Models of autoimmune demyelination in the central nervous system: on the way to translational medicine

Multiple sclerosis (MS) is the most common neurologic disease of young adults. In the recent years, our understanding on disease pathomechanisms has considerably improved and new therapies have emerged. Yet a cure for this devastating disorder is still a far cry away and human resources on ex vivo specimens are limited. More than 70 years after its first description, experimental autoimmune encephalomyelitis (EAE) remains an important tool to understand concepts of T cell mediated autoimmunity as well as the roles of the innate and the humoral immune systems. Some EAE models also well reflect mechanisms of tissue damage including demyelination, axonal injury and also cortical changes. A limitation of the classical EAE model is a neglect of CD8 T cell mediated immune mechanisms. Moreover, well characterized models for primary progressive MS or demyelination patterns involving primary oligodendrocyte dystrophy are still not available. Yet many current therapeutic concepts including glatiramer acetate or natalizumab stem from their successful first application in EAE models. New strategies include the widespread use of conditional knockout mice to understand the cell-type specific function of single genes, innovative approaches to establish models on the roles of B cells and CD8 T cells as well as on the relation of inflammation to primary degeneration. In summary, EAE models continue to play an important role in neuroimmunology thereby also stimulating research in other fields of the neurosciences and immunobiology

Euro-Korean Perspectives on the Use of Arbitration and ADR Mechanisms for Solving Intellectual Property Disputes

The complexities of international intellectual property litigation (including jurisdictional issues, choice of law, lis pendens, and the recognition and enforcement of foreign judgments) contribute to explain why arbitration and alternative dispute resolution systems constitute an attractive method for solving intellectual property disputes. At a time when the European Union has created a new patent court system (as a result of the recent adoption of the European Patent with Unitary Effect and of the Agreement on a Unified Patent Court signed in February 2013) which will include the setting up of a new patent arbitration and mediation center, it is critical that this new institution shall take into account the best practices and the experience developed in these fields in other parts of the world, particularly in Korea which has gained considerable experience on these issues. On this basis, the goal of this article is to present the recent developments relating to the use of arbitration and alternative dispute resolution mechanisms for solving intellectual property disputes in Korea and in Europe from a comparative perspectiv

Cognitive functions over the course of 1 year in multiple sclerosis patients treated with disease modifying therapies

Objectives: Disease-modifying therapies (DMTs) are applied to delay or prevent disease progression in multiple sclerosis (MS). While this has mostly been proven for physical symptoms, available studies regarding long-term effects of DMTs on cognitive functions are rare and sometimes inconsistent due to methodological shortcomings. Particularly in the case of fingolimod, comprehensive data on cognitive functions are not yet available. Therefore, we set out to reliably assess cognitive functions in patients with relapsing-remitting MS (RRMS) treated with DMTs over 1 year. Methods: Cognitive functions were assessed with eight tests at three timepoints: baseline, 6-month follow up and 12-month follow up. First, we investigated whether the stability of cognitive functions (i.e. not falling below the 5% cut-off in more than one test) over 1 year in RRMS patients (n = 41) corresponds to the stability in healthy individuals (n = 40) of a previous study. Second, we compared the percentage of declined and improved patients in the different tests. Third, we compared patients treated with fingolimod (n = 22) with patients treated with natalizumab (n = 11) with regard to cognitive stability. Fourth, based on the patient data, the Reliable Change Index was applied to compute cut-offs for reliable cognitive change. Results: Approximately 75% of RRMS patients treated with DMTs remained stable over the course of 1 year. The Paced Auditory Serial Addition Test (PASAT) and the Spatial Recall Test (SPART), produced improvements in 12.5% and 30.6%, respectively, probably due to practice effects. Patients treated with fingolimod did not differ from patients treated with natalizumab with regard to cognitive stability. Conclusions: Cognitive functions remain relatively stable under DMT treatment over 1 year, irrespective of the type of medication. Furthermore, the tests PASAT and SPART should be interpreted cautiously in studies examining performance changes over time. The provided RCI norms may help clinicians to determine whether a difference in two measurements observed in a RRMS patient is reliable

Equilibrium and Dynamical Evolution of Self-Gravitating System Embedded in a Potential Well

Isothermal and self-gravitating systems bound by non-conducting and conducting walls are known to be unstable if the density contrast between the center and the boundary exceeds critical values. We investigate the equilibrium and dynamical evolution of isothermal and self-gravitating system embedded in potential well, which can be the situation of many astrophysical objects such as the central parts of the galaxies, or clusters of galaxies with potential dominated by dark matter, but is still limited to the case where the potential well is fixed during the evolution. As the ratio between the depth of surrounding potential well and potential of embedded system becomes large, the potential well becomes effectively the same boundary condition as conducting wall, which behaves like a thermal heat bath. We also use the direct N-body simulation code, NBODY6 to simulate the dynamical evolution of stellar system embedded in potential wells and propose the equilibrium models for this system. In deep potential well, which is analogous to the heat bath with high temperature, the embedded self-gravitating system is dynamically hot, and loosely bound or can be unbound since the kinetic energy increases due to the heating by the potential well. On the other hand, the system undergoes core collapse by self-gravity when potential well is shallow. Binary heating can stop the collapse and leads to the expansion, but the evolution is very slow because the potential as a heat bath can absorb the energy generated by the binaries. The system can be regarded as quasi-static. Density and velocity dispersion profiles from the N-body simulations in the final quasi-equilibrium state are similar to our equilibrium models assumed to be in thermal equilibrium with the potential well.Comment: 12 pages, 12 figures, Submitted to MNRA

Developmental programming of thermonastic leaf movement

Plants exhibit diverse polar behaviors in response to directional and non-directional environmental signals, termed tropic and nastic movements, respectively. The ways in which plants incorporate directional information into tropic behaviors is well understood, but it is less well understood how non-directional stimuli, such as ambient temperatures, specify the polarity of nastic behaviors. Here, we demonstrate that a developmentally programmed polarity of auxin flow underlies thermo-induced leaf hyponasty in Arabidopsis (Arabidopsis thaliana). In warm environments, PHYTOCHROME-INTERACTING FACTOR 4 (PIF4) stimulates auxin production in the leaf. This results in the accumulation of auxin in leaf petioles, where PIF4 directly activates a gene encoding the PINOID (PID) protein kinase. PID is involved in polarization of the auxin transporter PIN-FORMED 3 to the outer membranes of petiole cells. Notably, the leaf polarity-determining ASYMMETRIC LEAVES 1 (AS1) directs the induction of PID to occur predominantly in the abaxial petiole region. These observations indicate that the integration of PIF4-mediated auxin biosynthesis and polar transport, and the AS1-mediated developmental shaping of polar auxin flow, coordinate leaf thermonasty, which facilitates leaf cooling in warm environments. We believe that leaf thermonasty is a suitable model system for studying the developmental programming of environmental adaptation in plants

Clinical features of Epstein-Barr virus-associated infectious mononucleosis in hospitalized Korean children

PurposeFew studies have been conducted on the recent status of infectious mononucleosis (IM) in Korean children. The aim of this study was to evaluate the recent trend in the clinical manifestations of Epstein-Barr virus (EBV)-associated IM as well as the clinical differences according to age.MethodsA retrospective study was performed on 81 children hospitalized with EBV-associated IM who fulfilled the serological criteria for the diagnosis of EBV infection (viral capsid antigen immunoglobulin M positive). The patients were divided into 3 age groups: <5 years, 5 to 9 years, and ≥10 years. We evaluated the recent trend in clinical manifestations and the differences in clinical and laboratory findings among the 3 age groups.ResultsThirty (37%) children were under 5 years of age, 38 (46.9%) were 5 to 9 years of age, and 13 (16%) were 10 years of age or older. The differences in the symptoms and signs among the 3 age groups were not statistically significant, except for headache. The mean duration of fever was 7.7 days (range, 0 to 18 days). A comparison of liver enzyme elevation among the age groups showed an association with advancing age (26.6%, 63.1%, and 76.9%, respectively, P=0.04)ConclusionThis study showed that EBV-associated IM in Korean children continues to occur mostly in children under 10 years of age. In children with EBV-associated IM, the incidence of headache and liver enzyme elevation, the duration of fever, and the proportion of females to males were all positively associated with advancing age

Pengaruh Facilitated Tucking Dan Musik Terhadap Respon Nyeri Bayi Prematur Ketika Pengambilan Darah

Manajemen nyeri yang tidak terkontrol pada bayi akan mempengaruhi pertumbuhan dan perkembangan selanjutnya. Salah satu tindakan manajemen nyeri non-farmakologi yang aman bagi bayi prematur adalah facilitated tucking dan pemberian musik. Penelitian ini untuk mengidentifikasi pengaruh kombinasi fasilitated tucking dan musik dalam mengurangi respon nyeri dan durasi menangis bayi prematur saat pengambilan darah. Rancangan kuasi eksperimen dengan pos-ttest control group design dipilih. Sampel penelitian ini adalah 60 bayi prematur yang dirawat di rumah sakit dan dilakukan pengambilan darah. Uji hipotesis menggunakan independent t-test. Kelompok intervensi diberikan facilitated tucking dan musik ketika pengambilan darah. Pengukuran nyeri menggunakan Premature Infant Pain Profile (PIPP) dan durasi menangis diukur dalam detik. Hasil penelitian menunjukkan bahwa rata-rata skor nyeri bayi adalah 7,03 pada kelompok intervensi dan 12,4 pada kelompok kontrol. Rata-rata durasi menangis bayi pada kelompok intervensi adalah 68,5 detik dan kelompok kontrol adalah 105 detik. Uji t menunjukkan perbedaan yang bermakna skor nyeri p 0,000 (α=0,05) dan durasi menangis 0,009 (α=0,05) bayi premature antara kelompok intervensi dan kelompok kontrol. DIsimpulkan bahwa facilitated tucking dan musik telah mengurangi respon nyeri dan durasi tangisan bayi prematur ketika pengambilan darah

A Case of Hypoglycemic Brain Injuries with Cortical Laminar Necrosis

We report a case of 68-yr-old male who died from brain injuries following an episode of prolonged hypoglycemia. While exploring controversies surrounding magnetic resonance imaging (MRI) findings indicating the bad prognosis in patients with hypoglycemia-induced brain injuries, we here discuss interesting diffusion-MRI of hypoglycemic brain injuries and their prognostic importance focusing on laminar necrosis of the cerebral cortex

Solitary Fibrous Tumor of the Trachea: CT Findings with a Pathological Correlation

We present the multidetector CT findings with a pathologic correlation for the case of a solitary fibrous tumor located in the trachea. The MDCT revealed a well-circumscribed intraluminal mass arising from the trachea, with strong nodular enhancement in the periphery of the mass. The enhancement pattern of the mass corresponded histopathologically to a focal hypocellular area in the center and prominent blood vessels along the periphery of the mass. We also present volume-rendered and virtual bronchoscopic images of this rare submucosal tracheal tumor