A Novel Mix of Polyphenols and Micronutrients Reduces Adipogenesis and Promotes White Adipose Tissue Browning via UCP1 Expression and AMPK Activation

Background: Obesity is a pandemic disease characterized by excessive severe body comorbidities. Reduction in fat accumulation represents a mechanism of prevention, and the replacement of white adipose tissue (WAT) with brown adipose tissue (BAT) has been proposed as one promising strategy against obesity. In the present study, we sought to investigate the ability of a natural mixture of polyphenols and micronutrients (A5(+)) to counteract white adipogenesis by promoting WAT browning. Methods: For this study, we employed a murine 3T3-L1 fibroblast cell line treated with A5(+), or DMSO as control, during the differentiation in mature adipocytes for 10 days. Cell cycle analysis was performed using propidium iodide staining and cytofluorimetric analysis. Intracellular lipid contents were detected by Oil Red O staining. Inflammation Array, along with qRT-PCR and Western Blot analyses, served to measure the expression of the analyzed markers, such as pro-inflammatory cytokines. Results: A5(+) administration significantly reduced lipids' accumulation in adipocytes when compared to control cells (p < 0.005). Similarly, A5(+) inhibited cellular proliferation during the mitotic clonal expansion (MCE), the most relevant stage in adipocytes differentiation (p < 0.0001). We also found that A5(+) significantly reduced the release of pro-inflammatory cytokines, such as IL-6 and Leptin (p < 0.005), and promoted fat browning and fatty acid oxidation through increasing expression levels of genes related to BAT, such as UCP1 (p < 0.05). This thermogenic process is mediated via AMPK-ATGL pathway activation. Conclusion: Overall, these results demonstrated that the synergistic effect of compounds contained in A5(+) may be able to counteract adipogenesis and then obesity by inducing fat browning

Il naturalismo oggi. Abbozzo di una mappa e alcune riflessioni

This paper tries to draw a map of the various versions of naturalism to which the current philosophical debate aims – from the most radical, or ‘hard’ ones, to the mild-est, or liberal ones – and of the different projects of naturalization that are associated to them. In particular, in the first paragraphs, the present article will consider Timothy Williamson’s and Penelope Maddy’s attempts to inherit the demands of naturalism with-out declaring to be a naturalist (Williamson), or without making naturalism an empty slogan or a kind of masked first philosophy (Maddy). In the second part, the connec-tions between epistemological naturalism and ontological or metaphysical naturalism will be analysed. The questions will be: (1) is it possible to be naturalist with regard to epistemology without being naturalist with regard to ontology?; (2) is it possible to be ontologically naturalist without being epistemologically naturalist

Psychosocial Predictors of Colorectal Cancer Screening Intention: An Experiment on the Invitation Letter

Background: In Italy, attendance rates for colorectal cancer (CRC) screening are suboptimal. The present work analysed cognitive and emotional predictors of CRC screening intention and tested an intervention on a real invitation letter to improve CRC screening intention, both directly and in interaction with the predictors of our model. Methods: Our model included variables from the theory of planned behaviour and the emotional barriers to bowel screening scale. We applied six changes to an invitation letter used in Italy to avoid the repetition of words like ‘faeces’, ‘blood’, or ‘occult’ and reduce the prompting of disgust. The 228 participants were randomly assigned to a between-participants design (original letter vs. manipulated letter). Results: Disgust hindered CRC screening intention, while embarrassment, fear, and subjective norms (i.e., perception of the social pressures to attend CRC screening) were not associated with intention to screen. More positive attitudes towards CRC screening were associated with a higher intention to screen. The positive association between perceived behavioural control and CRC screening intention was stronger for participants who read the letter with fewer (vs. more) references to bodily waste. Letter manipulation did not affect intention to screen. Conclusions: The disgust associated with faecal matter is a critical factor in determining CRC screening attendance, and it should be acknowledged as such in public policies. Until new screening tests avoiding the activation of this emotional reaction are concretely available, public campaigns should improve CRC screening participation by boosting both positive attitudes towards screening and patients’ perceived behavioural contro

Simultaneous determination of water-soluble organic tracers in atmospheric aereosol using silyl-derivatization and GC-MS analysis

A GC-MS analysis method has been developed for the simultaneous determination of water-soluble organic tracers in atmospheric aereosol. The method, based on silyl-derivatization, has been successfully applied in PM monitoring campaigns to evaluate air quality in Northen Italy regions

Immune Monitoring Using QuantiFERON\uae-CMV Assay in Congenital Cytomegalovirus Infection: Correlation With Clinical Presentation and CMV DNA load.

Background: CMV-specific CD8+ T-cell responses can be detected early in fetal life, but their role in the manifestations of congenital CMV (cCMV) infection remains largely unknown. Methods: CMV-specific CD8+ T-cell responses were assessed in neonates with cCMV using QuantiFERON\uae-CMV assay, within day 14th of life (T0) and during the second month of life (T1). Detection and quantification of CMV DNA in whole blood and urine samples were performed at both time points. QuantiFERON\uae-CMV results were evaluated in relation to timing of maternal infection, clinical manifestations of cCMV and CMV DNA levels. Results: Thirty neonates were enrolled (10/30 [33%] symptomatic; 20/30 [67%] asymptomatic). At T0 16/30 (53%) subjects had a reactive QuantiFERON\uae-CMV result and 16/16 (100%) were asymptomatic, while 14/30 (47%) had a non-reactive or indeterminate QuantiFERON\uae-CMV result and 4/14 (29%) were asymptomatic. At T1, 17/29 (59%) subjects had a reactive QuantiFERON\uae-CMV result and 17/17 (100%) were asymptomatic, while 12/29 (41%) had a non-reactive or indeterminate result and 3/12 (25%) were asymptomatic. At both T0 and T1 reactive QuantiFERON\uae-CMV results correlated with lack of symptoms (P=0.0001). At T1 median CMV DNAemia was lower in subjects with reactive QuantiFERON\uae-CMV results as compared with subjects with non-reactive or indeterminate results (1.82 log IU/mL [1.82-2.89] versus 2.55 log IU/mL [1.82-4.42], P=0.009). No correlation was found between QuantiFERON\uae-CMV results and gestational age at maternal infection nor with urine CMV DNA levels. Conclusions: A detectable CMV-specific CD8+ T-cell response, evaluated using the QuantiFERON\uae-CMV assay, correlates with the lack of CMV-related symptoms and the control of CMV DNAemi

First independent replication of the involvement of LARS2 in Perrault syndrome by whole-exome sequencing of an Italian family

Perrault syndrome (MIM #233400) is a rare autosomal recessive disorder characterized by ovarian dysgenesis and primary ovarian insufficiency in females, and progressive hearing loss in both genders. Recently, mutations in five genes (HSD17B4, HARS2, CLPP, LARS2 and C10ORF2) were found to be responsible for Perrault syndrome, although they do not account for all cases of this genetically heterogeneous condition. We used whole-exome sequencing to identify pathogenic variants responsible for Perrault syndrome in an Italian pedigree with two affected siblings. Both patients were compound heterozygous for two novel missense variants within the mitochondrial leucyl-tRNA synthetase (LARS2): NM_015340.3:c.899C4T(p.Thr300Met) and c.1912G4A(p.Glu638Lys). Both variants cosegregated with the phenotype in the family. p.Thr300 and p.Glu638 are evolutionarily conserved residues, and are located, respectively, within the editing domain and immediately before the catalytically important KMSKS motif. Homology modeling using as template the E. coli leucyl-tRNA synthetase provided further insights on the possible pathogenic effects of the identified variants. This represents the first independent replication of the involvement of LARS2 mutations in Perrault syndrome, contributing valuable information for the further understanding of this disease