Additional effect of erenumab for patients with chronic migraine treated with onabotulinumtoxin A-real-world data from a preliminary cohort study.

Background: This preliminary retrospective cohort study investigates the potential additive prophylactic effect of erenumab, a fully human monoclonal antibody that blocks the calcitonin gene-related peptide receptor, in combination with ongoing onabotulinumtoxin A (onaBoNT-A) treatment in patients suffering from chronic migraine.

Methods: The study included 218 patients and investigated the effects of adding erenumab to the existing treatment regimen. The primary outcome was the MIDAS (Migraine Disability Assessment) score assessed 3 months after the introduction of erenumab.

The Use of Nitrosative Stress Molecules as Potential Diagnostic Biomarkers in Multiple Sclerosis.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) of still unclear etiology. In recent years, the search for biomarkers facilitating its diagnosis, prognosis, therapy response, and other parameters has gained increasing attention. In this regard, in a previous meta-analysis comprising 22 studies, we found that MS is associated with higher nitrite/nitrate (NOx) levels in the cerebrospinal fluid (CSF) compared to patients with non-inflammatory other neurological diseases (NIOND).

Real-world evidence of ocrelizumab-treated relapsing multiple sclerosis cohort shows changes in progression independent of relapse activity mirroring phase 3 trials.

Ocrelizumab is a B cell-depleting drug widely used in relapsing-remitting multiple sclerosis (RRMS) and primary-progressive MS. In RRMS, it is becoming increasingly apparent that accumulation of disability not only manifests as relapse-associated worsening (RAW) but also as progression independent of relapse activity (PIRA) throughout the disease course. This study's objective was to investigate the role of PIRA in RRMS patients treated with ocrelizumab.

Classifying flow cytometry data using Bayesian analysis helps to distinguish ALS patients from healthy controls.

Introduction: Given its wide availability and cost-effectiveness, multidimensional flow cytometry (mFC) became a core method in the field of immunology allowing for the analysis of a broad range of individual cells providing insights into cell subset composition, cellular behavior, and cell-to-cell interactions. Formerly, the analysis of mFC data solely relied on manual gating strategies. With the advent of novel computational approaches, (semi-)automated gating strategies and analysis tools complemented manual approaches.

On-Site Sensor Calibration Procedure for Quality Assurance of Barometric Process Separation (BaPS) Measurements.

Barometric process separation (BaPS) is an automated laboratory system for the simultaneous measurement of microbial respiration and gross nitrification rates in soil samples. To ensure optimal functioning, the sensor system, consisting of a pressure sensor, an O sensor, a CO concentration sensor, and two temperature probes, must be accurately calibrated. For the regular on-site quality control of the sensors, we developed easy, inexpensive, and flexible calibration procedures.

Effect of Previous Disease-Modifying Therapy on Treatment Effectiveness for Patients Treated With Ocrelizumab.

Background And Objectives: B cell-depleting antibodies were proven as effective strategy for the treatment of relapsing multiple sclerosis (RMS). The monoclonal antibody ocrelizumab was approved in 2017 in the United States and in 2018 in the European Union, but despite proven efficacy in randomized, controlled clinical trials, its effectiveness in the real-world setting remains to be fully elucidated. In particular, most study patients were treatment naive or switched from injectable therapies, whereas oral substances or monoclonal antibodies made up >1% of previous treatments.

Immune response to SARS-CoV-2 vaccination in relation to peripheral immune cell profiles among patients with multiple sclerosis receiving ocrelizumab.

Background: Vaccination has proven to be effective in preventing SARS-CoV-2 transmission and severe disease courses. However, immunocompromised patients have not been included in clinical trials and real-world clinical data point to an attenuated immune response to SARS-CoV-2 vaccines among patients with multiple sclerosis (MS) receiving immunomodulatory therapies.

Methods: We performed a retrospective study including 59 ocrelizumab (OCR)-treated patients with MS who received SARS-CoV-2 vaccination.

CNS Involvement in Chronic Inflammatory Demyelinating Polyneuropathy: Subtle Retinal Changes in Optical Coherence Tomography.

Background And Objectives: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disease primarily affecting the peripheral nervous system. However, several noncontrolled studies have suggested concomitant inflammatory CNS demyelination similar to multiple sclerosis. The aim of this study was to investigate an involvement of the visual pathway in patients with CIDP.

Ocrelizumab Extended Interval Dosing in Multiple Sclerosis in Times of COVID-19.

Objective: To evaluate the clinical consequences of extended interval dosing (EID) of ocrelizumab in relapsing-remitting multiple sclerosis (RRMS) during the coronavirus disease 2019 (COVID-19) pandemic.

Methods: In our retrospective, multicenter cohort study, we compared patients with RRMS on EID (defined as ≥4-week delay of dose interval) with a control group on standard interval dosing (SID) at the same period (January to December 2020).

Results: Three hundred eighteen patients with RRMS were longitudinally evaluated in 5 German centers.

Does silica addition affect translocation and leaching of cadmium and copper in soil?

Soil and groundwater contamination with potentially toxic elements (PTEs) including cadmium (Cd) and copper (Cu) has become a serious problem for ecosystem functioning. Silicon (Si) may precipitate these metals as silicates, and may also form, at undersaturation of silicates, 'Si-contaminant compounds', i.e.

Altered energy partitioning across terrestrial ecosystems in the European drought year 2018.

Drought and heat events, such as the 2018 European drought, interact with the exchange of energy between the land surface and the atmosphere, potentially affecting albedo, sensible and latent heat fluxes, as well as CO exchange. Each of these quantities may aggravate or mitigate the drought, heat, their side effects on productivity, water scarcity and global warming. We used measurements of 56 eddy covariance sites across Europe to examine the response of fluxes to extreme drought prevailing most of the year 2018 and how the response differed across various ecosystem types (forests, grasslands, croplands and peatlands).

Contribution of plant-induced pressurized flow to CH emission from a Phragmites fen.

The widespread wetland species Phragmites australis (Cav.) Trin. ex Steud.

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.

Factors associated with headache in intravenous immunoglobulin treatment for neurological diseases.

Objectives: To identify possible risk factors influencing the incidence of intravenous immunoglobulin (IVIg) treatment-related cephalalgia in neurological diseases.

Materials & Methods: Retrospective chart review of neurological patients receiving IVIg treatment between July 13, 2017, and August 14, 2017. Patients with MS receiving natalizumab in the same setting were observed as a reference group.

Regulation of sirtuin expression in autoimmune neuroinflammation: Induction of SIRT1 in oligodendrocyte progenitor cells.

In multiple sclerosis (MS) regeneration of oligodendrocytes following inflammatory demyelination is limited by the compromised ability of progenitors to repopulate lesioned areas and transition to functionally competent oligodendrocytes. Regarding underlying mechanisms, the involvement of epigenetic processes has been suggested, e.g.

Multifocal visual evoked potentials in chronic inflammatory demyelinating polyneuropathy.

Objective: Studies using conventional full-field visual evoked potentials (ffVEP) have reported subtle abnormalities in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). We hypothesize that these abnormalities can be detected in the majority of CIDP patients using enhanced methods.

Methods: We performed a cross-sectional noninterventional study comparing 18 CIDP patients and 18 matched healthy controls using multifocal VEP (mfVEP) as a technique with enhanced sensitivity to detect conduction abnormalities across the spectrum of optic nerve fibers.

Nimodipine confers clinical improvement in two models of experimental autoimmune encephalomyelitis.

Multiple sclerosis is characterised by inflammatory neurodegeneration, with axonal injury and neuronal cell death occurring in parallel to demyelination. Regarding the molecular mechanisms responsible for demyelination and axonopathy, energy failure, aberrant expression of ion channels and excitotoxicity have been suggested to lead to Ca overload and subsequent activation of calcium-dependent damage pathways. Thus, the inhibition of Ca influx by pharmacological modulation of Ca channels may represent a novel neuroprotective strategy in the treatment of secondary axonopathy.

Activation of Wnt signaling promotes hippocampal neurogenesis in experimental autoimmune encephalomyelitis.

Background: Disease progression in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), as one of its animal models, is characterized by demyelination and neuronal damage in white and gray matter structures, including the hippocampus. It is thought that dysfunction of the hippocampus, a primary locus of learning and memory consolidation, may contribute to cognitive impairment in MS patients. Previously, we reported an increased generation of hippocampal neuronal progenitors in the acute stage of EAE, whereas the microenvironmental signals triggering this process remained uninvestigated.

Dual roles of the adenosine A2a receptor in autoimmune neuroinflammation.

Background: Conditions of inflammatory tissue distress are associated with high extracellular levels of adenosine, due to increased adenosine triphosphate (ATP) degradation upon cellular stress or the release of extracellular ATP upon cell death, which can be degraded to adenosine by membrane-bound ecto-enzymes like CD39 and CD73. Adenosine is recognised to mediate anti-inflammatory effects via the adenosine A2a receptor (A2aR), as shown in experimental models of arthritis. Here, using pharmacological interventions and genetic inactivation, we investigated the roles of A2aR in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS).

Advances in and Algorithms for the Treatment of Relapsing-Remitting Multiple Sclerosis.

Treatment options in relapsing-remitting multiple sclerosis have increased considerably in recent years; currently, a dozen different preparations of disease-modifying therapies are available and some more are expected to be marketed soon. For the treating neurologist this broad therapeutic repertoire not only greatly improves individualized management of the disease, but also makes choices more complex and difficult. A number of factors must be considered, including disease activity and severity, safety profile, and patient preference.

Non-hazardous pesticide concentrations in surface waters: An integrated approach simulating application thresholds and resulting farm income effects.

Pesticide application rates are high and increasing in upland agricultural systems in Thailand producing vegetables, fruits and ornamental crops, leading to the pollution of stream water with pesticide residues. The objective of this study was to determine the maximum per hectare application rates of two widely used pesticides that would achieve non-hazardous pesticide concentrations in the stream water and to evaluate how farm household incomes would be affected if farmers complied with these restricted application rates. For this purpose we perform an integrated modeling approach of a hydrological solute transport model (the Soil and Water Assessment Tool, SWAT) and an agent-based farm decision model (Mathematical Programming-based Multi-Agent Systems, MPMAS).