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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Chronic and acute alcohol exposure prevents monocyte-derived dendritic cells from differentiating and maturing.

Increasing evidence suggests that alcohol abuse may be linked to adverse immunomodulatory effects on immune responses. Our study was undertaken to clarify the immunological consequences of chronic and acute alcohol exposure on differentiation and maturation of human dendritic cells (DCs). Using immunochemical and cytofluorimetric analysis we determined the phenotype and functions of monocyte-derived DCs from alcoholics and healthy subjects and analyzed their ability to respond to lipopolysaccharide (LPS) in the presence or absence of ethanol (EtOH) exposure. Our results showed that alcoholics inverted exclamation mark| monocytes differentiated to immature DCs with altered phenotype and functions (alc-iDCs). Alc-iDCs showed fewer CD1a+ cells, weaker CD86 expression and higher HLA-DR expression associated with lower endocytosis and allostimulatory functions than iDCs from healthy subjects (control-iDCs). Despite these impairments, alc-iDCs produced TNF-alpha and IL-6 in large amounts. LPS stimulation failed to induce full phenotypical and functional alc-iDC maturation. In vitro acute EtOH exposure also prevented alc-iDCs and control-iDCs from maturing in response to LPS. T-cell priming experiments showed that EtOH treatment prevented LPS-stimulated control-iDCs from priming and polarizing naïve allogeneic T cells into Th1 cells, thus favouring a predominant Th2 environment. Collectively, our results provide evidence that chronic and acute alcohol exposure prevents DCs from differentiating and maturing in response to a microbial stimulus.

Hydration of sodium, potassium, and chloride ions in solution and the concept of structure maker/breaker.

Neutron diffraction data with hydrogen isotope substitution on aqueous solutions of NaCl and KCl at concentrations ranging from high dilution to near-saturation are analyzed using the Empirical Potential Structure Refinement technique. Information on both the ion hydration shells and the microscopic structure of the solvent is extracted. Apart from obvious effects due to the different radii of the three ions investigated, it is found that water molecules in the hydration shell of K+ are orientationally more disordered than those hydrating a Na+ ion and are inclined to orient their dipole moments tangentially to the hydration sphere. Cl- ions form instead hydrogen-bonded bridges with water molecules and are readily accommodated into the H-bond network of water. The results are used to show that concepts such as structure maker/breaker, largely based on thermodynamic data, are not helpful in understanding how these ions interact with water at the molecular level.

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.

Biphasic effects of NMDA on the motility of the rat portal vein.

The effect of NMDA on the motility of the rat portal vein was studied in an isolated preparation. NMDA induced a concentration-dependent (10(-7) - 10(-4) M) increase of the contraction frequency (maximum increase, 148+/-6% of control at NMDA 10(-4) M). The NMDA-induced excitatory response was prevented by the competitive NMDA receptor antagonists (+/-)-2-Amino-5-phosphonopentanoic acid (AP-5, 5x10(-4) M) or (RS)-3-(2-carboxypiperazine-4-yl) propyl-1-phosphonic acid (CPP, 10(-4) M). Tetrodotoxin (TTX, 10(-6) M) or atropine (10(-4) M) abolished the NMDA-induced increase of the portal vein motility and reversed the excitatory effect to a concentration-dependent inhibition (maximum inhibition, 52+/-8 and 29+/-7% of controls, respectively, at NMDA 10(-3) M). Removal of the endothelium abolished the NMDA-induced inhibitory response. Sodium nitroprusside concentration-dependently (10(-7) - 10(-5) M) inhibited the portal vein motility, while L-N(G)-nitro-arginine methyl ester (L-NAME, 10(-4) M) reversed the inhibitory effect of NMDA (in the presence of TTX), restoring the portal vein spontaneous activity to control values. These results show that NMDA modulates the portal vein motility in a biphasic manner: via indirect activation, through prejunctional NMDA receptors presumably located on intrinsic excitatory neuronal afferences, or via direct inhibition, through endothelial NMDA receptors activating the nitric oxide pathway. Overall these findings support the hypothesis of the existence of a peripheral glutamatergic innervation modulating the contractile activity of the rat portal vein. British Journal of Pharmacology (2000) 129, 156 - 162

Thinking of biology: asteroid impacts, microbes, and the cooling of the atmosphere.

NASA: The authors examine the cooling of the Earth's surface from 3.75 to 1 billion years ago. Three effects of the bombardment of Earth by asteroids and comets that may have delayed surface cooling include time to form continents, volatilization of carbonate rocks which released carbon dioxide into the atmosphere, and inability of microbes to inhabit land masses during large impact events. Continental microbes may have helped reduce high temperatures from 3.75 to 3.5 billion years ago. If so, the evolutionary sequence of microbes is proposed to be anaerobic heterotrophs, chemoautotrophs, and then photoautotrophs.^ieng

The occurrence of denitrification in extremely halophilic bacteria.

The ability of Halobacterium vallismortis, Halobacterium mediterranei and Halobacterium marismortui (Ginzburg strain) to grow anaerobically and denitrify was determined. Each organism grew anaerobically only in the presence of nitrate. H. marismortui produced nitrite and dinitrogen from nitrate during exponential growth. However, as the culture entered stationary phase, dinitrogen production ceased and nitrous oxide was detected. H. vallismortis produced nitrous oxide and dinitrogen during exponential growth, with dinitrogen production ceasing at the onset of stationary phase. H. mediterranei produced dinitrogen during exponential growth and did not produce nitrous oxide. These results confirm the occurrence of denitrification in the halobacteria.

Positive action of propionyl-L-carnitine on mechanical performance of papillary muscle from Syrian hamsters with hereditary dilated cardiomyopathy.

Propionyl-L-carnitine has been shown to exert a beneficial effect on cardiac function in different experimental models of cardiomyopathy in the rat, most likely by improving cardiac metabolism and energy production. We have previously shown that, in a strain of hamsters with hereditary dilated cardiomyopathy (BIO TO.2), the mechanical activity of papillary muscle (length-tension, velocity of shortening, shortening, work and power relationship) is significantly depressed when compared to the same parameter in normal hamsters (BIO F1.B). The repeated oral treatment with propionyl-L-carnitine (60 mg/kg per os for 7 weeks) to BIO TO.2 hamsters had a significant positive inotropic effect, as indicated by an increase in developed tension up to the levels observed in papillary muscles from normal hamsters. This action is most likely associated with metabolic effects similar to those observed in rats.

Nitric oxide regenerates the normal colonic peristaltic activity in mdx dystrophic mouse.

We demonstrated in vitro that the colonic peristaltic activity is modified in dystrophin-deficient mdx mouse indicating a defect in the enteric nervous system (ENS). Since nitric oxide (NO) has been proposed as a putative inhibitory mediator of ENS, here we have examined the effects of both L-Arginine (L-Arg) and Nomega-nitro-L-arginine methyl ester (L-NAME) on the peristaltic activity of mdx mouse distal colon. The motor pattern of colonic segment showed irregular peristaltic waves. L-Arg (10(-7) - 10(-5) M) induced the peristaltic activity to slow down. At a concentration of 10(-5) M, L-Arg produced hypomotility, characterised by a decrease in amplitude, frequency and ejected fluid volume. Conversely, L-NAME elicited hypermotility, this effect being reversed once again by the subsequent addition of L-Arg. Interestingly the addition of 10(-5) M L-Arg to the organ bath led to the normal progression, in an oral to aboral direction, of 90% of the peristaltic waves. This last result strongly suggests that exogenous application of L-Arg restores the integrative circuits of the ENS responsible for programming and co-ordinating peristaltic activity in the distal colon of mdx mouse.

Analysis of peristaltic reflex in young mdx dystrophic mice.

Experiments have been carried out in isolated distal colon of young normal and mdx dystrophic mice, the animal homologous of Duchenne muscular dystrophy. Intraluminal pressure, longitudinal displacement, ejected fluid volume and changes in morphology during peristaltic events were recorded. In both male and female normal animals, pressure waves were observed to be generally regular in shape, amplitude (14.19 +/- 2.45 (SD) cm H2O), frequency (54.00 +/- 10.78 h-1) and duration (31.12 +/- 3.47 s). The propulsive activity resulted in orthograde transport of intraluminal content. Mdx mice exhibited great changes in relation to sex, since clear and more marked dysfunctions were recorded in female mice. In male mdx animals, an increase of intraluminal pressure (22%) and ejected fluid volume (38%) were recorded. In females, a remarkable significant (P < 0.001) increase (78%) of intraluminal pressure was observed. Simultaneous anterograde and retrograde propulsive activity also occurred. Localized annular constrictions in proximal, central and distal portions of colonic segment were observed. The implications of the results are discussed in terms of injury of myogenic and nervous pathways controlling mdx colonic smooth muscle.