Static hot air and infrared rays roasting are efficient methods for aflatoxin decontamination on hazelnuts

Aflatoxins are a group of secondary metabolites produced by members of Aspergillus Section Flavi that are dangerous to humans and animals. Nuts can be potentially contaminated with aflatoxins, often over the legal threshold. Food processes, including roasting, may have different effects on mycotoxins, and high temperatures have proven to be very effective in the reduction of mycotoxins. In this work, two different roasting methods—traditional static hot air roasting and infra-red rays roasting—were applied and compared for the detoxification of hazelnuts from Italy and Turkey. At the temperature of 140 °C for 40 min of exposure, detoxification was effective for both roasting techniques. Residual aflatoxins after infra-red rays treatments were lower compared to static hot air roasting. On Italian hazelnuts, residual aflatoxins were lower than 5%, while for Turkish hazelnuts they were lower than 15% after 40 min of exposure to an infra-red rays roaster. After roasting, the perisperm was detached from the nuts and analyzed for aflatoxin contents. Residual aflatoxins in the perisperm ranged from 80% up to 100%. After roasting, the lipid profile and the nutritional quality of hazelnuts were not affected. Fatty acid methyl esters analyses showed a similar composition for Italian and Turkish hazelnuts

Atrial and ventricular function in thalassemic patients with supra-ventricular arrhythmias

The aims of this study were to evaluate through Color Doppler Myocardial Imaging (CDMI) echocardiography if atrial or ventricular myocardial alterations could be detectable in patients with thalassemia major (THAL) and if these alterations could be considered as predictive elements for supra-ventricular arrhythmic events. Twenty-three patients with THAL underwent clinical and electrocardiographic evaluation; patients were grouped in THAL1 (9 with supra-ventricular arrhythmias) and THAL2 (14 without arrhythmias); 12 healthy subjects were considered as control group (C). We examined through conventional 2D Color Doppler echocardiography some morphological and functional parameters regarding left ventricular (LV) systolic and diastolic function, and through CDMI the velocities at mitral annulus level, the regional LV and left atrial (LA) strain and strain rate. All THAL patients had LV dimension (p<0.05), LA area (p<0.01) and E/Em ratio (p<0.001) to be significantly higher than controls. The mitral annulus longitudinal velocities were significantly lower in THAL1 than in THAL2 (p<0.001); the E/Em ratio was higher in THAL1 than THAL2 (p<0.001). The THAL1 showed a lower systolic strain rate of atrial wall than THAL2 and C (p<0.05). The multiple regression highlighted a significantly inverse correlation among E/Em and atrial strain (p<0.02). CDMI showed both THAL subgroups had subtle systolic and diastolic left ventricular myocardial alterations, which could represent the onset of developing “iron cardiomyopathy” and are related to supra-ventricular arrhythmia. Monitoring these parameters in the THAL patients could contribute to decisions about follow-up and therapy

Targeted and untargeted quantification of quorum sensing signalling molecules in bacterial cultures and biological samples via HPLC-TQ MS techniques

Quorum sensing (QS) is the ability of some bacteria to detect and to respond to population density through signalling molecules. QS molecules are involved in motility and cell aggregation mechanisms in diseases such as sepsis. Few biomarkers are currently available to diagnose sepsis, especially in high-risk conditions. The aim of this study was the development of new analytical methods based on liquid chromatography-mass spectrometry for the detection and quantification of QS signalling molecules, including N-acyl homoserine lactones (AHL) and hydroxyquinolones (HQ), in biofluids. Biological samples used in the study were Pseudomonas aeruginosa bacterial cultures and plasma from patients with sepsis. We developed two MS analytical methods, based on neutral loss (NL) and product ion (PI) experiments, to identify and characterize unknown AHL and HQ molecules. We then established a multiple-reaction-monitoring (MRM) method to quantify specific QS compounds. We validated the HPLC-MS-based approaches (MRM-NL-PI), and data were in accord with the validation guidelines. With the NL and PI MS-based methods, we identified and characterized 3 and 13 unknown AHL and HQ compounds, respectively, in biological samples. One of the newly found AHL molecules was C12-AHL, first quantified in Pseudomonas aeruginosa bacterial cultures. The MRM quantitation of analytes in plasma from patients with sepsis confirmed the analytical ability of MRM for the quantification of virulence factors during sepsis

Ethnic background and risk perception in construction workers: development and validation of an exploratory tool

Among occupational sectors, construction is still one of the branches with the highest reported numbers of work-related injuries and diseases, which can even lead to death and in many cases induce permanent health consequences. The vast majority of these occupational injuries and diseases are preventable; accordingly, an improvement in preventive strategies, also through a better knowledge of the main factors involved in these events, is one of the most important objectives for better occupational health and safety in the construction sector. Considering the individual factors associated with a higher risk of work-related adverse health effects in workers, an inadequate perception of occupational risks is among the most relevant issues. Risk perception can vary according to different cultural backgrounds, highly influenced by ethnicity, and it affects the relations between workers in the work environment, and the way by with they undergo the specific occupational tasks and manage risky situations frequently occurring on construction sites. Accordingly, the aim of the authors was to develop a new tool for the assessment of risk perception in construction workers with different ethnic backgrounds

Performance comparison of two commercial human whole-exome capture systems on formalin-fixed paraffin-embedded lung adenocarcinoma samples

Background: Next Generation Sequencing (NGS) has become a valuable tool for molecular landscape characterization of cancer genomes, leading to a better understanding of tumor onset and progression, and opening new avenues in translational oncology. Formalin-fixed paraffin-embedded (FFPE) tissue is the method of choice for storage of clinical samples, however low quality of FFPE genomic DNA (gDNA) can limit its use for downstream applications. Methods: To investigate the FFPE specimen suitability for NGS analysis and to establish the performance of two solution-based exome capture technologies, we compared the whole-exome sequencing (WES) data of gDNA extracted from 5 fresh frozen (FF) and 5 matched FFPE lung adenocarcinoma tissues using: SeqCap EZ Human Exome v.3.0 (Roche NimbleGen) and SureSelect XT Human All Exon v.5 (Agilent Technologies). Results: Sequencing metrics on Illumina HiSeq were optimal for both exome systems and comparable among FFPE and FF samples, with a slight increase of PCR duplicates in FFPE, mainly in Roche NimbleGen libraries. Comparison of single nucleotide variants (SNVs) between FFPE-FF pairs reached overlapping values &gt;90 % in both systems. Both WES showed high concordance with target re-sequencing data by Ion PGM\u2122 in 22 lung-cancer genes, regardless the source of samples. Exon coverage of 623 cancer-related genes revealed high coverage efficiency of both kits, proposing WES as a valid alternative to target re-sequencing. Conclusions: High-quality and reliable data can be successfully obtained from WES of FFPE samples starting from a relatively low amount of input gDNA, suggesting the inclusion of NGS-based tests into clinical contest. In conclusion, our analysis suggests that the WES approach could be extended to a translational research context as well as to the clinic (e.g. to study rare malignancies), where the simultaneous analysis of the whole coding region of the genome may help in the detection of cancer-linked variants

Heterocycle-containing tranylcypromine derivatives endowed with high anti-LSD1 activity

As regioisomers/bioisosteres of 1a, a 4-phenylbenzamide tranylcypromine (TCP) derivative previously disclosed by us, we report here the synthesis and biological evaluation of some (hetero)arylbenzoylamino TCP derivatives 1b-6, in which the 4-phenyl moiety of 1a was shifted at the benzamide C3 position or replaced by 2- or 3-furyl, 2- or 3-thienyl, or 4-pyridyl group, all at the benzamide C4 or C3 position. In anti-LSD1-CoREST assay, all the meta derivatives were more effective than the para analogues, with the meta thienyl analogs 4b and 5b being the most potent (IC50 values ¼ 0.015 and 0.005 lM) and the most selective over MAO-B (selectivity indexes: 24.4 and 164). When tested in U937 AML and prostate cancer LNCaP cells, selected compounds 1a,b, 2b, 3b, 4b, and 5a,b displayed cell growth arrest mainly in LNCaP cells. Western blot analyses showed increased levels of H3K4me2 and/or H3K9me2 confirming the involvement of LSD1 inhibition in these assays

Non-neural phenotype of spinal and bulbar muscular atrophy: Results from a large cohort of Italian patients

Objective: To carry out a deep characterisation of the main androgen-responsive tissues involved in spinal and bulbar muscular atrophy (SBMA). Methods: 73 consecutive Italian patients underwent a full clinical protocol including biochemical and hormonal analyses, genitourinary examination, bone metabolism and densitometry, cardiological evaluation and muscle pathology. Results: Creatine kinase levels were slightly to markedly elevated in almost all cases (68 of the 73; 94%). 30 (41%) patients had fasting glucose above the reference limit, and many patients had total cholesterol (40; 54.7%), low-density lipoproteins cholesterol (29; 39.7%) and triglyceride (35; 48%) levels above the recommended values. Although testosterone, luteinising hormone and follicle-stimulating hormone values were generally normal, in one-third of cases we calculated an increased Androgen Sensitivity Index reflecting the presence of androgen resistance in these patients. According to the International Prostate Symptom Score (IPSS), 7/70 (10%) patients reported severe lower urinal tract symptoms (IPSS score >19), and 21/73 (30%) patients were moderately symptomatic (IPSS score from 8 to 19). In addition, 3 patients were carriers of an indwelling bladder catheter. Videourodynamic evaluation indicated that 4 of the 7 patients reporting severe urinary symptoms had an overt prostate-unrelated bladder outlet obstruction. Dual-energy X-ray absorptiometry scan data were consistent with low bone mass in 25/61 (41%) patients. Low bone mass was more frequent at the femoral than at the lumbar level. Skeletal muscle biopsy was carried out in 20 patients and myogenic changes in addition to the neurogenic atrophy were mostly observed. Conclusions: Our study provides evidence of a wide non-neural clinical phenotype in SBMA, suggesting the need for comprehensive multidisciplinary protocols for these patients. \ua9 2016 Published by the BMJ Publishing Group Limited

Multiple unbiased approaches identify oxidosqualene cyclase as the molecular target of a promising anti-leishmanial

Phenotypic screening identified a benzothiophene compound with activity against Leishmania donovani, the causative agent of visceral leishmaniasis. Using multiple orthogonal approaches, oxidosqualene cyclase (OSC), a key enzyme of sterol biosynthesis, was identified as the target of this racemic compound and its enantiomers. Whole genome sequencing and screening of a genome-wide overexpression library confirmed that OSC gene amplification is associated with resistance to compound 1. Introduction of an ectopic copy of the OSC gene into wild-type cells reduced susceptibility to these compounds confirming the role of this enzyme in resistance. Biochemical analyses demonstrated the accumulation of the substrate of OSC and depletion of its product in compound (S)-1-treated-promastigotes and cell-free membrane preparations, respectively. Thermal proteome profiling confirmed that compound (S)-1 binds directly to OSC. Finally, modeling and docking studies identified key interactions between compound (S)-1 and the LdOSC active site. Strategies to improve the potency for this promising anti-leishmanial are proposed

Integrated Somatic and Germline Whole-Exome Sequencing Analysis in Women with Lung Cancer after a Previous Breast Cancer

open20Women treated for breast cancer (BC) are at risk of developing secondary tumors, such as lung cancer (LC). Since rare germline variants have been linked to multiple cancer development, we hypothesized that BC survivors might be prone to develop LC as a result of harboring rare variants. Sixty patients with LC with previous BC (the study population; SP) and 53 women with either BC or LC and no secondary cancer (control population; CP) were enrolled. Whole exome sequencing was performed in both tumors and unaffected tissues from 28/60 SP patients, and in germline DNA from 32/53 CP. Candidate genes were validated in the remaining individuals from both populations. We found two main mutational signature profiles: S1 (C&gt;T) in all BCs and 16/28 LCs, and S2 (C&gt;A) which is strongly associated with smoking, in 12/28 LCs. The burden test over rare germline variants in S1-LC vs CP identified 248 genes. Validation confirmed GSN as significantly associated with LC in never-smokers. In conclusion, our data suggest two signatures involved in LC onset in women with previous BC. One of these signatures is linked to smoking. Conversely, regardless of smoking habit, in a subgroup of BC survivors genetic susceptibility may contribute to LC risk.openCoco, Simona; Bonfiglio, Silvia; Cittaro, Davide; Vanni, Irene; Mora, Marco; Genova, Carlo; Dal Bello, Maria Giovanna; Boccardo, Simona; Alama, Angela; Rijavec, Erika; Sini, Claudio; Rossella, Valeria; Barletta, Giulia; Biello, Federica; Truini, Anna; Bruzzo, Cristina; Gallo, Maurizio; Lazarevic, Dejan; Ballestrero, Alberto; Grossi, FrancescoCoco, Simona; Bonfiglio, Silvia; Cittaro, Davide; Vanni, Irene; Mora, Marco; Genova, Carlo; Dal Bello, Maria Giovanna; Boccardo, Simona; Alama, Angela; Rijavec, Erika; Sini, Claudio; Rossella, Valeria; Barletta, Giulia; Biello, Federica; Truini, Anna; Bruzzo, Cristina; Gallo, Maurizio; Lazarevic, Dejan; Ballestrero, Alberto; Grossi, Francesc