Search

Background: The prevalence of hepatitis C virus infection increases with advancing age, but elderly hepatitis C virus patients remain an understudied population. Aim: To define the virological, epidemiological and clinical profiles of Italian outpatients aged 65 years and over infected by hepatitis C virus. Methods: We evaluated 1544 anti-hepatitis C virus positive patients aged >=65 years referred to 34 Italian outpatient specialty clinics over a two-year period. Results: The study population included 1134 (73%) early elderly (65-74 years) and 410 (27%) late elderly patients (>=75 years). Late elderly subjects were less likely to have their virus genotyped, their viral load assessed or a histological evaluation of liver disease. Overall, 30% of patients had advanced liver disease whose prevalence increased with increasing age. In both age groups, about 40% of patients had normal transaminase levels. Excluding patients with past infection, 51% had not received any antiviral treatment and only 25% were treated after the age of 65. Late elderly patients, women and patients with advanced liver diseases had been less frequently treated. The main reason for exclusion from treatment was age followed by the presence of comorbid conditions. Conclusions: Elderly hepatitis C virus patients referred to Italian specialty clinics have advanced and underestimated liver disease. Nevertheless, they are progressively understudied in parallel with increasing age. © 2012 Editrice Gastroenterologica Italiana S.r.l.

a b s t r a c t Background: Data on the efficacy of Peg-interferon/ribavirin therapy for chronic hepatitis C are mostly derived from treatment of selected patients enrolled in clinical trials. This study aimed to assess the effectiveness of Peg-interferon/ribavirin therapy in “real world” chronic hepatitis C patients in Italy. Methods: Independent observational multicentre study including consecutive patients receiving Peginterferon/ribavirin in the 18 months before (retrospective phase) and after (prospective phase) the start of the study. Results: 4176 patients were eligible. The final study population consisted of 2051 patients in the retrospective and 2073 in the prospective phase. Sustained virological response was achieved by 1036 patients (50.5%) during the retrospective phase: 325 were genotypes 1/4 (34.1%) and 684 were genotypes 2/3 (67.2%) and by 800 patients (38.6%) during the prospective phase: 300 were genotypes 1/4 (28.4%) and 473 were genotypes 2/3 (51.5%). During multivariate analysis genotypes 2/3 were significantly associated with higher sustained virological response rates; cirrhosis and -glutamil-transpeptidase >2 times the normal limit were associated with poorer response. Conclusions: The response to Peg-interferon/ribavirin therapy in “real world” clinical practice is distinctly lower than in registration trials. The difference in response rates was more pronounced among easy-totreat than among difficult-to-treat hepatitis C virus genotypes.

Aims: The aim of this study was to assess the incidence of fatal, life-threatening side effects and the de novo appearance of non-hepatic morbidity during interferon alfa therapy for chronic viral hepatitis. The relationship of these adverse events to actual total dose and duration of interferon was also evaluated. Methods: We conducted a retrospective study at 73 Italian centers of 11 241 consecutive patients with chronic vital hepatitis who underwent interferon alfa treatment. Results: Five patients died during interferon therapy due to liver failure ( n =4) or complications arising from sepsis. Life-threatening side effects were observed in eight patients: two cases where depression developed and led to a suicide attempt and six patients with bone marrow suppression (granulocytes 3 or platelets 3 ). These symptoms and signs completely disappeared after interferon withdrawal. During interferon treatment, 131 patients developed the following de novo non-hepatic disorders: symptomatic thyroid disease ( n =71), impotence ( n =5), systemic autoimmune disease ( n =5), immune-mediated dermatologic disease ( n =14), diabetes mellitus ( n =10), cardiovascular disease ( n =7), psychosis n =10), seizures ( n =4), peripheral neuropathy ( n =3) and hemolytic anemia ( n =2). Most of these complications are reversible or can be ameliorated. Fatal or life-threatening side effects were not related to actual total dose or duration of interferon alfa, while the majority of patients with de novo non-hepatic morbidity received medium/high doses ( > 200 million units) of interferon alfa or were treated for periods longer than 16 weeks (68% and 80%, respectively). Conclusions: Treatment with interferon alfa may have fatal or life-threatening side effects, their incidence in this study being low (0.04% and 0.07%, respectively) and perhaps no different than in untreated patients with chronic viral hepatitis. Moreover de novo non-hepatic morbidity occurred in 1.2% of patients, and the dose and duration of interferon therapy seem important in determining the frequency of this complication. The development of clinically-overt thyroid disease was most common.

The development of Frames of Reference (FoRs) as coordinate systems in space language has gained increasing attention in current linguistic, neurolinguistic, and psycholinguistic research (Diessel 2013: 687; Kemmerer 2010). Previous studies on typology of spatial expressions have traditionally been based on the universal status of the egocentric or relative FoR found in the Indo- European languages, in which the relation between Figure and Ground is specified by the deictic observer’s viewpoint (Mühlhäusler 2001). However, there is growing crosslinguistic evidence that many non-Indo-European languages do not make use of such deictic or ternary FoR, but interpret spatial relations by referring to binary non-egocentric absolute (geocentric) and intrinsic (objectcentered) FoRs (Levinson 2003; O’Meara & Pérez Báez 2011). Contrary to the hypothesis according to which children’s spatial representations are primarily egocentric, the most recent results on spatial language acquisition similarly suggest that children initially exhibit a strong bias toward absolute rather than relative FoRs (Shusterman & Li 2016). If one takes a historical perspective, it can be found that spatial cognition in the Indo-European language is different from that found in modern European languages. After investigating the contexts of use of spatial terms of FRONT, BEHIND, LEFT, RIGHT in Vedic Sanskrit and Ancient Greek in a comparative perspective, this paper aims at reconstructing the proto-language spatial FoRs. Specifically, data from the Rigveda and the Homeric poems prove that the egocentric relative FoR could not have existed yet in Indo- European, which indeed reveals traces of an absolute language. The close association between those spatial terms and east and west cardinal directions shows a projection of the front-back axis to spatial relations according to the positions of the sun within a geocentric FoR. These findings are also in line with recent studies on the existence of deictically-neutral temporal sequences in Indo- European space-time metaphors (Bartolotta 2018). References Bartolotta, A. 2018. Spatio-temporal deixis and cognitive models in early Indo-European. «Cognitive Linguistics» 29 (1), 1-44. Kemmerer, D. 2010. A neuroscientific perspective on the linguistic encoding of categorical spatial relations, in Evans, V. & P. Chilton (Eds), Language, cognition and space. Equinox, pp. 139-170. Levinson, S. C. 2003. Space in Language and Cognition. Cambridge University Press. Mühlhäusler, P. 2001. Universals and typology of space, in Haspelmath M. (Ed.), Language typology and language universals: An international handbook. Vol. 20. Walter de Gruyter. O’Meara, C. & Pérez Báez, G. 2011. Spatial frames of reference in Mesoamerican languages. «Language Sciences» 33, 837-852. Shusterman, A. & Li, P. 2016. Frames of reference in spatial language acquisition. «Cognitive Psychology» 88, 115-161.

This study is part of a broader research project on temporal and spatial deixis in the Proto-Indo-European language. Specifically, the aim of this paper is to investigate the basic motion verbs go and come in Vedic. The deictic component of PATH has often been considered as inherent to the lexical semantics of these verbs cross-linguistically. However, I will show that Vedic i “go”, gā “go; come; step” and gam “go; come” express a deictically-neutral meaning of ‘moving along a path’, which is not characterized with regard to both MANNER and PATH. Data suggest that these verbs can take on a deictic interpretation by cooccurring with specific particles, adverbs, demonstratives, and personal pronouns. Syntactic and discourse analysis of the Rigveda shows that motion verbs occurring in the same syntactic context are selected depending on their inherent lexical aspect (Aktionsart). Telic verbs gā and gam turn out to be intrinsically compatible with the entailment of arrival of the FIGURE to the GROUND, whereas the atelic verb i is used when the prominent information is PATH rather than GOAL of movement.

Genetic and cytogenetic comparison in between man and non-human primates has largely contributed to the knowledge of the evolution of the Order Primates, and in particular of man. Recently, the "Chromosome painting" approach indicated a strong conservation of syntenies in Eutheria. At present, a more precise identification of breakpoints and evolutionary related rearrangements can be obtained by BAC and locus specific in situ hybridi- sation. In spite to this situation the evolutionary history of different human autosomes remains a dilemma; at the same time, high resolution banded chromosome analysis confirms to be a valuable tool for the preliminary detection of fine rearrangements. This review critically describes current information concerning the evolution of human chro- mosome 7 orthologous in several Eutherian groups. Included in this analysis are data on species belonging to 11 or- ders. Nevertheless, this study has been mainly focused on Primates were we considered data from 9 species of Prosimians, 25 species of Platirrhinae, and 51 species of Catarrhinae. Chromosome 7 synteny appeared in a mamma- lian ancestor in a dual form, generally described as 7a and 7b forms. These chromosomes underwent to several line- specific rearrangements in the different orders. A particular complexity in chromosome rearrangements has been highlighted in Primates. A chronologically fossil-tuned dynamic of the synteny is proposed, starting from classical and molecular cytogenetics specific landmarks which appeared throughout evolution.

Human chromosome 7 (HSA7) derives, by a pericentric inversion and a paracentric inversion, from an ancestral chromosome homologous to chromosome 10 of Pongo pygmaeus (the Asiatic Orang-Utan). Nevertheless the genesis of this autosome during primates evolution is not clear. Even if chromosome painting shows that HAS 7 synteny is highly conserved, GTG-banding comparison in Hominoidea and Cercopithecoidea indicates the probable occurrence of complex rearrangements during the evolution. In this study we used a single locus FISH approach, a powerful tool to detect fine rearrangements, in order to investigate the evolution of HAS 7. We report the chromosome mapping of Williams-Beuren syndrome locus (WS - HSA 7q11.23) on Macaca fascicularis (MFA), Cercopithecus (Chlorocebus) aethiops (CAE) and Trachypithecus cristatus (TCR) (Cercopithecoidea, Primates). The probe hybridises on all species tested and demonstrates the occurrence of rearrangements like fusion, fission and pericentric plus paracentric inversions respectively in MFA, CAE and TCR. Together with the first chromosome mapping of WS locus in Cercopithecoidea, this study confirms that single locus mapping is a very efficacious tool for the analysis of chromosomal rearrangements as it gave the opportunity to have a fine molecular confirmation to proposed banding patterns homologies.