A highly endemic area of Echinococcus multilocularis identified through a comparative re-assessment of prevalence in the red fox (Vulpes vulpes), Alto Adige (Italy: 2019-2020)

Surveillance of Echinococcus multilocularis at the edge of its range is hindered by fragmented distributional patterns and low prevalence in definitive hosts. Thus, tests with adequate levels of sensitivity are especially important for discriminating between infected and non-infected areas. In this study we reassessed the prevalence of E. multilocularis at the southern border of its distribution in Province of Bolzano (Alto Adige, northeastern Alps, Italy), to improve surveillance in wildlife and provide more accurate estimates of exposure risk. We compared the diagnostic test currently implemented for surveillance based on coproscopy and multiplex PCR (CMPCR) to a real-time quantitative PCR (qPCR) in 235 fox faeces collected in 2019 and 2020. The performances of the two tests were estimated using a scraping technique (SFCT) applied to the small intestines of a subsample (n = 123) of the same foxes as the reference standard. True prevalence was calculated and the sample size required by each faecal test for the detection of the parasite was then estimated. True prevalence of E. multilocularis in foxes (14.3%) was markedly higher than reported in the last decade, which was never more than 5% from 2012 to 2018 in the same area. In addition, qPCR showed a much higher sensitivity (83%) compared to CMPCR (21%) and agreement with the reference standard was far higher for qPCR (0.816) than CMPCR (0.298) meaning that for the latter protocol, a smaller sample size would be required to detect the disease. Alto Adige should be considered a highly endemic area. Routine surveillance on definitive hosts at the edges of the E. multilocularis distribution should be applied to smaller geographic areas, and rapid, sensitive diagnostic tools using directly host faeces, such as qPCR, should be adopted

Environmental Enrichment Promotes Plasticity and Visual Acuity Recovery in Adult Monocular Amblyopic Rats

Loss of visual acuity caused by abnormal visual experience during development (amblyopia) is an untreatable pathology in adults. In some occasions, amblyopic patients loose vision in their better eye owing to accidents or illnesses. While this condition is relevant both for its clinical importance and because it represents a case in which binocular interactions in the visual cortex are suppressed, it has scarcely been studied in animal models. We investigated whether exposure to environmental enrichment (EE) is effective in triggering recovery of vision in adult amblyopic rats rendered monocular by optic nerve dissection in their normal eye. By employing both electrophysiological and behavioral assessments, we found a full recovery of visual acuity in enriched rats compared to controls reared in standard conditions. Moreover, we report that EE modulates the expression of GAD67 and BDNF. The non invasive nature of EE renders this paradigm promising for amblyopia therapy in adult monocular people

Randomized trial on the effects of a combined physical/cognitive training in aged MCI subjects: the Train the Brain study

Age-related cognitive impairment and dementia are an increasing societal burden. Epidemiological studies indicate that lifestyle factors, e.g. physical, cognitive and social activities, correlate with reduced dementia risk; moreover, positive effects on cognition of physical/cognitive training have been found in cognitively unimpaired elders. Less is known about effectiveness and action mechanisms of physical/cognitive training in elders already suffering from Mild Cognitive Impairment (MCI), a population at high risk for dementia. We assessed in 113 MCI subjects aged 65-89 years, the efficacy of combined physical-cognitive training on cognitive decline, Gray Matter (GM) volume loss and Cerebral Blood Flow (CBF) in hippocampus and parahippocampal areas, and on brain-blood-oxygenation-level-dependent (BOLD) activity elicited by a cognitive task, measured by ADAS-Cog scale, Magnetic Resonance Imaging (MRI), Arterial Spin Labeling (ASL) and fMRI, respectively, before and after 7 months of training vs. usual life. Cognitive status significantly decreased in MCI-no training and significantly increased in MCI-training subjects; training increased parahippocampal CBF, but no effect on GM volume loss was evident; BOLD activity increase, indicative of neural efficiency decline, was found only in MCI-no training subjects. These results show that a non pharmacological, multicomponent intervention improves cognitive status and indicators of brain health in MCI subjects

Pattern of care and effectiveness of treatment for glioblastoma patients in the real world: Results from a prospective population-based registry. Could survival differ in a high-volume center?

BACKGROUND: As yet, no population-based prospective studies have been conducted to investigate the incidence and clinical outcome of glioblastoma (GBM) or the diffusion and impact of the current standard therapeutic approach in newly diagnosed patients younger than aged 70 years. METHODS: Data on all new cases of primary brain tumors observed from January 1, 2009, to December 31, 2010, in adults residing within the Emilia-Romagna region were recorded in a prospective registry in the Project of Emilia Romagna on Neuro-Oncology (PERNO). Based on the data from this registry, a prospective evaluation was made of the treatment efficacy and outcome in GBM patients. RESULTS: Two hundred sixty-seven GBM patients (median age, 64 y; range, 29-84 y) were enrolled. The median overall survival (OS) was 10.7 months (95% CI, 9.2-12.4). The 139 patients 64aged 70 years who were given standard temozolomide treatment concomitant with and adjuvant to radiotherapy had a median OS of 16.4 months (95% CI, 14.0-18.5). With multivariate analysis, OS correlated significantly with KPS (HR = 0.458; 95% CI, 0.248-0.847; P = .0127), MGMT methylation status (HR = 0.612; 95% CI, 0.388-0.966; P = .0350), and treatment received in a high versus low-volume center (HR = 0.56; 95% CI, 0.328-0.986; P = .0446). CONCLUSIONS: The median OS following standard temozolomide treatment concurrent with and adjuvant to radiotherapy given to (72.8% of) patients aged 6470 years is consistent with findings reported from randomized phase III trials. The volume and expertise of the treatment center should be further investigated as a prognostic factor

La capitalizzazione delle aziende di credito: gli anni '80

Il lavoro analizza l'entità del processo di ricapitalizzazione e le diversità di comportamento fra banche esaminando sia la relazione crescita-patrimonio-redditività, sia le modalità in cui la crescita patrimoniale ha avuto luogo nel periodo 1980-1988

Impact of Environmental and Familial Factors in a Cohort of Pediatric Patients with Inflammatory Bowel Disease

OBJECTIVES: The primary role of environment on Inflammatory Bowel Disease (IBD) onset has been recently stressed. We aimed to investigate the impact of environmental factors in an IBD pediatric cohort. METHODS: A total of 467 subjects (264 IBD and 203 controls) were enrolled. All patients underwent a questionnaire including 5 different groups of environmental risk factors: family history of IBD and autoimmune diseases, perinatal period, home amenities and domestic hygiene, childhood diseases and vaccinations, diet. RESULTS: In a multivariate model, mother's degree (OR: 5.5; 2.5-11.6), duration of breast feeding >3 month (OR: 4.3; 1.6-10.5), father's employment (OR: 3.7; 1.2-8.7), gluten introduction <6 month (OR: 2.8; 1.5-5), number of siblings <2 (OR: 2.8; 1.5-5.3) and family history of autoimmune diseases (OR: 2.7; 1-4-5.3) were significant risk factors for CD. Low adherence to Mediterranean diet (OR: 2.3; 1.2-4.5), gluten introduction <6 month (OR: 2.8; 1.6-4.9) and number of siblings <2 (OR: 2; 1.1-3.6) were significant risk factors for UC. Owning pets (OR: 0.3; 0.1-0.7) and bed sharing (OR: 0.2; 0.1-0.6) were protective factors for CD, while owning pets (OR: 0.4; 0.2-0.8) and family parasitosis (OR: 0.07; 0.01-0.4) resulted protective factors for UC. CONCLUSIONS: Our study confirms that environmental factors are closely linked to IBD onset and may partly explain IBD rise in developed countries

P046 Effects of CB2 and TRPV1 stimulation on osteoclast overactivity induced by iron in pediatric inflammatory bowel disease

Abstract Background The reduction of bone mineral density and osteoporosis (OP) has an high impact on inflammatory bowel disease (IBD) patients’ health. We have previously shown that a dysregulated iron metabolism occurs in IBD and leads to a decrease in circulating iron concentration and an excessive intracellular sequestration of iron. Studies suggest that iron overload affects the bone, accelerating osteoclasts (OCs) differentiation and activation with consequent bone resorption. The aim of this study was to evaluate the role of Cannabinoid Receptor type 2 (CB2) and transient receptor potential vanilloid type-1 (TRPV1) and of the iron in the development of osteoporosis in pediatric IBD. Methods We enrolled 21 young subjects aged less than 18 years stratified into 3 groups on the basis of the clinical diagnosis: 7 with Ulcerative Colitis (UC) 7 with Crohn’s disease (CD) and 7 were non-IBD controls (CTR). We evaluated the role of CB2 and TRPV1 receptors and of iron in the development of OP in pediatric IBD at diagnosis and analyzed the effects of the pharmacological modulation of CB2 and TRPV1 receptors on osteoclast activity and on iron metabolism by Western Blotting, Tartrate-resistant acid phosphatase assay (TRAP assay) and Iron Assay Kit. We evaluated bone resorption through a commercially available kit visualizing and counting the resorption pits with the optical microscope. Results We observed higher levels of TRPV1 and lower levels of CB2 in the OCs from UC and CD patients compared to CTR. In IBD patients we found a significant up-regulation of osteoclast markers TRAP and Cathepsin K and a consequent osteoclast hyper-activation. The treatments of OCs from IBD patients with the CB2 agonist JWH-133 and the TRPV1 agonist Resinferatoxin, RTX, led to a significant reduction of osteoclastic hyper-activation affecting bone markers expression, number and size of active OCs, and bone resorption area. We also analyzed the [Fe3+] concentration and the expression of iron metabolism modulators, ferroportin1(FPN-1) and divalent metal transporter1(DMT1), in OCs derived from IBD patients. We demonstrated an increase of [Fe3+] and accordingly a decrease of FPN-1 in both groups of patients and an increase of DMT1 levels. After 48h of exposure to JWH-133 and RTX we observed a significant reduction of DMT1 expression in OCs from IBD patients together with a strong increase of FPN-1. Conclusion Our data confirm the well-known role of CB2 and TRPV1 receptors in bone metabolism and suggest that their stimulation can reduce the osteoclast overactivity induced by iron, thus providing new insights into the pathogenesis and in the treatment of pediatric IBD-related bone resorption

Does Azathioprine induce endoscopic and histologic healing in pediatric inflammatory bowel disease? A prospective, observational study

Background: The new concept of disease remission for pediatric inflammatory bowel diseases (IBD) implies the achievement of mucosal healing. Aims: We aimed to evaluate endoscopic and histologic healing in children with Ulcerative Colitis (UC) and Crohn's disease (CD) in clinical remission after 52 weeks of Azathioprine. Methods: From December 2012 to July 2015 we prospectively enrolled IBD children starting Azathioprine. Enrolled patients in clinical remission underwent colonoscopy after 52 weeks. Macroscopic assessment was described with Mayo score and the simplified endoscopic score for UC and CD, respectively. For microscopic assessment, an average histology score was used. Data on inflammatory markers and fecal calprotectin were also collected. Results: Fourty-seven patients were included in the analysis. Endoscopic healing was detected in 20/26 (76.9%) UC children and 10/21 (47.6%) CD patients. Median Mayo score and simplified endoscopic score were significantly decreased at week 52 (p < 0.001; p = 0.005). Median average histology score was not significantly different at week 52 in both diseases. Fecal calprotectin was directly correlated with simplified endoscopic score (T0: r = 0.4, p = 0.05; T52: r = 0.5, p = 0.01), but not with Mayo score. No correlation was found between endoscopic and histologic scores. Conclusions: IBD children under Azathioprine reach endoscopic healing, but not histological remission

Effects of CB2 Receptor Modulation on Macrophage Polarization in Pediatric Celiac Disease

Celiac Disease (CD) represents an autoimmune disorder triggered by the exposure to gluten in genetically susceptible individuals. Recent studies suggest the involvement of macrophages in CD pathogenesis. Macrophages are immune cells, present as pro-inflammatory classically activated macrophages (M1) or as anti-inflammatory alternatively activated macrophages (M2). The Cannabinoid Receptor 2 (CB2) has important anti-inflammatory and immunoregulatory properties. We previously demonstrated that a common CB2 functional variant, Q63R, causing CB2 reduced function, is associated with several inflammatory and autoimmune diseases The first aim of this study was to investigate the phenotype of macrophages isolated from peripheral blood of CD patients and CB2 expression. The second aim was to evaluate the effects of CB2 pharmacological modulation on CD macrophage polarization. Moreover, by an in vitro model of "immunocompetent gut" we investigated the role of CD macrophages in inducing intestinal barrier damage and the possibility to restore its functionality modulating their polarization. We found an increased expression of M1 macrophages and a CB2 reduced expression. We also demonstrated CD M1 macrophages in inducing the typical mucosal barrier damage of CD. CB2 stimulation switches macrophage polarization towards the anti-inflammatory M2 phenotype thus reducing inflammation but also limiting the epithelial dysfunction. Therefore, we suggest CB2 receptor as a possible novel therapeutic target for CD by regulating macrophages polarization and by preventing mucosal barrier damage

Effects of CB2 Receptor Modulation on Macrophage Polarization in Pediatric Celiac Disease

Celiac Disease (CD) represents an autoimmune disorder triggered by the exposure to gluten in genetically susceptible individuals. Recent studies suggest the involvement of macrophages in CD pathogenesis. Macrophages are immune cells, present as pro-inflammatory classically activated macrophages (M1) or as anti-inflammatory alternatively activated macrophages (M2). The Cannabinoid Receptor 2 (CB2) has important anti-inflammatory and immunoregulatory properties. We previously demonstrated that a common CB2 functional variant, Q63R, causing CB2 reduced function, is associated with several inflammatory and autoimmune diseases The first aim of this study was to investigate the phenotype of macrophages isolated from peripheral blood of CD patients and CB2 expression. The second aim was to evaluate the effects of CB2 pharmacological modulation on CD macrophage polarization. Moreover, by an in vitro model of &ldquo;immunocompetent gut&rdquo; we investigated the role of CD macrophages in inducing intestinal barrier damage and the possibility to restore its functionality modulating their polarization. We found an increased expression of M1 macrophages and a CB2 reduced expression. We also demonstrated CD M1 macrophages in inducing the typical mucosal barrier damage of CD. CB2 stimulation switches macrophage polarization towards the anti-inflammatory M2 phenotype thus reducing inflammation but also limiting the epithelial dysfunction. Therefore, we suggest CB2 receptor as a possible novel therapeutic target for CD by regulating macrophages polarization and by preventing mucosal barrier damage