Persisting SARS-CoV-2 viraemia after rituximab therapy: two cases with fatal outcome and a review of the literature

SARS-CoV-2 infection can cause severe pneumonia (COVID-19). There is evidence that patients with comorbidities are at higher risk of a severe disease course. The role of immunosuppression in the disease course is not clear. In the present report, we first describe two cases of persisting SARS-CoV-2 viraemia with fatal outcome in patients after rituximab therapy.     

Enhanced cognitive flexibility in reversal learning induced by removal of the extracellular matrix in auditory cortex

During brain maturation, the occurrence of the extracellular matrix (ECM) terminates juvenile plasticity by mediating structural stability. Interestingly, enzymatic removal of the ECM restores juvenile forms of plasticity, as for instance demonstrated by topographical reconnectivity in sensory pathways. However, to which degree the mature ECM is a compromise between stability and flexibility in the adult brain impacting synaptic plasticity as a fundamental basis for learning, lifelong memory formation, and higher cognitive functions is largely unknown. In this study, we removed the ECM in the auditory cortex of adult Mongolian gerbils during specific phases of cortex-dependent auditory relearning, which was induced by the contingency reversal of a frequency-modulated tone discrimination, a task requiring high behavioral flexibility. We found that ECM removal promoted a significant increase in relearning performance, without erasing already established—that is, learned—capacities when continuing discrimination training. The cognitive flexibility required for reversal learning of previously acquired behavioral habits, commonly understood to mainly rely on frontostriatal circuits, was enhanced by promoting synaptic plasticity via ECM removal within the sensory cortex. Our findings further suggest experimental modulation of the cortical ECM as a tool to open short-term windows of enhanced activity-dependent reorganization allowing for guided neuroplasticity.Structural remodeling and stabilization of synaptic networks are key mechanisms underlying learning in the adult brain. During early life, high structural and functional plasticity is required for the experience-shaped development of basic neuronal circuits (1). With brain maturation, juvenile plasticity of so-called critical or sensitive periods is decreased and is accompanied by the appearance of the brain’s extracellular matrix (ECM) and its specialized compact form named “perineuronal net” (PNN) enwrappping cell bodies and synaptic contacts (2, 3). Enzymatic degradation of the ECM in adult animals has been demonstrated to restore such forms of developmental (juvenile) plasticity with respect to topographical map plasticity in the visual cortex (4), fear-response–mediating circuits in the amygdala (5), spinal cord injuries (6, 7), and song learning circuits of zebra finches (8). In addition, enzymatic ECM removal altered several forms of synaptic plasticity in vitro and in vivo (9–12). However, even though structural stability of networks acquired during developmental phases is essential for neuronal efficiency, mechanisms allowing synaptic remodeling are key events during learning and memory formation throughout life (13). We recently demonstrated that endogenous proteases moderately digesting specific components of the ECM are regulated in an activity-dependent manner (2, 14) and ECM removal modulates synaptic short-term plasticity by synaptic exchange of postsynaptic glutamate receptors (10, 15). Further, ECM modulation enhances synaptic short-term plasticity by affecting voltage-dependent calcium channels (9). These findings challenge the view of the purely stabilizing role of ECM in the brain and indicate a potential regulatory switch for plastic network adaptations within the adult brain at the level of individual synapses by modulating the extracellular space (16). However, it remains open to what extent ECM modulations influence learning-related plasticity in the adult brain and its specific effects on behavior during a cognitive task.In the present study, we aimed at evaluating the potential role of experimental ECM removal within the auditory cortex (ACx) of Mongolian gerbils, which has been found to be particularly rich in ECM (17), during a cognitively demanding auditory go/no go shuttle-box task. We selected discrimination and reversal learning of frequency-modulated (FM) tones as a cognitive task, which necessarily requires ACx plasticity (18, 19). Injections of the ECM-degrading enzyme hyaluronidase (HYase) into the ACx after the first acquisition phase significantly enhanced subsequent reversal learning compared with sham-treated animals (injection of 0.9% saline). Particularly, after ECM degradation, animals abandoned the inappropriate discrimination strategy from the initial acquisition phase faster and thus promoted successful discrimination performance of the new contingency during reversal learning. ECM removal did not further influence the initial acquisition learning or interfere with already established—that is, learned—capacities in later learning stages, suggesting an enhanced activity-dependent neuroplastic reorganization of established synaptic networks in ACx during reversal learning.Our findings suggest that experimental degradation of the ECM in sensory cortex, although not affecting general sensory learning, does, however, enhance the cognitive flexibility that can build on the learned behaviors. Thereby, ECM degradation could be used as a tool for guided neuroplasticity, which might also bear therapeutic potential.     

Correction to: Internal and marginal adaptation of high-viscosity bulk-fill composites in class II cavities placed with different adhesive strategies

Odontology - The aim of this study was to evaluate internal and marginal adaptation of high-viscosity bulk-fill composites to enamel and dentin with a self-etch (SE) and an etch-and-rinse...     

A graphene-based hybrid material with quantum bits prepared by the double Langmuir–Schaefer method

The scalability and stability of molecular qubits deposited on surfaces is a crucial step for incorporating them into upcoming electronic devices. Herein, we report on the preparation and characterisation of a molecular quantum bit, copper(ii)dibenzoylmethane [Cu(dbm)₂], deposited by a modified Langmuir–Schaefer (LS) technique onto a graphene-based substrate. A double LS deposition was used for the preparation of a few-layer-graphene (FLG) on a Si/SiO₂ substrate with subsequent deposition of the molecules. Magnetic properties were probed by high-frequency electron spin resonance (HF-ESR) spectroscopy and found maintained after deposition. Additional spectroscopic and imaging techniques, such as Raman spectroscopy (RS), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and scanning electron microscopy (SEM) were performed to characterise the deposited sample. Our approach demonstrated the possibility to utilise a controlled wet-chemistry protocol to prepare an array of potential quantum bits on a disordered graphene-based substrate. The deployed spectroscopic techniques showed unambiguously the robustness of our studied system with a potential to fabricate large-scale, intact, and stable quantum bits.

Graphene-based hybrid material with array of copper(ii)-based quantum bits was prepared by a wet-chemistry protocol and characterised by HF-ESR, XPS, Raman, and AFM.     

Training Paraprofessionals to Improve Socialization in Students with ASD

An important line of research relates to whether school personnel, such as paraprofessionals, who are present during unstructured social periods, such as lunch-recess, could successfully implement interventions to improve socialization between students with ASD and their typical peers in a group setting. Therefore, within the context of a multiple baseline across participants design, we assessed whether training paraprofessionals to provide social interventions would enhance social development in students with ASD in a group setting. Results showed that paraprofessionals who were not providing any social opportunities during baseline were able to meet fidelity of implementation following a brief training. Consequently, the children with ASD increased their levels of engagement and rates of initiation with typically developing peers following intervention. Implications for training paraprofessionals to implement effective social interventions for students with ASD are discussed.     

Three-Dimensional Reconstruction of the Genial Spinal Canal

The aim of this anatomical study was to investigate the genial spinal canal histologically and to reconstruct it three-dimensionally to improve understanding of its anatomy and to reveal any differences between dentate and edentulous specimens. Two tissue blocks from the mandible between the left and right second incisors, one dentate and one edentulous, were fixed in 4.5% formaldehyde, decalcified and embedded in paraffin. Serial histological sections were prepared, stained with Azan and examined microscopically. Additionally, three-dimensional models of the blocks were reconstructed using microphotographs of the sections. The genial spinal canal in the dentate specimen contained a neurovascular bundle, which branched into a nerve innervating the incisor and a neurovascular bundle, whereas that in the edentulous specimen contained some nerves for vestibular gingival innervation and a vascular bundle. The results suggest differences in the genial spinal canal between dentate and edentulous mandibles. Further research is needed to confirm this finding. Clin. Anat., 33:1102–1108, 2020. © 2019 Wiley Periodicals, Inc.     

Safety and Immunogenicity of a Vero Cell Culture-Derived Whole-Virus H5N1 Influenza Vaccine in Chronically Ill and Immunocompromised Patients

The development of vaccines against H5N1 influenza A viruses is a cornerstone of pandemic preparedness. Clinical trials of H5N1 vaccines have been undertaken in healthy subjects, but studies in risk groups have been lacking. In this study, the immunogenicity and safety of a nonadjuvanted cell culture-derived whole-virus H5N1 vaccine were assessed in chronically ill and immunocompromised adults. Subjects received two priming immunizations with a clade 1 A/Vietnam H5N1 influenza vaccine, and a subset also received a booster immunization with a clade 2.1 A/Indonesia H5N1 vaccine 12 to 24 months later. The antibody responses in the two populations were assessed by virus neutralization and single radial hemolysis assays. The T-cell responses in a subset of immunocompromised patients were assessed by enzyme-linked immunosorbent spot assay (ELISPOT). The priming and the booster vaccinations were safe and well tolerated in the two risk populations, and adverse reactions were predominantly mild and transient. The priming immunizations induced neutralizing antibody titers of ≥1:20 against the A/Vietnam strain in 64.2% of the chronically ill and 41.5% of the immunocompromised subjects. After the booster vaccination, neutralizing antibody titers of ≥1:20 against the A/Vietnam and A/Indonesia strains were achieved in 77.5% and 70.8%, respectively, of chronically ill subjects and in 71.6% and 67.5%, respectively, of immunocompromised subjects. The T-cell responses against the two H5N1 strains increased significantly over the baseline values. Substantial heterosubtypic T-cell responses were elicited against the 2009 pandemic H1N1 virus and seasonal A(H1N1), A(H3N2), and B subtypes. There was a significant correlation between T-cell responses and neutralizing antibody titers. These data indicate that nonadjuvanted whole-virus cell culture-derived H5N1 influenza vaccines are suitable for immunizing chronically ill and immunocompromised populations. (This study is registered at ClinicalTrials.gov under registration no. {"type":"clinical-trial","attrs":{"text":"NCT00711295","term_id":"NCT00711295"}}NCT00711295.)