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Khufu's Pyramid is one of the largest archaeological monument all over the world, which still holds many mysteries. In 2016 and 2017, the ScanPyramids team reported on several discoveries of previously unknown voids by cosmic-ray muon radiography that is a non-destructive technique ideal for the investigation of large-scale structures. Among these discoveries, a corridor-shaped structure has been observed behind the so-called Chevron zone on the North face, with a length of at least 5 meters. A dedicated study of this structure was thus necessary to better understand its function in relation with the enigmatic architectural role of this Chevron. Here we report on new measurements of excellent sensitivity obtained with nuclear emulsion films from Nagoya University and gaseous detectors from CEA, revealing a structure of about 9 m length with a transverse section of about 2.0 m by 2.0 m., (© 2023. The Author(s).)

Extractable denuders were designed to collect trace atmospheric semivolatile organic compounds with high volume (38.30 and 200 L/ min) samplers. Denuders were made of multichannel ceramic support coated with sodium silicate and functionalised with phenyl moieties. Polycyclic aromatic hydrocarbons, polychlorinated biphenyls, polychlorinated dibenzodioxins and polychlorinated dibenzofurans and chlorobenzenes in ambient air of a sub-urban area of Monterotondo, Italy, were sampled. Samplings were of 24 h, 48 h and 1 week period. Precision was determined using field triplicates and compared to the conventional high volume sampler methods. The fraction of analytes in the particle phase measured with the filter/ PUF system ranged from 0.2 % for naphthalene to 98.5 % for benzo(ghi)perylene; this fraction measured with the denuder ranged from 0.5 % for naphthalene to 99.0 % for benzo(ghi)perylene. A paired t-test indicated that these values were significantly (t = 3.58, P < 0.01) higher for the denuder. Results showed good repeatability (0.4-4.6 %), sampling efficiency (>99 %) and good capacity as variations in experimental efficiency were not observed also for longer (1 week) period sampling. As significant changes in efficiency were observed (0.7-5.6 %), the developed denuder cannot be reused more than once. However, it is possible to regenerate the denuder with a new silanization step. A good linear correlation was found plotting the vapour/particle distribution ratio versus the vapour pressure (R 2 ranged between 0.59 and 0.84) and versus the octanol/air partition coefficient (R 2 ranged between 0.85 and 0.88) of each selected SVOCs, in good agreement with the theoretical models for partitioning of SVOCs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The growing global energy demand requires the continuous development and optimization of the production of alternative energy sources. According to the circular economy approach, waste conversion into biogas and biomethane represent an interesting energy source. The input into the distribution network and energy conversion systems of biomethane requires quality monitoring and the use of cleaning up systems. Therefore, there is a need to constantly invest in the development of sampling and analysis systems that save time, costs, and materials. The purpose of this study was to use activated porous carbon fiber (APCF), an extremely versatile material for sampling and analysis by thermal desorption, to show the advantages it has over the adsorbents traditionally used for siloxane monitoring. Siloxanes are among the contaminating compounds that are mainly present in biogas and biomethane, and if not removed sufficiently, they endanger the quality and use of the gas. These are highly harmful compounds since during combustion, they produce quartz particles that are abrasive to the surfaces of the materials involved in the energy production process. In addition, siloxanes directly hinder the energy properties of biomethane during combustion, due to their radical scavenger properties. In this work, the efficiency of APCF tube was evaluated by comparing it with common multilayer tube thought sampling and analyzing siloxanes in lab scale and in real scale (biogas plant). Thermal desorption analysis coupled with GC-MS for the determination of siloxanes showed that the use of APCF allows to obtain better performance. This allows to deduce that APCF is an innovative material for the establishment of a better sampling and analysis method than the current ones, enabling better results to be achieved in the process of monitoring fuel quality in biomethane production and storage facilities.

The quality of honey is assessed through the determination of some commodity parameters: a certain importance is to be attributed to the absence of contaminating residues, in particular of Polycyclic Aromatic Hydrocarbons (PAHs). This paper deeply investigates the presence of 22 PAHs in 57 honey samples collected in Central Italy and identifies the possible source apportionment and fingerprint identification by DLLME-GC-MS analysis and a chemometric approach. Cluster Analysis and Principal Component Analysis have allowed to identify the main PAHs responsible of the contamination, benzo[a]anthracene and phenanthrene, characteristics pollutants of areas constantly exposed. The entire database has been compared to similar ones present in literature, particularly data from Serbia and Belgrado samples. The PCA applied to overall the data confirms the combustion to be the main contamination source in Italian samples whereas highlights the importance of the role of naphthalene, added during beekeeping practices in the other data-set., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Due to the increasing tattoo practicing in Eastern countries and general concern on tattoo ink composition and safety, the green tattoo inks Green Concentrate by Eternal, for European and "for Asia Market Only" were analyzed, under the premise that only the former falls under a composition regulation. A separation of the additives from the pigment was carried out by successive extraction in solvents of different polarities, i.e., water, acetone and dichloromethane. The solid residues were analyzed by IR and Raman spectroscopies, the liquid fractions by GC/mass spectrometry. The relative pigment load and element traces were also estimated. We found that the European and the Asian inks are based on the same pigment, PG7, restricted in Europe, though at different loads. They have a similar content of harmful impurities, such as Ni, As, Cd and Sb and both contain siloxanes, including harmful D4. Furthermore, they have different physical-chemical properties, the European ink being more hydrophilic, the Asian more hydrophobic. Additionally, the Asian ink contains harmful additives for the solubilization of hydrophobic matrices and by-products of the phthalocyanine synthesis. Teratogenic phthalates are present as well as chlorinated teratogenic and carcinogenic compounds usually associated to the laser treatment for removal purposes, to a larger extent in the European ink. The composition of the inks does not seem to reflect regulatory restrictions, where issued.

This paper would like to show all the data related to an intensive field campaign focused on the characterization of the Polyaromatic Hydrocarbons (PAHs) composition profile in almost 60 honey samples collected in Central Italy. The analytical data here reported are the base for a study aimed to identify the pollution sources in a region. 22 PAHs were analyzed by means of ultrasound-vortex-assisted dispersive liquid-liquid micro-extraction (DLLME) procedure followed by a triple quadrupole gas chromatograph/mass spectrometer (GC-MS). A chemometrics approach has been carried out for evaluating all the data: in particular, principal component analysis and cluster analysis has been used both for the identification of the main natural/anthropogenic pollutants affecting a site and for evaluating the air quality., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier Inc.)

The adverse effects of atmospheric particulate matter (PM) on health and ecosystems, as well as on meteorology and climate change, are well known to the scientific community. It is therefore undeniable that a good understanding of the sources of PM is crucial for effective control of emissions and to protect public health. One of the major contributions to atmospheric PM is biomass burning, a practice used both in agriculture and home heating, which can be traced and identified by analyzing sugars emitted from the combustion of cellulose and hemicellulose that make up biomass. In this review comparing almost 200 selected articles, we highlight the most recent studies that broaden such category of tracers, covering research publications on residential wood combustions, open-fire or combustion chamber burnings and ambient PM in different regions of Asia, America and Europe. The purpose of the present work is to collect data in the literature that indicate a direct correspondence between biomass burning and saccharides emitted into the atmosphere with regard to distinguishing common sugars attributed to biomass burning from those that have co-causes of issue. In this paper, we provide a list of 24 compounds, including those most commonly recognized as biomass burning tracers (i.e., levoglucosan, mannosan and galactosan), from which it emerges that monosaccharide anhydrides, sugar alcohols and primary sugars have been widely reported as organic tracers for biomass combustion, although it has also been shown that emissions of these compounds depend not only on combustion characteristics and equipment but also on fuel type, combustion quality and weather conditions. Although it appears that it is currently not possible to define a single compound as a universal indicator of biomass combustion, this review provides a valuable tool for the collection of information in the literature and identifies analytes that can lead to the determination of patterns for the distribution between PM generated by biomass combustion.

The tattoos removal has become an issue upon spread of the tattooing practice worldwide and hindsight regrets. Lasers are typically used for the purpose, though some colours such as green are considered "recalcitrant" to the treatment. In the current investigation, we aim at determining the efficacy of removal of a green ink water dispersion, using 5 laser treatments: Nd:YAG nano- and picosecond lasers in normal and array mode and Ruby nanosecond laser, keeping the total irradiated energy constant. The UV-Vis spectroscopy of the treated samples indicate that Nd:YAG picosecond laser is most effective, and the Ruby nanosecond laser is the least efficient. Fragment compounds generated from the pigment and siloxanes are common to all treatments, whereas hydrocarbon emerge by a larger amount upon Nd:YAG nanosecond treatment. Fibres are formed upon picosecond treatments and when operating in array mode, and lamellae are achieved by Ruby nanosecond laser treatment. Residual particles suspensions are very heterogeneous upon nanosecond treatments., (© 2022. The Author(s).)

The combustion of biomass is a process that is increasingly used for the generation of heat and energy through different types of wood and agricultural waste. The emissions generated by the combustion of biomass include different kinds of macro- and micropollutants whose formation and concentration varies according to the physical and chemical characteristics of the biomass, the combustion conditions, the plants, and the operational parameters of the process. The aim of this work is to evaluate the effect of biomass moisture content on the formation of volatile organic compounds (VOCs) during the combustion process. Wet and dry poplar chips, with a moisture content of 43.30% and 15.00%, respectively, were used in a cogeneration plant based on a mobile grate furnace. Stack's emissions were sampled through adsorbent tubes and subsequently analyzed by thermal desorption coupled with the GC/MS. The data obtained showed that, depending on the moisture content of the starting matrix, which inevitably influences the quality of combustion, there is significant variation in the production of VOCs.

Magnetite (Fe 3 O 4 ) nano-particles (MNPs) have been found in human tissues and causally linked to serious illnesses. The possible negative role of MNPs has been not still fully ascertained even though MNPs might cause health effects due to their magnetic property, redox activity and surface charge. The origin of MNPs in human tissues still remains to be unambiguously identified since biological processes, natural phenomena and anthropogenic production have been proposed. According to this latter increasingly convincing hypothesis, anthropogenic MNPs might enter mainly in the human body via inhalation, penetrate deeply into the lungs and in the alveoli and also migrate into the blood circulation and gather in the extrapulmonary organs and central nervous system. In order to identify the releasing source of the potentially inhalable MNPs, we pioneered an innovative approach to rapidly investigate elemental profile and morphology of a large number of airborne micron and sub-micron-sized Fe-bearing particles (FePs). The study was performed by collecting a large amount of micron and sub-micron sized inhalable airborne FePs in trafficked and densely frequented areas of Rome (Italy). Then, we have investigated individually the elemental profile and morphology of the collected particles by means of high-spatial resolution scanning electron microscopy, energy dispersive spectroscopy and an automated software purposely developed for the metal-bearing particles analysis. On the basis of specific elemental tracing features, the investigation reveals that almost the total amount of the airborne FePs is released by the vehicle braking systems mainly in the form of magnetite. Furthermore, we point out that our approach might be more generally used to identify the releasing sources of different inorganic airborne particles and to contribute to establish more accurately the impact of specific natural or anthropogenic particles on the environment and human health., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Active carbon-based sorbents are well known and are used in analytical chemistry. Activated carbon fibers (ACFs) are mainly used as abatement systems in industrial emission pollution control. The objective of this study was to extend the use of ACFs in analytical chemistry for the analysis of polychlorodibenzo-p-dioxins (PCDDs), polychlorodibenzofurans (PCDFs), dioxin-like polychlorobiphenyls (PCBs), and chlorobenzenes (CBs). For this purpose, the extraction efficiency was evaluated based on the QA/QC criteria defined by EPA/ISO reference methods on 13 C-standards recovery rates. The procedures tested were ultrasonic assisted extraction (UAE), Soxhlet extraction (SE), accelerated solvent extraction (ASE), and microwave-assisted extraction (MAE). Each experiment was performed in triplicate to ensure the repeatability of the results, and a second extraction assessed the complete extraction. The comparison of the results of each set of experiments with the minimum requirements of the reference methods for each class of compounds led to SE being chosen as the best technique. SE with toluene resulted in a reduction of time and costs and with respect to the other investigated techniques. The present work demonstrated that ACFs can be used in environmental fields means of both prevention and control (exploiting the adsorbent characteristics) and for analytical purposes (exploiting the desorption) for the described chlorinated classes of pollutants.

Purpose: Cerebellar ataxias are a large and heterogeneous group of disorders. The evaluation of brain parenchyma via MRI plays a central role in the diagnostic assessment of these conditions, being mandatory to exclude the presence of other underlying causes in determining the clinical phenotype. Once these possible causes are ruled out, the diagnosis is usually researched in the wide range of hereditary or sporadic ataxias., Methods: We here propose a review of the main clinical and conventional imaging findings of the most common hereditary degenerative ataxias, to help neuroradiologists in the evaluation of these patients., Results: Hereditary degenerative ataxias are all usually characterized from a neuroimaging standpoint by the presence, in almost all cases, of cerebellar atrophy. Nevertheless, a proper assessment of imaging data, extending beyond the mere evaluation of cerebellar atrophy, evaluating also the pattern of volume loss as well as concomitant MRI signs, is crucial to achieve a proper diagnosis., Conclusion: The integration of typical neuroradiological characteristics, along with patient's clinical history and laboratory data, could allow the neuroradiologist to identify some conditions and exclude others, addressing the neurologist to the more appropriate genetic testing.

Comparative laser and thermal treatments were carried out on PG36, a green phthalocyanine-based pigment, permitted in European countries where legislation on tattoo composition was issued. Prior to the treatments, PG36 was characterized by SEM imaging, EDX, IR and UV-Vis spectroscopies, revealing an excess of Si and C and O as compared to the pure halogenated Cu-phthalocyanine. Laser treatments were carried out with a Nd:YAG device applied to H 2 O and propan-2-ol dispersions. Pyrolysis and calcinations were carried out in air or under N 2 flow. The outcome of the different procedures was analyzed by UV-Vis spectroscopy, GC-mass spectrometry, X-ray diffraction of the solid residues, SEM microscopy and dynamic light scattering. The comparative analysis indicated the production of different fragment compounds depending on the treatment, (pyrolysis or laser), and, to some extent, to the solvent of the dispersion, with pyrolysis generating a larger number of hazardous compounds. Hydrocarbons and cyclic siloxanes present as additives in PG36 were stable or degraded depending on the treatment. The morphology of the products is also treatment-dependent with nanoparticles < 20 nm and fibers being produced upon laser treatments only. Based on the experimental findings, the equivalence of laser and thermal treatments is evaluated.

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). First identified in December 2019, in Wuhan, China, it has since become a global pandemic. Complications of COVID-19 are not limited to the pulmonary system, but also include neurologic manifestations such as stroke. We report two cases of coincidental presentation of COVID-19 and cerebrovascular accident. Further studies are needed for a comprehensive understanding of the neurological pathology of COVID-19 and its effects on the nervous system, but stroke teams should be wary of the fact that COVID-19 patients may present with cerebrovascular accidents.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). First identified in December 2019 in Wuhan, China, it has since become a global pandemic. Although the reference standard for SARS-CoV-2 diagnosis is real-time reverse transcription polymerase chain reaction (RT-PCR), computed tomography (CT) is recommended for both initial evaluation and follow-up. The CT findings in COVID-19 are varied, but typical ground-glass opacities are usually reported to occupy a peripheral costal subpleural distribution. Here we report eight confirmed COVID-19 cases who underwent clinical evaluation, laboratory testing, and unenhanced chest CT. In all patients, chest CT showed the presence of ground-glass opacities in the mediastinal subpleural parenchyma. While these cases also showed the typical CT features of COVID-19, involvement of the mediastinal subpleural parenchyma should not lower the index of suspicion for COVID-19., (Copyright Journal of Radiology Case Reports.)

Purpose: A new form of autosomal dominant hereditary spinocerebellar ataxia (SCA) has been recently described (SCA48), and here we investigate its conventional MRI findings to identify the presence of a possible imaging feature of this condition., Methods: In this retrospective observational study, we evaluated conventional MRI scans from 10 SCA48 patients (M/F = 5/5; 44.7 ± 7.8 years). For all subjects, atrophy of both supratentorial and infratentorial compartments were recorded, as well as the presence of possible T2-weighted imaging (T2WI) signal alterations., Results: In SCA48 patients, no meaningful supratentorial changes were found, both in terms of volume loss or MRI signal changes. Atrophy of the cerebellum was present in all cases, involving both the vermis and the hemispheres, but particularly affecting the postero-lateral portions of the cerebellar hemispheres. In all patients, with the exception of only one subject (90.0% of the cases), a T2WI hyperintensity of both dentate nuclei was found. The association of such signal alteration with the pattern of cerebellar atrophy resembled the appearance of a crab ("crab sign")., Conclusion: Our findings suggest that SCA48 patients are characterized by cerebellar atrophy, mainly involving the postero-lateral hemisphere areas, along with a T2WI hyperintensity of dentate nuclei. We propose that the association of such signal change, along with the atrophy of the lateral portion of the cerebellar hemispheres, resembled the appearance of a crab, and therefore, we propose the "crab sign" as a neuroradiological sign present in SCA48 patients.

It is known that when fires or explosions involve electrical systems, along with PCDDs and PCDFs, polychlorinated biphenylenes (PCBPs) are also produced. These chlorinated tricyclic aromatic pollutants were noticed in fire rubbles and after the World Trade Center destruction. However, the analytical difficulties in developing an efficient method have limited the knowledge of their environmental distribution. In light of the equipotency of 2,3,6,7-TeCBP and 2,3,7,8-TeCDD, PCBPs call for more accurate investigations. In this paper, for the first time, the level and persistence of 2,3,6,7-TeCBP have been investigated in air samples (both indoor and outdoor) after a fire broke out in an industrial building. GC-MS/MS analysis revealed that 2,3,6,7-TeCBP concentrations after the fire (3046 fg/m 3 at the "epicentre") were remarkably higher than that of the 2,3,7,8-TeCDD. Moreover, the monitoring for over two years has demonstrated the persistent nature of this compound. 2,3,6,7-TeCBP was also analyzed in two different ambient air scenario: industrial and periurban areas and in both cases its concentrations were no matter of concern, confirming the correlation of 2,3,6,7-TeCBP with fire episodes. Collectively, 2,3,6,7-TeCBP, because of its toxicity, concentration and persistence, is a crucial compound in the evaluation of the health effects correlated with fires of electrical systems., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Co-combustion of biomass and plastic waste has emerged as one of the most promising approach at the plastic waste management challenge. This strategy is particularly attractive since it can simultaneously solve the increasing energy demand and reduce the plastic wastes volume. However, since the combustion of both plastic wastes and natural materials is a potential source of organic micropollutants, such as polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs) and of polycyclic aromatic hydrocarbons (PAHs), beside particulate matter, the environmental sustainability of the waste to energy (WtE) co-combustion strategy has to be assessed. To this end, the emissions of dioxin like (dl)-PCBs, PCDD/Fs and PAHs from a 4-MW thermal power plant fueled with rice husk, partially replaced by end-of-life polyethylene (PE) industrial waste (up to 15% of the thermal power of the plant), were investigated. GC-MS/MS analyses have demonstrated that the co-combustion of PE waste and rice husk presents a profile of environmental sustainability. The concentrations of dl-PCBs, PCDD/Fs and PAHs were extremely low and they have remained almost unaffected by introducing PE in feed. In particular, emissions of PCCD/Fs and dl-PCBs in flue gas were in the range 0.6-1.0 and 0.2-0.6 pg TEQ/Nm 3 , respectively, while PAHs concentrations ranged from 410 to 825 ng/Nm 3 . Furthermore, the emission factors of these organic pollutants were found to be lower with PE increasing rate while particulate matter emissions were not affected by co-combustions. Collectively, the investigation has demonstrated that the noils of the industrial PE, due to the low content in halides and metals, can be used as auxiliary fuel and energetically recycled through co-combustion with rice husk. This case of study represents an effective application of the WtE strategy and a concrete approach to mitigate the threat of plastic pollution., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In-line filtration is increasingly used in critically-ill infants but its benefits, by preventing micro-particle infusion in very preterm neonates, remain to be demonstrated. We conducted a randomized controlled trial among very preterm infants allocated to receive either in-line filtration of all the intra-venous lines or standard care without filters. The primary outcome was differences greater than 20% in the median changes in pro-inflammatory cytokine serum concentrations measured at day 3 and day 8 (+/-1) using a Luminex multianalytic profiling technique. Major neonatal complications were analyzed as secondary predefined outcomes. We randomized 146 infants, assigned to filter (n = 73) or control (n = 73) group. Difference over 20% in pro-inflammatory cytokine concentration between day 3 and day 8 was not found statistically different between the two groups, both in intent-to-treat (with imputation) and per protocol (without imputation) analyses. The incidences of most of neonatal complications were found to be similar. Hence, this trial did not evidence a beneficial effect of in-line filtration in very preterm infants on the inflammatory response syndrome and neonatal morbidities. These data should be interpreted according to local standards in infusion preparation and central line management.

The toxicity of polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) is well known, and for this reason studying and monitoring these chemicals is fundamental. Activated carbon fibers (ACFs) are made of an adsorbent material widely used in the industrial field for the removal of micropollutants. The first step in this work was to perform a physico-chemical characterization of the adsorbent, focused on the analytical use of it. In particular, its specific surface area was defined around 2500 m 2 /g consisting in a homogeneous microporosity distribution and the characterization of ACF surface functional groups pointed out a balance between basic and acidic group. The validity of using the ACF as solid phase extraction and as passive sampler for PCDD/Fs and PCBs in water, has been evaluated by the percentage recovery (R %) of 13 C 12 -labeled standards of PCDD/Fs and PCBs added in a known volume of water. The results were compared to the R% of Liquid-Liquid Extraction which showed a better reproducibility of the results and the proposed method satisfy completely the requirements of US EPA reference methods., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Selenophosphate synthetase 2 (SEPHS2) synthesizes selenide and ATP into selenophosphate, the selenium donor for selenocysteine (Sec), which is cotranslationally incorporated into selenoproteins. The action and regulatory mechanisms of SEPHS2 as well as its role in carcinogenesis (especially breast cancer) remain ambiguous and need further clarification. Therefore, lacking an experimentally determined structure for SEPHS2, we first analyzed the physicochemical properties of its sequence, modeled its three-dimensional structure and studied its conformational behavior to identify the key residues (named HUB nodes) responsible for protein stability and to clarify the molecular mechanisms by which it induced its function. Bioinformatics analysis evidenced higher amplification frequencies of SEPHS2 in breast cancer than in other cancer types. Therefore, because triple negative breast cancer (TNBC) is biologically the most aggressive breast cancer subtype and its treatment represents a challenge due to the absence of well-defined molecular targets, we evaluated SEPHS2 expression in two TNBC cell lines and patient samples. We demonstrated mRNA and protein overexpression to be correlated with aggressiveness and malignant tumor grade, suggesting that this protein could potentially be considered a prognostic marker and/or therapeutic target for TNBC.

Ultrasonography is the first-line imaging modality in the evaluation of the female pelvis in childhood and adolescence, because it is easy to perform, non-invasive and it does not require sedation. The transabdominal approach is preferred in children and adolescents, after filling the bladder to move away the bowel loops from the pelvis. The probe frequency must be adapted to age, thickness of tissues and depth of the structures under examination. High-frequency (4-12 MHz) linear or convex probes are used in newborns; high-frequency linear probes (4-12 MHz) in toddler, convex 5-7.5 MHz probes in girls and convex 3.5-5 MHz probes in teenagers. In this article, the main pathological conditions of the genital female tract in pediatric age are examined, such as congenital anomalies, disorders of sex development, ovarian cysts, ovarian tumors, adnexal torsion, primary amenorrhea, precocious puberty and pelvic inflammatory disease.

Laboratory and field studies were carried out to assess the effects of oxidative degradation and volatilization on PM 10 bound polycyclic aromatic hydrocarbons (PAHs), collected at low volume condition according to the EU sampling reference method EN12341:2014 (flow rate 2.3 m 3  h -1 ), on 47 mm quartz filters. For the laboratory experiments, pairs of twin samples were collected in field and, after treatments favoring decomposition or/and volatilization of PAHs on one sample, the PAH amount was compared with that of the corresponding untreated sample. Ozone exposure caused a general PAHs decay with more marked effects on benzo [a]pyrene, perylene and benz [a]anthracene; these compounds showed, similarly to benzo [ghi]perylene, correlations between ozone dose and losses. Treatments with zero air exhibited losses due to volatilization even for 5-ring PAHs up to benzo [a]pyrene, whereas a linear dependence was observed between filter PAH load and losses for benzo [a]anthracene, chrysene and benzofluoranthenes. Concentrations on samples collected simultaneously over 48, 24, 12 and 6 h were compared. Results confirmed a lack of temporal auto-consistency in the PAHs sampling methodology here adopted. In particular higher atmospheric PAH concentrations were ascertained on samples constituted by cumulative filters exposed over shorter sampling times. When 24-h and 2 × 12-h samples were compared, comparable losses were evaluated in the hot and cold seasons. This finding shows that, although in summer meteorology conditions favor sampling artifacts, the effectiveness of these phenomena continue in the winter, probably due to the larger amount of PAH available on the sampling filter (total PAHs ∼ 10 vs 0.5 ng m -3 )., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The Great Pyramid, or Khufu's Pyramid, was built on the Giza plateau in Egypt during the fourth dynasty by the pharaoh Khufu (Cheops), who reigned from 2509 bc to 2483 bc. Despite being one of the oldest and largest monuments on Earth, there is no consensus about how it was built. To understand its internal structure better, we imaged the pyramid using muons, which are by-products of cosmic rays that are only partially absorbed by stone. The resulting cosmic-ray muon radiography allows us to visualize the known and any unknown voids in the pyramid in a non-invasive way. Here we report the discovery of a large void (with a cross-section similar to that of the Grand Gallery and a minimum length of 30 metres) situated above the Grand Gallery. This constitutes the first major inner structure found in the Great Pyramid since the nineteenth century. The void, named ScanPyramids' Big Void, was first observed with nuclear emulsion films installed in the Queen's chamber, then confirmed with scintillator hodoscopes set up in the same chamber and finally re-confirmed with gas detectors outside the pyramid. This large void has therefore been detected with high confidence by three different muon detection technologies and three independent analyses. These results constitute a breakthrough for the understanding of the internal structure of Khufu's Pyramid. Although there is currently no information about the intended purpose of this void, these findings show how modern particle physics can shed new light on the world's archaeological heritage.

The artifacts induced by oxidative degradation and volatilization were assessed with regards to determination of particulate atmospheric PAHs collected at low volume conditions (2.3 m 3  h -1 ) according to the EU Reference Method EN 12341:2014. In order to evaluate the oxidative degradation, PAH measures carried out through collecting airborne particulate with and without ozone denuders were examined. Simultaneously, the influence of volatilization was investigated by comparing concentrations of PAHs in particulate samples collected over 24-h and 12-h using conventional instruments. Summer and winter/spring campaigns were carried out in order to assess the influence of environmental contour on the artifact processes. Oxidative degradation led to a general decrease of PAH concentrations in both periods; in particular, the highest losses were observed for benzo[a]pyrene and perylene reaching, in average, ca. 20%. In the summer, the effect of volatilization exceeded that of oxidative degradation for light PAHs up to benzo[e]pyrene. In the winter/spring time, the influence of both artifact typologies could be mitigated by splitting the normal 24-h collection interval starting at midnight into two 12-h intervals. A mitigation of the losses could even be obtained by fixing the start time sampling fixed at noon or in the first hours of the day. Finally, the feasibility of collecting PAHs through prolonged sampling (>1 month) at the flow rate of 1.1 L min -1 was preliminarily investigated. Results indicated that this approach is unsuitable for minimizing the oxidative artifacts., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Marine sponges are an excellent source of bioactive secondary metabolites for pharmacological applications. In the present study, we evaluated the chemistry, cytotoxicity and metabolomics of an organic extract from the Mediterranean marine sponge Geodia cydonium , collected in coastal waters of the Gulf of Naples. We identified an active fraction able to block proliferation of breast cancer cell lines MCF-7, MDA-MB231, and MDA-MB468 and to induce cellular apoptosis, whereas it was inactive on normal breast cells (MCF-10A). Metabolomic studies showed that this active fraction was able to interfere with amino acid metabolism, as well as to modulate glycolysis and glycosphingolipid metabolic pathways. In addition, the evaluation of the cytokinome profile on the polar fractions of three treated breast cancer cell lines (compared to untreated cells) demonstrated that this fraction induced a slight anti-inflammatory effect. Finally, the chemical entities present in this fraction were analyzed by liquid chromatography high resolution mass spectrometry combined with molecular networking., Competing Interests: The authors declare no conflict of interest

The European and American methods for the determination of polychlorodibenzo-p-dioxins and polychlorodibenzofurans in stationary source emissions require a high-resolution mass spectrometer detector. At the same time, all of the 17 toxic 2,3,7,8-chlorine-substituted isomers have to be separated by an appropriate chromatographic method. The resulting analysis has long runtimes and sometimes a double-column run is needed, which results in a huge waste of time, money and manual labor. To obtain a fast and cost-effective but still reliable analytical system, a single-column gas chromatography with hydrogen as carrier gas and tandem mass spectrometry detection is proposed. The use of hydrogen as the carrier gas is a good choice to shorten runtimes and improve the chromatographic resolution, while tandem mass spectrometry is a well-known alternative for this analysis. All the chromatographic and mass spectrometric parameters fill the requirements of the reference methods with a 35% reduction of runtimes. The accuracy is tested with three fly ash samples of a proficiency interlaboratory test. A good correlation between the results is obtained (R 2  = 0.992, slope = 0.9675), and no coelutions are noted. The system robustness is tested during 5 years of constant use and the maximal relative standard deviation of the relative response factor is 18.8%., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The high-frequency performance of transistors is usually assessed by speed and gain figures of merit, such as the maximum oscillation frequency f max , cutoff frequency f T , ratio f max /f T , forward transmission coefficient S 21 , and open-circuit voltage gain A v . All these figures of merit must be as large as possible for transistors to be useful in practical electronics applications. Here we demonstrate high-performance graphene field-effect transistors (GFETs) with a thin AlOx gate dielectric which outperform previous state-of-the-art GFETs: we obtained f max /f T  > 3, A v  > 30 dB, and S 21  = 12.5 dB (at 10 MHz and depending on the transistor geometry) from S-parameter measurements. A dc characterization of GFETs in ambient conditions reveals good current saturation and relatively large transconductance ~600 S/m. The realized GFETs offer the prospect of using graphene in a much wider range of electronic applications which require substantial gain.

Objectives: Tacrolimus is an immunosuppressive agent that has been proposed in the treatment of severe ulcerative colitis. The present study examined the effectiveness and safety of tacrolimus in treating refractory Crohn disease (CD) colitis in children., Methods: All children treated by oral tacrolimus for CD colitis at a tertiary pediatric center were included in the study. All patients were refractory to steroids and infliximab. Clinical response (decreased pediatric CD activity index [PCDAI] >15 and PCDAI <30) and remission (PCDAI <10) were monitored at 2, 4, 6, 12, and 24 months after induction. Tacrolimus blood levels and adverse effects were also noted., Results: Among 220 patients with CD, 8 children (including 3 girls, median age 14 [9.5-18] years) were registered with a median PCDAI of 58.7 (32.5-65) before tacrolimus initiation. In patients treated with tacrolimus, the overall clinical response rates were 6/8, 3/8, 2/8, 2/8, and 1/8 with a remission rate of 4/8, 0/8, 0/8, 2/8, and 0/8 at 2, 4, 6, 12, and 24 months, respectively. At 2 months, the PCDAI scores were lower than those at induction (median 11.2; P = 0.004) with the mean whole plasma level of tacrolimus being 8.75 ng/mL (5.9-10 ng/mL). Adverse events occurred in 6 of 8 patients, including renal dysfunction, insulin-dependent diabetes, paresthesia, and tremor. Tacrolimus interruption was required in 2 cases., Conclusions: Tacrolimus could be considered to transiently treat refractory CD colitis. Tacrolimus could be used as a "bridge" toward another medical option in pediatric CD, although its adverse events are frequent.

Breast cancer is one of the most frequently diagnosed forms of cancer and different treatments are used to block its progression. However, it still represents a very common cause of death in women. Doxorubicin (Dox) is reported as an effective agent in breast cancer treatment nonetheless it induces many side‑effects. For this reason, many laboratories are engaged in understanding how it is possible to decrease the drug concentration, considering that one of the possible solutions is to use drug synergy, combining it with natural substances. Recently we showed that a phenolic extract from flaxseed (FS) oil, named PEFSO, induced on MCF‑7 cell line an increase of apoptosis with related modification of G0/G1 phase cell cycle, and the activation of signaling and pro‑oxidant pathways. In this study we present data on the combined effect of Dox and PEFSO on two different breast cancer cell lines to define the conditions to use lower doses of this chemotherapeutic agent. We report the data relating to the ability of this mixture to induce cytotoxicity and apoptosis, cell cycle modification, mitochondrial membrane depolarization and activation of extrinsic and/or intrinsic apoptotic pathway.

In this study, a hydroalcoholic chestnut shell extract was characterized and tested on six different human cell lines. Gallic, ellagic, and syringic acids were the most abundant non-condensed compounds in the chestnut extract, as determined by high performance liquid chromatography (HPLC). Tannins were mainly represented by condensed monomeric units of epigallocatechin and catechin/epicatechin. After 48 h of treatment, only the human hepatoblastoma HepG2 cells reached an inhibition corresponding to IC 50 with an increase of apoptosis and mitochondrial depolarization. The cytokinome evaluation before and after treatment revealed that the vascular endothelial growth factor (VEGF) and the tumor necrosis factor (TNF)-α decreased after the treatment, suggesting a potential anti-angiogenic and anti-inflammatory effect of this extract. Moreover, the metabolome evaluation by ¹H-NMR evidenced that the polyphenols extracted from chestnut shell (PECS) treatment affected the levels of some amino acids and other metabolites. Overall, these data highlight the effects of biomolecules on cell proliferation, apoptosis, cell cycle and mitochondrial depolarization, and on cytokinomics and metabolomics profiles.

Many studies have evidenced that the phenolic components from flaxseed (FS) oil have potential health benefits. The effect of the phenolic extract from FS oil has been evaluated on two human breast cancer cell lines, MCF7 and MDA-MB231, and on the human non-cancerous breast cell line, MCF10A, by SRB assay, cellular death, cell cycle, cell signaling, lipid peroxidation and expression of some key genes. We have evidenced that the extract shows anti-proliferative activity on MCF7 cells by inducing cellular apoptosis, increase of the percentage of cells in G0/G1 phase and of lipid peroxidation, activation of the H2AX signaling pathway, and upregulation of a six gene signature. On the other hand, on the MDA-MB2131 cells we verified only an anti-proliferative activity, a weak lipid peroxidation, the activation of the PI3K signaling pathway and an up-regulation of four genes. Overall these data suggest that the extract has both cytotoxic and pro-oxidant effects only on MCF7 cells, and can act as a metabolic probe, inducing differences in the gene expression. For this purpose, we have performed an interactomic analysis, highlighting the existing associations. From this approach, we show that the phenotypic difference between the two cell lines can be explained through their differential response to the phenolic extract.

Methods for the manipulation of single magnetic particles have become very interesting, in particular for in vitro biological studies. Most of these studies require an external microscope to provide the operator with feedback for controlling the particle motion, thus preventing the use of magnetic particles in high-throughput experiments. In this paper, a simple and compact system with integrated electrical feedback is presented, implementing in the very same device both the manipulation and detection of the transit of single particles. The proposed platform is based on zig-zag shaped magnetic nanostructures, where transverse magnetic domain walls are pinned at the corners and attract magnetic particles in suspension. By applying suitable external magnetic fields, the domain walls move to the nearest corner, thus causing the step by step displacement of the particles along the nanostructure. The very same structure is also employed for detecting the bead transit. Indeed, the presence of the magnetic particle in suspension over the domain wall affects the depinning field required for its displacement. This characteristic field can be monitored through anisotropic magnetoresistance measurements, thus implementing an integrated electrical feedback of the bead transit. In particular, the individual manipulation and detection of single 1-μm sized beads is demonstrated., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In recent years, many researchers are focusing their attention on the link between inflammation and cancer. The inflammation is involved in the tumor development and suppression, by stimulating the immune response. In particular, the transition from chronic inflammation to cancer produces angiogenic and growth factors able to repair the tissue and to promote cancer cell survival, implantation, and growth. In this contest, the cytokines contribute to the development of these processes becoming active before and during the inflammatory process and playing an important function at the various disease levels. Thus, these proteins can represent specific markers of tumor development and progression. Therefore the "cytokinome" term is used to indicate the evaluation of cytokine pattern by using an "omics" approach. Newly, specific protein chips of considerable and improved sensitivity are being developed to determine simultaneously several and different cytokines. This can be achieved by a multiplex technology that, through the use of small amounts of serum or other fluids, is used to determine the presence and the levels of underrepresented cytokines. Since this method is an accurate, sensitive, and reproducible cytokine assay, it is already used in many different studies. Thus, this review focuses on the more latest aspects related to cytokinome profile evaluation in different cancers., Competing Interests: The authors declare that they have no competing interests.

CO2 adsorption on synthetic zeolites has become a consolidated approach for biogas upgrading to biomethane. As an alternative to synthetic zeolites, tuff waste from building industry was investigated in this study: indeed, this material is available at a low price and contains a high fraction of natural zeolites. A selective adsorption of CO2 and H2S towards CH4 was confirmed, allowing to obtain a high-purity biomethane (CO2 <2 g m(-3), i.e. 0.1%; H2S <1.5 mg m(-3)), suitable for injection in national grids or as vehicle fuel. The loading capacity was found to be 45 g kg(-1) and 40 mg kg(-1), for CO2 and H2S, respectively. Synthetic gas mixtures and real biogas samples were used, and no significant effects due to biogas impurities (e.g. humidity, dust, moisture, etc.) were observed. Thermal and vacuum regenerations were also optimized and confirmed to be possible, without significant variations in efficiency. Hence, natural zeolites from tuffs may successfully be used in a pressure/vacuum swing adsorption process.

Understanding the dynamics of the complex interaction network of cytokines, defined as ''cytokinome'', can be useful to follow progression and evolution of hepatocellular carcinoma (HCC) from its early stages as well as to define therapeutic strategies. Recently we have evaluated the cytokinome profile in patients with type 2 diabetes (T2D) and/or chronic hepatitis C (CHC) infection and/or cirrhosis suggesting specific markers for the different stages of the diseases. Since T2D has been identified as one of the contributory cause of HCC, in this paper we examined the serum levels of cytokines, growth factors, chemokines, as well as of other cancer and diabetes biomarkers in a discovery cohort of patients with T2D, chronic hepatitis C (CHC) and/or CHC-related HCC comparing them with a healthy control group to define a profile of proteins able to characterize these patients, and to recognize the association between diabetes and HCC. The results have evidenced that the serum levels of some proteins are significantly and differently up-regulated in all the patients but they increased still more when HCC develops on the background of T2D. Our results were verified also using a separate validation cohort. Furthermore, significant correlations between clinical and laboratory data characterizing the various stages of this complex disease, have been found. In overall, our results highlighted that a large and simple omics approach, such as that of the cytokinome analysis, supplemented by common biochemical and clinical data, can give a complete picture able to improve the prognosis of the various stages of the disease progression. We have also demonstrated by means of interactomic analysis that our experimental results correlate positively with the general metabolic picture that is emerging in the literature for this complex multifactorial disease.

The influence of transistor size reduction (scaling) on the speed of realistic multi-stage integrated circuits (ICs) represents the main performance metric of a given transistor technology. Despite extensive interest in graphene electronics, scaling efforts have so far focused on individual transistors rather than multi-stage ICs. Here we study the scaling of graphene ICs based on transistors from 3.3 to 0.5 μm gate lengths and with different channel widths, access lengths, and lead thicknesses. The shortest gate delay of 31 ps per stage was obtained in sub-micron graphene ROs oscillating at 4.3 GHz, which is the highest oscillation frequency obtained in any strictly low-dimensional material to date. We also derived the fundamental Johnson limit, showing that scaled graphene ICs could be used at high frequencies in applications with small voltage swing.

Many research groups are working to find new possible anti-inflammatory molecules, and marine sponges represent a rich source of biologically active compounds with pharmacological applications. In the present study, we tested different concentrations of the methanol extract from the marine sponge, Geodia cydonium, on normal human breast epithelial cells (MCF-10A) and human breast cancer cells (MCF-7). Our results show that this extract has no cytotoxic effects on both cell lines whereas it induces a decrease in levels of VEGF and five proinflammatory cytokines (CCL2, CXCL8, CXCL10, IFN-γ, and TNF-α) only in MCF-7 cells in a dose-dependent manner, thereby indicating an anti-inflammatory effect. Moreover, interactomic analysis suggests that all six cytokines are involved in a network and are connected with some HUB nodes such as NF-kB subunits and ESR1 (estrogen receptor 1). We also report a decrease in the expression of two NFKB1 and c-Rel subunits by RT-qPCR experiments only in MCF-7 cells after extract treatment, confirming NF-kB inactivation. These data highlight the potential of G. cydonium for future drug discovery against major diseases, such as breast cancer.

Cement plants are responsible for particle and gaseous emissions into the atmosphere. With respect to particle emission, the greater part of is in the range from 0.05 to 5.0 µm in diameter. In the last years attention was paid to submicron particles, but there is a lack of available data on the emission from stationary sources. In this paper, concentration and size distribution of particles emitted from four cement kilns, in relationship to operational conditions (especially the use of alternative fuel to coal) of the clinker process are reported. Experimental campaigns were carried out by measuring particles concentration and size distribution at the stack of four cement plants through condensation particle counter (CPC) and scanning mobility particle sizer spectrometer (SMPS). Average total particle number concentrations were between 2000 and 4000 particles/cm³, about 8-10 times lower that those found in the corresponding surrounding areas. As for size distribution, for all the investigated plants it is stable with a unimodal distribution (120-150 nm), independent from the fuel used.

In recent years the use of natural dietary antioxidants to minimize the cytotoxicity and the damage induced in normal tissues by antitumor agents is gaining consideration. In literature, it is reported that vitamin C exhibits some degree of antineoplastic activity whereas Mitoxantrone (MTZ) is a synthetic anti-cancer drug with significant clinical effectiveness in the treatment of human malignancies but with severe side effects. Therefore, we have investigated the effect of vitamin C alone or combined with MTZ on MDA-MB231 and MCF7 human breast cancer cell lines to analyze their dose-effect on the tumor cellular growth, cellular death, cell cycle and cell signaling. Our results have evidenced that there is a dose-dependence on the inhibition of the breast carcinoma cell lines, MCF7 and MDA-MB231, treated with vitamin C and MTZ. Moreover, their combination induces: i) a cytotoxic effect by apoptotic death, ii) a mild G2/M elongation and iii) H2AX and mild PI3K activation. Hence, the formulation of vitamin C with MTZ induces a higher cytotoxicity level on tumor cells compared to a disjointed treatment. We have also found that the vitamin C enhances the MTZ effect allowing the utilization of lower chemotherapic concentrations in comparison to the single treatments.

Nitrous oxide (N2O) is the third most important greenhouse gas after carbon dioxide and methane, and contributes about 6% to the greenhouse effect. Nitrous oxide is a minor component of the atmosphere, and it is a thousand times less than carbon dioxide (CO2). Nevertheless, it is much more potent than CO2 and methane, owing to its long stay in the atmosphere of approximately 120 yr and the high global warmingpotential (GWP) of298 times that of CO2. Although greenhouse gases are natural in the atmosphere, human activities have changed the atmospheric concentrations. Most of the values of emission of nitrous oxide are still obtained by means ofemission factors and not actually measured; the lack ofreal data may result in an underestimation ofcurrent emissions. The emission factors used for the calculation of N2O can be obtained from the "Guidelines for the implementation of the national inventory of emissions" of the Intergovernmental Panel on Climate Change, which refer to all nations for the realization of their inventory. This study will present real data, measured in several Italian cement plants with different characteristics. The work also shows a comparison between N2O concentration measured with in situ-Fourier transform IR (FTIR) and the reference method EN ISO 21258 based on nondispersive IR (NDIR), in order to investigate the interfering compounds in the measurement with NDIR.

Background: Non-Alcoholic Fatty Liver Disease (NAFLD) is a distinct coronary artery disease (CAD) risk factor. The atherosclerotic process predisposing to CAD includes altered lipid profile and inflammatory processes. The available evidence suggests that increased circulating levels of eotaxin, an eosinophil chemoattractant cytokine implicated in allergic responses, are detected in the serum of patients with CAD. Relationships were sought between serum eotaxin on the one hand, and intima-media thickness--an early predictor of the atherosclerotic process, hepatic steatosis, arterial blood pressure values, as well as inflammation/immune markers and angiogenetic factors--on the other., Methods: Eighty obese patients with NAFLD, diagnosed at ultrasonography, without evident cytolysis, formed our study population. Anthropometric measures, metabolic profile, serum concentrations of interleukin-1β, C-reactive protein, interleukin-6, fibrinogen, ferritin, TNF-α, spleen size, vascular endothelial growth factor, platelet-derived growth factor-BB and heat shock protein-70 were evaluated., Results: Serum eotaxin concentrations were distinctly associated with TNF α, IL-6, IL-1β, VEGF and PDGF-BB levels but not with CRP, fibrinogen, heat shock protein-70 or spleen size. Among the metabolic and anthropometric parameters, a significant predictive power emerged when comparing eotaxin to insulin resistance, expressed as HOMA. NAFLD was distinctly associated with HOMA (P = 0.0005). Intima-media thickness was well predicted by both eotaxin levels and severity of NAFLD at ultrasonography, although no relation was detected between these last two variables., Discussion and Conclusion: A role for insulin resistance in mediating the interplay between eotaxin and other inflammation/immune parameters could be evidenced in the induction/maintenance of atherosclerosis of obese patients with NAFLD.

Atherosclerosis is a chronic inflammatory process of the vessel walls, and CD4+ T-cells are peculiar to both human and murine atherosclerotic lesions. There is a recent line of research favoring hypothetic allergic mechanisms in the genesis of atherosclerosis and, consequently, coronary artery disease (CAD), among which Interleukin (IL)-17 appears to be a key cytokine regulating local tissue inflammation. The objective was to add a piece of information on the role of IL-17 in the genesis of atherosclerosis. Eighty obese patients with normal liver enzyme levels but presenting with ultrasonographic evidence of NAFLD formed the population of this cross-sectional study. Anthropometric measures, data on excess adiposity, metabolic profile, serum concentrations of IL-17, eotaxin-3, IL-8, and CCL4/MIP1β, C-reactive protein, fibrinogen, ferritin, TNF-α, as well carotid intima-media thickness (IMT), a marker of atherosclerosis, and the main risk factors for CAD, such as blood pressure and smoking status, but also less determinant ones such as degree of NAFLD severity, Intramuscular Triglyceride storage and Resting Metabolic Rate were evaluated. Serum concentrations of Il-17 were detected as related to those of inflammatory cytokines, IL-6, IFN-γ and TNF-α. Furthermore, circulating levels of IL-17 were linked to those mirroring allergic process, IL-8, CCL4/MIP1β and eotaxin. Early atherosclerosis, evidenced as increased IMT, was not associated with circulating IL-17 levels. At multiple regression,IMT was predicted, other than by age, by the amount of the visceral adiposity, expressed as visceral adipose tissue at ultrasonography, and by serum eotaxin. In conclusion, a strong relationship was found between the IL-17-related chemokine eotaxin and IMT. The association found between the amount of visceral fat and circulating levels of eotaxin on the one hand, and IMT on the other, could reinforce the hypothesis that IL-17, released by the visceral adipose tissue, induces eotaxin secretion via the smooth muscle cells present in the atheromatosus vessels.

Background: At this center, therapeutic drug monitoring of methotrexate (MTX) used to be performed by fluorescence polarization immunoassay (FPIA). We observed an increasing number of unusual high MTX concentrations at 48 and 72 hours during a couple of years. This study aimed to identify the causes of this variation., Methods: A retrospective analysis was conducted on 272 patients hospitalized between January 2008 and October 2012. The whole MTX use system was analyzed using Ishikawa's method. The proportion of MTX concentrations ≤0.2 μmole/L at 48 (P48h) and 72 hours (P72h) was recorded and compared between both FPIA and EMITSiemens assays. A χ or a Fisher exact test was used (α = 0.05)., Results: Because of an announced withdrawal of the FPIA reagent, the method was switched in 2009 to an immunoenzymatic technique (EMITSiemens). Both P48h and P72h dropped significantly after 2009 (P48h: 45% versus 5% and P72h: 91% versus 47%; P < 0.0001). The replacement of the EMITSiemens reagent by the EMITARK Diagnostics reagent in 2012 led to an increase in both P48h and P72h. No significant difference was found in the proportions of MTX ≤0.2 μmole/L concentrations between FPIA and EMITARK Diagnostics at 48 (45% and 40%; P = 0.556) and 72 hours (91% and 100%; P = 0.231). Both internal and external quality control assessments gave regular satisfactory results during the study period. Furthermore, the interassay comparisons that were performed with internal quality controls and spiked serum samples showed similar results at the time of both shifts. The other changes observed in the MTX circuit were not associated with MTX concentration variations., Conclusions: The overestimation of the plasma concentration of MTX was concluded to be because of the assay reagent. A further study is consequently necessary to assess the impact of this analytical pitfall on the patients' survival.

The ''omics sciences'' (genomics, transcriptomics, proteomics) are often used to study living organisms as a whole system by evaluating the complex expression patterns of genes, miRNA, proteins, and metabolites. This study aimed, through bioinformatics and systems biology, to decipher the cytokinome profile in the evolution of inflammatory processes leading to cancer. The cytokinome was defined as the totality of cytokines and their interactions in and around biological cells. The system biology approach would provide a better understanding of the complex interaction network of cytokines, especially in cancer patients. Acquired knowledge would enable health providers with tools to evaluate disease onset through progression as well as identifying innovative therapeutic strategies. Understanding the role each cytokine plays in the metabolic network is of great importance. This paper reviews our group's ''omics'' work. In particular, it addresses the role cytokines play in liver disease in six different scenarios. The first is the role the cytokines play in chronic inflammatory diseases and cancers. The second is the significance of the cytokinome profile. The third is the role of liver cirrhosis as an inflammatory disease. The fourth is the comparison of cytokine levels evaluated in patients with chronic hepatitis C virus (HCV) or with HCV-related cirrhosis. The fifth is the comparison of cytokine levels evaluated in patients with HCV-related cirrhosis in the presence and absence of type 2 diabetes. And lastly, we present a comparison of cytokine levels evaluated in patients with HCV-related cirrhosis in the presence and absence of hepatocellular carcinoma.

In this work, we characterized conjugated linolenic acids (e.g., punicic acid) as the major components of the hydrophilic fraction (80% aqueous methanol extract) from pomegranate (Punica granatum L.) seed oil (PSO) and evaluated their anti-inflammatory potential on some human colon (HT29 and HCT116), liver (HepG2 and Huh7), breast (MCF-7 and MDA-MB-231) and prostate (DU145) cancer lines. Our results demonstrated that punicic acid and its congeners induce a significant decrease of cell viability for two breast cell lines with a related increase of the cell cycle G0/G1 phase respect to untreated cells. Moreover, the evaluation of a great panel of cytokines expressed by MCF-7 and MDA-MB-231 cells showed that the levels of VEGF and nine pro-inflammatory cytokines (IL-2, IL-6, IL-12, IL-17, IP-10, MIP-1α, MIP-1β, MCP-1 and TNF-α) decreased in a dose dependent way with increasing amounts of the hydrophilic extracts of PSO, supporting the evidence of an anti-inflammatory effect. Taken together, the data herein suggest a potential synergistic cytotoxic, anti-inflammatory and anti-oxidant role of the polar compounds from PSO.

Ascorbic acid (AA), also known as vitamin C, was initially identified as the factor preventing the scurvy disease, and became very popular for its antioxidant properties. It is an important co-substrate of a large class of enzymes, and regulates gene expression by interacting with important transcription factors. AA is important in all stressful conditions that are linked to inflammatory processes and involve immunity. It has been known for decades that the persistence of an inflammatory stimulus is responsible for the onset of many diseases. AA is essential to stimulate the immune system by increasing the strength and protection of the organism. Therefore, its immunostimulant, antinflammatory, antiviral and antibacterial roles are well known, we have summarized its main functions in different types of diseases related to the immune system and chronic inflammation. We can conclude that AA, due to its effects and diversity of regulated pathways, is suitable for use in various fields of medicine including immunology, toxicology, radiobiology and others. AA is not preferable to be used as an isolated mode of treatment, but it can be co-applied as an adjuvant to regulate immunity, gene expression and other important physiological processes. However, we propose that future studies will take into consideration the research of new combinations of antioxidant natural substances and drugs.

Hepatocellular carcinoma is the fifth most common cancer worldwide and shows a complex clinical course, poor response to pharmacological treatment, and a severe prognosis. Thus, the aim of this study was to investigate whether tacrolimus (FK506) has synergistic antitumor effects with doxorubicin on two human hepatocellular carcinoma cell lines, Huh7 and HepG2. Cell viability was analyzed by Sulforhodamine B assay and synergic effect was evaluated by the software CalcuSyn. Cell apoptosis was evaluated using Annexin V and Dead Cell assay. Apoptosis-related protein PARP-1 cleaved and autophagy-related protein expressions (Beclin-1 and LC3B) were measured by western blotting analysis. Cytokines concentration in cellular supernatants after treatments was studied by Bio-Plex assay. Interestingly the formulation with doxorubicin and tacrolimus induced higher cytotoxicity level on tumor cells than single treatment. Moreover, our results showed that the mechanisms involved were (i) a strong cell apoptosis induction, (ii) contemporaneous decrease of autophagy activation, understood as prosurvival process, and (iii) downregulation of proinflammatory cytokines. In conclusion, future studies could relate to the doxorubicin/tacrolimus combination effects in mice models bearing HCC in order to see if this formulation could be useful in HCC treatment.