Current emerging SARS-CoV-2 pandemic: Potential direct/indirect negative impacts of virus persistence and related therapeutic drugs on the aquatic compartments.

The purpose of the present work is to provide a complete overview of possible direct/indirect implications on the quality of aquatic compartments due to the recent SARS-CoV-2 outbreak. With this aim, the environmental impacts are mainly related to i) the virus persistence in sewage and wastewaters, and ii) possible fate in aquatic compartments of drugs tested and administered to SARS-CoV-2 infected patients. Because SARS-CoV-2 spread is very recent, and there is a lack of specific studies on this strain, the virus persistence in wastewaters, the parameters influencing the persistence, as well as the detection methodologies are referenced to the general coronaviruses group. However, the present detailed report of up-to-date knowledge on this topic can provide a useful source for further studies focusing on more deepened investigations of SARS-CoV-2 behaviour in the environment. Such a perspective is significant not only for the control of virus diffusion but also represents a crucial point for the identification of produced alteration to the environmental quality.

Plasma peroxiredoxin changes and inflammatory cytokines support the involvement of neuro-inflammation and oxidative stress in Autism Spectrum Disorder.

BACKGROUND: It has been established that children with Autism Spectrum Disorders (ASD) are affected by oxidative stress, the origin of which is still under investigation. In the present work, we evaluated inflammatory and pro-oxidant soluble signature in non-syndromic ASD and age-matched typically developing (TD) control children. METHODS: We analyzed leukocyte gene expression of inflammatory cytokines and inflammation/oxidative-stress related molecules in 21 ASD and 20 TD children. Moreover, in another-comparable-group of non-syndromic ASD (N = 22) and TD (N = 21) children, we analyzed for the first time the protein expression of the four members of the antioxidant enzyme family of peroxiredoxins (Prx) in both erythrocyte membranes and in plasma. RESULTS: The gene expression of IL6 and of HSP70i, a stress protein, was increased in ASD children. Moreover, gene expression of many inflammatory cytokines and inflammation/oxidative stress-related proteins correlated with clinical features, and appeared to be linked by a complex network of inter-correlations involving the Aryl Hydrocarbon Receptor signaling pathway. In addition, when the study of inter-correlations within the expression pattern of these molecules was extended to include the healthy subjects, the intrinsic physiological relationships of the inflammatory/oxidative stress network emerged. Plasma levels of Prx2 and Prx5 were remarkably increased in ASD compared to healthy controls, while no significant differences were found in red cell Prx levels. CONCLUSIONS: Previous findings reported elevated inflammatory cytokines in the plasma of ASD children, without clearly pointing to the presence of neuro-inflammation. On the other hand, the finding of microglia activation in autoptic specimens was clearly suggesting the presence of neuro-inflammation in ASD. Given the role of peroxiredoxins in the protection of brain cells against oxidative stress, the whole of our results, using peripheral data collected in living patients, support the involvement of neuro-inflammation in ASD, and generate a rational for neuro-inflammation as a possible therapeutic target and for plasma Prx5 as a novel indicator of ASD severity.

Polymicrobial antibiofilm activity of the membranotropic peptide gH625 and its analogue.

This work illustrates a new role for the membranotropic peptide gH625 and its derivative gH625-GCGKKK in impairing formation of polymicrobial biofilms. Mixed biofilms composed of Candida and bacterial species cause frequently infections and failure of medical silicone devices and also show a major drug resistance than single-species biofilms. Inhibition and eradication of biofilms were evaluated by complementary methods: XTT-reduction, and crystal violet staining (CV). Our results indicate that gH625-GCGKKKK, better than the native peptide, strongly inhibited formation of mixed biofilms of clinical isolates of C. tropicalis/S. marcescens and C. tropicalis/S. aureus and reduced the biofilm architecture, interfering with cell adhesion and polymeric matrix, as well as eradicated the long-term polymicrobial biofilms on silicone surface.

Emerging Concern from Short-Term Textile Leaching: A Preliminary Ecotoxicological Survey.

Textile dyes and their residues gained growing attention worldwide. Textile industry is a strong water consumer potentially releasing xenobiotics from washing and rinsing procedures during finishing processes. On a decentralised basis, also final consumers generate textile waste streams. Thus, a procedure simulating home washing with tap water screened cotton textiles leachates (n = 28) considering physico-chemical (COD, BOD5, and UV absorbance) and ecotoxicological data (Daphnia magna, Pseudokirchneriella subcapitata and Lepidium sativum). Results evidenced that: (i) leachates presented low biodegradability levels; (ii) toxicity in more than half leachates presented slight acute or acute effects; (iii) the remaining leachates presented "no effect" suggesting the use of green dyes/additives, and/or well established finishing processes; (iv) no specific correlations were found between traditional physico-chemical and ecotoxicological data. Further investigations will be necessary to identify textile residues, and their potential interactions with simulated human sweat in order to evidence potential adverse effects on human health.

Recovery of ammonia in digestates of calf manure through a struvite precipitation process using unconventional reagents.

Land spreading of digestates causes the discharge of large quantities of nutrients into the environment, which contributes to eutrophication and depletion of dissolved oxygen in water bodies. For the removal of ammonia nitrogen, there is increasing interest in the chemical precipitation of struvite, which is a mineral that can be reused as a slow-release fertilizer. However, this process is an expensive treatment of digestate because large amounts of magnesium and phosphorus reagents are required. In this paper, a struvite precipitation-based process is proposed for an efficient recovery of digestate nutrients using low-cost reagents. In particular, seawater bittern, a by-product of marine salt manufacturing and bone meal, a by-product of the thermal treatment of meat waste, have been used as low-cost sources of magnesium and phosphorus, respectively. Once the operating conditions are defined, the process enables the removal of more than 90% ammonia load, the almost complete recovery of magnesium and phosphorus and the production of a potentially valuable precipitate containing struvite crystals.

Multigenerational tests on Daphnia spp.: a vision and new perspectives.

Multigenerational toxicity testing is a valuable tool for understanding the long-term effects of contaminants on aquatic organisms. This review focuses on the use of multigenerational tests with Daphnia, a widely used model organism in aquatic toxicological studies. The review highlights the importance of studying multiple generations to assess Daphnia spp. reproductive, growth, and physiological responses to various contaminants. We discuss the outcomes of multigenerational tests involving different contaminants, including nanoparticles, pesticides, and pharmaceuticals. The results reveal that multigenerational exposure can lead to transgenerational effects, where the impacts of contaminants are observed in subsequent generations even after the initial exposure has ceased. These transgenerational effects often manifest as reproduction, growth, and development alterations. Furthermore, we emphasize the need for standardized protocols in multigenerational testing to ensure comparability and reproducibility of results across studies. We also discuss the implications of multigenerational testing for ecological risk assessment, as it provides a more realistic representation of the long-term effects of contaminants on populations and ecosystems. Overall, this review highlights the significance of multigenerational tests with Daphnia in advancing our understanding of the ecological impacts of contaminants. Such tests provide valuable insights into the potential risks associated with long-term exposure to pollutants and contribute to the development of effective mitigation strategies for aquatic ecosystems.

Second-line treatment strategies for RAS wild-type colorectal cancer: A systematic review and Network Meta-analysis (NMA).

BACKGROUND: The optimal strategy for second-line (IIL) treatment in KRAS wt metastatic colorectal cancer (mCRC) is not determined yet. METHODS: A random-effect NMA of phase II/III RCTs was conducted to evaluate IIL treatment for all-RAS wt mCRC, comparing anti-EGFR or anti-VEGF, and chemotherapy (CT). RESULTS: Overall, 11 RCTs (3613 patients) were included. In KRAS wt patients, PFS was improved with anti-VEGF (HR 0.43) and anti-EGFR (HR 0.63) vs CT. However, anti-VEGF based therapy had the highest likelihood of being ranked as the best treatment in terms of PFS (SUCRA 99.3%) and OS (SUCRA 99.4%). Bevacizumab-based treatment is most likely to be the best treatment in terms of PFS (SUCRA 89.1%) and OS (SUCRA 86.7%). CONCLUSIONS: Second line treatment with anti-VEGF and anti-EGFR improved PFS in mCRC patients, however, anti-VEGF based therapy, particularly CT plus bevacizumab, is the best treatment according to SUCRA in terms of PFS and OS.

Expression of growth factors in brain tumors: correlation with tumor grade, recurrence and survival.

OBJECTIVE: The aim of this study is to evaluate the correlation between the expression of some growth factors (GFs) and the tumor grade, recurrence and survival of brain glial and ependymal tumors. MATERIAL AND METHODS: The expression of vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), tenascine, transforming growth factor (TGFbeta), isomeres, platelet-derived growth factor (PDGF) and p53 was studied in 40 primary brain tumors, both low-grade and high-grade, including astrocytomas, oligodendrogliomas, glioblastomas and ependymomas. The same GFs were also studied in 46 specimens of recurrent tumors from the same patients. The positivity and intensity of the immunohistochemical expression were correlated with the tumor grade, the interval and type of recurrence, and the survival. RESULTS: The expression of all GFs, excepting TGFbeta1, TGFbetaRI and tenascine, was found to be correlated with the tumor grade in all tumors of both astroglial and oligodendroglial origin, whereas ependymomas showed significant differences only for EGFR. Low-grade (Grade II) tumors recurring as anaplastic (Grade III) forms showed GF expression rather similar to initially high-grade gliomas and significantly higher than that of low-grade (Grade II) tumors in both initial surgery and recurrence. Besides, low-grade (Grade II) tumors recurring as low-grade showed significantly longer median recurrence time (5.4 vs. 3.5 years) and better median survival (8.3 vs. 5.4 years) than those recurring as anaplastic forms (WHO III). CONCLUSION: The immunohistochemical study of expression of VEGF, EGFR, TGFbeta2, TGFbeta3, PDGF and p53 in all low-grade (Grade II) brain gliomas at the first operation may help to differentiate cases with slower evolution and longer survival from those with higher potential of anaplastic transformation.

Sentinel lymph node biopsy with intraoperative touch imprint cytology (TIC) in breast cancer: experience of a mild-volume center.

Although considered the gold standard in treatment of EBC, sentinel node biopsy still remains a debated issue. What to do in case of positive sentinel node and the need of intraoperative histological examination are the most topics under discussion. In this study we have retrospectively evaluate our case series of 359 sentinel node biopsy in the managing of breast cancer from January 2011 to December 2018, focusing on the TIC technique for performing intraoperative examination. It results in 12,8% "FALSE NEGATIVE" rate, in which only 4,2% in macrometastases, with an overall sensitivity of 68,4% (macrometastases: 86%; micrometastases: 11%), overall specificity of 98,7% and an overall accuracy of 89,7%. The intraoperative examination of SLN allows to reduce delayed surgery procedures and greater therapeutic safety in case of mastectomy. The TIC method can be considered valid, simple and rapid in identifying macrometastases, also allowing to avoid under-staging. The low sensitivity for micrometastases is not a limit, considering that recent evidence has drastically reduced the indications for ALND in these cases. Further ongoing trials and the possible validation of NOMOGRAMMS and SCORE are necessary to identify low risk cases in which to definitively omit the ALND and/or even the SLNB itself.

Species-specific sensitivity of three microalgae to sediment elutriates.

Microalgae are considered good bioindicators of marine environmental quality. Frequently, they are used to investigate the toxicity of sediment elutriates, but their sensitivity is disputed. This paper compared the sensitivity of Phaeodactylum tricornutum (diatom), Skeletonema costatum (diatom), and Dunaliella tertiolecta (green alga), analyzing 257 samples of elutriates (1:4 sediment: water ratio), considering growth inhibition (72 h) as the reference endpoint and sediment chemical (metals, metalloids and polyaromatic hydrocarbons) and grain size. Results of the toxicity tests showed that the microalgae sensitivity was not correlated. The integration of chemical data did not allow to discriminate toxicity effects but contributed to highlight that D. tertiolecta was the most sensitive microalgae (no cell wall) followed by P. tricornutum and S. costatum. Further analysis, including lines of evidence and weight of evidence approaches to calculate risk quotients of elutriate samples, confirmed these results.

Cerium and erbium effects on Daphnia magna generations: A multiple endpoints approach.

Cerium (Ce, CeCl3) and Erbium (Er, ErCl3) are increasingly used in many electronic devices facilitating the alteration of their biogeochemical cycles (e.g. e-waste). Previous surveys stated that their environmental concentrations due to natural or anthropogenic events can reach up to 161 µg/L in ore mine effluent for Ce with a mean water concentration of 0.79 µg/L, and 11.9 µg/L for Er in ore mine effluents with a mean water concentration of 0.004 µg/L. Their potential effects onto aquatic organisms are still relatively unexplored. In this study, long-term multigenerational effects on Daphnia magna were assessed using various exposure times (3, 7, 14, and 21 days) in three generations (F0, F1 and F2). Each generation was exposed to environmental concentrations of Ce and Er (0.54 and 0.43 µg/L, respectively - mean values) and effects included organisms' size, parental reproduction, and survival, determination of reactive oxygen species (ROS), enzymatic activity (superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST)), gene expression of ATP-binding cassette (ABC) transporter, and uptake. Results evidenced that chronic multi-generational exposure of daphnids to Ce and Er reduced survival, growth and reproduction, decreasing ROS, SOD and CAT from F0 to F2. Ce reduced the number of generated offsprings after each generation, while Er delayed the time of offsprings emergence, but not their number. ROS, SOD, CAT and GST evidenced that Er is slightly more toxic than Ce. Up- and downregulation of genes was limited, but Ce and Er activated the ABC transporters. Uptake of Ce and Er decreased through exposure time and generations.

Municipal wastewater spiramycin removal by conventional treatments and heterogeneous photocatalysis.

This study assessed the effects and removal options of the macrolide spiramycin, currently used for both in human and veterinary medicine- with a special focus on advanced oxidation processes based on heterogeneous TiO2_assisted photocatalysis. Spiramycin real concentrations were investigated on a seasonal basis in a municipal wastewater treatment plant (up to 35µgL-1), while its removal kinetics were studied considering both aqueous solutions and real wastewater samples, including by-products toxicity assessment. High variability of spiramycin removal by activated sludge treatments (from 9% (wintertime) to >99.9% (summertime)) was observed on a seasonal basis. Preliminary results showed that a total spiramycin removal (>99.9%) is achieved with 0.1gL-1 of TiO2 in aqueous solution after 80min. Integrated toxicity showed residual slight acute effects in the photocatalytic treated solutions, independently from the amount of TiO2 used, and could be linked to the presence of intermediate compounds. Photolysis of wastewater samples collected after activated sludge treatment during summer season (SPY 5µgL-1) allowed a full SPY removal after 80min. When photocatalysis with 0.1gL-1 of TiO2 was carried out in wastewater samples collected in winter season (SPY 30µgL-1) after AS treatment, SPY removal was up to 91% after 80min.

Effects of ZnO nanoparticles in the Caspian roach (Rutilus rutilus caspicus).

Most studies investigating the toxicity of zinc oxide nanoparticles (ZnO NPs) focused on the effect of size, whereas exposure concentration and duration remained poorly understood. In this study, the effect of acute and sub-acute exposures of ZnO NPs on Zn compartmentalization and biomarkers' expression were investigated in Rutilus rutilus caspicus (Caspian roach) considering various exposure scenarios: i) the assessment of the concentration-response curves and median lethal concentration (LC50); ii) the assessment of the effects of organisms exposed at LC50 value and one tenth of LC50 value of ZnO NPs suspensions for 4 d and 28 d, respectively; iii) the assessment of 14 d depuration period. The same concentrations of ZnSO4 were investigated. The highest Zn accumulation was detected in gill after sub-acute exposure (4.8 mg/L; 28 d) followed by liver, kidney and muscle. In gill, liver and muscle, Zn from Zn NPs accumulated higher concentrations. Depuration (14 d) decreased Zn content in each organ, but no complete removal occurred except for muscle. Biomarkers' activity was significantly over expressed after treatments, but depuration brought back their values to background levels and most effects were related to acute concentrations (48 mg/L; 4 d) and in presence of ZnSO4. Histopathological analyses showed that the exposure to ZnO NPs increased lesions in gill, liver and kidney, with a direct proportionality between alterations and Zn accumulated in the target organs. After depuration, lesions regressed for both ZnO NPs and ZnSO4, but not in a complete way. These data could contribute to increase the knowledge about ZnO NPs risk assessment in aquatic vertebrates, suggesting that the size of ZnO NPs can influence biomarker and histopathological effects.

Biodegradation, ecotoxicity and UV254/H2O2 treatment of imidazole, 1-methyl-imidazole and N,N'-alkyl-imidazolium chlorides in water.

Imidazole-based compounds are used as reagents for the manufacturing of other compounds including imidazolium-based ionic liquids, which have been recently proposed as a green alternative to conventional solvents. Since some imidazole-based compounds have been demonstrated to be harmful to aquatic organisms, the removal of imidazole, 1-methylimidazole, 1-ethyl-3-methyl-imidazolium chloride and 1-butyl-3-methyl-imidazolium chloride from aqueous solutions was attempted by biological oxidation, direct UV254 photolysis, and UV254/H2O2 process at pH 5.5 and 8.5. Results showed that UV254/H2O2 treatment is an effective tool for the removal of the selected compounds at both pHs. In fact, the kinetic constants of the reaction between the photogenerated HO radicals and the four target compounds, estimated by means of both numerical and competition kinetic method, range between 2.32·109 M-1 s-1 and 5.52 ·109 M-1 s-1. Moreover, an ecotoxicity assessment of the contaminated water before and after initial treatment without further processing was assessed by using two living aquatic organisms: Raphidocelis subcapitata and Daphnia magna. The results of this assessment not only corresponded closely to previous findings (in terms of EC50 values) reported in the literature, but also indicated that, in some cases, UV254/H2O2 oxidation by-products could be even more toxic than parent compounds.

Removal of benzoylecgonine from water matrices through UV254/H2O2 process: Reaction kinetic modeling, ecotoxicity and genotoxicity assessment.

Benzoylecgonine (BE), the main cocaine metabolite, has been detected in numerous surface water and treatment plants effluents in Europe and there is urgent need for effective treatment methods. In this study, the removal of BE by the UV254/H2O2 process from different water matrices was investigated. By means of competition kinetics method, the kinetic constant of reaction between BE and the photogenerated hydroxyl radicals (OH) was estimated resulting in kOH/BE=5.13×10(9)M(-1)s(-1). By-products and water matrices scavengers effects were estimated by numerical modeling of the reaction kinetics for the UV254/H2O2 process and validated in an innovative microcapillary film (MCF) array photoreactor and in a conventional batch photoreactor. The ecotoxicity of the water before and after treatment was evaluated with four organisms Raphidocelis subcapitata, Daphnia magna, Caenorhabditis elegans, and Vicia faba. The results provided evidence that BE and its transformation by-products do not have significant adverse effects on R. subcapitata, while D. magna underwent an increase of lipid droplets. C. elegans was the most sensitive to BE and its by-products. Furthermore, a genotoxicity assay, using V. faba, showed cytogenic damages during the cell mitosis of primary roots.

CT and MR imaging evaluation of neck infections with clinical correlations.

Infection of the neck is a common clinical problem in all age groups, especially children and young adults. The clinical symptoms and signs are often suggestive of the diagnosis. Imaging studies including CT and MR imaging are frequently required to confirm the diagnosis but more importantly to localize the infectious process and search for and delineate an abscess cavity. Ultrasound has also been used in the evaluation of superficial neck infections, especially to determine fluid accumulation. Conventional films consisting of an anteroposterior and lateral view were the examination before the introduction of CT in 1972. Conventional films can still be used for a preliminary survey, especially of the retropharyngeal space when there is a question of a retropharyngeal phlegmon or abscess.

Pleomorphic xanthoastrocytoma: clinical, imaging and pathological features of four cases.

Four cases of pleomorphic xanthoastrocytoma (PXA) were collected from among 688 glioma patients who underwent operation at the Institute of Neurosurgery, University of Naples "Federico II" between January 1973 and December 1994. Three were females and one male, ranging in age from 10 months to 65 years. Three tumors were superficial in location, appearing as a meningo-cerebral mass in the temporo-parietal region. In one case, the tumor was situated deep within the brain (capsulo-thalamic region), without contact with leptomeninges. Three patients had experienced epileptic seizures, whereas one patient presented with an ictal episode. Tumor excision was grossly total in two cases, and subtotal in the remaining two. In three cases, histological examination demonstrated a "typical" PXA; conversely one tumor (subtotal excised) was an "atypical" PXA. The two patients with incomplete surgical resection were postoperatively treated with fractionated brain radiation therapy. Of the two patients who had grossly total removals, one showed tumor recurrence 6 years after surgery, and underwent operation (the recurrent neoplasm did not exhibit malignant transformation); the second patient was free of tumor at 14 months following craniotomy. Of the two patients who had undergone subtotal removals, one died because of massive regrowth of the lesion 22 months after surgery, whereas the second patient was asymptomatic at 1 year follow up.

Polyurethane-covered mammary prosthesis: a nine year follow-up assessment.

We have examined ten tissue capsules from patients ranging from five months to nine years of mammary implantation. Contrary to published reports of polyurethane foam "fragmentation" or "disappearance" in the capsules evaluated, the polyurethane foam was still present and embedded in the surrounding tissue capsule. The foam was nearly always invisible by gross observation, or manual palpation. Only after enzymatic digestion of the tissue capsule did the foam become clearly visible as continuous sheets. ESCA analyses show that explanted foams are devoid of nitrogen peaks. Only carbon, oxygen and silicone signals are observed. The same foams do show nitrogen peaks (due to urethane linkages) when probed by FTIR. Since ESCA only analyzes the first 40-50 Angstroms of a surface, we believe that a "protective coating" composed of soft segments has formed. Beneath this "coating" the original polyurethane composition is still present as evidenced by FTIR analysis. Three possible explanations are advanced: (1) The surface hydrolysis, which takes place within the soft segment of the polyurethane polymer, results in the formation of oligomer(s). These oligomers, devoid of urethane linkages, appear to protect the polymer from further bioresorption, by significantly retarding the rate of additional surface hydrolysis. (2) Chain cleavage occurs in the soft segment producing a hydrophilic polyester chain end which orients into the interfacial area. These chain ends then produce a skin effect which increases the distance from the surface to the hard segments, or urethane-containing linkages. (3) Macromolecular motion in the soft segment phases of the polymer could be reorienting under the influence of the in vivo environment, thus producing a surface layer or "coating" which is predominantly soft segment in composition. Regardless of which of the three hypotheses proves to be most plausible, we interpret the data as showing that the polyurethane foam cover undergoes very slow bioresorption, even after 9 years of human implantation. The data further suggests that the in vivo surface of the polyurethane foam cover is biocompatible and interfacial interactions with inflammatory cells are downregulated or reduced because of the apparent biocompatibility of the material.

An assessment of 2,4 TDA formation from Surgitek polyurethane foam under simulated physiological conditions.

Samples of polyurethane foam used in the manufacture of mammary prostheses were enzymatically treated for a total of thirty days. Papain (a plant thiol endopeptidase which has similar activity to the human lysosomal enzyme cathepsin B) was our enzyme of choice since it has both amidase as well as esterase activity. The experiment was conducted under physiological conditions closely simulating the microenvironment likely to be found around an implanted mammary prosthesis. In our tests, 2,4 TDA was formed during enzymatic attack of this TDI-based polyurethane foam for the first four (4) days, reaching a maximum of 8.3 parts per million. After the initial burst, no further TDA was observed within the limits of detection of the experiment (10 parts per billion). Based on standard risk assessment, this amount of TDA translates into a risk of developing cancer of one in four hundred million.

In vivo testing of a biostable polyurethane.

At present all the commercially available "medical grade" urethane elastomers exhibit a phenomenon known as environmental stress cracking (ESC). This phenomenon is characterized by surface microcracking when the elastomer is elongated while in vivo. The degree of strain that is required to initiate microcracking varies from composition to composition. It has been found that harder compounds generally tend to have a higher strain threshold than corresponding softer ones. We theorized that this degradation occurs when certain enzymes (present only in vivo) attack and break down the ether linkages that link the polymer molecules together. Those elastomers that contain more ether linkages (such as the softer compositions) appear to microcrack more easily than elastomers with fewer ether linkages (such as the harder ones). The molecular composition of ChronoFlex urethane has been chosen so that the finished elastomer will be free of ether linkages; thus, it is expected to be immune from environmental stress cracking.