Therapeutic plasma exchange in multiple sclerosis patients with an aggressive relapse: an observational analysis in a high-volume center.

An evidence-based treatment for a Multiple Sclerosis (MS) relapse is an intravenous administration of 3-5 g of Methylprednisolone. In case of insufficient effect or corticosteroids intolerance, the therapeutic plasma exchange (TPE) is indicated. To assess the clinical effect of TPE in treatment of relapse in patients with relapsing-remitting MS (RRMS), we enrolled 155 patients meeting the following criteria (study period: January 2011 to February 2021): (1) age > 18, (2) RRMS according to the McDonald´s 2017 criteria, (3) MS relapse and insufficient effect of corticosteroids/corticosteroids intolerance, (4) baseline EDSS < 8. Exclusion criteria: (1) progressive form of disease, (2) history of previous TPE. Following parameters were monitored: EDSS changes (before and after corticosteroid treatment, before and after TPE; EDSS after TPE was assessed at the next clinical follow-up at the MS Center), and improvement of EDSS according to the number of procedures and baseline severity of relapse. 115 females (74%) and 40 males (26%) were included. The median age was 41 years (IQR 33-47)-131 patients underwent the pulse corticosteroids treatment and TPE, while 24 patients underwent only TPE without any previous corticosteroid treatment. Median baseline EDSS was 4.5 (IQR 3.5-5.5), median EDSS after finishing steroids was 4.5 (IQR 4.0-5.5). EDSS prior to the TPE was 4.5 (IQR 4-6), EDSS after TPE was 4.5 (IQR 3.5-5.5). We observed a significant improvement in the EDSS after TPE (p < 0.001). Sex differences were seen in TPE effectiveness, with median improvement of EDSS in females being -0.5 (IQR 1-0) and in males being 0 (IQR -0.5 to 0), p = 0.048. There was no difference in EDSS improvement by age category: 18-30 years, 31-40 years, 41-50 years, > 50 (p = 0.94), nor by total TPE count (p = 0.91). In this retrospective study of patients with an aggressive relapse and insufficient effect of intravenous corticosteroid treatment, a significant effect of TPE on EDSS improvement was observed. There was no significant difference in TPE effectivity according to the number of procedures, age, nor severity of a relapse. In this cohort, TPE was more effective in females.

Serum neurofilament levels in patients with multiple sclerosis: A comparison of SIMOA and high sensitivity ELISA assays and contributing factors to ELISA levels.

BACKGROUND: Serum neurofilaments (sNfs), especially the most investigated serum neurofilament light chain (sNfL), are promising biomarkers in multiple sclerosis (MS). However, their clinical utility is still limited, given the availability and costs of accessible analytical methods. The gold standard for the detection of sNfs is represented by the single molecule arrays (SIMOA). Recently, a high sensitivity enzyme-linked immunosorbent assay (hsELISA) has also been introduced. The objective of the study was to compare both assays for the determination of sNfL and neurofilament heavy chain (sNfH) concentrations in a defined MS cohort. The second objective was to identify contributing factors to sNfs concentrations determined by hsELISA. METHODS: Serum samples were collected from MS patients attending the MS Centre, University Hospital Ostrava, Czech Republic. The levels of sNfs were detected using SIMOA and hsELISA assays. RESULTS: The Spearman's rank correlation coefficient between the sNfL SIMOA and sNfL hsELISA and between the sNfH SIMOA and sNfH hsELISA was moderate rs= 0.543 (p = 0.001) and rs= 0.583 (p = 0.001), respectively. The Passing-Bablok regression analysis demonstrated bias between both methods. Equally significant bias between the methods was confirmed by the Bland-Altman plots. Furthermore, confounding factors affecting the sNfL levels were glomerular filtration rate (eGFR; 95% CI -2.34 to -0.04) and sex (95% CI -2.38 to -0.10). The sNfH levels were affected by age (95% CI 0.01 to 0.07), eGFR (95% CI -2.45 to -0.02), body mass index (BMI; 95% CI -0.31 to -0.05), and blood volume (95% CI 0.69 to 3.35). CONCLUSION: This analytical study showed significant differences between hsELISA and SIMOA methods, especially for the sNfH concentrations. We identified confounding factors for sNfs levels determined by hsELISA. The sNfs levels were influenced by renal function and sex, whilst sNfH levels were affected by age, BMI, and total blood volume.

Chemical and electronic structure of the heavily intermixed (Cd,Zn)S:Ga/CuSbS2 interface.

The interface formation and chemical and electronic structure of the (Cd,Zn)S:Ga/CuSbS2 thin-film solar cell heterojunction were studied using hard X-ray photoelectron spectroscopy (HAXPES) of the bare absorber and a buffer/absorber sample set for which the buffer thickness was varied between 1 and 50 nm. We find a heavily intermixed interface, involving Cu, Zn, and Cd as well as significant Ga and Cu profiles in the buffer. The valence band (VB) offset at the buffer/absorber interface was derived as (-1.3 ± 0.1) eV, which must be considered an upper bound as the Cu diffused into the buffer might form a Cu-derived VB maximum located closer to the Fermi level. The estimated conduction band minimum was 'cliff'-like; a situation made more severe considering the Cu-deficiency found for the CuSbS2 surface. The complex interface structure's effect on the performance of (Cd,Zn)S:Ga/CuSbS2-based solar cells and its limitation is discussed together with possible mitigation strategies.

Acute Toxicity of Insecticide Thiamethoxam to Crayfish (Astacus leptodactylus): Alterations in Oxidative Stress Markers, ATPases and Cholinesterase.

Thiamethoxam (Thmx) is a globally used neonicotinoid pesticide contaminated in freshwater ecosystems with residues detected in fishery products. Astacus leptodactylus is a popular freshwater crustacean that is cultivated and exported in many countries. In this study, we investigated the acute toxic effects of Thmx on A. leptodactylus using various biomarkers (acetylcholinesterase, carboxylesterase, glutathione S-transferase, glutathione, superoxide dismutase, glutathione peroxidase, glutathione reductase, and adenosinetriphosphatases). The 96-h LC50 value of Thmx was calculated as 8.95 mg active ingredient L-1. As the dose of Thmx increased, oxidative stress was induced by the inhibition/activation of antioxidant enzymes, while the activities of acetylcholinesterase, carboxylesterase and adenosinetriphosphatases were inhibited. As a result, it can be said that Thmx has highly toxic effects on crayfish, therefore they are under threat in the areas where this pesticide is used.

Local electronic structure of the peptide bond probed by resonant inelastic soft X-ray scattering.

The local valence orbital structure of solid glycine, diglycine, and triglycine is studied using soft X-ray emission spectroscopy (XES), resonant inelastic soft X-ray scattering (RIXS) maps, and spectra calculations based on density-functional theory. Using a building block approach, the contributions of the different functional groups of the peptides are separated. Cuts through the RIXS maps furthermore allow monitoring selective excitations of the amino and peptide functional units, leading to a modification of the currently established assignment of spectral contributions. The results thus paint a new-and-improved picture of the peptide bond, enhance the understanding of larger molecules with peptide bonds, and simplify the investigation of such molecules in aqueous environment.

SlPRA1A/RAB attenuate EIX immune responses via degradation of LeEIX2 pattern recognition receptor.

Pattern recognition receptors (PRR) are plasma membrane (PM) proteins that recognize microbe-associated molecular patterns (MAMPs), triggering an immune response. PRR are classified as receptor like kinases (RLKs) or receptor like proteins (RLPs). The PM localization of PRRs, which is crucial for their availability to sense MAMPs, depends on their appropriate trafficking through the endomembrane system. Recently, we have identified SlPRA1A, a prenylated RAB acceptor type-1 (PRA1) from S. lycopersicum, as a regulator of RLP-PRR localization and protein levels. SlPRA1A overexpression strongly decreases RLP-PRR protein levels, particularly those of LeEIX2, redirecting it to the vacuole for degradation. Interestingly, SlPRA1A does not affect RLK-PRRs, indicating its activity to be specific to RLP-PRR systems. As PRA1 proteins stabilize RABs on membranes, promoting RABs activity, we aimed to identify a RAB target of SlPRA1A. Screening of a set of A. thaliana RABs revealed that AtRABA1e is able to mimic SlPRA1A activity. Through live cell imaging, we observed that SlPRA1A enhances AtRABA1e localization on SlPRA1A positive punctuated structures. These results indicate that AtRABA1e is a putative target of SlPRA1, and a co-regulator of LeEIX2 trafficking and degradation.

Site-specific electronic structure of imidazole and imidazolium in aqueous solutions.

The occupied and unoccupied electronic structure of imidazole (C3N2H4) and imidazolium (C3N2H5+) in aqueous solutions is studied by X-ray emission spectroscopy (XES) and resonant inelastic soft X-ray scattering (RIXS). Both systems show distinct RIXS fingerprints with strong resonant effects. A comparison with calculated X-ray emission spectra of isolated imidazole and imidazolium suggests only a small influence of hydrogen bonding in the aqueous solution on the electronic structure of imidazole and imidazolium, and allows the attribution of specific spectral features to the non-equivalent nitrogen and carbon atoms in the molecules. In the case of nitrogen, this can also be achieved by site-selective resonant excitation. Furthermore, we find spectator shifts and symmetry selectivity in the RIXS spectra, as well as indications for rapid proton dynamics on the femtosecond timescale of the RIXS process, and derive the HOMO-LUMO gaps for the two molecules in aqueous solution.

Endoscopic management of Atypical sellar cavernous hemangioma: A case report and review of the literature.

INTRODUCTION: supratentorial cavernous hemangiomas, particularly those found in the sellar region, are extremely rare. We present a case of sellar cavernous hemangioma with radiological characteristics that have never been reported. Due to the difficulty diagnosing these lesions, misdiagnosis might occur. Thus, briefing surgeons about the clinico-radiological features of such rare lesions is crucial for better understanding the enigmatic features of such rare lesions and to develop early management approaches that could result in better surgical excision with a lower tendency for complications. PRESENTATION OF CASE: A 43-year-old male presented with headache, blurred vision, and impotence for the last 2 years. Brain magnetic resonance imaging showed an atypical sellar mass displaying signals of heterogeneous intensity on T1- and T2-weighted imaging. The mass exhibited heterogeneous enhancement after gadolinium injection. Endoscopic endonasal surgery was subsequently performed, during which an uneventful subtotal resection of the mass was achieved. Histopathological analysis confirmed the diagnosis of intrasellar cavernous hemangioma. DISCUSSION: Many questions regarding how best to manage such lesions remain unanswered. Hence, we summarize the relevant surgical techniques and discuss misconceptions. CONCLUSION: Seller cavernous hemangioma (SCH) is an extremely rare lesion that can be misdiagnosed. It is characterized by clinico-radiological features similar to those of other lesions such as pituitary macroadenoma and should be included in the differential diagnosis. The endoscopic endonasal transsphenoidal (EET) approach with subtotal/total resection appears to be a feasible option for debulking, with less surgical complications. Nonetheless, combining stereotactic radiosurgery will reduce postsurgical morbidities.

X-ray Emission Spectroscopy of Proteinogenic Amino Acids at All Relevant Absorption Edges.

Nonresonant N K, O K, C K, and S L2,3 X-ray emission spectra of the 20 most common proteinogenic amino acids in their solid zwitterionic form are reported. They represent a comprehensive database that can serve as a reliable basis for the X-ray absorption spectroscopy (XES) studies of peptides and proteins. At the most important N and O K edges, clear similarities and differences between the spectra of certain amino acids are observed and associated with the specific chemical structure of these molecules and their functional groups. Analysis of these spectra allows the generation of spectral fingerprints of the protonated amino group, the deprotonated carboxylic group, and, using a building block approach, the specific nitrogen- and oxygen-containing functional groups in the side chains of the amino acids. Some of these fingerprints are compared to the spectra of reference compounds with the respective functional groups; they exhibit reasonable similarity, underlining the validity of the spectral fingerprint approach. The C K and S L2,3 XES spectra are found to be specific for each amino acid, in accordance with the different local environments of the involved C and S atoms, respectively.

Spontaneous improvement in both obstructive sleep apnea and cognitive impairment after stroke.

BACKGROUND: Knowledge available about the relationship between obstructive sleep apnea (OSA) and cognitive impairment after stroke is limited. The evolution of OSA and cognitive performance after stroke is not sufficiently described. METHODS: We prospectively enrolled and examined acute stroke patients without previously diagnosed OSA. The following information was collected: (1) demographics, (2) sleep cardio-respiratory polygraphy (PG) at 72 h, day seven, month three, and month 12 after stroke, (3) post-stroke functional disability tests at entry and at months three and 12, and (4) cognition (attention and orientation, memory, verbal fluency, language, and visual-spatial abilities) using the revised Addenbrooke's Cognitive Examination (ACE-R) at months three and 12. RESULTS: Of 68 patients completing the study, OSA was diagnosed in 42 (61.8%) patients. The mean apnea/hypopnea index (AHI) at study entry of 21.0 ± 13.7 spontaneously declined to 11.6 ± 11.2 at month 12 in the OSA group (p < 0.0005). The total ACE-R score was significantly reduced at months three (p = 0.005) and 12 (p = 0.004) in the OSA group. Poorer performance on the subtests of memory at months 3 (p = 0.039) and 12 (p = 0.040) and verbal fluency at months 3 (p < 0.005) and 12 (p < 0.005) were observed in the OSA group compared to non-OSA group. Visual-spatial abilities in both the OSA (p = 0.001) and non-OSA (p = 0.046) groups and the total ACE-R score in the OSA (p = 0.005) and non-OSA (p = 0.002) groups improved. CONCLUSIONS: A high prevalence of OSA and cognitive decline were present in patients after an acute stroke. Spontaneous improvements in both OSA and cognitive impairment were observed.

Investigation of the Ionic Hydration in Aqueous Salt Solutions by Soft X-ray Emission Spectroscopy.

Understanding the molecular structure of the hydration shells and their impact on the hydrogen bond (HB) network of water in aqueous salt solutions is a fundamentally important and technically relevant question. In the present work, such hydration effects were studied for a series of representative salt solutions (NaCl, KCl, CaCl2, MgCl2, and KBr) by soft X-ray emission spectroscopy (XES) and resonant inelastic soft X-ray scattering (RIXS). The oxygen K-edge XES spectra could be described with three components, attributed to initial state HB configurations in pure water, water molecules that have undergone an ultrafast dissociation initiated by the X-ray excitation, and water molecules in contact with salt ions. The behavior of the individual components, as well as the spectral shape of the latter component, has been analyzed in detail. In view of the role of ions in such effects as protein denaturation (i.e., the Hofmeister series), we discuss the ion-specific nature of the hydration shells and find that the results point to a predominant role of anions as compared to cations. Furthermore, we observe a concentration-dependent suppression of ultrafast dissociation in all salt solutions, associated with a significant distortion of intact HB configurations of water molecules facilitating such a dissociation.

Blood glucose control using a computer-guided glucose management system in allogeneic hematopoietic cell transplant recipients.

Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative treatment for patients with hematological malignancies. However, is associated with substantial rates of morbidity and mortality. We and others have shown that malglycemia is associated with adverse transplant outcome. Therefore, improving glycemic control may improve transplant outcome. In this prospective study we evaluated the feasibility of using Glucommander (a Computer-Guided Glucose Management System; CGGM) in order to achieve improved glucose control in hospitalized HCT patients. Nineteen adult patients contributed 21 separate instances on CGGM. Patients were on CGGM for a median of 43 h. Median initial blood glucose (BG) on CGGM was 244 mg/dL, and patients on 20 study instances reached the study BG target of 100-140 mg/dL after a median of 6 h. After BG reached the target range, the median average BG level per patient was 124 mg/dL. Six patients had a total of 10 events of BG <70 mg/dL (0.9% of BG measurements), and no patients experienced BG level <40 mg/dL. The total estimated duration of BG <70 mg/dL was 3 h (0.2% of the total CGGM time). In conclusion, our study demonstrates that stringent BG control in HCT patients using CGGM is feasible.

Isotope Effects in the Resonant Inelastic Soft X-ray Scattering Maps of Gas-Phase Methanol.

The electronic structure of gas-phase methanol molecules (H3COH, H3COD, and D3COD) at atmospheric pressure was investigated using resonant inelastic soft X-ray scattering (RIXS) at the O K and C K edges. We observe strong changes of the relative emission intensities of all valence orbitals as a function of excitation energy, which can be related to the symmetries of the involved orbitals causing an angularly anisotropic RIXS intensity. Furthermore, all observed emission lines are subject to strong spectator shifts of up to -0.9 eV at the O K edge and up to -0.3 eV at the C K edge. At the lowest O K resonance, we find clear evidence for dissociation of the methanol molecule on the time scale of the RIXS process, which is illustrated by comparing X-ray emission spectra of regular and deuterated methanol.

Probing hydrogen bonding orbitals: resonant inelastic soft X-ray scattering of aqueous NH3.

To probe the influence of hydrogen bonding on the electronic structure of ammonia, gas phase and aqueous NH3 have been investigated using soft X-ray absorption (XAS), resonant inelastic soft X-ray scattering (RIXS), and electronic structure calculations including dynamical effects. Strong spectral differences in the XAS scans as well as in the RIXS spectra between gas phase and aqueous NH3 are attributed to orbital mixing with the water orbitals, dipole-dipole interactions, differences in vibronic coupling, and nuclear dynamics on the time-scale of the RIXS process. All of these effects are consequences of hydrogen bonding and the impact of the associated orbitals, demonstrating the power of XAS and RIXS as unique tools to study hydrogen bonding in liquids.

Cardiac contraction induces discordant alternans and localized block.

In this paper we use a simplified model of cardiac excitation-contraction coupling to study the effect of tissue deformation on the dynamics of alternans, i.e., alternations in the duration of the cardiac action potential, that occur at fast pacing rates and are known to be proarrhythmic. We show that small stretch-activated currents can produce large effects and cause a transition from in-phase to off-phase alternations (i.e., from concordant to discordant alternans) and to conduction blocks. We demonstrate numerically and analytically that this effect is the result of a generic change in the slope of the conduction velocity restitution curve due to electromechanical coupling. Thus, excitation-contraction coupling can potentially play a relevant role in the transition to reentry and fibrillation.

Forming first impressions of others in schizophrenia: impairments in fast processing and in use of spatial frequency information.

Individuals form first impressions of others all the time, which affects their social functioning. Typical adults form threat impressions in faces with neutral expressions quickly, requiring less than 40 ms. These impressions appear to be mediated by low spatial frequency (LSF) content in the images. Little is known, however, about mechanisms of first impression formation in schizophrenia. The current study investigated how quickly individuals with schizophrenia can form consistent impressions of threat compared with controls and explored the mechanisms involved. Patients and controls were presented intact, LSF- or high spatial frequency (HSF)-filtered faces with durations that varied from 39 to 1703 ms and were asked to rate how threatening each face was on a scale from 1 to 5. In order to assess the speed of impression formation for intact faces, correlations were calculated for ratings made at each duration compared to a reference duration of 1703 ms for each group. Controls demonstrated a significant relation for intact faces presented for 39 ms, whereas patients required 390 ms to demonstrate a significant relation with the reference duration. For controls, LSFs primarily contributed to the formation of consistent threat impressions at 39 ms, whereas patients showed a trend for utilizing both LSF and HSF information to form consistent threat impressions at 390 ms. Results indicate that individuals with schizophrenia require a greater integration time to form a stable "first impression" of threat, which may be related to the need to utilize compensatory mechanisms such as HSF, as well as LSF, information.

The complex interface chemistry of thin-film silicon/zinc oxide solar cell structures.

The interface between solid-phase crystallized phosphorous-doped polycrystalline silicon (poly-Si(n(+))) and aluminum-doped zinc oxide (ZnO:Al) was investigated using spatially resolved photoelectron emission microscopy. We find the accumulation of aluminum in the proximity of the interface. Based on a detailed photoemission line analysis, we also suggest the formation of an interface species. Silicon suboxide and/or dehydrated hemimorphite have been identified as likely candidates. For each scenario a detailed chemical reaction pathway is suggested. The chemical instability of the poly-Si(n(+))/ZnO:Al interface is explained by the fact that SiO2 is more stable than ZnO and/or that H2 is released from the initially deposited a-Si:H during the crystallization process. As a result, Zn (a deep acceptor in silicon) is "liberated" close to the silicon/zinc oxide interface presenting the inherent risk of forming deep defects in the silicon absorber. These could act as recombination centers and thus limit the performance of silicon/zinc oxide based solar cells. Based on this insight some recommendations with respect to solar cell design, material selection, and process parameters are given for further knowledge-based thin-film silicon device optimization.

"Building block picture" of the electronic structure of aqueous cysteine derived from resonant inelastic soft X-ray scattering.

The electronic structure of the amino acid L-cysteine in an aqueous environment was studied using resonant inelastic soft X-ray scattering (RIXS) in a 2D map representation and analyzed in the framework of a "building block" approach. The element selectivity of RIXS allows a local investigation of the electronic structure of the three functional groups of cysteine, namely, the carboxyl, amino, and thiol groups, by measuring at the O K, N K, and S L2,3 edges, respectively. Variation of the pH value allows an investigation of molecules with protonated and deprotonated functional groups, which can then be compared with simple reference molecules that represent the isolated functional groups. We find that such building blocks can provide an excellent description of X-ray emission spectroscopy (XES) and RIXS spectra, but only if all nearest-neighbor atoms are included. This finding is analogous to the building block principle commonly used in X-ray absorption spectroscopy. The building blocks show a distinct spectral character (fingerprint) and allow a comprehensive interpretation of the cysteine spectra. This simple approach opens the path to investigate the electronic structure of more complex biological molecules in aqueous solutions using XES and RIXS.

Setup for in situ investigation of gases and gas/solid interfaces by soft x-ray emission and absorption spectroscopy.

We present a novel gas cell designed to study the electronic structure of gases and gas/solid interfaces using soft x-ray emission and absorption spectroscopies. In this cell, the sample gas is separated from the vacuum of the analysis chamber by a thin window membrane, allowing in situ measurements under atmospheric pressure. The temperature of the gas can be regulated from room temperature up to approximately 600 °C. To avoid beam damage, a constant mass flow can be maintained to continuously refresh the gaseous sample. Furthermore, the gas cell provides space for solid-state samples, allowing to study the gas/solid interface for surface catalytic reactions at elevated temperatures. To demonstrate the capabilities of the cell, we have investigated a TiO2 sample behind a mixture of N2 and He gas at atmospheric pressure.