Neurodegeneration-associated proteins in human olfactory neurons collected by nasal brushing

The olfactory neuroepithelium is located in the upper vault of the nasal cavity, lying on the olfactory cleft and projecting into the dorsal portion of the superior and middle turbinates beyond the mid-portion of the nasal septum. It is composed of a variety of cell types including olfactory sensory neurons, supporting glial-like cells, microvillar cells, and basal stem cells. The cells of the neuroepithelium are often intermingled with respiratory and metaplastic epithelial cells. Olfactory neurons undergo a constant self-renewal in the timespan of 2\u20133 months; they are directly exposed to the external environment, and thus they are vulnerable to physical and chemical injuries. The latter might induce metabolic perturbations and ultimately be the cause of cell death. However, the lifespan of olfactory neurons is biologically programmed, and for this reason, these cells have an accelerated metabolic cycle leading to an irreversible apoptosis. These characteristics make these cells suitable for research related to nerve cell degeneration and aging. Recent studies have shown that a non-invasive and painless olfactory brushing procedure allows an efficient sampling from the olfactory neuroepithelium. This approach allows to detect the pathologic prion protein in patients with sporadic Creutzfeldt\u2013Jakob disease, using the real-time quaking-induced conversion assay. Investigating the expression of all the proteins associated to neurodegeneration in the cells of the olfactory mucosa is a novel approach toward understanding the pathogenesis of human neurodegenerative diseases. Our aim was to investigate the expression of \u3b1-synuclein, \u3b2-amyloid, tau, and TDP-43 in the olfactory neurons of normal subjects. We showed that these proteins that are involved in neurodegenerative diseases are expressed in olfactory neurons. These findings raise the question on whether a relationship exists between the mechanisms of protein aggregation that occur in the olfactory bulb during the early stage of the neurodegenerative process and the protein misfolding occurring in the olfactory neuroepithelium

Post-traumatic taste disorders: presentation of three meaningful cases

Since the late 1800s there are reports of post-traumatic anosmia [1], but few studies investigated post-traumatic gustatory deficit and adopted validated evaluation tests [2,3,4,5,6,7]. Post-traumatic ageusia is rare, occurring in ~ 0.5% of head traumas, while a gustatory deficit is more frequently referred (5-7%) when olfaction is impaired [2,4]. Unlike olfaction, gustatory sensation is mediated by several cranial nerves (VII, IX, X) and taste receptors are widely spread in the oral cavity, so that taste is considered a “robust” sense. Peripheral and/or central mechanisms may be involved in the genesis of post-traumatic gustatory dysfunction. Beyond a reduction/loss of gustatory function following a trauma, taste changes (dysgeusia) may occur, even if they are reported to be rare [7,8,9]. Gustatory disorders might not be immediately reported because patient often pays attention to other post-traumatic sequelae. Especially when persistent, taste deficits might be particularly relevant for patients’ quality of life. Physicians are often not well-informed on the possible implications or treatment strategies. Fifty-three consecutive patients with previous head trauma and chemosensory disorders were recruited by the olfactory and taste research group of the University of Verona. Every patient underwent a careful clinical examination, olfactory and gustatory testing by Sniffin’Sticks Extended test, Whole Mouth taste test and Taste Strips Test respectively (Burghart, Germany). Among them, we found 10 cases with hyposmia, 43 with functional anosmia, while 10 cases showed taste deficits (dysgeusia: n = 3, dysgeusia with hypogeusia: n = 1, hypogeusia: n = 5, ageusia: n = 1). Here we report anatomical, clinical correlations and detailed description of three cases representing central and peripheral injury patterns

Evaluation of liquefaction potential in an intermountain Quaternary lacustrine basin (Fucino basin, central Italy)

In this study, we analyse the susceptibility to liquefaction of the Pozzone site, which is located on the northern side of the Fucino lacustrine basin in central Italy. In 1915, this region was struck by a M 7.0 earthquake, which produced widespread coseismic surface effects that were interpreted to be liquefaction-related. However, the interpretation of these phenomena at the Pozzone site is not straightforward. Furthermore, the site is characterized by an abundance of fine-grained sediments, which are not typically found in liquefiable soils. Therefore, in this study, we perform a number of detailed stratigraphic and geotechnical investigations (including continuous-coring borehole, CPTu, SDMT, SPT, and geotechnical laboratory tests) to better interpret these 1915 phenomena and to evaluate the liquefaction potential of a lacustrine environment dominated by fine-grained sedimentation. The upper 18.5 m of the stratigraphic succession comprises fine-grained sediments, including four strata of coarser sediments formed by interbedded layers of sand, silty sand and sandy silt. These strata, which are interpreted to represent the frontal lobes of an alluvial fan system within a lacustrine succession, are highly susceptible to liquefaction. We also find evidence of paleo-liquefaction, dated between 12.1–10.8 and 9.43–9.13 kyrs ago, occurring at depths of 2.1–2.3 m. These data, along with the aforementioned geotechnical analyses, indicate that this site would indeed be liquefiable in a 1915-like earthquake. Although we found a broad agreement among CPTu, DMT and shear wave velocity ‘‘simplified procedures’’ in detecting the liquefaction potential of the Pozzone soil, our results suggest that the use and comparison of different in situ techniques are highly recommended for reliable estimates of the cyclic liquefaction resistance in lacustrine sites characterized by high content of fine-grained soils. In geologic environments similar to the one analysed in this work, where it is difficult to detect liquefiable layers, one can identify sites that are susceptible to liquefaction only by using detailed stratigraphic reconstructions, in situ characterization, and laboratory analyses. This has implications for basic (Level 1) seismic microzonation mapping, which typically relies on the use of empirical evaluations based on geologic maps and pre-existing sub-surface data (i.e., age and type of deposits, prevailing grain size, with particular attention paid to clean sands, and depth of the water table).Published91-1115T. Sismologia, geofisica e geologia per l'ingegneria sismicaJCR Journa

West Nile virus transmission. results from the integrated surveillance system in Italy, 2008 to 2015

IIn Italy a national Plan for the surveillance of imported and autochthonous human vector-borne diseases (chikungunya, dengue, Zika virus disease and West Nile virus (WNV) disease) that integrates human and veterinary (animals and vectors) surveillance, is issued and revised annually according with the observed epidemiological changes. Here we describe results of the WNV integrated veterinary and human surveillance systems in Italy from 2008 to 2015. A real time data exchange protocol is in place between the surveillance systems to rapidly identify occurrence of human and animal cases and to define and update the map of affected areas i.e. provinces during the vector activity period from June to October. WNV continues to cause severe illnesses in Italy during every transmission season, albeit cases are sporadic and the epidemiology varies by virus lineage and geographic area. The integration of surveillance activities and a multidisciplinary approach made it possible and have been fundamental in supporting implementation of and/or strengthening preventive measures aimed at reducing the risk of transmission of WNV trough blood, tissues and organ donation and to implementing further measures for vector control

Clinical and genetic characteristics of late-onset Huntington's disease in a large European cohort

Background and purpose Huntington's disease (HD) is an autosomal dominant condition caused by CAG-triplet repeat expansions. CAG-triplet repeat expansion is inversely correlated with age of onset in HD and largely determines the clinical features. The aim of this study was to examine the phenotypic and genotypic correlates of late-onset HD (LoHD) and to determine whether LoHD is a more benign expression of HD. Methods This was a retrospective observational study of 5053 White European HD patients from the ENROLL-HD database. Sociodemographic, genetic and phenotypic variables at baseline evaluation of subjects with LoHD, common-onset HD (CoHD) and young-onset HD (YoHD) were compared. LoHD subjects were compared with healthy subjects (HS) aged >= 60 years. Differences between the CoHD and LoHD groups were also explored in subjects with 41 CAG triplets, a repeat number in the lower pathological expansion range associated with wide variability in age at onset. Results Late-onset HD presented predominantly as motor-onset disease, with a lower prevalence of both psychiatric history and current symptomatology. Absent/unknown HD family history was significantly more common in the LoHD group (31.2%) than in the other groups. The LoHD group had more severe motor and cognitive deficits than the HS group. Subjects with LoHD and CoHD with 41 triplets in the larger allele were comparable with regard to cognitive impairment, but those with LoHD had more severe motor disorders, less problematic behaviors and more often an unknown HD family history. Conclusions It is likely that cognitive disorders and motor symptoms of LoHD are at least partly age-related and not a direct expression of the disease. In addition to CAG-triplet repeat expansion, future studies should investigate the role of other genetic and environmental factors in determining age of onset

Detection of TDP-43 seeding activity in the olfactory mucosa from patients with frontotemporal dementia

Introduction: We assessed TAR DNA-binding protein 43 (TDP-43) seeding activity and aggregates detection in olfactory mucosa of patients with frontotemporal lobar degeneration with TDP-43-immunoreactive pathology (FTLD-TDP) by TDP-43 seeding amplification assay (TDP43-SAA) and immunocytochemical analysis. Methods: The TDP43-SAA was optimized using frontal cortex samples from 16 post mortem cases with FTLD-TDP, FTLD with tau inclusions, and controls. Subsequently, olfactory mucosa samples were collected from 17 patients with FTLD-TDP, 15 healthy controls, and three patients carrying MAPT variants. Results: TDP43-SAA discriminated with 100% accuracy post mortem cases presenting or lacking TDP-43 neuropathology. TDP-43 seeding activity was detectable in the olfactory mucosa, and 82.4% of patients with FTLD-TDP tested positive, whereas 86.7% of controls tested negative (P < 0.001). Two out of three patients with MAPT mutations tested negative. In TDP43-SAA positive samples, cytoplasmatic deposits of phosphorylated TDP-43 in the olfactory neural cells were detected. Discussion: TDP-43 aggregates can be detectable in olfactory mucosa, suggesting that TDP43-SAA might be useful for identifying and monitoring FTLD-TDP in living patients