Newborn Screening for Severe T and B Cell Lymphopenia Using TREC/KREC Detection: A Large-Scale Pilot Study of 202,908 Newborns.

Newborn screening (NBS) for severe inborn errors of immunity (IEI), affecting T lymphocytes, and implementing measurements of T cell receptor excision circles (TREC) has been shown to be effective in early diagnosis and improved prognosis of patients with these genetic disorders. Few studies conducted on smaller groups of newborns report results of NBS that also include measurement of kappa-deleting recombination excision circles (KREC) for IEI affecting B lymphocytes. A pilot NBS study utilizing TREC/KREC detection was conducted on 202,908 infants born in 8 regions of Russia over a 14-month period.

Rare Variants in Primary Immunodeficiency Genes and Their Functional Partners in Severe COVID-19.

The development of severe COVID-19, which is a complex multisystem disease, is thought to be associated with many genes whose action is modulated by numerous environmental and genetic factors. In this study, we focused on the ideas of the omnigenic model of heritability of complex traits, which assumes that a small number of core genes and a large pool of peripheral genes expressed in disease-relevant tissues contribute to the genetics of complex traits through interconnected networks. We hypothesized that primary immunodeficiency disease (PID) genes may be considered as core genes in severe COVID-19, and their functional partners (FPs) from protein-protein interaction networks may be considered as peripheral near-core genes.

COVID-19 severity: does the genetic landscape of rare variants matter?

Rare variants affecting host defense against pathogens may be involved in COVID-19 severity, but most rare variants are not expected to have a major impact on the course of COVID-19. We hypothesized that the accumulation of weak effects of many rare functional variants throughout the exome may contribute to the overall risk in patients with severe disease. This assumption is consistent with the omnigenic model of the relationship between genetic and phenotypic variation in complex traits, according to which association signals tend to spread across most of the genome through gene regulatory networks from genes outside the major pathways to disease-related genes.

Serial Changes in Blood-Cell-Count-Derived and CRP-Derived Inflammatory Indices of COVID-19 Patients.

The aim of the study was to investigate the serial changes in inflammatory indices derived from blood cell counts and C-reactive protein (CRP) levels in COVID-19 patients with good and poor outcomes. We retrospectively analyzed the serial changes in the inflammatory indices in 169 COVID-19 patients. Comparative analyses were performed on the first and last days of a hospital stay or death and serially from day 1 to day 30 from the symptom onset.

Pneumonia and Related Conditions in Critically Ill Patients-Insights from Basic and Experimental Studies.

Pneumonia is an acute infectious disease with high morbidity and mortality rates. Pneumonia's development, severity and outcome depend on age, comorbidities and the host immune response. In this study, we combined theoretical and experimental investigations to characterize pneumonia and its comorbidities as well as to assess the host immune response measured by TREC/KREC levels in patients with pneumonia.

Splice-site variant in the RPS7 5'-UTR leads to a decrease in the mRNA level and development of Diamond-Blackfan anemia.

Diamond-Blackfan anemia (DBA) is an inherited bone marrow failure syndrome characterized by erythroid aplasia. Pathogenic variants in ribosomal protein (RP) genes, GATA1, TSR2, and EPO, are considered to be the etiology of DBA. Variants in 5'-untranslated regions (UTRs) of these genes are poorly studied and can complicate the variant interpretation.

TREC/KREC Levels in Young COVID-19 Patients.

COVID-19 patients with acute respiratory distress syndrome (ARDS) have an immune imbalance when systemic inflammation and dysfunction of circulating T and B cells lead to a more severe disease. Using TREC/KREC analysis, we studied the level of mature naive T and B cells in peripheral blood of COVID-19 patients and its relationship with clinical and laboratory data. TREC/KREC analysis was performed by multiplex real-time quantitative PCR on a sample of 36 patients aged 45 years or younger.

Cytokines mapping for tissue-specific expression, eQTLs and GWAS traits.

Dysregulation in cytokine production has been linked to the pathogenesis of various immune-mediated traits, in which genetic variability contributes to the etiopathogenesis. GWA studies have identified many genetic variants in or near cytokine genes, nonetheless, the translation of these findings into knowledge of functional determinants of complex traits remains a fundamental challenge. In this study we aimed at collection, analysis and interpretation of data on cytokines focused on their tissue-specific expression, eQTLs and GWAS traits.

Pneumonia: host susceptibility and shared genetics with pulmonary function and other traits.

Pneumonia is a common and severe infectious lung disease. Host genetics, together with underlying medical and lifestyle conditions, determine pneumonia susceptibility. We performed a secondary analysis of the results of two genome-wide studies for pneumonia in 23andMe participants (40 600 cases/90 039 controls) (Tian et al.

Expression changes in pelvic organ prolapse: a systematic review and in silico study.

Pelvic organ prolapse (POP) is a highly disabling condition common for a vast number of women worldwide. To contribute to existing knowledge in POP pathogenesis, we performed a systematic review of expression studies on both specific gene and whole-genome/proteome levels and an in silico analysis of publicly available datasets related to POP development. The most extensively investigated genes in individual studies were related to extracellular matrix (ECM) organization.

[Elastogenesis-Related Gene Polymorphisms and the Risk of Pelvic Organ Prolapse Development].

Pelvic organ prolapse (POP) represents a urologic and gynecological disease, the development of which is governed both by environmental and genetic factors. We describe the results of our association study of polymorphic variants of genes involved in the assembly of elastic fibrils, namely, the lysyl oxidase protein 1 (LOXL1) and fibulin-3 (FBLN3) genes. We revealed an association of the rs2304719-T allele and rs2165241 (C)-rs2304719(T)-rs893821(T) haplotype of the LOXL1 gene with an increased risk of POP development, as well as a weak association with the disease of the rs3791660-C allele and the rs3791679(T)- rs1367228(A)-rs3791660(C)-rs2033316(A) haplotype of the FBLN3 gene.

Biological findings from the PheWAS catalog: focus on connective tissue-related disorders (pelvic floor dysfunction, abdominal hernia, varicose veins and hemorrhoids).

Pelvic floor dysfunction, specifically genital prolapse (GP) and stress urinary inconsistency (SUI) presumably co-occur with other connective tissue disorders such as hernia, hemorrhoids, and varicose veins. Observations on non-random coexistence of these disorders have never been summarized in a meta-analysis. The performed meta-analysis demonstrated that varicose veins and hernia are associated with GP.

Verification of the Chromosome Region 9q21 Association with Pelvic Organ Prolapse Using RegulomeDB Annotations.

Pelvic organ prolapse (POP) is a common highly disabling disorder with a large hereditary component. It is characterized by a loss of pelvic floor support that leads to the herniation of the uterus in or outside the vagina. Genome-wide linkage studies have shown an evidence of POP association with the region 9q21 and six other loci in European pedigrees.

Fibulin-5 (FBLN5) gene polymorphism is associated with pelvic organ prolapse.

Objective: FBLN5 encodes a key protein of elastic fiber matrix assembly and function that contributes to maintaining pelvic support and plays the important role in the pathophysiology of pelvic organ prolapse (POP). The aim of the study was to investigate whether there is an association between common single-nucleotide polymorphisms (SNPs) of the FBLN5 gene and POP.

Study Design: A total of eleven tag SNPs of the FBLN5 gene were genotyped using the polymerase chain reaction with confronting two-pair primers (PCR-CTPP) in 210 patients with POP (stages III-IV) and 292 controls with no even minimal POP.

Association of oxidative stress-related genes with idiopathic recurrent miscarriage.

Oxidative stress may play a role in the recurrent miscarriage (RM) with no known etiology. This study was conducted to investigate the association of polymorphisms in oxidative stress-related genes with idiopathic RM. A total of 331 idiopathic RM patients and 197 controls were genotyped for ABCB1 rs1045642, CYP1A1 rs1048943 and rs4646903, COMT rs4680, CAT rs17880664, GCLC rs17883901, GPX4 rs713041, NRF2 rs6721961, SOD2 rs4880, and OGG1 rs1052133.

[Effect of infrared low-intensity laser therapy on orbital blood circulation in children with progressive short sightedness].

This work was designed to study effect of low-intensity infrared laser radiation (LIIRR) on orbital circulation in children with progressive progressive short-handedness. Parameters of the blood flow in the orbital artery, central retinal artery, and posterior ciliary artery were evaluated in a total of 88 patients at the age from 6 to 14 years. The study group (group 1) comprised 66 children with moderately severe progressive myopia (112 eyes), the control one (group 2) included 22 patients without visual disturbances (44 eyes).

[Vibrations as an experimental factor affecting intestinal resorption].

The authors treated white rats daily at one and the same time for a period of one hour with vibrations. One of the groups of animals were treated with vibrations and examined after that, but the other two groups were treated respectively for 45 and 90 days. Examination was carried out during vibration, immediately after that and three hours after the vibrations.