Bridging the clinicopathological gap in the frontotemporal dementia spectrum

Frontotemporal dementia (FTD) is a currently incurable neurodegenerative disease comprising a spectrum of clinical syndromes and underlying neuropathologies. Each neuropathology is characterized by the accumulation of a specific protein (tau, TDP-43) in the brain, which cannot be easily detected during life nor predicted by clinical syndromes, hampering proper disease diagnosis. This thesis contributes to bridging this diagnostic gap by studying brain tissue from patients with FTD who underwent autopsy, and blood biomarkers in families carrying genetic variants associated with FTD. First, through pathological studies, we find that the two main underlying neuropathologies, TDP-43 and tau, show a different regional distribution in the brains of patients with FTD. Next, in a specific subtype of tau pathology, that associated with MAPT genetic variants, we observe a strongly heterogeneous pathological profile, in part explained by the biochemical structure of tau aggregates. Moreover, we find evidence of iron accumulation, associated with neuroinflammation, in two different subtypes of FTD (with MAPT and C9orf72 genetic variants), and we uncover neurovascular dysfunction as a core disease mechanism in TDP-43 pathology associated with GRN genetic variants. Finally, we study blood biomarkers suggestive of brain neurodegeneration. We find that the protein neurofilament light chain (in short, NfL) is helpful to diagnose the early (prodromal) stage of genetic FTD, and we identify altered methylation of cell-free DNA as a potential presymptomatic marker of neuronal death

A Participatory Approach to Assess the Effectiveness of Responses to Cope With Flood Risk

This work illustrates the preliminary findings of a participatory research process aimed at identifying responses for sustainable water management in a climate change perspective, in two river basins in Europe and Asia. The paper describes the methodology implemented through local workshops, aimed at eliciting and evaluating possible responses to flood risk. Participatory workshops allowed for the identification of four categories of possible responses and a set of nine evaluation criteria, three for each of the three pillars of sustainable development. The main outcome of such activities consists in the ranking of broad response categories instrumental to the objective of the Brahmatwinn research project, i.e. the identification of Integrated Water Resource Management Strategies (IWRMS) based upon the issues and preferences elicited from local experts. The mDSS tool was used to facilitate transparent and robust management of the information collected through Multi-Criteria Decision Analysis (MCDA) and communication of the outputs.Participatory Process, Climate Change, Flood Risk, Decision Support System, Multi Criteria Analysis, MCA, Eliciting Responses, Evaluating Responses, Integrated Water Resources Management, IWRM, Mulino Decision Support System, mDSS

A participatory approach for assessing alternative climate change adaptation responses to cope with flooding risk in the upper Brahmaputra and Danube river basins

This work illustrates the preliminary findings of a participatory research process aimed at identifying responses for sustainable water management in a climate change perspective, in two river basins in Europe and Asia. The paper describes the methodology implemented through local workshops, aimed at eliciting and evaluating possible responses to flooding risk. Participatory workshops allowed for the identification of four categories of possible responses and a set of nine evaluation criteria, three for each of the three pillars of sustainable development. The main result of such activities consists in the ranking of broad response categories, to contribute to the orientation of the Brahmatwinn research project towards the identification of Integrated Water Resource Management Strategies (IWRMS) well grounded upon the issues and preferences elicited from local experts. The mDSS tool was used to facilitate transparent and robust management of the information collected through Multi-Criteria Decision Analysis (MCDA) and the communication of the outputs.Participatory process, Climate Change, Flooding Risk, Decision Support System, MCDA

Investigation of adaptive optics imaging biomarkers for detecting pathological changes of the cone mosaic in patients with type 1 diabetes mellitus

Purpose To investigate a set of adaptive optics (AO) imaging biomarkers for the assessment of changes of the cone mosaic spatial arrangement in patients with type 1 diabetes mellitus (DM1). Methods 16 patients with 20/20 visual acuity and a diagnosis of DM1 in the past 8 years to 37 years and 20 age-matched healthy volunteers were recruited in this study. Cone density, cone spacing and Voronoi diagrams were calculated on 160x160 μm images of the cone mosaic acquired with an AO flood illumination retinal camera at 1.5 degrees eccentricity from the fovea along all retinal meridians. From the cone spacing measures and Voronoi diagrams, the linear dispersion index (LDi) and the heterogeneity packing index (HPi) were computed respectively. Logistic regression analysis was conducted to discriminate DM1 patients without diabetic retinopathy from controls using the cone metrics as predictors. Results Of the 16 DM1 patients, eight had no signs of diabetic retinopathy (noDR) and eight had mild nonproliferative diabetic retinopathy (NPDR) on fundoscopy. On average, cone density, LDi and HPi values were significantly different (P<0.05) between noDR or NPDR eyes and controls, with these differences increasing with duration of diabetes. However, each cone metric alone was not sufficiently sensitive to discriminate entirely between membership of noDR cases and controls. The complementary use of all the three cone metrics in the logistic regression model gained 100% accuracy to identify noDR cases with respect to controls. PLOS ONE | DOI:10.1371/journal.pone.0151380 March 10, 2016 1 / 14 OPEN ACCESS Citation: Lombardo M, Parravano M, Serrao S, Ziccardi L, Giannini D, Lombardo G (2016) Investigation of Adaptive Optics Imaging Biomarkers for Detecting Pathological Changes of the Cone Mosaic in Patients with Type 1 Diabetes Mellitus. PLoS ONE 11(3): e0151380. doi:10.1371/journal. pone.0151380 Editor: Knut Stieger, Justus-Liebig-University Giessen, GERMANY Received: December 17, 2015 Accepted: February 27, 2016 Published: March 10, 2016 Copyright: © 2016 Lombardo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: Research for this work was supported by the Italian Ministry of Health (5x1000 funding), by the National Framework Program for Research and Innovation PON (grant n. 01_00110) and by Fondazione Roma. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Vision Engineering Italy srl funder provided support in the form of salaries for author GL, but did not have any Conclusion The present set of AO imaging biomarkers identified reliably abnormalities in the spatial arrangement of the parafoveal cones in DM1 patients, even when no signs of diabetic retinopathy were seen on fundoscopy

Sagittal and vertical effects of transverse sagittal maxillary expander (TSME) in three different malocclusion groups

Background: The aim of this retrospective study was to cephalometrically evaluate the skeletal and dental effects of the transverse sagittal maxillary expander (TSME), for the correction of sagittal and transverse maxillary deficiency in class I, II, and III malocclusions. Methods: The sample for this retrospective study included 45 patients (mean age, 8.4 years; 26 females, 19 males; 15 skeletal class I subjects, 15 skeletal class II subjects, and 15 skeletal class III subjects) with maxillary bilateral cross-bite. For each patient, a lateral cephalogram was obtained before treatment and at the end of the retention period. Changes in the groups during the observation period were calculated, compared, and statistically analyzed with a t-test. Results: The cephalometric values before T0 and T1 showed significant changes. Conclusions: The TSME can produce skeletal changes due to the transverse force and sagittal effects on the maxillary alveolar process. These modifications have benefic effects in classes I, II, and III. The data obtained in this study permit us to underline the fact that TSME can be used in all of the skeletal classes, with good vertical and sagittal results

Pseudo 2D Hidden Markov Model and Neural Network Coefficients in Face Recognition

Non

Occlus-o-Guide� versus Andresen activator appliance: neuromuscular evaluation

BACKGROUND: The aim of the present study was to assess the muscular variations at the electromyography (EMG) level for the anterior temporalis muscles and masseter muscles during treatment with Occlus-o-Guide(®) and Andresen activator appliances. METHODS: Eighty-two patients (35 males and 47 females) aged between 8 and 12 years (mean age, 10.5 ± 0.8 years) participated in the study. Fifty patients underwent treatment with an Occlus-o-Guide(®) and 32 patients with an Andresen activator. All patients underwent EMG examination using a Freely EMG (De Gotzen, Legnano, Italy) and surface bipolar electrodes when the appliances were worn for the first time (T0), and after 6 months (T1) and after 12 months (T2) of appliance use. RESULTS: Statistical analysis showed that both at T0 and T2, the percent overlapping coefficient (POC) of the anterior temporalis muscles was not statistically different between the appliance groups. At T0, the POC of the masseter muscles was significantly lower for the Andresen appliance as compared to the Occlus-o-Guide(®) (p = 0.02), while at T2 this significance was lost. CONCLUSIONS: At insertion of an appliance, all patients show neuromuscular balance that does not correspond to orthognathic occlusion. Both appliances work by creating muscular imbalance. With the appliances in situ, EMG responses were generally analogous for the Occlus-o-Guide(®) and the Andresen activator; however, the imbalance was greater and the recovery of the orthological muscular balance was slower in patients under treatment with the Andresen activator as compared to those with the Occlus-o-Guide(®)

How Do Metal Ion Levels Change over Time in Hip Resurfacing Patients? A Cohort Study

Metal-on-metal hip resurfacing (MOM-HR) is offered as an alternative to traditional hip arthroplasty for young, active adults with advanced osteoarthritis. Nevertheless, concerns remain regarding wear and corrosion of the bearing surfaces and the resulting increase in metal ion levels. We evaluated three cohorts of patients with Birmingham hip resurfacing (BHR) at an average follow-up of 2, 5, and 9 years. We asked whether there would be differences in ion levels between the cohorts and inside the gender. Nineteen patients were prospectively analyzed. The correlation with clinical-radiographic data was also performed. Chromium, cobalt, nickel, and molybdenum concentrations were measured by atomic absorption spectrophotometry. Chromium and cobalt levels demonstrated a tendency to decrease over time. Such tendency was present only in females. An inverse correlation between chromium, implant size, and Harris hip score was present at short term; it disappeared over time together with the decreased ion levels. The prospective analysis showed that, although metal ion levels remained fairly constant within each patient, there was a relatively large variation between subjects, so mean data in this scenario must be interpreted with caution. The chronic high exposure should be carefully considered during implant selection, particularly in young subjects, and a stricter monitoring is mandatory