External Validation of the ELAPSS Score for Prediction of Unruptured Intracranial Aneurysm Growth Risk

Mayte Sánchez van Kammen,Jacoba P. Greving,Satoshi Kuroda,Daina Kashiwazaki,Akio Morita,Yoshiaki Shiokawa,Toshikazu Kimura,Christophe Cognard,Anne C. Januel,Antti Lindgren,Timo Koivisto,Juha E. Jääske 대한뇌졸중학회 2019 Journal of stroke Vol.21 No.3

Background and purpose Prediction of intracranial aneurysm growth risk can assist physicians in planning of follow-up imaging of conservatively managed unruptured intracranial aneurysms. We therefore aimed to externally validate the ELAPSS (Earlier subarachnoid hemorrhage, aneurysm Location, Age, Population, aneurysm Size and Shape) score for prediction of the risk of unruptured intracranial aneurysm growth. Methods From 11 international cohorts of patients ≥18 years with ≥1 unruptured intracranial aneurysm and ≥6 months of radiological follow-up, we collected data on the predictors of the ELAPSS score, and calculated 3- and 5-year absolute growth risks according to the score. Model performance was assessed in terms of calibration (predicted versus observed risk) and discrimination (c-statistic). Results We included 1,072 patients with a total of 1,452 aneurysms. During 4,268 aneurysm-years of follow-up, 199 (14%) aneurysms enlarged. Calibration was comparable to that of the followdevelopment cohort with the overall observed risks within the range of the expected risks. The c-statistic was 0.69 (95% confidence interval [CI], 0.64 to 0.73) at 3 years, compared to 0.72 (95% CI, 0.68 to 0.76) in the development cohort. At 5 years, the c-statistic was 0.68 (95% CI, 0.64 to 0.72), compared to 0.72 (95% CI, 0.68 to 0.75) in the development cohort. Conclusions The ELAPSS score showed accurate calibration for 3- and 5-year risks of aneurysm growth and modest discrimination in our external validation cohort. This indicates that the score is externally valid and could assist patients and physicians in predicting growth of unruptured intracranial aneurysms and plan follow-up imaging accordingly.

Susceptibility of Ceftolozane-Tazobactam and Ceftazidime-Avibactam Against a Collection of β-Lactam-Resistant Gram-Negative Bacteria

Mark D. Gonzalez,Allison R. McMullen,Meghan A. Wallace,Matthew P. Crotty,David J. Ritchie,Carey-Ann D. Burnham 대한진단검사의학회 2017 Annals of Laboratory Medicine Vol.37 No.2

Dear Editor, Ceftolozane-tazobactam (C/T) and ceftazidime-avibactam (CZA) were recently approved for the treatment of complicated intra-abdominal infections and complicated urinary tract infections (http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm427534.htm, http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm435629.htm, both accessed February 24, 2016). To date, only one study has simultaneously evaluated the activities of C/T and CZA in vitro against Pseudomonas aeruginosa, and few studies have evaluated the effects of these antibiotics on multi-drug resistant (MDR) gram-negative bacteria [1-3]. This study aimed to examine the activities of C/T and CZA against β-lactam-resistant Enterobacteriaceae and P. aeruginosa clinical isolates.

Indoleamine 2,3-Dioxygenase-Expressing Aortic Plasmacytoid Dendritic Cells Protect against Atherosclerosis by Induction of Regulatory T Cells

Yun, T.,Lee, J.,Machmach, K.,Shim, D.,Choi, J.,Wi, Y.,Jang, H.,Jung, I.H.,Kim, K.,Yoon, W.,Miah, M.,Li, B.,Chang, J.,Bego, Mariana G.,Pham, Tram N.Q.,Loschko, J.,Fritz, J.,Krug, Anne B.,Lee, S.P.,Kele Cell Press 2016 Cell metabolism Vol.23 No.5

<P>Plasmacytoid dendritic cells (pDCs) are unique bone-marrow-derived cells that produce large amounts of type I interferon in response to microbial stimulation. Furthermore, pDCs also promote T cell tolerance in sterile-inflammation conditions. However, the immunomodulatory role of aortic pDCs in atherosclerosis has been poorly understood. Here, we identified functional mouse and human pDCs in the aortic intima and showed that selective, inducible pDC depletion in mice exacerbates atherosclerosis. Aortic pDCs expressed CCR9 and indoleamine 2,3-dioxygenase 1 (IDO-1), an enzyme involved in driving the generation of regulatory T cells (Tregs). As a consequence, loss of pDCs resulted in decreased numbers of Tregs and reduced IL-10 levels in the aorta. Moreover, antigen presentation by pDCs expanded antigen-specific Tregs in the atherosclerotic aorta. Notably, Tregs ablation affected pDC homeostasis in diseased aorta. Accordingly, pDCs in human atherosclerotic aortas colocalized with Tregs. Collectively, we identified a mechanism of atheroprotection mediated by tolerogenic aortic pDCs.</P>

The Wnt Receptor Ryk Reduces Neuronal and Cell Survival Capacity by Repressing FOXO Activity During the Early Phases of Mutant Huntingtin Pathogenicity

Tourette, Cendrine,Farina, Francesca,Vazquez-Manrique, Rafael P.,Orfila, Anne-Marie,Voisin, Jessica,Hernandez, Sonia,Offner, Nicolas,Parker, J. Alex,Menet, Sophie,Kim, Jinho,Lyu, Jungmok,Choi, Si Ho,C Public Library of Science 2014 PLoS biology Vol.12 No.6

<▼1><P>A study of Huntington's disease reveals that neurons might fail to cope with maintaining their function during the pre-symptomatic, pathogenic phases of HD, possibly due to the early repression of key longevity-promoting transcription factors by abnormal developmental signaling.</P></▼1><▼2><P>The Wnt receptor Ryk is an evolutionary-conserved protein important during neuronal differentiation through several mechanisms, including γ-secretase cleavage and nuclear translocation of its intracellular domain (Ryk-ICD). Although the Wnt pathway may be neuroprotective, the role of Ryk in neurodegenerative disease remains unknown. We found that Ryk is up-regulated in neurons expressing mutant huntingtin (HTT) in several models of Huntington's disease (HD). Further investigation in <I>Caenorhabditis elegans</I> and mouse striatal cell models of HD provided a model in which the early-stage increase of Ryk promotes neuronal dysfunction by repressing the neuroprotective activity of the longevity-promoting factor FOXO through a noncanonical mechanism that implicates the Ryk-ICD fragment and its binding to the FOXO co-factor β-catenin. The Ryk-ICD fragment suppressed neuroprotection by <I>lin-18</I>/Ryk loss-of-function in expanded-polyQ nematodes, repressed FOXO transcriptional activity, and abolished β-catenin protection of mutant htt striatal cells against cell death vulnerability. Additionally, Ryk-ICD was increased in the nucleus of mutant htt cells, and reducing γ-secretase PS1 levels compensated for the cytotoxicity of full-length Ryk in these cells. These findings reveal that the Ryk-ICD pathway may impair FOXO protective activity in mutant polyglutamine neurons, suggesting that neurons are unable to efficiently maintain function and resist disease from the earliest phases of the pathogenic process in HD.</P></▼2><▼3><P><B>Author Summary</B></P><P>Neuronal cell decline in neurodegenerative disease can be caused by inherited mutations and involves neuronal dysfunction followed by neuronal death. The ability of neurons to cope with the chronic stress induced by mutant protein expression may determine the course of their decline and eventual demise. Although the pathophysiological importance of these stress responses has been previously shown, very little is known about the signaling networks that regulate neuronal homeostasis during the early presymptomatic—but pathogenic—phases of a neurodegenerative disorder such as Huntington's disease (HD). In particular, it remains unclear whether neuronal differentiation factors regulate stress response pathways during neurodegenerative disease and how this might impact the overall capacity of neurons to cope with stress and maintain their function. Here, we show that the Wnt receptor Ryk, a protein known to be important for neurogenesis, is increased in different animal models of HD, before or during the early phases of the disease process. Interestingly, increased levels of Ryk repress activity of the FOXO proteins—a family of transcription factors that play a role in cell survival/longevity and in neuronal homeostasis and protection. Ryk represses FOXO protective activity, possibly directly, through its intracellular domain, a product of γ-secretase–mediated cleavage previously implicated in the birth of new cortical neurons. This highlights the regulation of HD neuron survival by a Ryk-dependent pathway that is distinct from canonical Wnt/Ryk signaling. From our findings, we postulate that neurons are unable to develop an efficient FOXO-mediated survival response during the very early, pathogenic phases of HD.</P></▼3>

CAUGHT IN THE ACT: STRONG, ACTIVE RAM PRESSURE STRIPPING IN VIRGO CLUSTER SPIRAL NGC 4330

Abramson, Anne,Kenney, Jeffrey D. P.,Crowl, Hugh H.,Chung, Aeree,van Gorkom, J. H.,Vollmer, Bernd,Schiminovich, David American Institute of Physics 2011 The Astronomical journal Vol.141 No.5

<P>We present a multi-wavelength study of NGC 4330, a highly inclined spiral galaxy in the Virgo Cluster which is a clear example of strong, ongoing intracluster medium-interstellar medium (ICM-ISM) ram pressure stripping. The H <SPAN CLASS='sml'>I</SPAN> has been removed from well within the undisturbed old stellar disk, to 50%-65% of R<SUB>25</SUB>. Multi-wavelength data (WIYN BVR-Hα, Very Large Array 21 cm H <SPAN CLASS='sml'>I</SPAN> and radio continuum, and Galaxy Evolution Explorer NUV and FUV) reveal several one-sided extraplanar features likely caused by ram pressure at an intermediate disk-wind angle. At the leading edge of the interaction, the Hα and dust extinction curve sharply out of the disk in a remarkable and distinctive 'upturn' feature that may be generally useful as a diagnostic indicator of active ram pressure. On the trailing side, the ISM is stretched out in a long tail which contains 10% of the galaxy's total H <SPAN CLASS='sml'>I</SPAN> emission, 6%-9% of its NUV-FUV emission, but only 2% of the Hα. The centroid of the H <SPAN CLASS='sml'>I</SPAN> tail is downwind of the UV/Hα tail, suggesting that the ICM wind has shifted most of the ISM downwind over the course of the past 10-300 Myr. Along the major axis, the disk is highly asymmetric in the UV, but more symmetric in Hα and H <SPAN CLASS='sml'>I</SPAN>, also implying recent changes in the distributions of gas and star formation. The UV-optical colors indicate very different star formation histories for the leading and trailing sides of the galaxy. On the leading side, a strong gradient in the UV-optical colors of the gas-stripped disk suggests that it has taken 200-400 Myr to strip the gas from a radius of >8 to 5 kpc, but on the trailing side there is no age gradient. All our data suggest a scenario in which NGC 4330 is falling into the cluster center for the first time and has experienced a significant increase in ram pressure over the last 200-400 Myr. Many of the UV-bright stars that form outside the thin disk due to ram pressure will ultimately produce stellar thick disk and halo components with characteristic morphologies and age distributions distinct from those produced by gravitational interactions.</P>

실험적 신장장해 가토에서 Furosemide 의 약물동태

이진환 ( J H Lee ),최준식 ( J S Choi ),범진필 ( J P Burm ),최토마 ( T M Choi ),안선엽 ( S Y Ann ) 한국약제학회 1989 Journal of Pharmaceutical Investigation Vol.19 No.4

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LRRK2 functions as a scaffolding kinase of ASK1-mediated neuronal cell death

Yoon, J.H.,Mo, J.S.,Kim, M.Y.,Ann, E.J.,Ahn, J.S.,Jo, E.H.,Lee, H.J.,Lee, Y.C.,Seol, W.,Yarmoluk, S.M.,Gasser, T.,Kahle, P.J.,Liu, G.H.,Belmonte, J.C.I.,Park, H.S. Elsevier Biomedical Press 2017 Biochimica et biophysica acta, Molecular cell rese Vol.1864 No.12

Leucine-rich repeat kinase 2 (LRRK2), a multi-domain protein, is a key causative factor in Parkinson's disease (PD). Identification of novel substrates and the molecular mechanisms underlying the effects of LRRK2 are essential for understanding the pathogenesis of PD. In this study, we showed that LRRK2 played an important role in neuronal cell death by directly phosphorylating and activating apoptosis signal-regulating kinase 1 (ASK1). LRRK2 phosphorylated ASK1 at Thr832 that is adjacent to Thr845, which serves as an autophosphorylation site. Moreover, results of binding and kinase assays showed that LRRK2 acted as a scaffolding protein by interacting with each components of the ASK1-MKK3/6-p38 MAPK pathway through its specific domains and increasing the proximity to downstream targets. Furthermore, LRRK2-induced apoptosis was suppressed by ASK1 inhibition in neuronal stem cells derived from patients with PD. These results clearly indicate that LRRK2 acts as an upstream kinase in the ASK1 pathway and plays an important role in the pathogenesis of PD.

200GHz DWDM 10km용 10Gbps Bi-Di SFP+ 광트랜시버 개발

노기평(G.P. Roh),문민중(M.J. Moon),한준모(J.M. Han),이병규(B.K. Lee),신종윤(J.Y. Shin),안세경(S.G. Ann),박경현(K.H. Park) 한국생산제조학회 2017 한국생산제조시스템학회 학술발표대회 논문집 Vol.2017 No.12

Stochastic dynamics of coupled active particles in an overdamped limit

Ann, M.,Lee, K.J.B.,Park, P.J. North-Holland Pub. Co 2015 PHYSICA A-STATISTICAL MECHANICS AND ITS APPLICATIO Vol.436 No.-

We introduce a model for Brownian dynamics of coupled active particles in an overdamped limit. Our system consists of several identical active particles and one passive particle. Each active particle is elastically coupled to the passive particle and there is no direct coupling among the active particles. We investigate the dynamics of the system with respect to the number of active particles, viscous friction, and coupling between the active and passive particles. For this purpose, we consider an intracellular transport process as an application of our model and perform a Brownian dynamics simulation using realistic parameters for processive molecular motors such as kinesin-1. We determine an adequate energy conversion function for molecular motors and study the dynamics of intracellular transport by multiple motors. The results show that the average velocity of the coupled system is not affected by the number of active motors and that the stall force increases linearly as the number of motors increases. Our results are consistent with well-known experimental observations. We also examine the effects of coupling between the motors and the cargo, as well as of the spatial distribution of the motors around the cargo. Our model might provide a physical explanation of the cooperation among active motors in the cellular transport processes.

The Incidence of Acute Traumatic Tendon Injuries in the Hand and Wrist: A 10-Year Population-based Study

Johanna P. de Jong,Jesse T. Nguyen,Anne J. M. Sonnema,Emily C. Nguyen,Peter C. Amadio,Steven L. Moran 대한정형외과학회 2014 Clinics in Orthopedic Surgery Vol.6 No.2

Background:Acute traumatic tendon injuries of the hand and wrist are commonly encountered in the emergency department. Despite the frequency, few studies have examined the true incidence of acute traumatic tendon injuries in the hand and wrist or compared the incidences of both extensor and flexor tendon injuries. Methods: We performed a retrospective population-based cohort study of all acute traumatic tendon injuries of the hand and wrist in a mixed urban and rural Midwest county in the United States between 2001–2010. A regional epidemiologic database and medical codes were used to identify index cases. Epidemiologic information including occupation, year of injury, mechanism of injury and the injured tendon and zone were recorded. Results: During the 10-year study period there was an incidence rate of 33.2 injuries per 100,000 person-years. There was a decreasing rate of injury during the study period. Highest incidence of injury occurred at 20–29 years of age. There was significant association between injury rate and age, and males had a higher incidence than females. The majority of cases involved a single tendon, with extensor tendon injuries occurring more frequently than flexor tendons. Typically, extensor tendon injuries involved zone three of the index finger, while flexor tendons involved zone two of the index finger. Work-related injuries accounted for 24.9% of acute traumatic tendon injuries. The occupations of work-related injuries were assigned to major groups defined by the 2010 Standard Occupational Classification structure. After assigning these patients' occupations to respective major groups, the most common groups work-related injuries occurred in construction and extraction occupations (44.2%), food preparation and serving related occupations (14.4%), and transportation and material moving occupations (12.5%). Conclusions: Epidemiology data enhances our knowledge of injury patterns and may play a role in the prevention and treatment of future injuries, with an end result of reducing lost work time and economic burden.