Congenital Heart Defects Are Rarely Caused by Mutations in Cardiac and Smooth Muscle Actin Genes

Background. Congenital heart defects (CHDs) often have genetic background due to missense mutations in cardiomyocyte-specific genes. For example, cardiac actin was shown to be involved in pathogenesis of cardiac septum defects and smooth muscle actin in pathogenesis of aortic aneurysm in combination with patent ductus arteriosus (PDA). In the present study, we further searched for mutations in human α-cardiac actin (ACTC1) and smooth muscle α-actin (ACTA2) genes as a possible cause of atrial septum defect type II (ASDII) and PDA. Findings. Total genomic DNA was extracted from peripheral blood of 86 individuals with ASDs and 100 individuals with PDA. Coding exons and flanking intron regions of ACTC1 (NM_005159.4) and ACTA2 (NM_001613) were amplified by PCR with specific primers designed according to the corresponding gene reference sequences. PCR fragments were directly sequenced and analyzed. Sequence analysis of ACTC1 and ACTA2 did not identify any nucleotide changes that altered the coding sense of the genes. In ACTC1 gene, we were able to detect one previously described nucleotide polymorphism (rs2307493) resulting in a synonymous substitution. The frequency of this SNP was similar in the study and control group, thus excluding it from the possible disease-associated variants. Conclusions. Our results confirmed that the mutations in ACTC1 gene are rare (at least <1%) cause of ASDII. Mutations in ACTA2 gene were not detected in patients with PDA, thus being excluded from the list of frequent PDA-associated genetic defects

Necrotizing Enterocolitis: The Role of Hypoxia, Gut Microbiome, and Microbial Metabolites

Necrotizing enterocolitis (NEC) is a life-threatening disease that predominantly affects very low birth weight preterm infants. Development of NEC in preterm infants is accompanied by high mortality. Surgical treatment of NEC can be complicated by short bowel syndrome, intestinal failure, parenteral nutrition-associated liver disease, and neurodevelopmental delay. Issues surrounding pathogenesis, prevention, and treatment of NEC remain unclear. This review summarizes data on prenatal risk factors for NEC, the role of pre-eclampsia, and intrauterine growth retardation in the pathogenesis of NEC. The role of hypoxia in NEC is discussed. Recent data on the role of the intestinal microbiome in the development of NEC, and features of the metabolome that can serve as potential biomarkers, are presented. The Pseudomonadota phylum is known to be associated with NEC in preterm neonates, and the role of other bacteria and their metabolites in NEC pathogenesis is also discussed. The most promising approaches for preventing and treating NEC are summarized

Necrotizing Enterocolitis: The Role of Hypoxia, Gut Microbiome, and Microbial Metabolites

Necrotizing enterocolitis (NEC) is a life-threatening disease that predominantly affects very low birth weight preterm infants. Development of NEC in preterm infants is accompanied by high mortality. Surgical treatment of NEC can be complicated by short bowel syndrome, intestinal failure, parenteral nutrition-associated liver disease, and neurodevelopmental delay. Issues surrounding pathogenesis, prevention, and treatment of NEC remain unclear. This review summarizes data on prenatal risk factors for NEC, the role of pre-eclampsia, and intrauterine growth retardation in the pathogenesis of NEC. The role of hypoxia in NEC is discussed. Recent data on the role of the intestinal microbiome in the development of NEC, and features of the metabolome that can serve as potential biomarkers, are presented. The Pseudomonadota phylum is known to be associated with NEC in preterm neonates, and the role of other bacteria and their metabolites in NEC pathogenesis is also discussed. The most promising approaches for preventing and treating NEC are summarized

Additional file 2: of Ring chromosome 18 in combination with 18q12.1 (DTNA) interstitial microdeletion in a patient with multiple congenital defects

Confirmation of DTNA deletion in the patient using quantitative real-time PCR analysis (qPCR). Description of data: qPCR data revealed one copy of the DTNA gene (18q12.1) in a patient DNA sample as compared to two copies of the gene in a normal control DNA sample. The data was normalized against GAPDH gene using the comparative ΔΔCt method. RQ (relative quantity) value is presented along the vertical axis. Each reaction was reproduced (repeated) in triplicate for both DNA samples (patient and control) and both genes (DTNA and GAPDH). The series of four ten-fold dilutions were included into analysis with the starting amount of DNA ~ 1 ng. The results obtained for one of the dilutions are depicted in the figure; for the rest dilutions, the ratio of quantity values between test and control samples was the same. (PNG 8 kb

Simplified Convolutional Neural Network Application for Cervix Type Classification via Colposcopic Images

The inner parts of the human body are usually inspected endoscopically using special equipment. For instance, each part of the female reproductive system can be examined endoscopically (laparoscopy, hysteroscopy, and colposcopy). The primary purpose of colposcopy is the early detection of malignant lesions of the cervix. Cervical cancer (CC) is one of the most common cancers in women worldwide, especially in middle- and low-income countries. Therefore, there is a growing demand for approaches that aim to detect precancerous lesions, ideally without quality loss. Despite its high efficiency, this method has some disadvantages, including subjectivity and pronounced dependence on the operator’s experience. The objective of the current work is to propose an alternative to overcoming these limitations by utilizing the neural network approach. The classifier is trained to recognize and classify lesions. The classifier has a high recognition accuracy and a low computational complexity. The classification accuracies for the classes normal, LSIL, HSIL, and suspicious for invasion were 95.46%, 79.78%, 94.16%, and 97.09%, respectively. We argue that the proposed architecture is simpler than those discussed in other articles due to the use of the global averaging level of the pool. Therefore, the classifier can be implemented on low-power computing platforms at a reasonable cost

Generation of iPSC line from patient with arrhythmogenic right ventricular cardiomyopathy carrying mutations in PKP2 gene

Human iPSC line was generated from patient-specific adipose tissue-derived mesenchymal multipotent stromal cells carrying two mutations in plakophilin-2 (PKP2) gene using non-integrative reprogramming method. Reprogramming factors OCT4, KLF4, SOX2, CMYC were delivered using Sendai viruses. Pluripotency was confirmed in vitro using immunofluorescence and RT-PCR analysis and in vivo by teratoma assay. The reported iPSC line could be useful tool for in vitro modeling of arrhythmogenic right ventricular cardiomyopathy

Gestational Trophoblastic Disease with Coexisting Progressing Pregnancy: Personalised Treatment Modalities

Purpose. Gestational trophoblastic disease (GTD) coexisting with a steadily progressing pregnancy is an extremely rare condition presented in the literature as a single case or case series of successful delivery. The purpose of this study was to describe five cases of GTD and present possible management strategies for such patients. Methods. Clinical data of five pregnancies with coexisting GTD were identified within the Almazov National Medical Research Centre from 2018 to 2021. Results. Three cases of multiple pregnancies with complete hydatidiform moles and two cases of singleton pregnancies with intraplacental choriocarcinoma and invasive hydatidiform moles were identified. Three pregnancies were prolonged and ended with preterm deliveries. Malignant transformation of the GTD accounted for 60% of the cases. The condition of newborns was based on the level of prematurity and functional immaturity, and in all cases, it was aggravated by anemia. Conclusion. GTD coexisting with progressing pregnancy is threatened by the risks of preterm delivery, miscarriage, hemorrhage, and disease progression and requires monitoring in a multidisciplinary clinic experienced in the management of patients with malignant tumors during pregnancy. In cases of prolonged pregnancy against the background of GTD, we suggest the following monitoring during pregnancy: pelvic, abdominal ultrasound/MRI (without contrast), prenatal invasive fetal karyotype testing in cases of singleton pregnancy, lung X-ray/CT with uterine shielding, weekly assessment of β-hCG levels, and dynamic monitoring of the fetus. The following postnatal monitoring should be performed: morphological examination of the placenta, weekly assessment of β-hCG levels up to normalization, then monthly assessment up to six months, and control of β-hCG level of the newborn

Genetic Spectrum of Idiopathic Restrictive Cardiomyopathy Uncovered by Next-Generation Sequencing.

BACKGROUND:Cardiomyopathies represent a rare group of disorders often of genetic origin. While approximately 50% of genetic causes are known for other types of cardiomyopathies, the genetic spectrum of restrictive cardiomyopathy (RCM) is largely unknown. The aim of the present study was to identify the genetic background of idiopathic RCM and to compile the obtained genetic variants to the novel signalling pathways using in silico protein network analysis. PATIENTS AND METHODS:We used Illumina MiSeq setup to screen for 108 cardiomyopathy and arrhythmia-associated genes in 24 patients with idiopathic RCM. Pathogenicity of genetic variants was classified according to American College of Medical Genetics and Genomics classification. RESULTS:Pathogenic and likely-pathogenic variants were detected in 13 of 24 patients resulting in an overall genotype-positive rate of 54%. Half of the genotype-positive patients carried a combination of pathogenic, likely-pathogenic variants and variants of unknown significance. The most frequent combination included mutations in sarcomeric and cytoskeletal genes (38%). A bioinformatics approach underlined the mechanotransducing protein networks important for RCM pathogenesis. CONCLUSIONS:Multiple gene mutations were detected in half of the RCM cases, with a combination of sarcomeric and cytoskeletal gene mutations being the most common. Mutations of genes encoding sarcomeric, cytoskeletal, and Z-line-associated proteins appear to have a predominant role in the development of RCM

List of pathogenic, likely pathogenic and variants of unknown significance in patients with RCM.

<p>List of pathogenic, likely pathogenic and variants of unknown significance in patients with RCM.</p