Pfas environmental pollution and antioxidant responses: An overview of the impact on human field

Due to their unique properties, perfluorinated substances (PFAS) are widely used in multiple industrial and commercial applications, but they are toxic for animals, humans included. This review presents some available data on the PFAS environmental distribution in the world, and in particular in Europe and in the Veneto region of Italy, where it has become a serious problem for human health. The consumption of contaminated food and drinking water is considered one of the major source of exposure for humans. Worldwide epidemiological studies report the negative effects that PFAS have on human health, due to environmental pollution, including infertility, steroid hormone perturbation, thyroid, liver and kidney disorders, and metabolic disfunctions. In vitro and in vivo researches correlated PFAS exposure to oxidative stress effects (in mammals as well as in other vertebrates of human interest), produced by a PFAS-induced increase of reactive oxygen species formation. The cellular antioxidant defense system is activated by PFAS, but it is only partially able to avoid the oxidative damage to biomolecules

Phenylboronic Acids Probing Molecular Recognition against Class A and Class C beta-Lactamases

Worldwide dissemination of pathogens resistant to almost all available antibiotics represent a real problem preventing efficient treatment of infectious diseases. Among antimicrobial used in therapy, \u392-lactam antibiotics represent 40% thus playing a crucial role in the management of infections treatment. We report a small series of phenylboronic acids derivatives (BAs) active against class A carbapenemases KPC-2 and GES-5, and class C cephalosporinases AmpC. The inhibitory profile of our BAs against class A and C was investigated by means of molecular docking, enzyme kinetics and X-ray crystallography. We were interested in the mechanism of recognition among class A and class C to direct the design of broad serine \u392-Lactamases (SBLs) inhibitors. Molecular modeling calculations vs GES-5 and crystallographic studies vs AmpC reasoned, respectively, the ortho derivative 2 and the meta derivative 3 binding affinity. The ability of our BAs to protect \u392-lactams from BLs hydrolysis was determined in biological assays conducted against clinical strains: Fractional inhibitory concentration index (FICI) tests confirmed their ability to be synergic with \u392-lactams thus restoring susceptibility to meropenem. Considering the obtained results and the lack of cytotoxicity, our derivatives represent validated probe for the design of SBLs inhibitors

The current role of touch imprint cytology in sentinel lymph node intra-operatory examination

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Separable spatio-temporal kriging for fast virtual sensing

Environmental monitoring is a task that requires to surrogate system-wide information with limited sensor readings. Under the proximity principle, an environmental monitoring system can be based on the virtual sensing logic and then rely on distance-based prediction methods, such as $k$-nearest-neighbors, inverse distance weighted regression and spatio-temporal kriging. The last one is cumbersome with large datasets, but we show that a suitable separability assumption reduces its computational cost to an extent broader than considered insofar. Only spatial interpolation needs to be performed in a centralized way, while forecasting can be delegated to each sensor. This simplification is mostly related to the fact that two separate models are involved, one in time and one in the space domain. Any of the two models can be replaced without re-estimating the other under a composite likelihood approach. Moreover, the use of convenient spatial and temporal models eases up computation. We show that this perspective on kriging allows to perform virtual sensing even in the case of tall datasets.Comment: Submitted to Applied Stochastic Models in Business and Industry on September 30, 202

INHIBITORY EFFECT OF BIOCIDES ON ENVIRONMENTAL S. AUREUS STRAINS

The aim of this study was to evaluate the inhibitory effect of biocides on S.aureus strains isolated in dairy environment. After a contact time of 5' all tested molecules showed total growth inhibition of bacteria; for lower contact time results were depending on strains and biocides

MTOR, p70S6K, AKT, and ERK1/2 levels predict sensitivity to mTOR and PI3K/mTOR inhibitors in human bronchial carcinoids

Bronchial carcinoids (BCs) are rare neuroendocrine tumors that are still orphans of medical treatment. Human BC primary cultures may display resistance to everolimus, an inhibitor of the mammalian target of rapamycin (mTOR), in terms of cell viability reduction. Our aim was to assess whether the novel dual phosphatidylinositol 3-kinase (PI3K)/mTOR inhibitor NVP-BEZ235 is effective in everolimus-resistant human BC tissues and cell lines. In addition, we searched for possible markers of the efficacy of mTOR inhibitors that may help in identifying the patients who may benefit from treatment with mTOR inhibitors, sparing them from ineffective therapy. We found that NVP-BEZ235 is twice as potent as everolimus in reducing cell viability and activating apoptosis in human BC tissues that display sensitivity to mTOR inhibitors, but is not effective in everolimus-resistant BC tissues and cell lines that bypass cyclin D1 downregulation and escape G0/G1 blockade. Rebound AKT activation was not observed in response to treatment with either mTOR inhibitor in the 'resistant' BC cells. In addition to total mTOR levels, putative markers of the sensitivity of BCs to mTOR inhibitors are represented by AKT, p70S6K (RPS6KB2), and ERK1/2 (MAPK3/1) protein levels. Finally, we validated these markers in an independent BC group. These data indicate that the dual PI3K/mTOR inhibitor NVP-BEZ235 is more potent than everolimus in reducing the proliferation of human BC cells. 'Resistant' cells display lower levels of mTOR, p70S6K, AKT, and ERK1/2, indicating that these proteins may be useful as predictive markers of resistance to mTOR and PI3K/mTOR inhibitors in human BCs. \ua9 2013 Society for Endocrinology

Correlations between immunogenicity, drug levels, and disease activity in an Italian cohort of rheumatoid arthritis patients treated with tocilizumab

The aim of this study was to evaluate the real-life immunogenicity of anti-drug antibodies, drug levels, and disease activity in an Italian cohort of rheumatoid arthritis patients treated with tocilizumab (TCZ). We evaluated 126 TCZ-treated patients with rheumatoid arthritis (16 males and 110 females; mean age 59\ub112 years, range 26-83; mean disease duration 11\ub15 years) with inadequate 12-week response to any synthetic and biological disease-modifying anti-rheumatic drugs, in a retrospective analysis. One-hundred and seven patients were treated with methotrexate mean dose 12.6\ub1 1.3 mg/week in combination with TCZ, 13 received TCZ monotherapy, and six received leflunomide 20 mg/day plus TCZ; all patients were treated with prednisone mean dose 6.4\ub11.2 mg/day. They had a 28-joint Disease Activity Score (DAS28) of >3.2, an erythrocyte sedimentation rate (ESR) of >30 mm/hour, and CRP levels of >1.0 mg/dL. We evaluated at baseline and after 6 months of treatment: DAS28; rheumatoid factor (RF) IgM, IgA, and IgG; anti-citrullinated peptide antibody; ESR; CRP; TNF-a; and IL-6. TCZ and anti- TCZ antibodies were detected using LISA-TRACKER Duo TCZ. TCZ levels of 10 \u3bcg/mL high. After 6 months of treatment only one patient was positive for anti-TCZ antibodies. There were correlations between DAS28, ESR, and CRP and IL-6 levels in all patients. Comparison of the 84 patients with TCZ levels of 10 \u3bcg/mL showed the following differences: DAS28: 3.09\ub11.32 vs 2.78\ub11.32, P=0.0005; ESR: 27\ub114.8 vs 14\ub112 mm/hour, P=0.0001; CRP: 1.47\ub11.05 vs 0.65\ub10.80 mg/dL, P=0.0086; TNF-a: 10.2\ub11.2 vs 9.9\ub11.1 pg/mL, P=0.999; IL-6: 3.65\ub14.75 vs 3.62\ub14.41 pg/mL, P=0.97; anti-citrullinated peptide antibody: 85.2\ub193.7 vs 86.7\ub190.3 IU/mL, P=0.94; RF IgM: 72.4\ub162.7 vs 68.3\ub161.6 IU/mL, P=0.754; RF IgA: 41.7\ub136.4 vs 47.8\ub142.1 U/mL, P=0.449; and RF IgG: 46.4\ub146.1 vs 59.3\ub158.2 U/mL, P=0.212. These findings show that the occurrence of anti-drug antibodies against TCZ is very rare and that there are statistically significant correlations between TCZ levels of >10 \u3bcg/mL and ESR, CRP levels, and DAS28