Assigning UPDRS Scores in the Leg Agility Task of Parkinsonians: Can It Be Done through BSN-based Kinematic Variables?

In this paper, by characterizing the Leg Agility (LA) task, which contributes to the evaluation of the degree of severity of the Parkinson's Disease (PD), through kinematic variables (including the angular amplitude and speed of thighs' motion), we investigate the link between these variables and Unified Parkinson's Disease Rating Scale (UPDRS) scores. Our investigation relies on the use of a few body-worn wireless inertial nodes and represents a first step in the design of a portable system, amenable to be integrated in Internet of Things (IoT) scenarios, for automatic detection of the degree of severity (in terms of UPDRS score) of PD. The experimental investigation is carried out considering 24 PD patients.Comment: 10 page

Sex Is the Main Determinant of Levodopa Clinical Pharmacokinetics: Evidence from a Large Series of Levodopa Therapeutic Monitoring

Background: Different studies, mostly with limited cohorts, have suggested the effects of patients' characteristics on levodopa (LD) pharmacokinetics. Objective: We primarily aimed at investigating in a large population the relationship between patients' features and LD kinetic variables, to assess the main demographic and clinical predictors of LD clinical pharmacokinetics. Methods: The study was retrospective, based on data collected from subjects with parkinsonism on chronic LD undergoing LD therapeutic monitoring (TM). LD TM includes serial quantitative motor tests and blood samples to measure plasma drug concentrations after each subject's chronically taken first-morning LD dose intake. Results: Five hundred patients, 308 males (61.6%), mean (SD) age of 65 (10.1) years were included. Parkinsonian symptoms and LD therapy lasted 5.5 (4.5) and 3.4 (3.9) years, respectively. MDS-UPDRS part III "off" score was 28.8 (15.2). LD dose was 348.2 (187.1) mg/day. From multiple linear regression analysis, test dose, sex, type of LD decarboxylase inhibitor, weight and MDS-UPDRS part III score were linear predictors of both LD peak plasma concentration (Cmax) (R2 = 0.52) and area under the 3-h plasma concentration-time curve (AUC) (R2 = 0.71), while age was a further predictor only for AUC. Besides test dose, sex was the strongest independent contributing variable to LD AUC, which resulted 27% higher in females compared to males. Conclusion: This is the largest collection of data on the relationship between demographic and clinical-therapeutic variables and LD kinetics in patients with parkinsonian symptoms. As a main clinically practical finding, women might require a 25% reduced weight-normalized LD dose compared with men to achieve the same LD bioavailability

Biostimulant Action of Dissolved Humic Substances From a Conventionally and an Organically Managed Soil on Nitrate Acquisition in Maize Plants

Conversion of conventional farming (CF) to organic farming (OF) is claimed to allow a sustainable management of soil resources, but information on changes induced on dissolved organic matter (DOM) are scarce. Among DOM components, dissolved humic substances (DHS) were shown to possess stimulatory effects on plant growth. DHS were isolated from CF and OF soil leacheates collected from soil monolith columns: first in November (bare soils) and then in April and June (bare and planted soils). DHS caused an enhancement of nitrate uptake rates in maize roots and modulated several genes involved in nitrogen acquisition. The DHS from OF soil exerted a stronger biostimulant action on the nitrate uptake system, but the first assimilatory step of nitrate was mainly activated by DHS derived from CF soil. To validate the physiological response of plants to DHS exposure, real-time RT-PCR analyses were performed on those genes most involved in nitrate acquisition, such as ZmNRT2.1, ZmNRT2.2, ZmMHA2 (coding for two high-affinity nitrate transporters and a PM H+-proton pump), ZmNADH:NR, ZmNADPH:NR, and ZmNiR (coding for nitrate reductases and nitrite reductase). All tested DHS fractions induced the upregulation of nitrate reductase (NR), and in particular the OF2 DHS stimulated the expression of both tested transcripts encoding for two NR isoforms. Characteristics of DHS varied during the experiment in both OF and CF soils: a decrease of high molecular weight fractions in the OF soil, a general increase in the carboxylic groups content, as well as diverse structural modifications in OF vs. CF soils were observed. These changes were accelerated in planted soils. Similarity of chemical properties of DHS with the more easily obtainable water-soluble humic substance extracted from peat (WEHS) and the correspondence of their biostimulant actions confirm the validity of studies which employ WEHS as an easily available source of DHS to investigate biostimulant actions on agricultural crops

AMPLICON-BASED NGS: AN EFFECTIVE APPROACH FOR THE MOLECULAR DIAGNOSIS OF EPIDERMOLYSIS BULLOSA

Background: Epidermolysis Bullosa (EB) is caused by mutations in genes that encode proteins belonging to the epidermal-dermal junction assembly. Due to the extreme clinical/genetic heterogeneity of the disease, the current methods available for diagnosing EB involve immunohistochemistry of bioptic samples and transmission electron microscopy followed by single candidate gene Sanger Sequencing (SS), which are labour intensive and expensive clinical pathways. Objectives: According to the recently published recommendations for the EB diagnosis and treatment, the assessment of the mutational landscape is now a fundamental step for developing a comprehensive diagnostic path. Next-Generation Sequencing (NGS) via the parallel ultra-deep sequencing of many genes represents a proper method for reducing the processing time and costs of EB diagnostics. Methods: We developed an EB disease-comprehensive AmpliSeq panel to accomplish the NGS on the Ion Torrent PGM platform. The panel was performed on ten patients with known genetic diagnoses and was then employed in eight family trios with unknown molecular footprints. Results: The panel was successful in finding the causative mutations in all ten of the patients with known mutations, fully confirming the SS data and providing proof of concept of the sensitivity, specificity, and accuracy of this procedure. In addition to being consistent with the clinical diagnosis, it was also effective in the trios, identifying all of the variants, including ones that the SS missed or de novo mutations. Conclusions: The NGS and AmpliSeq were shown to be an effective approach for the diagnosis of EB, resulting in a costand time-effective 72-hour procedure

Contamination by mercury affects methane oxidation capacity of aerobic arable soils

Effects of long term Hg contamination and addition of Hg2+ on soil CH4 oxidation were investigated in laboratory incubation experiments. Non contaminated soils had CH4 oxidation rate constants (k) between 5.2 and 24.5 x 10-3 h-1, whereas Hg contaminated soils had rates ranging from 2.4 to 8.0 x 10-3 h-1. Specific oxidation rates (qK=k/Cbio), normalized with respect to soil microbial biomass C (Cbio), allowed complete separation between the two groups and ranged between 32.6 and 56.2 x 10-6 h-1 \u3bcg-1 Cbio in non contaminated soils and between 6.5 and 14.3 x 10-6 h-1 \u3bcg-1 Cbio in long-term Hg contaminated soils. To test short-term toxicity effects and eventual adaptation of methane oxidizers, Hg2+ was added at two levels, 50 and 100 \u3bcg g-1, to two soils, one non contaminated and the other contaminated for centuries by Hg, having about the same Cbio. Methane oxidation capacity and Cbio of the soil exposed for centuries to high levels of Hg, were not affected by Hg2+ additions. In the non contaminated soil Cbio was not affected, but methane oxidation rate decreased from 21.4 to 9.8 x 10-3 h-1. Our results show that Hg contamination, either long-term or short term, may negatively impair the CH4 oxidizing capacity of aerobic arable soils

The long and winding road that leads to a cure for epidermolysis bullosa

Inherited epidermolysis bullosa (EB) is a family of rare genetic skin disorders characterized by structural and mechanical fragility of skin and mucosal membranes. The main feature of EB is the presence of recurrent skin blistering or erosions, which have a profound impact in the quality of life of EB patients and, in the most severe forms, cause early lethality. During the past two decades, it became possible to identify mutations in genes responsible for different types of EB and characterize the abnormalities of the related proteins. Nowadays, there is no cure for EB; all the treatments are palliative and focused on the relief of the devastating EB clinical picture. Recent advancements in molecular biology, stem cell biology and regenerative medicine have fostered new therapeutic approaches for EB. This review is focused on recent developments in gene therapy, protein replacement and cell-based therapy for EB, all aimed at finding a cure for this devastating disease