Magnetic resonance imaging 3t and total fibrotic volume in autosomal dominant polycystic kidney disease

INTRODUCTION: Autosomal dominant polycystic kidney disease (ADPKD) is the most common renal hereditary disorder. Several authors have attempted to identify a kidney damage marker for predicting the prognosis and the effectiveness of therapy in ADPKD. The aim of this study was to identify and quantify in ADPKD, through a novel MR protocol with 3 Tesla (MRI 3Tesla), the presence of parenchymal fibrotic tissue at early stage of disease, able to correlate the glomerular filtrate and to predict the loss of the function renal. MATERIAL AND METHODS: 15 ADPKD patients undergone to renal MRI 3Tesla at T0 and revaluated after follow up (T1) of 5 years. We have evaluated renal function, plasma aldosterone concentration (PAC), insulin resistance and surrogate markers of atherosclerosis (carotid intima media thickness (IMT), ankle/brachial index (ABI) and left ventricular mass index (LVMI). RESULTS: Our study showed a significant negative correlation between total kidney volume and estimated glomerular filtration rate (eGFR) during observational observation (p<0.02). Moreover, we showed a negative correlation between eGFR with Total Fibrotic Volume (TFV) (p<0.04) and Total Perfusion Volume/Total kidney Volume(<0.02). Moreover TFV was correlated positively with PAC (p<0.05), insulin values (p<0.05), ABI (p <0.05) and LVMI(p<0.01). CONCLUSIONS: The MRI 3Tesla, despite the high costs, could be considered an useful and non-invasive method in the evaluation of fibrotic tissue and progression of the disease in ADPKD patients. Further clinical trials on larger group are due to confirm the results of this pilot study, suggesting that MRI 3Tesla can be useful to evaluate the effectiveness of new therapeutic strategies. This article is protected by copyright. All rights reserved

Forecasting seasonal influenza fusing digital indicators and a mechanistic disease model

The availability of novel digital data streams that can be used as proxy for monitoring infectious disease incidence is ushering in a new era for real-time forecast approaches to disease spreading. Here, we propose the first seasonal influenza forecast framework based on a stochastic, spatially structured mechanistic model (individual level microsimulation) initialized with geo-localized microblogging data. The framework provides for more than 600 census areas in the United States, Italy and Spain, the initial conditions for a stochastic epidemic computational model that generates an ensemble of forecasts for the main indicators of the epidemic season: peak time and intensity. We evaluate the forecasts accuracy and reliability by comparing the results from our framework with the data from the official influenza surveillance systems in the US, Italy and Spain in the seasons 2014/15 and 2015/16. In all countries studied, the proposed framework provides reliable results with leads of up to 6 weeks that became more stable and accurate with progression of the season. The results for the United States have been generated in real-time in the context of the Centers for Disease Control and Prevention “Forecasting the Influenza Season Challenge". A characteristic feature of the mechanistic modeling approach is in the explicit estimate of key epidemiological parameters relevant for public health decision-making that cannot be achieved with statistical models not considering the disease dynamic. Furthermore, the presented framework allows the fusion of multiple data streams in the initialization stage and can be enriched with census, weather and socioeconomic data

Epoetin alfa increases frataxin production in Friedreich's ataxia without affecting hematocrit.

Objective of the study was to test the efficacy, safety, and tolerability of two single doses of Epoetin alfa in patients with Friedreich's ataxia. Ten patients were treated subcutaneously with 600 IU/kg for the first dose, and 3 months later with 1200 IU/kg. Epoetin alfa had no acute effect on frataxin, whereas a delayed and sustained increase in frataxin was evident at 3 months after the first dose (+35%; P < 0.05), and up to 6 months after the second dose (+54%; P < 0.001). The treatment was well tolerated and did not affect hematocrit, cardiac function, and neurological scale. Single high dose of Epoetin alfa can produce a considerably larger and sustained effect when compared with low doses and repeated administration schemes previously adopted. In addition, no hemoglobin increase was observed, and none of our patients required phlebotomy, indicating lack of erythropoietic effect of single high dose of erythropoietin. © 2010 Movement Disorder Society

Social data mining and seasonal influenza forecasts: The FluOutlook platform

FluOutlook is an online platform where multiple data sources are integrated to initialize and train a portfolio of epidemic models for influenza forecast. During the 2014/15 season, the system has been used to provide real-time forecasts for 7 countries in North America and Europe

Bioelectrical Impedance Vector Analysis and Brain Natriuretic Peptide in the Evaluation of Patients with Chronic Kidney Disease in Hemodialitic Treatment

Introduction: Setting dry weight (DW) in hemodialysis (HD) patients is still a hard issue. Several clinical, hematochemical, and instrumental parameters have been considered. In the last years, bioelectrical impedance vector analysis (BIVA) became the main method to evaluate body composition and water body percentage. However, it is still difficult to assess the nutritional status and identify a correct DW in HD patients. Aim: The aim of the study was to set DW and nutritional status, combining BIVA with phase angle (PhA) and serum brain natriuretic peptide (BNP) in HD patients. Methods: We evaluated PhA and BNP modifications before (T0), after HD section (T1), and after 60 days (T2), in all patients treated in our HD center. Results: A total of 50 patients (36 males) with a mean age of 70.1 ± 8.85 years were recruited. We did not report significant changes in BNP and PhA between T0 and T1, while they were significantly different between T0 and T2. We also reported a significant difference between T0 and T2 in ECW/TBW, while we did not show significant variations in ECM/BMC between T0, T1, and T2 indicating a stability of the nutritional status. PhA, BNP, and ECW/TBW returned to a normal value in patients in which we reached a DW, also considering clinical parameters such as blood pressure and antihypertensive therapy. The weight loss obtained with the evaluation of the BIVA and the BNP was 1.2–5.7 kg, greater than that calculated empirically which stood at around 0.9–4.3 kg. Conclusion: We suggest to carry out BIVA with PhA combined with BNP to assess an adequate DW and evaluate a correct nutritional status in HD patients

PROGNOSTIC IMPACT OF DISCORDANT VERSUS CONCORDANT LEFT BUNDLE BRANCH BLOCK IN HEART FAILURE PATIENTS UNDERGOING CARDIAC RESYNCHRONIZATION THERAPY

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Membrane association of peroxiredoxin-2 in red cells is mediated by n-terminal cytoplasmic domain of band 3

Band 3(B3),the anion transporter, is an integral membrane protein that plays a key structural role by anchor in the plasmamembrane to the spectrin-based membrane skeleton in the red cell. In addition, it also plays a critical role in the assembly of glycolytic enzymes to regulate red cell metabolism. However, its ability to recruit proteins that can prevent membrane oxidation has not been previously explored. In this study, using a variety of experimental approaches including cross-linking studies, fluorescence and dichroic measurements,surface plasmon resonance analysis, and proteolytic digestion assays, we document that the antioxidant protein peroxiredoxin-2(PRDX2), the third most abundant cytoplasmic protein in RBCs, interacts with the cytoplasmic domain of B3. The surface electrostatic potential analysis and stoichiometry measurements revealed that the N-terminal peptide of B3 is involved in the interaction. PRDX2 underwent a conformational change upon its binding to B3 without losing its peroxidase activity. Hemichrome formation induced by phenylhydrazine of RBCs prevented membrane association of PRDX2, implying overlapping binding sites. Documentation of the absence of binding of PRDX2 to B3 Neapolis red cell membranes, in which the initial N-terminal 11 amino acids are deleted, enabled us to conclude that PRDX2 binds to the N-terminal cytoplasmic domain of B3 and that the first 11 amino acids of this domain are crucial for PRDX2 membrane association in intact RBCs. These findings imply yet another important role for B3 in regulating red cell membrane function

Combining participatory influenza surveillance with modeling and forecasting

Background: Influenza outbreaks affect millions of people every year and its surveillance is usually carried out in developed countries through a network of sentinel doctors who report the weekly number of Influenza-like Illness cases observed among the visited patients. Monitoring and forecasting the evolution of these outbreaks supports decision makers in designing effective interventions and allocating resources to mitigate their impact. Objectives: Describe the existing participatory surveillance approaches that have been used for modeling and forecasting of the seasonal influenza epidemic, and how they can help strengthen real-time epidemic science and provide a more rigorous understanding of epidemic conditions. Methods: We describe three different participatory surveillance systems, WISDM (Widely Internet Sourced Distributed Monitoring), InfluenzaNet and Flu Near You (FNY), and show how modeling and simulation can be or has been combined with participatory disease surveillance to: i) measure the non-response bias in a participatory surveillance sample using WISDM; and ii) nowcast and forecast influenza activity in different parts of the world (using InfluenzaNet and Flu Near You). Results: WISDM based results measure the participatory and sample bias for three epidemic metrics i.e. attack rate, peak infection rate, and time-to-peak, and find the participatory bias to be the largest component of the total bias. InfluenzaNet platform shows that digital participatory surveillance data combined with a realistic data-driven epidemiological model can provide both short-term and long-term forecasts of epidemic intensities; and the ground truth data lie within the 95 percent confidence intervals for most weeks. The statistical accuracy of the ensemble forecasts increase as the season progresses. The Flu Near You platform shows that participatory surveillance data provide accurate short-term flu activity forecasts and influenza activity predictions. The correlation of the HealthMap Flu Trends estimates with the observed CDC ILI rates is 0.99 for 2013-2015. Additional data sources lead to an error reduction of about 40% when compared to the estimates of the model that only incorporates CDC historical information. Conclusions: While the advantages of participatory surveillance, compared to traditional surveillance, include its timeliness, lower costs, and broader reach, it is limited by a lack of control over the characteristics of the population sample. Modeling and simulation can help overcome this limitation as well as provide real-time and long term forecasting of Influenza activity in data poor parts of the world

Auditory cortex hypoperfusion: a metabolic hallmark in Beta Thalassemia

Abstract Background Sensorineural hearing loss in beta-thalassemia is common and it is generally associated with iron chelation therapy. However, data are scarce, especially on adult populations, and a possible involvement of the central auditory areas has not been investigated yet. We performed a multicenter cross-sectional audiological and single-center 3Tesla brain perfusion MRI study enrolling 77 transfusion-dependent/non transfusion-dependent adult patients and 56 healthy controls. Pure tone audiometry, demographics, clinical/laboratory and cognitive functioning data were recorded. Results Half of patients (52%) presented with high-frequency hearing deficit, with overt hypoacusia (Pure Tone Average (PTA) > 25 dB) in 35%, irrespective of iron chelation or clinical phenotype. Bilateral voxel clusters of significant relative hypoperfusion were found in the auditory cortex of beta-thalassemia patients, regardless of clinical phenotype. In controls and transfusion-dependent (but not in non-transfusion-dependent) patients, the relative auditory cortex perfusion values increased linearly with age (p < 0.04). Relative auditory cortex perfusion values showed a significant U-shaped correlation with PTA values among hearing loss patients, and a linear correlation with the full scale intelligence quotient (right side p = 0.01, left side p = 0.02) with its domain related to communication skills (right side p = 0.04, left side p = 0.07) in controls but not in beta-thalassemia patients. Audiometric test results did not correlate to cognitive test scores in any subgroup. Conclusions In conclusion, primary auditory cortex perfusion changes are a metabolic hallmark of adult beta-thalassemia, thus suggesting complex remodeling of the hearing function, that occurs regardless of chelation therapy and before clinically manifest hearing loss. The cognitive impact of perfusion changes is intriguing but requires further investigations