Intravenous immunoglobulin treatment for acute attacks in myelin oligodendrocyte glycoprotein antibody disease

BACKGROUND: The potential therapeutic benefit of intravenous immunoglobulins (IVIGs) for acute attacks of myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is unknown. OBJECTIVE: The objective was to describe the outcomes of IVIG treatment for acute MOGAD attacks. METHODS: A retrospective observational study involving seven tertiary neuroimmunology centers. Data collection included patients' demographics, Expanded Disability Status Scale (EDSS), and visual acuity (VA) before the attack, at the nadir of the attack before IVIG treatment, and at follow-up visits ⩾3 months after treatment. RESULTS: Thirty-nine patients were included, of which 21 (53.8%) were female. The median age was 23 years (range 5-74 years), and the median disease duration was 4 months (range 0-93 months). The most common type of attack treated with IVIG was isolated optic neuritis (ON) (unilateral n = 14, bilateral n = 5, associated with transverse myelitis (TM), n = 1), followed by acute disseminated encephalomyelitis (ADEM) (n = 8), multifocal (n = 7), TM (n = 3), brainstem (n = 1), and other encephalitis (n = 1). A significant improvement in both the EDSS and VA measures was observed at follow-up compared to the time of IVIG treatment initiation (p < 0.0001 for both outcome measures). CONCLUSION: IVIG may be an effective treatment option for acute MOGAD attacks. Further prospective studies are warranted to validate our results

Algebraic Bethe ansatz method for the exact calculation of energy spectra and form factors: applications to models of Bose-Einstein condensates and metallic nanograins

In this review we demonstrate how the algebraic Bethe ansatz is used for the calculation of the energy spectra and form factors (operator matrix elements in the basis of Hamiltonian eigenstates) in exactly solvable quantum systems. As examples we apply the theory to several models of current interest in the study of Bose-Einstein condensates, which have been successfully created using ultracold dilute atomic gases. The first model we introduce describes Josephson tunneling between two coupled Bose-Einstein condensates. It can be used not only for the study of tunneling between condensates of atomic gases, but for solid state Josephson junctions and coupled Cooper pair boxes. The theory is also applicable to models of atomic-molecular Bose-Einstein condensates, with two examples given and analysed. Additionally, these same two models are relevant to studies in quantum optics. Finally, we discuss the model of Bardeen, Cooper and Schrieffer in this framework, which is appropriate for systems of ultracold fermionic atomic gases, as well as being applicable for the description of superconducting correlations in metallic grains with nanoscale dimensions. In applying all of the above models to physical situations, the need for an exact analysis of small scale systems is established due to large quantum fluctuations which render mean-field approaches inaccurate.Comment: 49 pages, 1 figure, invited review for J. Phys. A., published version available at http://stacks.iop.org/JPhysA/36/R6

1,8-Bis(silylamido)naphthalene complexes of magnesium and zinc synthesized through alkane elimination reactions

The reactions between magnesium or zinc alkyls and 1,8-bis(triorganosilyl)diaminonaphthalenes afford the 1,8-bis(triorganosilyl)diamidonaphthalene complexes with elimination of alkanes. The reaction between 1,8-C10H6(NSiMePh2H)2 and one or two equivalents of MgnBu2 affords two complexes with differing coordination environments for the magnesium; the reaction between 1,8-C10H6(NSiMePh2H)2 and MgnBu2 in a 1:1 ratio affords 1,8-C10H6(NSiMePh2)2{Mg(THF)2} (1), which features a single magnesium centre bridging both ligand nitrogen donors, whilst treatment of 1,8-C10H6(NSiR3H)2 (R3 = MePh2, iPr3) with two equivalents of MgnBu2 affords the bimetallic complexes 1,8-C10H6(NSiR3)2{nBuMg(THF)}2 (R3 = MePh2 2, R3 = iPr3 3), which feature four-membered Mg2N2 rings. Similarly, 1,8-C10H6(NSiiPr3)2{MeMg(THF)}2 (4) and 1,8-C10H6(NSiMePh2)2{ZnMe}2 (5) are formed through reactions with the proligands and two equivalents of MMe2 (M = Mg, Zn). The reaction between 1,8-C10H6(NSiMePh2H)2 and two equivalents of MeMgX affords the bimetallic complexes 1,8-C10H6(NSiMePh2)2(XMgOEt2)2 (X = Br 6; X = I 7). Very small amounts of [1,8-C10H6(NSiMePh2)2{IMg(OEt2)}]2 (8), formed through the coupling of two diamidonaphthalene ligands at the 4-position with concomitant dearomatisation of one of the naphthyl arene rings, were also isolated from a solution of 7

Side Chain Hydrophobicity Modulates Therapeutic Activity and Membrane Selectivity of Antimicrobial Peptide Mastoparan-X

The discovery of new anti-infective compounds is stagnating and multi-resistant bacteria continue to emerge, threatening to end the "antibiotic era". Antimicrobial peptides (AMPs) and lipo-peptides such as daptomycin offer themselves as a new potential class of antibiotics; however, further optimization is needed if AMPs are to find broad use as antibiotics. In the present work, eight analogues of mastoparan-X (MPX) were investigated, having side chain modifications in position 1, 8 and 14 to modulate peptide hydrophobicity. The self-association properties of the peptides were characterized, and the peptide-membrane interactions in model membranes were compared with the bactericidal and haemolytic properties. Alanine substitution at position 1 and 14 resulted in higher target selectivity (red blood cells versus bacteria), but also decreased bactericidal potency. For these analogues, the gain in target selectivity correlated to biophysical parameters showing an increased effective charge and reduction in the partitioning coefficient for membrane insertion. Introduction of an unnatural amino acid, with an octyl side chain by amino acid substitution, at positions 1, 8 and 14 resulted in increased bactericidal potency at the expense of radically reduced membrane target selectivity. Overall, optimized membrane selectivity or bactericidal potency was achieved by changes in side chain hydrophobicity of MPX. However, enhanced potency was achieved at the expense of selectivity and vice versa in all cases

Phase II study of helical tomotherapy in the multidisciplinary treatment of oligometastatic colorectal cancer

<p>Abstract</p> <p>Background</p> <p>Complete metastasectomy provides a real chance for long-term survival in patients with oligometastatic colorectal cancer (CRC). For inoperable patients, we evaluated in this study intensity-modulated and image-guided radiotherapy (IMRT-IGRT) by helical tomotherapy.</p> <p>Methods</p> <p>Twenty-four CRC patients with ≤ 5 metastases were enrolled, receiving a dose of 50 Gy in fractions of 5 Gy. No limitations concerning dimension or localization of the metastases were imposed. Whole body PET-CT was performed at baseline and 3 months after the initiation of RT to evaluate the metabolic response rate according to PET Response Criteria in Solid Tumors (PERCIST) version 1.0.</p> <p>Results</p> <p>A total of 53 metastases were treated. Seventeen patients (71%) received previously ≥ 1 line of chemotherapy for metastatic disease, displaying residual (n = 7) or progressive (n = 10) metabolic active oligometastatic disease at time of inclusion. Most common sites were the lung, liver and lymphnodes. One patient (4%) experienced grade 3 dysphagia. Twenty-two patients were evaluated by post-treatment PET-CT. Twelve patients achieved a complete (n = 6) or partial (n = 6) metabolic response, resulting in an overall metabolic response rate of 55%. At a median follow-up of 10 months, 7 patients (29%) are in remission, of which 5 received previous chemotherapy with residual oligometastatic disease at time of inclusion. The actuarial 1-year local control, progression-free survival, and overall survival were 54%, 14% and 78%.</p> <p>Conclusions</p> <p>Helical tomotherapy delivering 10 fractions of 5 Gy resulted in a metabolic response rate of 55%, and appeared to be attractive as consolidation of inoperable oligometastatic disease after effective chemotherapy.</p> <p>Trial registration</p> <p>Eudract 2008-008300-40; <a href="http://www.clinicaltrials.gov/ct2/show/NCT00807313">NCT00807313</a></p

Protein-altering germline mutations implicate novel genes related to lung cancer development

Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio = 8.82, P = 1.18 × 10−15) and replication (adjusted OR = 2.93, P = 2.22 × 10−3) that is more pronounced in females (adjusted OR = 6.81 and 3.19 and for discovery and replication). We observe an excess loss of heterozygosity in lung tumors among ATM L2307F allele carriers. L2307F is more frequent (4%) among Ashkenazi Jewish populations. We also observe an association in discovery (adjusted OR = 2.61, P = 7.98 × 10−22) and replication datasets (adjusted OR = 1.55, P = 0.06) with a loss-of-function mutation, Q4X (rs150665432) of an uncharacterized gene, KIAA0930. Our findings implicate germline genetic variants in ATM with lung cancer susceptibility and suggest KIAA0930 as a novel candidate gene for lung cancer risk