An integration into the diagnostic workflow in a pediatric patient suspected of having Marfan syndrome

Abstract Background The genetic approach to Marfan syndrome (MFS) has evolved over the last few decades, as has our understanding of the variants' potential structural and functional consequences. It has been proposed that next-generation sequencing be used to improve genetic diagnosis and patient management. To this end, we used a targeted NGS custom panel to perform genetic analysis in a patient with MFS and his or her family members. Case presentation Here, we describe a novel germ-line heterozygous missense variant (transversion c.5371 T > A) found in exon 43 of the FBN1 gene of a patient (proband) with MFS. FBN1 (ENSG0000166147) and TGFB2 (ENSG0000166147) were included in a targeted sequencing panel for MFS (ENSG0000163513). This new variant c.5371 T > A was identified only in the proband, not in unaffected family members or healthy controls. Conclusions Given the massive amount of data generated by gene panel analysis, clinical interpretation of genetic variants may become more difficult. As a result, 3D modeling and multidisciplinary approaches should be used in the analysis and annotation of observed variants. The analysis of the protein's conformational structure in relation to the identified variant could provide useful information. These data can be used to classify observed variants (pathogenic vs non-pathogenic) linked to the MFS phenotype, as well as to track disease progression and potential target treatments

Viaggio in Sudan di Evliya Čelebi (1671-1672)

Donated by Klaus KreiserReprinted from in : Annali dell'Istituto Orientale di Napoli, 1964

First‐trimester screening based on cell‐free DNA

Objective: To compare women's experience of first-trimester combined screening (FTCS), with women's experience of an approach that uses the combination of a detailed early anatomy scan and cell-free DNA (cfDNA) analysis. Methods: This was single-center, open label, parallel group, randomized clinical trial. Pregnant women were randomized at the time of their first prenatal visit to either a policy of first-trimester risk assessment based on FTCS, or to a policy of first-trimester risk assessment based on ultrasound findings and cfDNA. Control group included first-trimester risk assessment based on FTCS. FTCS included ultrasound evaluation with crown-rump length, nuchal translucency (NT) measurement, and a detailed ultrasound scan, along with biochemistry (PAPP-A and free beta hCG). In this group, diagnostic testing was offered to patients with risk >1 in 100, or NT >3.5 mm, or any fetal abnormalities on ultrasound. Women randomized in the intervention group received an approach of first-trimester risk assessment based on ultrasound findings and cfDNA. cfDNA analysis included a simultaneous microarray-based assay of non-polymorphic (chromosomes 13, 18, 21, X and Y) and polymorphic loci to estimate chromosome proportion and fetal fraction. In the intervention group, diagnostic testing was offered to patients with abnormal cfDNA screening results, or NT >3.5 mm, or any fetal abnormalities on ultrasound. Participants received pre-test and post-test questionnaires regarding to measure reassurance, satisfaction, and anxiety. The primary outcome was the post-test reassurance, defined as mean score of reassurance post-test questionnaire. The effect of the assigned screening test on the cumulative incidence or on the mean of each outcome was quantified as the relative risk (RR) or mean difference (MD) with 95% confidence interval (CI). Results: 40 women with singleton gestations were included in the trial. Mean score for reassurance was significantly higher in the cfDNA group compared to the FTCS group in the pre-test questionnaire (MD 0.80 points, 95% CI 0.27 to 1.33) and in the post-test questionnaire (MD 16.50 points, 95% CI 2.18 to 30.82). Women randomized to the cfDNA group had higher satisfication and lower mean anxiety score as assessed in the STAI pre-test questionnaire. Conclusions: First-trimester risk assessment for trisomy 21 with a combination of a detailed ultrasound examination and cfDNA is associated with better maternal reassurance and better maternal satisfaction compared to the standard first-trimester combined screening with nuchal trasclucency, and maternal serum free beta-human chorionic gonadotrophin (FbetahCG) and pregnancy-associated plasma protein A (PAPP-A). This article is protected by copyright. All rights reserved

First-trimester screening based on cell-free DNA vs combined screening: a randomized clinical trial on women's experience

Objective: To compare women's experience of first-trimester combined screening (FTCS), with women's experience of an approach that uses the combination of a detailed early anatomy scan and cell-free DNA (cfDNA) analysis. Methods: This was single-center, open label, parallel group, randomized clinical trial. Pregnant women were randomized at the time of their first prenatal visit to either a policy of first-trimester risk assessment based on FTCS, or to a policy of first-trimester risk assessment based on ultrasound findings and cfDNA. Control group included first-trimester risk assessment based on FTCS. FTCS included ultrasound evaluation with crown-rump length, nuchal translucency (NT) measurement, and a detailed ultrasound scan, along with biochemistry (PAPP-A and free beta hCG). In this group, diagnostic testing was offered to patients with risk >1 in 100, or NT >3.5 mm, or any fetal abnormalities on ultrasound. Women randomized in the intervention group received an approach of first-trimester risk assessment based on ultrasound findings and cfDNA. cfDNA analysis included a simultaneous microarray-based assay of non-polymorphic (chromosomes 13, 18, 21, X and Y) and polymorphic loci to estimate chromosome proportion and fetal fraction. In the intervention group, diagnostic testing was offered to patients with abnormal cfDNA screening results, or NT >3.5 mm, or any fetal abnormalities on ultrasound. Participants received pre-test and post-test questionnaires regarding to measure reassurance, satisfaction, and anxiety. The primary outcome was the post-test reassurance, defined as mean score of reassurance post-test questionnaire. The effect of the assigned screening test on the cumulative incidence or on the mean of each outcome was quantified as the relative risk (RR) or mean difference (MD) with 95% confidence interval (CI). Results: 40 women with singleton gestations were included in the trial. Mean score for reassurance was significantly higher in the cfDNA group compared to the FTCS group in the pre-test questionnaire (MD 0.80 points, 95% CI 0.27 to 1.33) and in the post-test questionnaire (MD 16.50 points, 95% CI 2.18 to 30.82). Women randomized to the cfDNA group had higher satisfication and lower mean anxiety score as assessed in the STAI pre-test questionnaire. Conclusions: First-trimester risk assessment for trisomy 21 with a combination of a detailed ultrasound examination and cfDNA is associated with better maternal reassurance and better maternal satisfaction compared to the standard first-trimester combined screening with nuchal trasclucency, and maternal serum free beta-human chorionic gonadotrophin (FbetahCG) and pregnancy-associated plasma protein A (PAPP-A). This article is protected by copyright. All rights reserved

Estimation of heavy metals emissions in agricultural productions: The case of Italian products

The agri-food sector is more complex than the industrial sector due to different climatic, geomorphologic and cultivation practice factors. Agriculture operations can significantly affect phenomena, such as erosion and leaching, and generate different types of emissions into the environment. These aspects should be considered when performing a Life Cycle Assessment (LCA) study on agri-food products, mainly because these elements are influenced by both natural and human factors that generate negative health and ecotoxicological impacts. The “Swiss Agricultural Life Cycle Assessment - heavy metals (SALCA-HM)” allows for calculating heavy metal emissions at the life cycle inventory level as part of LCA at a regional level. This study aims to customise the SALCA-HM for five Italian agricultural products (i.e., durum and common wheat, grapes, olives, and citrus fruits), using region- and crop-specific data. The results showed that, even though all the factors relating to cultivation techniques are constant, the use of site-specific data makes it possible to highlight the influence of the orographic characteristics of the territory. Therefore, the high variability of the results can be perceived as a strength of this regionalised approach, thus overcoming several limitations by using national average data instead. More effort is needed to enable greater data availability both for policy and the scientific community