NEUROFILAMENTS AS A POTENTIAL BIOMARKER IN PATIENTS WITH MULTIPLE SCLEROSIS: A REVIEW OF LITERATURE

Background: Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease of the central nervous system (CNS) characterized by demyelination, axonal damage and loss of neurons. Its growing incidence has determined the need for more intensive research towards effective models for managing disease progression and evaluation of treatment response. Finding clinically relevant biomarkers has been a significant challenge. Purpose: This review aims to summarize the findings from current relevant literature sources on neurofilaments as a potential biomarker of diagnostic and prognostic value in patients with MS. Results: Recently, neurofilaments have been identified as the most promising and informative biomarkers of axonal damage and loss. Neurofilament concentration demonstrates a strong association with the disease course, activity and progression, disability accumulation and response to disease-modifying treatment. A significant correlation with future relapse rates, symptom worsening and risk of conversion from clinically isolated syndrome (CIS) to definite MS has also been established. Several MS therapies have demonstrated a substantial reduction in neurofilament levels upon treatment initiation. Conclusion: The results available from real-world studies and clinical trials regarding neurofilaments as a reliable predictor and indicator of MS disease course are encouraging. They have consistently proven to be of utility if integrated into the diagnostic and therapeutic algorithm of MS patients. This review encompasses undeniable data confirming the considerable potential of neurofilaments for becoming the first globally verified biomarker for MS. The accessibility, safety, low cost and possibility for serial evaluation make the neurofilaments the perfect component to be implemented in routine clinical tests for MS

TUMEFACTIVE MULTIPLE SCLEROSIS: A DIAGNOSTIC ENIGMA. A CASE REPORT

Purpose: To present a clinical case of tumefactive multiple sclerosis (TMS), which is an inflammatory demyelinating disease of the central nervous system considered to be a rare form of multiple sclerosis (MS). It belongs to the group of borderline forms of MS – a collective term used to define a spectrum of demyelination-associated neurological conditions that share similar clinical, neuroimaging and histopathological features but vary widely in severity, clinical course and outcome. Materials/Methods: We describe the case of a 31-year-old female who was admitted to the Neurology clinic of UMHAT “Dr Georgi Stranski” in Pleven, Bulgaria, with a rapid onset of neurological deficit including right-sided hemiparesis, dysarthria, imbalance, cognitive impairment and urinary incontinence. MRI of the brain showed several tumor-like concentric lesions of demyelination surrounded by moderate brain edema, consistent with the radiological criteria for the demyelinating disease. Results: High-dosage corticosteroids were applied intravenously for this patient as acute therapy. A progressive improvement in the patient was achieved after the extended pulse corticosteroid therapy in combination with physiotherapy. Glatiramer acetate as a disease-modifying treatment was initiated within three months and had substantial efficacy. Conclusions: The diagnosis of TMS is always difficult and requires not only complex clinical and neuroimaging investigations but also an extensive follow-up of the patient. It is believed that TMS usually has a progressive course and an unfavorable outcome, but a relapsing-remitting course of TMS, albeit rare, is also possible. Our case report confirms that such benign variants of TMS exist. We believe that highlighting such complex clinical cases will contribute to a better understanding of the mystery of MS

COLD ARGON PLASMA TORCH FOR WATER TREATMENT

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Ru-Catalyzed Isomerization of Achmatowicz Derivatives : A Sustainable Route to Biorenewables and Bioactive Lactones

A Ru-catalyzed isomerization of Achmatowicz derivatives that opens unexplored routes to diversify the biogenic furanic platform is reported. The mechanistic insights of this formally redox-neutral intramolecular process were studied computationally and by deuterium labeling. The transformation proved to be a robust synthetic tool to achieve the synthesis of bioderived-monomers and a series of 4-keto-δ-valerolactones that further enabled the development of a flexible strategy for the synthesis of acetogenins. A concise and protective group-free asymmetric total synthesis of two natural products, namely, (S,S)-muricatacin and the (S,S)-L-factor, is also described.publishedVersionPeer reviewe

Linking cause and effect: Nanoscale vibrational spectroscopy of space weathering from asteroid Ryugu

Airless bodies are subjected to space-weathering effects that modify the first few microns of their surface. Therefore, understanding their impact on the optical properties of asteroids is key to the interpretation of their color variability and infrared reflectance observations. The recent Hayabusa2 sample return mission to asteroid Ryugu offers the first opportunity to study these effects, in the case of the most abundant spectral type among the main-asteroid belt, C-type objects. This study employs vibrational electron energy-loss spectroscopy in the transmission electron microscope to achieve the spatial resolution required to measure the distinct mid-infrared spectral signature of Ryugu's space-weathered surface. The comparison with the spectrum of the pristine underlying matrix reveals the loss of structural -OH and C-rich components in the space-weathered layers, providing direct experimental evidence that exposure to the space environment tends to mask the optical signatures of phyllosilicates and carbonaceous matter. Our findings should contribute to rectifying potential underestimations of water and carbon content of C-type asteroids when studied through remote sensing with new-generation telescopes.The Hayabusa2 project has been developed and led by JAXA in collaboration with Deutsches Zentrum für Luft- und Raumfahrt (DLR) and Centre national d'études spatiales (CNES), and supported by NASA and Australian Space Agency (ASA). We thank all the members of the Hayabusa2 project for their technical and scientific contributions. This work was carried out on the electron microscopy facility of the Advanced Characterization Platform of the Chevreul Institute, University of Lille—CNRS. This project has been funded by ISITE ULNE and the "Métropole Européenne de Lille" through the "TEM-Aster project," the LARCAS ANR (Reference No. SAN-22199). It has also been funded by in part by the National Agency for Research (ANR) under the program of future investment TEMPOS-CHROMATEM (Reference No. ANR-10-EQPX-50). Micro-infrared spectroscopy was performed at the Institut de Planétologie et d'Astrophysique de Grenoble (IPAG). European Union's Horizon 2020 research and innovation program under grant Agreements No. 823717 (ESTEEM3). The Chevreul Institute is thanked for its help in the development of this work through the CHEMACT project supported by the "Ministère de l'Enseignement Supérieur de la Recherche et de l'Innovation," the region "Hauts-de-France" and the "Métropole Européenne de Lille." JSPS KAKENHI grant numbers related to this study are 19H00725, 19K0094, and 21H05424. This research was supported by the H2020 European Research Council (ERC) (SOLARYS ERC-CoG2017-771691). We acknowledge the funding by the Spanish University Ministry and Next Generation EU through a Margarita Salas fellowship.Peer reviewe

Linking Cause and Effect: Nanoscale Vibrational Spectroscopy of Space Weathering from Asteroid Ryugu

Airless bodies are subjected to space-weathering effects that modify the first few microns of their surface. Therefore, understanding their impact on the optical properties of asteroids is key to the interpretation of their color variability and infrared reflectance observations. The recent Hayabusa2 sample return mission to asteroid Ryugu offers the first opportunity to study these effects, in the case of the most abundant spectral type among the main-asteroid belt, C-type objects. This study employs vibrational electron energy-loss spectroscopy in the transmission electron microscope to achieve the spatial resolution required to measure the distinct mid-infrared spectral signature of Ryugu's space-weathered surface. The comparison with the spectrum of the pristine underlying matrix reveals the loss of structural -OH and C-rich components in the space-weathered layers, providing direct experimental evidence that exposure to the space environment tends to mask the optical signatures of phyllosilicates and carbonaceous matter. Our findings should contribute to rectifying potential underestimations of water and carbon content of C-type asteroids when studied through remote sensing with new-generation telescopes

Influx of nitrogen-rich material from the outer Solar System indicated by iron nitride in Ryugu samples

Large amounts of nitrogen compounds, such as ammonium salts, may be stored in icy bodies and comets, but the transport of these nitrogen-bearing solids into the near-Earth region is not well understood. Here, we report the discovery of iron nitride on magnetite grains from the surface of the near-Earth C-type carbonaceous asteroid Ryugu, suggesting inorganic nitrogen fixation. Micrometeoroid impacts and solar wind irradiation may have caused the selective loss of volatile species from major iron-bearing minerals to form the metallic iron. Iron nitride is a product of nitridation of the iron metal by impacts of micrometeoroids that have higher nitrogen contents than the CI chondrites. The impactors are probably primitive materials with origins in the nitrogen-rich reservoirs in the outer Solar System. Our observation implies that the amount of nitrogen available for planetary formation and prebiotic reactions in the inner Solar System is greater than previously recognized

Four‐dimensional‐STEM analysis of the phyllosilicate‐rich matrix of Ryugu samples

Ryugu asteroid grains brought back to the Earth by the Hayabusa2 space mission are pristine samples containing hydrated minerals and organic compounds. Here, we investigate the mineralogy of their phyllosilicate-rich matrix with four-dimensional scanning transmission electron microscopy (4D-STEM). We have identified and mapped the mineral phases at the nanometer scale (serpentine, smectite, pyrrhotite), observed the presence of Ni-bearing pyrrhotite, and identified the serpentine polymorph as lizardite, in agreement with the reported aqueous alteration history of Ryugu. Furthermore, we have mapped the d-spacings of smectite and observed a broad distribution of values, ranging from 1 to 2 nm, with an average d-spacing of 1.24 nm, indicating significant heterogeneity within the sample. Such d-spacing variability could be the result of either the presence of organic matter trapped in the interlayers or the influence of various geochemical conditions at the submicrometer scale, suggestive of a range of organic compounds and/or changes in smectite crystal chemistry

A dehydrated space-weathered skin cloaking the hydrated interior of Ryugu

Without a protective atmosphere, space-exposed surfaces of airless Solar System bodies gradually experience an alteration in composition, structure and optical properties through a collective process called space weathering. The return of samples from near-Earth asteroid (162173) Ryugu by Hayabusa2 provides the first opportunity for laboratory study of space-weathering signatures on the most abundant type of inner solar system body: a C-type asteroid, composed of materials largely unchanged since the formation of the Solar System. Weathered Ryugu grains show areas of surface amorphization and partial melting of phyllosilicates, in which reduction from Fe3+ to Fe2+ and dehydration developed. Space weathering probably contributed to dehydration by dehydroxylation of Ryugu surface phyllosilicates that had already lost interlayer water molecules and to weakening of the 2.7 µm hydroxyl (–OH) band in reflectance spectra. For C-type asteroids in general, this indicates that a weak 2.7 µm band can signify space-weathering-induced surface dehydration, rather than bulk volatile loss