Short-term increases of plasma cardiac troponin I are better evaluated by comparison with the reference change value

Introduction: We have investigated consecutive troponin I measurements using the Reference Change Value (RCV) at low concentrations, in patients admitted in Emergency Department (ED). Materials and methods: Patients admitted for chest pain (N = 103) were evaluated retrospectively on the basis of two consecutive cardiac tro-ponin-I (cTn-I) tests. The second test levels exceeding the "Critical Reference Change Value" (CrRCV), a quantity calculated on the basis of the first result and the RCV of cTn-I, were considered particularly relevant. Clinical cases were analysed matching the concentration change (significative or not) with acute coronary syndrome (clinically confirmed or not). Healthy individuals (N = 70) results and internal quality control results were evaluated for the calculation of, respectively, the biological and the analytical variation of plasma cTn-I. Results: The cTn-I RCV was very high because of the high analytical variation of cTn-I in proximity of its decision limit, as shown by its imprecision profile study. Analysing data with the first result < 0.1 µg/L we have obtained an cTn-I RCV negative predictive value - NPV = 88% (95% CI = 82-92%). The 4 groups of patients have demonstrated a clinically significant difference (Chi square test; P < 0.001). Conclusions: The RCV allows to statistically evaluating the cTn-I increased levels in presence of the high imprecision of commercial cTn-I assay at low concentrations. This parameter could be applied in medical practice only for low cTn-I concentrations around the decision limit for the myocardial necrosis

Social life cycle assessment of an innovative industrial wastewater treatment plant

Abstract Background The social impacts generated by industrial waste treatment processes have not been studied enough, as shown in the literature. Social life cycle assessment studies have mainly focused on the assessment of products and less on industrial waste, especially wastewater, although potentially relevant from an environmental point of view, and also from a social one for various stakeholders. Purpose This case study concerns the social assessment of an innovative technology to treat the wastewater of a microelectronics company. In order to produce electronic components and semiconductors, the company has to treat and dispose of relevant wastewater streams containing various toxic substances. The wastewater streams need to be treated in order to protect the eco-system, representing a high cost for the company and a potential impact on the environment. For this reason, the company developed a LIFE project to demonstrate the viability to decrease the burdens on water bodies. The positive outcome of the test on the pilot plant paved the way for the construction of the full-scale plant that will treat all the wastewater generated by the company. The objective of this paper is the socio-economic assessment of a full-scale plant designed to treat three different kinds of wastewater. Methods The assessment of socio-economic potential impacts of a new technology has been carried out through the PSILCA (Product Social Impact Life Cycle Assessment) database implementation to evaluate 65 social indicators of a wastewater treatment plant. Results The line with the highest impact is the one which treats tetramethylammonium hydroxide; this is because this wastewater flow is the most abundant (14 and 43 times greater than the other wastewaters, respectively). The most affected stakeholder is the Local Community, followed by the Actors of the Value Chain; in fact, the results referred to the functional unit considered exceed 300,000 medium risk hours in both cases. For the Local Community this result arises from the indicator "Contribution to environmental load," which is understandable considering the object of the study since this indicator includes health effects. As far as the Value Chain Actors stakeholder is concerned, the two indicators most impacted are "Corruption" and "Social responsibility along the supply chain". The analysis conducted has also shown that upstream has a fundamental relevance for the social risks detected. Conclusions Considering the current lack of studies on both environmental and social impacts of wastewater treatment, and the fact that Social Life Cycle Assessment has not been widely used in this field, as emerged from literature review, this work is the first use of the PSILCA database to assess an industrial wastewater plant. The use of a social life cycle assessment database allows the value chain of a product system to be considered: the results show that most of the overall social risk derives from upstream sectors

Short-term increases of plasma cardiac troponin I are better evaluated by comparison with the reference change value

Introduction: We have investigated consecutive troponin I measurements using the Reference Change Value (RCV) at low concentrations, in patients admitted in Emergency Department (ED). Materials and methods: Patients admitted for chest pain (N = 103) were evaluated retrospectively on the basis of two consecutive cardiac tro-ponin-I (cTn-I) tests. The second test levels exceeding the "Critical Reference Change Value" (CrRCV), a quantity calculated on the basis of the first result and the RCV of cTn-I, were considered particularly relevant. Clinical cases were analysed matching the concentration change (significative or not) with acute coronary syndrome (clinically confirmed or not). Healthy individuals (N = 70) results and internal quality control results were evaluated for the calculation of, respectively, the biological and the analytical variation of plasma cTn-I. Results: The cTn-I RCV was very high because of the high analytical variation of cTn-I in proximity of its decision limit, as shown by its imprecision profile study. Analysing data with the first result < 0.1 µg/L we have obtained an cTn-I RCV negative predictive value - NPV = 88% (95% CI = 82-92%). The 4 groups of patients have demonstrated a clinically significant difference (Chi square test; P < 0.001). Conclusions: The RCV allows to statistically evaluating the cTn-I increased levels in presence of the high imprecision of commercial cTn-I assay at low concentrations. This parameter could be applied in medical practice only for low cTn-I concentrations around the decision limit for the myocardial necrosis

Progression of coronary artery calcification and cardiac events in patients with chronic renal disease not receiving dialysis

We tested for the presence of coronary calcifications in patients with chronic renal disease not on dialysis and studied its progression in 181 consecutive non-dialyzed patients who were followed for a median of 745 days. Coronary calcifications (calcium score) were tallied in Agatston units by computed tomography, and the patients were stratified into two groups by their baseline calcium score (100 U or less and over 100 U). Survival was measured by baseline calcium score and its progression. Cardiac death and myocardial infarction occurred in 29 patients and were significantly more frequent in those patients with calcium scores over 100 U (hazard ratio of 4.11). With a calcium score of 100 U or less, the hazard ratio for cardiac events was 0.41 and 3.26 in patients with absent and accelerated progression, respectively. Thus, in non-dialyzed patients, the extent of coronary calcifications was associated to cardiac events, and progression was an independent predictive factor of cardiac events mainly in less calcified patients. Hence, assessment of coronary calcifications and progression might be useful for earlier management of risk factors and guiding decisions for prevention of cardiac events in this patient population

Hypoxia Modifies the Transcriptome of Human NK Cells, Modulates Their Immunoregulatory Profile, and Influences NK Cell Subset Migration

Hypoxia, which characterizes most tumor tissues, can alter the function of different immune cell types, favoring tumor escape mechanisms. In this study, we show that hypoxia profoundly acts on NK cells by influencing their transcriptome, affecting their immunoregulatory functions, and changing the chemotactic responses of different NK cell subsets. Exposure of human peripheral blood NK cells to hypoxia for 16 or 96 h caused significant changes in the expression of 729 or 1,100 genes, respectively. Gene Set Enrichment Analysis demonstrated that these changes followed a consensus hypoxia transcriptional profile. As assessed by Gene Ontology annotation, hypoxia-targeted genes were implicated in several biological processes: metabolism, cell cycle, differentiation, apoptosis, cell stress, and cytoskeleton organization. The hypoxic transcriptome also showed changes in genes with immunological relevance including those coding for proinflammatory cytokines, chemokines, and chemokine-receptors. Quantitative RT-PCR analysis confirmed the modulation of several immune-related genes, prompting further immunophenotypic and functional studies. Multiplex ELISA demonstrated that hypoxia could variably reduce NK cell ability to release IFNγ, TNFα, GM-CSF, CCL3, and CCL5 following PMA+Ionomycin or IL15+IL18 stimulation, while it poorly affected the response to IL12+IL18. Cytofluorimetric analysis showed that hypoxia could influence NK chemokine receptor pattern by sustaining the expression of CCR7 and CXCR4. Remarkably, this effect occurred selectively (CCR7) or preferentially (CXCR4) on CD56bright NK cells, which indeed showed higher chemotaxis to CCL19, CCL21, or CXCL12. Collectively, our data suggest that the hypoxic environment may profoundly influence the nature of the NK cell infiltrate and its effects on immune-mediated responses within tumor tissues

Search for heavy neutral lepton production in K+ decays

A search for heavy neutral lepton production in K + decays using a data sample collected with a minimum bias trigger by the NA62 experiment at CERN in 2015 is reported. Upper limits at the 10−7 to 10−6 level are established on the elements of the extended neutrino mixing matrix |Ue4| 2 and |Uμ4| 2 for heavy neutral lepton mass in the ranges 170–448 MeV/c2 and 250–373 MeV/c2, respectively. This improves on the previous limits from HNL production searches over the whole mass range considered for |Ue4|2 and above 300 MeV/c2 for |Uμ4|2

Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF-platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage

Gain- and Loss-of-Function CFTR Alleles Are Associated with COVID-19 Clinical Outcomes

Carriers of single pathogenic variants of the CFTR (cystic fibrosis transmembrane conductance regulator) gene have a higher risk of severe COVID-19 and 14-day death. The machine learning post-Mendelian model pinpointed CFTR as a bidirectional modulator of COVID-19 outcomes. Here, we demonstrate that the rare complex allele [G576V;R668C] is associated with a milder disease via a gain-of-function mechanism. Conversely, CFTR ultra-rare alleles with reduced function are associated with disease severity either alone (dominant disorder) or with another hypomorphic allele in the second chromosome (recessive disorder) with a global residual CFTR activity between 50 to 91%. Furthermore, we characterized novel CFTR complex alleles, including [A238V;F508del], [R74W;D1270N;V201M], [I1027T;F508del], [I506V;D1168G], and simple alleles, including R347C, F1052V, Y625N, I328V, K68E, A309D, A252T, G542*, V562I, R1066H, I506V, I807M, which lead to a reduced CFTR function and thus, to more severe COVID-19. In conclusion, CFTR genetic analysis is an important tool in identifying patients at risk of severe COVID-19