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Using density functional theory, we study the influence of hydrostatic pressure on the crystal structure of lanthanide monoxides, focusing on the monoxides formed by the fifteen elements of the lanthanide series, from La to Lu. Calculations are performed using two methods for the ambient pressure B1 (NaCl type) structure, the general gradient approximation (GGA) and the local density approximation (LDA). Through a systematic comparison with existent experimental data, we find that the first method agrees better with the experiments. In addition, considering other cubic structures previously reported for lanthanide monoxides, as B2 (CsCl type) and B3 (ZnS type), we explore the possibility of the occurrence of pressure-induced phase transitions. Based on the better accuracy of GGA to describe the B1 phase at ambient conditions, we exclusively use GGA for the high pressure study. We find, for the fifteen studied compounds, that, at ambient pressure, the B1 structure is the one with the lowest enthalpy, being therefore the most thermodynamically stable structure. We also determine that, at elevated pressures, all the studied compounds undergo a structural phase transition to the B2 phase. We finally establish the relationship between pressure and volume of the unit cell, along with the associated isothermal equation of state, determining the bulk modulus.

BackgroundA biallelic intronic AAGGG repeat expansion in the Replication Factor C subunit 1 (RFC1) gene has been recently associated with Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome, a disorder often presenting as a slowly evolving sensory neuropathy at the onset. “Chronic Idiopathic Axonal Polyneuropathy” (CIAP) is a common indolent axonal neuropathy of adulthood which remains without an identifiable cause despite thorough investigations.MethodsWe screened 234 probands diagnosed with CIAP for a pathogenic biallelic RFC1 AAGGG repeat expansion. Patients were selected from 594 consecutive patients with neuropathy referred to our tertiary-care center for a sural nerve biopsy over 10 years.ResultsThe RFC1 AAGGG repeat expansion was common in patients with pure sensory neuropathy (21/40, 53%) and less frequent in cases with predominantly sensory (10/56, 18%, P < 0.001) or sensorimotor (3/138, 2%, P < 0.001) neuropathy. The mutation was associated with sensory ataxia (τb = 0.254, P < 0.001), autonomic disturbances (35% vs 8%, Prevalence Odds Ratio—POR 6.73 CI 95% 2.79–16.2, P < 0.001), retained deep tendon reflexes (score 18.0/24 vs 11.5/24, R = 0.275, P < 0.001). On pathology, we observed absent/scant regenerative changes (τb = − 0.362, P < 0.001), concomitant involvement of large (100% and 99%, n.s.), small myelinated (97% vs 81%, POR 7.74 CI 95% 1.03–58.4, P = 0.02) and unmyelinated nerve fibers (85% vs 41%, POR 8.52 CI 95% 3.17–22.9, P < 0.001). Cerebellar or vestibular involvement was similarly rare in the two groups.ConclusionsThis study highlights the frequent occurrence of the RFC1 AAGGG repeat expansion in patients diagnosed with CIAP and characterizes the clinical and pathological features of the related neuro(no)pathy.

Anti-myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) recently emerged as a potential biomarker in patients with inflammatory demyelinating diseases of the central nervous system. We here compare the clinical and laboratory findings observed in a cohort of MOG-Ab seropositive and seronegative cases and describe IgG subclass analysis results. Consecutive serum samples referred to Verona University Neuropathology Laboratory for aquaporin-4 (AQP4)-Ab and/or MOG-Ab testing were analysed between March 2014 and May 2017. The presence of AQP4-Ab was determined using a cell-based assay. A live cell immunofluorescence assay was used for the detection of MOG-IgG and IgG subclass analysis. Among 454 analysed samples, 29 were excluded due to AQP4-Ab positivity or to the final demonstration of a disorder not compatible with MOG-Ab. We obtained clinical data in 154 out of 425 cases. Of these, 22 subjects resulted MOG-Ab positive. MOG-Ab positive patients were mainly characterised by the involvement of the optic nerve and/or spinal cord. Half of the cases presented relapses and the recovery was usually partial. Brain MRI was heterogeneous while short lesions were the prevalent observation on spinal cord MRI. MOG-Ab titre usually decreased in non-relapsing cases. In all MOG-IgG positive cases, we observed IgG1 antibodies, which were predominant in most subjects. IgG2 (5/22), IgG3 (9/22) and IgG4 (3/22) antibodies were also detectable. We confirm that MOG-Ab-related syndromes have distinct features in the spectrum of demyelinating conditions, and we describe the possible role of the different IgG subclasses in this condition.

The aim of the present study is to detect the presence of SARS-CoV-2 of patients affected by COVID-19 in olfactory mucosa (OM), sampled with nasal brushing (NB) and biopsy, and to assess whether a non-invasive procedure, such as NB, might be used as a large-scale procedure for demonstrating SARS-CoV-2 presence in olfactory neuroepithelium. Nasal brushings obtained from all the COVID-19 patients resulted positive to SARS-CoV-2 immunocytochemistry while controls were negative. Double immunofluorescence showed that SARS-CoV-2 positive cells included supporting cells as well as olfactory neurons and basal cells. OM biopsies showed an uneven distribution of SARS-CoV-2 positivity along the olfactory neuroepithelium, while OM from controls were negative. SARS-CoV-2 was distinctively found in sustentacular cells, olfactory neurons, and basal cells, supporting what was observed in NB. Ultrastructural analysis of OM biopsies showed SARS-CoV-2 viral particles in the cytoplasm of sustentacular cells. This study shows the presence of SARS-CoV-2 at the level of the olfactory neuroepithelium in patients affected by COVID-19. For the first time, we used NB as a rapid non-invasive tool for assessing a potential neuroinvasion by SARS-CoV-2 infection.

Cognitive impairment (CI) is common in α-synucleinopathies, i.e., Parkinson’s disease, Lewy bodies dementia, and multiple system atrophy. We summarize data from systematic reviews/meta-analyses on neuroimaging, neurophysiology, biofluid and genetic diagnostic/prognostic biomarkers of CI in α-synucleinopathies. Diagnostic biomarkers include atrophy/functional neuroimaging brain changes, abnormal cortical amyloid and tau deposition, and cerebrospinal fluid (CSF) Alzheimer’s disease (AD) biomarkers, cortical rhythm slowing, reduced cortical cholinergic and glutamatergic and increased cortical GABAergic activity, delayed P300 latency, increased plasma homocysteine and cystatin C and decreased vitamin B12 and folate, increased CSF/serum albumin quotient, and serum neurofilament light chain. Prognostic biomarkers include brain regional atrophy, cortical rhythm slowing, CSF amyloid biomarkers, Val66Met polymorphism, and apolipoprotein-E ε2 and ε4 alleles. Some AD/amyloid/tau biomarkers may diagnose/predict CI in α-synucleinopathies, but single, validated diagnostic/prognostic biomarkers lack. Future studies should include large consortia, biobanks, multi-omics approach, artificial intelligence, and machine learning to better reflect the complexity of CI in α-synucleinopathies.

Chronic infection with hepatitis C virus (HCV) is associated with a wide spectrum of extrahepatic manifestations, affecting different organ systems. Neurological complications occur in a large number of patients and range from peripheral neuropathy to cognitive impairment. Pathogenetic mechanisms responsible for nervous system dysfunction are mainly related to the upregulation of the host immune response with production of autoantibodies, immune complexes, and cryoglobulins. Alternative mechanisms include possible extrahepatic replication of HCV in neural tissues and the effects of circulating inflammatory cytokines and chemokines.

The metallic impregnation invented by Camillo Golgi in 1873 has allowed the visualization of individual neurons in their entirety, leading to a breakthrough in the knowledge on the structure of the nervous system. Professor of Histology and of General Pathology, Golgi worked for decades at the University of Pavia, leading a very active laboratory. Unfortunately, most of Golgi's histological preparations are lost. The present contribution provides an account of the original slides on the nervous system from Golgi's laboratory available nowadays at the Golgi Museum and Historical Museum of the University of Pavia. Knowledge on the organization of the nervous tissue at the time of Golgi's observations is recalled. Notes on the equipment of Golgi's laboratory and the methodology Golgi used for his preparations are presented. Images of neurons from his slides (mostly from hippocampus, neocortex and cerebellum) are here shown for the first time together with some of Golgi's drawings. The sections are stained with the Golgi impregnation and Cajal stain. Golgi-impregnated sections are very thick (some more than 150 μm) and require continuous focusing during the microscopic observation. Heterogeneity of neuronal size and shape, free endings of distal dendritic arborizations, axonal branching stand out at the microscopic observation of Golgi-impregnated sections and in Golgi's drawings, and were novel findings at his time. Golgi also pointed out that the axon only originates from cell bodies, representing a constant and distinctive feature of nerve cells which distinguishes them from glia, and subserving transmission at a distance. Dendritic spines can be seen in some cortical neurons, although Golgi, possibly worried about artifacts, did not identify them. The puzzling intricacy of fully impregnated nervous tissue components offered to the first microscopic observations still elicit nowadays the emotion Golgi must have felt looking at his slides.

Co-doped SnO2 nanocrystals (with a particle size of 10 nm) with a tetragonal rutile-type (space group P42/mnm) structure have been investigated for their use in in situ high-pressure synchrotron angle dispersive powder X-ray diffraction up to 20.9 GPa and at an ambient temperature. An analysis of experimental results based on Rietveld refinements suggests that rutile-type Co-doped SnO2 undergoes a structural phase transition at 14.2 GPa to an orthorhombic CaCl2-type phase (space group Pnnm), with no phase coexistence during the phase transition. No further phase transition is observed until 20.9 GPa, which is the highest pressure covered by the experiments. The low-pressure and high-pressure phases are related via a group/subgroup relationship. However, a discontinuous change in the unit-cell volume is detected at the phase transition; thus, the phase transition can be classified as a first-order type. Upon decompression, the transition has been found to be reversible. The results are compared with previous high-pressure studies on doped and un-doped SnO2. The compressibility of different phases will be discussed.

West Nile virus (WNV) is a neurotropic mosquito-borne orthoflavivirus, representing a relevant public health threat. Identification of biomarkers that would predict the course of WNV infection is of interest for the early identification of patients at risk and for supporting decisions on therapeutic interventions. In this study, serum levels of glial fibrillary acidic protein (sGFAP) and neurofilament light chain (sNfL), which are markers of brain tissue damage and inflammation, were analysed in 103 subjects with laboratory-confirmed WNV infection, comprising 13 asymptomatic blood donors, 23 with WN fever (WNF), 50 with encephalitis/meningoencephalitis (E/ME) and 17 with acute flaccid paralysis (AFP). In addition, 55 WNV-negative subjects with fever, encephalitis or healthy asymptomatic were included as controls. Age-adjusted levels of both sNfL and sGFAP were significantly higher in patients with neuroinvasive disease than in those with fever or asymptomatic (both WNV-positive and WNV-negative), suggesting a broad association of these biomarkers with systemic inflammation and brain injury resulting from infection. In WNV patients, the combined analysis of sNfL and sGFAP early after symptom onset allowed discrimination between neuroinvasive disease and fever with 67.2% sensitivity and 91.3% specificity, but not between E/ME and AFP. Furthermore, high levels of sNfL and sGFAP were significantly associated with prolonged hospital stay, intensive care unit admission and the occurrence of death or severe sequelae. Detection of WNV RNA in CSF was associated with increased sGFAP. In conclusion, our study indicates the potential utility of sNfL and sGFAP as biomarkers of WNV disease severity and adverse outcome.