The still under-investigated role of cognitive deficits in PML diagnosis.

Background Despite cognitive deficits frequently represent the first clinical manifestations of Progressive Multifocal Leukoencephalopathy (PML) in Natalizumab-treated MS patients, the importance of cognitive deficits in PML diagnosis is still under-investigated. The aim of the current study is to investigate the cognitive deficits at PML diagnosis in a group of Italian patients with PML. Methods Thirty-four PML patients were included in the study. The demographic and clinical data, the lesion load and localization, and the longitudinal clinical course was compared between patients with (n = 13) and without (n = 15) cognitive deficit upon PML suspicion (the remaining six patients were asymptomatic). Clinical presentation of cognitive symptoms was described in detail. Result After symptoms detection, the time to diagnosis resulted to be shorter for patients presenting with cognitive than for patients with non cognitive onset (p = 0.03). Within patients with cognitive onset, six patients were presenting with language and/or reading difficulties (46.15%); five patients with memory difficulties (38.4%); three patients with apraxia (23.1%); two patients with disorientation (15.3%); two patients with neglect (15.3%); one patients with object agnosia (7.7%), one patient with perseveration (7.7%) and one patient with dementia (7.7%). Frontal lesions were less frequent (p = 0.03), whereas temporal lesions were slightly more frequent (p = 0.06) in patients with cognitive deficits. The longitudinal PML course seemed to be more severe in cognitive than in non cognitive patients (F = 2.73, p = 0.03), but differences disappeared (F = 1.24, p = 0.29) when balancing for the incidence of immune reconstitution syndrome and for other treatments for PML (steroids, plasma exchange (PLEX) and other therapies (Mefloquine, Mirtazapine, Maraviroc). Conclusion Cognitive deficits at PML onset manifest with symptoms which are absolutely rare in MS. Their appearance in MS patients should strongly suggest PML. Clinicians should be sensitive to the importance of formal neuropsychological evaluation, with particular focus on executive function, which are not easily detected without a formal assessment

Notulae to the Italian native vascular flora: 14

In this contribution, new data concerning the distribution of native vascular flora in Italy are presented. It includes new records, confirmations, and status changes to the Italian administrative regions. Nomenclatural and distribution updates, published elsewhere, and corrigenda are provided as Suppl. material

Prenatal Famine and Genetic Variation Are Independently and Additively Associated with DNA Methylation at Regulatory Loci within IGF2/H19

Both the early environment and genetic variation may affect DNA methylation, which is one of the major molecular marks of the epigenome. The combined effect of these factors on a well-defined locus has not been studied to date. We evaluated the association of periconceptional exposure to the Dutch Famine of 1944–45, as an example of an early environmental exposure, and single nucleotide polymorphisms covering the genetic variation (tagging SNPs) with DNA methylation at the imprinted IGF2/H19 region, a model for an epigenetically regulated genomic region. DNA methylation was measured at five differentially methylated regions (DMRs) that regulate the imprinted status of the IGF2/H19 region. Small but consistent differences in DNA methylation were observed comparing 60 individuals with periconceptional famine exposure with unexposed same-sex siblings at all IGF2 DMRs (PBH<0.05 after adjustment for multiple testing), but not at the H19 DMR. IGF2 DMR0 methylation was associated with IGF2 SNP rs2239681 (PBH = 0.027) and INS promoter methylation with INS SNPs, including rs689, which tags the INS VNTR, suggesting a mechanism for the reported effect of the VNTR on INS expression (PBH = 3.4×10−3). Prenatal famine and genetic variation showed similar associations with IGF2/H19 methylation and their contributions were additive. They were small in absolute terms (<3%), but on average 0.5 standard deviations relative to the variation in the population. Our analyses suggest that environmental and genetic factors could have independent and additive similarly sized effects on DNA methylation at the same regulatory site

Glucose transporter 2 gene polymorphisms and beta-cell function in isolated human pancreatic islets

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Evaluation of the Italian transport infrastructures: A technical and economic efficiency analysis

By applying a DEA (Data Envelopment Analysis) framework and Tobit analysis, this paper aims to measure 32 Italian airports’ technical efficiency and investigate how several characteristics impact on their productivity and sustainability. Our findings show that some Italian hubs are technically efficient, although smaller airports that are dominated by lowcost carriers prove to be not least productive. Another conclusion of this paper is that efficiency and environmental impact is independent of an airport’s size, although the size matters in determining an airport’s superior performance. This article highlights how the Italian public shareholder’s system became decisive to increase efficiency in small airports due to the lack of private financing

The direct effects of GLP-1 and GIP, alone or in combination, on human pancreatic islets

GLP-1 and GIP are incretins known to affect beta-cell function and turnover. However, information on the direct actions of these hormones on human islet cells is limited. We tested the effects of acute (45min) or prolonged (2days) exposure to GLP-1 or GIP, alone or in combination, on the function and some molecular features of human islets isolated from non-diabetic and type 2 diabetic multiorgan donors. Acutely, both GLP-1 and, more markedly so, GIP, significantly potentiated glucose-stimulated insulin release, with no apparent synergic action. Some of these effects were observed with type 2 diabetic islets as well. Following prolonged exposure to the incretins, improved insulin secretion was observed, and transcription of insulin, PDX-1 and Bcl-2 was increased in both non-diabetic and diabetic islets, with the combination of GLP-1 and GIP showing more significant effects. Although it is still unclear at what extent these beta-cell direct actions of individual or combined incretins occur in-vivo in humans, nevertheless the results of the present study suggest that enhancing the exposure of pancreatic islets to circulating levels of both incretins may be useful for therapeutical purposes