Treatment of Myasthenia Gravis Based on Its Immunopathogenesis

The prognosis of myasthenia gravis (MG) has improved dramatically due to advances in critical-care medicine and symptomatic treatments. Its immunopathogenesis is fundamentally a T-cell-dependent autoimmune process resulting from loss of tolerance toward self-antigens in the thymus. Thymectomy is based on this immunological background. For MG patients who are inadequately controlled with sufficient symptomatic treatment or fail to achieve remission after thymectomy, remission is usually achieved through the addition of other immunotherapies. These immunotherapies can be classified into two groups: rapid induction and long-term maintenance. Rapid induction therapy includes intravenous immunoglobulin (IVIg) and plasma exchange (PE). These produce improvement within a few days after initiation, and so are useful for acute exacerbation including myasthenic crisis or in the perioperative period. High-dose prednisone has been more universally preferred for remission induction, but it acts more slowly than IVIg and PE, commonly only after a delay of several weeks. Slow tapering of steroids after a high-dose pulse offers a method of maintaining the state of remission. However, because of significant side effects, other immunosuppressants (ISs) are frequently added as "steroid-sparing agents". The currently available ISs exert their immunosuppressive effects by three mechanisms: 1) blocking the synthesis of DNA and RNA, 2) inhibiting T-cell activation and 3) depleting the B-cell population. In addition, newer drugs including antisense molecule, tumor necrosis factor alpha receptor blocker and complement inhibitors are currently under investigation to confirm their effectiveness. Until now, the treatment of MG has been based primarily on experience rather than gold-standard evidence from randomized controlled trials. It is hoped that well-organized studies and newer experimental trials will lead to improved treatments

A Pilot Study on High Amplitude Low Frequency-music Impulse Stimulation as an Add-on Treatment for Depression

OBJECTIVE: High Amplitude Low Frequency-Music Impulse Stimulation (HALF-MIS) is a form of Vagus Nerve Stimulation (VNS). The aim of the study was to determine the feasibility, efficacy, and potential side effects of HALF-MIS, used as an add-on treatment for depression. METHODS: This is an open randomized controlled pilot study. Patients with depressive disorder were randomly allocated to either a HALF-MIS group with eight add-on HALF-MIS sessions (over a period of 3-4 weeks) or a control group which received treatment as usual. Seated in a specially designed chair() embedded with a transducer, their central nervous system was stimulated through the abdomen, () using music and vibration. Hamilton rating was performed. Side effects were registered. RESULTS: Eighteen patients were randomized to the add-on treatment and 20 patients to the control group. Both groups show in Hamilton Depression Rating Scale (HDRS)-17 and in HDRS-6, although the HALF-MIS group had a greater decline of symptoms. This was a significant difference in intergroup analysis (p = .011, CI 95% for the HALF-MIS group 3.0588-8.5327 and CI 95% for the control group 0.2384-3.0). The (HDRS)-6 difference was also significant (p = .020, CI 95% for the HALF-MIS group 1.5911-5.0487 and for the control group -0.297 to 1.7058). No side effects were observed. CONCLUSIONS: High Amplitude Low Frequency-Music Impulse Stimulation treatment seems to give beneficial effect as an add-on treatment for depression. HALF-MIS appears to be a safe and effective add-on treatment for depression

New methods for sorghum transformation in temperate climates

Sorghum (Sorghum bicolor) is an emerging cereal crop in temperate climates due to its high drought tolerance and other valuable traits. Genetic transformation is an important tool for the improvement of cereals. However, sorghum is recalcitrant to genetic transformation which is almost only successful in warmer climates. Here, we test the application of two new techniques for sorghum transformation in temperate climates, namely transient transformation by Agrobacterium tumefaciens-mediated agroinfiltration and stable transformation using gold particle bombardment and leaf whorls as explants. We optimized the transient transformation method, including post-infiltration incubation of plants in the dark and using Agrobacterium grown on plates with a high cell density (OD600 = 2.0). Expression of the green fluorescence protein (GFP)-tagged endogenous sorghum gene SbDHR2 was achieved with low transformation efficiency, and our results point out a potential weakness in using this approach for localization studies. Furthermore, we succeeded in the production of callus and somatic embryos from leaf whorls, although no genetic transformation was accomplished with this method. Both methods show potential, even if they seem to be influenced by climatic conditions and therefore need further optimization to be applied routinely in temperate climates.The research was funded by VILLUM FONDEN, Denmark, grant no. 19151, awarded to N.B., and the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 801199, awarded to S.M.Peer reviewe