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Y-box binding protein 1 (YBX-1 or YB-1) is an oncoprotein that promotes replicative immortality, tumor cell invasion and metastasis. The increase in the abundance of YB-1 in the cell or YB-1 translocation from the cytoplasm to the nucleus is characteristic of malignant cell growth. We have previously reported that ΔNp63α, a transcription factor that is known to play a pivotal role in keratinocyte proliferation and differentiation, promotes YB-1 nuclear accumulation. Here, we show that YB-1 is highly expressed in proliferating keratinocytes and is down-regulated during keratinocyte differentiation. ΔNp63α reduces YB-1 protein turnover and leads to accumulation of ubiquitin-conjugated YB-1 into the nucleus. Reduction of YB-1 protein level, following treatment with a DNA-damaging agent, is inhibited by ΔNp63α suggesting that YB-1 and ΔNp63α interplay can support keratinocyte proliferation and protect cells from apoptosis under genotoxic stress.

Background & Aims: Irritable Bowel Syndrome (IBS) patients still require effective treatment. The anti-inflammatory property of curcumin and the antispasmodic and carminative effect of fennel suggests that combination of these nutraceutical compounds would be useful in functional bowel disorders including IBS. We assessed the efficacy and tolerability of a combination of curcumin and fennel essential oil (CU-FEO) in IBS symptoms relief. Methods: 121 patients with mild-to-moderate symptoms of IBS defined by an Irritable Bowel Syndrome- symptom severity score (IBS-SSS) 100-300 and abdominal pain score 30-70 on a 100 mm Visual Analogue Scale (VAS), were randomly assigned to CU-FEO or placebo (2 capsules b.d. for 30 days). Primary endpoint was the mean decrease of IBS-SSS at the end of the treatment corrected for the mean baseline score (relative decrease). The impact of the treatment on quality of life was assessed through IBS-QoL questionnaire. Results: CU-FEO was safe, well-tolerated and induced symptom relief in patients with IBS; a significant decrease in the mean relative IBS-SSS was observed after 30 days of treatment (50.05 ± 28.85% vs 26.12 ± 30.62%, P

In mice, 2,4-dinitrofluorobenzene (DNFB) induces contact allergic dermatitis (CAD), which, in a late phase, is characterized by mast cell (MC) infiltration and angiogenesis. Palmitoylethanolamide (PEA), an endogenous anti-inflammatory molecule, acts by down-modulating MCs following activation of the cannabinoid CB 2 receptor and peroxisome proliferator-activated receptor-α (PPAR-α). We have previously reported the anti-inflammatory effect of PEA in the early stage of CAD. Here, we examined whether PEA reduces the features of the late stage of CAD including MC activation, angiogenesis and itching. After sensitization to DNFB, female C57BL/6J mice underwent to three DNFB challenges at days 5, 12 and 19 and treatments were given at each challenge and for two more days. CAD was expressed as Δ increase in ear thickness between challenged and un-challenged mice. PEA (5 mg/kg/i.p.) reduced: i) the DNFB-induced Δ increase; ii) the number of MCs per tissue area; iii) the expression of VEGF and its receptor Flk-1. These effects were reversed by co-administration of AM630 (1 mg/kg/i.p.), a CB 2 antagonist, but not GW6471 (1 mg/kg/i.p.), a PPAR-α antagonist. Finally, PEA reduced the number of ear scratchings 48 h after DNFB challenge and this effect was reversed by both CB2 and PPAR-α antagonists, suggesting the involvement of both receptors. PEA, by reducing the features of late stage CAD in mice, may be beneficial in this pathological condition.

The aim of the study was to perform a study on the western slope of the Monti Parioli hill (Rome, Italy) affected by frequent rock-fall phenomena, such as the one that occurred on 13 November 2007. This goal was achieved by defining a detailed reconstruction of the stratigraphical, geological and geomechanical structure of the slope and by conducting a back-analysis of the rock-fall event using 2-D and 3-D modeling tools. The reconstruction of the slope's geological structure, characterized by the presence of two anthropogenic cavity systems, and the characterisation of geomechanical properties of outcropping terrains have been realized by means of a detailed geological survey and a campaign of direct and indirect investigations. Therefore, continuous rotary, coring boreholes up to 60 m, collecting undisturbed samples for laboratory tests and performing direct investigations such as SPTs and pressuremeter tests were carried out. The indirect investigations included electrical tomography surveys, linear surface seismic refraction surveys and seismic cross-hole tests. Using the reconstructed geological-technical model, it was possible to define the stability conditions of the slope at the time of collapse by using a computational two-dimensional explicit finite difference program (FLAC) and a 3-D finite element analysis (FEMLAB).

BACKGROUND The long-term effect of liver transplantation (LT) on cognitive functions and the complete reversibility of minimal hepatic encephalopathy are poorly documented. Much evidence indicates that spatial attention improves starting from the immediate period after LT. However, at least in the first 2 years, some cognitive defects seem to persist to some degree, especially for supramodal nonverbal cognitive functions. The aim of this study is to investigate (i) whether the improvements observed in the perioperative period fluctuate or remain stable 10 years after LT and (ii) whether the functions that have been found defective also improve. METHODS We called patients previously included in a prospective study (Mattarozzi et al., Arch Neurol 2004; 61: 242) for a further neuropsychological evaluation. We compared the cognitive evaluation after 7 to 10 years with previous data gathered 6 and 18 months after LT. RESULTS The improvements obtained in the first 2 years after transplantation remain stable during the 7 to 10 years thereafter, especially for visuospatial attention, F(12,96) 1.70; P=0.04 and selective attention, F(6,66) 3.51; P=0.005. Furthermore, these findings also seem to suggest an improvement in supramodal cognitive functions, such as spatial planning intelligence, measured by the Elithorn Maze Test, F(3,33) 7.42; P=0.002. Verbal short-term memory, F(3,33) 3.69; P=0.038, and visuospatial short-term memory, F(6,64) 2.97; P=0.013, show a more fluctuating trend over time. CONCLUSIONS Despite the risk of surgery, the neurotoxicity of immunosuppression therapy, and the effects of aging and related comorbidities, our data indicate that LT is able to significantly improve patients' cognitive functions in the long term.

About 190 anthropogenic sinkholes occurred within the territory of the city of Naples (Southern Italy) between 1915 and 2010. In the study area, the genesis of sinkholes can be ascribed to two major factors, often strongly interacting with each other: the existence of a complex network of underground man-made cavities, and the inadequacy of the sewage disposal system. Rainfall has been identified as the main triggering factor combined with anthropogenic activity. Based on such predisposing factors, in addition to the geological setting, a susceptibility map of the territory has been realised.

The limbs of the three-toed skink Chalcides chalcides are reduced to such a degree that the three digits are too small for skeletochronology. This study, performed on animals collected near Isernia (central Italy), describes the structure of the caudal vertebrae, which are often naturally lost due to autotomy, in order to determine whether they can be used to obtain data on age and growth with skeletochronological techniques. The reliability of the autotomous caudal vertebrae for skeletochronology was verified by performing skeletochronological analyses also on femora. Although the identification of the lines of arrested growth (LAGs) was easier in femora than in autotomous caudal vertebrae, a high correspondence of the LAG count between the two bones was observed. Females were larger and lived longer than males (4 and 3 years, respectively). For both sexes, the snout vent length (SVL) was significantly correlated with age. For both sexes, sexual maturity was attained after two hibernations from birth, beginning at the 20th month of age. At first reproduction, males had an SVL of 91–106 mm and females one of 111–150 mm. Von Bertalanffy growth curves of age versus SVL showed that females had slower growth rates than males for attaining their asymptotic SVL (females: 197 mm; males: 143 mm). The results provide the first data on age and growth of C. chalcide, and show that autotomous caudal vertebrae are reliable alternatives for obtaining such data for limb-reduced reptiles, avoiding the need to sacrifice or disable animals, as occurs when long bones are used.

Orthotopic liver transplantation (OLT) represents the sole etiological treatment for Wilson's disease (WD), but its efficacy in resolving the neurological symptoms is still a matter of debate. We present the case of a young male affected with WD with hepatic and neurological involvement, who underwent OLT for subacute liver failure. Clinical, neuropsychological and neuroradiological assessment were performed before and after OLT. OLT had no effect on neurological symptoms, suggesting that the basal ganglia damage may be irreversible. Nineteen months after OLT, the patient went on to develop new permanent extrapyramidal symptoms. We postulate a sequela of an early post-operative central pontine and extrapontine myelinolysis.

The prevalence of mental retardation related to chromosomal abnormalities, including fragile X syndrome, was studied among 2735 males aged between five and 20 years living in the Republic of San Marino. Five cases of chromosomal abnormalities were found, including one case with fragile X syndrome, with partial epilepsy and a CT scan showing a large arachnoid cyst in the posterior fossa. The prevalence of mental retardation due to chromosomal abnormality was 1.83 per 1000, and that due to fragile X syndrome was 0.37 per 1000. Although these findings relate to only a small population, they are the first from a Mediterranean area.

The effects on the hypothalamus–pituitary–testicular axis of the well-known antispermatogenic drug lonidamine (LND) has not been elucidated so far. In the present study, the possible changes of the testicular steroid hormones were evaluated in immature mice for a better characterization of the LND adverse effects both in its use as antitumoral agent and male contraceptive. Male CD1 mice were orally treated on postnatal day 28 (PND28) with LND single doses (0 or 100 mg/kg b.w.) and euthanized every 24 h from PND29 to PND32, on PND35 and on PND42 (1 and 2 weeks after the administration, respectively). Severe testicular effects were evidenced in the LND treated groups, including: a) significant testis weight increase, 24 h and 48 h after dosing; b) sperm head counts decrease (more than 50% of the control) on PND29–32; c) damage of the tubule morphology primarily on the Sertoli cell structure and germ cell exfoliation. All these reproductive endpoints were recovered on PND42. At the same time, a significant impairment of the testicular steroid balance was observed in the treated mice, as evidenced by the decrease of testosterone (T) and androstenedione (ADIONE) and the increase of 17OH-progesterone (17OH-P4) on the first days after dosing, while the testicular content of 17β-estradiol (E2) was unchanged. The hormonal balance was not completely restored afterwards, as levels of T, ADIONE and 17OH-P4 tended to be higher in the treated mice than in the controls, on PND35 and PND42. These data showed for the first time that LND affects intratesticular steroids in experimental animals. However further data are needed both to elucidate the mechanism responsible for the impairment of these metabolic pathways and to understand if the androgens decrease observed after LND administration could be partially involved in the testicular damage.

Objectives: We compared levodopa (LD) kinetic-dynamic profile of a dose of LD/aromatic amino acid decarboxylase peripheral inhibitors versus a nominally equivalent dose of a commercial Mucuna pruriens (Mucuna) seeds extract in 2 patients with Parkinson disease chronically taking LD standard combined with self-prescribed Mucuna. Methods: Patients were challenged with a fasting morning dose of 100 mg LD/25 mg carbidopa (patient 1) or benserazide (patient 2) versus 100 mg LD from Mucuna capsules in 2 different sessions, after a 12-hour standard LD formulations’ washout. They underwent kinetic-dynamic LD monitoring based on LD dose intake and simultaneous serial assessments of plasma drug concentrations and motor test performances. Quantitative analysis of LD in Mucuna capsules was also performed. Results: Levodopa bioavailability was markedly lower after Mucuna administration compared with LD standard formulations: in patient 1, peak plasma LD concentration (Cmax) decreased from 2.0 to 1.0 mg/L and the area under the plasma concentration time curve from 137 to 33.6 mg/L per minute; in patient 2, Cmax was 0.7 mg/L after LD/benserazide and nearly undetectable afterMucuna. In patient 1, impaired LD bioavailability from Mucuna resulted in reduced duration and overall extent of drug response compared with LD/carbidopa. In patient 2, no significant subacute LD motor response was observed in either condition. Quantitative analysis of Mucuna formulation confirmed the 100 mg LD content for the utilized capsules. Conclusions: Our results show an impaired LD bioavailability from Mucuna preparation, as expected by the lacking aromatic amino acid decarboxylase inhibitors coadministration,whichmight explain the suggested lower dyskinetic potential of Mucuna compared with standard LD formulations.

Currently, the BCLC classification, which links tumor stage with treatment option, is the standard system for clinical management of HCC. Thus far, this approach has been considered the standard of care worldwide. This study aimed to evaluate the survival of patients with HCC according to the BCLC Stage, surveillance, and adherence to standards of care. A 3-year prospective study enrolled 92 consecutive patients with HCC in the Gastroenterology Unit of the University of Naples "Federico II". Predictors of the likelihood of death were evaluated by the multivariate Cox model. Forty out of 92 (43%) subjects died during three years of follow up. The overall mortality rate per 100 person-years was 16.7, while the mortality rate for hepatic causes was only 14.2; it was lower in subjects under surveillance (11.4 vs. 28.2), in subjects adherent to standards of care (12.0 vs. 21.1), and in those who were in a better BCLC stage (10.6 vs. 45.8). The multivariate Cox model showed that advanced BCLC stage (HR 4.1, 95% C.I. = 1.8-9.4) was the sole independent predictor of the likelihood of mortality. In this regard, we observed lack of evidence that the adherence to the BCLC recommendations reduces the mortality of patients with HCC; and that the BCLC system cannot be accepted as a "commandment" to be invariably followed in everyday practice. Strategies to help improve adherence to international guidelines for HCC in clinical practice are required.

Stearoyl-Coenzyme A desaturase 1 (SCD1) belongs to the fatty acid family of desaturases. In lactating ruminants, the SCD1 protein is highly expressed in the mammary gland and is relevant for the fatty acid composition of milk and dairy products. Bovine mammary epithelial cells (BME-UV1), cultured in vitro, have been proposed as a model to reproduce the biology of the mammary gland. The present study was designed to investigate the responsiveness of bovine SCD1 promoter to serum, insulin, oleic acid, and NFY transcription factor in BME-UV1 cells. A luciferase-based reporter assay was used to monitor the transcriptional activity of the SCD1 promoter region in BME-UV1 cells treated or not with insulin and/or oleic acid. The level of endogenous SCD1 mRNA was evaluated by Real time PCR. Insulin (20 ng/mL) induced a 2.0 to 2.5-fold increase of SCD1 promoter activity. Additionally, the effect of insulin was inhibited by oleic acid, serum components, and NFY enforced expression. Serum and NFY showed no synergistic or additive effect on SCD1 promoter activity suggesting that they repress SCD1 transcription through the same responsive element.

Karyological studies continue to clarify the evolutionary history of many taxa. We report here on the first chromosome survey of the frog Pseudhymenochirus merlini (Pipidae) in comparison with the related species Hymenochirus boettgeri . In addition to the 2 n = 20 regular (A) chromosomes (eight metacentric and two subtelocentric pairs), H. boettgeri has an accessory B chromosome in about half of the scored karyotypes (2 n = 21). P. merlini showed a karyotype of 2 n = 20 chromosomes, differing from the set of A chromosomes of H . boettgeri by three inversions. Other differences are in the location of the nucleolus organizer regions (NORs), on the 10th chromosome pair in P. merlini instead of the 4th pair in H. boettgeri . Heterochromatin is less abundant in P. merlini , and localized in centromeric and telomeric regions of all chromosomes. The patterns in H. boettgeri resemble those of another pipid species, Silurana tropicalis , as to chromosome number (2 n = 20), morphology, and G-banding patterns. We propose that these characteristics are symplesiomorphic in Pipidae, allowing us to present a scenario for the chromosome evolution in this family. Our results identify a third mechanism of increase in chromosome numbers among pipid frog species, the addition of B chromosomes in Hymenochirus , besides the known processes of polyploidization in Xenopus / Silurana , and centric fission in Pipa .

Exposure to methylphenidate (MPH) during adolescence is the elective therapy for attention deficit/hyperactivity disorder (ADHD) children, but raises major concerns for public health, due to possibly persistent neurobehavioral changes. Rats (30- to 44-days old) were administered MPH (2 mg/kg, i.p once daily) or saline (SAL). At the end of the treatment we collected plasma, testicular, liver, and brain (striatum) samples. The testes and liver were used to evaluate conventional reproductive and metabolic endpoints. Testes of MPH-exposed rats weighed more and contained an increased quantity of sperm, whereas testicular levels of testosterone (TST) were markedly decreased. The MPH treatment exerted an inductive effect on enzymatic activity of TST hydroxylases, resulting in increased hepatic TST catabolism. These findings suggest that subchronic MPH exposure in adolescent rats could have a trophic action on testis growth and a negative impact on TST metabolism. We have analyzed striatal gene expression profiles as a consequence of MPH exposure during adolescence, using microarray technology. More than 700 genes were upregulated in the striatum of MPH-treated rats (foldchange1.5). A first group of genes were apparently involved in migration of immature neural/glial cells and/or growth of novel axons. These genes include matrix proteases (ADAM-1, MMP14), their inhibitors (TIMP-2, TIMP-3), the hyaluronan-mediated motility receptor (RHAMM), and growth factors (transforming growth factor-beta3 [TGF-beta3] and fibroblast growth factor 14 [FGF14]). A second group of genes were suggestive of active axonal myelination. These genes mediate survival of immature cells after contact with newly produced axonal matrix (laminin B1, collagens, integrin alpha 6) and stabilization of myelinating glia-axon contacts (RAB13, contactins 3 and 4). A third group indicated the appearance and/or upregulation of mature processes. The latter included genes for: K+ channels (TASK-1, TASK-5), intercellular junctions (connexin30), neurotransmitter receptors (adrenergic alpha 1B, kainate 2, serotonin 7, GABA-A), as well as major proteins responsible for their transport and/or anchoring (Homer 1, MAGUK MPP3, Shank2). All these genes were possibly involved in synaptic plasticity, namely the formation, maturation, and stabilization of new neural connections within the striatum. MPH treatment seems to potentiate synaptic plasticity, which is an age-dependent developmental phenomenon that adolescent rats are very likely to show, compared to adults. Our observations suggest that adolescent MPH exposure causes only transient changes in reproductive and hormonal parameters, and a more enduring enhancement of neurobehavioral plasticity.

Background HBV and HCV reactivation have been widely reported in patients undergoing immunosuppressive therapy (IT); however, few data are available on the risk of reactivation in patients with psoriasis receiving IT. The aim of our study was to assess the prevalence of HBV and HCV infection in patients with psoriasis and to evaluate the effects of IT during the course of the infection. Methods The study included psoriatic patients who attended an Italian tertiary referral hospital from 2009 to 2012. A total of 224 patients were enrolled. We evaluated: HBV and HCV markers, type of IT and the occurrence of viral reactivation. The observational period ranged from the beginning of IT to the last visit, with a mean follow-up period of 54 months. Results Two hundred and twenty patients (135 males and 89 females; mean age 59 years; range 18–86 years) with psoriasis, with or without psoriatic arthritis, receiving conventional IT and/or biological drugs were tested for markers of infection. We identified 23/224 patients (10.2%) with isolated positivity for HBcAb positivity, 36/224 (16%) with positivity for HBsAb/HBcAb, and 15/224 (6.6%) with positivity for HCV-Ab. No patient was HBsAg positive, none of them underwent pre-emptive therapy with lamivudine or other antiviral drugs and no one showed episodes of viral reactivation. Conclusions The prevalence of HBsAg in patients with psoriasis is lower than that observed in the general population. The prevalence of isolated positivity for HBcAb and of combined positivity for HBcAb and HBsAb is 10.2% and 16%, respectively. The prevalence of HCV infection (HCV-RNA+) is 4%. In patients with psoriasis and HCV-Ab or HBcAb positivity, the IT seems to be safe, regardless of the type of drugs.

The morphometry, age structure, and abundance of the panther chameleon Furcifer pardalis (Cuvier 1829) were studied at Nosy Be (NW Madagascar). Males were larger and heavier than females (SVL, 138.38 ± 35.94 vs 91.92 ± 18.48 mm; mass, 61.06 ± 39.86 vs 22.62 ± 13.17 g). The age, assessed by skeletochronology, was usually less than one year, with a maximum of 2 years. The density estimate for adult individuals was higher along roads (42.21/ha) than in agricultural habitats far from roads (17.43/ha). Compared to other species of Malagasy chameleons, F. pardalis is infrequent in pristine and close forests, while, like other Furcifer species, it is more closely associated with riverine habitats. The higher concentration of individuals in forest-like bands along roads is explained by the presence of a suitable vegetation band along roads and the similarity of this habitat to the riverine and ecotonal forests preferred by chameleons of the genus Furcifer. The life history traits, high fecundity and short life sp...

Lonidamine (LND) [1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid], a well-known antispermatogenic drug, was studied for the first time in pubertal mice to assess its possible effects on spermatogenesis. Male CD1 mice were orally treated on Postnatal Day (PND) 28 with a single dose of LND (100 mg/kg body weight) and sacrificed on PND30, PND42, PND74 and PND123. On PND30 (48 h after dosing), severe testicular effects were evidenced in the treated animals: (a) reduction of the testicular sperm head concentration (approximately 50% of the control value); (b) changes in the spermatogenic cell type distribution (mild decrease of the elongated spermatids and S-phase cells fractions); and (c) morphological alterations of the Sertoli cell cytoplasm and germ cell exfoliation. These changes were recovered in adulthood, on PND74 and PND123. However, no effect on sperm chromatin structure was detected on the epididymal sperm of mature mice by sperm chromatin structure assay, suggesting that LND did not interfere with the process of chromatin reorganization and DNA packaging.

There are always more evidences indicating that 17β-estradiol (E2) is to be necessary for normal male fertility. Here we report the expression of the most ubiquitously expressed member of the akt family of genes, akt1, in the lizard (Podarcis s. sicula) testis. We have used a nonmammalian vertebrate model (the lizard P. s. sicula) to investigate the regulation of the serine/threonine kinase Akt activity, implicated in the control of cell proliferation, survival, and metabolism, in the testis during the annual sexual cycle and to study whether E2 exerts a role in the spermatogenesis through Akt-1 activity. Immunocytochemistry analysis show that Akt-1 proteins are present in the spermatogonia (SPG), and spermatocytes (SPC), and spermatids (SPT). The annual E2 profile shows a progressive increase during the active spermatogenesis (from April to June) and a peak in the month of August (spermatogonial mitosis). In parallel, Akt-1 (molecular weight 60 kDa) are highly phosphorylated during the period of active spermatogenesis and in post-refractory period (August) compared with the winter stasis (from November to March). Present results demonstrate that E2 treatment induces the activation of Akt-1, and this effect is counteracted by the anti-estrogen ICI 182–780. Mol. Reprod. Dev. 71: 52–57, 2005. © 2005 Wiley-Liss, Inc.

Background: Brain edema and increased intracranial pressure worsen prognosis in patients with end-stage chronic cirrhosis. Objective: To use diffusion-weighted imaging (DWI) to quantify water apparent diffusion coefficient (ADC) in different brain regions of patients with chronic liver failure with or without hepatic encephalopathy. Methods: The authors studied 14 patients with viral liver cirrhosis and 12 sex- and age-matched healthy volunteers. Seven patients had no clinical evidence of hepatic encephalopathy; six had grade I hepatic encephalopathy; and one had grade II hepatic encephalopathy. Brain DWI was obtained using a single-shot echo-planar imaging sequence, and four gradient strengths ( b values = 0, 300, 600, and 900 s/mm 2 ) were applied to calculate the average diffusivity maps. Results: Mean ADC values in the brains of patients with cirrhosis were significantly increased in all selected regions of interest (caudate, putamen, and pallidus nuclei; occipital, parietal, and frontal lobe white matter) except in the thalamus. Venous ammonia was linearly related to ADC values in deep gray and white matter regions of interest. Conclusions: Brain water apparent diffusion coefficient is increased in patients with chronic liver disease and may be useful in monitoring patients with hepatic encephalopathy.

The present paper reports data on distribution, demographic parameters, ecological preferences and conservation status of Bombina variegata variegata and B. v. pacbypus from the Italian peninsula. Owing to the wide distribution, we selected as a sample the following regions as sample regions: Lombardy, Veneto, Friuli-Venezia Giulia, Abruzzi, Latium, Campania, Basilicata, Apulia and Calabria, and the autonomous province of Trento3. For each region, we carried out bibliographic and museum researches, together with field surveys in order to collect updated faunistic data. B. v. variegata showed a general preference for hilly and mountain areas at medium/low elevation, under 1100 m. Our field surveys confirmed 44 sites out of 49 investigated; so the number of populations in northern Italy seems to be substantially stable. However, in several sites, particularly as regards prealpine Lombardy, a numerical decrease of individuals was observed; this fact suggests that this taxon could be threatened. B. v. pacbypu...

The results are presented of a microsatellite study performed on melanic and normal specimens of Podarcis sicula found sympatric in a very small area in the Cilento mountain region (Roscigno, southern Italy). The melanic sub‐population showed low variability and departure from HW equilibrium in the considered loci (three out of five). We also provide evidence that genetic exchanges between normal and melanic phenotypes are minimal. This genetic evidence is discussed and an eco‐biogeographic based hypothesis is advanced.

Skeletochronological analysis was performed on Loggerhead sea turtles (Caretta caretta) stranded on the Italian Adriatic and Mediterranean coasts from July 1999 to October 2002. Only the phalanxes of the forelimbs were analysed. The bones were cut at mid‐diaphyseal level. After decalcification, they were sectioned by cryostat and stained with Erlich's hematoxylin. Phalanx cross‐sections showed well‐defined and grossly concentric lines of arrested growth (LAGs). The number of which was correlated with the curved carapax length (CCL). In order to more accurately estimate the individual age, also the number of LAGs lost due to bone resorption was calculated, using osteometric analysis, and added to the number of visible LAGs. Our study showed a longevity ranging from 9 to 18 years for individuals with CCL between 28 and 49 cm; longevity was often greater than 20 years in individuals with CCL over 50 cm. The oldest individual had 83 cm of CCL and was approximately 32–37 years old.

Glycosylation of the foeto-maternal interface of the skink Chalcides chalcides has been examined at various stages of gestation using lectin histochemistry. Specimens of incubatory chamber or placenta from early, mid-, late- and near-term pregnancy were fixed and embedded in epoxy resin. Areas of foeto-maternal apposition were probed with a panel of biotinylated lectins followed by an avidin-peroxidase revealing system to identify various classes of glycan at the interface. Both the external epithelium of unspecialized bilaminar omphalopleure, which forms by early pregnancy, and chorioallantoic membrane which develops by mid-pregnancy, were composed of two phenotypes, one of which secreted a wide range of glycans including high mannose and complex N-glycan, N-acetyl glucosamine, lactosamine and galactosamine, which became less prominent from mid-pregnancy onwards. The uterine epithelium also contained a well-developed secretory apparatus producing a similar range of glycans and there were indications that glycosylated secretions were taken up by the overlying chorioallantois. Foetal vasculature was well developed while maternal vessels appeared more contracted, and both were richly sialylated like their therian equivalents. Our findings indicate that this reptile has evolved a true epitheliochorial placenta with many aspects in common with its therian counterparts but also with unique features of its own.

The age structure of the extinct giant Cape Verde skink Macroscincus coctei was studied using skeletochronology applied to 11 preserved males, 15 females, and one juvenile, collected at the end of the 19th century. Counts of lines of arrested growth (LAGs) indicated that in this species — which lived on islets with extreme natural conditions (e.g., hard aridity, lack of rainfall) — the maximum life span was estimated as 16 years for males and 12 years for females; the single juvenile was 4 years old. Although the sexes had similar mean ages, mean body length of males was significantly higher than that of females (283 versus 255 mm). There was no clear relationship between body length and estimated age, although the largest males were also the oldest. The analysis of LAGs revealed a sexual difference in growth rates, males reaching greater size earlier than females.

During a zoological survey in north-west Madagascar (Sahamalaza Peninsula) we documented aspects of the natural history of Boophis occidentalis (formerly a subspecies of B. albilabris and here raised to species level). Individual age assessed by skeletochronology ranged from 4 to 11 years. Breeding behaviour was observed at a seasonal stream after heavy rainfalls: five choruses of eight to 90 males aggregated in shallow brook sections. The males emitted low frequency calls and engaged in scramble battles. Only two females were found. A couple laid a large number of eggs, attached as a single layer on submerged stones. Tadpoles reared from these eggs had the typical morphology of brook-breeding Boophis species with a 1:5+5/3 keratodont formula and a relatively flattened body. Adult males had an anteroventrally oriented cloaca, a morphological trait shared with B. albilabris. Advertisement calls were similar in general structure to those of B. albilabris recorded at Anjanaharibe-Sud. They were unharmonious and consisted of pulsed notes emitted at irregular intervals. Much lower pulse rates in B. albilabris (30‐38 pulses/s) than in B. occidentalis (90‐109 pulses/s) support the specific distinctness of these taxa. The combination of characters related to reproductive biology in B. occidentalis and B. albilabris is unique in Boophis. The acontinuous breeding behaviour and large number of eggs per clutch are traits found in the pond-breeding species of the B. tephraeomystax group, while larval morphology and habitat are characteristic of brook-breeding species. Available morphological and molecular data place B. albilabris and B. occidentalis into the brookbreeding Boophis radiation. The acontinuous timing of reproduction and large egg number may be secondary adaptations that allowed the species to colonize arid regions of western Madagascar.

There are always more evidences indicating that 17β-estradiol (E2) is necessary for normal male fertility. We have used a nonmammalian vertebrate model (the lizard Podarcis s. sicula) to investigate the regulation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) activity in the testis during the annual sexual cycle and to study whether E2 exerts a role in the spermatogenesis through ERK1/2 activity. Immunocytochemistry analysis shows that ERK1/2 proteins are present in the nucleus of the spermatogonia (SPG), and in primary (1) spermatocytes (SPC). The annual E2 profile shows a progressive increase during the active spermatogenesis (from April to June) and a peak in the month of August (spermatogonial mitosis). In parallel, ERK1/2 (molecular weight 44 and 42 kDa, respectively) are highly phosphorylated during the period of active spermatogenesis and in post-refractory period (August) compared with the winter stasis (from November to March). Present results demonstrate that E2 treatment induces spermatogonial proliferation, possibly via the activation of ERK1/2, and this effect is counteracted by the antiestrogen ICI 182-780. © 2002 Wiley-Liss, Inc.

In 2012 Roma Municipality commissioned the Geological Survey of Italy the study of an area affected by a slow landslide movement along the south-eastern slope of Monteverde/Gianicolo Hill in Rome (Italy). The origin of the geomorphological instability of this area is probably a drawback of the anthropogenic activities for the construction of the railway station in Piazza Ippolito Nievo (in 1889) when huge amounts of terrain were dug from the foothill itself, removing the support for the overlying terrains and triggering mass movements since 1894 onwards. After the main event in 1964, some remediation works have been realized by Municipality consisting in a bulkhead at the foot of the buildings standing on top of the hill and surficial and deep drainage networks. Many monitoring surveys were conducted from 1964 to 2009 along both piezometers and inclinometers, but the landslide kinematic still remain undefined for a reliable evaluation of residual risk at present. This paper describes the equipments and the procedures used to assess the reliability of inclinometer measurements, analyzing the existing data and comparing them with the ones coming from the present measurement along some still-working instruments. The main outcomes are the classification of movements along the slope, the positions in depth of potential sliding surface and the preliminary estimate of the annual rate of displacements.

Objective.To describe a patient with a new onset bipolar disorder (BD) type II, secondary to a lacunar state.Background.Poststroke BD is rare and mainly associated with lesion in the prefrontal-striatal-thalamic circuit.Materials and Methods.A 51-year-old woman came to our attention for a mood disorder of recent onset. At 49, she had suffered acute left-sided limb weakness that improved spontaneously four days later. Arterial hypertension was subsequently diagnosed. After 6 months, she began to suffer from alternating brief periods of expansive and elevated mood with longer periods of depressed mood, with a suicide attempt. We performed extensive laboratory and instrumental investigations, as well as, psychiatric consultation, and a cognitive assessment, which was repeated 9 months later.Results.Brain magnetic resonance disclosed leukoaraiosis and a lacunar state of the basal ganglia. Transcranial Doppler showed a patent foramen ovale. A psychiatric consultation led to the diagnosis of BP type II. Neuropsychological evaluation detected deficits in attention/executive functions, verbal fluency, and memory. Nine months later, after specific psychiatric therapy, the psychiatric symptoms were remarkably improved.Conclusion.Our case sheds light on the role of the basal ganglia in mood disorders and the importance of ruling out brain injury in late onset BP.

The demand for referrals and diagnostic procedures in Italy has been rising constantly in recent years, making access to diagnostic services increasingly difficult with significant waiting times. A number of Health Authorities (known as Local Health Units) have responded by implementing formalised waiting-time prioritisation tools, giving rise to what are known as Homogeneous Waiting Groups (HWGs). The study describes the implementation of the HWG approach in Italy. This represents a promising tool for improving the prioritisation of patients waiting to see a specialist or to receive a diagnostic test. The study of the Italian HWG experience provides useful insights to improve the outpatient referral process for those countries where the demand prioritisation policies have focused more on inpatient care than outpatient specialist care and diagnostic services.

Intestinal transplantation has become a life-saving therapy in patients with irreversible loss of intestinal function and complications of total parenteral nutrition, but it entails a high incidence of neurologic complications, which occur more frequently than in other solid organ transplantations. Neurologic complications may be surgery-related or occur postoperatively, often within the first month. The etiology is various, often multifactorial, immunosuppression being one of the leading causes as intestine transplant recipients usually need potent immunosuppressive regimens. Neurologic problems after intestinal transplantation may present with a wide clinical spectrum, mainly mild to severe central nervous system disorders. Awareness of these complications is crucial for patients’ survival, since it will assist clinicians in prevention, prompt diagnosis, and treatment. This survey tackles the most common neurologic disorders and presents practice points of management which can help in the daily clinical care of intestinal transplant recipients.

Liver transplantation (LT) is the best treatment for end-stage liver diseases but it entails a high incidence of neuropsychiatric complications. These may be related to the operation or occur postoperatively, usually within the first month. The occurrence of neurological problems after LT increases the risk of mortality. The etiology of such complications is various, often multifactorial, immunosuppression being one of the most important causes. Immunosuppressive drugs may cause a wide spectrum of neuropsychiatric complications--mainly affecting the CNS--ranging from mild to severe disorders. A survey of the most frequent disorders is presented. In the management of liver-transplanted patients, the awareness of potential neurological and psychiatric problems is crucial for patients' survival, since it assists clinicians in prevention, prompt diagnosis, and treatment.

Neuroanatomical distribution of FMRFamide-like immunoreactivity was investigated in the brain and olfactory system of the viviparous skink, Chalcides chalcides. In the adult brain FMRFamide immunoreactive (ir) perikarya were observed in the diagonal band of Broca, medial septal nucleus, accumbens nucleus, bed nucleus of the anterior commissure, periventricular hypothalamic nucleus, lateral forebrain bundle, and lateral preoptic, subcommissural, suprachiasmatic and lateral hypothalamic areas. This pattern was seen in both male and female brains. Though all major brain areas showed FMRFamide-ir innervation, the densest ir fiber network was observed in the hypothalamus. During development, ir elements were observed for the first time in embryos at mid-pregnancy. FMRFamide perikarya were located along the ventral surface of the vomeronasal nerve, in the olfactory peduncle mediobasally, as well as in the anterior olfactory nucleus and olfactory tubercle. Furthermore, some ir neurons were observed in the rhombencephalic reticular substance; however, the ir fiber network was poorly developed. Later in development FMRFamide-ir neurons appeared also in the bed nucleus of the anterior commissure as well as the rhombencephalic nucleus of solitary tract and the dorsal motor nucleus of vagus nerve. In juveniles, the distribution profile of FMRFamide immunoreactivity was substantially similar to that of the adults, with a less widespread neuronal distribution and a more developed fiber network. Ontogenetic presence of FMRFamide immunoreactivity in the nasal area has been linked to the presence of a nervus terminalis in this reptile.

Intestinal transplantation has become a life-saving therapy in patients with irreversible loss of intestinal function and complications of total parenteral nutrition, but it entails a high incidence of neurologic complications, which occur more frequently than in other solid organ transplantations. Neurologic complications may be surgery-related or occur postoperatively, often within the first month. The etiology is various, often multifactorial, immunosuppression being one of the leading causes as intestine transplant recipients usually need potent immunosuppressive regimens. Neurologic problems after intestinal transplantation may present with a wide clinical spectrum, mainly mild to severe central nervous system disorders. Awareness of these complications is crucial for patients' survival, since it will assist clinicians in prevention, prompt diagnosis, and treatment. This survey tackles the most common neurologic disorders and presents practice points of management which can help in the daily clinical care of intestinal transplant recipients.

This paper examines the differences in body morphology, clutch size and viviparity between relatively elongated and non‐elongated species of Chalcides. Reduction in egg size and placentome development in snake‐like species seem to be necessary consequences of evolutionary body attenuation in this group of skinks. In particular, the elliptic placenta might have evolved to maintain adequate clutch size by compensating for yolk mass reduction.

We performed the first population-based case-control study on clinical risk factors and drug exposure in Guillain-Barre syndrome (GBS). Sixty patients with GBS were collected through an incidence survey performed in the Emilia-Romagna region of northern Italy. GBS patients were compared with 109 hospital controls (HC) and 59 population controls (PC) as for clinical events and drug exposure during the month preceding the study inclusion. Comparison of HC with PC showed no significant difference in the frequency of clinical events which occurred during the preceding month. This indicated that our HC were well representative of the general population for the risk factors investigated. GBS patients were compared with HC or both HC and PC using both univariate and multivariate analysis. Univariate analysis showed a significant association with fever and upper airway infection symptoms occurring in the preceding month. Furthermore, a significantly higher exposure to antibiotics, antipyretics/analgesics, and gangliosides was observed. However, multivariate analysis showed that only fever was significantly related to GBS onset (OR 28, 95% CI 5.2–313 for GBS vs. HC; OR 29, 95% CI 7.0–256 for GBS vs. HC and PC).

The structure of the corpus luteum and the steroidogenic activity of the corpus luteum and placenta in the viviparous reptile Chalcides chalcides have been investigated. The corpus luteum has a compact structure, almost without internal vascularized connective septa. It begins to degenerate after the middle of pregnancy, when plasma progesterone (P) remains high. The sections of the corpora lutea taken during early pregnancy showed an intense 3β-HSDH reaction, whereas the sections taken in late pregnancy gave weak reactions localized exclusively in the peripheral luteal cells. In contrast, sections of placentae taken at the beginning and in the middle of pregnancy always gave negative 3β-HSDH reactions, whereas those of late pregnancy were always strongly positive, localized in the maternal component of the placenta. In vitro, the corpora lutea from early pregnancy secreted significant amounts of P, whereas appreciable amounts of P were not detected in incubates of early pregnancy placentae. Near the time of delivery, P levels decreased in the culture medium of the corpora lutea, but increased in that of the placentae. The addition of pregnenolone (a precursor of P biosynthesis) to the culture medium caused an increase in the luteal and placental P levels, whereas the addition of trilostane (an inhibitor of 3β-HSDH) reduced them. The placenta of C. chalcides is suggested to have an endocrine function and to replace the corpus luteum in the production of P when the gland degenerates in late pregnancy.

Seasonal changes in gonadal morphology, secondary sexual characters, and plasma sex steroids were studied in male and female Bombina pachypus from southern Italy. In this species, frogs are active and breed from May to September. During the long breeding season, sperm were always present in the testes. However, the testes did not always exhibit all stages of spermatogene‐sis. In July, spermatogenesis did not exceed the stage of sperma‐tocyte I, whereas in August it included all stages. It is possible that males use sperm originating from the preceding fall for the earliest spring matings. Throughout the breeding season, females showed many follicles in advanced or complete vitellogenesis and many atretic vitellogenic follicles. Postovulatory follicles, if any, were rare. Females laid few eggs at each oviposition. Concerning male sex steroids, testosterone was at comparable levels from May to September, and it markedly decreased in October. In females, wide variations in plasma estradiol and proge...

We performed a case-control study to investigate the association between Campylobacter jejuni (CJ) infection and Guillain-Barr| syndrome (GBS) or Miller-Fisher syndrome. We compared 60 cases with 109 hospital controls matched for age, gender, hospital and geographical location. To diagnose the CJ infection, we considered the association between serologic positivity for CJ and a previous diarrheal illness within 3 months of inclusion in the study. Fifteen percent of cases versus 5% of hospital controls had CJ infection (p < 0.003, OR = 3.96, 95% CI: 1.0817.85). However, CJ infection was related to GBS only if it occurred during the previous month (p< 0.001, OR = 7.29, 95% CI: 1.4371.28). No statistical differences were found between the cases who were positive for CJ infection and those who were negative for CJ infection when studied by stepwise multivariate logistic regression for age, gender, clinical and electrophysiological features and outcome. Recent CJ infection may be a risk factor for GBS.

In recent years, a number of case reports and clinical studies have highlighted the risk of hepatitis B and C virus reactivation in patients with inflammatory bowel disease who are treated with immunosuppressive drugs. The cases of viral hepatitis reactivation that have been reported are characterized by a wide range of clinical manifestations, from viremia without clinically relevant manifestations to fulminant life-threatening hepatitis. The development and dissemination of biological immunosuppressive drugs have led to a significant increase in the number of reports of interest to physicians in a variety of clinical settings. On this topic, there have been a number of published guidelines and reviews that have collected the available evidence, providing recommendations on prophylactic and therapeutic strategies and methods for monitoring patients at risk. However, it should be noted that, to date, very few clinical studies have been published, and most of the recommendations have been borrowed from other clinical settings. The published studies are mostly retrospective and are based on very heterogeneous populations, using different therapeutic and prophylactic regimens and obtaining conflicting results. Thus, it seems clear that it is desirable to concentrate our efforts on prospective studies, not conducting further reviews of the literature in the continued absence of new evidence.

Hemichorea-hemiballism associated with non-ketotic hyperglycaemia is a rare dyskinetic syndrome during uncontrolled or undiagnosed diabetes. We reported a 41-year-old man suffering from sudden choreodystonic movements and undiagnosed hyperglycaemia. We described a combination of several rare aspects, emphasising the importance of screening for diabetes as a cause of acute onset of hyperkinetic movement disorders.

Objective: To assess the impact on stroke outcome of statin use in the acute phase after IV thrombolysis. Methods: Multicenter study on prospectively collected data of 2,072 stroke patients treated with IV thrombolysis. Outcome measures of efficacy were neurologic improvement (NIH Stroke Scale [NIHSS] ≤ 4 points from baseline or NIHSS = 0) and major neurologic improvement (NIHSS ≤ 8 points from baseline or NIHSS = 0) at 7 days and favorable (modified Rankin Scale [mRS] ≤ 2) and excellent functional outcome (mRS ≤ 1) at 3 months. Outcome measures of safety were 7-day neurologic deterioration (NIHSS ≥ 4 points from baseline or death), symptomatic intracerebral hemorrhage type 2 with NIHSS ≥ 4 points from baseline or death within 36 hours, and 3-month death. Results: Adjusted multivariate analysis showed that statin use in the acute phase was associated with neurologic improvement (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.26-2.25; p < 0.001), major neurologic improvement (OR 1.43, 95% CI 1.11-1.85; p = 0.006), favorable functional outcome (OR 1.63, 95% CI 1.18-2.26; p = 0.003), and a reduced risk of neurologic deterioration (OR: 0.31, 95% CI 0.19-0.53; p < 0.001) and death (OR 0.48, 95% CI 0.28-0.82; p = 0.007). Conclusion: Statin use in the acute phase of stroke after IV thrombolysis may positively influence short- and long-term outcome. © 2013 American Academy of Neurology.

Viral hepatitis reactivation has been widely reported in patients undergoing immunosuppressive therapy; however, few data are available about the risk of HBV and HCV reactivation in patients with inflammatory bowel disease, receiving immunosuppressive drugs. The aim of our study was to assess the prevalence of HBV and HCV infection in a consecutive series of patients with inflammatory bowel disease and to value the effects of immunosuppressive therapy during the course of the infection. Retrospective observational multicenter study included all consecutive patients with inflammatory bowel disease who have attended seven Italian tertiary referral hospitals in the last decade. A total of 5096 patients were consecutively included: 2485 Crohn's disease and 2611 Ulcerative Colitis. 30.5% and 29.7% of the patients were investigated for HBV and HCV infection. A total of 30 HBsAg positive, 17 isolated anti-HBc and 60 anti-HCV-positive patients were identified. In all, 20 patients with HBV or HCV infection received immunosuppressive therapy (six HBsAg+; four isolated anti-HBc+ and 10 anti-HCV+). One of six patients showed HBsAg+ and one of four isolated anti-HBc+ experienced reactivation of hepatitis. Two of six HBsAg patients received prophylactic therapy with lamivudine. Only one of 10 anti-HCV+ patients showed mild increase in viral load and ALT elevation. Screening procedures for HBV and HCV infection at diagnosis have been underused in patients with inflammatory bowel disease. We confirm the role of immunosuppressive therapy in HBV reactivation, but the impact on clinical course seems to be less relevant than previous reported.

Background & aims: We previously demonstrated the efficacy of garlic extract (GE) in the prevention of rat liver fibrosis by inhibiting tissue transglutaminase (tTG) activity. In the present study we aimed to evaluate the potential of GE in the regression of liver fibrosis and the underlining mechanism. Methods: Male Wistar rats were i.p. injected, twice a week, for 7 weeks, with CCl4 to develop liver fibrosis. Successively, a group was immediately sacrificed, while the remaining two groups received the GE or the vehicle, respectively, over the following 2 wks. A group of normal rats was also included in the study. Liver function, histology, and collagen deposition in parallel with gene and protein expression of α-SMA, tTG, TGF-β1, SEMA-7A, and metalloproteinase inhibitor 1 (TIMP1) as well as measure of active by total TGF-β1 were assessed. Results: CCl4 administration increased alanine-aminotransferase (ALT) activity, hepatic collagen deposition and gene and protein expression of all monitored markers. GE, but not the sole vehicle, restored liver histology and function by decreasing fibrogenesis markers (α-SMA, tTG, TGF-β1, SEMA-7A and TIMP1). Active by total TGF-β1 was significantly reduced (p < 0.05) in GE treated rats compared to the CCl4 at 7 weeks, and vehicle rats. Conclusions: These findings concurrently suggested that GE elicited therapeutic effect against liver fibrosis. Regression of liver fibrosis occurred by reducing myofibroblasts (through modulation of HSCs activation mechanisms), remodelling extracellular matrix (through increase of its degradation) and regenerating liver tissue and functions: three processes regulated by fine mechanisms where active TGF-β1 and tTG play a central role.

The Scura Valley involves the eastern slope of the complex of the Reatini Mountains (Central Apennines, Italy); it is crossed in its entirety by the Scura Torrent, tributary of the Velino River.

A 21-year-old woman with acute lymphoblastic leukemia underwent bone marrow transplantation (BMT). The conditioning regimen consisted of an association of busulfan (BU) and cyclophosphamide (Cy). The day after starting BU, she suffered a generalized tonic-clonic seizure. Electroencephalography (EEG) performed the day after the seizure showed diffuse polyspikes and spike-and-wave discharges. EEG on the following days showed persistent abnormalities (slowing of background activity intermixed with diffuse slow waves and isolated delta and theta bursts). These abnormalities persisted for about 20 days with complete normalization one month after the seizure. We suggest that BU is implicated in these abnormalities and emphasize the importance of EEG recording before and after bone marrow transplantation to disclose BU neurotoxicity.

We report the effects of treatment with plasma-exchange (PE) and intravenous immune globulins (IVIg) in 36 out of 50 patients with Guillain-Barre syndrome (GBS) recruited by an incidence study in the Emilia-Romagna region of Italy. Comparison of the patients treated with PE and IVIg showed no significant differences in terms of effectiveness in improving the clinical course of GBS: at one month, respectively 11.1% and 25% had recovered, and 55.5% and 58.3% had improved by at least one grade. These results are in agreement with those of the Dutch GBS trial. No relapses were observed in either group. Moreover, our results showed no difference in clinical outcome at 1 and 3 months between the patients receiving only one therapy and those receiving two; a second cycle of therapy did not seem to improve the clinical course of the disease significantly. We conclude that PE and IVIg are both safe and effective therapies for GBS.