STUDIES OF SOLVENT EXTRACTION AND SUPPORTED LIQUID MEMBRANE WITH REACTIVE DYES FROM AQUEOUS SOLUTIONS USING ALIQUOT 336 AS CARRIER

The liquid-liquid extraction (LLE) and supported liquid membrane (SLM) studies of reactive dyes namely Gold Yellow (GYHE-R) and Reactive Green HE 4BD (RGHE-4BD) from aqueous solution using Aliquot 336 as the carrier has been investigated. Polytetrafluoroethylene (PTFE) membrane with 0.5 μm pore size has been used after impregnated with Aliquot 336 in dichloromethane. In liquid liquid extraction the following parameters had been optimized; pH of feed, diluent, carrier , strip and dye concentration and the same parameters have been applied to supported liquid membrane (SLM) study to transport dye from aqueous solution.The main advantages SLM study is; the extraction and stripping as single stage process and low consumption of carrier in the membrane phase compared to the solvent extraction process. The other parameters such as transport time, stirring speed and mechanism of dye transport has also studied by SLM. The percentage of transport of dye and flux rate increases with increasing time. The stability of membrane is satisfactory over 5 days

Effects of ON and OFF subthalamic nucleus-DBS on prefrontal cortex activation during a cognitive task: an fNIRS study

Subthalamic nucleus (STN) deep brain stimulation (DBS) therapy is an effective treatment for the appendicular motor symptoms of Parkinson’s disease (PD). The STN contains multiple segregated circuits subserving motor, cognitive and mood functions through distinct connectivity to cortical regions. Therefore, we examined prefrontal cortical (PFC) effects of “ON” and “OFF” STN-DBS on executive function (Go/NoGo) using functional near-infrared spectroscopy (fNIRS). Methods Out of 8 PD STN-DBS patients, we present here preliminary analysis of a male (62y) PD patient with bilateral STN-DBS (unipolar, 180Hz, 3.5V). The patient was tested after 12h withdrawal of dopamine medications in both an “OFF” and “ON” DBS session separated by 30min. The subject performed a computerised GoNoGo task with 3 alternating Go/NoGo blocks of 30s duration (20 trials/block) interspersed with 30s rest. Reaction time (RT) and accuracy (omission-Om and commission-Cm errors) results were the average of the 3 Go/NoGo blocks. During performance of the Go/NoGo blocks, changes in oxygenated (O2Hb) and deoxygenated (HHb) haemoglobin concentrations were measured by a fNIRS system (Oxymon MkIII, Artinis Medical Systems) covering the bilateral PFC regions. Results/Discussion Clinical motor performance (UPDRSIII) improved from OFF (31) to ON (20). RT during Go and NoGo was ∼40ms faster in OFF (460 and 364ms) than ON (516 and 407ms). Furthermore, the NoGo condition increased misses (Om) in ON (7%) than OFF (0%); while false alarms (Cm) were similarly increased in ON (27%) and OFF (30%). The Go and NoGo conditions increased bilateral PFC activation (i.e., increase in O2Hb and decrease in HHb). However, there was a general decrease in PFC activation in OFF relative to ON, and this was more obvious in Go than NoGo (see Fig. 1) Conclusion These preliminary results indicate that STN-DBS modulates neurovascular responses in the bilateral PFC that are associated with response inhibition

PB15. Neurophysiological biomarker for the clinical development of tuberous sclerosis [Abstract]

Aim To investigate the neuronal networks in children with tuberous sclerosis complex (TS) undergoing treatment with Everolimus. Methods Sleep and wake electroencephalography (EEG) before and one year after the start of the treatment with Everolimus were investigated in 13 patients with TS. To investigate functional and effective connectivity within the network generating the delta and theta activity in the background sleep and wake EEG, the methods of dynamic imaging of coherent sources (DICS) and renormalized partial directed coherence (RPDC) were applied. Results Sources before the treatment. Independent of location of the tubera and severity of epilepsy, delta activity in the background EEG pattern in patients with TS was associated with the sources in the medial prefrontal cortex, the supplementary motor area and the putamen during sleep. Theta waves during sleep were associated with sources in the prefrontal cortex, sensory cortex, hippocampus and the thalamus. The sources of delta frequency during wakefulness were identified at the posterior parietal cortex, the parahippocampal gyrus and the Broca area. Sources at theta frequency were found at the sensorymotor cortex, the prefrontal cortex, the primary visual cortex and the thalamus at awake state. Sources after the treatment. The sources one year after the start of the therapy, for both delta and delta frequencies were located in the same areas as before, however with a significantly weaker strength of coherence. The RPDC analysis at baseline showed strong bidirectional connections between described sources. The RPDC analyses after the one year of treatment showed significantly weaker unidirectional connections within the described network. At the follow up patients were grouped in two groups; group 1: five patients with >50% reduction of seizures and spike wave index, group 2: eight patients with <50% reduction of seizures and spike wave index. Interestingly, at follow up patients from the group 1 had decreased values in absolute power of the sources, coherence values and strength of connections. Whereas, patients from the group 2 had increased values in all above mentioned parameters. Conclusion The current study described the neuronal network in children with severe epilepsies due to TS. Regardless of the locations of the tubera the DICS analyses showed a complex network of cortical and subcortical sources with strong bidirectional connections. The described network was significantly weaker after one year under the treatment with Everolimus and appears to be characteristic for the children with TS and severe epilepsy

Comparative effectiveness of natalizumab versus ocrelizumab in multiple sclerosis: a real-world propensity score–matched study

Background: For treatment of relapsing-remitting multiple sclerosis (RRMS), a broad range of disease-modifying therapies (DMT) is available. However, few comparative effectiveness studies between different drugs have been performed. Objectives: This study aimed to compare the efficacy and treatment continuation of natalizumab and ocrelizumab in a real-world cohort of patients with relapsing-remitting multiple sclerosis (RRMS) from two German university hospitals. Methods: We performed a retrospective analysis of RRMS patients who initiated treatment with natalizumab or ocrelizumab between January 2016 and April 2019 at the German university hospitals of Mainz and Düsseldorf. Bayesian propensity score matching was conducted to correct for differences in baseline characteristics. Our primary outcome was no evidence of disease activity [NEDA-3: no relapses, no confirmed disability progression, and no magnetic resonance imaging (MRI) activity] and its subcomponents. Secondary outcomes included measurement of neurofilament light chain (NfL) in serum, analysis of premature discontinuation, and evidence of rebound activity in patients switching from natalizumab to ocrelizumab. Results: We identified 63 patients starting treatment with natalizumab and 76 patients starting with ocrelizumab. Binary logistic regression showed that treatment with natalizumab or a higher number of relapses in the previous year were independently associated with a higher risk for relapses. Patients receiving natalizumab had a higher probability of premature discontinuation of therapy (p = 0.002). After propensity score matching of the two treatment arms, 55 patients remained per group. NEDA-3 after 30 months of follow-up was reached by 53.1% in the ocrelizumab group and 36.1% in the natalizumab group (p = 0.177). Ocrelizumab was superior to natalizumab concerning the occurrence of relapses in log-rank test (p = 0.019). NfL levels in serum were low under both treatments. Patients who switched from natalizumab to ocrelizumab showed no increased rebound activity. Discussion: This study provides class IV evidence that treatment of RRMS patients with ocrelizumab and natalizumab show comparable effectiveness in combined endpoints, while ocrelizumab might be more effective in preventing the occurrence of relapses

Coherent source and connectivity analysis on simultaneously measured EEG and MEG data during isometric contraction

The most well-known non-invasive electric and magnetic field measurement modalities are the electroencephalography (EEG) and magnetoencephalography (MEG). The first aim of the study was to implement the recently developed realistic head model which uses an integrative approach for both the modalities. The second aim of this study was to find the network of coherent sources and the modes of interactions within this network during isometric contraction (ISC) at (15-30 Hz) in healthy subjects. The third aim was to test the effective connectivity revealed by both the modalities analyzing them separately and combined. The Welch periodogram method was used to estimate the coherence spectrum between the EEG and the electromyography (EMG) signals followed by the realistic head modelling and source analysis method dynamic imaging of coherent sources (DICS) to find the network of coherent sources at the individual peak frequency within the beta band in healthy subjects. The last step was to identify the effective connectivity between the identified sources using the renormalized partial directed coherence method. The cortical and sub-cortical network comprised of the primary sensory motor cortex (PSMC), secondary motor area (SMA), and the cerebellum (C). The cortical and sub-cortical network responsible for the isometric contraction was similar in both the modalities when analysing them separately and combined. The SNR was not significantly different between the two modalities separately and combined. However, the coherence values were significantly higher in the combined modality in comparison to each of the modality separately. The effective connectivity analysis revealed plausible additional connections in the combined modality analysis

Gray matter integrity predicts white matter network reorganization in multiple sclerosis

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease leading to gray matter atrophy and brain network reconfiguration as a response to increasing tissue damage. We evaluated whether white matter network reconfiguration appears subsequently to gray matter damage, or whether the gray matter degenerates following alterations in white matter networks. MRI data from 83 patients with clinically isolated syndrome and early relapsing–remitting MS were acquired at two time points with a follow-up after 1 year. White matter network integrity was assessed based on probabilistic tractography performed on diffusion-weighted data using graph theoretical analyses. We evaluated gray matter integrity by computing cortical thickness and deep gray matter volume in 94 regions at both time points. The thickness of middle temporal cortex and the volume of deep gray matter regions including thalamus, caudate, putamen, and brain stem showed significant atrophy between baseline and follow-up. White matter network dynamics, as defined by modularity and distance measure changes over time, were predicted by deep gray matter volume of the atrophying anatomical structures. Initial white matter network properties, on the other hand, did not predict atrophy. Furthermore, gray matter integrity at baseline significantly predicted physical disability at 1-year follow-up. In a sub-analysis, deep gray matter volume was significantly related to cognitive performance at baseline. Hence, we postulate that atrophy of deep gray matter structures drives the adaptation of white matter networks. Moreover, deep gray matter volumes are highly predictive for disability progression and cognitive performance

Dynamic networks differentiate the language ability of children with cochlear implants

Background: Cochlear implantation (CI) in prelingually deafened children has been shown to be an effective intervention for developing language and reading skill. However, there is a substantial proportion of the children receiving CI who struggle with language and reading. The current study–one of the first to implement electrical source imaging in CI population was designed to identify the neural underpinnings in two groups of CI children with good and poor language and reading skill. Methods: Data using high density electroencephalography (EEG) under a resting state condition was obtained from 75 children, 50 with CIs having good (HL) or poor language skills (LL) and 25 normal hearing (NH) children. We identified coherent sources using dynamic imaging of coherent sources (DICS) and their effective connectivity computing time-frequency causality estimation based on temporal partial directed coherence (TPDC) in the two CI groups compared to a cohort of age and gender matched NH children. Findings: Sources with higher coherence amplitude were observed in three frequency bands (alpha, beta and gamma) for the CI groups when compared to normal hearing children. The two groups of CI children with good (HL) and poor (LL) language ability exhibited not only different cortical and subcortical source profiles but also distinct effective connectivity between them. Additionally, a support vector machine (SVM) algorithm using these sources and their connectivity patterns for each CI group across the three frequency bands was able to predict the language and reading scores with high accuracy. Interpretation: Increased coherence in the CI groups suggest overall that the oscillatory activity in some brain areas become more strongly coupled compared to the NH group. Moreover, the different sources and their connectivity patterns and their association to language and reading skill in both groups, suggest a compensatory adaptation that either facilitated or impeded language and reading development. The neural differences in the two groups of CI children may reflect potential biomarkers for predicting outcome success in CI children