Editors’ Choice—Visualizing the Impact of the Composite Cathode Microstructure and Porosity on Solid-State Battery Performance

The kinetics of composite cathodes for solid-state batteries (SSBs) relies heavily on their microstructure. Spatial distribution of the different phases, porosity, interface areas, and tortuosity factors are important descriptors that need accurate quantification for models to predict the electrochemistry and mechanics of SSBs. In this study, high-resolution focused ion beam-scanning electron microscopy tomography was used to investigate the microstructure of cathodes composed of a nickel-rich cathode active material (NCM) and a thiophosphate-based inorganic solid electrolyte (ISE). The influence of the ISE particle size on the microstructure of the cathode was visualized by 3D reconstruction and charge transport simulation. By comparison of experimentally determined and simulated conductivities of composite cathodes with different ISE particle sizes, the electrode charge transport kinetics is evaluated. Porosity is shown to have a major influence on the cell kinetics and the evaluation of the active mass of electrochemically active particles reveals a higher fraction of connected NCM particles in electrode composites utilizing smaller ISE particles. The results highlight the importance of homogeneous and optimized microstructures for high performance SSBs, securing fast ion and electron transport

Immune-Mediated Thrombotic Thrombocytopenic Purpura Following mRNA-Based COVID-19 Vaccine BNT162b2: Case Report and Mini-Review of the Literature.

Introduction An increasing number of case reports have associated vaccinations against coronavirus disease 2019 (COVID-19) with immune-mediated thrombotic thrombocytopenic purpura (iTTP), a very rare but potentially life-threatening thrombotic microangiopathy, which leads to ischemic organ dysfunction. Thrombus formation in iTTP is related to a severe deficiency of the specific von Willebrand-factor-cleaving protease ADAMTS13 due to ADAMTS13 autoantibodies. Methods We present a case of iTTP following exposure to the mRNA-based COVID-19 vaccine BNT162b2 (Comirnaty®, Pfizer-BioNTech). In addition, we review previously reported cases in the literature and assess current evidence. Results Apart from our case, twenty cases of iTTP occurring after COVID-19 vaccination had been published until the end of November 2021. There were 11 male and 10 female cases; their median age at diagnosis was 50 years (range 14-84 years). Five patients (24%) had a preexisting history of iTTP. Recombinant adenoviral vector-based vaccines were involved in 19%, mRNA-based vaccines in 81%. The median onset of symptoms after vaccination was 12 days (range 5-37), with 20 cases presenting within 30 days. Treatment included therapeutic plasma exchange in all patients. Additional rituximab, caplacizumab, or both these treatments were given in 43% (9/21), 14% (3/21), and 24% (5/21) of cases, respectively. One patient died, despite a prolonged clinical course in one patient, all surviving patients were in clinical remission at the end of the observational period. Conclusion Clinical features of iTTP following COVID-19 vaccination were in line with those of pre-pandemic iTTP. When timely initiated, an excellent response to standard treatment was seen in all cases. ADAMTS13 activity should be determined pre-vaccination in patients with a history of a previous iTTP episode. None of the reported cases met the WHO criteria for assessing an adverse event following immunization (AEFI) as a consistent causal association to immunization. Further surveillance of safety data and additional case-based assessment are needed

White Matter Atrophy and Cognitive Dysfunctions in Neuromyelitis Optica

Neuromyelitis optica (NMO) is an inflammatory disease of central nervous system characterized by optic neuritis and longitudinally extensive acute transverse myelitis. NMO patients have cognitive dysfunctions but other clinical symptoms of brain origin are rare. In the present study, we aimed to investigate cognitive functions and brain volume in NMO. The study population consisted of 28 patients with NMO and 28 healthy control subjects matched for age, sex and educational level. We applied a French translation of the Brief Repeatable Battery (BRB-N) to the NMO patients. Using SIENAx for global brain volume (Grey Matter, GM; White Matter, WM; and whole brain) and VBM for focal brain volume (GM and WM), NMO patients and controls were compared. Voxel-level correlations between diminished brain concentration and cognitive performance for each tests were performed. Focal and global brain volume of NMO patients with and without cognitive impairment were also compared. Fifteen NMO patients (54%) had cognitive impairment with memory, executive function, attention and speed of information processing deficits. Global and focal brain atrophy of WM but not Grey Matter (GM) was found in the NMO patients group. The focal WM atrophy included the optic chiasm, pons, cerebellum, the corpus callosum and parts of the frontal, temporal and parietal lobes, including superior longitudinal fascicle. Visual memory, verbal memory, speed of information processing, short-term memory and executive functions were correlated to focal WM volumes. The comparison of patients with, to patients without cognitive impairment showed a clear decrease of global and focal WM, including brainstem, corticospinal tracts, corpus callosum but also superior and inferior longitudinal fascicles. Cognitive impairment in NMO patients is correlated to the decreased of global and focal WM volume of the brain. Further studies are needed to better understand the precise origin of cognitive impairment in NMO patients, particularly in the WM

Management of biliary obstruction in patients with newly diagnosed alveolar echinococcosis: a Swiss retrospective cohort study

BACKGROUND AND STUDY AIMS: Alveolar echinococcosis, an orphan zoonosis affecting the liver, is of increasing concern worldwide. Most symptomatic cases present at an advanced and inoperable stage, sometimes with biliary obstruction prompting biliary tract interventions. These are, however, associated with a high risk of infectious complications. The aim of this retrospective study was to compare the effectiveness and safety of conservative and interventional treatment approaches in patients with newly diagnosed alveolar echinococcosis and biliary obstruction. PATIENTS AND METHODS: Alveolar echinococcosis patients treated at two referral centres in Switzerland, presenting with hyperbilirubinaemia (total bilirubin >1.5 Upper Limit of Normal) at diagnosis were included, unless another underlying aetiology, i.e. common bile duct stones or decompensated cirrhosis, was identified. Patients were divided into two groups, according to whether they initially received a biliary tract intervention. The primary endpoint was normalisation of bilirubin levels within a 6-month period. Secondary endpoints included, among others, the occurrence of early and late biliary complications, the need for biliary tract interventions during follow-up and overall duration of hospital stays for treatment initiation and for biliary complications. RESULTS: 28 patients were included in this study, of whom 17 received benzimidazole therapy alone and 11 additionally received a biliary tract intervention. Baseline characteristics did not differ between groups. All but one patient in each group achieved the primary endpoint (p=0.747). Biliary tract intervention was associated with faster laboratory improvement (t1/2 1.3 vs 3.0 weeks), but also with more frequent early biliary complications (7/11 vs 1/17, p=0.002) and longer initial hospital stay (18 days vs 7 days, p=0.007). CONCLUSION: Biliary obstruction in patients with newly diagnosed alveolar echinococcosis can be treated effectively with benzimidazole therapy alone. Biliary tract intervention, on the other hand, is associated with a high complication rate and should probably be reserved for patients with insufficient response to benzimidazole therapy

Cerebral venous thrombosis due to vaccine-induced immune thrombotic thrombocytopenia after a second ChAdOx1 nCoV-19 dose.

© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.Cerebral venous thrombosis (CVT) is the most common and severe manifestation of vaccine-induced immune thrombotic thrombocytopenia (VITT), which is a rare side effect of the SARS-CoV-2 vaccine ChAdOx1 nCoV-19 (Vaxzevria, AstraZeneca/Oxford). The absolute risk of VITT and VITT-related CVT is estimated at 20 and 8 per million first doses of ChAdOx1 nCoV-19, respectively. So far, no definite VITT cases occurring after a second ChAdOx1 nCoV-19 vaccine dose have been reported, raising the question of whether VITT only occurs after a first dose. Two pharmacovigilance studies reported cases of thrombosis with thrombocytopenia after a second ChAdOx1 nCoV-19 dose, but because of lack of clinical data, none of these could be classified as VITT. Knowledge on whether VITT can occur after a second ChAdOx1 nCoV-19 dose is relevant for clinicians and policymakers, especially in low- and middle-income countries, which are currently the main users of adenovirus-based vaccines. We used data from the “CVT after SARS-CoV-2 vaccination” registry to identify VITT-related CVT cases occurring after a second ChAdOx1 nCoV-19 dose. Details of this registry have been published. Briefly, this ongoing study collects data on patients with CVT with symptom onset ≤28 days from SARS-CoV-2 vaccination, regardless of the type and dose of vaccine. The study is endorsed by the European Academy of Neurology and the European Stroke Organization. Investigators are instructed to report consecutive cases from their hospitals. The ethical review board of the Academic Medical Centre issued a waiver of formal approval for this observational study. Each center obtained local permission to carry out the study and acquired informed consent for the use of pseudonymized care data according to national law. We used the case definition criteria of the United Kingdom expert hematology panel to classify cases as definite, probable, possible, or unlikely VITT after ChAdOx1 nCoV-19 administration among CVT cases reported until 1 December 2021.This work was supported by The Netherlands Organisation for Health Research and Development (ZonMw, grant number 10430072110005) (J.M.C.) and the Dr. C. J. Vaillant Foundation (J.M.C.).info:eu-repo/semantics/publishedVersio

Biallelic mutations in NBAS cause recurrent acute liver failure with onset in infancy

Acute liver failure (ALF) in infancy and childhood is a life-threatening emergency. Few conditions are known to cause recurrent acute liver failure (RALF), and in about 50% of cases, the underlying molecular cause remains unresolved. Exome sequencing in five unrelated individuals with fever-dependent RALF revealed biallelic mutations in NBAS. Subsequent Sanger sequencing of NBAS in 15 additional unrelated individuals with RALF or ALF identified compound heterozygous mutations in an additional six individuals from five families. Immunoblot analysis of mutant fibroblasts showed reduced protein levels of NBAS and its proposed interaction partner p31, both involved in retrograde transport between endoplasmic reticulum and Golgi. We recommend NBAS analysis in individuals with acute infantile liver failure, especially if triggered by fever

Interventions to prevent youth violence in Latin America: a systematic review

Objectives: This review aims to summarise evidence on the effectiveness of interventions to prevent youth violence in Latin America. Methods: A systematic search on 13 academic databases was conducted to locate studies evaluating a primary or secondary prevention intervention in Latin America. Studies could use any type of quantitative design to assess outcomes related to youth violence. A search of websites, references and citation searching was also carried out. The quality of each study was assessed. Results: Nine studies were identified. Most documented positive effects of the interventions on the perception of youth violence present in the community/school. Evidence was found of a reduction in homicides and juvenile crimes in three studies, two of which evaluated a community-based intervention. There were mixed results for the self-report of participation on violent acts. The majority of the studies lacked of a rigorous design. Conclusions: Most of the interventions had some promising results, including the reduction of homicides within communities. Community-based programmes were the most consistent regarding an effectiveness to prevent violence. However, the evidence for Latin America is still scarce and relies on non-rigorously designed studies

Amygdala inputs to prefrontal cortex guide behavior amid conflicting cues of reward and punishment

Orchestrating appropriate behavioral responses in the face of competing signals that predict either rewards or threats in the environment is crucial for survival. The basolateral nucleus of the amygdala (BLA) and prelimbic (PL) medial prefrontal cortex have been implicated in reward-seeking and fear-related responses, but how information flows between these reciprocally connected structures to coordinate behavior is unknown. We recorded neuronal activity from the BLA and PL while rats performed a task wherein competing shock- and sucrose-predictive cues were simultaneously presented. The correlated firing primarily displayed a BLA→PL directionality during the shock-associated cue. Furthermore, BLA neurons optogenetically identified as projecting to PL more accurately predicted behavioral responses during competition than unidentified BLA neurons. Finally photostimulation of the BLA→PL projection increased freezing, whereas both chemogenetic and optogenetic inhibition reduced freezing. Therefore, the BLA→PL circuit is critical in governing the selection of behavioral responses in the face of competing signals.National Institutes of Health (U.S.) (Award 1R25-MH092912-01)National Institute of Mental Health (U.S.) (Grant R01- MH102441-01)National Institutes of Health (U.S.) (Award DP2- DK-102256-01

Secretome Analysis of Mesenchymal Stem Cell Factors Fostering Oligodendroglial Differentiation of Neural Stem Cells In Vivo

Mesenchymal stem cell (MSC)-secreted factors have been shown to significantly promote oligodendrogenesis from cultured primary adult neural stem cells (aNSCs) and oligodendroglial precursor cells (OPCs). Revealing underlying mechanisms of how aNSCs can be fostered to differentiate into a specific cell lineage could provide important insights for the establishment of novel neuroregenerative treatment approaches aiming at myelin repair. However, the nature of MSC-derived differentiation and maturation factors acting on the oligodendroglial lineage has not been identified thus far. In addition to missing information on active ingredients, the degree to which MSC-dependent lineage instruction is functional in vivo also remains to be established. We here demonstrate that MSC-derived factors can indeed stimulate oligodendrogenesis and myelin sheath generation of aNSCs transplanted into different rodent central nervous system (CNS) regions, and furthermore, we provide insights into the underlying mechanism on the basis of a comparative mass spectrometry secretome analysis. We identified a number of secreted proteins known to act on oligodendroglia lineage differentiation. Among them, the tissue inhibitor of metalloproteinase type 1 (TIMP-1) was revealed to be an active component of the MSC-conditioned medium, thus validating our chosen secretome approach