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Objective: The balance between benefits and risks of discordant outcomes makes the Genome-Wide Non-Invasive Prenatal Test (GW-NIPT) controversial. This study aims to evaluate performance and clinical utility in a wide cohort of unselected clinical cases from a single center when a standardized protocol is applied and integrated with a secondary algorithm for data interpretation., Method: In 2 years, over 70,000 pregnant patients underwent GW-NIPT for fetal common trisomies, sex chromosome aneuploidies, rare autosomal aneuploidies, segmental abnormalities (CNVs ≥ 7 Mb) and microdeletions (CNVs < 7 Mb). All samples were uniformly processed with Veriseq NIPT Solution v2 and analyzed using all data metrics along with a home-made algorithm for sequencing data analysis. Results were retrospectively reviewed for clinical outcomes., Results: Among 71,883 eligible cases including twin pregnancies, 1011 (1.4%) received a positive result and 781 were confirmed by invasive prenatal diagnosis. Clinical sensitivity ranged from 99.65% for common trisomy (T21, T18, T13) to 83.33% for microdeletions, while specificity remained high (99.98%) for each class of fetal abnormalities detected., Conclusions: Integrating a standardized protocol with an internal algorithm allowed discordant results to be reduced, yielding high accuracy. Observed reliability in detecting genome-wide chromosomal conditions reinforced the expanded NIPT utility in clinical practice., (© 2024 John Wiley & Sons Ltd.)

Introduction: There is growing interest in the public health and transport sectors in research into exposure to biological hazards, considering not only the risks arising from inter-human contagion, but also those related to exposure to the flight environment itself. The aim of this paper is to report data from an investigation into the water and air-conditioning systems of commercial aircraft for the presence of Legionella contamination, with a total of 645 water samples taken during the period 2007−2021. Methods: The investigation involved 126 aircraft of six different commercial aircraft types: MD80, Airbus A320 F, Embraer 175/190, AIRBUS A330, Boeing 767 and Boeing 777. Water samples were taken from the water systems (toilet taps, galley and boilers). Each sample was preliminarily subjected to an evaluation of the following parameters: temperature, pH and residual chlorine. The ScanVit® Legionella kit was used for bacteria detection and enumeration. Results: Samples were considered positive if the number of colony-forming units/liter (CFU/L) was >100. For the entire observation period, 45% of the investigated aircraft tested positive. Regarding the overall number of samples analyzed, 68.4% (441/645) were below 100 CFU/L, and thus within the limits allowed by the Italian Guidelines. Conclusions: Water system contamination with Legionella in the air transport field is a real public health issue that should not be underestimated given the heavy passenger traffic. Infection should be considered an occupational risk to which crew members are exposed.

Introduction: Since 2008, Italian legislators, with the aim of ensuring public safety, have made it mandatory for an occupational doctor (OD) to assess specific categories of workers to exclude those who may have consumed drugs of abuse. Due to the relevance of work activities relating to the civil aviation and airport sector, a policy based on the use of training and information tools, as well as a health surveillance protocol, has been undertaken since 2009., Materials and Methods: A total of 61,008 workers at a commercial airline underwent health surveillance between 2009 and 2019. Following ≤24 h notification, their urine was screened for opiates, cocaine, cannabinoids, amphetamines, methamphetamines, and methylenedioxymethamphetamine (MDMA) using an immunochemical test. Positive results were confirmed using Gas Chromatography-Mass Spectrometry (GC/MS) or Liquid Chromatography -Mass Spectrometry (LC/MS). In confirmed cases, the workers were declared unfit and sent to a specialized laboratory for a second level analysis., Results: Positive results, initially >1%, have halved in the last four years (<0.5%). The percentage of positive results was consistently very low among pilots and, moreover, the rare positive cases detected were due to a cross-reactivity phenomena. The highest and most discontinuous percentages seen occurred in the population undergoing a pre-employment examination. Regarding the types of substance used, a prevalence of cannabis (58.52%) and cocaine (35.2%) use was observed., Conclusions: The data presented indicate that the air transport sector, in all its components (ground workers and air crews), has a very limited number of substance abusers, and this number tends to decrease over time and with work seniority. Another aspect of particular interest, and which is more specific to toxicology, concerns the detection of cross-reactivity in urinary immunochemical screening between the antibodies to drugs of abuse and certain other drugs, such as anti-inflammatories or antibiotics; as well as foods, and other commonly used substances.

Objective: In this study, we expanded conventional cell-free fetal DNA (cfDNA)-based non-invasive prenatal testing (NIPT) to cover the entire genome. We aimed to compare the performance of the two tests in a large general population of pregnant women, in order to assess the clinical utility of the genome-wide screening., Method: Genome-wide cfDNA analysis was offered to 12 114 pregnant women undergoing NIPT for common fetal aneuploidy. Sequencing data were analyzed using an algorithm optimized to identify aneuploidies and subchromosomal aberrations., Results: Genome-wide screening allowed detection of 12 (7.4%) potentially viable clinically relevant chromosomal abnormalities, which would have remained overlooked if only conventional NIPT had been performed. This resulted in a statistically significant higher sensitivity (100% vs 92.64%, p < 0.001) than did standard screening. This was achieved without sacrificing the specificity of the test, which resulted similar to that obtained with standard cfDNA testing (99.87% vs 99.77%, p = 0.064)., Conclusion: Genome-wide cfDNA analysis represents an enhanced screening tool for prenatal detection of chromosomal abnormalities, allowing identification of clinically relevant imbalances that are not detectable by conventional cfDNA testing. The results of this study demonstrate the clinical utility of genome-wide cfDNA analysis. This level of screening provides a significant higher sensitivity compared to standard screening while maintaining a high specificity, with the potential to improve overall pregnancy management. © 2017 John Wiley & Sons, Ltd., (© 2017 John Wiley & Sons, Ltd.)

Objective: Several non-invasive prenatal testing (NIPT) methods, which analyze circulating fetal cell-free DNA (cfDNA) in maternal plasma, suggest a fetal fraction (FF) ≥ 4% for a reportable result, with the assumption that fetal aneuploidies may not be detectable at lower FF. This study determined the actual limit of detection (LOD) of a massively parallel sequencing-based NIPT method and evaluated its performance in testing samples with low FF., Method: An experimental model, involving the creation of artificial plasma mixtures with a final aneuploid FF ranging from 1% to 4%, simulated samples at different proportions of fetal cfDNA. We then analyzed 7103 blood samples, from pregnant women undergoing NIPT, to assess the impact of low FF on the performance of cfDNA testing., Results: Detection of common aneuploidies in samples with an FF as low as 2% is well within the ability of this technology. Of 105 pregnancies confirmed chromosomally abnormal, 25 (23.8%) involving a 2% <  FF  <  4% were consistently detected. These high-risk pregnancies would have not been identified using the suggested 4% FF cut-off., Conclusion: This study underscores the importance of determining the actual LOD for each specific NIPT methodology. It may reduce the incidence of test cancelations and shorten the time required for the diagnosis of aneuploidy. © 2016 John Wiley & Sons, Ltd., (© 2016 John Wiley & Sons, Ltd.)

It is widely acknowledged that plant-made pharmaceuticals (PMPs) offer numerous benefits, including inexpensive production, biological safety and the facility for production at agricultural scale. At the same time, it is important to minimize any potential risk associated with this new technology, including the potential release of bioactive proteins into the environment. To address this issue, we studied transgenic Nicotiana benthamiana and Nicotiana tabacum plants expressing two recombinant single-chain variable fragment (scFv) antibodies, respectively scFvB9 and scFvH10. ScFvB9 was raised against glycoprotein G1 of Tomato spotted wilt virus (TSWV), and scFvH10 was raised against human tumor-associated antigen tenascin-C. Both antibodies were targeted to the secretory pathway using the N-terminal signal peptide from Phaseolus vulgaris polygalacturonase-inhibiting protein (PGIP), and scFvH10 carried in addition a C-terminal KDEL tetrapeptide for retention in the endoplasmic reticulum (ER). Sterile hydroponic cultures were established, allowing us to investigate whether scFvB9 and scFvH10 were present in root exudates. Intercellular fluids extracted from different plant tissues were analyzed by western blotting revealing the presence of scFvB9. Successful secretion of scFvB9 in hydroponic medium was also demonstrated, whereas no scFvH10 could be detected in the leaf, stem or root apoplast, nor secreted into the hydroponic medium. Our results show that scFvH10 release or diffusion from the roots of transgenic plants was not occurring, suggesting that the KDEL signal might contribute to the environmental biosafety of crops producing PMPs.