Oxidative stress and DNA damage in agricultural workers after exposure to pesticides

Background: Recent epidemiological studies on workers describe that exposure to pesticides can induce oxidative stress by increased production of free radicals that can accumulate in the cell and damage biological macromolecules, for example, RNA, DNA, DNA repair proteins and other proteins and/or modify antioxidant defense mechanisms, as well as detoxification and scavenger enzymes. This study aimed to assess oxidative stress and DNA damage among workers exposed to pesticides. Methods: For this purpose, 52 pesticide exposed workers and 52 organic farmers were enrolled. They were assessed: the pesticide exposure, thiobarbituric acid reactive substances (TBARS), total glutathione (TG), oxidized glutathione levels (GSSG), and 8-oxo-7,8-dihydro-2\u2032-deoxyguanosine (8-oxodG), levels. Results: Correlation between pesticide exposure was positively associated with high TBARS and 8-oxodG levels (p < 0.001). A negative association was founded with TG and GSSG and pesticide exposure. Conclusions: The present investigation results seem to indicate a mild augment in oxidative stress associated with pesticide exposure, followed by an adaptive response to increase the antioxidant defenses to prevent sustained oxidative adverse effects stress

numerical simulation of a solar domestic hot water system

An innovative transient numerical model is presented for the simulation of a solar Domestic Hot Water (DHW) system. The solar collectors have been simulated by using a zerodimensional analytical model. The temperature distributions in the heat transfer fluid and in the water inside the tank have been evaluated by one-dimensional models. The reversion elimination algorithm has been used to include the effects of natural convection among the water layers at different heights in the tank on the thermal stratification. A finite difference implicit scheme has been implemented to solve the energy conservation equation in the coil heat exchanger, and the energy conservation equation in the tank has been solved by using the finite difference Euler implicit scheme. Energy conservation equations for the solar DHW components models have been coupled by means of a home-made implicit algorithm. Results of the simulation performed using as input data the experimental values of the ambient temperature and the solar irradiance in a summer day are presented and discussed

Cytosine deaminase base editing to restore COL7A1 in dystrophic epidermolysis bullosa human:murine skin model

Recessive dystrophic epidermolysis bullosa (RDEB) is a debilitating blistering skin disorder caused by loss-of-function mutations in COL7A1 encoding type VII collagen (C7), the main component of anchoring fibrils (AFs) at the dermal-epidermal junction (DEJ). Although conventional gene therapy approaches through viral vectors have been tested in pre-clinical and clinical trials, they are limited by transgene size constraints and only support unregulated gene expression. Genome editing could potentially overcome some of these limitations, and CRISPR/Cas9 has already been applied in research studies to restore COL7A1 expression. Delivery of suitable repair templates for repair of DNA cleaved by Cas9 is still major challenge, and alternative base editing strategies may offer corrective solutions for certain mutations. We demonstrate highly targeted and efficient cytidine deamination and molecular correction of a defined RDEB mutation (c.425A>G) leading to restoration of full-length C7 protein expression in primary human fibroblasts and iPSCs. C7 basement membrane expression and skin architecture were restored with de novo AFs identified by electron microscopy in base edited human RDEB grafts recovered from immunodeficient mice. The results demonstrate the potential and promise of emerging base editing technologies in tackling inherited disorders with well-defined single nucleotide mutations

Palbociclib plus fulvestrant or everolimus plus exemestane for pretreated advanced breast cancer with lobular histotype in er+/her2 12 patients: A propensity score-matched analysis of a multicenter retrospective patient series

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) show meaningful efficacy and tolerability in patients with metastatic breast cancer (MBC), but the optimal sequence of ET has not been established. It is not clear if patients with lobular breast carcinomas (LBC) derive the same benefits when receiving second line CDK4/6i. This retrospective study compared the efficacy of palbociclib plus fulvestrant (PALBO\u2013FUL) with everolimus plus exemestane (EVE\u2013EXE) as second-line ET for hormone-resistant metastatic LBC. From 2013 to 2018, patients with metastatic LBC positivity for estrogen and/or progesterone receptors and HER2/neu negativity, who had relapsed during adjuvant hormonal therapy or first-line hormonal treatment, were enrolled from six centers in Italy in this retrospective study. A total of 74 out of 376 patients (48 treated with PALBO\u2013FUL and 26 with EVE\u2013EXE) with metastatic LBC were eligible for inclusion. Progression-free survival (PFS) was longer in patients receiving EVE\u2013EXE compared with PALBO\u2013FUL (6.1 vs. 4.5 months, univariate HR 0.58, 95% CI 0.35\u20130.96; p = 0.025). On the propensity score (PS) analysis, PFS was confirmed to be significantly longer for patients treated with EVE\u2013EXE compared to PALBO\u2013FUL (6.0 vs. 4.6 months, p = 0.04). This retrospective analysis suggests that EVE\u2013EXE is more effective than PALBO\u2013FUL for second line ET of metastatic LBC, allowing us to speculate on the optimal therapeutic sequence

Breast cancer "tailored follow-up" in Italian oncology units: a web-based survey

urpose: Breast cancer follow-up procedures after primary treatment are still a controversial issue. Aim of this study was to investigate, through a web-based survey, surveillance methodologies selected by Italian oncologists in everyday clinical practice. Methods: Referents of Italian medical oncology units were invited to participate to the study via e-mail through the SurveyMonkey website. Participants were asked how, in their institution, exams of disease staging and follow-up are planned in asymptomatic women and if surveillance continues beyond the 5th year. Results: Between February and May 2013, 125 out of 233 (53.6%) invited referents of Italian medical oncology units agreed to participate in the survey. Ninety-seven (77.6%) referents state that modalities of breast cancer follow-up are planned according to the risk of disease progression at diagnosis and only 12 (9.6%) oncology units apply the minimal follow-up procedures according to international guidelines. Minimal follow-up is never applied in high risk asymptomatic women. Ninety-eight (78.4%) oncology units continue follow-up in all patients beyond 5 years. Conclusions: Our survey shows that 90.4% of participating Italian oncology units declare they do not apply the minimal breast cancer follow-up procedures after primary treatment in asymptomatic women, as suggested by national and international guidelines. Interestingly, about 80.0% of interviewed referents performs the so called "tailored follow-up", high intensity for high risk, low intensity for low risk patients. There is an urgent need of randomized clinical trials able to determine the effectiveness of risk-based follow-up modalities, their ideal frequency and persistence in time

Analisi tecnico-progettuale sulla produzione di idrogeno da biomassa

ambito del progetto CE.S.I.B.A. – ROMA – Aprile – 200