assess the clinical effectiveness of fused images obtained from single-photon emission computed tomography (SPECT) and facial computed tomography (CT) for evaluating degenerative changes in the mandibular condylar head. This assessment was accomplished by comparing the Technetium-99 m methylene diphosphonate (99mTc-MDP) uptake ratio with the results of clinical and radiographic findings. METHODS: The study included 17 patients (3 males and 14 females) with suspected osteoarthritis of the mandibular condyle, totaling 34 temporomandibular joints (TMJs). Based on clinical and radiographic examinations, the TMJs were categorized into four groups: normal (group N), internal derangement (group ID), osteoarthritis (group OA), and osteoarthritis sequelae (group OAseq). For each patient, bone SPECT and facial CT scans were registered and reconstructed to create fused SPECT/CT images. The 99mTc-MDP uptake levels in the TMJs were statistically compared among the four groups. RESULTS: The 99mTc-MDP uptake ratio showed a gradual increase in the order of the following: group N, group OAseq, group ID, and group OA. There was a significant difference observed among groups (p = 0.003), mainly driven by the disparity between group OA and both group N (p < 0.001) and group OAseq (p = 0.048). CONCLUSION: Fused SPECT/CT image can be an effective tool for evaluating degenerative changes in the mandibular condylar head. The technique demonstrated the ability to differentiate between normal TMJs and those with internal derangement, osteoarthritis, or osteoarthritis sequelae. This approach holds promise as a valuable method in clinical assessments of TMJ degeneration.

Detection of Nα-terminally formylated native proteins by a pan-N-formyl methionine-specific antibody.

N-formyl methionine (fMet)-containing proteins are produced in bacteria, eukaryotic organelles mitochondria and plastids, and even in cytosol. However, Nα-terminally formylated proteins have been poorly characterized because of the lack of appropriate tools to detect fMet independently of downstream proximal sequences. Using a fMet-Gly-Ser-Gly-Cys peptide as an antigen, we generated a pan-fMet-specific rabbit polyclonal antibody called anti-fMet. The raised anti-fMet recognized universally and sequence context-independently Nt-formylated proteins in bacterial, yeast, and human cells as determined by a peptide spot array, dot blotting, and immunoblotting. We anticipate that the anti-fMet antibody will be broadly used to enable an understanding of the poorly explored functions and mechanisms of Nt-formylated proteins in various organisms.

The amoebicidal effect of Torreya nucifera extract on Acanthamoeba lugdunensis.

As the number of contact lens users increases, contact lens induced corneal infection is becoming more common. Acanthamoeba keratitis (AK) is a type of those which is caused by Acanthamoeba species, and may cause severe ocular inflammation and visual loss. We evaluated whether Torreya nucifera (T. nucifera) extract has an anti-amoebic effect and studied its mechanism of action on Acanthamoeba lugdunensis (A. lugdunensis). Cell viability was tested using the alamarBlue™ method, and the cell death mechanism was confirmed using the Tali® Apoptosis Kit. The SYTOX® Green assay was performed to check the plasma membrane permeability. The JC-1 dye was used to measure the mitochondrial membrane potential. A CellTiter-Glo® Luminescent Assay was used to measure the adenosine-triphosphate (ATP) level. Morphological changes in the mitochondria were examined by transmission electron microscopy (TEM). Cystic changes and a decrease in cell viability after treatment with T. nucifera were observed. Both apoptotic and necrotic cells were found in the Tali® Apoptosis assay. There was no significant difference in plasma membrane permeability between the control and T. nucifera treated groups. The collapse of the mitochondrial membrane potential and reduced ATP level in A. lugdunensis was confirmed in the groups treated with T. nucifera. Structural damage to the mitochondria was observed on TEM in the groups treated with T. nucifera. T. nucifera showed an anti-amoebic effect on A. lugdunensis, by inducing the loss of mitochondrial membrane potential. Thus, it could be a future therapeutic agent for AK.

Narcotics information management system in South Korea: system development and innovation.

BACKGROUND: As the misuse and abuse of medical narcotics are increasing in South Korea, an information system for the integrated information management of medical narcotic drugs across the nation is needed. This paper presents the development process of the Narcotics Information Management System (NIMS) for the monitoring of medical narcotics usage and the results of its implementation. METHODS: As the NIMS enforces that all narcotics handlers digitally report all information on handling medical narcotic drugs, the functional requirements of the NIMS have been identified in accordance with the Narcotics Control Act. In addition to the functional requirements, the non-functional requirements of the NIMS have been elicited by major narcotics handlers and their associations. The non-functional requirements include privacy, availability, connectivity, interoperability, and data integrity. The system design with entity-relationship diagrams and its implementation processes have been presented. RESULTS: The NIMS encompasses all narcotic handlers, which comprise exporting, importing, and pharmaceutical companies; wholesalers; hospitals and clinics; and pharmacies, collecting over 120 million cases annually. It enables transparent monitoring throughout the life cycle, from manufacturing, sales, purchase, and disposal of narcotics. As a result, the number of prescriptions for medical narcotics has been reduced by 9.2%. CONCLUSIONS: To the best of our knowledge, the NIMS is the world's first system to manage all information on the total life cycle of medical narcotics, including imports, production, distribution, use, and disposal of drugs. This system has enabled the safety management and monitoring of medical narcotic drugs. Additionally, it provides consistent and transparent information to physicians and patients, leading to the autonomous safety management of narcotics. The successful development of the NIMS can provide guidelines for implementing a narcotics management system in other countries.

The choroidal microvasculature of the parapapillary area as a biomarker of glaucoma development in the fellow eye of patients with unilateral glaucoma.

PURPOSE: To investigate the factors associated with the development of glaucoma in the healthy eyes of unilateral glaucoma patients. MATERIALS AND METHODS: This was a retrospective observational case series study. All participants had unilateral primary open-angle glaucoma at the initial visit and were divided into two groups: one in which the fellow eyes developed glaucoma during the follow-up period and one in which the fellow eyes remained healthy. A complete ophthalmic examination, including best-corrected visual acuity testing, slit-lamp examination, intraocular pressure measurement, retinal nerve fiber layer and optic disk photographs, a 30-2 visual field test, and optical coherence tomography with angiography, was performed over a follow-up period of at least 3 years. RESULTS: A total of fifty-six patients were enrolled, and over the course of the study period, 11 patients developed glaucoma in the fellow eyes, while the fellow eyes of 45 patients remained healthy. At the baseline, the glaucomatous eye had a larger area of beta parapapillary atrophy, lower parapapillary choroidal vascular density (pCVD) within the area, and a lower prevalence of microvascular dropout than normal fellow eyes (P < 0.001, 0.013, 0.001, respectively). In the multivariate analysis, a reduced pCVD in the gamma parapapillary atrophy (γPPA) region was significantly associated with the development of glaucoma in normal eyes (odds ratio, 0.566; 95% CI, 0.342, 0.935; P = 0.026). CONCLUSIONS: The pCVD within the γPPA region at baseline is the risk factor for the development of glaucoma in the normal fellow eye of patients with unilateral glaucoma.

Disynaptic effect of hilar cells on pattern separation in a spiking neural network of hippocampal dentate gyrus.

We study the disynaptic effect of the hilar cells on pattern separation in a spiking neural network of the hippocampal dentate gyrus (DG). The principal granule cells (GCs) in the DG perform pattern separation, transforming similar input patterns into less-similar output patterns. In our DG network, the hilus consists of excitatory mossy cells (MCs) and inhibitory HIPP (hilar perforant path-associated) cells. Here, we consider the disynaptic effects of the MCs and the HIPP cells on the GCs, mediated by the inhibitory basket cells (BCs) in the granular layer; MC → BC → GC and HIPP → BC → GC. The MCs provide disynaptic inhibitory input (mediated by the intermediate BCs) to the GCs, which decreases the firing activity of the GCs. On the other hand, the HIPP cells disinhibit the intermediate BCs, which leads to increasing the firing activity of the GCs. In this way, the disynaptic effects of the MCs and the HIPP cells are opposite. We investigate change in the pattern separation efficacy by varying the synaptic strength K ( BC , X ) [from the pre-synaptic X (= MC or HIPP) to the post-synaptic BC]. Thus, sparsity for the firing activity of the GCs is found to improve the efficacy of pattern separation, and hence the disynaptic effects of the MCs and the HIPP cells on the pattern separation become opposite ones. In the combined case when simultaneously changing both K ( BC , MC ) and K ( BC , HIPP ) , as a result of balance between the two competing disynaptic effects of the MCs and the HIPP cells, the efficacy of pattern separation is found to become the highest at their original default values where the activation degree of the GCs is the lowest. We also note that, while the GCs perform pattern separation, sparsely synchronized rhythm is found to appear in the population of the GCs. Hence, we examine quantitative association between population and individual firing behaviors in the sparsely synchronized rhythm and pattern separation. They are found to be strongly correlated. Consequently, the better the population and individual firing behaviors in the sparsely synchronized rhythm are, the more pattern separation efficacy becomes enhanced.

Binocular function in patients with intermittent exotropia accompanied by unilateral congenital ptosis.

Patients with intermittent exotropia (IXT) have a wide range of binocular deficits. This study aims to evaluate the effect of ptosis on the binocular function of patients with IXT. Clinical records of 45 IXT patients with congenital ptosis (IXT-ptosis group) and 58 age-matched IXT patients without ptosis (IXT only group) who presented for eye examination between January 2017 and June 2020 were retrospectively reviewed. Patients with amblyopia were excluded to rule out the effects of visual acuity on binocularity. Best-corrected visual acuity (BCVA), the magnitude of exodeviation at distance and at near, stereopsis, and office-based control scores at the first visit were reviewed. The binocular functions of the two groups were compared. The mean ± SD age of the overall patients was 6.6 ± 2.7 years. There were no significant differences in the distribution of age, sex, spherical equivalent refraction, or BCVA between the two groups (all p > 0.05). Although the office-based control scores at distance and near were slightly worse in the IXT-ptosis group, the differences were not statistically significant (at distance, 2.8 ± 1.87 vs. 2.2 ± 1.13, p = 0.08; at near, 1.8 ± 0.67 vs. 1.6 ± 0.74, p = 0.11). Furthermore, the IXT-ptosis group had worse stereopsis at distance (p = 0.01). There were no significant differences between the two groups in near stereopsis or exodeviation magnitude (p > 0.05). A larger proportion of patients had suppression on the Bagolini test in the IXT-ptosis group than in the IXT-only group (p = 0.04). The IXT-ptosis group had worse distance stereoacuity, and a larger proportion of patients had suppression on the Bagolini test than the IXT only group. In IXT patients, the presence of coexisting ptosis can have a further deleterious impact on binocular function.

A randomized multicenter evaluation of the efficacy of 0.15% hyaluronic acid versus 0.05% cyclosporine A in dry eye syndrome.

Hyaluronic acid (HA) and cyclosporine A (CsA) eyedrops are commonly prescribed in dry eye syndrome (DES). The effectiveness of each preparation in DES is well-known, yet the superiority of one over another has been studied little. We assessed the efficacy and tolerability of 0.15% HA compared to combinations of 0.05% CsA plus 0.5% carboxymethylcellulose (CMC), and 0.15% HA plus 0.05% CsA in patients with moderate to severe DES. Total 438 patients with moderate to severe DES were recruited and randomized for one of the three treatments for 12 weeks. Effectiveness was assessed at baseline, 4- and 12-weeks. The primary endpoint was change in corneal staining score. The secondary endpoints were tear break-up time (TBUT), strip meniscometry (SM) score, ocular surface disease index (OSDI) score, and tolerability questionnaire. The change in corneal staining score for 0.15% HA from the baseline was non-inferior to that of 0.05% CsA. Corneal staining score, TBUT, SM score, and OSDI score improved in all groups without statistically significant intergroup differences. Better tolerability and lower prevalence of adverse drug reactions were seen in 0.15% HA. Our findings suggest that 0.15% HA may be equivalently effective and safer than 0.05% CsA in treating moderate to severe DES.

The Efficacy of Atelocollagen to Inhibit Fibrotic Proliferation in Tenon Tissue: in vitro study.

INTRODUCTION: To evaluate the safety and efficacy of atelocollagen in preventing the fibrotic change of human tenon tissue induced by transforming growth factor ß1 (TGFß1) Methods: Primary cultured human Tenon's fibroblasts (HTFs) were incubated with TGFß1 alone, and with a various concentrations of atelocollagen respectively. Cell viability was measured by cell counting kit-8 (CCK8). The mRNA levels of α-smooth muscle actin (α-SMA), vimentin, fibronectin, zonular occludens scaffolding protein (ZO-1), cellular communication network factor 2 (CCN2) and interleukin-6 (IL-6) were measured by quantitative reverse transcription polymerase chain reaction (RT-PCR), western blot and immunofluorescence analysis. Wound healing assay and collagen contraction assay were additionally evaluated for identifying the inhibitory effect of atelocollagen in HTFs. To elucidate the mechanism by which atelocollagen affects HTFs proliferation, the phospho-extracellular-signal-regulated kinases (pERK)/total-extracellular-signal-regulated kinases (tERK), phospho-focal adhesion kinase (pFAK)/total-focal adhesion kinase (tFAK), and pSmad3/tSmad3 protein expression ratios were measured by Western blot. RESULTS: The safety of atelocollagen in HTF was identified by CCK8 analysis. The expression of α-SMA and vimentin in HTFs treated with 0.023% and 0.046% atelocollagen significantly decreased at both mRNA and protein levels, while that of ZO-1 in 0.046% atelocollagen increased compared with TGFß1-treated cells. The protein expression of fibronectin, CCN2, and IL-6 in HTFs treated with 0.023% and 0.046% atelocollagen significantly decreased. Immunofluorescence microscopy of α-SMA and ZO-1 showed results similar to those of the western blot. In the wound scratch assays, cell migration was significantly attenuated in HTFs treated with 0.005% atelocollagen. Atelocollagen at 0.005, 0.011, and 0.023% significantly inhibited the gel contraction induced by TGFß1 at both 24 h and 48 h. The increase in pERK/tERK and pSmad3/tSmad3 protein expression ratios in TGFß1-treated HTFs significantly decreased after treatment with 0.023 and 0.046% atelocollagen. CONCLUSION: Since atelocollagen gel effectively suppresses the proliferation of HTFs in TGFß1 - induced transdifferentiation, it may be a potential therapeutic agent in glaucoma surgery.

Luteolin-7-O-Glucuronide Improves Depression-like and Stress Coping Behaviors in Sleep Deprivation Stress Model by Activation of the BDNF Signaling.

Stress exposure is a major risk factor for mental disorders such as depression. Because of the limitations of classical antidepressants such as side effects, low efficacy, and difficulty in long-term use, new natural medicines and bioactive molecules from plants with greater safety and efficacy have recently attracted attention. Luteolin-7-O-glucuronide (L7Gn), a bioactive molecule present in Perilla frutescens, is known to alleviate severe inflammatory responses and oxidative stress in macrophages. However, its antistress and antidepressant effects have not been elucidated. The present study aims to explore the antidepressant the effect of L7Gn on stress-induced behaviors and the underlying mechanism in a mouse sleep deprivation (SD) model. L7Gn treatment improved depression-like and stress coping behaviors induced by SD stress, as confirmed by the tail suspension test and forced swimming test. Furthermore, L7Gn treatment reduced the blood corticosterone and hippocampal proinflammatory cytokine levels which were increased by SD stress, and L7Gn also increased the mRNA and protein levels of hippocampal brain-derived neurotrophic factor (BDNF) which were reduced by SD stress. Additionally, treatment with L7Gn resulted in increases in the phosphorylation of tropomyosin-related kinase B (TrkB), extracellular signal-regulated kinase (ERK), and cAMP response element-binding protein (CREB), which are downstream molecules of BDNF signaling. These findings suggest that L7Gn have therapeutic potential for SD-induced stress, via activating the BDNF signaling.

Population and individual firing behaviors in sparsely synchronized rhythms in the hippocampal dentate gyrus.

We investigate population and individual firing behaviors in sparsely synchronized rhythms (SSRs) in a spiking neural network of the hippocampal dentate gyrus (DG). The main encoding granule cells (GCs) are grouped into lamellar clusters. In each GC cluster, there is one inhibitory (I) basket cell (BC) along with excitatory (E) GCs, and they form the E-I loop. Winner-take-all competition, leading to sparse activation of the GCs, occurs in each GC cluster. Such sparsity has been thought to enhance pattern separation performed in the DG. During the winner-take-all competition, SSRs are found to appear in each population of the GCs and the BCs through interaction of excitation of the GCs with inhibition of the BCs. Sparsely synchronized spiking stripes appear successively with the population frequency f p ( = 13.1 Hz) in the raster plots of spikes. We also note that excitatory hilar mossy cells (MCs) control the firing activity of the GC-BC loop by providing excitation to both the GCs and the BCs. SSR also appears in the population of MCs via interaction with the GCs (i.e., GC-MC loop). Population behaviors in the SSRs are quantitatively characterized in terms of the synchronization measures. In addition, we investigate individual firing activity of GCs, BCs, and MCs in the SSRs. Individual GCs exhibit random spike skipping, leading to a multi-peaked inter-spike-interval histogram, which is well characterized in terms of the random phase-locking degree. In this case, population-averaged mean-firing-rate (MFR) < f i ( GC ) > is less than the population frequency f p . On the other hand, both BCs and MCs show "intrastripe" burstings within stripes, together with random spike skipping. Thus, the population-averaged MFR ⟨ f i ( X ) ⟩ ( X = MC and BC) is larger than f p , in contrast to the case of the GCs. MC loss may occur during epileptogenesis. With decreasing the fraction of the MCs, changes in the population and individual firings in the SSRs are also studied. Finally, quantitative association between the population/individual firing behaviors in the SSRs and the winner-take-all competition is discussed.

Effect of resolvin D1 on experimental bacterial keratitis to prevent corneal scar.

PURPOSE: The study aims to investigate the role of the lipid mediator resolvin D1 (RvD1) in bacterial keratitis in a murine model. METHODS: The effect of RvD1 on Pseudomonas aeruginosa-stimulated human corneal epithelial cells (HCECs) and mouse macrophages and dendritic cells (DCs) was assessed. C57BL/6 mouse corneas were abraded and treated with RvD1 after stimulation with P. aeruginosa, following which cytokine production level in the cornea and drainage lymph nodes was compared with that in controls. Corneal opacity and thickness were assessed using anterior segment photographs, and optical coherence tomography and corneal infiltrates were analyzed using immunohistochemistry for neutrophils. RESULTS: RvD1 significantly inhibited pro-inflammatory cytokine production in HCECs, mouse macrophages, and DCs. Corneal opacity and corneal thickness were reduced, and the development of corneal infiltrates, specifically neutrophils, was also significantly inhibited by RvD1 in response to stimulation with P. aeruginosa. CONCLUSIONS: RvD1 inhibits P. aeruginosa-induced corneal inflammation. This finding supports a potential therapeutic approach for patients with bacterial keratitis.

N-Terminal Modifications of Ubiquitin via Methionine Excision, Deamination, and Arginylation Expand the Ubiquitin Code.

Ubiquitin (Ub) is post-translationally modified by Ub itself or Ub-like proteins, phosphorylation, and acetylation, among others, which elicits a variety of Ub topologies and cellular functions. However, N-terminal (Nt) modifications of Ub remain unknown, except the linear head-to-tail ubiquitylation via Nt-Met. Here, using the yeast Saccharomyces cerevisiae and an Nt-arginylated Ub-specific antibody, we found that the detectable level of Ub undergoes Nt-Met excision, Nt-deamination, and Nt-arginylation. The resulting Nt-arginylated Ub and its conjugated proteins are upregulated in the stationary-growth phase or by oxidative stress. We further proved the existence of Nt-arginylated Ub in vivo and identified Nt-arginylated Ub-protein conjugates using stable isotope labeling by amino acids in cell culture (SILAC)-based tandem mass spectrometry. In silico structural modeling of Nt-arginylated Ub predicted that Nt-Arg flexibly protrudes from the surface of the Ub, thereby most likely providing a docking site for the factors that recognize it. Collectively, these results reveal unprecedented Nt-arginylated Ub and the pathway by which it is produced, which greatly expands the known complexity of the Ub code.

Dynamical origin for winner-take-all competition in a biological network of the hippocampal dentate gyrus.

We consider a biological network of the hippocampal dentate gyrus (DG). Computational models suggest that the DG would be a preprocessor for pattern separation (i.e., a process transforming a set of similar input patterns into distinct nonoverlapping output patterns) which could facilitate pattern storage and retrieval in the CA3 area of the hippocampus. The main encoding cells in the DG are the granule cells (GCs) which receive the input from the entorhinal cortex (EC) and send their output to the CA3. We note that the activation degree of GCs is very low (∼5%). This sparsity has been thought to enhance the pattern separation. We investigate the dynamical origin for winner-take-all (WTA) competition which leads to sparse activation of the GCs. The whole GCs are grouped into lamellar clusters. In each cluster, there is one inhibitory (I) basket cell (BC) along with excitatory (E) GCs. There are three kinds of external inputs into the GCs: the direct excitatory EC input; the indirect feedforward inhibitory EC input, mediated by the HIPP (hilar perforant path-associated) cells; and the excitatory input from the hilar mossy cells (MCs). The firing activities of the GCs are determined via competition between the external E and I inputs. The E-I conductance ratio R_{E-I}^{(con)}^{*} (given by the time average of the ratio of the external E to I conductances) may represent well the degree of such external E-I input competition. It is thus found that GCs become active when their R_{E-I}^{(con)}^{*} is larger than a threshold R_{th}^{*}, and then the mean firing rates of the active GCs are strongly correlated with R_{E-I}^{(con)}^{*}. In each cluster, the feedback inhibition from the BC may select the winner GCs. GCs with larger R_{E-I}^{(con)}^{*} than the threshold R_{th}^{*} survive, and they become winners; all the other GCs with smaller R_{E-I}^{(con)}^{*} become silent. In this way, WTA competition occurs via competition between the firing activity of the GCs and the feedback inhibition from the BC in each cluster. Finally, we also study the effects of MC death and adult-born immature GCs on the WTA competition.