Utility of Gene Panels for the Diagnosis of Inborn Errors of Metabolism in a Metabolic Reference Center

Next-generation sequencing (NGS) technologies have been proposed as a first-line test for the diagnosis of inborn errors of metabolism (IEM), a group of genetically heterogeneous disorders with overlapping or nonspecific phenotypes. Over a 3-year period, we prospectively analyzed 311 pediatric patients with a suspected IEM using four targeted gene panels. The rate of positive diagnosis was 61.86% for intermediary metabolism defects, 32.84% for complex molecular defects, 19% for hypoglycemic/hyperglycemic events, and 17% for mitochondrial diseases, and a conclusive molecular diagnosis was established in 2-4 weeks. Forty-one patients for whom negative results were obtained with the mitochondrial diseases panel underwent subsequent analyses using the NeuroSeq panel, which groups all genes from the individual panels together with genes associated with neurological disorders (1870 genes in total). This achieved a diagnostic rate of 32%. We next evaluated the utility of a tool, Phenomizer, for differential diagnosis, and established a correlation between phenotype and molecular findings in 39.3% of patients. Finally, we evaluated the mutational architecture of the genes analyzed by determining z-scores, loss-of-function observed/expected upper bound fraction (LOEUF), and haploinsufficiency (HI) scores. In summary, targeted gene panels for specific groups of IEMs enabled rapid and effective diagnosis, which is critical for the therapeutic management of IEM patients.info:eu-repo/semantics/publishedVersio

Synthesis, molecular structure, and spectral analysis of copper(II) complexes derived from pyridinediols

<div><p>A series of mononuclear copper(II) complexes was synthesized by reaction of different 2,6-disubstituted pyridines with elemental Cu in a CCl₄/DMSO solvent system. Physical properties were analyzed using IR, optical spectroscopy, mass spectrometry, and EPR. Single-crystal X-ray diffraction for complexes <b>2a</b> and <b>4a</b> revealed that the molecular structure of <b>2a</b> is composed of a six-coordinate unit in which two ligands are linked to Cu(II) by oxygen and nitrogen donors. Conversely, in the molecular structure of <b>4a</b>, the Cu(II) has a slightly distorted trigonal bipyramidal arrangement, where the coordination environment around the copper ion is five-coordinate. EPR spectra of Cu(II) complexes were illustrated elaborately and some theoretical data were abstracted from EPR curves to support the proposed structures.</p></div

A new approach based on equivalent LEFM

Glued-in-rods in timber structures lead to overcome the use of traditional bolted connections, preserve a large part of the original timber and offeraesthetic benefits. Several research programs were achieved to improve the mechanical knowledge of this technique, exhibiting experimentally the influence of materials and the effect of the geometric configuration. From these experimental results, some design rules predicting the axial strength are available, but a common criterion is still lacking. This paper relates to experimental investigations and finite element computations on glued-in rods, with the aim of providing a better knowledge about their mechanical behavior until failure. An experimental campaign is carried out on single glued-in rod connections. The finite element modeling reproduces the experimental configuration: it exhibits significant normal stress (to the interface)at the onset of the bonding, in comparison with shear stress. Within the framework of equivalent linear elastic fracture mechanics, resistance curves in mode I and mode II are established for each specimen. Finally, a mixed mode fracture criterion (I/II) is used to describe the fracture process zone development at the woodadhesive interface (failure zone). An analytical formulation is then proposed allowing the evaluation of peak load of each specimen, which highlights a new approach for the design of such connections