Artificial Neural Networks Link One-Carbon Metabolism to Gene-Promoter Methylation in Alzheimer's Disease

Background: There is increasing interest in DNA methylation studies in Alzheimer's disease (AD), but little is still known concerning the relationship between gene-promoter methylation and circulating biomarkers of one-carbon metabolism in patients. Objective: To detect the connections among circulating folate, homocysteine (hcy) and vitamin B12 levels and promoter methylation levels of PSEN1, BACE1, DNMT1, DNMT3A, DNMT3B, and MTHFR genes in blood DNA. Methods: We applied a data mining system called Auto Contractive Map to an existing database of 100 AD and 100 control individuals. Results: Low vitamin B12 was linked to the AD condition, to low folates, and to high hcy. Low PSEN1 methylation was linked to low folate levels as well as to low promoter methylation of BACE1 and DNMTs genes. Low hcy was linked to controls, to high folates and vitamin B12, as well as to high methylation levels of most of the studied genes. Conclusions: The present pilot study suggests that promoter methylation levels of the studied genes are linked to circulating levels of folates, hcy, and vitamin B12

Inequities in Organ Donation and Transplantation Among Immigrant Populations in Italy: A Narrative Review of Evidence, Gaps in Research and Potential Areas for Intervention

Immigrants from outside Europe have increased over the past two decades, especially in Southern European countries including Italy. This influx coincided with an increased number of immigrants with end-stage organ diseases. In this narrative review, we reviewed evidence of the gaps between native-born and immigrant populations in the Organ Donation and Transplantation (ODT) process in Italy. Consistent with prior studies, despite the availability of a publicly funded health system with universal healthcare coverage, non-European-born individuals living in Italy are less likely to receive living donor kidney transplantation and more likely to have inferior long-term kidney graft function compared with EU-born and Eastern European-born individuals. While these patients are increasingly represented among transplant recipients (especially kidney and liver transplants), refusal rates for organ donation are higher in some ethnic groups compared with native-born and other foreign-born referents, with the potential downstream effects of prolonged waiting times and inferior transplant outcomes. In the process, we identified gaps in relevant research and biases in existing studies. Given the Italian National Transplant Center’s (CNT) commitment to fighting inequities in ODT, we illustrated actions taken by CNT to tackle inequities in ODT among immigrant communities in Italy

A molecular characterization of the invasive fig weevil Aclees taiwanensis in Italy

An economically important pest of Ficus carica L. is causing severe infestations in many fig nurseries and orchards in Italy. Belonging to the genus Aclees spp. (Coleoptera Curculionidae), this Asiatic species was accidentally introduced in Europe about 15 years ago, in a Tuscan nursery. Originally identified as Aclees cribratus Gyllenhal, it has been then reported as Aclees sp.cf. foveatus Voss and, more recently, identified as Aclees taiwanensis Kono. A serious damage to fig plants is caused mainly by the larvae, which drill tunnels into the wood and by adults that feed on buds, leaves and young fruits. The present survey applies molecular genetics techniques to reconstruct the genetic profile of the species. To this purpose, the partial sequence of the 18S rRNA gene and the hypervariable region ITS2 of the ribosomal cistron were used as molecular markers for specimens of A. taiwanensis collected in Italy and Aclees hirayamai Kono from Philippines. The analysis of the partial sequences of the 18S rRNA allowed the distinction of two haplotypes for each insect, except for a sample from Philippines, for which one haplotype does exist. The use of the ITS2 hypervariable region highlighted the existence of only one haplotype in the Italian accessions. Only in the sample collected in Lucca (2LU) two haplotypes were highlighted in ITS2. These results are discussed with the occurrence of A. taiwanensis in Italy

Plasmatic microRNA levels by ddPCR as peripheral biomarkers for IDH-wild type glioblastomas: a pilot study

BACKGROUND: Glioblastoma (GBM) is the most frequent malignant brain tumour in adults with a dismal prognosis and peripheral biomarkers may be useful and effective in managing patients with GBM. The main aim of our study was the use of ddPCR to assess the absolute quantification of the plasmatic levels of three miRNAs as possible GBM-specific biomarkers. We focused on: miR-21-5p, an onco-miR overexpressed in blood, tumour tissue and cell cultures derived from patients affected by GBM, miR-23b-3p and miR-34a-5p, tumour suppressor miRs dysregulated in GMB. MATERIALS AND METHODS: Eight patients presenting with firstly-diagnosed IDH-wild type GBM and 10 age- and gender-matched healthy control donors (hC) have been enrolled in the study. Peripheral blood samples were collected at diagnosis and one month after surgery. Total RNA was isolated from plasma by means of miRNeasy Serum/Plasma Kit (Qiagen), according to the manufacturer’s instructions. Digital droplet PCR (ddPCR) was performed to assess the absolute quantification of each miRNA level according to the QX200 ddPCR protocol. RESULTS: The expression analysis revealed: i) different levels of each miRNA in hC: 98.74 copies/L (±123.60), 2.56 copies/L (±5.57), 0.73 copies/L (±0.85) for miR-21-5p, miR-23b-3p and miR-34a-5p, respectively; ii) a trend of downregulation of miR-21-5p and miR-23b-3p in GMB patients at diagnosis compared to hC; iii) a trend of upregulation of each miRNA in GMB patients one month after surgery compared with the levels measured at diagnosis, in particular 3.02, 6.2 and 1.7 fold increase for miR-21-5p, miR-23b-3p and miR-34a-5p, respectively. CONCLUSIONS: In this pilot study we reported higher amounts of circulating miR-21-5p, miR-23b-3p and miR-34a-5p in plasma of patients affected by IDH-wild type GBM one month after surgery compared to the levels at diagnosis

Determination of plasmatic microRNA levels by ddPCR as peripheral biomarkers for IDH-wild type glioblastomas: a pilot study

BACKGROUND: Glioblastoma (GBM) is the most frequent malignant brain tumour in adults with a dismal prognosis. Peripheral biomarkers may be useful and effective in managing patients affected by GBM. The aim of our study was to analyse the plasmatic levels of three miRNAs as possible GBM-specific biomarkers. We focused on miR-21-5p – an onco-miR overexpressed in blood, tumour tissue and cell cultures derived from patients affected by GBM – miR-23b-3p – overexpressed in GBM, especially under hypoxic conditions – and miR-34a-5p – a tumour suppressor miR downregulated in tumour tissue and serum of patients with GBM. MATERIALS AND METHODS: Eight patients presenting with firstly-diagnosed IDH-wild type GBM and 10 age- and gender-matched healthy volunteers (hV) have been enrolled in the study. Peripheral blood samples were collected at diagnosis and one month after surgery. Total RNA was isolated from plasma by means of miRNeasy Serum/Plasma Kit (Qiagen), according to the manufacturer’s instructions. Digital droplet PCR (ddPCR) was performed for each miRNA according to the QX200 EvaGreen ddPCR protocol. RESULTS: The circulating concentrations of miR-21-5p were in mean 24.00 (28.44) and 72.40 (147.88) copies/L in patients with GBM at diagnosis and one month after surgery (p=0.38), respectively, compared with 98.74 copies/L ( 123.60) quantified in hV (p=0.09; p=0.69). The mean peripheral levels of miR-23b-3p were 0.49 copies/L (0.49) at diagnosis and 3.02 copies/L (6.88) one month after surgery (p=0.32) in patients with GBM, and 2.56 copies/L (5.57) in hV (p=0.31; p=0.88). Analysing plasmatic expression of miR-34a-5p, 1.11 (1.55) and 1.85 copies/L (1.87) were measured on average at diagnosis and one month after surgery in patients with GBM (p=0.41), while 0.73 copies/L (0.85) in hV (p=0.52; p=0.11). CONCLUSIONS: We preliminarily reported higher concentrations of circulating miR-21-5p, miR-23b-3p and miR-34a-5p in plasma of patients affected by IDH-wild type GBM one month after surgery compared to the levels at diagnosis

Semi-analytic galaxy formation in early dark energy cosmologies

We study the impact of early dark energy (EDE) cosmologies on galaxy properties by coupling high-resolution numerical simulations with semi-analytic modeling (SAM) of galaxy formation and evolution. EDE models are characterized by a non-vanishing high-redshift contribution of dark energy, producing an earlier growth of structures and a modification of large-scale structure evolution. They can be viewed as typical representatives of non-standard dark energy models in which only the expansion history is modified, and hence the impact on galaxy formation is indirect. We show that in EDE cosmologies the predicted space density of galaxies is enhanced at all scales with respect to the standard LCDM scenario, and the corresponding cosmic star formation history and stellar mass density is increased at high-redshift. We compare these results with a set of theoretical predictions obtained with alternative SAMs applied to our reference LCDM simulation, yielding a rough measure of the systematic uncertainty of the models. We find that the modifications in galaxy properties induced by EDE cosmologies are of the same order of magnitude as intra-SAM variations for a standard LCDM realization (unless rather extreme EDE models are considered), suggesting that is difficult to use such predictions alone to disentangle between different cosmological scenarios. However, when independent information on the underlying properties of host dark matter haloes is included, the SAM predictions on galaxy bias may provide important clues on the expansion history and the equation-of-state evolution.Comment: 7 pages; 4 figures, MNRAS submitte

Gut to brain interaction in Autism Spectrum Disorders: A randomized controlled trial on the role of probiotics on clinical, biochemical and neurophysiological parameters

Background: A high prevalence of a variety of gastrointestinal (GI) symptoms is frequently reported in patients with Autism Spectrum Disorders (ASD). The GI disturbances in ASD might be linked to gut dysbiosis representing the observable phenotype of a "gut-brain axis" disruption. The exploitation of strategies which can restore normal gut microbiota and reduce the gut production and absorption of toxins, such as probiotics addition/supplementation in a diet, may represent a non-pharmacological option in the treatment of GI disturbances in ASD. The aim of this randomized controlled trial is to determine the effects of supplementation with a probiotic mixture (Vivomixx®) in ASD children not only on specific GI symptoms, but also on the core deficits of the disorder, on cognitive and language development, and on brain function and connectivity. An ancillary aim is to evaluate possible effects of probiotic supplementation on urinary concentrations of phthalates (chemical pollutants) which have been previously linked to ASD. Methods: A group of 100 preschoolers with ASD will be classified as belonging to a GI group or to a Non-GI (NGI) group on the basis of a symptom severity index specific to GI disorders. In order to obtain four arms, subjects belonging to the two groups (GI and NGI) will be blind randomized 1:1 to regular diet with probiotics or with placebo for 6 months. All participants will be assessed at baseline, after three months and after six months from baseline in order to evaluate the possible changes in: (1) GI symptoms; (2) autism symptoms severity; (3) affective and behavioral comorbid symptoms; (4) plasmatic, urinary and fecal biomarkers related to abnormal intestinal function; (5) neurophysiological patterns. Discussion: The effects of treatments with probiotics on children with ASD need to be evaluated through rigorous controlled trials. Examining the impact of probiotics not only on clinical but also on neurophysiological patterns, the current trial sets out to provide new insights into the gut-brain connection in ASD patients. Moreover, results could add information to the relationship between phthalates levels, clinical features and neurophysiological patterns in ASD. Trial registration: ClinicalTrials.gov Identifier: NCT02708901. Retrospectively registered: March 4, 2016

Accounting, Transparency and Governance: the Heritage Assets Problem

Purpose – This paper aims at offering a contribution which addresses one particular issue – heritage assets – as an exemplar of the challenges facing accounting practices in achieving transparency in government and public services. Design/methodology/approach – After having identified three levels of transparency, a documentary analysis is used as the primary research method. Findings – The investigation carried out reveals that the first level, or minimal level, of transparency is unlikely to be achieved for public organizations with heritage assets, mainly due to deep seated, pernicious problems of asset recognition and valuation. Originality/value – This paper contributes to the debate on what constitutes “good public governance” by examining whether accounting can foster or enhance “good governance” through the lens of transparency

Prenatal Environmental Stressors and DNA Methylation Levels in Placenta and Peripheral Tissues of Mothers and Neonates Evaluated by Applying Artificial Neural Networks

Exposure to environmental stressors during pregnancy plays an important role in influencing subsequent susceptibility to certain chronic diseases through the modulation of epigenetic mechanisms, including DNA methylation. Our aim was to explore the connections between environmental exposures during gestation with DNA methylation of placental cells, maternal and neonatal buccal cells by applying artificial neural networks (ANNs). A total of 28 mother-infant pairs were enrolled. Data on gestational exposure to adverse environmental factors and on mother health status were collected through the administration of a questionnaire. DNA methylation analyses at both gene-specific and global level were analyzed in placentas, maternal and neonatal buccal cells. In the placenta, the concentrations of various metals and dioxins were also analyzed. Analysis of ANNs revealed that suboptimal birth weight is associated with placental H19 methylation, maternal stress during pregnancy with methylation levels of NR3C1 and BDNF in placentas and mother's buccal DNA, respectively, and exposure to air pollutants with maternal MGMT methylation. Associations were also observed between placental concentrations of lead, chromium, cadmium and mercury with methylation levels of OXTR in placentas, HSD11B2 in maternal buccal cells and placentas, MECP2 in neonatal buccal cells, and MTHFR in maternal buccal cells. Furthermore, dioxin concentrations were associated with placental RELN, neonatal HSD11B2 and maternal H19 gene methylation levels. Current results suggest that exposure of pregnant women to environmental stressors during pregnancy could induce aberrant methylation levels in genes linked to several pathways important for embryogenesis in both the placenta, potentially affecting foetal development, and in the peripheral tissues of mothers and infants, potentially providing peripheral biomarkers of environmental exposure