COVID-19 is a global threat that has spread since the end of 2019, causing severe clinical sequelae and deaths, in the context of a world pandemic. The infection of the highly pathogenetic and ...infectious SARS-CoV-2 coronavirus has been proven to exert systemic effects impacting the metabolism. Yet, the metabolic pathways involved in the pathophysiology and progression of COVID-19 are still unclear. Here, we present the results of a mass spectrometry-based targeted metabolomic analysis on a cohort of 52 hospitalized COVID-19 patients, classified according to disease severity as mild, moderate, and severe. Our analysis defines a clear signature of COVID-19 that includes increased serum levels of lactic acid in all the forms of the disease. Pathway analysis revealed dysregulation of energy production and amino acid metabolism. Globally, the variations found in the serum metabolome of COVID-19 patients may reflect a more complex systemic perturbation induced by SARS-CoV-2, possibly affecting carbon and nitrogen liver metabolism.
Invertebrates represent about 95% of existing species, and most of them belong to aquatic ecosystems. Marine invertebrates are found at intermediate levels of the food chain and, therefore, they play ...a central role in the biodiversity of ecosystems. Furthermore, these organisms have a short life cycle, easy laboratory manipulation, and high sensitivity to marine pollution and, therefore, they are considered to be optimal bioindicators for assessing detrimental chemical agents that are related to the marine environment and with potential toxicity to human health, including neurotoxicity. In general, albeit simple, the nervous system of marine invertebrates is composed of neuronal and glial cells, and it exhibits biochemical and functional similarities with the vertebrate nervous system, including humans. In recent decades, new genetic and transcriptomic technologies have made the identification of many neural genes and transcription factors homologous to those in humans possible. Neuroinflammation, oxidative stress, and altered levels of neurotransmitters are some of the aspects of neurotoxic effects that can also occur in marine invertebrate organisms. The purpose of this review is to provide an overview of major marine pollutants, such as heavy metals, pesticides, and micro and nano-plastics, with a focus on their neurotoxic effects in marine invertebrate organisms. This review could be a stimulus to bio-research towards the use of invertebrate model systems other than traditional, ethically questionable, time-consuming, and highly expensive mammalian models.
Hereditary hemolytic anemias are a group of disorders with a variety of causes, including red cell membrane defects, red blood cell enzyme disorders, congenital dyserythropoietic anemias, thalassemia ...syndromes and hemoglobinopathies. As damaged red blood cells passing through the red pulp of the spleen are removed by splenic macrophages, splenectomy is one possible therapeutic approach to the management of severely affected patients. However, except for hereditary spherocytosis for which the effectiveness of splenectomy has been well documented, the efficacy of splenectomy in other anemias within this group has yet to be determined and there are concerns regarding short- and long-term infectious and thrombotic complications. In light of the priorities identified by the European Hematology Association Roadmap we generated specific recommendations for each disorder, except thalassemia syndromes for which there are other, recent guidelines. Our recommendations are intended to enable clinicians to achieve better informed decisions on disease management by splenectomy, on the type of splenectomy and the possible consequences. As no randomized clinical trials, case control or cohort studies regarding splenectomy in these disorders were found in the literature, recommendations for each disease were based on expert opinion and were subsequently critically revised and modified by the Splenectomy in Rare Anemias Study Group, which includes hematologists caring for both adults and children.
Biallelic pathogenic variants in the
gene cause congenital dyserythropoietic anemia type II (CDA II), a rare hereditary disorder hallmarked by ineffective erythropoiesis, hemolysis, erythroblast ...morphological abnormalities, and hypo-glycosylation of some red blood cell membrane proteins. Abnormalities in
, which encodes the homonymous cytoplasmic COPII (coat protein complex II) component, disturb the endoplasmic reticulum to Golgi trafficking and affect different glycosylation pathways. The most harmful complication of CDA II is the severe iron overload. Within our case series (28 CDA II patients), approximately 36% of them exhibit severe iron overload despite mild degree of anemia and slightly increased levels of ERFE (the only erythroid regulator of hepcidin suppression). Thus, we hypothesized a direct role of SEC23B loss-of-function in the pathomechanism of hepatic iron overload. We established a hepatic cell line, HuH7, stably silenced for
. In silenced cells, we observed significant alterations of the iron status, due to both the alteration in BMP/SMADs pathway effectors and a reduced capability to sense BMP6 stimulus. We demonstrated that the loss-of-function of SEC23B is responsible of the impairment in glycosylation of the membrane proteins involved in the activation of the BMP/SMADs pathway with subsequent hepcidin suppression. Most of these data were confirmed in another hepatic cell line, HepG2, stably silenced for
. Our findings suggested that the pathogenic mechanism of iron overload in CDA II is associated to both ineffective erythropoiesis and to a specific involvement of
pathogenic variants at hepatic level. Finally, we demonstrated the ability of
paralog, i.e.,
, to rescue the hepcidin suppression, highlighting the functional overlap between the two SEC23 paralogs in human hepatic cells.
Background
Low-dose thoracic protocols were developed massively during the COVID-19 outbreak.
Purpose
To study the impact on image quality (IQ) and the diagnosis reliability of COVID-19 low-dose ...chest computed tomography (CT) protocols.
Material and Methods
COVID-19 low-dose protocols were implemented on third- and second-generation CT scanners considering two body mass index (BMI) subgroups (<25 kg/m2 and >25 kg/m2). Contrast-to-noise ratios (CNR) were compared with a Catphan phantom. Next, two radiologists retrospectively assessed IQ for 243 CT patients using a 5-point Linkert scale for general IQ and diagnostic criteria. Kappa score and Wilcoxon rank sum tests were used to compare IQ score and CTDIvol between radiologists, protocols, and scanner models.
Results
In vitro analysis of Catphan inserts showed in majority significantly decreased CNR for the low dose versus standard acquisition protocols on both CT scanners. However, in vivo, there was no impact on the diagnosis: sensitivity and specificity were ≥0.8 for all protocols and CT scanners. The third-generation scanner involved a significantly lower dose compared to the second-generation scanner (CTDIvol of 1.8 vs. 2.6 mGy for BMI <25 kg/m2 and 3.3 vs. 4.6 mGy for BMI >25 kg/m2). Still, the third-generation scanner showed a significantly higher IQ with the low-dose protocol compared to the second-generation scanner (30.9 vs. 28.1 for BMI <25 kg/m2 and 29.9 vs. 27.8 for BMI >25 kg/m2). Finally, the two radiologists had good global inter-reader agreement (kappa ≥0.6) for general IQ.
Conclusion
Low-dose protocols provided sufficient IQ independently of BMI subgroups and CT models without any impact on diagnosis reliability.
As the use of both clean energy technologies and alternative fuels in the maritime sector is spreading, studies dealing with the installation of multi-MW power generation plants on board ships have ...been increasing. Considering this, the present work proposes a 12 MW Solid Oxide Fuel Cell (SOFC) to be installed on board a cruise ship of about 175000 gross tonnes, 345 m length, and powered by Liquefied Natural Gas (LNG). It is supposed that the SOFC generates electrical energy and provides part of the thermal power demand by integrating a heat recovery system. A zero-dimensional (0D) Aspen Plus model has been developed to optimize the onboard layout and to predict the performance of the integrated power plant. Specific parameters, such as the fuel utilisation factor, the pre-heated air temperature, the anodic recycle flow rate, and the exhaust gas temperature, have been manipulated to evaluate the overall efficiency of the integrated power plant under different operating conditions. The model has been validated by comparing the results obtained with data from literature and commercial SOFC modules. A layout configuration of the SOFC plant is suggested and the performances are investigated by varying the efficiency in the range of 60-40%.
Hereditary stomatocytoses (HSts) are a wide spectrum of hemolytic anemias in which the erythrocyte membrane cation permeability is increased. Dehydrated hereditary stomatocytosis is the most frequent ...among HSts. It is caused by missense mutations in PIEZO1 and KCNN4 genes.
We described 123 patients enrolled in our Genetic Unit from 2013 to 2017. Overall HSt subjects exhibit macrocytic mild anemia. We found that PIEZO1 is the most frequent mutated gene within our families (47% of pedigrees). In 59.1% of cases the mutations localized in the nonpore protein domain, while in 40.9% of patients they localized in the central pore region. The genotype‐phenotype correlation analysis on 29 PIEZO1‐patients demonstrated that most of severely affected patients carried mutations in the pore domain, suggesting that the severity of this condition is related to the pore properties and intracellular domain that could be responsible of interactions with intracellular components.
This is the first cohort study on a large set of hereditary stomatocytosis patients, stratified according to their causative gene useful for diagnosis, prognosis, and management of these patients.
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