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Background and purpose Hereditary ataxias are heterogeneous groups of neurodegenerative disorders, characterized by cerebellar syndromes associated with dysarthria, oculomotor and corticospinal signs, neuropathy and cognitive impairment. Recent reports have suggested mutations in the SPG7 gene, causing the most common form of autosomal recessive spastic paraplegia (MIM#607259), as a main cause of ataxias. The majority of described patients were homozygotes or compound heterozygotes for the c.1529C>T (p.Ala510Val) change. We screened a cohort of 895 Italian patients with ataxia for p.Ala510Val in order to define the prevalence and genotype-phenotype correlation of this variant. Methods We set up a rapid assay for c.1529C>T using restriction enzyme analysis after polymerase chain reaction amplification. We confirmed the diagnosis with Sanger sequencing. Results We identified eight homozygotes and 13 compound heterozygotes, including two novel variants affecting splicing. Mutated patients showed a pure cerebellar ataxia at onset, evolving in mild spastic ataxia (alternatively) associated with dysarthria (similar to 80% of patients), urinary urgency (similar to 30%) and pyramidal signs (similar to 70%). Comparing homozygotes and compound heterozygotes, we noted a difference in age at onset and Scale for the Assessment and Rating of Ataxia score between the two groups, supporting an earlier and more severe phenotype in compound heterozygotes versus homozygotes. Conclusions The SPG7 c.1529C>T (p.Ala510Val) mutants accounted for 2.3% of cerebellar ataxia cases in Italy, suggesting that this variant should be considered as a priority test in the presence of late-onset pure ataxia. Moreover, the heterozygous/homozygous genotype appeared to predict the onset of clinical manifestation and disease progression.

Common genetic risk factors are associated with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Intermediate repeat expansions at the Ataxin-2 locus (ATXN2) are a risk factor for ALS and influence the phenotype. We assessed whether ATXN2 is a risk factor for FTD or modify clinical features in a data set of Italian patients. Three hundred sixty-eight unrelated FTD cases and 342 controls were enrolled. The frequency of intermediate CAG repeats in ATXN2 gene was not different comparing patients and controls. CAG repeats were interrupted by CAA in all patients carrying intermediate repeats. Interestingly, patients with an increased number of CAG repeats had an earlier onset of the disease than those without expansions (p = 0.011), and presented more frequently with parkinsonism (p = 0.010), and psychotic symptoms (p = 0.013) at disease onset. Our study does not support a major role of ATXN2 intermediate CAG expansions in predisposing to FTD but suggests that ATXN2 may act as a phenotype modifier.

Bipolar disorder is a chronic psychiatric illness characterised by fluctuation in mood state, with a relapsing and remitting course. Frontotemporal dementia (FTD) is a clinically and genetically heterogeneous syndrome, with the most frequent phenotype being behavioural variant frontotemporal dementia (bvFTD). Here, we report the case of an Italian male presenting with late-onset bipolar disorder that developed into bvFTD over time, carrying a mutation in the GRN gene. Interestingly, the patient carried the c.1639 C T variant in the GRN gene, resulting in a R547C substitution. Our case report further corroborates the notion that, in addition to FTD, progranulin may be involved in the neurobiology of bipolar disorder type 1, and suggests to screen patients with late-onset bipolar disorder for GRN mutations.

To the best of our knowledge no multicenter studies have been published using standardized semi-quantitative evaluation of [123I]FP-CIT scan (DAT-SPECT). The aims of this study were: 1) to cross-compare semi-quantitative software-assisted evaluations of DAT-SPECTs performed in three centers with different equipments; 2) to assess the accuracy of semi-quantitative evaluations of DAT-SPECT and 3) to identify the threshold with the best accuracy, sensitivity and specificity in a patient population with suspected parkinsonian syndrome. Materials and Methods: Two hundred twenty patients (mean age at the time of SPECT acquisition, 67.4 ± 9.5 yy) acquired in three centers (Ospedale San Luigi Gonzaga; Ospedale San Giovanni Battista Molinette; Ospedale Mauriziano Umberto I) were included. All of them underwent DAT-SPECT from January 2006 to July 2010. All exams were analyzed with the freely available software BASGAN and semi-quantitative data were used to predict disease. In particular, analyses were based on the values from the most deteriorated putamen and caudate, normalized for age and corrected for equipment. ROC analysis was performed and area under the curve (AUC) was estimated. Results: Analysis showed high AUCs (0.898, 0.864, 0.900 and 0.891 for each center and for the multicenter setting, respectively) confirming the very good accuracies reached. The best cut-off were 0.72 and 0.82 for putamen and caudate respectively. These thresholds allowed sensitivities and specificities in each center and in the multicenter setting of 76% and 96%, 91% and 82%, 93% and 90%, 86% and 89% respectively. No significant differences were observed between sensibility and specificity in each center. Conclusion: A unique threshold useful for all centers with high and similar sensitivities and specificities is possible after correction for age and equipments. The high accuracy reached in this multicenter trial by the semi-quantitative analysis seems similar to accuracies from qualitative analysis in other multicenter studies.

Amyotrophic lateral sclerosis (ALS) is generally considered to be a paradigm of pure motor neuron disorder; nevertheless, the possible occurrence of cognitive impairment up to a frank dementia in patients affected by ALS is recognized. The appraisal of the cognitive impairment in ALS patients is crucial not only to the therapeutic trials of this incurable disease, but also to the planning of care, compliance to interventions, the end-of-life decisions. The cognitive/behavioral changes of ALS patients are consistent with frontotemporal dysfunctions; the overlap of neuropathological features of ALS and frontotemporal lobe degeneration (FTLD) supports, in addition, the putative spectrum of ALS and FTD. In the present review, the pertinent clinical, genetic, neuropathological, neuropsychological and neuroimaging data of the literature are comprehensively and critically discussed. The distinct and overlapping features of ALS and FTD are pointed out, as well as the undisclosed questions deserving additional studies.

Background/Aim: Recent studies showed that TAR DNA-binding protein 43 (TDP-43), encoded by the TARDBP gene, is a major pathological protein in both sporadic and familial frontotemporal lobar degeneration (FTLD). The aim of this study was to search for mutations of the TARDBP gene in the disease. Methods: We sequenced the TARDBP gene in 172 unrelated FTLD patients recruited from 2 Italian memory clinics. Results: We identified 3 different variants of the TARDBP gene in 12 FTLD patients. Three patients showed a silent variant, Ala66Ala (c.332T → C) in exon 2. A novel heterozygous mutation was found in intron 4 (c.543 + 51A → G) in 1 patient, which is not located at the splicing site. Finally, a c.208C → T variant in the 3′ untranslated region was detected in 8 probands. None of the aforementioned variants were predicted to affect TDP-43. Hence, pathogenic mutations were not identified in any of the FTLD cases. Conclusion: Our study, in accord with previous studies in different populations, found no evidence for a major genetic role of the TARDBP gene in FTLD.

An inflammatory response has been hypothesised to be involved in the pathogenesis of primary dementias, above all Alzheimer's disease (AD). This study was aimed at evaluating interleukin (IL)-12 and a panel of related cytokine levels in paired CSF and sera of demented patients. IL-12 (p70 heterodimer and total IL-12 p40 chain), interferon (IFN)-gamma, IL-10 and transforming growth factor (TGF)-beta1 levels were measured in 30 patients with probable Alzheimer's disease (PrAD), 57 patients with other dementing disorders, including probable vascular dementia (PrVD), Parkinson's disease (PD) and normal pressure hydrocephalus (NPH), and 25 cognitively normal control subjects. In the presence of unchanged concentrations of IL-12, IFN-gamma and IL-10, the mean CSF level of TGF-beta1 and the correspondent TGF-beta1 index, but not the serum level, were significantly increased in PrAD compared to controls and PrVD, whereas no difference was found vs. NPH and PD. Our results support the pathophysiological role of TGF-beta1 system in AD.

Although multiple sclerosis (MS) has been classically regarded as a primarily white matter disorder, recent histopathologic studies have shown that the gray matter may be also heavily affected. Subpial demyelination appears as large bands of myelin loss extending from the surface of the cortex into its deeper layers.1 In vivo this change can only be visualized by ultra-high-fields MRI.2 We describe a patient presenting a neurologic disease that rapidly led to spastic paraplegia and death. Plaques of demyelination were absent in the white matter of the brain, but the neuropathologic diagnosis was MS, based on severe and widespread loss of myelin in the spinal cord. Extensive subpial demyelination involved the …

Background Idiopathic basal ganglia calcifications (IBGC), also known as Fahr’s disease, are neurological diseases characterized by symmetric calcium deposits in basal ganglia and other brain regions. Clinically, IBGC patients show high phenotypic heterogeneity, both in the clinical manifestations and neuroradiological findings. Recently, PDGFRB, PDGFB, XPR1 and SLC20A2 have been identified as causative genes for IBGC [1]. The aim of this study was to report on two Italian patients with idiopathic basal ganglia calcifications associated with novel mutations in the SLC20A2 gene who both presented with episodic migraine.

SIN DOCUMENT*The Dementia Study Group is co-ordinated by Sandro Sorbi andincludes: Margherita Alberoni, Milan; Pasquale Alfieri, SommaVesuviana (NA); Serena Amici, Perugia; Daniele Antana, Rome;Ildebrando Appollonio, Monza (MI); Stefano Avanzi,Castelgoffredo (MN); Antonella Bartoli, Pescara; BrunoBergamasco, Turin; Laura Bracco, Florence; Amalia Bruni,Lamezia Terme (CZ); Orso Bugiani, Milan; Paolo Caffarra, Parma;Carlo Caltagirone, Rome; Antonio Carolei, L’Aquila; Anna RosaCasini, Rome; Luciana Ciannella, Benevento; Antonietta Citterio,Pavia; Antonio Daniele, Rome; Graziella D’Achille, Isernia;Giuseppe Del Curatolo, Grosseto; Grazia Dell’Agnello, Pisa;Daniele Durante, Parma; Elisabetta Farina, Milan; Patrizia Ferrero,Turin; Paolo Forleo, Florence; Guido Gainotti, Rome; PaoloGabriele, Cassino (FR); Emanuela Galante, Castelgoffredo (MN);Virgilio Gallai, Perugia; Roberto Gallassi, Bologna; MaddalenaGasparini, Milan; Bernardino Ghetti, Indianapolis (USA); GiorgioGiaccone, Milan; Floriano Girotti, Milan; Luigi Grimaldi, Milanand Caltanisetta; Serenella Grioli, Catania; Bianca MariaGuarnieri, Pescara; Stefano Grottoli, Fossombrone (PS); FrancescoIemolo, Ragusa; Stefania Latorraca, Florence; Francesco Le Pira,Catania; Gian Luigi Lenzi, Rome; Sebastiano Lorusso, Rimini;Claudio Mariani, Milan; Gabriella Marcon, Udine; VincenzoMascia, Carbonia (CA); Simonetta Mearelli, L’Aquila; MariaMorante, Senigallia (AN); Michela Morbin, Milan; MassimoMusicco, Segrate (MI); Ettore Nardelli, Verona; Paolo Nichelli,Modena; Alessandro Padovani, Brescia; Marco Paganini, Florence;Roberta Pantieri, Bologna; Pietro Parisen, Vicenza; LucillaParnetti, Perugia; Bruno Passerella, Brindisi; Carla Pettenati, Rho(MI); Silvia Piacentini, Florence; Federico Piccoli, Palermo; CarloPiccolini, Perugia; Gilberto Pizzolato, Padova; LeandroProvinciali, Ancona; Nicola Pugliese, Salerno; Francesco Redi,Arezzo; Rosa Maria Ruggieri, Palermo; Umberto Ruggiero,Naples; Marco Saetta, Siracusa; Rudolf Schoenuber, Bolzano;Maria Caterina Silveri, Rome; Sandro Sorbi, Florence; GiuseppeSorrentino, Naples; Patrizia Sucapane, L’Aquila; Andrea Stracciari,Bologna; Massimo Tabaton, Genova; Fabrizio Tagliavini, Milan;Vito Toso, Vicenza; Francesco Valluzzi, Putignano Noci (BA)S. Sorbi ( )Department of Neurological and Psychiatric SciencesUniversity of FlorenceViale Morgagni 85, I-50131 Florence, Italy

The relative content of peripheral benzodiazepine receptor (pBR) mRNA was examined by reverse transcriptase-polymerase chain reaction in lymphocytes of obsessive-compulsive disorder (OCD) patients, according to their clinical course of illness. pBR mRNA significantly decreased only in chronic OCD patients (n=8) as compared to controls (n=10), whereas no significant changes were observed in episodic OCD patients (n=7). We suggest that modulation of pBR gene expression might delineate a clinical heterogeneity in OCD.

Background: The aim of this study was to assess whether the decrease of peripheral benzodiazepine receptor (pBR) number in peripheral blood mononuclear cells (PBMC), previously observed in patients with generalized anxiety disorder, is paralleled by changes in the relative content of messenger RNA (mRNA) encoding pBR. Methods: Eight patients with a DSM-III-R diagnosis of generalized anxiety disorder were examined before, during, and after 2′-chloro-N-desmethyl-diazepam treatment. Eight healthy subjects were analyzed in parallel. The relative content of pBR mRNA was determined by reverse-transcriptase-polymerase chain reaction, using β -actin as internal standard. Kinetic binding properties of pBR were measured using 3 H-PK11195 as a ligand. Results: pBR and pBR mRNA were significantly decreased in untreated generalized anxiety disorder patients as compared to controls (by 45% and 70%, respectively). Both pBR density and mRNA levels returned to control values during treatment or after withdrawal, which also coincided with recovery from anxiety. Conclusions: These results suggest that the turnover rate of pBR is reduced in PBMC of generalized anxiety disorder patients, and that this change occurs at the transcriptional level.

Background: A hexanucleotide repeat expansion in the first intron of C9ORF72 has been shown to be responsible for a high number of familial cases of amyotrophic lateral sclerosis or frontotemporal lobar degeneration (FTLD). Atypical presentations have been described, particularly psychosis. Methods: We determined the frequency of the hexanucleotide repeat expansions in a population of 651 FTLD patients and compared the clinical characteristics of carriers and noncarriers. In addition, we genotyped 21 patients with corticobasal syndrome, 31 patients with progressive supranuclear palsy, and 222 control subjects. Results: The pathogenic repeat expansion was detected in 39 (6%) patients with FTLD (17 male and 22 female subjects); however, it was not detected in any corticobasal syndrome and progressive supranuclear palsy patients or controls. Twenty-four of 39 carriers had positive family history for dementia and/or amyotrophic lateral sclerosis (61.5%), whereas only 145 of 612 noncarriers had positive family history (23.7%; p

Gamma-ray bursts (GRBs) have been proposed as a tool for studying star formation in the Universe, so it is crucial to investigate whether their host galaxies and immediate environments are in any way special compared with other star-forming galaxies. Here we present spatially resolved maps of dust emission of the host galaxy of the closest known GRB 980425 at z=0.0085 using our new high-resolution observations from Herschel, Atacama Pathfinder Experiment (APEX), Atacama Large Millimeter Array (ALMA) and Australia Telescope Compact Array (ATCA). We modelled the spectral energy distributions of the host and of the star-forming region displaying the Wolf-Rayet signatures in the spectrum (WR region), located 800 pc from the GRB position. The host is characterised by low dust content and a high fraction of UV-visible star formation, similar to other dwarf galaxies. These galaxies are abundant in the local universe, so it is not surprising to find a GRB in one of them, assuming the correspondence between the GRB rate and star formation. The WR region contributes substantially to the host emission at the far-infrared, millimetre, and radio wavelengths and we propose that this is a consequence of its high gas density. If dense environments are also found close to the positions of other GRBs, then the ISM density should also be considered, along with metallicity, an important factor influencing whether a given stellar population can produce a GRB., Comment: Accepted by A&A. 14 pages, 7 figures, 2 tables. V2: minor updates to match the published version

We present a list of 13 candidate gravitationally lensed submillimeter galaxies (SMGs) from 95 square degrees of the Herschel Multi-tiered Extragalactic Survey, a surface density of 0.14\pm0.04deg^{-2}. The selected sources have 500um flux densities (S_500) greater than 100mJy. Gravitational lensing is confirmed by follow-up observations in 9 of the 13 systems (70%), and the lensing status of the four remaining sources is undetermined. We also present a supplementary sample of 29 (0.31\pm0.06deg^{-2}) gravitationally lensed SMG candidates with S_500=80--100mJy, which are expected to contain a higher fraction of interlopers than the primary candidates. The number counts of the candidate lensed galaxies are consistent with a simple statistical model of the lensing rate, which uses a foreground matter distribution, the intrinsic SMG number counts, and an assumed SMG redshift distribution. The model predicts that 32--74% of our S_500>100mJy candidates are strongly gravitationally lensed (mu>2), with the brightest sources being the most robust; this is consistent with the observational data. Our statistical model also predicts that, on average, lensed galaxies with S_500=100mJy are magnified by factors of ~9, with apparently brighter galaxies having progressively higher average magnification, due to the shape of the intrinsic number counts. 65% of the sources are expected to have intrinsic 500micron flux densities less than 30mJy. Thus, samples of strongly gravitationally lensed SMGs, such as those presented here, probe below the nominal Herschel detection limit at 500 micron. They are good targets for the detailed study of the physical conditions in distant dusty, star-forming galaxies, due to the lensing magnification, which can lead to spatial resolutions of ~0.01" in the source plane., ApJ in press. 31 pages, 16 figures, 5 tables. This version updated to match accepted version

The association of Type Ic SNe with long-duration GRBs is well established. We endeavor, through accurate ground-based observational campaigns, to characterize these SNe at increasingly high redshifts. We obtained a series of optical photometric and spectroscopic observations of the Type Ic SN2012bz associated with the Swift long-duration GRB120422A (z=0.283) using the 3.6-m TNG and the 8.2-m VLT telescopes. The peak times of the light curves of SN2012bz in various optical filters differ, with the B-band and i'-band light curves reaching maximum at ~9 and ~23 rest-frame days, respectively. The bolometric light curve has been derived from individual bands photometric measurements, but no correction for the unknown contribution in the near-infrared (probably around 10-15%) has been applied. Therefore, the present light curve should be considered as a lower limit to the actual UV-optical-IR bolometric light curve. This pseudo-bolometric curve reaches its maximum (Mbol = -18.56 +/- 0.06) at 13 +/- 1 rest-frame days; it is similar in shape and luminosity to the bolometric light curves of the SNe associated with z, 7 pages, 6 figures, 2 tables, accepted for publication in Astronomy & Astrophysics

We present the spectroscopic and photometric evolution of the nearby (z = 0.059) spectroscopically confirmed type Ic supernova, SN 2010bh, associated with the soft, long-duration gamma-ray burst (X-ray flash) GRB 100316D. Intensive follow-up observations of SN 2010bh were performed at the ESO Very Large Telescope (VLT) using the X-shooter and FORS2 instruments. Owing to the detailed temporal coverage and the extended wavelength range (3000--24800 A), we obtained an unprecedentedly rich spectral sequence among the hypernovae, making SN 2010bh one of the best studied representatives of this SN class. We find that SN 2010bh has a more rapid rise to maximum brightness (8.0 +/- 1.0 rest-frame days) and a fainter absolute peak luminosity (L_bol~3e42 erg/s) than previously observed SN events associated with GRBs. Our estimate of the ejected (56)Ni mass is 0.12 +/- 0.02 Msun. From the broad spectral features we measure expansion velocities up to 47,000 km/s, higher than those of SNe 1998bw (GRB 980425) and 2006aj (GRB 060218). Helium absorption lines He I lambda5876 and He I 1.083 microm, blueshifted by ~20,000--30,000 km/s and ~28,000--38,000 km/s, respectively, may be present in the optical spectra. However, the lack of coverage of the He I 2.058 microm line prevents us from confirming such identifications. The nebular spectrum, taken at ~186 days after the explosion, shows a broad but faint [O I] emission at 6340 A. The light-curve shape and photospheric expansion velocities of SN 2010bh suggest that we witnessed a highly energetic explosion with a small ejected mass (E_k ~ 1e52 erg and M_ej ~ 3 Msun). The observed properties of SN 2010bh further extend the heterogeneity of the class of GRB supernovae., 37 pages and 12 figures (one-column pre-print format), accepted for publication in ApJ

We report here a study of peripheral type benzodiazepine receptors (pBZr) in mononuclear cells (MNC) from blood of patients with multiple sclerosis (MS) during periods of stable and active disease and from normal controls. Most active MS patients were retested in a longitudinal study, both during a treatment with high dose steroids and while medication free. Active MS produces a significant decrease of receptor density compared with the controls whereas remission of the disease shows no effect. Four weeks of steroid treatment restore binding density to normal levels, and two weeks of drug withdrawal result in a small, but significant increase in number of the binding sites compared with the control value. We suggest that the number of pBZr in blood MNC might change during the clinical course and steroid therapy of MS.

Background/Aims: Recent studies suggested a role for pro-inflammatory mediators in frontotemporal lobar degeneration (FTLD). The objective of this study was to evaluate the association of functionally active polymorphisms in pro-inflammatory cytokine genes with the occurrence and the clinical features of the disease. Methods: Using a case-control study, we compared allelic and genotypic frequencies of several polymorphisms in the interleukin (IL)-1α, interleukin (IL)-1β, interleukin (IL)-6 and tumor necrosis factor (TNF)-α genes between 110 FTLD patients and 119 healthy controls. Results: No significant association between the examined polymorphisms and the disease was found. However, in comparison with remaining genotypes, patients carrying the T/T genotype of the IL-1β gene showed a significantly lower age at onset of the disease. In addition, scores of the Frontal Assessment Battery were significantly modified by the IL-6 –174G>C polymorphism. Conclusion: Our findings support a role for pro-inflammatory cytokine genes in the pathogenesis of frontotemporal lobar degeneration.

Recent studies showed that TAR DNA-binding protein 43 (TDP-43), encoded by the TARDBP gene, is a major pathological protein in both sporadic and familial frontotemporal lobar degeneration (FTLD). The aim of this study was to search for mutations of the TARDBP gene in the disease.We sequenced the TARDBP gene in 172 unrelated FTLD patients recruited from 2 Italian memory clinics.We identified 3 different variants of the TARDBP gene in 12 FTLD patients. Three patients showed a silent variant, Ala66Ala (c.332T --C) in exon 2. A novel heterozygous mutation was found in intron 4 (c.543 + 51A --G) in 1 patient, which is not located at the splicing site. Finally, a c.208C --T variant in the 3' untranslated region was detected in 8 probands. None of the aforementioned variants were predicted to affect TDP-43. Hence, pathogenic mutations were not identified in any of the FTLD cases.Our study, in accord with previous studies in different populations, found no evidence for a major genetic role of the TARDBP gene in FTLD.

In an attempt to assess the involvement of the "peripheral-type" benzodiazepine receptors (pBDZR) in hepatic encephalopathy (HE), we examined the binding of the isoquinoline carboxamide derivative 3 H-PK 11 195 to lymphocyte membranes from a group of patients with liver cirrhosis with or without clinical signs of HE and normal controls. Lymphocyte 3 H-PK 11 195 binding is saturable, with high affinity and presents the pharmacological specificity corresponding to pBDZR. A significant 40% decrease in the number of 3 H-PK 11 195 binding sites, without a concomitant change in the apparent affinity, is observed in the group with HE as compared to the controls, but not in that with liver diseases without HE. The decrease in binding capacity correlates significantly with the clinical grading of HE, but not with age, sex, aetiology of cirrhosis or presence of surgical shunt. In contrast to the reduction of pBDZR, 3 H-N-methylscopolamine binding to lymphocyte muscarinic receptors is not affected in HE. These findings are consistent with a role for pBDZR in HE and may stimulate studies of endogenous modulators and pharmacological agents for these receptors in the disease.

The nature of the dark bursts is still not fully understood. Here, we report on some of our recent studies on Swift dark bursts. Thereby, we pay particular attention to GRB 050717, for which we obtained a deep imaging of the X‐ray error circle with the newly commissioned GROND camera mounted at the 2.2 m telescope on La Silla.

The long and relatively faint gamma-ray burst GRB 060605 detected by \emph{Swift}/BAT lasted about 20 sec. Its afterglow could be observed with \emph{Swift}/XRT for nearly 1 day, while \emph{Swift}/UVOT could detect the afterglow during the first 6 hours after the event. Here, we report on integral field spectroscopy of its afterglow performed with PMAS/PPak mounted at the Calar Alto 3.5 m telescope. In addition, we report on a detailed analysis of XRT and UVOT data and on the results of deep late-time VLT observations that reveal the GRB host galaxy. We find that the burst occurred at a redshift of $z$=3.773, possibly associated with a faint, $R_C=26.4 \pm 0.3$ host. Based on the optical and X-ray data, we deduce information on the SED of the afterglow, the position of the cooling frequency in the SED, the nature of the circumburst environment, its collimation factor, and its energetics. We find that the GRB fireball was expanding into a constant-density medium and that the explosion was collimated with a narrow half-opening angle of about 2.4 degrees. The initial Lorentz factor of the fireball was about 250; however, its beaming-corrected energy release in the gamma-ray band was comparably low. The optical, X-ray afterglow, on the other hand, was rather luminous. Finally, we find that the data are consistent within the error bars with an achromatic evolution of the afterglow during the suspected jet break time at about 0.27 days after the burst., Comment: accepted in A&A; changed title, major reviews after referee's report; 15 pages and 14 figures

The supernova SN 2006aj associated with GRB 060218 is the second-closest GRB-SN observed to date ($z$=0.033) and is the clearest example of a SN associated with a Swift GRB with the earliest optical spectroscopy. Its optical data showed that this is the fastest evolving and among the least luminous GRB-SNe (70% as luminous as SN1998bw). However, its expansion velocity and a comparison with other stripped-envelope SNe suggest that SN2006aj is an intermediate object between Type Ic GRB-SNe and those not accompained by a GRB. High-resolution optical spectroscopy together with SDSS pre-burst observations revealed that the host galaxy of SN2006aj is a low-luminosity, metal-poor star-forming dwarf galaxy., Comment: To appear in conf. proc. of "The Multicoloured Landscape of Compact Objects and their Explosive Progenitors: Theory vs Observations", a conference held in Cefalu, Sicily, June 11-24, 2006

This study was aimed at identifying, in 203 patients with Alzheimer's disease followed during long-term treatment with Acetylcholinesterase inhibitors (ChEIs), the predictive factors of the clinical response among cognition (MMSE), functioning (BADL and IADL) measures and age and gender at the baseline (T0). The ANCOVA test showed a significant association between MMSE scores at time T0 and T3, and the variation T9 to T0, T15 to T0 and T21 to T0 of the MMSE scores, using also gender, age and drug as covariates. The significance was higher for the patients affected by mild dementia. Regarding functional activities, a significant relationship was detected, by the ANCOVA test, only between the scores at T3 and the variation T15 to T0 for BADL, and the variation T9 to T0, T15 to T0 for IADL, respectively. Our results confirm, in a real world setting, that ChEIs provide long-term cognitive benefit, which is correlated to, and predictable by, the short-term response (within the third month) as well as the cognitive status (evaluated by means of the MMSE) at the beginning of the treatment. These factors should be the basis of any cost/effectiveness algorithm in health economic decision models.

We discuss the results of the analysis of multi-wavelength data for the afterglows of GRB 081007 and GRB 090424, two bursts detected by Swift. One of them, GRB 081007, also shows a spectroscopically confirmed supernova, SN 2008hw, which resembles SN 1998bw in its absorption features, while the maximum luminosity is only about half as large as that of SN 1998bw. Bright optical flashes have been detected in both events, which allows us to derive solid constraints on the circumburst-matter density profile. This is particularly interesting in the case of GRB 081007, whose afterglow is found to be propagating into a constant-density medium, yielding yet another example of a GRB clearly associated with a massive star progenitor which did not sculpt the surroundings with its stellar wind. There is no supernova component detected in the afterglow of GRB 090424, likely due to the brightness of the host galaxy, comparable to the Milky Way. We show that the afterglow data are consistent with the presence of both forward- and reverse-shock emission powered by relativistic outflows expanding into the interstellar medium. The absence of optical peaks due to the forward shock strongly suggests that the reverse shock regions should be mildly magnetized. The initial Lorentz factor of outflow of GRB 081007 is estimated to be \Gamma ~ 200, while for GRB 090424 a lower limit of \Gamma > 170 is derived. We also discuss the prompt emission of GRB 081007, which consists of just a single pulse. We argue that neither the external forward-shock model nor the shock-breakout model can account for the prompt emission data and suggest that the single-pulse-like prompt emission may be due to magnetic energy dissipation of a Poynting-flux dominated outflow or to a dissipative photosphere., Comment: 15 pages, 8 figures, accepted for publication in the Astrophysical Journal

Peripheral-type benzodiazepine receptors (pBZr) have been shown to be sensitive to hormonal perturbations, including changes in ovarian steroids. This study examines whether estradiol and progesterone modulate pBZr binding in membranes of human blood mononuclear cells, as measured by binding of both 3H-PK 11195 and 3H-Ro 5-4864. Our findings were negative. There was no steroidal modulation of pBZr binding to these membrane preparations in vivo in normal women studied at different sex-steroid phases of the menstrual cycle, or during 8–30 weeks of pregnancy. There was also no effect of hormones on the binding sites in cultures of mononuclear cells treated with estradiol or progesterone (up to 10−5 M) over a period between 2 and 72 h. Further, we performed in vitro competition experiments, which showed that both steroids are not active at the pBZr. Our data suggest that pBZr located in human blood mononuclear cells are insensitive to the physiological variations of circulating female hormones.

According to our present understanding, long GRBs originate from the collapse of massive stars while short bursts are due to the coalescence of compact stellar objects. Since the afterglow evolution is determined by the circumburst density profile, n(r), traversed by the fireball, it can be used to distinguish between a so-called ISM profile, n(r) = const., and a free stellar wind, $n(r) \propto r^{-2}$. Our goal is to derive the most probable circumburst density profile for a large number of Swift-detected bursts using well-sampled afterglow light curves in the optical and X-ray bands. We combined all publicly available optical and Swift/X-ray afterglow data from June 2005 to September 2009 to find the best-sampled late-time afterglow light curves. After applying several selection criteria, our final sample consists of 27 bursts, including one short burst. The afterglow evolution was then studied within the framework of the fireball model. We find that the majority (18) of the 27 afterglow light curves are compatible with a constant density medium (ISM case). Only 6 of the 27 afterglows show evidence for a wind profile at late times. In particular, we set upper limits on the wind termination-shock radius, $R_T$, for GRB fireballs which are propagating into an ISM profile and lower limits on $R_T$ for those which were found to propagate through a wind medium. Observational evidence for ISM profiles dominates in GRB afterglow studies, implying that most GRB progenitors might have relatively small wind termination-shock radii. A smaller group of progenitors, however, seems to be characterised by notably more extended wind regions., Comment: A&A, accepted (Oct 26, 2010); 20 pages in journal format; 6 pages main text, 13 pages Appendix, 1 page references, 6 tables and 2 figures; included comments by the referee and language editor; removed grey colouring of the tables

The possible existence of a continuum encompassing the diversity of explosive stellar deaths,ranging from ordinary SNe to relativistic hypernovae associated with long duration GRBs, is under intense debate. In this context, SN2008D associated with XT080109 could represent a paradigmatic case, since it might exemplify a potential borderline event. The main aim is to infer geometric information of SN2008D through the evolution of its linear optical polarization. We also report the polarization evolution of SN2007uy, and discuss the properties of the host ISM towards the XT. The final goal is to compare the polarization properties, and hence the geometries of both SNe, which shone contemporaneously in NGC2770. This fortunate coincidence brought us the opportunity to observe both SNe simultaneously, and most importantly, with identical instrumental setups. The observations span 74.9 days, starting 3.6 days after the XT and are distributed in 11 visits. In addition we performed observations in the mm range in order to identify the dominant polarization. We report positive linear polarization detections at several epochs for SN2008D at a level of ~1% and at ~1.5% for SN2007uy. SN2007uy shows constant polarization, which could be described by the host interstellar polarization plus a constant eccentricity expansion on the sky plane. A statistical analysis of the distribution of the SN2008D Stokes parametres suggests that it could show an intrinsic variable polarization component. Assuming the SN2007uy polarization is constant, we find that the evolution of the intrinsic SN2008D polarization could be explained by an aspherical axisymmetric expansion with variable eccentricity. We come to the same result even if we make no assumption on SN2007uy, although at a lower significance level. We suggest that at least the projected, if not the intrinsic, geometries of both SNe could differ., 10 pages, 3 figures, accepted for publication in A&A

We report a case in which an acute Guillain-Barre-like syndrome was quickly followed by a central demyelinating disease, documented by the clinical findings as well as by magnetic resonance imaging (MRI), electrophysiological and cerebrospinal fluid examinations. The close follow-on of the clinical signs seems to exclude a simple coincidence of two separate diseases and it may constitute further evidence for a possible etiological link between central and peripheral myelin damage. We discuss the possibility of a common pathogenic factor underlying central and peripheral demyelination.

Peripheral benzodiazepine receptors (pBDZr) were analyzed in lymphocyte membranes from patients with anxiety disorders (generalized anxiety disorder (GAD), n = 15; panic disorder (PD), n = 10; obsessive-compulsive disorder (OCD), n = 18), other mental disorders (n = 40) and 50 healthy controls, by the specific binding of 3H-PK11195. The number of binding sites (Bmax) was significantly decreased in groups with both GAD and OCD as compared with age-matched controls, by 45% and 25% respectively, whereas the binding affinity (Kd) was the same in all disorder and control groups. Conversely, no changes in binding capacity was observed in the other disorder groups and particularly in the one with PD. The abnormality in pBDZr observed in patients with GAD was restored to a normal value after long-term treatment with 2'-chloro-N-desmethyldiazepam, which also coincided with their recovery from anxiety. Our data suggest that the clinical heterogeneity in anxiety disorders might be related to different biological mechanisms and that lymphocyte pBDZr might be useful in demonstrating these differences.

A historical cohort study was undertaken to determine the risk of epilepsy in a population of 371 newborns with an acute neurological disorder related to fetal and/or neonatal hypoxia compared with a control population of 362 normal newborns. The results showed that the risk of epilepsy was 5.1 times higher in the group of subjects affected at birth by a hypoxia-related acute neurological syndrome than in the control group. (Although the incidence of epilepsy is higher in the first year of life, epileptic seizures connected to perinatal hypoxia may occur in early childhood or later on.) Also, there were frequently persistent neuropsychiatric disorders in children with perinatal hypoxia (5.4%). There was no difference in the two groups regarding the incidence of febrile convulsions. The data show that perinatal hypoxia plays a role in the etiology of epilepsy, although at birth the hypoxia might result in only a modest and oftentimes completely reversible neurological syndrome.

The properties of the binding of the muscarinic receptor ligands, [3H]quinuclidinyl benzilate ([3H]QNB) and [3H]N-methylscopolamine ([3H]NMS) in human mononuclear cells were compared. The binding of [3H]QNB showed a high, non-specific component and lack of saturability in both intact mononuclear cells and preparations of lysed mononuclear cell membranes. Conversely the specific binding of [3H]NMS had a high affinity and was saturable at concentrations greater than 30 nM in both intact and broken cells. Classical muscarinic receptor antagonists displaced specific binding of [3H]NMS binding according to the law of mass action, while displacement curves for pirenzepine and muscarinic agonists were very shallow (nH less than 1), suggesting the presence of more than one subtype of muscarinic receptor on mononuclear cell membranes. Binding studies with [3H]NMS to purified mononuclear cell subpopulations demonstrated that muscarinic binding sites were mainly localized on thymus-derived (T) lymphocytes and large granule lymphocytes. Moreover evidence is presented of an age-dependent increase of the density of muscarinic binding sites on T-lymphocytes. The results are discussed in terms of the usefulness of the binding of [3H]NMS in studying the physiological function of muscarinic receptors on human T-lymphocytes and their possible changes in patients with neurological diseases.

Cerebrospinal fluid (CSF) levels of the anxiogenic neuropeptide diazepam binding inhibitor (DBI) were determined by radioimmunoassay in 281 patients who underwent evaluation for neurological problems. Serial dilution curves and reverse-phase high pressure liquid chromatography showed that the immunoreactive material in CSF behaved just as authentic DBI extracted from human brain. Furthermore in the assay there was no evidence of interference from CSF samples deprived of DBI by immunoaffinity. In 82 patients with no evidence of major lesions in the central nervous system, who acted as controls, the CSF DBI content was shown to be age- and sex-related. No correlation was observed with the CSF protein concentration. In patients with different types of dementia, the levels of CSF DBI were significantly increased in a group with normal pressure hydrocephalus. No significant differences were found between Alzheimer's disease, multi-infarct dementia, or dementia with Parkinson's disease and controls. In non-demented patients with Parkinson's disease the levels of DBI were increased in a subgroup with depressive disturbances whereas no differences was observed in the non-depressed cases. The content of DBI was markedly reduced in 5 cases with olivopontocerebellar atrophy and in 4 with spinocerebellar ataxia. In all the other disorders studied the levels of DBI were similar to or slightly lower (multiple sclerosis) than those of the controls. The origin of DBI in cerebrospinal fluid is uncertain; a number of various possibilities are discussed concerning the proposed role of DBI as modulator of brain GABAergic transmission.

An epidemiological survey of primary dementia syndromes was conducted in the city of Bra (26287 residents) in the Piedmont region. All the patients for whom a diagnosis of senile dementia had already been recorded together with the cases coming to light as a result of a questionary circulated to general practitioners and neuropsychiatrists were subjected to a broad battery of neuropsychological tests. The prevalence rate proved to be 255 (+/- 61) per 100 000 of the population and 2028 (+/- 476) per 100 000 of the over 65s. Close attention was paid to dements living in nursing facilities. Factors favoring institutionalisation were: advanced age, severe motor impairment and female sex. No correlation between severity or dementia and institutionalisation was found.

Brainstem auditory evoked potentials (BAEPs) were recorded from 55 patients with postconcussion syndrome (PCS) to elicit evidence of an organic and subclinical brainstem disorder. Fifteen patients (27.3%) showed abnormal responses unilaterally or bilaterally, especially for one or more interpeak latencies prolonged beyond the upper 99% confidence limits. Other 9 patients had borderline responses. The BAEP alterations were not correlated either with dizziness at the time of recording, or with vestibular troubles in the routine caloric test. Though BAEP abnormalities may be present a long time after injury, we found an improvement of responses in the majority of 14 re-tested patients. These data show that BAEP can give an objective demonstration of a reversible brainstem disorder in patients with PCS.