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Background and Purpose: Differential diagnosis between Parkinson's disease (PD) and Atypical Parkinsonisms, mainly Progressive Supranuclear Palsy (PSP) and Multiple System Atrophy (MSA), remains challenging. The low sensitivity of macroscopic findings at imaging might limit early diagnosis. The availability of iron-sensitive MR techniques and high magnetic field MR scanners provides new insights in evaluating brain structures in degenerative parkinsonisms. Quantitative Susceptibility Mapping (QSM) allows quantifying tissue iron content and could be sensitive to microstructural abnormalities which precede the appearence of regional atrophy. We measured the magnetic susceptibility (χ) of nigral and extranigral regions in patients with PD, PSP and MSA to evaluate the potential utility of the QSM technique for differential diagnosis., Materials and Methods: 65 patients (36 PD, 14 MSA, 15 PSP) underwent clinical and radiological evaluation with 3 T MRI. QSM maps were obtained from GRE sequences. ROI were drawn on substantia nigra (SN), red nucleus (RN), subthalamic nucleus (STN), putamen, globus pallidus and caudate. χ values were compared to detect inter-group differences., Results: The highest diagnostic accuracy for PSP (area under the ROC curve, AUC, range 0.9-0.7) was observed for increased χ values in RN, STN and medial part of SN whereas in MSA (AUC range 0.8-0.7) iron deposition was significantly higher in the putamen, according to the patterns of pathological involvement that characterize the different diseases., Conclusion: QSM could be used for iron quantification of nigral and extranigral structures in all degenerative parkinsonisms and should be tested longitudinally in order to identify early microscopical changes., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

In the present case, we report the association of multiple ileal neuroendocrine tumors and idiopathic myointimal hyperplasia of the mesenteric veins, 2 rare conditions that could have an etiopathogenetic relationship. Idiopathic myointimal hyperplasia of mesenteric veins implies a near-total obliteration of venular vessels, which can lead to hypoxic disorders. Hypoxia in tumors is associated with increased metastatic potential and resistance to radiotherapy and chemotherapy. Herein we speculated on the existence of a relationship between hypoxia and multiple location of neuroendocrine tumors., (© The Author(s) 2016.)

Background: Large evidence supports the role of microRNAs as new important inflammatory mediators by regulating both the adaptive and innate immunity. In the present study, we speculated that miR-320 controls NOD2 (nucleotide-binding oligomerization domain) expression, because it contains multiple binding sites in the 3'-untranslated region of the gene. NOD2, the first gene associated to increased susceptibility to Crohn's disease, is a cytosolic receptor that senses wall peptides of bacteria and promotes their clearance through initiation of a proinflammatory transcriptional program. This study aims at demonstrating that NOD2 is a target of miR-320 as well as investigating the role of inflammation in modulating the miR-320 control on NOD2 expression and analyzing miR-320 expression in intestinal biopsies of children with inflammatory bowel disease., Methods: The colonic adenocarcinoma cell line HT29 was used to assess the miR-320-mediated regulation of NOD2 expression. MiR-320 and NOD2 expression were analyzed in mucosal samples of 40 children with inflammatory bowel disease., Results: During inflammation, NOD2 expression is inversely correlated with miR-320 expression in vitro and ex vivo. Exogenous miR-320 transfection in HT29 cells leads to a significant decrease of NOD2 expression, whereas the miR-320 inhibitor transfection leads to increase of NOD2 expression, nuclear translocation of nuclear factor κB, and activation of downstream cytokines., Conclusions: We show for the first time that NOD2 expression is under the control of miR-320. We also show in vitro and ex vivo that inflammation induces a decrease of miR-320 and the latter correlates negatively with NOD2 expression.

Background: Krill oil is a marine derived oil rich in phospholipids, astaxanthin and omega-3 fatty acids. Several studies have found benefits of krill oil against oxidative and inflammatory damage., Aims: We aimed at assessing the ability of krill oil to reduce intestinal inflammation by improving epithelial barrier integrity, increasing cell survival and reducing pathogenicity of adherent-invasive Escherichia coli., Methods: CACO2 and HT29 cells were exposed to cytomix (TNFα and IFNγ) to induce inflammation and co-exposed to cytomix and krill oil. E-cadherin, ZO-1 and F-actin levels were analyzed by immunofluorescence to assess barrier integrity. Scratch test was performed to measure wound healing. Cell survival was analyzed by flow cytometry. Adherent-invasive Escherichia coli LF82 was used for adhesion/invasion assay., Results: In inflamed cells E-cadherin and ZO-1 decreased, with loss of cell-cell adhesion, and F-actin polymerization increased stress fibres; krill oil restored initial conditions and improved wound healing, reduced bacterial adhesion/invasion in epithelial cells and survival within macrophages; krill oil reduced LF82-induced mRNA expression of pro-inflammatory cytokines., Conclusions: Krill oil improves intestinal barrier integrity and epithelial restitution during inflammation and controls bacterial adhesion and invasion to epithelial cells. Thus, krill oil may represent an innovative tool to reduce intestinal inflammation., (Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Introduction: Dopamine agonists are highly effective as adjunctive therapy to levodopa in advanced Parkinson's disease. These drugs have rapidly gained popularity as a monotherapy in the early stages of Parkinson's disease for patients less than 65-70 years old since they are about as effective as levodopa but patients demonstrate a lower tendency to develop motor complications. However, dopamine agonists could have peripheral and central side-effects which are often the reason for the discontinuation of the treatment., Areas Covered: This article presents an overview of the efficacy and the potential negative effects related to the use of dopamine agonists in the treatment of Parkinson's disease., Expert Opinion: Beyond the new generation non ergot dopamine agonists, no strong evidences allow the choice of a specific dopamine agonists for Parkinson 's disease treatment and by now dopamine agonists treatment should be tailored on specific adverse events profile.

Purpose: Deep brain stimulation provides benefits for people with Parkinson disease by managing some of their complications. None of the few reports in the current literature establishes the functionality of deep brain stimulation when activated during phacoemulsification., Methods: A 70-year-old woman with subthalamic deep brain stimulator (DBS) for advanced Parkinson disease was referred to our center for cataract surgery. To evaluate any possible interference between ultrasounds and the DBS, we registered the impedance of the electrodes before and after surgery., Results: The patient underwent uneventful phacoemulsification of her right eye under topical anesthesia with her internal pulse generator device activated. During the surgical procedure, all potential variations of the impedance of the electrodes were recorded., Conclusions: This report demonstrates that phacoemulsification under topical anesthesia is a feasible procedure in patients with DBS, showing no interference between the ultrasounds and the internal pulse generator.

Background: Migraine, anxiety and depression often coexist. A "neurolimbic" model of migraine has been recently proposed accounting for a dynamic influence of pain, mood and anxiety on the migraine disease. However, very few data exist concerning clinical migraine features in patients reporting anxiety-depression symptoms., Objective: Aim of our study was to test differences in clinical migraine features between migraineurs with anxiety-depression symptoms and migraineurs without ones., Materials and Methods: We recruited 200 consecutive migraineurs. Other primary headaches comorbidity and migraine prophylaxis were exclusion criteria. Each patient was interviewed following a structured questionnaire including general features about migraine, triggers, allodynia. Anxiety and depression symptoms were evaluated in each patient by two brief self-reported scales: the generalized anxiety disorder 7-item scale (GAD-7) and the Patient Health Questionnaire 9-item scale (PHQ-9). A cut-off of 5 in both the GAD-7 and the PHQ-9 was considered positive for the presence of anxiety-depressive symptoms., Results: One hundred and one patients (51.5%) had anxiety-depression symptoms (GAD-7 and PHQ-9 ≥ 5). They reported a more headaches/month (p = 0.004), higher number of triggers (p < 0.001), and were more allodynic (p = 0.005). In a binary logistic regression model triggers and allodynia made a unique statistical contribution on reporting anxiety-depression symptoms., Conclusion: Our results showed that the presence of anxiety-depression symptoms affects migraine clinical presentation. They are associated with enhanced migraine triggers susceptibility, more ictal allodynic symptoms as well as more headaches/month. An altered sensation in migraineurs with anxiety-depression symptoms could be a result of a lower pain threshold and an increased cortical excitability in a broader context of a neurolimbic dysfunction., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Endoplasmic reticulum stress and unfolded protein response have been recently associated with the development of inflammatory bowel diseases in adults. We aimed at assessing the involvement of these pathways also in paediatric inflammatory bowel disease by analysing the expression of the main genes involved in endoplasmic reticulum stress and correlating them with the degree of intestinal inflammation., Methods: Real-time PCR and Western blot analysis of the expression of the endoplasmic reticulum stress marker HSPA5 and of selected genes representing the three pathways of unfolded protein response (IRE-XBP1, PERK-ATF4, ATF6p90-p50) in inflamed and uninflamed biopsies from 28 inflammatory bowel disease paediatric patients and 10 controls., Results: HSPA5, PDIA4, as well as unspliced and spliced XBP1 mRNAs were significantly increased in patients' inflamed colonic mucosa compared to uninflamed mucosa and controls. HSPA5, PDIA4, ATF6, and phospho-IRE proteins were also upregulated, indicating the activation of the IRE-XBP1 and ATF6p90-p50 branches of unfolded protein response. A positive significant correlation between interleukin-8 levels, as a marker of inflammation, and upregulated genes was found in the inflamed colonic mucosa., Conclusion: A deregulation of the genes involved in the endoplasmic reticulum stress and unfolded protein response pathways may be a key component of the inflammatory response in paediatric patients with inflammatory bowel disease., (Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Objectives: A new caspase-independent mode of programmed cell death, termed necroptosis, has recently been identified. Altered expression of molecules involved in the necroptosis pathway has been shown to trigger intestinal inflammation. The initiation of necroptosis is principally mediated by the release of receptor interacting protein 3 (RIP3) from suppression by caspase-8. Furthermore, it has been suggested that the mixed lineage kinase domain-like (MLKL) factor is an interacting target of RIP3 in active necroptosis. This study aims at investigating the occurrence of necroptosis in children with inflammatory bowel disease (IBD) and its contribution to human intestinal inflammation., Methods: Biopsy samples were collected from the ileum and colon of 33 children with Crohn's disease, 30 with ulcerative colitis, and 20 healthy controls. Ten children with allergic colitis (AC) were used as non-IBD comparators. RIP3, caspase-8, and MLKL protein expression levels were evaluated by western blotting. The adenocarcinoma cell line HT29 was used for in vitro experiments., Results: RIP3 and MLKL increased (P<0.01) in inflamed tissues of IBD and AC patients, whereas caspase-8 was reduced. No variations were observed in uninflamed tissues of patients. The relationship between RIP3 increase, active necroptosis, and intestinal inflammation was confirmed by in vitro analyses., Conclusions: We show for the first time that necroptosis is strongly associated with intestinal inflammation in children with IBD and contributes to strengthen the inflammatory process. We believe that RIP3 and MLKL could represent attractive targets for the management of human IBD.

In silico modeling of the cardiovascular system (CVS) can help both in understanding pharmacological or pathophysiological process and in providing information which could not be obtained by means of traditional clinical research methods due to practical or ethical reasons. In this work the numerical CVS was used to study the effect of interaction between mechanical ventilation and biventricular pacemaker by haemodynamic and energetic point of view. Starting from literature data on patients with intra and/or inter-ventricular activation time delay and treated using biventricular pacemaker, we used in silico simulator to analyse the effects induced by mechanical ventilatory assistance (MVA). After reproducing baseline and CRT conditions, the MVA was simulated changing the mean intrathoracic pressure value. Results show that simultaneous application of CRT and MVA yields a reduction of cardiac output, left ventricular end-diastolic and end-systolic volume when positive mean intrathoracic pressure is applied. In the same conditions, when MVA is applied, left ventricular ejection fraction, mean left (right) atrial and pulmonary arterial pressure increase., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Ready-to-eat meals packed in polyethylene terephthalate (PET) and aluminium dishes, supplied to patients in two hospitals in the Campania region (Italy), were studied to evaluate the probable migration of di-n-butylphthalate (DBP) and di(2-ethylhexyl)phthalate (DEHP) from the packaging into the food. The influence of temperature, storage time and type of package on the migration process was considered, analysing the meals according to three time ranges, before the packaging (T(0)) and after 60 min (T(1)) and 120 min (T(2)) from packaging during the storage in thermostatic delivery carts. At T(0) in the meals sampled before packaging in PET dishes, mean levels of DBP and DEHP were 0.023 ± 0.002 µg/g and 0.069 ± 0.041 µg/g, respectively; the DBP level increased 230% and that of DEHP increased 208% by time T(0) versus T(2). In the meals sampled before packaging (T(0)) in aluminium dishes, the mean levels of DBP and DEHP were 0.030 ± 0.001 µg/g and 0.057 ± 0.015 µg/g, respectively. The significant increase in contaminant levels over storage times for meals packed in PET dishes demonstrates that from packages made of plastic materials the migration of phthalic acid esters into foods is possible. In meals packed in PET dishes, the highest DBP and DEHP increases were observed in the T(0) to T(1) range, which represented the time interval over which meals were kept hot, and mainly in the first ones, where the highest temperatures have been recorded.

In the present study we investigated whether glucose deprivation contributes to feeding induced by mercaptoacetate (MA), an inhibitor of fatty acid oxidation, in Sprague-Dawley rats fed a carbohydrate-free, high-fat diet (HF-rats). The results show that inhibition of fatty acid oxidation by MA, reflected by a decrease in plasma beta-hydroxybutyrate, elicited eating in the HF-rats and that the eating response was not associated with a decrease in circulating glucose. The effect of MA on food intake was tested in two different substrains (Zur:SD and Ico:OFA SD) of Sprague-Dawley rats. The threshold dose of MA for eliciting eating was much higher in Zur:SD (between 800 and 1,600 micromol/kg) in comparison to Ico:OFA SD rats (between 200 and 400 micromol/kg). At a high dose of MA (1,200 micromol/kg), but not at a low dose (400 micromol/kg) the feeding response in the Ico:OFA SD rats was associated with hyperglycemia due to an increase in glycogenolysis. Unlike in Zur:SD, in Ico:OFA SD rats the higher doses of MA (800 and 1,200 micromol/kg but not 400 micromol/kg) produced a long-term suppression of feeding, which partly might be causally related to the observed inhibitory effect of MA on gastric emptying. The present results indicate that glucose deprivation does not contribute to feeding elicited by MA-induced inhibition of fatty acid oxidation in rats fed a carbohydrate-free, high-fat diet.

Several lines of evidence indicate that fatty acid oxidation contributes to control of eating. We examined the effect of inhibitors of fatty acid oxidation (mercaptoacetate, R-3-amino-4-trimethylaminobutyric acid = emeriamine) on food intake in mice because fatty acid oxidation has been shown recently to increase the hepatic membrane potential in mouse liver, and this potential has been proposed to represent a signal for control of food intake. The effect of intraperitoneal injection of mercaptoacetate (200, 400, or 600 micromol/kg body weight) and emeriamine dihydrochloride (8.7, 17.4, 34.8, or 69.6 micromol/kg body weight) was investigated in mice fed a fat-enriched diet (18% fat). Both mercaptoacetate (400 or 600 micromol/kg) and emeriamine (34.8 or 69.6 micromol/kg) significantly increased food intake. These results suggest that fatty acid oxidation is also involved in feeding control in mice. Therefore, the pertinent mechanisms can be studied in mice.

The combined effect of the histamine receptor antagonists Dexbrompheniramine (DXB: H1-receptor antagonist) and Cimetidine (C: H2-receptor antagonist) on food and water intake was investigated in pygmy goats. DXB (1 mg/kg BW0.75) and C (16 mg/kg BW0.75) were injected together intraperitoneally (i.p.). Cumulative food and water intake, as well as meal and draft pattern, were recorded. DXB and C significantly reduced cumulative water intake, whereas cumulative food intake did not change. Water to food ratio was also significantly diminished. Draft frequency and the percentage of drafts associated with meals were significantly reduced during the 6 h post injection, while meal frequency and meal size did not change during this period. The results show that blockade of the H1- and H2-histamine receptors attenuates the association between water and food intake in pygmy goats. Therefore, mechanisms responsible for meal-associated drinking seem to depend upon activation of histamine receptors.

Because previous studies had suggested that the anorectic effects of cholecystokinin (CCK) and bombesin (BBS) depend partly on the release of amylin or calcitonin gene-related peptide (CGRP), we investigated the influence of the amylin and CGRP receptor antagonist CGRP (8-37) on the anorectic effects of CCK and BBS in streptozotocin (STZ)-diabetic and nondiabetic rats. STZ-diabetic rats had significantly lower plasma amylin and insulin concentrations than nondiabetic control rats. Amylin (5 micrograms/kg or 2.5 micrograms/rat) injected IP at dark onset after 24-h food deprivation elicited an anorectic effect of similar extent in STZ-diabetic and control rats. Under similar conditions, CCK (0.25 and 2 micrograms/kg) and BBS (5 micrograms/kg) reduced food intake in both STZ-diabetic and nondiabetic rats. These effects were markedly attenuated by CGRP (8-37) (10 micrograms/kg) in non-diabetics but not in STZ-diabetic rats. It is concluded that part of the anorectic effects of CCK and BBS depend on the release of amylin from pancreatic B-cells.

The aim of this study was to investigate the effect of microwave oven heating for antigen retrieval on the immunoreactivity of human prostate carcinoma androgen receptor (AR) in tissue sections. Formalin-fixed, paraffin-embedded tissue sections were microwaved at 5-min intervals for a total of 15, 20, 25, 30, 35 minutes at maximum power (700W). The monoclonal antibody F39.4.1 directed against human AR was used at a 1:10 dilution. Without microwave oven heating, prostatic tissue did not exhibit any AR immunoreactivity. Moderate positivity appeared after three 5-minute cycles of microwave heating. The intensity of immunoreactivity improved progressively with heating times of 20 and 25 min up to an optimum time of 30 minutes, when nuclear staining was most intense with the absence of background staining and without loss of morphological details. While antigen retrieval is effective in restoring antigenicity in a variety of setting, the length of time prostate tissue is exposed to microwave radiation is critical in order to obtain optimal AR immunostaining. AR immunostaining reliably permitted evaluation of the distribution and intensity of positively stained nuclei and the distinction of the various cell types in archival material.

Conflicting prognostic results have been published as to the DNA variables, such as DNA ploidy, DNA index, and % S-phase cells for breast cancer patients. These variables can be obtained by interpreting DNA histograms by cell cycle analysis. Explanations for these conflicting results might be found on the level of the interpretation of the DNA histograms. In a previous study, the semi automated cell cycle analysis computer program MultiCycle (Phoenix Flow Systems, San Diego, CA) showed high intralaboratory reproducibility. However, what types of DNA histograms may cause disagreements was still unclear. The aim of this study was to determine the interlaboratory reproducibility of MultiCycle-based cell cycle analysis of 1,295 flow cytometric DNA histograms derived from fresh frozen breast cancer material and to clarify potential sources of interobserver variation when analyzing DNA histograms. DNA ploidy classification into diploid, hyperdiploid, tetraploid, hypertetraploid, and multiploid showed an interlaboratory agreement of 94% (kappa value = 0.92). The 6% discrepancies (n = 74) were caused by tetraploid peaks, as established in one laboratory, which shifted outside the tetraploid region on reanalysis by the other laboratory (37%), shoulders sometimes interpreted as peaks (24%), small peaks not always recognized as such (24%), fitting failures (10%), and overlooking of tetraploid peaks (5%). Furthermore, the cell cycle analysis variables showed variable reproducibility. The % S-phase cells of the first, second, and third cell cycle showed overall a moderate reproducibility (0.62 < or = R < or = 0.79), but the average % S-phase cells and the average aneuploid % S-phase cells were more reproducible with correlation coefficients of 0.89 and 0.81, respectively. The coefficient of variation of the G0/G1 peak of the first cell cycle, the DNA indices and the % diploid cells were highly reproducible (R > or = 0.94), and the % G2/M-phase cells of the first, second, and third cell cycle were poorly reproducible (0.22 < or = R < or = 0.68). When a cut-point was used at the mean value of 7% for the average % S-phase cells, the number of "threshold discrepancy cases" was 6%. Sources of variation for cell cycle analysis were variations in the debris correction procedures, disagreement about the modes of the aneuploid peaks, disagreement about small peaks, shoulders sometimes interpreted as peaks, and overlooking of tetraploid peaks.

Objective: To develop and test a Bayesian belief network (BBN) for the identification of prostatic adenocarcinomas (PACs) with combination endocrine therapy (CET) changes from PACs with poor to no treatment CET effect and from untreated PACs., Methods: A network was designed with a decision node containing three diagnostic alternatives (PAC with CET effect, PAC with poor to no treatment effect, and untreated PAC) and seven first-level evidence nodes for the diagnostic features: nuclear enlargement; frequency of prominent nucleoli; cell cytoplasm vacuolization; shrunken acini; individual infiltrating tumor cells; WHO prostate cancer pattern recognition, and amount of interstitial tissue stroma. Three prototype cases, one for each diagnostic alternative, were used to develop the BBN. The BBN performance was then evaluated in 40 prostatectomies for PAC, consisting of 20 CET treated and 20 untreated cases., Results: The results obtained with the three prototypes showed that the network can identify the diagnostic alternatives with certainty when seven features are polled. When the performance was evaluated in the 40 PACs, the belief values were 1.0 or close to it in most of the cases (the value range is 0.0-1.0; the closer to 1.0, the greater the belief). Moreover, the BBN allowed an identification with high certainty of PACs with treatment-related changes from those either with poor to no treatment effect or untreated., Conclusions: A BBN for the evaluation of androgen-deprived PAC offers a descriptive classifier which is readily implemented and allows the use of descriptive, linguistic terms.

The authors report a case of mediastinal extraskeletal osteosarcoma showing immunohistochemical and ultrastructural features of epithelial differentiation and associated with a long-term patient survival. The possible role of flow cytometric DNA analysis in defining the prognosis of this tumor is discussed.

Several subjective grading systems have been proposed for different premalignant and malignant lesions with varying emphasis on the nuclear component. However, all subjective grading systems are prone to a significant degree of observer error because the subjective evaluation of nuclear features like size and staining density may be inaccurate and not reproducible. Therefore, quantitation-based methods are to be preferred to evaluate accurately the cell and its architectural features and to eliminate the subjective element of microscopy. The problems which have so far been considered and solved in some quantitation-based grading systems are as follows: 1. feature evaluation, selection and combination into indices and grading systems; 2. number of grades to be identified; 3. degree of certainty in the grading systems; 4. quality control and standardisation of the grading systems; 5. routine application of the grading systems and their efficacy in predicting tumour progression and/or regression (also in response to treatment); 6. current and future aims in researching new grading systems and improving the current ones. The solution of these problems has allowed the grading to be accurately evaluated; thus avoiding the poor reproducibility observed when features have been subjectively investigated.