The National Institute of Health and the Italian Poison Centers Network: results of a collaborative study for the surveillance of exposures to chemicals.

Background: The Public Health Surveillance Systems are essential to improve and protect public health, as highlighted by the World Health Organization. According with this consideration, a systematic collaboration between the National Institute of Health and the Poison Centers of Northern, Central and Southern Italy was established. Its aim was to improve the national network for the surveillance of dangerous exposures to chemicals. The developed network provided harmonized data essential for evidence-based interventions and significantly ameliorated the data flow between the Poison Centers and the Central Health Institutions. Methods: The improvement of the system was obtained through several actions, such as the development of the "Online Surveillance Card" for the detection of sentinel events in real time and the harmonization of the data collection flow, including the product categorization according to the European Product Categorization System. Data analysis was carried out by Microsoft's IBM SPSS Statistics version 26, Access and Excel. Results: Important information was obtained, regarding also exposures to chemicals and their management in pediatric populations. The surveillance network was proved effective not only under "normal" conditions but also to promptly monitor changes during exceptional health emergencies, such as the COVID-19 pandemic. During the 2020 lockdown the surveillance system registered a significant increase in the frequency of exposures to disinfectants (p-value=0.002), an evidence that highlighted the need of tailored intervention. Conclusions: This Italian Project model proves to be reliable and suitable to be transferred to other European countries, in order to realize an European Poison Centers' Network, able to overcome unsolved health problems and to globally improve the "evidence-based" prevention of exposures to chemicals.

Pure and Oxidized Copper Materials as Potential Antimicrobial Surfaces for Spaceflight Activities.

Microbial biofilms can lead to persistent infections and degrade a variety of materials, and they are notorious for their persistence and resistance to eradication. During long-duration space missions, microbial biofilms present a danger to crew health and spacecraft integrity. The use of antimicrobial surfaces provides an alternative strategy for inhibiting microbial growth and biofilm formation to conventional cleaning procedures and the use of disinfectants. Antimicrobial surfaces contain organic or inorganic compounds, such as antimicrobial peptides or copper and silver, that inhibit microbial growth. The efficacy of wetted oxidized copper layers and pure copper surfaces as antimicrobial agents was tested by applying cultures of Escherichia coli and Staphylococcus cohnii to these metallic surfaces. Stainless steel surfaces were used as non-inhibitory control surfaces. The production of reactive oxygen species and membrane damage increased rapidly within 1 h of exposure on pure copper surfaces, but the effect on cell survival was negligible even after 2 h of exposure. However, longer exposure times of up to 4 h led to a rapid decrease in cell survival, whereby the survival of cells was additionally dependent on the exposed cell density. Finally, the release of metal ions was determined to identify a possible correlation between copper ions in suspension and cell survival. These measurements indicated a steady increase of free copper ions, which were released indirectly by cells presumably through excreted complexing agents. These data indicate that the application of antimicrobial surfaces in spaceflight facilities could improve crew health and mitigate material damage caused by microbial contamination and biofilm formation. Furthermore, the results of this study indicate that cuprous oxide layers were superior to pure copper surfaces related to the antimicrobial effect and that cell density is a significant factor that influences the time dependence of antimicrobial activity. Key Words: Contact killing-E. coli-S. cohnii-Antimicrobial copper surfaces-Copper oxide layers-Human health-Planetary protection. Astrobiology 17, 1183-1191.

Dual role of the caspase enzymes in satellite cells from aged and young subjects.

Satellite cell (SC) proliferation and differentiation have critical roles in skeletal muscle recovery after injury and adaptation in response to hypertrophic stimuli. Normal ageing hinders SC proliferation and differentiation, and is associated with increased expression of a number of pro-apoptotic factors in skeletal muscle. In light of previous studies that have demonstrated age-related altered expression of genes involved in SC antioxidant and repair activity, this investigation was aimed at evaluating the incidence of apoptotic features in human SCs. Primary cells were obtained from vastus lateralis of nine young (27.3±2.0 years old) and nine old (71.1±1.8 years old) subjects, and cultured in complete medium for analyses at 4, 24, 48, and 72 h. Apoptosis was assessed using AnnexinV/propidium iodide staining, the terminal deoxynucleotidyl transferase dUTP nick-end labelling technique, RT-PCR, DNA microarrays, flow cytometry, and immunofluorescence analysis. There was an increased rate of apoptotic cells in aged subjects at all of the experimental time points, with no direct correlation between AnnexinV-positive cells and caspase-8 activity. On the other hand, CASP2, CASP6, CASP7, and CASP9 and a number of cell death genes were upregulated in the aged SCs. Altogether, our data show age-related enhanced susceptibility of human SCs to apoptosis, which might be responsible for their reduced response to muscle damage.

Microscopic structure of water in a water/oil emulsion.

We have determined the microscopic structure of water within a water/oil emulsion, by combining neutron diffraction data, exploiting the isotopic H/D substitution, and a fully atomistic Monte Carlo simulation of a portion of a water droplet, containing the water/oil interface. The dependence of the data on the simulation box size and the reliability of the water-water radial distribution functions are discussed. Although water in the emulsion forms shorter and stronger hydrogen bonds compared to pure bulk water, its overall microscopic structure looks more disordered.

Stress and ano-colorectal surgery in newborn/infant: role of anesthesia.

PURPOSE: The best anesthesia for newborns/infants necessitating colorectal surgery remains questionable. Endovenous and locoregional anesthesiological approaches were compared to determine the influence on stress response. METHODS: Patients with anorectal malformations or Hirschsprung's disease were randomized to inhalatory/epidural anesthesia (IPA) or inhalatory/endovenous anesthesia (IEA). Heart rate, blood pressure, oxygen saturation, serum concentrations of dehydroepiandrosterone, cortisol, and glucose were recorded 24 h before operation (T0), after tracheal intubation (T1), 120 min after skin incision (T2), 60 min (T3) and 24 h after operation (T4). RESULTS: Seventeen patients were enrolled in the study, 8 receiving IPA, and 9 IEA. Heart rate, blood pressure, oxygen saturation remained stable and normal, without statistical differences between the two groups, during the study period. Similar cortisol and glucose levels showed no statistical differences between groups. Dehydroepiandrosterone values were significantly higher in IEA during anesthesia (T1-T3) compared with IPA (T1: 494.0 vs. 266.5, p < 0.05; T2: 444.0 vs. 201.0, p < 0.05; T3: 385.0 vs. 305.0, p < 0.05). CONCLUSION: This study suggests that epidural and endovenous anesthesia are both effective in intra- and postoperative period. This preliminary report suggests that IPA is more efficient compared to IEA in controlling stress reaction related to surgery. Further larger studies are needed to confirm these findings.

Aqueous solutions of divalent chlorides: ions hydration shell and water structure.

By combining neutron diffraction and Monte Carlo simulations, we have determined the microscopic structure of the hydration ions shell in aqueous solutions of MgCl(2) and CaCl(2), along with the radial distribution functions of the solvent. In particular the hydration shell of the cations, show cation specific symmetry, due to the strong and directional interaction of ions and water oxygens. The ions and their hydration shells likely form molecular moieties and bring clear signatures in the water-water radial distribution functions. Apart from these signatures, the influence of divalent salts on the microscopic structure of water is similar to that of previously investigated monovalent solutes, and it is visible as a shift of the second peak of the oxygen-oxygen radial distribution function, caused by distortion of the hydrogen bond network of water.

Multiple relaxation processes versus the fragile-to-strong transition in confined water.

Broadband dielectric spectroscopy data on water confined in three different environments, namely at the surface of a globular protein or inside the small pores of two silica substrates, in the temperature range 140 K ≤ T ≤ 300 K, are presented and discussed in comparison with previous results from different techniques. It is found that all samples show a fast relaxation process, independently of the hydration level and confinement size. This relaxation is well known in the literature and its cross-over from Arrhenius to non-Arrhenius temperature behavior is the object of vivid debate, given its claimed relation to the existence of a second critical point of water. We find such a cross-over at a temperature of ~180 K, and assign the relaxation process to the layer of molecules adjacent and strongly interacting with the substrate surface. This is the water layer known to have the highest density and slowest translational dynamics compared to the average: its apparent cross-over may be due to the freezing of some degree of freedom and survival of very localized motions alone, to the onset of finite size effects, or to the presence of a calorimetric glass transition of the hydration shell at ~170 K. Another relaxation process is visible in water confined in the silica matrices: this is slower than the previous one and has distinct temperature behaviors, depending on the size of the confining volume and consequent ice nucleation.

Transcriptional profile of denervated vastus lateralis muscle derived from a patient 8 months after spinal cord injury: a case-report.

A lack of motor neurons abolishes both neurotrophic factor secretion and contractile activity in muscle, which impairs mass, contractile properties, and fibre-type characteristics of the muscle. However, the molecular pathways that can be stimulated or repressed in the scenario of spinal cord injury remain unknown. We investigated for the first time the transcriptional profile of a young male patient 8 months after spinal cord injury. Adaptive metabolic changes of complete denervated skeletal muscle were revealed. In particular, the main molecular pathways involved include metabolic and proteolitic pathways, mitochondrial and synaptic function, calcium homeostasis, sarcomere and anchorage structures. Our data depict the molecular signalling still present in complete denervated skeletal muscle fibres a few months after spinal cord injury. These data could be of interest also to design a specific therapeutic approach aimed at the electrical-stimulation of severe atrophied skeletal muscle.

Viscosity of aqueous solutions and local microscopic structure.

The effect of solutes on the structure of water has been debated intensively over the past years. Typical scenarios label different ions as water structure "makers" or "breakers": this is a quite elusive definition, which has been first introduced in the description of the effect of solutes on the viscosity of water and, although criticized, is still used in the current literature. Here, using a combination of neutron diffraction and computer modeling, we present a possible relation between the viscosity B coefficient and a local structural property of the solution. In particular, B appears in the Jones-Dole relation and its sign is traditionally used to characterize a solute as "structure maker" or "breaker". We find that B is linearly correlated to the difference between the average solute-water distance and the water-water distance in the pure liquid, in the case of monovalent electrolyte solutions.

Effect of pre-breathing oxygen at different depth on oxidative status and calcium concentration in lymphocytes of scuba divers.

AIM: In-water pre-breathing oxygen at various depths reduces decompression-induced bubble formation and platelet activation, but it could induce side effects such as oxidative stress. The aim of this study was to investigate the effect of in-water pre-breathing oxygen, at different depths, on the oxidative status and intracellular calcium ([Ca(2+) ]i) of peripheral blood lymphocytes isolated from six divers. They participated in a 4-diving protocol. Two week recovery time was allowed between successive dives. Before diving, all divers, for 20 min, breathed normally at sea level (dive 1), 100% oxygen at sea level (dive 2), 100% oxygen at 6 msw (dive 3), 100% oxygen at 12 msw (dive 4). Then they dived to 30 msw for 20 min with air tank. METHODS: Blood samples were collected before and after each dive. Hydrogen peroxide (H(2) O(2) ) levels, catalase (CAT) activity, mRNA expression of CAT, glutathione peroxidase (GPx) and superoxide dismutase (SOD), and the [Ca(2+) ]i in lymphocytes were measured. RESULTS: The dives slightly decreased lymphocyte number and significantly reduced lymphocyte H(2) O(2) levels. CAT activity was higher after scuba diving and, dive 3 enhanced mRNA gene expression of CAT, GPx and SOD. The [Ca(2+) ]i was higher after dive 1 and 2 than pre-diving, while was maintained at pre-diving value after dive 3 and 4. CONCLUSION: Our results suggest that pre-breathing oxygen, in particular at 12 msw, may enhance lymphocyte antioxidant activity and reduce reactive oxygen species levels. Pre-breathing oxygen in water may also preserve calcium homeostasis, suggesting a protective role in the physiological lymphocyte cell functions.

Structural study of low concentration LiCl aqueous solutions in the liquid, supercooled, and hyperquenched glassy states.

Neutron diffraction experiments on a solution of LiCl in water (R = 40) at ambient conditions and in the supercooled and hyperquenched states are reported and analyzed within the empirical potential structure refinement framework. Evidence for the modifications of the microscopic structure of the solvent in the presence of such a small amount of salt is found at all investigated thermodynamic states. On the other hand, it is evident that the structure of the hyperquenched salty sample is similar to that of pure low density amorphous water, although all the peaks of the radial distribution functions are broader in the present case. Changes upon supercooling or hyperquenching of the ion's hydration shells and contacts are of limited size and evidence for segregation phenomena at these states does not clearly show up, although the presence of water separated contacts between ion of the same sign is intriguing.

Cellular and molecular responses of human skeletal muscle exposed to hypoxic environment.

The effects of a hypobaric, hypoxic environment and exercise performed under extreme conditions, such as at high altitudes, are intriguing physiological aspects that need to be investigated directly on human climbers. Their skeletal muscle is one of the main tissues that can suffer from hypoxia and physical challenges, which will both define the muscle adaptation and the molecular signature of regenerative capacity. We investigated the muscle regenerative capacity characterizing satellite cells. Our study shows that satellite cells are altered by hypobaric, hypoxic environments and exercise performed at high altitudes. Of note, in human skeletal muscle after this 5,000 m a.s.l. expedition, SCs showed a significantly lower ability to regenerate skeletal muscle, in respect to before this high-altitude expedition. This impairment appears to be due to reduced satellite cell activity, consistent with their decreased myogenicity and fusion ability. Furthermore, at the transcriptional level several pathways, such as cell cycle, myogenesis, oxidative metabolism, proteolysis and sarcomeric protein synthesis, were found dysregulated.

Polycystic liver diseases.

Polycystic liver diseases (PCLDs) are genetic disorders with heterogeneous etiologies and a range of phenotypic presentations. PCLD exhibits both autosomal or recessive dominant pattern of inheritance and is characterized by the progressive development of multiple cysts, isolated or associated with polycystic kidney disease, that appear more extensive in women. Cholangiocytes have primary cilia, functionally important organelles (act as mechanosensors) that are involved in both normal developmental and pathological processes. The absence of polycystin-1, 2, and fibrocystin/polyductin, normally localized to primary cilia, represent a potential mechanism leading to cyst formation, associated with increased cell proliferation and apoptosis, enhanced fluid secretion, abnormal cell-matrix interactions, and alterations in cell polarity. Proliferative and secretive activities of cystic epithelium can be regulated by estrogens either directly or by synergizing growth factors including nerve growth factor, IGF1, FSH and VEGF. The abnormalities of primary cilia and the sensitivity to proliferative effects of estrogens and different growth factors in PCLD cystic epithelium provide the morpho-functional basis for future treatment targets, based on the possible modulation of the formation and progression of hepatic cysts.

The effect of confinement on water structure.

Neutron diffraction experiments with hydrogen isotope substitution on water confined in MCM41-S15 have been performed at temperatures of 300 and 210 K. Data are analyzed at a microscopic level using a revised version of the empirical potential structure refinement technique. It is found that the influence of the substrate on the water structure is not negligible and depends on the temperature: owing to the geometrical constraints and the symmetry breaking induced by the wall, comparison with the corresponding bulk phases is not straightforward and standard analysis should be replaced by a more suitable one.

Multiscale approach to the structural study of water confined in MCM41.

We present a protocol for simultaneous structural characterization of a confined fluid and the confining substrate, along with the extraction of site-site pair correlation functions of the liquid of interest. This is based on neutron diffraction experiments, exploiting where feasible the isotopic substitution technique, analyzed through numerical coarse graining calculations and atomistic simulations. All of the subtleties of the experimental procedure, the needed ancillary measurements, and the recipe for tailoring the numerical codes to the real experiment and sample are described in the case of water confined in MCM41-S-15. In particular the excluded volume effects and the relevance of liquid-substrate cross-correlation terms in the neutron cross section are quantitatively discussed. The results obtained for the microscopic structure of water evidence a non-homogeneous distribution of molecules within the pore, with the presence of water-substrate hydrogen bonds, and a strong distortion of the water-water radial distribution functions with respect to those of bulk water extending at least up to three hydration layers.

Transcription profile analysis of vastus lateralis muscle from patients with chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is a disabling condition characterized by unexplained chronic fatigue that impairs normal activities. Many body systems are affected and etiology has not yet been identified. In addition to immunological and psychological aspects, skeletal muscle symptoms are prominent in CFS patients. In an effort to establish which pathways might be involved in the onset and development of muscle symptoms, we used global transcriptome analysis to identify genes that were differentially expressed in the vastus lateralis muscle of female and male CFS patients. We found that the expression of genes that play key roles in mitochondrial function and oxidative balance, including superoxide dismutase 2, were altered, as were genes involved in energy production, muscular trophism and fiber phenotype determination. Importantly, the expression of a gene encoding a component of the nicotinic cholinergic receptor binding site was reduced, suggesting impaired neuromuscular transmission. We argue that these major biological processes could be involved in and/or responsible for the muscle symptoms of CFS.

The impact and recovery of asteroid 2008 TC(3).

In the absence of a firm link between individual meteorites and their asteroidal parent bodies, asteroids are typically characterized only by their light reflection properties, and grouped accordingly into classes. On 6 October 2008, a small asteroid was discovered with a flat reflectance spectrum in the 554-995 nm wavelength range, and designated 2008 TC(3) (refs 4-6). It subsequently hit the Earth. Because it exploded at 37 km altitude, no macroscopic fragments were expected to survive. Here we report that a dedicated search along the approach trajectory recovered 47 meteorites, fragments of a single body named Almahata Sitta, with a total mass of 3.95 kg. Analysis of one of these meteorites shows it to be an achondrite, a polymict ureilite, anomalous in its class: ultra-fine-grained and porous, with large carbonaceous grains. The combined asteroid and meteorite reflectance spectra identify the asteroid as F class, now firmly linked to dark carbon-rich anomalous ureilites, a material so fragile it was not previously represented in meteorite collections.

Extracellular guanosine and GTP promote expression of differentiation markers and induce S-phase cell-cycle arrest in human SH-SY5Y neuroblastoma cells.

SH-SY5Y neuroblastoma cells, a model for studying neuronal differentiation, are able to differentiate into either cholinergic or dopaminergic/adrenergic phenotypes depending on media conditions. Using this system, we asked whether guanosine (Guo) or guanosine-5'-triphosphate (GTP) are able to drive differentiation towards one particular phenotype. Differentiation was determined by evaluating the frequency of cells bearing neurites and assessing neurite length after exposure to different concentrations of Guo or GTP for different durations. After 6 days, 0.3 mM Guo or GTP induced a significant increase in the number of cells bearing neurites and increased neurite length. Western blot analyses confirmed that purines induced differentiation; cells exposed to purines showed increases in the levels of GAP43, MAP2, and tyrosine hydroxylase. Proliferation assays and cytofluorimetric analyses indicated a significant anti-proliferative effect of purines, and a concentration-dependent accumulation of cells in S-phase, starting after 24 h of purine exposure and extending for up to 6 days. A transcriptional profile analysis using gene arrays showed that an up-regulation of cyclin E2/cdk2 evident after 24 h was responsible for S-phase entry, and a concurrent down-regulation of cell-cycle progression-promoting cyclin B1/B2 prevented S-phase exit. In addition, patch-clamp recordings revealed that 0.3 mM Guo or GTP, after 6 day incubation, significantly decreased Na(+) currents. In conclusion, we showed Guo- and GTP-induced cell-cycle arrest in neuroblastoma cells and suggest that this makes these cells more responsive to differentiation processes that favor the dopaminergic/adrenergic phenotype.

Influence of concentration and anion size on hydration of H+ ions and water structure.

Neutron diffraction experiments with hydrogen isotope substitution on aqueous solutions of HCl and HBr have been performed at concentrations ranging from 1:17 to 1:83 solute per water molecules, at ambient conditions. Data are analyzed using the empirical potential structure refinement technique in order to extract information on both the ion hydration shells and the microscopic structure of the solvent. It is found that the influence of these solutes on the water structure is less concentration dependent than that of salts or hydroxides. Moreover protons readily form a strong H-bond with a water molecule upon solvation, at all proportions. The majority of them is also bonded via a longer bond to another water molecule, giving a prepeak in the g(OwOw). At high solute concentration, the second water molecule may be substituted by the counterion. In particular at solute concentrations of the order of 1:17 or higher, all protons have an anion within a distance of 4.5 A.

Study of percolation and clustering in supercritical water-CO2 mixtures.

The microscopic structure of supercritical water-CO(2) mixture is investigated by neutron diffraction experiments exploiting the isotopic HD substitution. The investigated water reach mixtures are in the liquidlike region of the phase diagram, according to the behavior of the radial distribution functions, yet a reduction of the average number of hydrogen bonds, compared to equivalent states of pure water, is found. As a consequence, the average dimension of water clusters is reduced and the system stays below the percolation threshold. These results, along with the shift of the main peaks of the site-site radial distribution functions, suggest that the excess volume in these supercritical mixtures is likely associated with the CO(2) solvation shell.