The Italian registry for patients with Prader-Willi syndrome

Background: Prader-Willi syndrome (PWS) is a rare and complex genetic disease, with numerous implications on metabolic, endocrine, neuropsychomotor systems, and with behavioural and intellectual disorders. Rare disease patient registries are important scientific tools (1) to collect clinical and epidemiologic data, (2) to assess the clinical management including the diagnostic delay, (3) to improve patients' care and (4) to foster research to identify new therapeutic solutions. The European Union has recommended the implementation and use of registries and databases. The main aims of this paper are to describe the process of setting up the Italian PWS register, and to illustrate our preliminary results. Materials and methods: The Italian PWS registry was established in 2019 with the aims (1) to describe the natural history of the disease, (2) to determine clinical effectiveness of health care services, (3) to measure and monitor quality of care of patients. Information from six different variables are included and collected into this registry: demographics, diagnosis and genetics, patient status, therapy, quality of life and mortality. Results: A total of 165 patients (50.3% female vs 49.7% male) were included into Italian PWS registry in 2019-2020 period. Average age at genetic diagnosis was 4.6 years; 45.4% of patients was less than 17 years old aged, while the 54.6% was in adult age (> 18 years old). Sixty-one percent of subjects had interstitial deletion of the proximal long arm of paternal chromosome 15, while 36.4% had uniparental maternal disomy for chromosome 15. Three patients presented an imprinting centre defect and one had a de novo translocation involving chromosome 15. A positive methylation test was demonstrated in the remaining 11 individuals but the underlying genetic defect was not identified. Compulsive food-seeking and hyperphagia was present in 63.6% of patients (prevalently in adults); 54.5% of patients developed morbid obesity. Altered glucose metabolism was present in 33.3% of patients. Central hypothyroidism was reported in 20% of patients; 94.7% of children and adolescents and 13.3% of adult patients is undergoing GH treatment. Conclusions: The analyses of these six variables allowed to highlight important clinical aspects and natural history of PWS useful to inform future actions to be taken by national health care services and health professionals

Phenotyping, Genotyping, and Selections within Italian Local Landraces of Romanesco Globe Artichoke

Ten Italian globe artichoke clones belonging to the Romanesco typology were characterized in the western coastal area of Italy (Cerveteri, Rome), using a combination of morphological (UPOV descriptors), biochemical (HPLC analysis), and molecular (AFLP, ISSR, and SSR markers) traits. Significant differences among clones were found for many of the quantitative and qualitative morphological traits. Multivariate analyses (Principal Component Analysis) showed that, of the 47 morphological descriptors assessed, four (i.e., plant height, central flower-head weight, earliness, and total flower-head weight) presented a clear grouping of the clones. Biochemical analyses showed that the clones significantly differed in the polyphenolic profiles of the flower-head, with the suggestion that some of these, such as S2, S3, S5, and S18, are more suitable for the fresh market. The clones, clustered by a UPGMA dendrogram based on 393 polymorphic AFLP and ISSR loci, showed that the clones were genetically separated from each other. This highlights the importance of characterizing, evaluating, and conserving autochthonous germplasm for future plant breeding activities. Overall, these studies resulted in the identification of two new clones, selected on the basis of flower-head morphology and earliness. These clones, named Michelangelo and Raffaello, are registered on the Italian National Register of Varieties (DM n. 6135, 3/29/2013 G.U. 91, 18 April 2013)

Agrobacterium rhizogenes rolA gene promotes tolerance to Fusarium oxysporum.f. sp. lycopersici in transgenic tomato plants (Solanum lycopersicum L.)

In order to assess the role of Agrobacterium rhizogenes rol genes on the defence response of plants to pathogens, tomato plants (Solanum lycopersicum L.) weretransformed with the rolA gene. Consistently with previous descriptions of rolA-induced phenotype, insertion of this gene had a pleiotropic effect determining highly aberrant plants, with wrinkled, intensely green leaves, thick stems and small fruits often lacking seeds. Infection of transgenic plants with the phytopathogenic fungus Fusarium oxysporum f. sp. lycopersici showed the acquirement of resistance/tolerance to the pathogen as evaluated both on the primary transformants by electrolyte leakage and on the transgenic progenies by direct infection. Determination of the endogenous levels of indole-3-acetic acid (IAA) and abscisic acid (ABA) showed a 30–35 % decrease of both phytohormones in rolA plants harbouring three copies of the transgene compared to the controls, while a significantly lower level of ABA was observed in plants with one copy of the transgene. This is the first demonstration of the direct involvement of rolA gene in plant pathogen tolerance acquisition

The Role of <i>TP53</i> Mutations in <i>EGFR</i>-Mutated Non-Small-Cell Lung Cancer: Clinical Significance and Implications for Therapy

Non-Small-Cell Lung Cancer (NSCLC) is the primary cause of cancer-related death worldwide. Oncogene-addicted patients usually benefit from targeted therapy, but primary and acquired resistance mechanisms inevitably occur. Tumor protein 53 (TP53) gene is the most frequently mutated gene in cancer, including NSCLC. TP53 mutations are able to induce carcinogenesis, tumor development and resistance to therapy, influencing patient prognosis and responsiveness to therapy. TP53 mutants present in different forms, suggesting that different gene alterations confer specific acquired protein functions. In recent years, many associations between different TP53 mutations and responses to Epidermal Growth Factor Receptor (EGFR) targeted therapy in NSCLC patients have been found. In this review, we discuss the current landscape concerning the role of TP53 mutants to guide primary and acquired resistance to Tyrosine-Kinase Inhibitors (TKIs) EGFR-directed, investigating the possible mechanisms of TP53 mutants within the cellular compartments. We also discuss the role of the TP53 mutations in predicting the response to targeted therapy with EGFR-TKIs, as a possible biomarker to guide patient stratification for treatment

Assessing the Impact of Water Salinization Stress on Biomass Yield of Cardoon Bio-Energetic Crops through Remote Sensing Techniques

Various species of cultivated thistle, such as Cynara cardunculus L. (cardoon), exhibit interesting features for industrial biomass production as bioenergy crops, given also their advantageous adaptation capacities to typical Mediterranean climate trends, with noticeable resilience to drought and salinization stresses. The in situ hyperspectral reflectance responses of three genotypes of cardoon plants, irrigated with water at different salinity levels, have been tested for assessing the effects on their biophysical parameters, aiming at improving the biomass yield for bioenergy production, minimizing at same time the environmental impacts and the exploitation of soils and waters resources. The leaf and canopy reflectance hyperspectral signatures, acquired at three different growth stages with biometric measurements, were statistically analyzed (ANOVA, Tukey&rsquo;s test, graphs), as noise-resilient spectral indices, sensible to different plant features of interest. Their broadband versions, based on the Landsat 8 OLI and Sentinel 2 MSI satellite sensors, were also evaluated in perspective of operative and extensive remote crop monitoring from space. The results highlighted significant differences in some spectral index responses, related to different cardoon genotypes and water salt concentration. The biometric data supported by red-edge indices modelling evidenced the impact of the highest salt water concentration (200 mM/L) on the plant growth and yield

Wide Next-Generation Sequencing Characterization of Young Adults Non-Small-Cell Lung Cancer Patients

Simple Summary Molecular characterization of advanced non-small-cell lung cancer (NSCLC) is mandatory before any treatment decision making. Next-generation sequencing (NGS) approaches represent the best strategy in this context. In our study, we analyzed a case series of young (under 65 years old) NSCLC patients with a wide NGS gene panel assay. The most frequent altered genes were TP53 (64.55%), followed by KRAS (44.1%), STK11 (26.9%), CDKN2A (21.5%), CDKN2B (14.0%), EGFR (16.1%), and RB1 (10.8%). Tumor mutational burden (TMB) was also evaluated considering different cut-offs, and we found a significant association between TMB and STK11 and KRAS mutations. Conversely, EGFR and EML4-ALK alterations were more frequently found in tumors with low TMB. We compared results obtained from this approach with those obtained from a single or few genes approach, observing perfect concordance of the results. Molecular characterization of advanced non-small-cell lung cancer (NSCLC) is mandatory before any treatment decision making. Next-generation sequencing (NGS) approaches represent the best strategy in this context. The turnaround time for NGS methodologies and the related costs are becoming more and more adaptable for their use in clinical practice. In our study, we analyzed a case series of young (under 65 years old) NSCLC patients with a wide NGS gene panel assay. The most frequent altered genes were TP53 (64.55%), followed by KRAS (44.1%), STK11 (26.9%), CDKN2A (21.5%), CDKN2B (14.0%), EGFR (16.1%), and RB1 (10.8%). Tumor mutational burden (TMB) was also evaluated. Considering the cut-off of 10 mut/Mb, 62 (68.9%) patients showed a TMB = 10 mut/Mb. STK11 and KRAS mutations were significantly associated with a higher TMB (p = 0.019 and p = 0.004, respectively). Conversely, EGFR and EML4-ALK alterations were more frequently found in tumors with low TMB (p = 0.019 and p < 0.001, respectively). We compared results obtained from this approach with those obtained from a single or few genes approach, observing perfect concordance of the results

Wide Next-Generation Sequencing Characterization of Young Adults Non-Small-Cell Lung Cancer Patients

Molecular characterization of advanced non-small-cell lung cancer (NSCLC) is mandatory before any treatment decision making. Next-generation sequencing (NGS) approaches represent the best strategy in this context. The turnaround time for NGS methodologies and the related costs are becoming more and more adaptable for their use in clinical practice. In our study, we analyzed a case series of young (under 65 years old) NSCLC patients with a wide NGS gene panel assay. The most frequent altered genes were TP53 (64.55%), followed by KRAS (44.1%), STK11 (26.9%), CDKN2A (21.5%), CDKN2B (14.0%), EGFR (16.1%), and RB1 (10.8%). Tumor mutational burden (TMB) was also evaluated. Considering the cut-off of 10 mut/Mb, 62 (68.9%) patients showed a TMB &lt; 10 mut/Mb, whereas 28 (31.1%) showed a TMB &ge; 10 mut/Mb. STK11 and KRAS mutations were significantly associated with a higher TMB (p = 0.019 and p = 0.004, respectively). Conversely, EGFR and EML4-ALK alterations were more frequently found in tumors with low TMB (p = 0.019 and p &lt; 0.001, respectively). We compared results obtained from this approach with those obtained from a single or few genes approach, observing perfect concordance of the results

Antioxidant Properties of Seeds from Lines of Artichoke, Cultivated Cardoon and Wild Cardoon

The artichoke (Cynara cardunculus L. subsp. scolymus L.), the cultivated cardoon (Cynara cardunculus var. altilis DC.) and the wild cardoon (Cynara cardunculus var. sylvestris L.) are species widely distributed in the Mediterranean area. The aim of this research was to evaluate the antioxidant properties of seeds from lines of artichoke and cultivated and wild cardoon in both aqueous-organic extracts and their residues by FRAP (Ferric Reducing Antioxidant Power) and TEAC (Trolox Equivalent Antioxidant Capacity) evaluations. Both artichoke and cardoon seeds are a good source of antioxidants. Among artichoke seeds, hydrolysable polyphenols contribution to antioxidant properties ranged from 41% to 78% for FRAP values and from 17% to 37% for TEAC values. No difference between cultivated and wild cardoon in antioxidant properties are reported. Our results could provide information about the potential industrial use and application of artichoke and/or cardoon seeds