Loggerhead sea turtle (
C. caretta
) is the official European bioindicator of marine litter in the Mediterranean Sea. In 2019, 8 sea turtles, out of 28 specimens loggerhead on the Adriatic coast of ...Molise, were subjected to necropsy. The intestinal contents were collected and the microplastics until 0.45 μm were extracted. Qualitative and quantitative assessments were performed by stereomicroscope observation and spectroscopic analyses (attenuated total reflection-Fourier transform infrared spectroscopy, ATR-FTIR and Raman microspectroscopy, RMS). Moreover, the analytical quantification of polyethylene terephthalate (PET), polycarbonate (PC), para phthalic acid (PTA) and bisphenol A (BPA) in fat and liver tissues was performed by LC-MS/MS. Microparticles ranging from 0.45 μm to 1 mm were found in all turtles, for a total of 623, while plastic litter greater than 1 mm were found only in 4 specimens (ranging from 0.03 to 0.11 g). Nineteen different polymers and 10 pigments, including polyester (100% of animals), high-density polyethylene (50%) and polypropylene (50%) were identified. BPA, PTA and PET were detected in fat and liver tissues of all animals, while PC was found only in 50%. A major prevalence was registered in the abdominal fat tissue, although only PC compounds were significantly higher in abdominal tissue (
p
< 0.05), except for free PTA with liver tissue being the most contaminated (
p
< 0.05). Microplastics and additives surely impact the health status of turtles that showed gastrointestinal impairment and an important level of contamination in tissues.
Graphical abstract
Summary
In physiological conditions, red blood cells (RBCs) are capable of dramatic deformations when passing through the microvasculature. This extreme deformability is closely related to the RBC ...biconcave shape, to the fluidic nature of the haemoglobin and the cell membrane structure, primarily consisting of a phospholipid bilayer with an underlying two‐dimensional spectrin network. In many pathological and inflammatory conditions, the shape and the extreme deformability of erythrocytes appear to be significantly altered. These findings have stimulated intense research towards the search and validation of novel erythrocyte‐based mechanical biomarkers, useful for disease diagnosis and therapy monitoring. In this study, we investigated with Atomic Force Microscopy (AFM) the mechanical properties of erythrocytes obtained from a 68 years old cirrhotic man diagnosed with spur cell anaemia and cold agglutinated disease, before and after liver transplantation. Mechanical changes are compared with ultrastructural alterations as studied by scanning electron microscopy and discussed according to confocal fluorescence microscopy results, showing possible alterations induced by the cirrhotic environment at the level of the RBCs cytoskeletal organisation and lipidic composition. Taken together, the results here presented show that liver transplantation not only contributes to restoring the proper RBC morphology, but it also induces recovery of the physiological viscous behaviour of cells, further stressing the relevance of viscous and dissipative forces in determining the RBC biomechanical response.
Hepatocellular carcinoma (HCC) is the most common form of liver cancer, with cirrhosis being a major risk factor. Traditional blood markers like alpha-fetoprotein (AFP) demonstrate limited efficacy ...in distinguishing between HCC and cirrhosis, underscoring the need for more effective diagnostic methodologies. In this context, extracellular vesicles (EVs) have emerged as promising candidates; however, their practical diagnostic application is restricted by the current lack of label-free methods to accurately profile their molecular content. To address this gap, our study explores the potential of mid-infrared (mid-IR) spectroscopy, both alone and in combination with plasmonic nanostructures, to detect and characterize circulating EVs.
EVs were extracted from HCC and cirrhotic patients. Mid-IR spectroscopy in the Attenuated Total Reflection (ATR) mode was utilized to identify potential signatures for patient classification, highlighting significant changes in the Amide I-II region (1475-1700 cm−1). This signature demonstrated diagnostic performance comparable to AFP and surpassed it when the two markers were combined. Further investigations utilized a plasmonic metasurface suitable for ultrasensitive spectroscopy within this spectral range. This device consists of two sets of parallel rod-shaped gold nanoantennas (NAs); the longer NAs produced an intense near-field amplification in the Amide I-II bands, while the shorter NAs were utilized to provide a sharp reflectivity edge at 1800–2200 cm−1 for EV mass-sensing. A clinically relevant subpopulation of EVs was targeted by conjugating NAs with an antibody specific to Epithelial Cell Adhesion Molecule (EpCAM). This methodology enabled the detection of variations in the quantity of EpCAM-presenting EVs and revealed changes in the Amide I-II lineshape.
The presented results can positively impact the development of novel laboratory methods for the label-free characterization of EVs, based on the combination between mid-IR spectroscopy and plasmonics. Additionally, data obtained by using HCC and cirrhotic subjects as a model system, suggest that this approach could be adapted for monitoring these conditions.
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•Late diagnosis is a key issue affecting Hepatocellular Carcinoma (HCC) prognosis.•Patient derived extracellular vesicles (EVs) were analyzed by Mid-IR spectroscopy.•ATR-FTIR revealed alterations in Amide I-II regions of EVs from HCC patients.•A plasmonic metasurface was designed to enhance the signal in Amide I-II regions.•Potential spectral differences between healthy and HCC patients are observed.
The aim of this study was to examine, in biochemical detail, the functional role of the Arg152 residue in the selenoprotein Glutathione Peroxidase 4 (GPX4), whose mutation to His is involved in ...Sedaghatian-type Spondylometaphyseal Dysplasia (SSMD). Wild-type and mutated recombinant enzymes with selenopcysteine (Sec) at the active site, were purified and structurally characterized to investigate the impact of the R152H mutation on enzymatic function. The mutation did not affect the peroxidase reaction's catalytic mechanism, and the kinetic parameters were qualitatively similar between the wild-type enzyme and the mutant when mixed micelles and monolamellar liposomes containing phosphatidylcholine and its hydroperoxide derivatives were used as substrate. However, in monolamellar liposomes also containing cardiolipin, which binds to a cationic area near the active site of GPX4, including residue R152, the wild-type enzyme showed a non-canonical dependency of the reaction rate on the concentration of both enzyme and membrane cardiolipin. To explain this oddity, a minimal model was developed encompassing the kinetics of both the enzyme interaction with the membrane and the catalytic peroxidase reaction. Computational fitting of experimental activity recordings showed that the wild-type enzyme was surface-sensing and prone to “positive feedback” in the presence of cardiolipin, indicating a positive cooperativity. This feature was minimal, if any, in the mutant. These findings suggest that GPX4 physiology in cardiolipin containing mitochondria is unique, and emerges as a likely target of the pathological dysfunction in SSMD.
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•GPX4 activity on artificial membranes requires docking at the interface.•The R152 residue and cardiolipin are essential components of high-affinity docking.•When operating on interface GPX4 has a slower catalytic turnover than in micelles.•The docking triggers a “positive feedback” effect on activity on the interface.•The R152H mutation restrains enzyme accumulation at the interface.
Exosomes are nano-sized extracellular vesicles considered as a promising source of cancer biomarkers originating from the parent cells. We develop mid-infrared plasmonic nanoantenna arrays to detect, ...in the liquid phase, the specific vibrational absorption signal of the protein cargo of exosomes. The unspecific refractive index change is simultaneously detected by the same plasmonic array to monitor the reaction dynamics.
Summary
Novel coronavirus 2019 is a single‐stranded, ribonucleic acid virus that has led to an international pandemic of coronavirus disease 2019. Clinical data from the Chinese outbreak have been ...reported, but experiences and recommendations from clinical practice during the Italian outbreak have not. We report the impact of the coronavirus disease 2019 outbreak on regional and national healthcare infrastructure. We also report on recommendations based on clinical experiences of managing patients throughout Italy. In particular, we describe key elements of clinical management, including: safe oxygen therapy; airway management; personal protective equipment; and non‐technical aspects of caring for patients diagnosed with coronavirus disease 2019. Only through planning, training and team working will clinicians and healthcare systems be best placed to deal with the many complex implications of this new pandemic.
We present here a characterization of the low background NaI(Tl) crystal NaI-33 based on a period of almost one year of data taking (891 kg
×
days exposure) in a detector configuration with no use of ...organic scintillator veto. This remarkably radio-pure crystal already showed a low background in the SABRE Proof-of-Principle (PoP) detector, in the low energy region of interest (1–6 keV) for the search of dark matter interaction via the annual modulation signature. As the vetoable background components, such as
40
K, are here sub-dominant, we reassembled the PoP setup with a fully passive shielding. We upgraded the selection of events based on a Boosted Decision Tree algorithm that rejects most of the PMT-induced noise while retaining scintillation signals with > 90% efficiency in 1–6 keV. We find an average background of 1.39 ± 0.02 counts/day/kg/keV in the region of interest and a spectrum consistent with data previously acquired in the PoP setup, where the external veto background suppression was in place. Our background model indicates that the dominant background component is due to decays of
210
Pb, only partly residing in the crystal itself. The other location of
210
Pb is the reflector foil that wraps the crystal. We now proceed to design the experimental setup for the physics phase of the SABRE North detector, based on an array of similar crystals, using a low radioactivity PTFE reflector and further improving the passive shielding strategy, in compliance with the new safety and environmental requirements of Laboratori Nazionali del Gran Sasso.
Thyroid dysfunction in COVID-19 patients Baldelli, R.; Nicastri, E.; Petrosillo, N. ...
Journal of endocrinological investigation,
12/2021, Letnik:
44, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Purpose
“Non thyroidal illness syndrome” (NTIS) or “euthyroid sick syndrome” (ESS) is a possible biochemical finding in euthyroid patients with severe diseases. It is characterized by a reduction of ...serum T
3
(fT3), sometimes followed by reduction of serum T
4
(fT4). The relationship between thyroid hormones levels and mortality is well known and different studies showed a direct association between NTIS and mortality. The sudden spread of the 2019 novel coronavirus (SARS-CoV 2) infection (COVID-19) and its high mortality become a world healthcare problem. Our aim in this paper was to investigate if patients affected by COVID-19 presented NTIS and the relationship between thyroid function and severity of this infection.
Methods
We evaluated the thyroid function in two different groups of consecutive patients affected by COVID-19 with respect to a control group of euthyroid patients. Group A included patients hospitalized for COVID-19 pneumonia while patients requiring intensive care unit (ICU) for acute respiratory syndrome formed the group B. Group C identified the control group of euthyroid patients.
Results
Patients from group A and group B showed a statistically significant reduction in fT3 and TSH compared to group C. In group B, compared to group A, a further statistically significant reduction of fT3 and TSH was found.
Conclusions
COVID-19 in-patients can present NTIS. FT3 and TSH serum levels are lower in patients with more severe symptoms.
In the last few years, molecular targeted therapies have replaced traditional cytotoxic chemotherapy in the fight against many cancers to the extent that our understanding of tumor biology has become ...more sophisticated. This shift has markedly changed adverse event profiles, compared to cytotoxic chemotherapy, affecting a diverse range of organ systems. Everolimus was approved by the FDA in 2011 for the treatment of progressive pancreatic NE tumors. It is an inhibitor of mammalian target of rapamycin (mTOR) and exhibits antitumor activity via disruption of various signaling pathways and it's used in the treatment of advanced renal cell cancer, breast cancer and neuroendocrine tumors (NET); it’s used also as anti-rejection agent for transplantation but with lower doses for anti-rejection (1.5–3.0 mg/day) than for anti-cancer (5–10 mg/day) treatment. Metabolic side effects are the most frequent reported and will be discussed in this review.
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