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Oocyte cryopreservation for non-medical reasons has been widely promoted among young women who tend to delay their reproduction. As the methodology has proved its safety and efficiency in the field of assisted reproduction technology and the embryo laboratory, the interest in oocyte cryopreservation has increased highly. However, do social freezers ever come back and use these oocytes, or they keep them as a safety boat with no real near-future plans for reproduction?

The large amount of excess adipose tissue affects negatively every single step of the assisted reproductive treatment process – from the controlled ovarian hyperstimulation (COH) to obstetric complications and health consequences for the fetus. A number of scientific data show correlation between impaired clinical pregnancy rates (CPR) and obese patients maintaining high body mass index (BMI). The debate whether high proportion of body fat negatively affects oocyte quality or only impacts endometrial receptivity remains open.

Recent advances in molecular genetics and the invention of new technologies led to an advance in the development of gene therapy. Gene therapy is used to correct defective genes in order to cure a disease or help the body better fight a disease. It works by restoring or modifying cellular functions through the introduction of a functional gene into the target cell. The concept of gene therapy is simple, but introducing it to routine clinical practice is not. The main concerns are related to some safety issues as well as to the problem that maintaining a stable and prolonged expression in target cells may not be easily achieved. In spite of the difficulties, gene therapy remains a hope for many hematological disorders that cannot be effectively treated so far. This article reviews the current status of gene therapy with a focus on hematological disorders. In addition, clinically applied approaches are presented through particular examples of approved gene therapy drugs.

Recent advances in molecular genetics and the invention of new technologies led to a development in our knowledge about human microbiota, specifically bacterial one. The microbiota plays a fundamental role in the immunologic, hormonal and metabolic homeostasis of the host. After the initiation of the Human Microbiome Project, it became clear that the human microbiota consists of the 10-100 trillion symbiotic microbial cells harbored by each person, primarily bacteria in the gut, but also in other spots as the skin, mouth, nose, and vagina. Despite of the differences in studying bacterial species, decreased bacterial diversity and persistence has been connected with several diverse human diseases primarily diabetes, IBD (inflammatory bowel disease) and others; attempts were made even to explain psychiatric pathology. Several species emerged as dominant and were clearly linked to certain disorders or accepted as biomarkers of others. The current review aims to discuss key issues of our current knowledge about bacteria in human, the difficulties and methods of its analysis, its contribution to human health and responsibility for human diseases.

Introduction: Azacitidine is one of the hypomethylating agents available for the treatment of elderly patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). It is also used as an appropriate treatment of chronic myelomonocytic leukemia (CMML) in the real life setting. As treatment of AML and CMML is not curative, and allogeneic stem cell transplantation (allo-SCT) remains traditionally the only option, significant clinical benefits by hypomethylating agents have been reported. According to the available data, 16% of subjects with MDS who received azacitidine had a complete or partial normalization of blood cell counts and bone marrow morphology, while two-thirds of patients who required blood transfusions no longer needed them. Nevertheless, it can also be hepatotoxic in patients with severe liver impairment and extensive liver tumors.

Gaucher disease (GD) is a multi-systemic disease with a low population frequency. It is a lysosomal storage disorder (LSD) that causes accumulation of glucocerebroside in the so called Gaucher cells predominantly in areas like the spleen, liver and bone marrow. Type I GD (GDI) is the most common form and usually does not involve the brain and the spinal cord. The symptoms can range from mild to severe and may appear anytime from childhood to adulthood. Diagnostics can often be challenging and imposes looking at person’s medical history, symptoms, physical exam, and laboratory test results. We present a difficult to diagnose case of a 34-year-old woman admitted to the Clinic of Hematology, “Sv. I. Rilski” hospital with splenomegaly, normal laboratory findings and non-enlarged liver. She didn’t show focal neurological symptoms. A series of tests were assigned including genetic targeted analysis. The case is an example of a rare genetic disease with mild clinical symptoms. Diagnosis of Gaucher disease, type I was confirmed by measurement of a GBA enzyme activity and identification of mutations in the GBA gene inherited in an autosomal recessive manner. Thanks to the efforts of the clinical team, the assignment of adequate clinical and laboratory tests and their correct interpretation, the patient was subjected to enzyme replacement therapy (ERT). Although the diagnosis was settled relatively late (at 34 years of age), the correct therapy slowed down the invalidation and improved the quality of life of the patient.

Myelofibrosis (MF) is characterized by a presence of an extra fibrous tissue in the bone marrow and additional hematopoiesis. The somatic mutation in the Janus kinase 2 (JAK2) gene (V617F) occurs gradually and is detected in about 50.0% of myelofibrosis or essential thrombo-cytopenia (ET) patients. Our aim was to determine the genotype status according to the carriers of the V617F mutation in patients with MF at the Hematology Ward of the University Hospital "Ivan Rilski" in Sofia, Bulgaria. DNA samples were isolated from venous blood of patients with various hematological disorders. DNA was amplified by polymerase chain reaction (PCR) and subsequent restriction analysis was performed using a BsaXI restriction enzyme. The genotype status was determined on 2.0% agarose gel. We analyzed 38 patients initially suspected of carrying MF or osteomyelofibrosis (OMF). After trepanobiopsy, 20 out of 38 patients were confirmed as myelofibrotic (52.6%), 5/38 (13.2%) were diagnosed as ET, 1/38 (2.6%) was diagnosed as myeloproliferative neoplasm (MPN), 6/38 (15.8%) had polycythemia vera (PV). In six patients, the presence of disease was rejected. Patients with MF were divided into three groups according to the JAK2 V617F genotype status: homozygous for the mutation (3/20 or 15.0%), heterozygous (9/20 or 45.0%) and homozygous for the wild type allele (8/20 or 40.0%). The triggering factor of MF is still unknown. It was considered that this factor could have a genetic nature. Mutations in three genes were mainly accepted as an actual predisposing events to this disease: point mutations leading to amino acid substitutions in JAK2 (V617F) and in MPL (W515L, W515K), as well as insertion or deletion in CALK We have proven that carriers of the V617F mutation prevailed in the group of patients with MF (altogether 12 patients or 60.0%). Previous studies also showed that JAK2 V617F is present in more than half of MF patients within their blood-forming cells. Therefore, the risk of evolution to MF could be associated with V617F-mutant allele burden in patients with MPN.

Mutations in the receptor of the epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) are used as biomarkers for predicting the response of treatment with EGFR tyrosine kinase inhibitors (EGFR TKIs). Non-small cell lung cancer patients usually have activating EGFR mutations that leads to a very good response when they are treated with EGFR TKIs. Our tumor samples were examined for the presence of sensitive mutations in the EGFR gene, resistant mutations or the absence of mutations. To identify the types of the mutation, we used a real-time polymerase chain reaction (RT-PCR) method. Additionally, we evaluated the frequency of EGFR mutations and their association with smoking status, gender and histology. The tumor samples (n = 551) were tested for 29 somatic mutations in the EGFR gene. Sensitive mutations in the EGFR genes were found in 55 NSCLC samples (10.0%). The prevalence of EGFR mutations was much higher for females than for males (27.1 vs. 3.9%, p

Epigenetic changes, in particular DNA methylation processes, play a role in the pathogenesis and progression of type 2 diabetes mellitus (T2DM) linking genetic and environmental factors. To clarify this role, we have analyzed in patients with different duration of T2DM: (i) expression levels of methyl-CpG-binding domain protein 2 (MBD2) as marker of DNA methylation, and ii) methylation changes in 22 genes connected to cellular stress and toxicity. We have analyzed MBD2 mRNA expression levels in16 patients and 12 controls and the methylation status of stress and toxicity genes in four DNA pools: (i) controls; (ii) newly-diagnosed T2DM patients; (iii) patients with T2DM duration of 5 years. The MBD2 expression levels were 10.4-times increased on average in T2DM patients compared to controls. Consistent increase in DNA methylation fraction with the increase in T2DM duration was observed in Prdx2 and SCARA3 genes, connected to oxidative stress protection and in BRCA1 and Tp53 tumor-suppressor genes. In conclusion, increased MBD2 expression in patients indicated general dysregulation of DNA methylation in T2DM. The elevated methylation of Prdx2 and SCARA3 genes suggests disturbance in oxidative stress protection in T2DM. The increased methylation of BRCA1 and Tp53 genes unraveled an epigenetic cause for T2DM related increase in cancer risk.

• Synergistic effect between components is found in most active KCoRe catalyst. • The Re4+/Re7+ ratio gives information about sour WGS activity of rhenium catalysts. • A balance between Re4+ sulphide and Re7+ oxide structures is found in KCoRe catalyst. • The KCoRe system is considered a promising sour WGS catalyst in the 250–400 °C range. Series of Re 2 O 7 /γ-Al 2 O 3 catalysts promoted with Ni, Co, and K were studied as sour gas shift catalysts. Samples were prepared by consecutive incipient wetness impregnation. Catalytic measurements were performed in a fixed bed reactor at atmospheric pressure in the range of 180–400 °C at GHSV of 4000 h−1 and steam/gas ratio of 0.3. The samples were characterised by means of N 2 physisorption, X-ray diffraction, diffuse reflectance UV–vis spectroscopy, and X-ray photoelectron spectroscopy. It was found that oxidation state ratio of rhenium sulphidic to rhenium oxygen-containing species, namely Re4+/(Re7+(+Re6+)), gives important information about redox relationship between Re4+ and Re7+ oxidation states according to additive type (K, Ni, and Co) and combinations among them. Three factors, namely, uniform deposition of K-Co-Re species on carrier surface, balance between Re sulphidic and oxidic species, and synergism among components were beneficial to the highest activity of KCoRe catalyst. This system was considered a promising catalyst for water-gas shift reaction with sulphur-containing feed in the 250–400 °C temperature range. [ABSTRACT FROM AUTHOR]

This study aims to reveal the reason for the increased force of 5-hydroxytryptamine-induced contraction of endotheliumdenuded skeletal muscle arteries of diabetic rats in the presence of perivascular adipose tissue (PVAT). Our data on rat gracilis arteries show that i) PVAT of skeletal muscle arteries of healthy and diabetic rats releases hydrogen peroxide (H2O2), ii) higher concentrations of 5-hydroxytryptamine increase the production of H2O2 in PVAT; iii) an enhanced PVAT production of H2O2 is the main, if not the only, reason for the sensitization of arterial contraction to 5-hydroxytriptamine-induced contraction in diabetes and iv) endothelium antagonizes the effect of PVATderived H2O2. [ABSTRACT FROM AUTHOR]

The behavioral responses of male mound-building mice Mus spicilegus to odours from males of their own species and odors from males of another species - house mouse Mus musculus musculus and yellow-necked mouse Apodemus flavicollis were studied in an attraction-avoidance test in order to clarify the role of odour in their relationships in wild populations in agricultural land. The experiments were carried out in the breeding season. M. spicilegus males showed attraction to conspecific odours from the same sex, but indifference to heterospecific odours of male M. m. musculus, and avoidance to odours of male A. flavicollis. The behavioural responses to conspecific and heterospecific odours are discussed in terms of attractiveness of odour cues, according to their significance in social relationships and spacing behaviour. [ABSTRACT FROM AUTHOR]

Highlights: [•] The components do not strongly change the primary mesoporous texture of γ-Al2O3. [•] The nature and bond strength of the oxide precursors generate different S species. [•] Both tungsten reducibility and sulphur stability to oxidation determine the activity. [•] The KNiW system exhibits both features to moderate extent and the highest activity. [ABSTRACT FROM AUTHOR]

The dispersion relations for surface plasmon polaritons propagating in the Voigt geometry in a metal-insulator-metal waveguide with a magneto-optically active dielectric medium are derived. The symmetry between the upper and lower interfaces is broken by the introduction of the magnetic field; the balance between the field distributions on the two interfaces can be controlled by the applied field. This control is illustrated by finite-element method numerical simulations of the field distributions around a point dipole placed in the center of the short waveguide; it is shown that both the total emission of radiation from the cavity and the distribution of the far-field radiation can be strongly modified by tuning the magnetization of the waveguide. This raises the possibility of using magnetic fields to control light propagation in nanostructures. [ABSTRACT FROM AUTHOR]

This paper is treating the problem of reducing energy consumption through heat integration system of bioreactors for antibiotics production. A scheme for heat integration with two heat tanks providing work in different time intervals is proposed. A practically feasible method for managing the processes of heat integration is designed. The task is formulated in terms of continuous nonlinear programming (NLP). The method has been applied to a real industrial process for the production of antibiotics. [ABSTRACT FROM AUTHOR]

In this study the problem of reduction of energy consumption in bioreactors system of antibiotics production by means of energy integration is considered. An energy integration scheme with two heat storage tanks ensuring the system operation at different time intervals is proposed. An approach for processes management of energy integration is developed. The problem is formulated in the terms of MINLP. The efficiency of proposed approach is illustrated on the example of the industry. [ABSTRACT FROM AUTHOR]