John Caspar Wild: Painter and Printmaker of Nineteenth-Century Urban America

Review of: "John Caspar Wild: Painter and Printmaker of Nineteenth-Century Urban America," by John W. Reps

John Caspar Wild: Painter and Printmaker of Nineteenth-Century Urban America

Review of: "John Caspar Wild: Painter and Printmaker of Nineteenth-Century Urban America," by John W. Reps

Cerebrospinal fluid biomarkers as a measure of disease activity and treatment efficacy in relapsing-remitting multiple sclerosis

Cerebrospinal fluid (CSF) biomarkers can reflect different aspects of the pathophysiology of relapsing-remitting multiple sclerosis (RRMS). Understanding the impact of different disease modifying therapies on the CSF biomarker profile may increase their implementation in clinical practice and their appropriateness for monitoring treatment efficacy. This study investigated the influence of first-line (interferon beta) and second-line (natalizumab) therapies on seven CSF biomarkers in RRMS and their correlation with clinical and radiological outcomes. We included 59 RRMS patients and 39 healthy controls. The concentrations of C-X-C motif chemokine 13 (CXCL13), C-C motif chemokine ligand 2 (CCL2), chitinase-3-like protein 1 (CHI3L1), glial fibrillary acidic protein, neurofilament light protein (NFL), and neurogranin were determined by ELISA, and chitotriosidase (CHIT1) was analyzed by spectrofluorometry. RRMS patients had higher levels of NFL, CXCL13, CHI3L1, and CHIT1 than controls (p < 0.001). Subgroup analysis revealed higher NFL, CXCL13 and CHIT1 levels in patients treated with first-line therapy compared to second-line therapy (p = 0.008, p = 0.001 and p = 0.026, respectively). NFL and CHIT1 levels correlated with relapse status, and NFL and CXCL13 levels correlated with the formation of new magnetic resonance imaging lesions. Furthermore, we found an association between inflammatory and degenerative biomarkers. The results indicate that CSF levels of NFL, CXCL13, CHI3L1, and CHIT1 correlate with the clinical and/or radiological disease activity, providing additional dimensions in the assessment of treatment efficacy

From vocational training to education: the development of a no-frontiers education policy for Europe?

This article focuses on developments towards an EU educational policy. Education was not included as one of the Community competencies in the Treaty of Rome. The first half of the article analyses the way that the European Court of Justice and the Commission of the European Communities between them managed to develop a series of substantial Community programmes out of Article 128 on vocational training. The second half of the article discusses educational developments in the community following the Treaty on European Union and the Treaty of Amsterdam. Whilst the legal competence of the community now includes education, the author's argument is that the inclusion of an educational competence will not result in further developments to mirror those in the years before the Treaty on Europe</p

Dynamics of cerebrospinal fluid levels of matrix metalloproteinases in human traumatic brain injury

Matrix metalloproteinases (MMPs) are extracellular enzymes involved in the degradation of extracellular matrix (ECM) proteins. Increased expression of MMPs have been described in traumatic brain injury (TBI) and may contribute to additional tissue injury and blood–brain barrier damage. The objectives of this study were to determine longitudinal changes in cerebrospinal fluid (CSF) concentrations of MMPs after acute TBI and in relation to clinical outcomes, with patients with idiopathic normal pressure hydrocephalus (iNPH) serving as a contrast group. The study included 33 TBI patients with ventricular CSF serially sampled, and 38 iNPH patients in the contrast group. Magnetic bead-based immunoassays were utilized to measure the concentrations of eight MMPs in ventricular human CSF. CSF concentrations of MMP-1, MMP-3 and MMP-10 were increased in TBI patients (at baseline) compared with the iNPH group (p < 0.001), while MMP-2, MMP-9 and MMP-12 did not differ between the groups. MMP-1, MMP-3 and MMP-10 concentrations decreased with time after trauma (p = 0.001–0.04). Increased concentrations of MMP-2 and MMP-10 in CSF at baseline were associated with an unfavourable TBI outcome (p = 0.002–0.02). Observed variable pattern of changes in MMP concentrations indicates that specific MMPs serve different roles in the pathophysiology following TBI, and are in turn associated with clinical outcomes

Successful combined targeting of B- and plasma cells in treatment refractory anti-NMDAR encephalitis

We describe an extremely severe case of therapy refractory NMDA receptor encephalitis (NMDAe) in a 26-year-old woman. After rituximab, bilateral oophorectomy, repeated cycles of high dose methylprednisolone and plasma exchange, she received repeated cyclophosphamide, tocilizumab (interleukin-6 inhibitor) and finally bortezomib (plasma cell depleting drug) leading to remission after 204 days in intensive care. Two years after disease onset her cognitive functions are still affected, but slowly improving and the cerebral atrophy has been partly reversed. The cerebrospinal fluid biomarker profile suggests an early synaptic/dendritic process, with subsequent neuroaxonal degeneration motivating aggressive treatment early on

No Evidence for Disease History as a Risk Factor for Narcolepsy after A(H1N1)pdm09 Vaccination

OBJECTIVES: To investigate disease history before A(H1N1)pdm09 vaccination as a risk factor for narcolepsy.METHODS: Case-control study in Sweden. Cases included persons referred for a Multiple Sleep Latency Test between 2009 and 2010, identified through diagnostic sleep centres and confirmed through independent review of medical charts. Controls, selected from the total population register, were matched to cases on age, gender, MSLT-referral date and county of residence. Disease history (prescriptions and diagnoses) and vaccination history was collected through telephone interviews and population-based healthcare registers. Conditional logistic regression was used to investigate disease history before A(H1N1)pdm09 vaccination as a risk-factor for narcolepsy.RESULTS: In total, 72 narcolepsy cases and 251 controls were included (range 3-69 years mean19-years). Risk of narcolepsy was increased in individuals with a disease history of nervous system disorders (OR range = 3.6-8.8) and mental and behavioural disorders (OR = 3.8, 95% CI 1.6-8.8) before referral. In a second analysis of vaccinated individuals only, nearly all initial associations were no longer statistically significant and effect sizes were smaller (OR range = 1.3-2.6). A significant effect for antibiotics (OR = 0.4, 95% CI 0.2-0.8) and a marginally significant effect for nervous system disorders was observed. In a third case-only analysis, comparing cases referred before vaccination to those referred after; prescriptions for nervous system disorders (OR = 26.0 95% CI 4.0-170.2) and ADHD (OR = 35.3 95% CI 3.4-369.9) were statistically significant during the vaccination period, suggesting initial associations were due to confounding by indication.CONCLUSION: The findings of this study do not support disease history before A(H1N1)pdm09 vaccination as a risk factor for narcolepsy

Plasma neurofilament light chain levels in patients with MS switching from injectable therapies to fingolimod

Background: Neurofilament light chain (NFL) is a cerebrospinal fluid (CSF) marker of neuroaxonal damage in multiple sclerosis (MS). Objective: To determine the correlation of NFL in CSF and serum/plasma, and in plasma after switching from injectable MS therapies to fingolimod. Methods: A first cohort consisted of MS patients (n = 39) and neurological disease controls (n = 27) where CSF and plasma/serum had been collected for diagnostic purposes. A second cohort (n = 243) consisted of patients from a post-marketing study of fingolimod. NFL was determined with Single Molecule Array (Simoa™) technology (detection threshold 1.95 pg/mL). Results: Mean NFL pg/mL (standard deviation (SD)) was 341 (267) and 1475 (2358) in CSF and 8.2 (3.58) and 17.0 (16.94) in serum from controls and MS, respectively. CSF/serum and plasma/serum levels were highly correlated (n = 66, rho = 0.672, p < 0.0001 and n = 16, rho = 0.684, p = 0.009, respectively). In patients starting fingolimod (n = 243), mean NFL pg/mL (SD) in plasma was reduced between baseline (20.4 (10.7)) and at 12 months (13.5 (7.3), p < 3 × 10−6), and levels remained stable at 24 months (13.2 (6.2)). Conclusion: NFL in serum and CSF are highly correlated and plasma NFL levels decrease after switching to highly effective MS therapy. Blood NFL measurement can be considered as a biomarker for MS therapy response