1,721,022 research outputs found
Fabbricazione di nuove strutture ibrida nel contesto Intrustria 4.0: comprensione della fisica e sviluppo del processo
No full textHereditary spastic paraplegia: Novel mutations and expansion of the phenotype variability in SPG56
No full textWe describe a novel sporadic case of SPG56, a rare complicated form of HSP, that expands the clinical and molecular spectrum of the disease, being associated to novel mutations in CYP2U1 and showing as novel feature dorsal hydromyelia at spinal cord MRI. The patient presented an early-onset, slowly progressive paraparesis associated with mild mental retardation. Neurological assessments included the Spastic Paraplegia Rating Scale (SPRS), Mental Deterioration Battery (MDB), and Wechsler Adult Intelligence Scale (WAIS), neurophysiological and neuroimaging studies. Targeted next-generation sequencing panels for the whole set of genes associated with HSP were performed in the probands and her relatives. Neuroimaging studies showed dorsal hydromyelia but no brain MRI abnormalities. Targeted next-generation identified two novel mutations: the c.5C > A/p.S2∗on the maternal allele in compound heterozygosity with the paternally-inherited c.1288+5G > C in CYP2U1. Both mutations predict early protein truncation and a loss of function. So far, only few SPG56 cases have been reported. This case, expands and further characterize the clinical and molecular spectrum of SPG56. In this regard, in consideration of the putative gene function in neurodevelopment, we suggest a causal association between CYP2U1 mutations and hydromyelia in our patient
Creutzfeldt-Jakob disease in a man surviving COVID-19. Disentangling a casual or causal association by neuropathology
No full textAbstract
Background Literature reporting the onset of Creutzfeldt-Jakob disease (CJD) immediately after COVID-19 infection has
strengthened a possible causal link between infection and neurodegeneration. Here, we report a novel case undergoing
detailed neuropathological assessment.
Case report Two months after he had contracted SARS-CoV-2 infection, a 54-year-old man manifested a subacute onset of ataxia, headache, anosmia, and hallucinations, followed by rapidly progressive cognitive decline.
Electroencephalography documented unspecific slowing with periodic polyphasic delta waves. Brain MRI showed
hyperintensities of basal ganglia and thalami on DWI/FLAIR. CSF tested positive for the 14-3-3 protein, and prion
seeding activity was demonstrated by the real-time quaking-induced conversion assay. The patient died 2 months
after the neurologic onset. The neuropathological examination confirmed the diagnosis of CJD and ruled out COVID19-related encephalitis.
Discussion To disentangle the link between COVID-19 infection and CJD, neuropathology is essential determining the
extent of changes related to both conditions. In our patient, we did not fnd any specifc abnormality related to COVID-19.
Our conclusion is in line with the current worldwide epidemiological data that do not show an increase in CJD cases since
the beginning of the COVID-19 pandemi
Nuclear Factor Erythroid 2-Related Factor 2 Activation Might Mitigate Clinical Symptoms in Friedreich’s Ataxia: Clues of an “Out-Brain Origin” of the Disease From a Family Study
Full text linkFriedreich’s ataxia (FRDA) is the most frequent autosomal recessive ataxia in western
countries, with a mean age of onset at 10–15 years. Patients manifest progressive
cerebellar and sensory ataxia, dysarthria, lower limb pyramidal weakness, and other
systemic manifestations. Previously, we described a family displaying two expanded
GAA alleles not only in the proband affected by late-onset FRDA but also in the two
asymptomatic family members: the mother and the younger sister. Both of them showed
a significant reduction of frataxin levels, without any disease manifestation. Here, we
analyzed if a protective mechanism might contribute to modulate the phenotype in this
family. We particularly focused on the transcription factor nuclear factor erythroid 2-
related factor 2 (NRF2), the first line of antioxidant defense in cells, and on the glutathione
(GSH) system, an index of reactive oxygen species (ROS) detoxification ability. Our
findings show a great reactivity of the GSH system to the frataxin deficiency, particularly
in the asymptomatic mother, where the genes of GSH synthesis [glutamate–cysteine
ligase (GCL)] and GSSG detoxification [GSH S-reductase (GSR)] were highly responsive.
The GSR was activated even in the asymptomatic sister and in the proband, reflecting
the need of buffering the GSSG increase. Furthermore, and contrasting the NRF2
expression documented in FRDA tissues, NRF2 was highly activated in the mother and
in the younger sister, while it was constitutively low in the proband. This suggests that,
also under frataxin depletion, the endogenous stimulation of NRF2 in asymptomatic
FRDA subjects may contribute to protect against the progressive oxidative damage,
helping to prevent the onset of neurological symptoms and highlighting an “out-brain
origin” of the disease
Creutzfeldt–Jakob Disease Associated with E200K Mutation and SARS-CoV-2 Infection: Pure Coincidence or Neurodegenerative Acceleration?
No full textSeveral recent studies reported on some patients developing Creutzfeldt–Jakob disease (CJD) following coronavirus disease 2019, but, to the best of our knowledge, this case is the first reported in Italy on an onset of a CJD genetic form (gCJD) immediately after COVID-19 infection. We present a 51-year-old woman with a positive family history for CJD, who, two months after a mild SARS-CoV-2 infection, presented a rapidly progressing dementia diagnosed as CJD through clinical features, imaging, electroencephalography, and cerebrospinal fluid analysis. Genetic testing revealed the E200K mutation (p.Glu200Lys) c.598G>A, with homozygosity for methionine (MET) at codon 129, thus confirming the diagnosis of Creutzfeldt–Jakob disease. She passed away two months later. Interestingly, our case confirms that homozygous E200K gCJD patients are characterized by a relatively younger age of onset; moreover, it also sheds light on the neurodegeneration underlying both prion diseases and COVID-19 infection. In our opinion, the rising global prevalence of neurodegenerative complications following COVID-19 disease adds urgency to the study of this potential relationship, mostly in elderly patients who may experience worse long-lasting outcomes systemically and within the nervous system
Reader response: High frequency of gastrointestinal manifestations in myotonic dystrophy type 1 and type 2
No full textInvestigating Fracture Behavior in Titanium Aluminides: Surface Roughness as an Indicator of Fracture Mechanisms in Ti-48Al-2Cr-2Nb Alloys
No full textTitanium aluminides, particularly the Ti-48Al-2Cr-2Nb alloy, have drawn significant attention for their potential in high-temperature aerospace and automotive applications due to their exceptional performances and reduced density compared to nickel-based superalloys. However, their intermetallic nature poses challenges such as limited room-temperature ductility and fracture toughness, limiting their widespread application. Additive manufacturing, specifically Electron Beam Melting (EBM), has emerged as a promising method for producing complex-shaped components of titanium aluminides, overcoming challenges associated with conventional production methods. This work investigates the fracture behavior of Ti-48Al-2Cr-2Nb specimens with different microstructures, including duplex and equiaxed, under tensile and high-cycle fatigue at elevated temperatures. Fracture surfaces were analyzed to distinguish between static and dynamic fracture modes. A novel method, employing confocal microscopy acquisitions, is proposed to correlate surface roughness parameters with the causes of failure, offering new insights into the fracture mechanisms of titanium aluminides. The results reveal significant differences in roughness values between the propagation and fracture zones for all the temperatures and microstructure tested. At 650 °C, the crack propagation zone exhibits lower Sq values than the fracture zone, with the fracture zone showing more pronounced roughness, particularly for the equiaxed microstructure. However, at 760 °C, the difference in Sq values between the propagation and fracture zones becomes more pronounced, with a more substantial increase in Sq values in the fracture zone. These findings contribute to understanding fracture behavior in titanium aluminides and provide a predictive framework for assessing structural integrity based on surface characteristics
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Investigating the Feasibility of Metallizing Reprocessable Vitrimeric Components through Cold Spray Technique
Full text linkEpoxy vitrimers, distinguished by their unique combination of the mechanical strength typical of thermosets with the reprocessability of thermoplastics, represent a promising class of materials for advanced technological applications. To optimize their performance in high-demand environments, surface functionalization of vitrimers and vitrimeric composites is crucial to enhance their durability and reliability in harsh conditions. This research work aims at studying the feasibility of metallising vitrimer-based components through cold spray technology. Aluminium coatings were applied under varying process parameters, inlet gas temperature (T = 150 –450 °C) and standoff distance (SoD = 70 mm–100 mm), to evaluate their impact on deposition quality and substrate behaviour. The deposition processes were performed on non-reinforced vitrimeric substrates as well as on vitrimeric matrix substrates reinforced with carbon fibre fabric. The results suggest that successful metallization occurs when the substrate temperature exceeds the topology freezing transition temperature (Tv ≈ 170 °C), enabling the ductile behaviour necessary for effective adhesion. At T = 300 °C and SoD = 100 mm, pure vitrimer coatings exhibited an average thickness of 50 ± 10 μm with minimal substrate deformation (grooves < 4% of panel thickness), while lower temperatures (T = 150 °C) resulted in brittle fracture and poor adhesion. Surface roughness increased from Sa = 0.15 ± 0.05 μm for uncoated substrates to Sa = 6.59 μm after coating. In contrast, composite substrates demonstrated enhanced stability due to fibre reinforcement, which constrained excessive substrate flow. At the best process conditions (T = 300 °C and SoD = 100 mm), composite panels achieved homogeneous coatings with Sa = 4.513 μm. However, excessive temperatures (T = 450 °C) led to substrate erosion and fibre damage in both pure vitrimer and composite panels
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