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Background Choroid plexus cysts (CPCs) are a type of neuroepithelial cysts, benign lesions located more frequently in the supratentorial compartment. Symptomatic CPCs in the posterior fossa are extremely rare and can be associated with obstructive hydrocephalus. Case Description A previously healthy elderly woman suffered intermittent attacks of headache and vomiting associated with gait instability. Magnetic resonance imaging documented a large cystic lesion occupying all the fourth ventricle. An endoscope-assisted fenestration of the lesion through a telovelar approach determined only temporary improvement, hence a second surgery with gross total resection of the cyst was performed, with successful long-term clinical and radiologic resolution. Histology revealed CPC. Conclusions Fourth ventricle symptomatic CPCs are extremely rare lesions, especially in the elderly. Their presence must be carefully evaluated as a possible rare cause of intermittent obstructive hydrocephalus. Even though cyst fenestration with restoration of the cerebrospinal fluid pathway represents the best treatment in the majority of cases, a more aggressive resection is sometimes necessary.

BACKGROUND Distal transradial access (dTRA) has been recently proposed as an innovative access for coronary procedures and a valuable alternative to conventional transradial access (cTRA). The aim of this study was to assess the safety of dTRA versus cTRA in patients undergoing percutaneous coronary angiography and intervention. METHODS In this single-center randomized trial, consecutive patients admitted for stable cardiac condition or acute coronary syndrome (ACS) were assigned to dTRA or cTRA. The primary endpoint was an early discharge after transradial stenting of coronary arteries (EASY) grade ≥II access-site hematoma (ASH). Vascular access failure, radial artery occlusion (RAO) at hospital discharge , 30-day rates of death, myocardial infarction, stroke and bleeding not related to coronary artery bypass grafting were considered as secondary endpoints. RESULTS A total of 204 patients were included and randomized to dTRA (n=100) or cTRA (n=104). The two populations were similar, except for a higher percentage of ACS in the dTRA than in the cTRA group (38% versus 24%, P=0.022). The rate of EASY grade ≥II ASH was lower in dTRA than in cTRA patients, but the difference was not statistically significant (4% versus 8.4%, respectively, P=0.25). Vascular access failure was more frequent in dTRA patients than in cTRA patients (34% versus 8.7%, P

Climate-Smart Forestry (CSF) is a developing concept to help policymakers and practitioners develop focused forestry governance and management to adapt to and mitigate climate change. Within the EU COST Action CA15226, CLIMO (Climate-Smart Forestry in Mountain Regions), a CSF definition was developed considering three main pillars: (1) adaptation to climate change, (2) mitigation of climate change, and (3) the social dimension. Climate mitigation occurs through carbon (C) sequestration by trees, C storage in vegetation and soils, and C substitution by wood. However, present and future climate mitigation depends on the adaptation of trees, woods, and forests to adapt to climate change, which is also driven by societal change.Criteria and Indicators (C & I) can be used to assess the climate smartness of forestry in different conditions, and over time. A suite of C & I that quantify the climate smartness of forestry practices has been developed by experts as guidelines for CSF. This chapter charts the development of this definition, presents initial feedback from forest managers across Europe, and discusses other gaps and uncertainties, as well as potential future perspectives for the further evolution of this concept.

Trees are long-lived organisms that contribute to forest development over centuries and beyond. However, trees are vulnerable to increasing natural and anthropic disturbances. Spatially distributed, continuous data are required to predict mortality risk and impact on the fate of forest ecosystems. In order to enable monitoring over sensitive and often remote forest areas that cannot be patrolled regularly, early warning tools/platforms of mortality risk need to be established across regions. Although remote sensing tools are good at detecting change once it has occurred, early warning tools require ecophysiological information that is more easily collected from single trees on the ground.Here, we discuss the requirements for developing and implementing such a tree-based platform to collect and transmit ecophysiological forest observations and environmental measurements from representative forest sites, where the goals are to identify and to monitor ecological tipping points for rapid forest decline. Long-term monitoring of forest research plots will contribute to better understanding of disturbance and the conditions that precede it. International networks of these sites will provide a regional view of susceptibility and impacts and would play an important role in ground-truthing remotely sensed data.

Climate-smart forestry can be regarded as the evolution of traditional silviculture. As such, it must rely on smart harvesting equipment and techniques for a reliable and effective application. The introduction of sensors and digital information technologies in forest inventories, operation planning, and work execution enables the achievement of the desired results and provides a range of additional opportunities and data. The latter may help to better understand the results of management options on forest health, timber quality, and many other applications. The introduction of intelligent forest machines may multiply the beneficial effect of digital data gathered for forest monitoring and management, resulting in forest harvesting operations being more sustainable in terms of costs and environment. The interaction can be pushed even further by including the timber processing industry, which assesses physical and chemical characteristics of wood with sensors to optimize the transformation process. With the support of an item-level traceability system, the same data could provide a formidable contribution to CSF. The “memory” of wood could support scientists to understand the response of trees to climate-induced stresses and to design accordingly an adaptive silviculture, contributing to forest resilience in the face of future changes due to human-induced climate alteration.

Background Glyphosate-based herbicides (GBHs) are the most widely used pesticides worldwide, and glyphosate is the active ingredient of such herbicides, including the formulation known as Roundup. The massive and increasing use of GBHs results in not only the global burden of occupational exposures, but also increased exposure to the general population. The current pilot study represents the first phase of a long-term investigation of GBHs that we are conducting over the next 5 years. In this paper, we present the study design, the first evaluation of in vivo parameters and the determination of glyphosate and its major metabolite aminomethylphosphonic acid (AMPA) in urine. Methods We exposed Sprague-Dawley (SD) rats orally via drinking water to a dose of glyphosate equivalent to the United States Acceptable Daily Intake (US ADI) of 1.75 mg/kg bw/day, defined as the chronic Reference Dose (cRfD) determined by the US EPA, starting from prenatal life, i.e. gestational day (GD) 6 of their mothers. One cohort was continuously dosed until sexual maturity (6-week cohort) and another cohort was continuously dosed until adulthood (13-week cohort). Here we present data on general toxicity and urinary concentrations of glyphosate and its major metabolite AMPA. Results Survival, body weight, food and water consumption of the animals were not affected by the treatment with either glyphosate or Roundup. The concentration of both glyphosate and AMPA detected in the urine of SD rats treated with glyphosate were comparable to that observed in animals treated with Roundup, with an increase in relation to the duration of treatment. The majority of glyphosate was excreted unchanged. Urinary levels of the parent compound, glyphosate, were around 100-fold higher than the level of its metabolite, AMPA. Conclusions Glyphosate concentrations in urine showed that most part of the administered dose was excreted as unchanged parent compound upon glyphosate and Roundup exposure, with an increasing pattern of glyphosate excreted in urine in relation to the duration of treatment. The adjuvants and the other substances present in Roundup did not seem to exert a major effect on the absorption and excretion of glyphosate. Our results demonstrate that urinary glyphosate is a more relevant marker of exposure than AMPA in the rodent model.

The challenge to harmonize nature-based tourism with species conservation is important both from an economic, cultural and ecological perspective. One approach for understanding this interaction is to compare the spatiotemporal overlap between tourism activities and the focal species’ space use, with the purpose to identify areas, periods, and conditions in which tourism exerts the highest negative impact. Here, we combine GPS data from 66 wild reindeer with on-site surveys of tourist (n = 13434 respondents at 66 locations) and trail use counters (n = 99 sites) in three Norwegian national parks. Our findings highlight a large-scale segregation during the summer season, as wild reindeer move to areas less prone to disturbance by humans. Based on these findings, we discuss a management model to segregate tourists from wild reindeer in space and/or time during summer with the goal of long-term sustainable coexistence.

Safety concerns on the toxic and carcinogenic effects of formalin exposure have drawn increasing attention to the search for alternative low risk fixatives for processing tissue specimens in laboratories worldwide. Alcohol-based fixatives are considered some of the most promising alternatives. We evaluated the performance of alcohol-fixed paraffin-embedded (AFPE) samples from Sprague-Dawley (SD) rats analyzing tissue morphology, protein and nucleic acid preservation after short and extremely long fixation times (up to 7 years), using formalin-fixed paraffin-embedded (FFPE) samples as a comparator fixative. Following short and long-term alcohol fixation, tissue morphology and cellular details in tissues, evaluated by scoring stained sections (Hematoxylin-Eosin and Mallory’s trichrome), were optimally preserved if compared to formalin fixation. Immunoreactivity of proteins (Ki67, CD3, PAX5, CD68), evaluated by immunohistochemistry, showed satisfactory results when the fixation period did not exceed 1 year. Finally, we confirm the superiority of alcohol fixation compared to formalin, in terms of quantity of nucleic acid extracted from paraffin blocks, even after an extremely long time of alcohol fixation. Our results confirm that alcohol fixation is a suitable and safe alternative to formalin for pathological evaluations. There is a need for standardization of formalin-free methods and harmonization of diagnosis in pathology department worldwide.

Anterior, benign epidural cysts are a rarely described cause of non discal lumbar radiculopathy. The differentiation between synovial, ganglion, fibrous annulus, posterior longitudinal ligament and disc cysts reflects the fragmentary nature of reports so far and it's probably misleading. A case of ventral L5-S1 synovial cyst is reported and the literature is reviewed. It is proposed that these lesions be all grouped together as anterior epidural degenerative cysts of the lumbar spine on the ground of shared clinical and MRI features and management options along with a common pathogenesis (response to degenerative spinal changes) and histological substrate. Keywords: Lumbar spine, Epidural cyst, Pathology

Human exposure to glyphosate has become ubiquitous because of its increasing agricultural use. Recent studies suggest endocrine disrupting effects of glyphosate. Specifically, in our work in rodents, low-dose early-life exposure to Roundup® (glyphosate-based herbicide) lengthened anogenital distance (AGD) in male and female offspring. AGD is a marker of the prenatal hormone milieu in rodents and humans. The relationship between glyphosate exposure and AGD has not been studied in humans. We conducted a pilot study in 94 mother-infant pairs (45 female and 49 male) from The Infant Development and the Environment Study (TIDES). For each infant, two AGD measurements were collected after birth; the anopenile (AGD-AP) and anoscrotal (AGD-AS) distances for males, and anoclitoral (AGD-AC) and anofourchette distances (AGD-AF) for females. We measured levels of glyphosate and its degradation product aminomethylphosphonic acid (AMPA) in 2nd trimester maternal urine samples using ultra-high-performance liquid chromatography-tandem mass spectrometry. We assessed the relationship between exposure and AGD using sex-stratified multivariable linear regression models. Glyphosate and AMPA were detected in 95% and 93% of the samples (median 0.22 ng/mL and 0.14 ng/mL, respectively). Their concentrations were moderately correlated (r = 0.55, p = 5.7 × 10−9). In female infants, high maternal urinary glyphosate (above the median) was associated with longer AGD-AC (β = 1.48, 95%CI (−0.01, 3.0), p = 0.05), but this was not significant after covariate adjustment. Increased AMPA was associated with longer AGD-AF (β = 1.96, 95%CI (0.44, 3.5), p = 0.01) after adjusting for infant size and age at AGD exam. No associations were detected in male offspring. These preliminary findings partially reproduce our previous results in rodents and suggest that glyphosate is a sex-specific endocrine disruptor with androgenic effects in humans. Given the increasing glyphosate exposures in the US population, larger studies should evaluate potential developmental effects on endocrine and reproductive systems.

An amendment to this paper has been published and can be accessed via the original article.

Background: Double pituitary adenomas (DA) are two morphologically and immunohystochemically different tumours in the same gland. They are rare, generally small adenomas and divided in: separated, when clearly recognizable before or during surgery, and contiguous, when diagnosed only in the following histopathological examination. Acromegaly and Cushing’s disease are the main prevalent clinical presentation. Objective: We described two cases of DA in a surgical series over 16 years in a single center. Methods: In September 2018, we diagnosed a DA in a man with acromegaly (case 1). In order to assess the presence of other cases of DA, we performed a retrospective analysis of the endonasal endoscopically operated sellar adenomas from January 2004 to December 2019. Results : 468 pituitary adenomas were found. A DA with a Pit-1 positive macroadenoma (GH-TSH- PRL positive) and an ACTH microadenoma clinically silent in an acromegalic woman was retrospectively found (case 2). Conclusion : Our analysis confirms that DA are rare (0.4% of the pituitary adenomas) and often associated with acromegaly. Their pre-operatively diagnosis is difficult but clinician’s awareness of DA can improve the diagnosis. The use of pituitary transcription factors could be useful in detecting DA.

Biochar is a carbonaceous material produced through the pyro-gasification of biomass. In the last decade, biochar has been proposed as a soil amendment because it can improve soil physico-chemical properties and carbon stocks, contributing to climate change mitigation.In the framework of the Wood-Up project (Optimization of WOOD gasification chain in South Tyrol to prodUce bioenergy and other high-value green Products to enhance soil fertility and mitigate climate change, FESR1028), we studied the impact of conifer wood biochar on the emissions of the main greenhouse gases (GHGs) from the soil: carbon dioxide (CO2), nitrous oxide (N2O) and methane (CH4), as well as on the soil carbon stock of agricultural fields in South Tyrol.In May 2017, 25 and 50 t ha-1 of pure biochar and biochar mixed with compost (45 t ha-1), were applied to the soil of a vineyard near Merano (South-Tyrol, northern Italy) following a randomized block experimental design with four replicates per treatment.Soil GHGs fluxes were monitored from June 2017 until December 2019. Fluxes were measured, in real time, with a high-resolution portable multi-gas analyzer based on cavity ring-down spectroscopy technology (Picarro inc., Santa Clara, CA, USA) connected to an automated dynamic chambers system (Eosense Inc., Dartmouth, NS, Canada). Gas emissions were measured monthly and were related to soil temperature and moisture to evaluate the impact of treatments on the sensitivity of GHGs fluxes to environmental parameters. The stability of conifer wood biochar in soil was assessed through the quantification of the Benzene PolyCarboxylic Acids (BPCA), specific biomarkers of black carbon, over time. The BPCA content in the soil was measured before the application of biochar and compost, three weeks after the application and two years later.During the first year of experiment, in biochar-amended soils, we observed a reduction of the temperature sensitivity of all GHGs fluxes in comparison to treatments without biochar (control and compost alone). In the second and third year an opposite trend was observed, with an increase of temperature sensitivity of GHGs fluxes in biochar-treated soil. The change of biochar effect over time might be linked to biochar ageing in soil. However, a role of soil moisture cannot be excluded, as it was higher in the first year of experiment. The experimental results will be presented in the broader context of the Wood-Up project.

Background In 2011, IARC classified radiofrequency radiation (RFR) as possible human carcinogen (Group 2B). According to IARC, animals studies, as well as epidemiological ones, showed limited evidence of carcinogenicity. In 2016, the NTP published the first results of its long-term bioassays on near field RFR, reporting increased incidence of malignant glial tumors of the brain and heart Schwannoma in rats exposed to GSM – and CDMA – modulated cell phone RFR. The tumors observed in the NTP study are of the type similar to the ones observed in some epidemiological studies of cell phone users. Objectives The Ramazzini Institute (RI) performed a life-span carcinogenic study on Sprague-Dawley rats to evaluate the carcinogenic effects of RFR in the situation of far field, reproducing the environmental exposure to RFR generated by 1.8 GHz GSM antenna of the radio base stations of mobile phone. This is the largest long-term study ever performed in rats on the health effects of RFR, including 2448 animals. In this article, we reported the final results regarding brain and heart tumors. Methods Male and female Sprague-Dawley rats were exposed from prenatal life until natural death to a 1.8 GHz GSM far field of 0, 5, 25, 50 V/m with a whole-body exposure for 19 h/day. Results A statistically significant increase in the incidence of heart Schwannomas was observed in treated male rats at the highest dose (50 V/m). Furthermore, an increase in the incidence of heart Schwann cells hyperplasia was observed in treated male and female rats at the highest dose (50 V/m), although this was not statistically significant. An increase in the incidence of malignant glial tumors was observed in treated female rats at the highest dose (50 V/m), although not statistically significant. Conclusions The RI findings on far field exposure to RFR are consistent with and reinforce the results of the NTP study on near field exposure, as both reported an increase in the incidence of tumors of the brain and heart in RFR-exposed Sprague-Dawley rats. These tumors are of the same histotype of those observed in some epidemiological studies on cell phone users. These experimental studies provide sufficient evidence to call for the re-evaluation of IARC conclusions regarding the carcinogenic potential of RFR in humans.

// Sandra Durante 1, * , Silvia Vecchiarelli 2, * , Annalisa Astolfi 1 , Elisa Grassi 2 , Riccardo Casadei 3 , Donatella Santini 4 , Riccardo Panzacchi 4 , Claudio Ricci 3 , Salvatore Serravalle 5 , Giuseppe Tarantino 1 , Mirella Falconi 6 , Gabriella Teti 6 , Valentina Indio 1 , Andrea Pession 5 , Francesco Minni 3 , Guido Biasco 1, 2 , Mariacristina Di Marco 2 1 Giorgio Prodi Cancer Research Centre, University of Bologna, Bologna, Italy 2 Department of Experimental, Diagnostic and Specialty Medicine University of Bologna, Sant’Orsola-Malpighi Hospital, Bologna, Italy 3 Department of Medical and Surgical Sciences, University of Bologna, Sant’Orsola-Malpighi Hospital, Bologna, Italy 4 Pathology Unit, Sant'Orsola-Malpighi Hospital, Bologna, Italy 5 Department of Medical and Surgical Sciences, “Lalla Seragnoli” Hematology-Oncology Unit, University of Bologna, Bologna, Italy 6 DIBINEM—Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy * These authors contributed equally to this work Correspondence to: Annalisa Astolfi, email: annalisa.astolfi@unibo.it Keywords: PDA, IPMN, chromosome 3, NGS, PIK3CA Received: April 11, 2016 Accepted: August 10, 2016 Published: August 22, 2016 ABSTRACT Background: Intraductal papillary mucinous neoplasm (IPMN) is the most common cystic preneoplastic lesion of pancreatic cancer. We used an approach coupling high resolution cytogenetic analysis (Affymetrix Oncoscan FFPE Array) with clinically-oriented bioinformatic interpretation of data to understand the most relevant alterations of precursor lesions at different stages to identify new diagnostic markers. Results: We identified multiple copy number alterations, particularly in lesions with severe dysplasia, with 7 IPMN with low-intermediate dysplasia carrying a nearly normal karyotype and 13 IPMN with complex Karyotype (> 4 alterations), showing high grade dysplasia. A specific gain of chromosome arm 3q was found in IPMN with complex Karyotype (92%). This gain of 3q is particularly interesting for the presence of oncogenes such as PIK3CA, GATA2 and TERC that are part of pathways that deregulate cell growth and promote disease progression. Quantitative PCR and FISH analysis confirmed the data . Further demonstration of the overexpression of the PIK3CA gene supports the identification of this alteration as a possible biomarker in the early identification of patients with IPMN at higher risk for disease progression. Materials and methods: High resolution cytogenetic analysis was performed in 20 formalin fixed paraffin embedded samples of IPMN by Oncoscan FFPE assay. Results were validated by qPCR and FISH analysis. Conclusions: The identification of these markers at an early stage of disease onset could help to identify patients at risk for cancer progression and new candidates for a more specific targeted therapy.

Background Glyphosate-based herbicides (GBHs) are broad-spectrum herbicides that act on the shikimate pathway in bacteria, fungi, and plants. The possible effects of GBHs on human health are the subject of an intense public debate for both its potential carcinogenic and non-carcinogenic effects, including potential effects on the endocrine system The present pilot study examine whether exposure to GBHs at the dose of glyphosate considered to be “safe” (the US Acceptable Daily Intake - ADI - of 1.75 mg/kg bw/day), starting from in utero life, affect the development and endocrine system across different life stages in Sprague Dawley (SD) rats. Methods Glyphosate alone and Roundup Bioflow, a commercial brand of GBHs, were administered in drinking water at 1.75 mg/kg bw/day to F0 dams starting from the gestational day (GD) 6 (in utero) up to postnatal day (PND) 120. After weaning, offspring were randomly distributed in two cohorts: 8 M + 8F/group animals belonging to the 6-week cohort were sacrificed after puberty at PND 73 ± 2; 10 M + 10F/group animals belonging to the 13-week cohort were sacrificed at adulthood at PND 125 ± 2. Effects of glyphosate or Roundup exposure were assessed on developmental landmarks and sexual characteristics of pups. Results In pups, anogenital distance (AGD) at PND 4 was statistically significantly increased both in Roundup-treated males and females and in glyphosate-treated males. Age at first estrous (FE) was significantly delayed in the Roundup-exposed group and serum testosterone concentration significantly increased in Roundup-treated female offspring from the 13-week cohort compared to control animals. A statistically significant increase in plasma TSH concentration was observed in glyphosate-treated males compared with control animals as well as a statistically significant decrease in DHT and increase in BDNF in Roundup-treated males. Hormonal status imbalances were more pronounced in Roundup-treated rats after prolonged exposure. Conclusions The present pilot study demonstrate that GBHs exposure, from prenatal period to adulthood, induced endocrine effects and altered reproductive developmental parameters in male and female SD rats. In particular, it was associated with androgen-like effects, including a statistically significant increase of AGDs in both males and females, delay of FE and increased testosterone in female. Electronic supplementary material The online version of this article (10.1186/s12940-019-0453-y) contains supplementary material, which is available to authorized users.

Lymphomas and leukaemias involving the lung have in some cases been hard to distinguish from respiratory tract infection in Sprague-Dawley (SD) rats from long-term bioassays. In order to differentiate between tumours and immune cell infiltrates, updated pathological criteria and nomenclature were used and immunohistochemistry (IHC) was applied to haematopoietic and lymphoid tissue tumours (HLTs) in the original prenatal long-term Aspartame (APM) study performed by the Ramazzini Institute (RI). All 78 cases of HLTs from treated and control groups were re-examined based on light microscopic morphological characteristics and subjected to a panel of IHC markers including Ki67, CD3, PAX5, CD20, CD68, TdT, CD45, CD14 and CD33. The analysis confirmed the diagnoses of HLTs in 72 cases, identified 3 cases of preneoplastic lesions (lymphoid hyperplasia), and categorized 3 cases as inflammatory lesions. A statistically significant increase in total HLTs (p = 0.006), total lymphomas (p = 0.032) and total leukaemias (p = 0.031) in treated female rats was confirmed (high dose vs control), and a statistically significant linear trend for each HLT type was also observed. After the HLT cases re-evaluation, the results obtained are consistent with those reported in the previous RI publication and reinforce the hypothesis that APM has a leukaemogenic and lymphomatogenic effect.

Background In 2002 the International Agency for Research on Cancer classified extremely low frequency magnetic fields (ELFMF) as a possible carcinogen on the basis of epidemiological evidence. Experimental bioassays on rats and mice performed up to now on ELFMF alone or in association with known carcinogens have failed to provide conclusive confirmation. Objectives To study the carcinogenic effects of combined exposure to sinusoidal-50 Hz (S-50 Hz) magnetic fields and acute γ radiation in Sprague-Dawley rats. Methods We studied groups of male and female Sprague-Dawley rats exposed from prenatal life until natural death to 20 or 1000 μT S-50 Hz MF and also to 0.1 Gy γ radiation delivered as a single acute exposure at 6 weeks of age. Results The results of the study showed significant carcinogenic effects for the mammary gland in males and females and a significant increased incidence of malignant schwannomas of the heart as well as increased incidence of lymphomas/leukemias in males. Conclusions These results call for a re-evaluation of the safety of non-ionizing radiation.

The cumulative impact of human activities has driven many species into severe declines across the globe. However, the recent focus on conservation optimism has begun to highlight case studies that go against this trend. Reforestation, agricultural abandonment, reintroduction and legislative change have led to a situation where large mammals have recovered and are now widespread across the European continent. This study summarizes the knowledge about wild ungulate distribution in Europe and review the diversity of ways in which they interact with humans. Drawn from a wide range of sources, we built distribution maps of European wild ungulates. Results show that 90% of Europe is home to at least 1 species of wild native ungulate, with roe deer and wild boar occupying 74% and 64% of Europe respectively. In contrast, wild native mountain ungulates only occupy 5% of Europe, and are often associated with protected areas. The wide distribution of most European ungulates combined with the extensive human activity within Europe result in a wide range of interactions between ungulates and humans. These interactions can be classified as services or disservices depending on the value orientation and economic position of the various stakeholders perceiving this relationship. Overall, our survey highlights the success of wildlife management policies in Europe and the potential for continental scale conservation of large mammals in human-dominated landscapes. However, maintaining the success of wild ungulate conservation requires actions from national and European institutions to improve coordinated management across jurisdictional borders and sectorial coordination for the whole landscape. This is an open access article distributed under the terms of the Creative Commons CC-BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The aim of this paper is to define an exact formulation of a curved beam finite element for static analysis. The basic equations are combined in the coupled fundamental system in terms of radial displacement v , tangential displacement u and rotation ϕ . An original procedure for solving the fundamental system of equations is used. A finite element formulation based on shape functions that satisfy the homogeneous form of the fundamental system of differential equations is developed. The effects of bending moment, axial extension and transverse shear are taken into account. The exact elastic solution renders the element obtained free of shear and membrane locking. An efficient numerical procedure is presented for determining the pressure curve in the case of circular arches under static loading and arbitrary bonding conditions. The solution obtained is applicable to the analysis of both thin and thick curved beams. Several examples of arches with various loading and boundary conditions are investigated to illustrate the validity and the accuracy of the method. Finally, the effect of the arch rise on the structural response is pointed out.

Introduction: Intraductal papillary mucinous neoplasm (IPMN) is the most common cystic precancerous lesion of pancreatic cancer (PDA). IPMNs can progress from low to high-grade dysplasia, to invasive PDAC, but exact data regarding cancer risks are limited. PDAC is the fourth leading cause of cancer death . The overall 5-year survival is 6%, but survival of patients with early stage PDAC is significantly better. AIM: We used an approach coupling high resolution cytogenetic analysis (Affymetrix Oncoscan FFPE Array) with a clinically-oriented bioinformatic interpretation of data to understand what are the most relevant pathways altered in precursor lesions. Materials and methods: High resolution cytogenetic analysis was performed in 20 formalin fixed paraffin embedded samples of IPMNs by Oncoscan FFPE assay. Genomic data were analyzed for copy number gains and losses, loss of heterozygosity and for a panel of recurrent somatic mutations. Results were validated by qPCR and FISH analysis. Results: Twenty samples, including 14 mixed-type IPMNs (70%), 4 branch-duct IPMNs (20%) and 2 main-duct IPMNs (10%), were collected. We identified micro-invasive carcinoma (< 1 mm) and invasive carcinoma in 25% and in 10% of IPMNs respectively. By our high resolution cytogenetic analysis we observed that 8 IPMNs (40%) presented a nearly normal karyotype (< 4 copy number alterations), while 12 IPMNs (60%) showed a complex karyotype (> 10 alterations). In the latter subgroup were detected specific copy number gains of TERC and c-MYC oncogenes. Interestingly we noticed that TERC and c-MYC overexpression, present in 92% and 45% of complex karyotype samples respectively, were only observed in high-grade IPMNs, suggesting a possible role in a progression to malignancy. Oncoscan data were confirmed by Real Time and FISH analysis. Conclusions: Those results suggest a role of TERC and c-MYC overexpression as a possible biomarkers in the early identification of patients with complex karyotype IPMNs in order to better stratification of cystic lesions that could require surgery

Treatment of Erdheim–Chester disease (ECD), a rare non-Langerhans histiocytosis, relies on interferon-α, chemotherapeutic agents such as purine analogs, cytokine-blocking agents and BRAF inhibitors. Since interleukin (IL)-6 levels are elevated in serum and lesions of ECD patients, we evaluated the therapeutic efficacy and safety of IL-6 blockade with tocilizumab. We conducted an open-label, single-arm, phase II, prospective study of tocilizumab in three patients with multisystem ECD and poor tolerance/contraindications to IFN-α. Modifications of symptoms attributed to ECD represented the criteria for evaluation of clinical response. Changes at positron emission tomography scan, computed tomography scan, and magnetic resonance imaging at month 6 represented the main criteria for the evaluation of radiological response. Sustained complete clinical response and partial radiological improvement were observed in two patients, paralleled by modulation of systemic pro-inflammatory mediators. In spite of disease stabilization or improvement at extra-neurological sites, a third patient experienced a radiologic and clinical progression of central nervous system involvement, mirrored by a dramatic increase of circulating IL-6 and related cytokines. These findings indicate that IL-6 inhibition can be effective in ECD, but caution is advisable in patients with neurologic involvement. IL-6 emerges as a central mediator in ECD pathogenesis.

Background:For nearly five decades long-term studies in rodents have been the accepted benchmark for assessing chronic long-term toxic effects, particularly carcinogenicity, of chemicals. The Europ...

Background Up to now, experimental studies on rodents have failed to provide definitive confirmation of the carcinogenicity of extremely low frequency electromagnetic fields (ELFEMF). Two recent studies performed in our laboratory on Sprague-Dawley rats reported a statistically significant increase in malignant tumors of different sites (mammary gland, C-cells carcinoma, hemolymphoreticular neoplasia, and malignant heart Schwannoma) when ELFEMF exposure was associated with exposure to formaldehyde (50 mg/l) or acute low dose of γ-radiation (0.1 Gy) (Soffritti et al., 2016a) (Soffritti et al., 2016b). The same doses of known carcinogenic agents (50 mg/l formaldehyde, or acute 0.1 Gy γ-radiation), when administered alone, previously failed to induce any statistically significant increase in the incidence of total and specific malignant tumors in rats of the same colony. Objectives A lifespan whole-body exposure study was conducted to evaluate the possible carcinogenic effects of ELFEMF exposure administered alone to Sprague-Dawley rats, as part of the integrated project of the Ramazzini Institute (RI) for studying the effects on health of ELFEMF alone or in combination with other known carcinogens. Methods Male and female Sprague-Dawley rats were exposed 19 h/day to continuous sinusoidal-50 Hz magnetic fields (S-50 Hz MF) at flux densities of 0 (control group), 2, 20, 100 or 1000µT, and to intermittent (30 min on/30 min off) S-50 Hz MF at 1000 µT, from prenatal life until natural death. Results Survival and body weight trends in all groups of rats exposed to ELFEMF were comparable to those found in sex-matched controls. The incidence and number of malignant and benign tumors was similar in all groups. Magnetic field exposure did not significantly increase the incidence of neoplasias in any organ, including those sites that have been identified as possible targets in epidemiological studies (leukemia, breast cancer, and brain cancer). Conclusions Life-span exposures to continuous and intermittent sinusoidal-50 Hz ELFEMFs, when administered alone, did not represent a significant risk factor for neoplastic development in our experimental rat model. In light of our previous results on the carcinogenic effects of ELFEMF in combination with formaldehyde and γ-radiation, further experiments are necessary to elucidate the possible role of ELFEMF as cancer enhancer in presence of other chemical and physical carcinogens.

The most common sites of metastatic differentiated thyroid cancer are the neck lymph nodes, while distant metastases typically involve the lungs, the bones, and less frequently the brain. Uncommon metastatic sites include the liver, adrenal gland, kidney, pancreas, and skin. The epidemiological aspects of thyroid metastases in rare sites are largely unknown and their identification could have a significant impact on patients management. A mini-series of unusual metastatic sites of thyroid carcinoma is proposed as a contribution to current knowledge on anatomopathological characteristics and clinical outcome. Of the six cases that were assessed, the metastases were the following: skin metastases (2), skin and pancreas metastases (1), renal metastasis (1), adrenal metastasis (1), and liver metastasis (1). In our experience, metastases in rare sites do not always represent a negative prognostic factor for disease outcome. In fact they can occur as single distant lesion and if surgically resectable, their treatment can also lead to local disease remission.

Diagnostic accuracy in FDG-PET imaging highly depends on the operating procedures. In this clinical study on dementia, we compared the diagnostic accuracy at a single-subject level of a) Clinical Scenarios, b) Standard FDG Images and c) Statistical Parametrical (SPM) Maps generated via a new optimized SPM procedure. We evaluated the added value of FDG-PET, either Standard FDG Images or SPM Maps, to Clinical Scenarios. In 88 patients with neurodegenerative diseases (Alzheimer's Disease—AD, Frontotemporal Lobar Degeneration—FTLD, Dementia with Lewy bodies—DLB and Mild Cognitive Impairment—MCI), 9 neuroimaging experts made a forced diagnostic decision on the basis of the evaluation of the three types of information. There was also the possibility of a decision of normality on the FDG-PET images. The clinical diagnosis confirmed at a long-term follow-up was used as the gold standard. SPM Maps showed higher sensitivity and specificity (96% and 84%), and better diagnostic positive (6.8) and negative (0.05) likelihood ratios compared to Clinical Scenarios and Standard FDG Images. SPM Maps increased diagnostic accuracy for differential diagnosis (AD vs. FTD; beta 1.414, p = 0.019). The AUC of the ROC curve was 0.67 for SPM Maps, 0.57 for Clinical Scenarios and 0.50 for Standard FDG Images. In the MCI group, SPM Maps showed the highest predictive prognostic value (mean LOC = 2.46), by identifying either normal brain metabolism (exclusionary role) or hypometabolic patterns typical of different neurodegenerative conditions., Highlights • Brain FDG-PET was evaluated with a new optimized SPM procedure in dementias. • We compared the diagnostic accuracy of clinical information, visual and SPM FDG-PET. • SPM had the best sensitivity (96%), specificity (84%) and positive and negative LR. • In an MCI subgroup, SPM had the highest predictive prognostic value.

An accurate identification and interpretation of neoplastic lesions by PET is related to PET image quality, and depends on several factors including data processing for image formation. The aim of this work was to assess the influence of data rebinning and reconstruction on lesion detectability and quantification for a high-resolution 3-D PET/CT system, in order to optimize 3-D PET/CT oncological protocols. Oncological /sup 18/F-FDG PET studies were Monte Carlo (MC) simulated, based on a normal-weight oncological patient study, varying lesion size, lesion-to-background ratio, statistics, and including or not attenuation and scatter effects. Single slice rebinned (SSR), Fourier rebinned (FORE) and Fully 3-D (3-D) sinograms were considered. Reconstruction was carried out using ordered subset expectation maximization (OSEM) and attenuation weighting OSEM (AWOSEM). Human observers evaluated images in terms of clinical parameters characteristic of lesion detectability and quantification: lesion number and lesion size. By comparison with the known activity map (input for MC simulations), identified lesions were classified as true and false positive; the true positive fraction (TPF) and sensitivity were derived, as indices of lesion detectability. % maximum number of lesions identified with erroneous size (MAX/sub ls/) and % errors on lesion-to-background ratio (/spl epsiv/LBR) were calculated as quantitative indices for lesion characterization. The results show that, when images corrected for scatter and attenuation are considered, 2-D rebinning allows more lesions to be identified than 3-D, with the best detectability found using FORE+AWOSEM: in this case, sensitivity was found equal to 0.43, higher than with SSR+OSEM (0.30), SSR+AWOSEM (0.23), FORE+OSEM (0.35) and 3-D (0.18 for both OSEM and AWOSEM). Quantitatively, smaller MAX/sub ls/ and smaller /spl epsiv/LBRs were found using FORE+AWOSEM, in comparison to 3-D+AWOSEM (p=0.125 for both parameters); FORE+OSEM presented the smallest /spl epsiv/LBRs. Our findings, from one single simulated patient with lesions in the abdomen, suggest that, in the considered case, FORE is more suitable for lesion detectability and quantification than 3-D, FORE+AWOSEM presenting better performance for lesion detectability and spatial characterization, FORE+OSEM for the quantification of lesion activity concentration.

The aim of this study was to evaluate the efficacy and safety of epidural premotor stimulation in patients with primary focal dystonia. Seven patients were selected: 6 had cervical dystonia and 1 had right upper limb dystonia. In 2 patients, sustained muscle contractions led to a prevalently fixed head posture. Patients with cervical dystonia received a bilateral implant, whereas the patient with hand dystonia received a unilateral implant. Neurological and neuropsychological evaluations were performed before surgery (baseline), and 1, 3, 6, and 12 months afterward. The Burke-Fahn-Marsden scale (BFMS) and the Toronto Western spasmodic torticollis rating scale (TWSTRS) were administered at the same time points. Patients underwent resting (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) scans, before and 12 months after surgery. No adverse events occurred. An overall improvement was observed on the BFMS and TWSTRS after surgery. Patients with prevalently fixed cervical dystonia had a reduced benefit. Presurgical neuroimaging revealed a significant bilateral metabolic increase in the sensorimotor areas, which was reduced after surgery.

Background: Reactive microgliosis, hallmark of neuroinflammation, may contribute to neuronal degeneration,as shown in several neurodegenerative diseases. We in vivo evaluated microglia activation inearly dementia with Lewy bodies, still not reported, and compared with early Parkinson’s disease, toassess possible differential pathological patterns. Methods: We measured the [11C]-PK11195 binding potentials with Positron Emission Tomography, usinga simplified reference tissue model, as marker of microglia activation, and cerebral spinal fluid proteincarbonylation levels, as marker of oxidative stress. Six dementia with Lewy bodies and 6 Parkinson’sdisease patients within a year from the onset, and eleven healthy controls were included. Clinicaldiagnosis was confirmed at a 4-year follow-up. Results: In dementia with Lewy bodies as well as in Parkinson’s disease, we found significant (p < 0.001)[11C]-PK11195 binding potential increases in the substantia nigra and putamen. Patients with Lewybodies dementia had extensive additional microglia activation in several associative cortices. This wasevident also at a single subject level. Significant increase of Cerebral Spinal Fluid proteincarbonizationwas shown in both patients’ groups. Conclusions: [11C]-PK11195 Positron Emission Tomography imaging revealed neuroinflammation indementia with Lewy bodies and Parkinson’s disease, mirroring, even at a single subject level, thecommon and the different topographical distribution of neuropathological changes, yet in the earlieststages of the disease process. Focusing on those events that characterize parkinsonisms and Parkinson’sdisease may be the key to further advancing the understanding of pathogenesis and to taking thesemechanisms forward as a means of defining targets for neuroprotection.

We describe a case of clinical benefit and partial response with Gemcitabine and Oxaliplatin (GEMOX) in a young patient with ovarian metastasis from cystadenocarcinoma of the pancreas. A young woman complained of abdominal pain and constipation. Computed tomography (CT) and magnetic resonance imaging (MRI) scans disclosed two bilateral ovarian masses with pancreatic extension. She underwent bilateral ovarian and womb resection. During surgery peritoneal carcinosis, a pancreatic mass and multiple abdominal lesions were found. The final diagnosis was mucinous pancreatic cystadenocarcinoma with ovarian and peritoneal metastases. She started chemotherapy with Gemcitabine 1000 mg/m2/d1 and Oxaliplatin 100 mg/m2/d2 every two weeks (GEMOX). After twelve cycles of chemotherapy a CT scan showed a reduction of the pancreatic mass. She underwent distal pancreatic resection, regional lymphadenectomy and splenectomy. Pathologic examination documented a prominent fibrous tissue and few neoplastic cells with mucin-filled cytoplasm. Chemotherapy was continued with Gemcitabine as “adjuvant treatment” for another three cycles. There is currently no evidence of disease. As reported in literature, GEMOX is associated with an improvement in progression-free survival and clinical benefit in patients with advanced pancreatic cancer. This is an interesting case in which GEMOX transformed inoperable pancreatic cancer into a resectable tumour.

Summary The differential diagnosis between oligodendrogliomas and other gliomas remains a critical issue. The aim of this study is to verify the diagnostic value of Olig-2, Nogo-A, and synaptophysin and their role in identifying 1p19q codeletion. A total of 168 cases of brain tumors were studied: 24 oligodendrogliomas, 23 anaplastic oligodendrogliomas, 2 oligoastrocytomas, 2 anaplastic oligoastrocytomas, 30 glioblastoma multiforme, 2 diffuse astrocytomas, 4 anaplastic astrocytomas, 10 pilocytic astrocytomas, 9 ependymomas, 12 anaplastic ependymomas, 10 central neurocytomas, 10 meningiomas, 10 choroid plexus papillomas, 10 dysembryoplastic neuroepithelial tumors, and 10 metastases. All cases were immunostained with Olig-2, Nogo-A, and synaptophysin. In 79 cases, the status of 1p/19q had already been assessed by fluorescence in situ hybridization. Thus, in selected cases, fluorescence in situ hybridization was repeated in areas with numerous Nogo-A–positive neoplastic cells. Nogo-A was positive in 18 (75%) of 24 oligodendrogliomas, 8 (80%) of 10 dysembryoplastic neuroepithelial tumors, 6 (20%) of 30 glioblastoma multiforme, and 2 (20%) of 10 pilocytic astrocytomas. Olig-2 stained 22 (91.6%) of 24 oligodendrogliomas and all dysembryoplastic neuroepithelial tumors but also 24 (80%) of 30 glioblastoma multiforme and 8 (80%) of 10 pilocytic astrocytomas. Finally, synaptophysin stained 13 (54.1%) of 24 oligodendrogliomas, 3 (10%) of 30 glioblastoma multiforme, 1 (10%) of 10 pilocytic astrocytomas, and all neurocytomas. Among the 79 tested cases, original fluorescence in situ hybridization showed 1p/19q codeletion in 12 (52.2%) of 23 oligodendrogliomas, 8 (38%) of 21 anaplastic oligodendrogliomas, and 1 (4%) of 25 glioblastoma multiforme. However, after carrying out the Nogo-A–driven fluorescence in situ hybridization, 1p/19q codeletion was observed in 8 additional cases. Nogo-A is more useful and specific than Olig-2 in differentiating oligodendrogliomas from other gliomas. Furthermore, using a Nogo-A–driven fluorescence in situ hybridization analysis, it is possible to identify a larger number of 1p19q codeletions in gliomas.

Background Despite its large clinical application, our understanding about the mechanisms of action of deep brain stimulation of the subthalamic nucleus is still limited. Aim of the present study was to explore cortical and subcortical metabolic modulations measured by Positron Emission Tomography associated with improved motor manifestations after deep brain stimulation in Parkinson disease, comparing the ON and OFF conditions. Patients and methods Investigations were performed in the stimulator off- and on-conditions in 14 parkinsonian patients and results were compared with a group of matched healthy controls. The results were also used to correlate metabolic changes with the clinical effectiveness of the procedure. Results The comparisons using Statistical parametric mapping revealed a brain metabolic pattern typical of advanced Parkinson disease. The direct comparison in ON vs OFF condition showed mainly an increased metabolism in subthalamic regions, corresponding to the deep brain stimulation site. A positive correlation exists between neurostimulation clinical effectiveness and metabolic differences in ON and OFF state, including the primary sensorimotor, premotor and parietal cortices, anterior cingulate cortex. Conclusion Deep brain stimulation seems to operate modulating the neuronal network rather than merely exciting or inhibiting basal ganglia nuclei. Correlations with Parkinson Disease cardinal features suggest that the improvement of specific motor signs associated with deep brain stimulation might be explained by the functional modulation, not only in the target region, but also in surrounding and remote connecting areas, resulting in clinically beneficial effects.

Changes in D-2 receptors during antidepressant therapy have been reported in patients with major depressive disorder using PET/SPET. The aim of this study was to evaluate modifications in D-2 receptors that might occur in patients affected by obsessive-compulsive disorder (OCD) during serotonin reuptake sites inhibitors (SSRIs). To this purpose, we measured the in vivo binding of [C-11]raclopride ([C-11]Rac)in the brain of a group of OCD naive patients before and after the repeated administration of the inhibitor SSRI fluvoxamine. Eight patients with a Diagnostic and Statistical Manual of Mental Disorders IVth edition diagnosis of OCD completed the study undergoing a PET scan and a complete clinical evaluation before and during treatment with fluvoxamine. Patients have been compared also with a group of nine age-matched normal volunteers. Fluvoxamine treatment significantly improved clinical symptoms and increased [C-11]Rac binding potential (BP) in the basal ganglia of OCD patients (7.5 +/- 5.2, 6.9 +/- 6.9, and 9.9 +/- 9.3% in dorsal caudate, dorsal putamen, and ventral basal ganglia, respectively; p < 0.01) to values closer to those observed in the group of normal subjects. Chronic treatment with fluvoxamine induces a slight but significant increase in striatal [C-11]Rac BP of previously drug-naive OCD patients. The modifications in D-2 receptor availability might be secondary to fluvoxamine effects on serotoninergic activity.

Summary 1. Impediments to animal movement are ubiquitous and vary widely in both scale and permeability. It is essential to understand how impediments alter ecological dynamics via their influence on animal behavioural strategies governing space use and, for anthropogenic features such as roads and fences, how to mitigate these effects to effectively manage species and landscapes. 2. Here, we focused primarily on barriers to movement, which we define as features that cannot be circumnavigated but may be crossed. Responses to barriers will be influenced by the movement capabilities of the animal, its proximity to the barriers, and habitat preference. We developed a mechanistic modelling framework for simultaneously quantifying the permeability and proximity effects of barriers on habitat preference and movement. 3. We used simulations based on our model to demonstrate how parameters on movement, habitat preference and barrier permeability can be estimated statistically. We then applied the model to a case study of road effects on wild mountain reindeer summer movements. 4. This framework provided unbiased and precise parameter estimates across a range of strengths of preferences and barrier permeabilities. The quality of permeability estimates, however, was correlated with the number of times the barrier is crossed and the number of locations in proximity to barriers. In the case study we found that reindeer avoided areas near roads and that roads are semi-permeable barriers to movement. There was strong avoidance of roads extending up to c. 1 km for four of five animals, and having to cross roads reduced the probability of movement by 68� 6% (range 3� 5–99� 5%). 5. Human infrastructure has embedded within it the idea of networks: nodes connected by linear features such as roads, rail tracks, pipelines, fences and cables, many of which divide the landscape and limit animal movement. The unintended but potentially profound consequences of infrastructure on animals remain poorly understood. The rigorous framework for simultaneously quantifying movement, habitat preference and barrier permeability developed here begins to address this knowledge gap.

Objectives To investigate the effects of the interaction between adenosine receptors and renal nerves on urinary sodium excretion and glomerular filtration rate. Methods and design The effects on water and sodium excretion and glomerular filtration rate of A1 [2-chloro-N6-cyclopentyl-adenosine (CCPA)] and A2 [2-hesinyl-5'-N-ethyl-carboxamido-adenosine (2HE-NECA)] adenosine agonists were studied in anaesthetized rats with one kidney surgically denervated. Arterial blood pressure, heart rate and rate of urine flow from each kidney were continuously recorded; inulin clearance was used as an index of glomerular filtration rate. The experiments were performed with three groups of rats, into which, after a control period of 20 min, CCPA, 2HE-NECA or vehicle was infused for two subsequent 20 min periods. Result During infusion of CCPA, the slight decrease in arterial pressure was associated with a transient decrease in glomerular filtration rate and marked long-lasting decreases in heart rate, water and sodium excretion and fractional sodium excretion. The response of the innervated kidney was similar to the response of the denervated kidney. Infusion of 2HE-NECA caused decreases in arterial pressure, glomerular filtration rate and excretion of water and sodium associated with an increase in heart rate. The reduction of water and sodium excretion from the innervated kidney was larger than that from the denervated kidney. Conclusions Activation both of Al and of A2 receptor causes a reduction in urinary water and sodium excretion. The renal response to activation of A2 receptors is enhanced by the presence of renal nerves, whereas the response to activation of Al receptors is not influenced by renal nerves.

Movement disorders, including Parkinson's disease and parkinsonian syndromes, e.g. progressive supranuclear palsy, multiple system atrophy, and Lewy body dementia, may be difficult to differentiate among each other at an early stage, since they may share similar clinical features and response to dopaminergic drugs. As new tracers for imaging the dopamine transporters become available, the use of positron emission tomography (PET) for the differential diagnosis of movement disorders is gaining clinical relevance. Visual interpretation is generally used for PET image analysis. However, the use of some form of less subjective analysis is desirable in order to detect subtle changes that may be difficult to identify by visual interpretation and to achieve an operator independent analysis. To this end this study was aimed at assessing the feasibility of using statistical parametric mapping (SPM) for the clinical evaluation of single PET scans performed with 2-beta-carbomethoxy-3-beta-(4-fluorophenyl)-tropane ( C-beta-CIT-FE). Eleven healthy volunteers and five patients with movement disorders (Parkinson's disease, essential tremor, PSP and Lewy body dementia) were included in this study. Each subject underwent a PET study after i.v. injection of C-beta-CIT-FE. The PET images of C-beta-CIT-FE distribution acquired between 60 and 90 min were spatially fitted into the Talairach and Tournoux space. A template of normal C-beta-CIT-FE distribution was derived from studies in the 11 normal control subjects. Different patterns of reduction of the uptake of the tracer were detected in the basal ganglia of the five patients, in relation to each pathological condition. The patterns of distribution were all consistent with the severity and type of disease. The results of this study demonstrate the feasibility of differentiating among different states of dopaminergic impairment, due to Parkinson's disease and parkinsonian syndromes, by using PET scans with C-beta-CIT-FE and by using the SPM procedure for analysis of the data.

e13009Background: Intraductal papillary mucinous neoplasm (IPMN) is the most common cystic precancerous lesion of pancreatic cancer (PDA). We used an approach coupling high resolution cytogenetic analysis (Affymetrix Oncoscan FFPE Array) with a clinically-oriented bioinformatic interpretation of data to understand what are the most relevant pathways altered in precursor lesions and overt cancers to identify new therapeutic options for patients affected by PDA. Methods: High resolution cytogenetic analysis was performed in 20 formalin fixed paraffin embedded samples of IPMN by Oncoscan FFPE assay. Genomic data were analysed for copy number gains and losses, loss of heterozygosity and for a panel of recurrent somatic mutations. Results were validated by qPCR and FISH analysis. Results: Of the 20 IPMNs 8 (40%) were multifocal, 8 (40%) were in the pancreatic head and 4 (20%) involved pancreatic body and tail. Macroscopically 14 samples (70%) were mixed-type, while 4 (20%) branch-duct type and 2 (10%) main-duc...

Neuroimaging studies of the striatal dopamine transporter (DAT) are useful in the assessment of the dopaminergic system in Parkinson's disease (PD). We used positron emisson tomography (PET) and the tracer [11-C]FE-CIT to measure DAT binding in the caudate nucleus and putamen of 31 patients with PD, 5 with essential tremor and 8 healthy control subjects. Of the patients with PD, 17 were drug naive, while the others were either on levodopa or dopamine agonist monotherapy. DAT binding was significantly reduced in the caudate nucleus and to a greater extent in the putamen of PD patients compared to both healthy controls and essential tremor individuals. No overlap was observed between putamen values in PD and normals. No differences were found between controls and essential tremor subjects. These data confirm that measurements of DAT binding can provide an accurate and highly sensitive measure of degeneration in the dopamine system in PD.

The article represents an overview of the activities of members of the géwél caste, or Wolof griots, in present-day Senegal. While seemingly little has changed in areas where traditional ways of life are still dominant, in the westernised urban culture many traditional artists have learned to cope with the use of mass media. Far from being threatened by extinction, traditional artists and historians have managed to adapt their art to the requirements of modern life and to make it accessible to a wider audience.

The effects of recombinant human erythropoietin (rHuEPO) administration on blood pressure and urinary albumin excretion were studied in normotensive Wistar-Kyoto rats (WKY), in spontaneously hypertensive rats (SHR), and in SHR rats treated with an angiotensin converting enzyme inhibitor (SHR-ACEi). Rats were housed in metabolic cages and treated with rHuEPO (150 U/kg body weight [bw] three times a week) for 6 weeks. Control animals received the vehicle only (0.25 mL of physiological saline). An angiotensin converting enzyme inhibitor was administered in the drinking water for 6 weeks (spirapril 5 mg/kg bw). Systolic blood pressure (SBP), and 24 h urinary albumin excretion (UAE) were measured once a week. No significant differences in SBP were observed between rHuEPO and vehicle-treated normotensive animals at the end of the treatment (171.9 +/- 4.9 v 172.1 +/- 5.6 mm Hg, respectively). After 6 weeks, SBP was significantly higher in SHR and SHR-ACEi groups treated with rHuEPO than in control groups (239.8 +/- 7.3 and 243.0 +/- 7.3 mm Hg v 218.1 +/- 6.0 and 187.9 +/- 4.6 mm Hg, respectively); UAE was significantly higher in groups treated with rHuEPO than in control groups (WKY: 265.9 +/- 19.5 v 127.0 +/- 12.3 microg/100 g bw, SHR: 1668.4 +/- 564.6 v 234.8 +/- 22.9 microg/100 g bw, and SHR-ACEi: 1522.7 +/- 448.3 v 143.0 +/- 18.9 microg/100 g bw, respectively). We concluded that erythropoietin treatment causes an increase in arterial pressure in SHR only, and an increase in UAE in both normotensive and hypertensive rats. The albuminuric effect was not entirely dependent on increased blood pressure. The treatment with an angiotensin converting enzyme inhibitor did not modify either the proteinuric or the pressor effects.

Objective : To investigate the effects of the interaction between adenosine receptors and renal nerves on renin release. Materials and methods : The effects on renin secretion of A 1 (2-chloro-N6-cyclopentil-adenosine) and A 2 (2-hexynil-5'-N-ethyl-carboxamido-adenosine) adenosine-receptor agonists were studied in two groups of anaesthetized rats, each with one kidney surgically denervated. Arterial blood pressure and the renal blood flow of innervated and denervated kidneys were continuously recorded. Cannulae were inserted into both renal veins through femoral veins. After 1 h of rest, A 1 and A 2 agonists were intravenously infused for 30 min in the two groups of rats. Plasma renin activity was measured by radioimmunoassay in blood samples drawn simultaneously from both renal veins and the femoral artery before and after the drug infusion. Results : Infusions of A 1 and A 2 agonists produced comparable hypotensive effects. During A 1 agonist administration, the heart rate decreased significantly, but it did not change after A 2 agonist treatment. Renal blood flow was reduced by administration of the A 1 agonist in both kidneys, while A 2 agonist administration significantly reduced the renal blood flow of the innervated kidney only. The veno-arterial difference in plasma renin activity decreased after the A 1 agonist infusion in both kidneys, but after the A 2 agonist infusion it increased significantly in the innervated kidney only. Conclusions : Renal nerves do not influence the inhibition of renin release mediated by A 1 adenosine receptors. In vivo, A 2 -receptor agonist administration can stimulate renin release only in the presence of intact renal nerves.

Lung function was assessed in 17 panic patients and 20 healthy controls. Panic patients had abnormal values for some dynamic lung volumes, namely Peak Expiratory Flow Rate (PEFR), Expiratory Flow at 75% of Vital Capacity (FEF75) and Maximum Mid-Expiratory Flow Rate (NMEF). Such functional abnormalities might indicate subclinical obstruction of lung airways, possibly relevant to the mechanisms related to panic disorder (PD).

Corrigendum to “In vivo microglia activation in very early dementia with Lewy bodies, comparison with Parkinson’s disease” [Parkinsonism Relat Disord 19 (2013) 47e52] S. Iannaccone , C. Cerami , M. Alessio , V. Garibotto , A. Panzacchi , S. Olivieri , G. Gelsomino , R.M. Moresco b,e, , D. Perani b,c,e,* Neurorehabilitation Unit, Department of Clinical Neurosciences, San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy Nuclear Medicine Unit and Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy Vita-Salute San Raffaele University, Milan, Italy d Proteome Biochemistry Unit, San Raffaele Scientific Institute, Milan, Italy e IBFM-CNR, Segrate, Italy University of Milano-Bicocca, Monza, Italy