Search

The phenomenon of high-frequency distortion (HFD) in the electric grids, at both low-voltage (LV) and medium-voltage (MV) levels, is gaining increasing interest within the scientific and technical community due to its growing occurrence and the associated impact. These disturbances are mainly injected into the grid by new installed devices, essential for achieving decentralized generation based on renewable sources. In fact, these generation systems are connected to the grid through power converters, whose switching frequencies are significantly increasing, leading to a corresponding rise in the frequency of the injected disturbances. HFD represents a quite recent issue, but numerous scientific papers have been published in recent years on this topic. Furthermore, various international standards have also covered it, to provide guidance on instrumentation and related algorithms and indices for the measurement of these phenomena. When measuring HFD in MV grids, it is necessary to use instrument transformers (ITs) to scale voltages and currents to levels fitting with the input stages of power quality (PQ) instruments. In this respect, the recently released Edition 2 of the IEC 61869-1 standard extends the concept of the IT accuracy class up to 500 kHz; however, the IEC 61869 standard family provides guidelines on how to test ITs only at power frequency. This paper provides an extensive review of literature, standards, and the main outputs of European research projects focusing on HFD and ITs. This preliminary study of the state-of-the-art represents an essential starting point for defining significant waveforms to test ITs and, more generally, to achieve a comprehensive understanding of HFD. In this framework, this paper provides a summary of the most common ranges of amplitude and frequency variations of actual HFD found in real grids, the currently adopted measurement methods, and the normative open challenges to be addressed.

Fishes are an important component of human nutrition, mainly acting as source of essential fatty acids in the prevention of cardiovascular disorders. The increase in their consumption has led to a growth of fishes waste; therefore, the disposal and recycling of waste has become a key issue to address, in accordance with circular economy principles. The Moroccan Hypophthalmichthys molitrix and Cyprinus carpio fishes, living in freshwater and marine environments, were collected at mature and immature stages. The fatty acid (FA) profiles of liver and ovary tissues were investigated by GC-MS and compared with edible fillet tissues. The gonadosomatic index, the hypocholesterolemic/hypercholesterolemic ratio, and the atherogenicity and thrombogenicity indexes were measured. Polyunsaturated fatty acids were found to be abundant in the mature ovary and fillet of both species, with a polyunsaturated fatty acids/saturated fatty acids ratio ranging from 0.40 to 1.06 and a monounsaturated fatty acids/polyunsaturated fatty acids ratio between 0.64 and 1.84. Saturated fatty acids were found to be highly abundant in the liver and gonads of both species (range 30-54%), as well as monounsaturated fatty acids (range 35-58%). The results suggested that the exploitation of fish wastes, such as the liver and ovary, may represent a sustainable strategy for the achievement of high value-added molecules with nutraceutical potential.

Objective: We aim to validate an algorithm based on routinely-collected healthcare data to detect incidence of multiple sclerosis (MS) in the Campania Region (South Italy) and to explore its spatial and temporal variations., Methods: We included individuals resident in the Campania Region who had at least one MS record in administrative datasets (drug prescriptions, hospital discharge, outpatients), from 2015 to 2020. We merged administrative to the clinical datasets to ascertain the actual date of diagnosis, and validated the minimum interval from our study baseline (Jan 1, 2015) to first MS records in administrative datasets to detect incident cases. We used Bayesian approach to explore geographical distribution, also including deprivation index as a covariate in the estimation model. We used the capture-recapture method to estimate the proportion of undetected cases., Results: The best performance was achieved by the 12-month interval algorithm, detecting 2,150 incident MS cases, with 74.4% sensitivity (95%CI = 64.1%, 85.9%) and 95.3% specificity (95%CI = 90.7%, 99.8%). The cumulative incidence was 36.68 (95%CI = 35.15, 38.26) per 100,000 from 2016 to 2020. The mean annual incidence was 7.34 (95%CI = 7.03, 7.65) per 100,000 people-year. The geographical distribution of MS relative risk shows a decreasing east-west incidence gradient. The number of expected MS cases was 11% higher than the detected cases., Conclusions: We validated a case-finding algorithm based on administrative data to estimate MS incidence, and its spatial/temporal variations. This algorithm provides up-to-date estimates of MS incidence, and will be used in future studies to evaluate changes in MS incidence in relation to different risk factors., Competing Interests: Declaration of Competing Interest Marcello Moccia has received research grants from the ECTRIMS-MAGNIMS, the UK MS Society, and Merck; honoraria from Biogen, Ipsen, Merck, Roche, and Sanofi-Genzyme. Vincenzo Brescia Morra has received research grants from the Italian MS Society, and Roche, and honoraria from Bayer, Biogen, Merck, Mylan, Novartis, Roche, Sanofi-Genzyme, and Teva. Raffaele Palladino has received research grants from Sanofi-Genzyme. Other authors have nothing to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: In kidney transplant recipients (KTR), the end-stage kidney disease (ESKD) risk dependent on the risk factors acting in native chronic kidney disease (CKD) remains undefined., Methods: We compared risk and determinants of ESKD between 757 adult KTR and 1940 patients with native CKD before and after propensity-score (PS) analysis matched for unmodifiable risk factors [(age, sex, diabetes, cardiovascular disease and estimated glomerular filtration rate (eGFR)]., Results: In unmatched cohorts, eGFR was lower in CKD versus KTR (45.9 ± 11.3 versus 59.2 ± 13.4 mL/min/1.73 m2, P < 0.001). During a median follow-up of 5.4 years, the unadjusted cumulative incidence of ESKD was consistently lower in unmatched KTR versus CKD. Conversely, in PS-matched analysis, the risk of ESKD in KTR was 78% lower versus CKD at 1 year of follow-up while progressively increased over time resulting similar to that of native CKD patients after 5 years and 2.3-fold higher than that observed in CKD at 10 years. R2 analysis in unmatched patients showed that the proportion of the outcome variance explained by traditional ESKD determinants was smaller in KTR versus native CKD (31% versus 70%). After PS matching, the risk of ESKD [hazard ratio (HR), 95% confidence interval (95% CI)] was significantly associated with systolic blood pressure (1.02, 1.01-1.02), phosphorus (1.31, 1.05-1.64), 24-h proteinuria (1.11, 1.05-1.17) and haemoglobin (0.85, 0.78-0.93) irrespective of KTR status. Similar data were obtained after matching also for modifiable risk factors., Conclusions: In KTR, when compared with matched native CKD patients, the risk of ESKD is lower in the first 5 years and higher later on. Traditional determinants of ESKD account for one-third of the variability of time-to-graft failure., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Gene therapy of Usher syndrome type 1B (USH1B) due to mutations in the large Myosin VIIA ( MYO7A ) gene is limited by the packaging capacity of adeno-associated viral (AAV) vectors. To overcome this, we have previously developed dual AAV8 vectors which encode human MYO7A (dual AAV8. MYO7A ). Here we show that subretinal administration of 1.37E+9 to 1.37E+10 genome copies of a good-manufacturing-practice-like lot of dual AAV8. MYO7A improves the retinal defects of a mouse model of USH1B. The same lot was used in non-human primates at doses 1.6× and 4.3× the highest dose proposed for the clinical trial which was based on mouse efficacy data. Long-lasting alterations in retinal function and morphology were observed following subretinal administration of dual AAV8. MYO7A at the high dose. These findings were modest and improved over time in the low-dose group, as also observed in other studies involving the use of AAV8 in non-human primates and humans. Biodistribution and shedding studies confirmed the presence of vector DNA mainly in the visual pathway. Accordingly, we detected human MYO7A mRNA expression predominantly in the retina. Overall, these studies pave the way for the clinical translation of subretinal administration of dual AAV vectors in USH1B subjects., Competing Interests: A.A. is Scientific Founder and Chief Scientific Officer of AAVantgarde BIO Srl, a company that has licensed dual AAV8.MYO7A and is further developing this program into the clinic. R.F. is currently an employee of AAVantgarde BIO Srl. J.-B.M. is an employee of Genosafe, a contract research organization involved in the further development of this program into the clinic. M.F., A.N., F.G., and V.A. are employees of Reithera Srl, a contract development and manufacturing organization involved in the further development of this program into the clinic. S.C. is Scientific Founder and Chief of Technology of Reithera Srl., (© 2023 The Authors.)

There is a strong need to develop eco-sustainable agricultural techniques to improve crop yields while preserving biomolecule contents and reducing the adverse environmental impact of agro-chemicals. The use of microorganisms in agriculture represents an attractive and innovative solution. Herein, a chemical study on the nutritional and sensory qualities of San Marzano Cirio 3 (SMC3), Corbarino (CO) and Brandywine (BW) tomato varieties cultivated with and without effective microorganisms (EM) is reported. LC-MS analysis of the methanolic extracts allowed for the identification of 21 polyphenol derivatives. In different proportions among the studied varieties, the two main polyphenols were rutin and naringenin chalcone; the latter was isolated and chemically identified by complementary HR-ESIMS/MS and NMR methods. SMC3 and CO were richer in naringenin chalcone. Conversely, BW showed higher proportions of rutin; however, in all cases, the relative amounts of the two polyphenols considered together increased over the other minor components after the EM treatment. The qualitative and quantitative HPLC analyses of taste-active compounds (aspartic acid, glutamic acid, AMP and GMP) revealed a significant difference in aspartic and glutamic acids and ribonucleotide contents according to the cultivation condition (±EM), particularly in BW. This study provides chemical data in support of the use of EM green technology for the cultivation of edible agricultural products, such as tomato preserves, and may even improve nutritional and sensory qualities while safeguarding the environment.

Challenges to the widespread application of gene therapy with adeno-associated viral (AAV) vectors include dominant conditions due to gain-of-function mutations which require allele-specific knockout, as well as long-term transgene expression from proliferating tissues, which is hampered by AAV DNA episomal status. To overcome these challenges, we used CRISPR/Cas9-mediated homology-independent targeted integration (HITI) in retina and liver as paradigmatic target tissues. We show that AAV-HITI targets photoreceptors of both mouse and pig retina, and this results in significant improvements to retinal morphology and function in mice with autosomal dominant retinitis pigmentosa. In addition, we show that neonatal systemic AAV-HITI delivery achieves stable liver transgene expression and phenotypic improvement in a mouse model of a severe lysosomal storage disease. We also show that HITI applications predominantly result in on-target editing. These results lay the groundwork for the application of AAV-HITI for the treatment of diseases affecting various organs., (© 2022. The Author(s).)