Residues of Aflatoxins B1 and M1 in different biological matrices of swine orally administered aflatoxin B1 and Saccharomyces cerevisiae

Residui di aflatossine B1 e M1 in differenti matrici biologiche di suino alimentato con diete contenenti aflatossina B1 e Saccharomyces cerevisiae. \u2013 Le micotossine, e la aflatossina B1 (AFB1) in particolare, rappresentano da sempre un problema di sanit\ue0 pubblica a livello mondiale di difficile risoluzione. Scopo del presente lavoro \ue8 stato quello di valutare le quantit\ue0 di aflatossine B1 e M1, in fegato, rene, muscolo e grasso di suini che hanno assunto per 5 settimane diete sperimentalmente contaminate con 280 \ub5g/kg di AFB1. E\u2019 stata valutata anche la capacit\ue0 adsorbente del Saccharomyces cerevisiae nei confronti di AFB1, somministrando la micotossina (280 ppb) insieme ad una dieta contenente lo 0.2% del lievito. Le quote residuali delle due aflatossine sono state determinate con metodo HPLC in fluorescenza, previa purificazione con estrazione solida (SPE). Muscolo e grasso sono risultati costantemente negativi per entrambe le micotossine, mentre i livelli rilevati in fegato e rene appaiono molto bassi per la AFB1 (valori compresi tra 0.03-0.12 ppb) e leggermente superiori per la AFM1 (valori compresi tra 0.39-0.72 ppb)

Carbonylation of dimethoxymethane: a study on the reactivity of different solid acid catalysts

The carbonylation of dimethoxymethane (DMM) to methyl methoxyacetate (MMA) has gained interest in recent years not only due to its application as an important fine chemical, but also as a possible intermediate to produce ethylene glycol (EG) as well as a possible fuel additive. Employing different zeolites and ion exchange resins as catalysts, this paper systematically studied the effects of catalyst amount, temperature, carbon monoxide (CO) pressure and reaction conditions on educt conversion and product selectivities, using a parallel high pressure reactor plant. The reaction was performed in the liquid phase without using an additional solvent. The highest DMM conversion was achieved by catalyst Z-30 (ZSM-5; MFI type zeolite) and Amberlyst 36 (sulfonated ion exchange resin). The lowest DMM conversion was shown by H-Y-30 (Y; FAU-type zeolite) and Amberlyst 46. According to the analytical measurements via off-line gas chromatography (GC), the product spectrum includes, besides MMA, higher oxymethylene ethers (OME) like OME2, OME3, the carbonylation products of higher OMEs, methyl formate (MeFo) and formaldehyde (FA). The herein reported catalysts and parameter screenings for the carbonylation of DMM to MMA will assist the optimisation of this reaction as a promising industrial manufacturing process

EVALUATION OF LIVER PARENCHYMA AND PERFUSION USING DYNAMIC CONTRAST-ENHANCED COMPUTED TOMOGRAPHY AND CONTRAST-ENHANCED ULTRASONOGRAPHY IN CAPTIVE GREEN IGUANAS (IGUANA IGUANA) UNDER GENERAL ANESTHESIA

Background: Contrast-enhanced diagnostic imaging techniques are considered useful in veterinary and human medicine to evaluate liver perfusion and focal hepatic lesions. Although hepatic diseases are a common occurrence in reptile medicine, there is no reference to the use of contrast-enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CECT) to evaluate the liver in lizards. Therefore, the aim of this study was to evaluate the pattern of change in echogenicity and attenuation of the liver in green iguanas (Iguana iguana) after administration of specific contrast media. Results: An increase in liver echogenicity and density was evident during CEUS and CECT, respectively. In CEUS, the mean \ub1 SD (median; range) peak enhancement was 19.9% \ub1 7.5 (18.3; 11.7-34.6). Time to peak enhancement was 134.0 \ub1 125.1 (68.4; 59.6-364.5) seconds. During CECT, first visualization of the contrast medium was at 3.6 \ub1 0.5 (4; 3-4) seconds in the aorta, 10.7 \ub1 2.2 (10.5; 7-14) seconds in the hepatic arteries, and 15 \ub1 4.5 (14.5; 10-24) seconds in the liver parenchyma. Time to peak was 14.1 \ub1 3.4 (13; 11-21) and 31 \ub1 9.6 (29; 23-45) seconds in the aorta and the liver parenchyma, respectively. Conclusion: CEUS and dynamic CECT are practical means to determine liver hemodynamics in green iguanas. Distribution of contrast medium in iguana differed from mammals. Specific reference ranges of hepatic perfusion for diagnostic evaluation of the liver in iguanas are necessary since the use of mammalian references may lead the clinician to formulate incorrect diagnostic suspicions

Genotype of Immunologically Hot or Cold Tumors Determines the Antitumor Immune Response and Efficacy by Fully Virulent Retargeted oHSV

We report on the efficacy of the non-attenuated HER2-retargeted oHSV named R-337 against the immunologically hot CT26-HER2 tumor, and an insight into the basis of the immune protection. Preliminarily, we conducted an RNA immune profiling and immune cell content characterization of CT26-HER2 tumor in comparison to the immunologically cold LLC1-HER2 tumor. CT26-HER2 tumor was implanted into HER2-transgenic BALB/c mice. Hallmarks of R-337 effects were the protection from primary tumor, long-term adaptive vaccination directed to both HER2 and CT26-wt cell neoantigens. The latter effect differentiated R-337 from OncoVEXGM-CSF. As to the basis of the immune protection, R-337 orchestrated several changes to the tumor immune profile, which cumulatively reversed the immunosuppression typical of this tumor (graphical abstract). Thus, Ido1 (inhibitor of T cell anticancer immunity) levels and T regulatory cell infiltration were decreased; Cd40 and Cd27 co-immunostimulatory markers were increased; the IFNγ cascade was activated. Of note was the dampening of IFN-I response, which we attribute to the fact that R-337 is fully equipped with genes that contrast the host innate response. The IFN-I shut-down likely favored viral replication and the expression of the mIL-12 payload, which, in turn, boosted the antitumor response. The results call for a characterization of tumor immune markers to employ oncolytic herpesviruses more precisely

Immunotherapeutic efficacy of retargeted ohsvs designed for propagation in an ad hoc cell line

Our laboratory has pursued the generation of cancer‐specific oncolytic herpes simplex viruses (oHSVs) which ensure high efficacy while maintaining a high safety profile. Their blueprint included retargeting to a Tumor‐Associated Antigen, e.g., HER2, coupled to detargeting from natural receptors to avoid off‐target and off‐tumor infections and preservation of the full complement of unmodified viral genes. These oHSVs are “fully virulent in their target cancer cells”. The 3rd generation retargeted oHSVs carry two distinct retargeting moieties, which enable infection of a producer cell line and of the target cancer cells, respectively. They can be propagated in an ad hoc Vero cell derivative at about tenfold higher yields than 1st generation recombinants, and more effectively replicate in human cancer cell lines. The R‐335 and R‐337 prototypes were armed with murine IL‐12. Intratumorally‐administered R‐337 conferred almost complete protection from LLC‐ 1‐HER2 primary tumors, unleashed the tumor microenvironment immunosuppression, synergized with the checkpoint blockade and conferred long‐term vaccination against distant challenge tumors. In summary, the problem intrinsic to the propagation of retargeted oHSVs—which strictly require cells positive for targeted receptors—was solved in 3rd generation viruses. They are effective as immunotherapeutic agents against primary tumors and as antigen‐agnostic vaccines

Does Bentonite Cause Cytotoxic and Whole-Transcriptomic Adverse Effects in Enterocytes When Used to Reduce Aflatoxin B1 Exposure?

Aflatoxin B1 (AFB1) is a major food safety concern, threatening the health of humans and animals. Bentonite (BEN) is an aluminosilicate clay used as a feed additive to reduce AFB1 presence in contaminated feedstuff. So far, few studies have characterized BEN toxicity and efficacy in vitro. In this study, cytotoxicity (WST-1 test), the effects on cell permeability (trans-epithelial electrical resistance and lucifer yellow dye incorporation), and transcriptional changes (RNA-seq) caused by BEN, AFB1 and their combination (AFB1 + BEN) were investigated in Caco-2 cells. Up to 0.1 mg/mL, BEN did not affect cell viability and permeability, but it reduced AFB1 cytotoxicity; however, at higher concentrations, BEN was cytotoxic. As to RNA-seq, 0.1 mg/mL BEN did not show effects on cell transcriptome, confirming that the interaction between BEN and AFB1 occurs in the medium. Data from AFB1 and AFB1 + BEN suggested AFB1 provoked most of the transcriptional changes, whereas BEN was preventive. The most interesting AFB1-targeted pathways for which BEN was effective were cell integrity, xenobiotic metabolism and transporters, basal metabolism, inflammation and immune response, p53 biological network, apoptosis and carcinogenesis. To our knowledge, this is the first study assessing the in vitro toxicity and whole-transcriptomic effects of BEN, alone or in the presence of AFB1

Interleukin-6 neutralization ameliorates symptoms in prematurely aged mice

Hutchinson\u2013Gilford progeria syndrome (HGPS) causes premature aging in children, with adipose tissue, skin and bone deterioration, and cardiovascular impairment. In HGPS cells and mouse models, high levels of interleukin-6, an inflammatory cytokine linked to aging processes, have been detected. Here, we show that inhibition of interleukin-6 activity by tocilizumab, a neutralizing antibody raised against interleukin-6 receptors, counteracts progeroid features in both HGPS fibroblasts and LmnaG609G/G609G progeroid mice. Tocilizumab treatment limits the accumulation of progerin, the toxic protein produced in HGPS cells, rescues nuclear envelope and chromatin abnormalities, and attenuates the hyperactivated DNA damage response. In vivo administration of tocilizumab reduces aortic lesions and adipose tissue dystrophy, delays the onset of lipodystrophy and kyphosis, avoids motor impairment, and preserves a good quality of life in progeroid mice. This work identifies tocilizumab as a valuable tool in HGPS therapy and, speculatively, in the treatment of a variety of aging-related disorders

The relationship between nurse managers' leadership style and patients' perception of the quality of the care provided by nurses: Cross sectional survey

Background:  In healthcare systems, human resources play a strategic role that has a significant impact on the whole caring process. When the wellbeing of professionals is low their performance decreases, counterproductive work behaviours may became more likely, and as a result the quality of care is compromised. Studies have shown that leadership style is particularly relevant in relation to the quality of work environments in healthcare organizations. Objective:  The main purpose of this study is to test a model that investigates the relationships between nurse managers’ leadership style and patients’ perception of the quality of the care provided by the nurses, through the mediation of the quality of the working environment (in terms of burnout, interpersonal strain and counterproductive work behaviour). Design:  A multi-centre cross-sectional study was conducted. Setting:  The study was conducted in five hospitals located two in the north, two in the centre and one in the south of Italy. Participants:  Participants were 479 registered nurses (working as staff nurses, while head nurses and nurse managers were excluded) and 829 patients aged 18 years or older, able to read and write Italian and hospitalized for at least 3 days. Severely ill or mentally disabled patients who were not able to fill in the questionnaire were excluded. Methods:  The data were collected through two different questionnaires, one for the nurses and one for the patients. A multilevel analysis was conducted to examine the hypothesized model. Results:  Results confirmed the hypothesis that, when nurses were satisfied with leadership, they felt less burned-out and strained in interpersonal relationships, they engaged less in misbehaviour, and, in turn, patients were more satisfied with the quality of the care provided by the nurses. Conclusions:  The results of this study showed that the characteristics of the organizational context, the leadership, and the behaviours of nurses, influenced patients’ perceptions of nurses’ care. Therefore, managers of healthcare services should take these results into account seriously in order to improve the quality of care provided to patients