Induction of Paralysis and Visual System Injury in Mice by T Cells Specific for Neuromyelitis Optica Autoantigen Aquaporin-4.

While it is recognized that aquaporin-4 (AQP4)-specific T cells and antibodies participate in the pathogenesis of neuromyelitis optica (NMO), a human central nervous system (CNS) autoimmune demyelinating disease, creation of an AQP4-targeted model with both clinical and histologic manifestations of CNS autoimmunity has proven challenging. Immunization of wild-type (WT) mice with AQP4 peptides elicited T cell proliferation, although those T cells could not transfer disease to naïve recipient mice. Recently, two novel AQP4 T cell epitopes, peptide (p) 135-153 and p201-220, were identified when studying immune responses to AQP4 in AQP4-deficient (AQP4-/-) mice, suggesting T cell reactivity to these epitopes is normally controlled by thymic negative selection. AQP4-/- Th17 polarized T cells primed to either p135-153 or p201-220 induced paralysis in recipient WT mice, that was associated with predominantly leptomeningeal inflammation of the spinal cord and optic nerves. Inflammation surrounding optic nerves and involvement of the inner retinal layers (IRL) were manifested by changes in serial optical coherence tomography (OCT). Here, we illustrate the approaches used to create this new in vivo model of AQP4-targeted CNS autoimmunity (ATCA), which can now be employed to study mechanisms that permit development of pathogenic AQP4-specific T cells and how they may cooperate with B cells in NMO pathogenesis

Optical coherence tomography in multiple sclerosis: A 3-year prospective multicenter study

Prospective multicenter study; Multiple sclerosis; TomographyEstudi prospectiu multicèntric; Esclerosi múltiple; TomografiaEstudio multicéntrico prospectivo; Esclerosis múltiple; TomografíaObjective To evaluate changes over 3 years in the thickness of inner retinal layers including the peripapillary retinal nerve fiber layer (pRNFL), and combined macular ganglion cell and inner plexiform layers (mGCIPL), in individuals with relapsing-remitting multiple sclerosis (RRMS) versus healthy controls; to determine whether optical coherence tomography (OCT) is sufficiently sensitive and reproducible to detect small degrees of neuroaxonal loss over time that correlate with changes in brain volume and disability progression as measured by the Expanded Disability Status Scale (EDSS). Methods Individuals with RRMS from 28 centers (n = 333) were matched with 64 healthy participants. OCT scans were performed on Heidelberg Spectralis machines (at baseline; 1 month; 6 months; 6-monthly thereafter). Results OCT measurements were highly reproducible between baseline and 1 month (intraclass correlation coefficient >0.98). Significant inner retinal layer thinning was observed in individuals with multiple sclerosis (MS) compared with controls regardless of previous MS-associated optic neuritis––group differences (95% CI) over 3 years: pRNFL: −1.86 (−2.54, −1.17) µm; mGCIPL: −2.03 (−2.78, −1.28) µm (both p 5 years (pRNFL: p < 0.05; mGCIPL: p < 0.01). Brain volume decreased by 1.3% in individuals with MS over 3 years compared to 0.5% in control subjects (effect size 0.76). mGCIPL atrophy correlated with brain atrophy (p < 0.0001). There was no correlation of OCT data with disability progression. Interpretation OCT has potential to estimate rates of neurodegeneration in the retina and brain. The effect size for OCT, smaller than for magnetic resonance imaging based on Heidelberg Spectralis data acquired in this study, was increased in early disease.The authors wish to thank Carolyn M. Ervin for her substantial contribution in the data analyses, as well as Mark Kirby, Aisling Towell, and Marie-Catherine Mousseau (Novartis Ireland Ltd.) for their writing support, funded by Novartis Pharma AG, Basel, Switzerland. FB is supported by the NIHR biomedical research center at UCLH

On Dislocations in a Special Class of Generalized Elasticity

In this paper we consider and compare special classes of static theories of gradient elasticity, nonlocal elasticity, gradient micropolar elasticity and nonlocal micropolar elasticity with only one gradient coefficient. Equilibrium equations are discussed. The relationship between the gradient theory and the nonlocal theory is discussed for elasticity as well as for micropolar elasticity. Nonsingular solutions for the elastic fields of screw and edge dislocations are given. Both the elastic deformation (distortion, strain, bend-twist) and the force and couple stress tensors do not possess any singularity unlike `classical' theories.Comment: 28 pages, to appear in: physica status solid

The Ultraviolet Emission Properties of Five Low-Redshift Active Galactic Nuclei at High Signal to Noise and Spectral Resolution

We analyze the ultraviolet (UV) emission line and continuum properties of five low-redshift active galactic nuclei (four luminous quasars: PKS~0405$-$123, H1821+643, PG~0953+414, and 3C273, and one bright Seyfert 1 galaxy: Mrk~205). The HST spectra have higher signal-to-noise ratios (typically $\sim 60$ per resolution element) and spectral resolution ($R = 1300$) than all previously- published UV spectra used to study the emission characteristics of active galactic nuclei. We include in the analysis ground-based optical spectra covering \hb\ and the narrow [O III] $\lambda\lambda$4959,5007 doublet. The following new results are obtained: \lyb/\lya=0.03$-$0.12 for the four quasars, which is the first accurate measurement of the long-predicted \lyb\ intensity in QSOs. The cores of \lya\ and C~IV are symmetric to an accuracy of better than 2.5% within about 2000 km s$^{-1}$ of the line peak. This high degree of symmetry of \lya\ argues against models in which the broad line cloud velocity field has a significant radial component. The observed smoothness of the \lya\ and C~IV line profiles requires at least $\sim 10^4$ individual clouds if bulk velocity is the only line-broadening mechanism. The overall similarity of the \lya\ and C IV $\lambda$1549 profiles rules out models for the broad line region (BLR) with a radial distribution of virialized....Comment: 39 pages (+ 6 pages of tables + 16 of figures), AST 93/2

Motivational Interviewing Effect on Medication Adherence and Other Outcomes in People with Schizophrenia (PwS): A Review

Adherence will have an impact on therapy because schizophrenia is a chronic mental disorder that requires long-term treatment. One strategy to improve adherence to medications is motivational interviewing (MI), although more study is needed to see how well it works and whether it has any other effects on schizophrenia. The study aimed to assess the effectiveness of motivational interviews in improving adherence to medications and other positive impacts on PwS. A literature review using PubMed, Science Direct, Springerlink, and google scholar databases from 2010-2023 focused on keywords adherence, schizophrenia, and motivational interviewing. The results showed that MI has inconsistencies in their effect on improving medication adherence in PwS, but some studies found evidence of an association between MI and other outcomes, such as improvement in psychotic symptoms and decreased hospitalisation rates. Differences in patient characteristics and MI interventions in each study, the to perform MI techniques, and the trusting relationship built by the counsellor with the patient will affect the impact of MI on adherence. MI showed inconsistencies in improving medication adherence in people with schizophrenia. Several factors will affect the effectiveness of MI. However, MI also has the potential to improve psychosis symptoms and reduce hospitalisation rates, although more research is needed

Monitoring retinal changes with optical coherence tomography predicts neuronal loss in experimental autoimmune encephalomyelitis.

BACKGROUND:Retinal optical coherence tomography (OCT) is a clinical and research tool in multiple sclerosis, where it has shown significant retinal nerve fiber (RNFL) and ganglion cell (RGC) layer thinning, while postmortem studies have reported RGC loss. Although retinal pathology in experimental autoimmune encephalomyelitis (EAE) has been described, comparative OCT studies among EAE models are scarce. Furthermore, the best practices for the implementation of OCT in the EAE lab, especially with afoveate animals like rodents, remain undefined. We aimed to describe the dynamics of retinal injury in different mouse EAE models and outline the optimal experimental conditions, scan protocols, and analysis methods, comparing these to histology to confirm the pathological underpinnings. METHODS:Using spectral-domain OCT, we analyzed the test-retest and the inter-rater reliability of volume, peripapillary, and combined horizontal and vertical line scans. We then monitored the thickness of the retinal layers in different EAE models: in wild-type (WT) C57Bl/6J mice immunized with myelin oligodendrocyte glycoprotein peptide (MOG35-55) or with bovine myelin basic protein (MBP), in TCR2D2 mice immunized with MOG35-55, and in SJL/J mice immunized with myelin proteolipid lipoprotein (PLP139-151). Strain-matched control mice were sham-immunized. RGC density was counted on retinal flatmounts at the end of each experiment. RESULTS:Volume scans centered on the optic disc showed the best reliability. Retinal changes during EAE were localized in the inner retinal layers (IRLs, the combination of the RNFL and the ganglion cell plus the inner plexiform layers). In WT, MOG35-55 EAE, progressive thinning of IRL started rapidly after EAE onset, with 1/3 of total loss occurring during the initial 2 months. IRL thinning was associated with the degree of RGC loss and the severity of EAE. Sham-immunized SJL/J mice showed progressive IRL atrophy, which was accentuated in PLP-immunized mice. MOG35-55-immunized TCR2D2 mice showed severe EAE and retinal thinning. MBP immunization led to very mild disease without significant retinopathy. CONCLUSIONS:Retinal neuroaxonal damage develops quickly during EAE. Changes in retinal thickness mirror neuronal loss and clinical severity. Monitoring of the IRL thickness after immunization against MOG35-55 in C57Bl/6J mice seems the most convenient model to study retinal neurodegeneration in EAE

The UV Properties of the Narrow Line Quasar I Zwicky 1

I Zw 1 is the prototype narrow line quasar. We report here the results of our study of the UV emission of I Zw 1 using a high S/N (50-120) spectrum obtained with the HST FOS. The following main new results are obtained: 1. The Mg II and Al III doublets are partially/fully resolved. The measured doublet ratios verify theoretical predictions that the lines are thermalized in the BLR. 2. A weak associated UV absorption system is detected in N~V, and possibly also in C IV and Lya, suggesting an outflow with a velocity of 1870 km/s and velocity dispersion <300 km/s. 3. Lines from ions of increasing ionization level show increasing excess blue wing flux, and an increasing line peak velocity shift, reaching a maximum blueshift of about 2000 km/s for He II 1640. This may indicate an out-flowing component in the BLR, where the ionization level increases with velocity, and which is visible only in the approaching direction. The highest velocity part of this outflow may produce the associated UV absorption system. 4. The small C III] 1909 EW, and the small C III] 1909/Lya and C III] 1909/Si III] 1892 flux ratios indicate a typical BLR density of 10^11, i.e. about an order of magnitude larger than implied by C III] 1909 in most quasars. A BLR component of a higher density is implied by the EW and doublet ratio of the Al III 1857 doublet. 5. Prominent Fe II UV 191 emission is seen, together with weaker line emission at 1294 and 1871 A. These three features have been proposed as evidence for significant Lya pumping of the 8-10 eV levels of Fe II. 6. Significant Fe III emission is present. The Fe III UV 34 and UV 48 multiplets are clearly resolved, and Fe III UV 1, UV 47, UV 50, and UV 68 may also be present. (Shortened version)Comment: 28 pages, 1 table and 7 figures included. Uses aas2pp4.sty. Scheduled for the Astrophysical Journal November 10, 1997 issue, Vol. 48