Genetic evaluation of newborns with critical congenital heart defects admitted to the intensive care unit.

Rapid and efficient diagnostics is crucial for newborns with congenital heart defects (CHD) in intensive care unit (ICU) but is often challenging. Given that genetic factors play a role in 20-30% cases of CHD, it is likely that genetic tests could improve both its speed and efficiency. We aimed to analyze the utility of rapid and cost-effective multiplex ligation dependent probe amplification analysis (MLPA) for chromosomal analysis in newborns with critical CHD. One hundred consecutive newborns admitted with critical CHD to the ICU were included in the study. Those with normal MLPA findings were further tested by chromosomal microarray and clinical exome sequencing. Overall, pathogenic/likely pathogenic variants were determined in ten (10%) newborns by MLPA, three (3%) by chromosomal microarray, and three (3%) by clinical exome sequencing. The most common variant detected was deletion of 22q11.2 region.Conclusion: MLPA is fast and cost-effective analysis that could be used as the first-tier test in newborns with critical CHD admitted to the ICU. What is Known: • MLPA is an established method for chromosome analysis in patients with CHD, but detection rate in newborns with critical CHD is unknown. What is New: • Study suggests that detection rate of casual variants using MLPA in newborns with critical CHD is 10%.

Modification of PLA-Based Films by Grafting or Coating.

Recently, the demand for the use of natural polymers in the cosmetic, biomedical, and sanitary sectors has been increasing. In order to meet specific functional properties of the products, usually, the incorporation of the active component is required. One of the main problems is enabling compatibility between hydrophobic and hydrophilic surfaces. Therefore, surface modification is necessary. Poly(lactide) (PLA) is a natural polymer that has attracted a lot ofattention in recent years. It is bio-based, can be produced from carbohydrate sources like corn, and it is biodegradable. The main goal of this work was the functionalization of PLA, inserting antiseptic and anti-inflammatory nanostructured systems based on chitin nanofibrils-nanolignin complexes ready to be used in the biomedical, cosmetics, and sanitary sectors. The specific challenge of this investigation was to increase the interaction between the hydrophobic PLA matrix with hydrophilic chitin-lignin nanoparticle complexes. First, chemical modification via the "grafting from" method using lactide oligomers was performed. Then, active coatings with modified and unmodified chitin-lignin nanoparticle complexes were prepared and applied on extruded PLA-based sheets. The chemical, thermal, and mechanical characterization of prepared samples was carried out and the obtained results were discussed.

Bioactive Properties of Nanofibres Based on Concentrated Collagen Hydrolysate Loaded with Thyme and Oregano Essential Oils.

This research aimed to obtain biocompatible and antimicrobial nanofibres based on concentrated collagen hydrolysate loaded with thyme or oregano essential oils as a natural alternative to synthesis products. The essential oils were successfully incorporated using electrospinning process into collagen resulting nanofibres with diameter from 471 nm to 580 nm and porous structure. The presence of essential oils in collagen nanofibre mats was confirmed by Attenuated Total Reflectance -Fourier Transform Infrared Spectroscopy (ATR-FTIR), Ultraviolet-visible spectroscopy (UV-VIS) and antimicrobial activity. Scanning Electron Microscopy with Energy Dispersive Spectroscopy analyses allowed evaluating the morphology and constituent elements of the nanofibre networks. Microbiological tests performed against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Candida albicans showed that the presence of essential oils supplemented the new collagen nanofibres with antimicrobial properties. The biocompatibility of collagen and collagen with essential oils was assessed by in vitro cultivation with NCTC clone 929 of fibroblastic cells and cell viability measurement. The results showed that the collagen and thyme or oregano oil composites have no cytotoxicity up to concentrations of 1000 µg·mL-1 and 500 µg mL-1, respectively. Optimization of electrospinning parameters has led to the obtaining of new collagen electrospun nanofibre mats loaded with essential oils with potential use for wound dressings, tissue engineering or protective clothing.

Diagnostic and Clinical Utility of Clinical Exome Sequencing in Children With Moderate and Severe Global Developmental Delay / Intellectual Disability.

Clinical exome sequencing is currently being used in diagnostics of various genetic disorders, but studies supporting its application in clinical setting are scarce. The aim of this study was to establish diagnostic and clinical utility of clinical exome sequencing in patients with moderate and severe global developmental delay/intellectual disability. Clinical diagnosis was made in 49 of 88 investigated patients, with overall diagnostic yield of 55.7%. Molecular findings are characterized in detail, including the impact of newly made diagnosis on clinical management. Several previously unreported genotype-phenotype correlations and 33 novel variants are described. Genetic and clinical data were shared through publicly available database. In conclusion, clinical exome sequencing allows identification of causative variants in a significant proportion of patients in investigated clinical subgroup. Compared to whole exome sequencing, it shows similar diagnostic and clinical utility with reduced costs, which could be of particular importance for institutions with limited resources.

Rare missense TUBGCP5 gene variant in a patient with primary microcephaly.

Primary microcephalies (MCPH) are characterized by microcephaly (HC -2 SD at birth) in the absence of visceral malformations. To date, less than 20 genes have been associated with MCHP, several of which are involved in the formation and function of the centrosome. Here, we report a novel missense variant in the TUBGCP5 gene in a patient with primary microcephaly and mild developmental delay. The TUBCGP5 gene (tubulin gamma complex associated protein 5) is a paralog of TUBGCP4 and TUBGCP6, both of which are known MCPH associated genes, and like its' paralogs, is involved in centrosome formation. Furthermore, the TUBGCP5 gene is located in the 15q11.2 BP1-BP2 microdeletion Burnside-Butler susceptibility locus that is part of the larger Prader-Willi/Angelman region. Common clinical features of the 15q11.2 BP1-BP2 microdeletion include general developmental and neurodevelopmental delay which may occasionally be accompanied by yet unexplained microcephaly. In our patient, the TUBGCP5:c.2180T > G, p.Phe727Cys missense variant was identified in compound heterozygous state with 15q11.2 BP1-BP2 microdeletion using whole exome sequencing, after the initial analyses of known MCPH genes failed to identify a conclusively causative variant. The identified variant is rare and highly conserved, as shown by population allele frequency data from ExAC and GnomAD, as well as comparisons with all other vertebrates. Based on this evidence we suggest that the identified TUBGCP5 variant in our patient may thus represent a novel cause of MCPH with mild developmental delay and may play a role in occurrence of microcephaly in 15q11.2 microdeletion carriers. Further studies are required to further clarify the causality and penetrance of TBGCP5 variants in primary microcephaly.