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Alternaria toxins (ATs) are a group of toxins produced by Alternaria fungi that frequently contaminate tomatoes and tomato products. Recently, the European Food Safety Authority evaluated ATs for their genotoxic and carcinogenic properties. Alternaria infestation is often controlled using ad hoc treatment strategies (fungicides). In this study, two analytical methods were developed, validated and applied for the determination of five ATs and 195 pesticides in tomato products collected from the Italian market. Two distinct groups, organic (n = 20) and conventional (n = 20) Italian tomato sauces, were characterized in depth. Tenuazonic acid, alternariol and alternariol monomethyl ether were found up to 517, 27 and 7.1 µg/kg, respectively, while pesticides were detected between 0.0026 and 0.0421 mg/kg in conventional products, and, interestingly, up to 0.0130 mg/kg in organic products. No correlation emerged between the detected levels of ATs and pesticides and the type of tomato cultivation, but the probability of pesticide contamination in conventional products was eight times higher than in organics. Some considerations about exposure assessment and risk characterization for ATs were also proposed in the overall population and in more sensitive and/or exposed subgroups, underlining the need for new focused toxicological and monitoring studies to establish reliable reference values. Moreover, these data highlight that fungicide treatments may not protect tomatoes from ATs contamination, although it may remove fungi infestation. As organic product consumption is increasing, it is important to lay down dedicated regulations for maximum permitted levels to ensure the food safety of these products that are often perceived by consumers as a healthier and environmentally friendlier choice. [ABSTRACT FROM AUTHOR]

Drug repositioning strategy represents a valid tool to accelerate the pharmacological development through the identification of new applications for already existing compounds. In this view, we aimed at discovering molecules able to trigger telomere‐localized DNA damage and tumor cell death. By applying an automated high‐content spinning‐disk microscopy, we performed a screening aimed at identifying, on a library of 527 drugs, molecules able to negatively affect the expression of TRF2, a key protein in telomere maintenance. FK866, resulting from the screening as the best candidate hit, was then validated at biochemical and molecular levels and the mechanism underlying its activity in telomere deprotection was elucidated both in vitro and in vivo. The results of this study allow us to discover a novel role of FK866 in promoting, through the production of reactive oxygen species, telomere loss and deprotection, two events leading to an accumulation of DNA damage and tumor cell death. The ability of FK866 to induce telomere damage and apoptosis was also demonstrated in advanced preclinical models evidencing the antitumoral activity of FK866 in triple‐negative breast cancer—a particularly aggressive breast cancer subtype still orphan of targeted therapies and characterized by high expression levels of both NAMPT and TRF2. Overall, our findings pave the way to the development of novel anticancer strategies to counteract triple‐negative breast cancer, based on the use of telomere deprotecting agents, including NAMPT inhibitors, that would rapidly progress from bench to bedside. [ABSTRACT FROM AUTHOR]

Canine prostatic serum esterase (CPSE) is considered a useful tool to identify prostate disorders in dogs, with increasing interest in ultrasound (US)‐based sonoelastography to non‐invasively detect prostate disorders. Since no report is available about a possible correlation between these diagnostic tools, we aimed to investigate a possible correlation between strain elastography (SE) and 2D‐shear wave elastography (SWE) and CPSE. Twenty‐one dogs were included and, on each animal, CPSE was evaluated followed by a complete US examination and SE and 2D‐SWE application. Healthy dogs were identified based on the CPSE results. All the dogs included were characterized by normal CPSE values (<52.3 ng/mL) and normal US prostate appearance. The prostate was characterized by intermediate stiffness with SE (pattern III – 84.7% for the left lobe and 79.27% for the right lobe) and softer than the abdominal wall (SR 0.6 for the left lobe and 0.56 for the right lobe), with low values for both m/s and kilopascals (kPa) for 2D‐SWE, pointing that the healthy tissue is not hard. 2D‐SWE results were, respectively, 13.51 ± 5.55 kPa and 2.31 ± 0.42 m/s for the left lobe and 18.05 ± 6.47 kPa and 2.39 ± 0.43 m/s for the right lobe. The significant difference between the right and left measurements expressed with kPa, not evidenced with m/s, can be considered indicative of m/s as the most reliable measurement to be considered regarding the prostate parenchyma. Even though no linear correlation was detected between CPSE and elastography values, these preliminary results evidence that the healthy prostates were characterized by a similar elastographic pattern, thus pointing that these techniques can be potentially useful to be applied in case of prostatic disorders to improve the accuracy of the final diagnosis in a non‐invasive way. [ABSTRACT FROM AUTHOR]

TERF2/TRF2 is a pleiotropic telomeric protein that plays a crucial role in tumor formation and progression through several telomere-dependent and -independent mechanisms. Here, we uncovered a novel function for this protein in regulating the macroautophagic/autophagic process upon different stimuli. By using both biochemical and cell biology approaches, we found that TERF2 binds to the non-histone chromatin-associated protein HMGB1, and this interaction is functional to the nuclear/cytoplasmic protein localization. Specifically, silencing of TERF2 alters the redox status of the cells, further exacerbated upon EBSS nutrient starvation, promoting the cytosolic translocation and the autophagic activity of HMGB1. Conversely, overexpression of wild-type TERF2, but not the mutant unable to bind HMGB1, negatively affects the cytosolic translocation of HMGB1, counteracting the stimulatory effect of EBSS starvation. Moreover, genetic depletion of HMGB1 or treatment with inflachromene, a specific inhibitor of its cytosolic translocation, completely abolished the pro-autophagic activity of TERF2 silencing. In conclusion, our data highlighted a novel mechanism through which TERF2 modulates the autophagic process, thus demonstrating the key role of the telomeric protein in regulating a process that is fundamental, under both physiological and pathological conditions, in defining the fate of the cells. Abbreviations: ALs: autolysosomes; ALT: alternative lengthening of telomeres; ATG: autophagy related; ATM: ATM serine/threonine kinase; CQ: Chloroquine; DCFDA: 2',7'-dichlorofluorescein diacetate; DDR: DNA damage response; DHE: dihydroethidium; EBSS: Earle's balanced salt solution; FACS: fluorescence-activated cell sorting; GFP: green fluorescent protein; EGFP: enhanced green fluorescent protein; GSH: reduced glutathione; GSSG: oxidized glutathione; HMGB1: high mobility group box 1; ICM: inflachromene; IF: immunofluorescence; IP: immunoprecipitation; NAC: N-acetyl-L-cysteine; NHEJ: non-homologous end joining; PLA: proximity ligation assay; RFP: red fluorescent protein; ROS: reactive oxygen species; TIF: telomere-induced foci; TERF2/TRF2: telomeric repeat binding factor 2. [ABSTRACT FROM AUTHOR]

Poultry is the most likely source of livestock-associated Extended Spectrum Beta-Lactamase (ESBL) and plasmid-mediated AmpC (pAmpC)-producing E. coli (EC) for humans. We tested the hypothesis that farming methods have an impact on the load of ESBL/pAmpC-EC in the gut of broilers at slaughter. Isolates (n = 156) of antibiotic-free (AF), organic (O), and conventional (C) animals were characterized for antibiotic susceptibility and antibiotic resistance genes. Thirteen isolates were whole-genome sequenced. The average loads of ESBL/pAmpC-EC in cecal contents were 4.17 Log CFU/g for AF; 2.85 Log CFU/g for O; and 3.88 Log CFU/g for C type (p < 0.001). ESBL/pAmpC-EC isolates showed resistance to antibiotic classes historically used in poultry, including penicillins, tetracyclines, quinolones, and sulfonamides. Isolates from O and AF farms harbored a lower proportion of resistance to antibiotics than isolates from C farms. Among the determinants for ESBL/pAmpC, CTX-M-1 prevailed (42.7%), followed by TEM-type (29%) and SHV (19.8%). Avian pathogenic E. coli (APEC), belonging to ST117 and ST349, were identified in the collection. These data confirm the possible role of a broiler as an ESBL/AmpC EC and APEC reservoir for humans. Overall, our study suggests that antibiotic-free and organic production may contribute to a reduced exposure to ESBL/AmpC EC for the consumer. [ABSTRACT FROM AUTHOR]

The 'instructive model' of aberrant DNA methylation in human tumors is based on the observation that CpG islands prone to hypermethylation in cancers are embedded in chromatin enriched in H3K27me3 in human embryonic stem cells (hESC). Recent studies also link methylation of CpG islands to the methylation status of H3K4, where H3K4me3 is inversely correlated with DNA methylation. To provide insight into these conflicting findings, we generated DNA methylation profiles for acute myeloid leukemia samples from patients and leukemic cell lines and integrated them with publicly available ChIp‐seq data, containing H3K4me3 and H3K27me3 CpG island occupation in hESC, or hematopoietic stem or progenitor cells (hHSC/MPP). Hypermethylated CpG islands in AML samples displayed H3K27me3 enrichments in hESC and hHSC/MPP; however, ChIp analysis of specific hypermethylated CpG islands revealed a significant reduction in H3K4me3 signal with a concomitant increase in H3K4me0 levels as opposed to a nonsignificant increase in H3K27me3 marks. The integration of AML DNA methylation profiles with the ChIp‐seq data in hESC and hHSC/MPP also led to the identification of Iroquois homeobox 2 (IRX2) as a previously unknown factor promoting differentiation of leukemic cells. Our results indicate that in contrast to the 'instructive model', H3K4me3 levels are strongly associated with DNA methylation patterns in AML and have a role in the regulation of critical genes, such as the putative tumor suppressor IRX2. [ABSTRACT FROM AUTHOR]

Background: Serum protein electrophoresis (SPE) reference intervals (RIs) have been evaluated in different horses, but no specific values are shown for equine breeds as previously described in other species (dogs, cats), and no studies have been performed on SPE in draft horses. Objectives: This study aimed to determine RIs for SPE in heavy draft horses (Italian Heavy Draft Horse‐IHDH) living in central Italy. A comparison between different physiologic states (pregnancy and no pregnancy) and ages (foals and adults) was executed. Materials and Methods: Blood samples were collected from 215 apparently healthy horses (mares, stallions, and foals). SPE (total proteins, albumin, α1‐, α2‐, β1‐, β2‐, and γ‐fractions, A/G) was evaluated in the Veterinary Teaching Hospital of the University of Perugia. RIs were determined using well‐described, modern analytical and statistical methods. The normality of distributions was assessed using the Anderson‐Darling test. Differences between subgroups were evaluated using the Mann‐Whitney U test. A P <.05 was considered statistically significant for all analyses. Results: Our results showed that IHDHs had increases in TPs and the α2‐, β1‐, β2‐, and γ‐fractions, and decreases in albumin, α1‐globulins, and A/G ratios compared with the data reported in other horses. We also found that foals had significantly higher α1‐globulins and significantly lower albumin concentrations, and A/G ratios compared with those of the adult horses. Conclusions: In the present study, SPE RIs using agarose gels have been determined for the first time in a large number of draft horses (represented by IHDH). The obtained results provide a basis for the further investigation of equine breeds with natural breeding, and the impact of age and physiologic states on SPE. [ABSTRACT FROM AUTHOR]

Cystic echinococcosis (CE) is a complex zoonosis with domestic and sylvatic life-cycles, involving different intermediate and definitive host species. Many previous studies have highlighted the lack of a surveillance system for CE, its persistence in Italy, and endemicity in several Italian regions. Because of the absence of a uniform surveillance program for both humans and animals, disease occurrence is widely underestimated. This study aimed to estimate the prevalence of ovine CE in Italy. Survey data on the prevalence of Echinococcus granulosus complex infections in Italian sheep farms from 2010 to 2015 were obtained in collaboration with Regional Veterinary Epidemiology Observatories (OEVRs). Bayesian analysis was performed to estimate the true CE farm prevalence. The prior true CE prevalence was estimated using data from Sardinia. Second, Bayesian modelling of the observed prevalence in different regions and the true prevalence estimation from the first step were used to ultimately estimate the prevalence of ovine CE in Italy. We obtained survey data from 10 OEVRs, covering 14 Italian regions. We observed that the risk of CE infection decreased over the years, and it was strictly correlated with the density of susceptible species. Using Sardinia as prior distribution, where the disease farm prevalence was approximately 19% (95% CI, 18.82–20.02), we estimated that the highest endemic CE farm prevalence was in Basilicata with a value of 12% (95% BCI: 7.49–18.9%) and in Piemonte 7.64%(95% BCI: 4.12–13.04%). Our results provide spatially relevant data crucial for guiding CE control in Italy. Precise information on disease occurrence location would aid in the identification of priority areas for disease control implementation by the authorities. The current underestimation of CE occurrence should urge the Italian and European governments to become aware of the public health importance of CE and implement targeted interventions for high-risk areas. [ABSTRACT FROM AUTHOR]

Infectious bovine rhinotracheitis (IBR)/infectious pustular vulvovaginitis (IPV) caused by Bovine alphaherpesvirus 1 (BoHV-1) is a significant disease in domestic and wild cattle. In June 2015, the Ministry of Agriculture, Food and Forestry in Italy approved a national surveillance plan to control and eradicate IBR in beef cattle breeds. The objective of this study was to evaluate the results of the first year of the IBR voluntary surveillance plan in Italy. The aim of the plan is to eradicate IBR in all bovines recorded in the National Herd Book for Italian beef cattle breeds over six years. Monetary incentives are used to encourage breeders to achieve the annual seroprevalence ranges stated in the plan. A Ministerial decree states that all bovines in breeding herds and aged older than 12 months should be serologically tested. Serum samples were tested for presence of the antibody to glycoprotein E of BoHV-1 using commercially available enzyme-linked immunosorbent assays. The national herd seroprevalence was 55.49% (95% confidence interval [CI] 52.01–58.92). Of 25,121 bovines tested for antibodies against BoHV-1, 8014 were positive. The seroprevalence in animals from autochthonous Italian cattle breeds was 31.89% (95% CI 31.31–32.47). Seroprevalence was highest in Podolica cattle (55.14%; 95% CI 54.07–56.21), lowest in Maremmana cattle (9.95%; 95% CI 7.99–12.31), and intermediate in Chianina (22.01%; 95% CI 21.03–23.01), Marchigiana (24.85%; 95% CI 23.52–26.23), and Romagnola (15.60%; 95% CI 14.62–16.64) cattle. These seroprevalence rates indicate a need for intervention to decrease the inevitable severe economic losses arising from BoHV-1 infection. Although some regions in Italy have a long history of combatting BoHV-1 infection, only the province of Bolzano has eradicated IBR. [ABSTRACT FROM AUTHOR]

Testudinid herpesviruses (TeHVs) have a worldwide distribution among tortoises. However, information such as risk factors promoting the occurrence or the recrudescence of the associated disease and the mid-term sequelae of an outbreak comprising the extent and dynamic of the viral shedding have been only minimally investigated. Critical management information is also lacking or anecdotal. Furthermore, major aspects of the viral pathogenesis including the likelihood of vertical transmission of the virus are virtually unknown. The present study describes the occurrence and the management of an outbreak of Testudinid herpesvirus genotype 3 (TeHV3) in a large, private collection of chelonians. Clinical, pathological, molecular and serological characterization of the outbreak were carried out. Seventy-five percent of the infected tortoises died. Complementation of molecular and serological testing was a critical point for successful management implementations. A case-control study was performed to analyze possible risk factors associated with the infection. Furthermore, a subgroup of six asymptomatic infected tortoises was monitored for two consecutive seasons after the outbreak: all the infected tortoises were determined to be intermittent shedders, except one, which was a persistent shedder. Post-hibernation was associated with the highest number of shedders. Finally, evidence of the most likely vertical transmission of the virus was obtained for the first time. [ABSTRACT FROM AUTHOR]

Objectives: Carcinomas of the left colon represent a neoplasm of older patients (late onset), but epidemiologic evidence has been showing an increasing incidence in patients 50 years or younger (early onset). In this study, we investigate pathologic and molecular features of early- and late-onset carcinoma of the left colon.Methods: We selected 22 patients 50 years or younger and 21 patients 70 years or older with left-sided colorectal carcinoma (CRC). All samples were evaluated for pathologic features, microsatellite instability, and KRAS and BRAF mutations. Moreover, both groups were analyzed to identify CpG island methylator phenotype features and assessed with restriction landmark genome scanning (RLGS) to unveil differential DNA methylation patterns.Results: Early-onset patients had advanced pathologic stages compared with late-onset patients (P = .0482). All cases showed a microsatellite stable profile and BRAF wild-type sequence. Early-onset patients (43%) more frequently had mutations at KRAS codon 12 compared with late-onset patients (14%) (P =.0413). RLGS showed that patients younger than 50 years who had CRC had a significantly lower percentage of methylated loci than did patients 70 years or older (P = .04124), and differential methylation of several genomic loci was observed in the two groups.Conclusions: Our results suggest that left-sided CRCs may present differential patterns of aberrant DNA methylation when they are separated by age. [ABSTRACT FROM AUTHOR]

Subclinical mastitis (SM) is one of the most important diseases affecting dairy ewes worldwide, with negative impact on the animal health, farm income and public health. Animals with SM often remain untreated because the disease may not be revealed. Increase in somatic cell count (SCC) and positive bacteriology for mastitis pathogens in milk samples are indicative of SM but the evidence of only one of these alterations must suggest an uncertain SM (UM). UM is defined when positive bacteriological examination (Latent-SM) or SCC>500 000 cells/ml (non-specific-SM) are detected in milk. Nevertheless, SCC and bacteriological examination are expensive, time consuming and are not yet in use at the farm level in dairy ewes. Recently, a sensitive acute phase protein, amyloid A, displaying multiple isoforms in plasma and different body fluids including mammary secretion (milk amyloid A-MAA), has been investigated as a marker of mastitis in cows and, in a few studies, in sheep. The aim of this trial was to compare the concentration of MAA of single udder-halves in ewes with healthy udder-halves (HU-control group) and naturally occurring subclinical mastitis, both confirmed (SM group) and uncertain (UM groups: Latent-SM and non-specific-SM), for monitoring udder health. The reliability of a specific ELISA kit for the measurement of MAA was also tested. During a 3-month trial period, 153 udder halves were assigned to the experimental groups based on their health status: 25 with SM, 40 with UM (11 with latent-SM and 29 with non-specific-SM) and 88 HU. SCC and bacteriological analysis were performed to establish the control and subclinical mastitis groups. MAA concentrations in milk samples were measured using a specific commercially milk ELISA kit. The data were submitted to statistical analysis. Significant (P<0·05) differences among the groups SM, non-specific-SM and HU were detected with the SM having the highest level and HU the lowest. MAA concentration is affected by the udder health status and is a useful indicator of subclinical mastitis and increased SCC in sheep. [ABSTRACT FROM AUTHOR]

Simple Summary: Clostridioides difficile is a leading cause of nosocomial and community-acquired diarrhoea in men. The infection most commonly occurs in people who have recently been treated with antibiotics. Indistinguishable C. difficile strains have been isolated from livestock and humans, which has shed light on a possible zoonotic origin of this infection. This study aimed to assess the prevalence and risk factors of C. difficile in calves bred in dairy and beef cattle farms of the Umbria, central Italy. We estimated a 19.8% prevalence of farms positive for C. difficile. The C. difficile isolates from calves were potentially toxigenic and resistant to antibiotics, including lincosamides, quinolones, vancomycin and linezolid. Isolates belonging to ribotype RT-126, which is also commonly reported in humans, showed the highest number of resistance to the antimicrobials tested. Furthermore, we observed an almost sixfold increased risk for C. difficile on farms where penicillins had been prescribed. This, together with the detection of toxigenic and antibiotic-resistant isolates, strongly suggests the need for a reduction of antibiotic use in cattle. The emergence of Clostridioides difficile as the main agent of antibiotic-associated diarrhoea has raised concerns about its potential zoonotic role in different animal species. The use of antimicrobials is a major risk factor for C. difficile infection. Here, we provide data on C. difficile infection in dairy and beef calves in Umbria, a region in central Italy. This cross-sectional study focuses on prevalence, risk factors, ribotypes, toxinotypes and antimicrobial resistance profiles of circulating ribotypes. A prevalence of 19.8% (CI95%, 12–27.6%) positive farms was estimated, and the prescription of penicillins on the farms was associated with C. difficile detection (OR = 5.58). Eleven different ribotypes were found, including the ST11 sublineages RT-126 and -078, which are also commonly reported in humans. Thirteen isolates out of 17 showed resistance to at least one of clindamycin, moxifloxacin, linezolid and vancomycin. Among them, multiple-drug resistance was observed in two isolates, belonging to RT-126. Furthermore, RT-126 isolates were positive for tetracycline resistance determinants, confirming that tetracycline resistance is widespread among ST11 isolates from cattle. The administration of penicillins increased the risk of C. difficile in calves: this, together with the recovery of multi-resistant strains, strongly suggests the need for minimising antibiotic misuse on cattle farms. [ABSTRACT FROM AUTHOR]

Clostridium (C.) perfringens is the causative agent of several diseases and enteric infections in animals and humans. The pathogenicity of the bacterium is largely mediated by the production of a wide range of toxins. Individual C. perfringens strains produce only subsets of this toxin repertoire, which permits the classification in seven toxinotypes (A–G). In addition, a variety of minor toxins further characterizes the single strains. The aim of this work was to evaluate, using Polymerase Chain Reaction (PCR) assays, the diversity of 632 C. perfringens strains isolated in Italy over 15 years. The genotyped strains were analyzed to determine the presence of major and minor toxins (cpe, consensus, and atypical cpb2), their geographical origins, and the source of isolation (animal species or food). Our study shows that toxinotype A had the greatest representation (93%) and correlated mainly with consensus cpb2 in a variety of animal species, as well as with atypical cpb2 in the five food samples. Type D, associated with cpe and atypical cpb2 minor toxins, was identified in 3% of the cases, and type F was identified in 2.5%. Seven type C isolates (1.1%) were detected in cattle, whereas the only type B atypical cpb2 isolated in Italy was detected in a goat, and one type E cpe+atypical cpb2 was detected in a sheep. Type G was not detected. [ABSTRACT FROM AUTHOR]

The overuse of antibiotics in livestock contributes to the antibiotic resistance pandemic. The assessment of the actual antibiotic consumption is crucial in limiting the expansion of the problem effectively. The aim of this study was to provide the first qualitative and quantitative analysis of antimicrobial usage using data from paper-based registers on dairy and beef farms located in the Umbria region, Italy. Antimicrobial therapies of a one-year period were collected from 101 farms with at least 50 cattle each. Defined daily doses (DDDvet) and defined course doses (DCDvet) were calculated per administration route and antimicrobial class. The total courses administered were fewer in beef (330.7 × 10−3 DCDvet/year) than in dairy farms (1034.1 × 10−3 DCDvet/year). The use of the highest priority critically important antimicrobials (HPCIAs) was higher (p = 0.0033) in dairy than in beef herds. In terms of DDDvet, the parenteral fluoroquinolone administration ranked second and fourth on dairy and beef farms, respectively; the consumption of beta-lactams was ten times higher on dairy than on beef farms. Our results confirm that intensive dairy management practices are associated with increased antibiotic consumption and highlight the necessity to strengthen the existing stewardship programs by involving all stakeholders in effective antimicrobial resistance reduction plans. [ABSTRACT FROM AUTHOR]

Most human tumors maintain telomere lengths by telomerase, whereas a portion of them (10–15%) uses a mechanism named alternative lengthening of telomeres (ALT). The telomeric G-quadruplex (G4) ligand RHPS4 is known for its potent antiproliferative effect, as shown in telomerase-positive cancer models. Moreover, RHPS4 is also able to reduce cell proliferation in ALT cells, although the influence of G4 stabilization on the ALT mechanism has so far been poorly investigated. Here we show that sensitivity to RHPS4 is comparable in ALT-positive (U2OS; SAOS-2) and telomerase-positive (HOS) osteosarcoma cell lines, unlinking the telomere maintenance mechanism and RHPS4 responsiveness. To investigate the impact of G4 stabilization on ALT, the cardinal ALT hallmarks were analyzed. A significant induction of telomeric doublets, telomeric clusterized DNA damage, ALT-associated Promyelocytic Leukaemia-bodies (APBs), telomere sister chromatid exchanges (T-SCE) and c-circles was found exclusively in RHPS4-treated ALT cells. We surmise that RHPS4 affects ALT mechanisms through the induction of replicative stress that in turn is converted in DNA damage at telomeres, fueling recombination. In conclusion, our work indicates that RHPS4-induced telomeric DNA damage promotes overactivation of telomeric recombination in ALT cells, opening new questions on the therapeutic employment of G4 ligands in the treatment of ALT positive tumors. [ABSTRACT FROM AUTHOR]

BRCA1/2 are tumor suppressor genes controlling genomic stability also at telomeric and subtelomeric loci. Their mutation confers a predisposition to different human cancers but also sensitivity to antitumor drugs including poly(ADP-ribose) polymerase (PARP) inhibitors and G-quadruplex stabilizers. Here we demonstrate that BRCA2 deletion triggers TERRA hyperexpression and alternative lengthening mechanisms (ALT) in colon cancer cells in presence of telomerase activity. This finding opens the question if cancer patients bearing BRCA2 germline or sporadic mutation are suitable for anti-telomerase therapies, or how ALT activation could influence the short or long-term response to anti-PARP inhibitors or anti-G-quadruplex therapies. [ABSTRACT FROM AUTHOR]

Among the fungi responsible for deep mycosis, the genus Aspergillus plays a predominant role both in human and veterinary medicine. From a "One Health" perspective, infections by Aspergillus spp. often represent a public health problem linked to specific occupational categories that could have a greater risk of inhaling spores and developing any respiratory disease. This preliminary investigation allowed to acquire information about the spread of Aspergillus spp. in avian livestock of the Umbria region (Central Italy), their sensitivity to antifungals, and the presence of mycotoxins in the considered farms. Environmental, feed, animal, and human samples were collected for mycological investigations; chemical analyses were also performed in feed samples. Moreover, prevalence estimated of the fungal isolates were provided for each individual farm sampled. Direct fungal identification was possible in 298 out of the 559 total samples; 162 of the samples were positive for Aspergillus spp. Mycotoxins were detected in 5 out of the 21 feed samples collected. All the aspergilli tested for antifungal susceptibility were resistant to fluconazole. The results obtained show how much the genus Aspergillus is widespread in the investigated farms; therefore, the poultry livestock represents a favorable environment for the maintenance and spread of fungal spores and their potential transmission to animals and humans.