Brain and cognitive changes in patients with long COVID compared with infection-recovered control subjects.

Between 2.5 and 28% of people infected with SARS-CoV-2 suffer Long COVID or persistence of symptoms for months after acute illness. Many symptoms are neurological, but the brain changes underlying the neuropsychological impairments remain unclear. This study aimed to provide a detailed description of the cognitive profile, the pattern of brain alterations in Long COVID and the potential association between them. To address these objectives, 83 patients with persistent neurological symptoms after COVID-19 were recruited, and 22 now healthy controls chosen because they had suffered COVID-19 but did not experience persistent neurological symptoms. Patients and controls were matched for age, sex and educational level. All participants were assessed by clinical interview, comprehensive standardized neuropsychological tests and structural MRI. The mean global cognitive function of patients with Long COVID assessed by ACE III screening test (Overall Cognitive level - OCLz= -0.39± 0.12) was significantly below the infection recovered-controls (OCLz= +0.32± 0.16, p< 0.01). We observed that 48% of patients with Long COVID had episodic memory deficit, with 27% also impaired overall cognitive function, especially attention, working memory, processing speed and verbal fluency. The MRI examination included grey matter morphometry and whole brain structural connectivity analysis. Compared to infection recovered controls, patients had thinner cortex in a specific cluster centred on the left posterior superior temporal gyrus. In addition, lower fractional anisotropy (FA) and higher radial diffusivity (RD) were observed in widespread areas of the patients' cerebral white matter relative to these controls. Correlations between cognitive status and brain abnormalities revealed a relationship between altered connectivity of white matter regions and impairments of episodic memory, overall cognitive function, attention and verbal fluency. This study shows that patients with neurological Long COVID suffer brain changes, especially in several white matter areas, and these are associated with impairments of specific cognitive functions.

Smart Electrode Surfaces by Electrolyte Immobilization for Electrocatalytic CO2 Conversion.

The activity and selectivity of molecular catalysts for the electrochemical CO2 reduction reaction (CO2RR) are influenced by the induced electric field at the electrode/electrolyte interface. We present here a novel electrolyte immobilization method to control the electric field at this interface by positively charging the electrode surface with an imidazolium cation organic layer, which significantly favors CO2 conversion to formate, suppresses hydrogen evolution reaction, and diminishes the operating cell voltage. Those results are well supported by our previous DFT calculations studying the mechanistic role of imidazolium cations in solution for CO2 reduction to formate catalyzed by a model molecular catalyst. This smart electrode surface concept based on covalent grafting of imidazolium on a carbon electrode is successfully scaled up for operating at industrially relevant conditions (100 mA cm-2) on an imidazolium-modified carbon-based gas diffusion electrode using a flow cell configuration, where the CO2 conversion to formate process takes place in acidic aqueous solution to avoid carbonate formation and is catalyzed by a model molecular Rh complex in solution. The formate production rate reaches a maximum of 4.6 gHCOO- m-2 min-1 after accumulating a total of 9000 C of charge circulated on the same electrode. Constant formate production and no significant microscopic changes on the imidazolium-modified cathode in consecutive long-term CO2 electrolysis confirmed the high stability of the imidazolium organic layer under operating conditions for CO2RR.

Diastereoselective multicomponent synthesis of dihydroisoindolo[2,1-a]quinolin-11-ones mediated by eutectic solvents.

In this contribution, a series of dihydroisoindolo[2,1-a]quinolin-11-ones was synthesized by a one-pot multicomponent Povarov reaction starting from anilines, alkenes (trans-anethole, methyl eugenol and indene) and 2-formylbenzoic acid. Different eutectic solvents bearing Lewis or Brønsted acids were evaluated as reaction media and catalysts for the model reaction employing p-toluidine and trans-anethole finding that the eutectic mixture ChCl/ZnCl2 (1/2) allowed the obtention of the target compound in 77% isolated yield. Under the optimized reaction conditions, 20 derivatives were obtained in good to moderated yields using meta- and para-susbstituted anilines, while the corresponding ortho-analogs followed a different pathway affording isoindolinones. In addition, the eutectic mixture was reused in six cycles without observing a detrimental catalytic activity. This methodology features mild reaction conditions, short reaction time, simple work-up, and utilization of a reusable solvent; and provides straightforward and diastereoselective access to these alkaloid-like heterocyclic molecules.

Enabling circular economy by N-recovery: Electrocatalytic reduction of nitrate with cobalt hydroxide nanocomposites on copper foam treating low conductivity groundwater effluents.

Fertilizers play a vital role in the food-energy-water nexus. The traditional method of artificial nitrogen fixation to produce ammonia is a high-energy intensive centralized process that has caused an imbalance of the N-cycle due to the release of N-species to water. Electrocatalytic nitrate reduction (ENR) to ammonia is a promising N-resource recovery alternative that can enable the circular reuse of ammonia in decentralized settings. However, the primary challenge is identifying selective and affordable electrocatalysts. Identifying electrodes that rely on something other than platinum-group metals is required to surpass barriers associated with using expensive and endangered elements. In this study, an earth-abundant bimetallic catalyst, Cu/Co(OH)x, prepared and optimized by electrodeposition, demonstrates superior ammonia production. Under environmentally relevant conditions of 30 mg NO3--N L-1, Cu/Co(OH)x showed higher ammonia production than pristine Cu foam with 0.7 and 0.3 mmol NH3 gcat-1 h-1, respectively. The experimental evaluation demonstrated direct reduction and catalytic hydrogenation mechanisms in Cu/Co(OH)x sites. Leaching analyses suggest that Cu/Co(OH)x has outstanding stability with negligible metal concentration below the maximum contaminant level for both Cu and Co. These results provide a framework for using earth-abundant materials in ENR with comparable efficiency and energy consumption to platinum-group materials.

Electrocatalytic Conversion of CO2 to Formate at Low Overpotential by Electrolyte Engineering in Model Molecular Catalysis.

An electrolyte engineering strategy was developed for CO2 reduction into formate with a model molecular catalyst, [Rh(bpy)(Cp*)Cl]Cl, by modifying the solvent (organic or aqueous), the proton source (H2 O or acetic acid), and the electrode/solution interface with imidazolium- and pyrrolidinium-based ionic liquids (ILs). Experimental and theoretical density functional theory investigations suggested that π+ -π interactions between the imidazolium-based IL cation and the reduced bipyridine ligand of the catalyst improved the efficiency of the CO2 reduction reaction (CO2 RR) by lowering the overpotential, while granting partial suppression of the hydrogen evolution reaction. This allowed tuning the selectivity towards formate, reaching for this catalyst an unprecedented faradaic efficiency (FEHCOO -) ≥90 % and energy efficiency of 66 % in acetonitrile solution. For the first time, relevant CO2 conversion to formic acid/formate was reached at low overpotential (0.28 V) using a homogeneous catalyst in acidic aqueous solution (pH=3.8). These results open up a new strategy based on electrolyte engineering for enhancing carbon balance in CO2 RR.

Overcoming barriers for nitrate electrochemical reduction: By-passing water hardness.

Water matrix composition impacts water treatment performance. However, matrix composition impacts have rarely been studied for electrochemical water treatment processes, and the correlation between the composition and the treatment efficiency is lacking. This work evaluated the electrochemical reduction of nitrate (ERN) using different complex water matrices: groundwater, brackish water, and reverse osmosis (RO) concentrate/brine. The ERN was conducted using a tin (Sn) cathode because of the high selectivity towards nitrogen evolution reported for Sn electrocatalysts. The co-existence of calcium (Ca2+), magnesium (Mg2+), and carbonate (CO32-) ions in water caused a 4-fold decrease in the nitrate conversion into innocuous nitrogen gas due to inorganic scaling formation on the cathode surface. XRF and XRD analysis of fouled catalyst surfaces detected brucite (Mg(OH)2), calcite (CaCO3), and dolomite (CaMg(CO3)2) mineral scales formed on the cathode surface. Surface scaling created a physical barrier on the electrode that decreased the ERN efficiency. Identifying these main sources of ERN inhibition was key to devising potential fouling mitigation strategies. For this reason, the chemical softening pre-treatment of a real brackish water was conducted and this significantly increased nitrate conversion and faradaic efficiency during subsequent ERN treatment, leading to a lower electric energy consumption per order. Understanding the ionic foulant composition responsible for influencing electrochemically-driven technologies are the first steps that must be taken to move towards niche applications such as decentralized ERN. Thus, we propose either direct ERN implementation in regions facing high nitrate levels in soft waters, or a hybrid softening/nitrate removal system for those regions where high nitrate and high-water hardness appear simultaneously.

Nature of viruses and pandemics: Coronaviruses.

Coronaviruses (CoVs) have the largest genome among RNA viruses and store large amounts of information without genome integration as they replicate in the cell cytoplasm. The replication of the virus is a continuous process, whereas the transcription of the subgenomic mRNAs is a discontinuous one, involving a template switch, which resembles a high frequency recombination mechanism that may favor virus genome variability. The origin of the three deadly human CoVs SARS-CoV, MERS-CoV and SARS-CoV-2 are zoonotic events. SARS-CoV-2 has incorporated in its spike protein a furine proteolytic site that facilitates the activation of the virus in any tissue, making this CoV strain highly polytropic and pathogenic. Using MERS-CoV as a model, a propagation-deficient RNA replicon was generated by removing E protein gene (essential for viral morphogenesis and involved in virulence), and accessory genes 3, 4a, 4b and 5 (responsible for antagonism of the innate immune response) to attenuate the virus: MERS-CoV-Δ[3,4a,4b,5,E]. This RNA replicon is strongly attenuated and elicits sterilizing protection after a single immunization in transgenic mice with the receptor for MERS-CoV, making it a promising vaccine candidate for this virus and an interesting platform for vector-based vaccine development. A strategy could be developed for the design of RNA replicon vaccines for other human pathogenic coronaviruses.

Real-world experience of ocrelizumab in multiple sclerosis in a Spanish population.

OBJECTIVE: Pivotal trial have shown that patients with multiple sclerosis (MS) receiving ocrelizumab had better outcomes. However, data on ocrelizumab in clinical practice are limited. The aim of this study was to evaluate the preliminary safety profile and effectiveness of ocrelizumab treatment for multiple sclerosis (MS) in a real-world clinical setting. METHODS: We conducted a retrospective study including consecutive patients from nine public hospitals in south-eastern Spain who received ocrelizumab after it was approved. RESULTS: A total of 228 MS patients were included (144 with relapsing-remitting MS [RRMS], 25 secondary progressive MS [SPMS], and 59 primary progressive MS [PPMS]). Median follow-up period was 12 months (range, 1-32). No evidence of disease activity (NEDA) status at year 1 was achieved in 91.2% of the relapsing MS (RMS) population, while disability progression was detected in 37.5% of the PPMS patients (median follow-up period, 19 months). The most common adverse events reported were infusion-related reactions and infections, with the most common infections being urinary tract infections followed by upper respiratory infections and COVID-19. INTERPRETATION: The preliminary results in our real-world setting show that ocrelizumab presented excellent results in suppressing disease activity with a favorable and consistent safety profile.

Involvement of N-methylpurine DNA glycosylase in resistance to temozolomide in patient-derived glioma cells.

Chemotherapy for high-grade astrocytic tumors is mainly based on the use of temozolomide (TMZ), whose efficacy is limited by resistance mechanisms. Despite many investigations pointing to O6-methylguanine-DNA-methyltransferase (MGMT) as being responsible for tumor chemo-resistance, its expression does not predict an accurate response in most gliomas, suggesting that MGMT is not the only determinant of response to treatment. In this sense, several reports indicate that N-methylpurine-DNA-glycosylase (MPG) may be involved in that resistance. With that in mind, we evaluated for the first time the degree of resistance to TMZ treatment in 18 patient-derived glioma cells and its association with MGMT and MPG mRNA levels. Viability cell assays showed that TMZ treatment hardly caused growth inhibition in the patient-derived cells, even in high concentrations, indicating that all primary cultures were chemo-resistant. mRNA expression analyses showed that the TMZ-resistant phenotype displayed by cells is associated with an elevated expression of MPG to a greater extent than it is with transcript levels of MGMT. Our findings suggest that not only is MGMT implicated in resistance to TMZ but MPG, the first enzyme in base excision repair processing, is also involved, supporting its potential role as a target in anti-resistance chemotherapy for astrocytoma and glioblastoma.

COVID-19 and multiple sclerosis: A description of two cases on alemtuzumab.

BACKGROUND: Alemtuzumab is a treatment for highly active multiple sclerosis (MS). Immunosuppression is considered a risk factor for SARS-CoV-2 infection and there is still lack of evidence to guide MS practice. METHODS/RESULTS: We describe the clinical and immunological evolution of two MS patients under alemtuzumab treatment who were affected by COVID-19, one of them only one week after receiving her last dose, and both recovered without sequelae. CONCLUSION: In selected patients (young, without comorbidities, and with high activity), MS itself could be more dangerous than COVID-19, so we should consider continuing MS treatment as previously planned, including alemtuzumab.

Scanning electrochemical microscopy screening of CO2 electroreduction activities and product selectivities of catalyst arrays.

The electroreduction of CO2 is one of the most investigated reactions and involves testing a large number and variety of catalysts. The majority of experimental electrocatalysis studies use conventional one-sample-at-a-time methods without providing spatially resolved catalytic activity information. Herein, we present the application of scanning electrochemical microscopy (SECM) for simultaneous screening of different catalysts forming an array. We demonstrate the potential of this method for electrocatalytic assessment of an array consisting of three Sn/SnOx catalysts for CO2 reduction to formate (CO2RF). Simultaneous SECM scans with fast scan (1 V s-1) cyclic voltammetry detection of products (HCOO-, CO and H2) at the Pt ultramicroelectrode tip were performed. We were able to consistently distinguish the electrocatalytic activities of the three compositionally and morphologically different Sn/SnOx catalysts. Further development of this technique for larger catalyst arrays and matrices coupled with machine learning based algorithms could greatly accelerate the CO2 electroreduction catalyst discovery.

Minimum Determinants of Transmissible Gastroenteritis Virus Enteric Tropism Are Located in the N-Terminus of Spike Protein.

Transmissible gastroenteritis virus (TGEV) is an enteric coronavirus causing high morbidity and mortality in porcine herds worldwide, that possesses both enteric and respiratory tropism. The ability to replicate in the enteric tract directly correlates with virulence, as TGEVs with an exclusive respiratory tropism are attenuated. The tissue tropism is determined by spike (S) protein, although the molecular bases for enteric tropism remain to be fully characterized. Both pAPN and sialic acid binding domains (aa 506-655 and 145-155, respectively) are necessary but not sufficient for enteric tract infection. Using a TGEV infectious cDNA and enteric (TGEV-SC11) or respiratory (TGEV-SPTV) isolates, encoding a full-length S protein, a set of chimeric recombinant viruses, with a sequential modification in S protein amino terminus, was engineered. In vivo tropism, either enteric, respiratory or both, was studied by inoculating three-day-old piglets and analyzing viral titers in lung and gut. The data indicated that U655>G change in S gene (S219A in S protein) was required to confer enteric tropism to a respiratory virus that already contains the pAPN and sialic acid binding domains in its S protein. Moreover, an engineered virus containing U655>G and a 6 nt insertion at position 1124 (Y374-T375insND in S protein) was genetically stable after passage in cell cultures, and increased virus titers in gut by 1000-fold. We postulated that the effect of these residues in enteric tropism may be mediated by the modification of both glycosaminoglycan binding and S protein structure.

Recombinant Chimeric Transmissible Gastroenteritis Virus (TGEV) - Porcine Epidemic Diarrhea Virus (PEDV) Virus Provides Protection against Virulent PEDV.

Porcine epidemic diarrhea virus (PEDV) is an enteric coronavirus causing high morbidity and mortality in porcine herds worldwide. Although both inactivated and live attenuated vaccines have been extensively used, the emergence of highly virulent strains and the recurrent outbreaks even in vaccinated farms highlight the need of effective vaccines. Engineering of genetically defined live attenuated vaccines is a rational approach for novel vaccine development. In this line, we engineered an attenuated virus based on the transmissible gastroenteritis virus (TGEV) genome, expressing a chimeric spike protein from a virulent United States (US) PEDV strain. This virus (rTGEV-RS-SPEDV) was attenuated in highly-sensitive five-day-old piglets, as infected animals did not lose weight and none of them died. In addition, the virus caused very minor tissue damage compared with a virulent virus. The rTGEV-RS-SPEDV vaccine candidate was also attenuated in three-week-old animals that were used to evaluate the protection conferred by this virus, compared with the protection induced by infection with a virulent PEDV US strain (PEDV-NVSL). The rTGEV-RS-SPEDV virus protected against challenge with a virulent PEDV strain, reducing challenge virus titers in jejunum and leading to undetectable challenge virus RNA levels in feces. The rTGEV-RS-SPEDV virus induced a humoral immune response specific for PEDV, including neutralizing antibodies. Altogether, the data indicated that rTGEV-RS-SPEDV is a promising vaccine candidate against virulent PEDV infection.

Characterization of LiCoO2 nanoparticle suspensions by single collision events.

Transient electrochemical experiments associated with the collisions between hydrothermally synthesized LiCoO2 (LCO) nanoparticles/aggregates of different sizes and a polarized gold ultramicroelectrode (UME) were used as a new additive-free analytical tool applied to Li ion insertion compounds. The size of the LCO nanoparticles/aggregates, ranging from 75 to 450 nm, the diffusion coefficient of the LCO nanoparticles/aggregates in suspension (∼8 × 10-9 cm2 s-1), and the Li ion diffusion coefficient within crystalline LCO nanoparticles (∼1.3 × 10-11 cm2 s-1) were estimated from single collision events. Interestingly, the charge exchanged during each nanoparticle collision was related to the size of the corresponding LCO aggregate, which enables electrochemical sizing distribution measurement displaying evident concordance with optical techniques, including dynamic light scattering (DLS) and cryo-transmission electron microscopy (cryo-TEM). Studying the nanoparticle collision frequency on the UME surface as a function of the LCO nanoparticle concentration allows estimation of the diffusion coefficient of LCO nanoparticles/aggregates in suspension. Finally, from the current decay observed in chronoamperometry after LCO nanoparticle collision on the polarized UME surface, which corresponds to the LCO oxidation (i.e. the Li+ deinsertion reaction), the Li ion diffusion coefficient within the host crystalline material is estimated. This is a key parameter, which controls the cycle lifetime and charge rate in Li ion battery performance. This new approach thus allows a fine description of the nanoparticle properties, which includes sizing as well as estimation of the Li ion diffusion coefficient within the host crystalline material.

Electrocatalytic studies on imidazolium based ionic liquids: defining experimental conditions.

The number of publications devoted to studying electrochemical reactions in room temperature ionic liquids (RTILs) is constantly growing, but very few of them have been devoted to defining proper experimental conditions to obtain reproducible electrochemical results. In this work, we demonstrate that the combination of a proper RTIL purification treatment and a filtered Ar gas stream allow us to obtain featureless voltammograms in [C4mim][BF4], [C4mim][NTf2], and [C4m2im][NTf2], which otherwise present signals associated with different types of impurities such as water and some minor electroactive impurities acquired during the RTIL synthesis process. Moreover, we demonstrate that bubbling Ar, or another inert gas, through the electrolyte in order to purge O2 dissolved in RTILs is one of the major sources of water and O2 impurities incorporated in RTILs within the electrochemical cell. To overcome this source of water uptake, we have incorporated a gas stream purification filter before the gas reaches the RTIL in the electrochemical cell. To illustrate the effect of these impurities in relevant electrocatalytic studies, we study the electrocatalytic reduction of CO2 on Pt nanoparticles and the key role of an appropiate filter when the CO2 gas stream is bubbled within imidazolium based RTILs. Our cyclic voltammetric studies point out that CO2 electroreduction on Pt nanoparticles only presents activity in [C4mim][NTf2] and [C4m2im][NTf2], thus suggesting that the C-2 position on the imidazolium ring is not the key position in CO2 electrochemical reduction. In contrast, the same Pt nanoparticles are inactive towards CO2 electroreduction in [C4mim][BF4], which is a more hydrophilic RTIL.

Estudio ultrasonográfico del nervio vago como herramienta diagnóstica en el síndrome de Guillain-Barré / Ultrasound study of the vagal nerve as a diagnostic tool in Guillain-Barré syndrome

No disponible

Levels of Participants Satisfaction with Initial Contact and Examination Visit: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

OBJECTIVE: This study examined perceived satisfaction among Hispanic/Latino individuals who participated in a baseline examination for the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a large cohort study of 16,415 adults living in four selected communities. METHOD: An estimated 22% (n= 3,584) of participants completed a questionnaire regarding satisfaction with staff attention, the overall experience during the study examination, and the influence of the informed consent digital video disc (DVD). RESULTS: The majority of participants who completed the questionnaire expressed overall satisfaction with the study. Most participants reported that staff were friendly, courteous and respectful and study test procedures were clearly explained. Participants who preferred to complete the interview in Spanish felt that the informed consent DVD positively influenced their ability to make an informed decision to enroll in the study. Participants who preferred to complete the interview in English tended to report that the baseline examination was longer than expected compared with participants who completed the interview in Spanish. CONCLUSION: Results demonstrate that culturally and linguistically trained staff and the use of the study's informed consent DVD were effective in explaining study procedures and positively influenced decisions to participate in the HCHS/SOL study. These results can inform recruitment and enrollment strategies for future participation of minority groups into longitudinal cohort studies.

Virulence factors in porcine coronaviruses and vaccine design.

Porcine enteric coronaviruses (CoVs) cause severe disease in the porcine herds worldwide, leading to important economic losses. Despite the knowledge of these viruses since the 1970s, vaccination strategies have not been implemented, leading to continuous re-emergence of novel virulent strains. Live attenuated vaccines historically have been the most efficient. We consider that the new trend is the development of recombinant vaccines by using reverse genetics systems to engineer attenuated viruses, which could be used as effective and safe modified live vaccine candidates. To this end, host cell signaling pathways influencing porcine CoV virulence should be identified. Similarly, the identity of viral proteins involved in the modulation of host cell pathways influencing CoV pathogenesis should be analyzed. With this information, and using reverse genetics systems, it is possible to design viruses with modifications in the viral proteins acting as virulence factors, which may lead to attenuated viruses and, therefore, vaccine candidates. In addition, novel antiviral drugs may be developed once the host cell pathways and the molecular mechanism affecting porcine CoV replication and virulence are known. This review is focused in the host cell responses to enteric porcine CoV infection and the viral proteins involved in pathogenesis.

Surface structured platinum electrodes for the electrochemical reduction of carbon dioxide in imidazolium based ionic liquids.

The direct CO2 electrochemical reduction on model platinum single crystal electrodes Pt(hkl) is studied in [C2mim(+)][NTf2(-)], a suitable room temperature ionic liquid (RTIL) medium due to its moderate viscosity, high CO2 solubility and conductivity. Single crystal electrodes represent the most convenient type of surface structured electrodes for studying the impact of RTIL ion adsorption on relevant electrocatalytic reactions, such as surface sensitive electrochemical CO2 reduction. We propose here based on cyclic voltammetry and in situ electrolysis measurements, for the first time, the formation of a stable adduct [C2mimH-CO2(-)] by a radical-radical coupling after the simultaneous reduction of CO2 and [C2mim(+)]. It means between the CO2 radical anion and the radical formed from the reduction of the cation [C2mim(+)] before forming the corresponding electrogenerated carbene. This is confirmed by the voltammetric study of a model imidazolium-2-carboxylate compound formed following the carbene pathway. The formation of that stable adduct [C2mimH-CO2(-)] blocks CO2 reduction after a single electron transfer and inhibits CO2 and imidazolium dimerization reactions. However, the electrochemical reduction of CO2 under those conditions provokes the electrochemical cathodic degradation of the imidazolium based RTIL. This important limitation in CO2 recycling by direct electrochemical reduction is overcome by adding a strong acid, [H(+)][NTf2(-)], into solution. Then, protons become preferentially adsorbed on the electrode surface by displacing the imidazolium cations and inhibiting their electrochemical reduction. This fact allows the surface sensitive electro-synthesis of HCOOH from CO2 reduction in [C2mim(+)][NTf2(-)], with Pt(110) being the most active electrode studied.