Retraction Note: Study of liver toxicity and DNA damage due to exposure to the pesticide Mancozeb in an experimental animal model - A pilot model.

The article "Study of liver toxicity and DNA damage due to exposure to the pesticide Mancozeb in an experimental animal model - A pilot model", by N.D. Suarez Uribe, M.F. Pezzini, J. Dall'Agnol, N. Marroni, S. Benitez, D. Benedetti, J. Da Silva, C.T. Cerski, E. Dallegrave, S. Macedo, S.C.W.S.E.F. de Oliveira, D. Joveleviths, published in Eur Rev Med Pharmacol Sci 2023; 27 (13): 6374-6383-DOI: 10.26355/eurrev_202307_32997-PMID: 37458654 has been retracted by the Editor in Chief for the following reasons: After publication, concerns were raised by an unidentified reader who underlined some similarities between this publication and a previous publication published in the Journal of Clinical and Experimental Gastroenterology. After being informed, the authors claimed the previous journal published the article without consent, and, therefore, the authors promptly withdrew the previous publication. The retraction published by the other journal does not contain any information regarding the reason for withdrawal. As a matter of fact, the journal does not have any evidence about the authors' claim and still considers this research a duplicate publication. For the above-mentioned reasons, the Editor in Chief decided to withdraw the manuscript. This manuscript has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/32997.

Study of liver toxicity and DNA damage due to exposure to the pesticide Mancozeb in an experimental animal model - A pilot model.

OBJECTIVE: Mancozeb is one of the most widely used Ethylenebisdithiocarbamates fungicides in Brazil. A pilot experimental model was created to evaluate its potential hepatotoxic effect. MATERIALS AND METHODS: An experimental study was performed with 27 male Wistar rats (3 groups). The Control Group received a saline solution, while Intervention Groups I and II received 250 mg/kg and 500 mg/kg of Mancozeb respectively, once a week, for 12 weeks. Anthropometric measurements were carried out, and the marker of biological exposure in urine was dosed. Biochemical tests, evaluation micronucleus count, comet and oxidative stress markers assay, and histological assessment of the liver were also performed. RESULTS: The hepatotoxic effect of Mancozeb was confirmed by anthropometric measurements, genotoxicity, and oxidative stress. Statistically significant results were found when the exposed groups were compared to the control group. CONCLUSIONS: These results were supported by inflammatory infiltration and balloonization in the treated groups. The experimental model effectively demonstrated the deleterious effect of Mancozeb on the liver.

Dual pulsed laser deposition system for the growth of complex materials and heterostructures.

Here, we present an integrated ultra-high-vacuum (UHV) apparatus for the growth of complex materials and heterostructures. The specific growth technique is the Pulsed Laser Deposition (PLD) by means of a dual-laser source based on an excimer KrF ultraviolet and solid-state Nd:YAG infra-red lasers. By taking advantage of the two laser sources-both lasers can be independently used within the deposition chambers-a large number of different materials-ranging from oxides to metals, to selenides, and others-can be successfully grown in the form of thin films and heterostructures. All of the samples can be in situ transferred between the deposition chambers and the analysis chambers by using vessels and holders' manipulators. The apparatus also offers the possibility to transfer samples to remote instrumentation under UHV conditions by means of commercially available UHV-suitcases. The dual-PLD operates for in-house research as well as user facility in combination with the Advanced Photo-electric Effect beamline at the Elettra synchrotron radiation facility in Trieste and allows synchrotron-based photo-emission as well as x-ray absorption experiments on pristine films and heterostructures.

Poor sleep quality and unhealthy lifestyle during the lockdown: an Italian study.

BACKGROUND: The lockdown measure implemented to face the 2019 Coronavirus Disease (COVID-19) first wave deeply modified the lifestyle of the Italian population. Despite its efficacy in limiting the number of infections, forced home confinement was paralleled by sleep/wake cycle disruptions, psychological distress and maladaptive coping strategies (i.e., unhealthy behaviours, such as tobacco and alcohol consumption). Under these unprecedented stress conditions, we explored a possible association between poor sleep quality and increased likelihood of engaging in an unhealthy lifestyle. METHODS: A cross-sectional study was conducted by disseminating an online survey via social networks and e-mail. We collected information on demographics, COVID-19-related data, sleep quality, chronotype, circadian misalignment, and lifestyle before and during the lockdown (i.e., consumption of cigarettes, alcoholic beverages, coffee, hypnotics, comfort food and fresh food; practice of physical activity). A global healthiness score was computed to assess participants' modifications in lifestyle since the beginning of the lockdown. RESULTS: 1297 respondents were included in the study: 414 (31.9%) from Northern Italy, 723 (55.8%) from Central Italy, 160 (12.3%) from Southern Italy. The following variables were found to be significant predictors of the adoption of an unhealthy lifestyle since the beginning of the lockdown: poor sleep quality, high BMI and considering the measures adopted by the government to fight the pandemic as excessive. Living in Northern Italy, instead, was associated with healthier habits compared to living in Central Italy. CONCLUSIONS: Poor sleepers may represent the share of the general population who paid the highest price for social isolation. Further investigations are required to explore the role of sleep quality assessment in the identification of individuals vulnerable to unhealthy behaviours under stressful conditions.

An integrated ultra-high vacuum apparatus for growth and in situ characterization of complex materials.

Here, we present an integrated ultra-high vacuum apparatus-named MBE-Cluster -dedicated to the growth and in situ structural, spectroscopic, and magnetic characterization of complex materials. Molecular Beam Epitaxy (MBE) growth of metal oxides, e.g., manganites, and deposition of the patterned metallic layers can be fabricated and in situ characterized by reflection high-energy electron diffraction, low-energy electron diffraction, Auger electron spectroscopy, x-ray photoemission spectroscopy, and azimuthal longitudinal magneto-optic Kerr effect. The temperature can be controlled in the range from 5 K to 580 K, with the possibility of application of magnetic fields H up to ±7 kOe and electric fields E for voltages up to ±500 V. The MBE-Cluster operates for in-house research as well as user facility in combination with the APE beamlines at Sincrotrone-Trieste and the high harmonic generator facility for time-resolved spectroscopy.

NOTCH1 mutations are associated with high CD49d expression in chronic lymphocytic leukemia: link between the NOTCH1 and the NF-κB pathways.

In chronic lymphocytic leukemia (CLL), stabilizing mutations of NOTCH1, affecting up to 10-15% of cases, have been associated to poor prognosis, disease progression and refractoriness to chemotherapy. NOTCH1 mutations are significantly overrepresented in trisomy 12 CLL, a disease subset frequently expressing CD49d, the α4 chain of the very-late-activation-4 integrin, a well-known key regulator of microenviromental interactions, and negative prognosticator in CLL. In the present study, by analysing a wide cohort of 1180 CLL, we observed a very strong association between the presence of NOTCH1 mutations and the expression of CD49d (P<0.0001), occurring also outside the trisomy 12 CLL subset. Using both the MEC-1 CLL-like cells stably transfected with the NOTCH1 intracellular domain and primary CLL cells bearing a mutated or wild-type NOTCH1 gene configuration, we provide evidence that triggering of the NOTCH1 pathway resulted in a positive CD49d expression regulation, which was driven by a NOTCH1-dependent activation of nuclear factot-κB (NF-κB). Consistently, pharmacological inhibition of the NOTCH1 and/or of the NF-κB pathways resulted in impaired NF-κB nuclear translocation with consequent down-modulation of CD49d expression. Altogether, our data link for the first time NOTCH1 mutations to CD49d expression regulation through the involvement of the NF-κB pathway in CLL.

CD49d prevails over the novel recurrent mutations as independent prognosticator of overall survival in chronic lymphocytic leukemia.

CD49d, the alpha-chain of the integrin heterodimer α4ß1, was identified among the strongest predictors of overall survival (OS) in chronic lymphocytic leukemia (CLL), along with IGHV mutational status and deletion of the 17p chromosome involving TP53. In addition to TP53, the clinical relevance of NOTCH1, SF3B1 and BIRC3 gene mutations has been recently emphasized. By analyzing a cohort of 778 unselected CLL patients, we assessed the clinical relevance of CD49d as an OS predictor in subgroups defined by mutation/deletion of the TP53, NOTCH1, SF3B1 and BIRC3 genes. In this context, CD49d emerged as an independent predictor of OS in multivariate Cox analysis (Hazard ratio =1.88, P<0.0001). Consistently, high CD49d expression identified CLL subsets with inferior OS in the context of each category of a previously reported hierarchical risk stratification model. Moreover, by evaluating the relative importance of biological prognosticators by random survival forests, CD49d was selected among the top-ranked OS predictor (variable importance =0.0410), along with IGHV mutational status and TP53 abnormalities. These results confirmed CD49d as an independent negative OS prognosticator in CLL also in comprehensive models comprising the novel recurrent mutations. In this context, TP53 disruption and NOTCH1 mutations retained prognostic relevance, in keeping with their roles in CLL cell immuno-chemoresistance.

NOTCH1 mutations associate with low CD20 level in chronic lymphocytic leukemia: evidence for a NOTCH1 mutation-driven epigenetic dysregulation.

In chronic lymphocytic leukemia (CLL), NOTCH1 mutations have been associated with clinical resistance to the anti-CD20 rituximab, although the mechanisms behind this peculiar behavior remain to be clarified. In a wide CLL series (n=692), we demonstrated that CLL cells from NOTCH1-mutated cases (87/692) were characterized by lower CD20 expression and lower relative lysis induced by anti-CD20 exposure in vitro. Consistently, CD20 expression by CLL cells was upregulated in vitro by γ-secretase inhibitors or NOTCH1-specific small interfering RNA and the stable transfection of a mutated (c.7541-7542delCT) NOTCH1 intracellular domain (NICD-mut) into CLL-like cells resulted in a strong downregulation of both CD20 protein and transcript. By using these NICD-mut transfectants, we investigated protein interactions of RBPJ, a transcription factor acting either as activator or repressor of NOTCH1 pathway when respectively bound to NICD or histone deacetylases (HDACs). Compared with controls, NICD-mut transfectants had RBPJ preferentially complexed to NICD and showed higher levels of HDACs interacting with the promoter of the CD20 gene. Finally, treatment with the HDAC inhibitor valproic acid upregulated CD20 in both NICD-mut transfectants and primary CLL cells. In conclusion, NOTCH1 mutations are associated with low CD20 levels in CLL and are responsible for a dysregulation of HDAC-mediated epigenetic repression of CD20 expression.

The CD49d/CD29 complex is physically and functionally associated with CD38 in B-cell chronic lymphocytic leukemia cells.

CD49d and CD38 are independent negative prognostic markers in chronic lymphocytic leukemia (CLL). Their associated expression marks a disease subset with a highly aggressive clinical course. Here, we demonstrate a constitutive physical association between the CD49d/CD29 integrin complex and CD38 in primary CLL cells and B-cell lines by (i) cocapping, (ii) coimmunoprecipitation and (iii) cell adhesion experiments using CD49d-specific substrates (vascular-cell adhesion molecule-1 or CS-1/H89 fibronectin fragments). The role of CD38 in CD49d-mediated cell adhesion was studied in CD49d(+)CD38(+) and CD49d(+)CD38(-) primary CLL cells, and confirmed using CD38 transfectants of the originally CD49d(+)CD38(-) CLL-derived cell line Mec-1. Results indicate that CD49d(+)CD38(+) cells adhered more efficiently onto CD49d-specific substrates than CD49d(+)CD38(-) cells (P < 0.001). Upon adhesion, CD49d(+)CD38(+) cells underwent distinctive changes in cell shape and morphology, with higher levels of phosphorylated Vav-1 than CD49d(+)CD38(-) cells (P = 0.0006) and a more complex distribution of F-actin to the adhesion sites. Lastly, adherent CD49d(+)CD38(+) cells were more resistant to serum-deprivation-induced (P < 0.001) and spontaneous (P = 0.03) apoptosis than the CD49d(+)CD38(-) counterpart. Altogether, our results point to a direct role for CD38 in enhancing CD49d-mediated adhesion processes in CLL, thus providing an explanation for the negative clinical impact exerted by these molecules when coexpressed in neoplastic cells.

The miR-17∼92 family regulates the response to Toll-like receptor 9 triggering of CLL cells with unmutated IGHV genes.

Chronic lymphocytic leukemia (CLL) cells from clinically aggressive cases have a greater capacity to respond to external microenvironmental stimuli, including those transduced through Toll-like-receptor-9 (TLR9). Concomitant microRNA and gene expression profiling in purified CLL cells (n=17) expressing either unmutated (UM) or mutated (M) IGHV genes selected microRNAs from the miR-17∼92 family as significantly upregulated and in part responsible for modifications in the gene expression profile of UM CLL cells stimulated with the TLR9 agonist CpG. Notably, the stable and sustained upregulation of miR-17∼92 microRNAs by CpG was preceded by a transient induction of the proto-oncogene MYC. The enforced expression of miR-17, a major member from this family, reduced the expression of the tumor suppressor genes E2F5, TP53INP1, TRIM8 and ZBTB4, and protected cells from serum-free-induced apoptosis (P ≤ 0.05). Consistently, transfection with miR-17∼92 family antagomiRs reduced Bromo-deoxy-uridine incorporation in CpG-stimulated UM CLL cells. Finally, miR-17 expression levels, evaluated in 83 CLL samples, were significantly higher in UM (P=0.03) and ZAP-70(high) (P=0.02) cases. Altogether, these data reveal a role for microRNAs of the miR-17∼92 family in regulating pro-survival and growth-promoting responses of CLL cells to TLR9 triggering. Overall, targeting of this pathway may represent a novel therapeutic option for management of aggressive CLL.

Total reflection X-ray fluorescence (TXRF) for direct analysis of aerosol particle samples.

Atmospheric aerosol particles have a great impact on the environment and on human health. Routine analysis of the particles usually involves only the mass determination. However, chemical composition and phases provide fundamental information about the particles' origins and can help to prevent health risks. For example, these particles may contain heavy metals such as Pb, Ni and Cd, which can adversely affect human health. In this work, filter samples were collected in Brescia, an industrial town located in Northern Italy. In order to identify the chemical composition and the phases of the atmospheric aerosols, the samples were analysed by means of total reflection X-ray fluorescence (TXRF) spectrometry with a laboratory instrument and X-ray microdiffraction at Synchrotron Daresbury Laboratories, Warrington (Cheshire, UK). The results are discussed and correlated to identify possible pollution sources. The novelty of this analytical approach is that filter samples for TXRF were analysed directly and did not require chemical pretreatment to leach elements from the aerosol particulates. The results of this study clearly show that TXRF is a powerful technique for the analysis of atmospheric aerosols on 'as-received' filters, thereby leaving samples intact and unaltered for possible subsequent analyses by other methods. In addition, the low detection limits for many elements (low ng/cm2) indicate that this method may hold promise in various application fields, such as nanotechnology.

Effects of fenoldopam infusion in complex cardiac surgical operations: a prospective, randomized, double-blind, placebo-controlled study.

AIM: Fenoldopam mesylate is a short-acting dopamine-1 agonist that has been suggested to be a possible reno-protective agent in patients undergoing cardiac surgery. The present study is a prospective, randomized, double-blind placebo controlled trial conducted to determine the effects of fenoldopam in a population of patients undergoing complex cardiac operations. METHODS: Eighty subjects undergoing complex cardiac operations with cardiopulmonary bypass (CPB) were enrolled in the study. Patients were randomly assigned either to the fenoldopam (0.1 microg . kg-1. min-1) or the placebo group. Fenoldopam infusion started at the onset of CPB and was maintained for the first twelve postoperative hours. CPB parameters and renal outcome data were collected. RESULTS: Patients in the fenoldopam group had higher oxygen delivery during CPB and a significantly lower perfusion pressure, although this parameter was still within the normal range. Blood lactate concentrations during CPB were similar in the two groups. Urine output during and after CPB did not differ between groups, nor did the renal function parameters. There was a significantly higher rate of acute kidney injury (AKI) in the placebo group (10% vs 0%). In the subgroup of patients requiring inotropic support for more than 48 hours, renal function parameters were significantly better, the peak arterial blood lactate was significantly lower, and the major morbidity rate was significantly lower (36% vs 100%) for patients who received fenoldopam. CONCLUSION: Fenoldopam improves the quality of perfusion during CPB. In patients receiving catecholamines to treat a postoperative low cardiac output state, fenoldopam significantly improves renal function and prevents AKI and major morbidity.

Advanced photoelectric effect experiment beamline at Elettra: A surface science laboratory coupled with Synchrotron Radiation.

We report the main characteristics of the advanced photoelectric effect experiments beamline, operational at Elettra storage ring, featuring a fully independent double branch scheme obtained by the use of chicane undulators and able to keep polarization control in both linear and circular mode. The paper describes the novel technical solutions adopted, namely, (a) the design of a quasiperiodic undulator resulting in optimized suppression of higher harmonics over a large photon energy range (10-100 eV), (b) the thermal stability of optics under high heat load via cryocoolers, and (c) the end station interconnected setup allowing full access to off-beam and on-beam facilities and, at the same time, the integration of users' specialized sample growth chambers or modules.

Analysis of crystalline phases in airborne particulate matter by two-dimensional X-ray diffraction (XRD2).

In this work, the potentiality of two-dimensional X-ray diffraction (XRD(2)) to characterise aerosol particles collected on commercial glass filters is presented. Indeed, even if routine analysis usually requires only mass determination, and rarely chemical composition, phase determination is fundamental to recognize the primary or secondary origin of the particulate matter and thus to determine the main sources of the pollution and to model contamination events. The experiments were performed at Daresbury Synchrotron (UK) Laboratory on 14.1 Beamline. The analysis of filters collected in Tuscany (Italy) is discussed with particular attention to the presence of arsenic sulfide. The first results of these experiments are very promising, showing the presence of unexpected compounds in the particulate matter of the investigated area.

Trillium biopassive surface: a new biocompatible treatment for extracorporeal circulation circuits.

139 patients undergoing cardiac surgery were included in a prospective, randomized trial. Patients were randomly allocated to receive cardiopulmonary bypass (CPB) with Trillium Biopassive Surface (TBS Group) coated oxygenators or conventional circuits (control group). 112 patients were studied with respect to postoperative biochemical profile; a subgroup of 27 patients was studied with respect to perioperative complement (C3a) activation. Patients in the TBS group demonstrated a significantly lower white blood cell count at the end of the operation (p=0.036) and a significantly higher platelet count the day after the operation (p=0.023) when compared to the control group. C3a was significantly higher (p=0.02) in the TBS group after 30 minutes of CPB, but the C3a increase after protamine administration was significantly less pronounced in the TBS group vs. the control group. Further studies involving platelet and leukocyte activation are required to better elucidate the action of this new coating in the setting of routine CPB.

[Indicators of continuous improvement of the transfer of neonatal emergency cases in the Trento province]. / Indicatori di miglioramento continuo delle cure dopo valutazione dell'attività di trasporto primario d'emergenza neonatale in provincia di Trento.

The nursing personnel of the Neonatology Unit of Trento Hospital cares for the transportation of newborns in the Trento Province (more than 7500 transportations have been performed to date). Aim of the study is the evaluation of the quality of care as documented in the ad hoc neonatal transportation data-bank. A further goal is the formulation and validation of simple and easy to collect indicators of "improvement of care". Examples of indicators used to assess the activities of the years 1996 and 1997 were the number of transportations with functioning equipment; the number of newborns with body temperature registered; the number of transportation cards correctly filled out. These simple indicators allowed to identify areas where the quality of care could be improved. The cause-effect diagram used allowed the involvement of all the nursing personnel in the identification of problems and of possible solutions. An example of the process followed for identifying and preventing hypothermia is presented and discussed.