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Uterine leiomyoma (ULM) is one of the most common gynecological pathologies in women of reproductive age. The prevalence of this pathology varies across different age groups, with approximately 10% in the 20–35 age range, increasing to 40–45% after the age of 35. ULM metastasis is an extremely rare phenomenon, with only 411 cases reported in the literature, including our 3 observations. Several definitions exist, with the most common being benign metastasizing ULM, found in both domestic and foreign literature. Each observation is crucial, as there are currently no clear treatment algorithms for this patient category. The study presents 3 cases of successful treatment of patients with metastatic ULM in two institutions. A systematic review of domestic and foreign literature on this pathology is conducted. Twenty-two clinical observations in the Russian Federation and neighboring countries are analyzed. Analysis of foreign literature revealed records of 386 clinical observations of benign metastasizing ULM. Benign metastasizing ULM of the uterus represents a rare nosological form. Systematization is advisable for determining the optimal treatment and observation tactics.

BackgroundTrichothiodystrophy-1 (TTD1) is an autosomal-recessive disease and caused by mutations in ERCC2, a gene coding for a subunit of the TFIIH transcription and nucleotide-excision repair (NER) factor. In almost half of these patients infectious susceptibility has been reported but the underlying molecular mechanism leading to immunodeficiency is largely unknown.ObjectiveThe aim of this study was to perform extended molecular and immunological phenotyping in patients suffering from TTD1.MethodsCellular immune phenotype was investigated using multicolor flow cytometry. DNA repair efficiency was evaluated in UV-irradiation assays. Furthermore, early BCR activation events and proliferation of TTD1 lymphocytes following DNA damage induction was tested. In addition, we performed differential gene expression analysis in peripheral lymphocytes of TTD1 patients.ResultsWe investigated three unrelated TTD1 patients who presented with recurrent infections early in life of whom two harbored novel ERCC2 mutations and the third patient is a carrier of previously described pathogenic ERCC2 mutations. Hypogammaglobulinemia and decreased antibody responses following vaccination were found. TTD1 B-cells showed accumulation of γ-H2AX levels, decreased proliferation activity and reduced cell viability following UV-irradiation. mRNA sequencing analysis revealed significantly downregulated genes needed for B-cell development and activation. Analysis of B-cell subpopulations showed low numbers of naïve and transitional B-cells in TTD1 patients, indicating abnormal B-cell differentiation in vivo.ConclusionIn summary, our analyses confirmed the pathogenicity of novel ERCC2 mutations and show that ERCC2 deficiency is associated with antibody deficiency most likely due to altered B-cell differentiation resulting from impaired BCR-mediated B-cell activation and activation-induced gene transcription.

Relevance. Bone tissue regeneration and the development of methods for directed influence on the processes of bone healing are of the most urgent problems of modern medicine. Defects in the jaw bones are widespread, which in turn leads to the search for modern bone - replacing materials that meet the basic characteristics of the bone. Information was searched based on the PubMed and E-library databases, using the keywords: “bone tissue” AND “bone regeneration” AND “osteoplastic materials” AND “osteoinduction” AND “osteoconduction”. Autologous bone is considered the clinical gold standard and the most effective method of bone regeneration. It is the autograft that has three main characteristics: osteogenicity, osteoinductive and osteoconductive. The autograft has limitations due to the limited amount of bone tissue and the soreness of the donor site. A viable alternative to autologous bone is an allograft. The most widely used allograft is demineralized freeze - dried bone allograft (FDBA). The freeze - drying process promotes damage to osteoblasts, which limits its osteoinductive potential, but it is a profitable alternative in terms of convenience, abundance of choice and absence of pain due to the absence of additional surgical intervention. The main component of xenogeneic materials is collagen, which has the ability to resorb in tissues and stimulate regenerative processes. The material has osteoconductive properties and is capable of bone ingrowth, with the formation of a new bone directly from the xenomaterial bed with the deposition of bone cells on its surface. Subsequently, the xenomaterial undergoes resorption with complete replacement with new bone tissue. Alloplastic materials are fully synthetic materials synthesized from inorganic sources. Alloplastic materials have the property of osteoconduction, and when various growth factors are added to their composition, the property of osteoinduction is added to osteoconductive. The clinical use of bone substitutes is limited by their fragility as well as their unpredictable rate of resorption, which render these materials generally less favorable in clinical outcomes. Conclusion. Until now, a scientific search for various materials capable of replacing an autogenous transplant is being carried out. At the moment, none of the currently available materials has all the desired characteristics and the choice of materials directly depends on the specific clinical situation in the oral cavity.

A striking feature of COVID-19 disease is the broad spectrum of risk factors associated with case severity, as well as the diversity of clinical manifestations. While no central agent has been able to explain the pathogenesis of SARS-CoV-2 infection, the factors that most robustly correlate with severity are risk factors linked to aging. Low serum levels of Klotho, an anti-aging protein, strongly correlate with the pathogenesis of the same risk factors and manifestations of conditions similar to those expressed in severe COVID-19 cases. The current manuscript presents original research on the effects of the exogenous application of Klotho, an anti-aging protein, in COVID-19 model mice. Klotho supplementation resulted in a statistically significant survival benefit in parametric and non-parametric models. Further research is required to elucidate the mechanistic role Klotho plays in COVID-19 pathogenesis as well as the possible modulation SARS-CoV-2 may have on the biological aging process.

Introduction: EP-11-1 (UEHLERALNSS) is a short-chain erythropoietin derivative without have erythropoietic activity. It was created by modifying a peptide mimicking the spatial structure of the erythropoietin a-helix B pHBSP. One of the promising directions of its administration is the correction of morphofunctional disorders that occur in traumatic brain injury (TBI). Materials and methods: The study was performed in 160 male Wistar rats, weighing 180–200 g.TBI was simulated using the drop-weight method. To assess the emerging morphofunctional disorders and a degree of their correction, we used the severity of neurological deficit, indicators of locomotor activity and exploration, a marker of brain injury S100B and morphological examination. Results and discussion: The combined administration of a new EPOR/CD131 heteroreceptor agonist EP-11-1 with citicoline and trimetazidine led to a more pronounced correction of the neurological deficit when compared not only to the group of the ”untreated” animals, but also to the groups of animals to which these drugs had been administered as monotherapy (p < 0.05). The same tendency was also observed in the study of locomotor activity and exploration. A biochemical study showed that the administration of all three combinations led to a statistically significant (p < 0.05) decrease in the S-100B concentration compared not only to the group of “untreated” animals, but also to the groups of animals to which these drugs had been administered as a monotherapy. Conclusion: The results of the conducted experiments prove the most pronounced positive dynamics in the combined administration of the new EPOR/CD131 heteroreceptor agonist EP-11-1with citicoline and trimetazidine.

The objective of this study was to create a nanofiber-based skin graft with an antimicrobial bandage that could accelerate the healing of an open wound while minimizing infection. To this end, we prepared a bi-layer construct where the top layer acts as bandage, and the bottom layer acts as a dermal equivalent graft. A collagen (CG) gel was combined without and with an electrospun polycaprolactone (PCL) membrane to prepare CG and CG-PCL dermal equivalent constructs. The antibacterial properties of PCL with and without an antibacterial agent (MgO nanoparticles) against Staphylococcus aureus (ATCC 6538) was also examined. Human dermal fibroblasts were cultured in each construct to make the dermal equivalent grafts. After culturing, keratinocytes were plated on top of the tissues to allow growth of an epidermis. Rheological and durability tests were conducted on in vitro dermal and skin equivalent cultures, and we found that PCL significantly affects CG-PCL graft biological and mechanical strength (rheology and durability). PCL presence in the dermal equivalent allowed sufficient tension generation to activate fibroblasts and myofibroblasts in the presence of transforming growth factor-beta. During culture of the skin equivalents, optical coherence tomography (OCT) showed layers corresponding to dermal and epidermal compartments in the presence or absence of PCL; this was confirmed after fixed specimens were histologically sectioned and stained. MgO added to PCL showed antibacterial activity against S. aureus. In vivo animal studies using a rat skin model showed that a polycaprolactone nanofiber bandage containing a type I collagen skin graft has potential for wound healing applications.

Background: Trichothiodystrophy-1 (TTD1) is an autosomal-recessive disease and caused by mutations in ERCC2, a gene coding for a subunit of the TFIIH transcription and nucleotide-excision repair (NER) factor. In almost half of these patients infectious susceptibility has been reported but the underlying molecular mechanism leading to immunodeficiency is largely unknown. Objective: The aim of this study was to perform extended molecular and immunological phenotyping in patients suffering from TTD1. Methods: Cellular immune phenotype was investigated using multicolor flow cytometry. DNA repair efficiency was evaluated in UV-irradiation assays. Furthermore, early BCR activation events and proliferation of TTD1 lymphocytes following DNA damage induction was tested. In addition, we performed differential gene expression analysis in peripheral lymphocytes of TTD1 patients. Results: We investigated three unrelated TTD1 patients who presented with recurrent infections early in life of whom two harbored novel ERCC2 mutations and the third patient is a carrier of previously described pathogenic ERCC2 mutations. Hypogammaglobulinemia and decreased antibody responses following vaccination were found. TTD1 B-cells showed accumulation of g-H2AX levels, decreased proliferation activity and reduced cell viability following UV irradiation. mRNA sequencing analysis revealed significantly downregulated genes needed for B-cell development and activation. Analysis of B-cell subpopulations showed low numbers of naïve and transitional B-cells in TTD1 patients, indicating abnormal B-cell differentiation in vivo. Conclusion: In summary, our analyses confirmed the pathogenicity of novel ERCC2 mutations and show that ERCC2 deficiency is associated with antibody deficiency most likely due to altered B-cell differentiation resulting from impaired BCR-mediated B-cell activation and activation-induced gene transcription. [ABSTRACT FROM AUTHOR]

Abstract Background Schistosomiasis continues to inflict significant morbidity and mortality in the tropical and subtropical regions of the world. The disease endemicity overlaps with the transmission of other parasitic diseases. Despite the ubiquity of polyparasitism in tropical regions, particularly in rural communities, little is known about the impact of multiple helminth infections on disease progression. In this pilot study, we describe the influence of chronic Trichuris trichiura infection on Schistosoma mansoni egg-induced hepatopathology in infected baboons. Methods Baboons with or without underlying whipworm infection were challenged with S. mansoni cercariae to establish schistosomiasis. Adult S. mansoni worms were recovered by perfusion and enumerated, hepatic granulomas were quantified via light microscopy, and transcriptional profiling of tissues were completed using RNA sequencing technologies. Results Co-infection with both S. mansoni and T. trichiura resulted in higher female schistosome worm burden and significantly larger liver granuloma sizes. Systems biology analyses of peripheral blood mononuclear cells (PBMC) revealed pathways associated with increased liver damage in co-infected baboons. Conclusions Underlying chronic whipworm infection intensified schistosome egg-induced liver pathology in infected baboons. RNA-Seq analysis provided insight into pathways associated with increased liver damage, corroborating histological findings.

Previous studies on immune responses following COVID-19 vaccination in patients with common variable immunodeficiency (CVID) were inconclusive with respect to the ability of the patients to produce vaccine-specific IgG antibodies, while patients with milder forms of primary antibody deficiency such as immunoglobulin isotype deficiency or selective antibody deficiency have not been studied at all. In this study we examined antigen-specific activation of CXCR5-positive and CXCR5-negative CD4+ memory cells and also isotype-specific and functional antibody responses in patients with CVID as compared to other milder forms of primary antibody deficiency and healthy controls six weeks after the second dose of BNT162b2 vaccine against SARS-CoV-2. Expression of the activation markers CD25 and CD134 was examined by multi-color flow cytometry on CD4+ T cell subsets stimulated with SARS-CoV-2 spike peptides, while in parallel IgG and IgA antibodies and surrogate virus neutralization antibodies against SARS-CoV-2 spike protein were measured by ELISA. The results show that in CVID and patients with other milder forms of antibody deficiency normal IgG responses (titers of spike protein-specific IgG three times the detection limit or more) were associated with intact vaccine-specific activation of CXCR5-negative CD4+ memory T cells, despite defective activation of circulating T follicular helper cells. In contrast, CVID IgG nonresponders showed defective vaccine-specific and superantigen-induced activation of both CD4+T cell subsets. In conclusion, impaired TCR-mediated activation of CXCR5-negative CD4+ memory T cells following stimulation with vaccine antigen or superantigen identifies patients with primary antibody deficiency and impaired IgG responses after BNT162b2 vaccination.

The study addresses the influence of milking duration of individual cows on the performance of conveyor-like rotary milking parlors and seeks to optimize their operation parameters and operating modes. The observational experiment was conducted in the Zhdanovsky Farm in Nizhny Novgorod Region, Russia. The dairy farm had a herd of 600 cows, divided into 10 groups by physiological characters and milk yield, and operated a 36 point milking parlor. Distribution of milking time of individual cows was studied using statistical analysis methods. The cyclogram of parlor operation and the functional connection of main parameters were analyzed using Maple analytical computing system, including its standard libraries and functions. The trends in idle time, which occurs due to undermilking of animals in one turn of the parlor, were studied. The idle time can result in overestimation of the number of stalls or decrease in the nameplate performance of the milking parlor by 30–40% from 120 to 93 cows per hour. Mathematical models, taking into account the influence of the milking time of individual animals (2 to 17 minutes) on the parameters of parlor operation, were developed. The algorithms of adaptive control over the rotational speed were proposed to minimize idle time in parlor operation and maintain the nameplate performance. The mathematical models, control algorithms and developed software can serves as a scientific basis for new designs of high-performance rotary milking parlors.