Metabesity: pathogenetic bases and predictive capabilities. A review

One of the most pressing problems of our time is obesity, recognized by the WHO as a pandemic of the XXI century. It is important to remember that obesity is a full-fledged nosological entity, but many women think that obesity is just a problem of beauty and aesthetics. It is important to note that this nosology has a number of serious consequences, starting with the development of cardiovascular disease and ending with cancer. However, the “problem in the problem” is the so-called “metabesity” – a new term that reflects a number of diseases, the pathogenesis of which is based on the metabolic syndrome. Obesity, metabolic syndrome and metabesity seem to be different concepts, but the absolute identity of the pathogenetic basis characterizes them as successive stages of one global process. In this regard, it is necessary to highlight the key mechanisms of the development of the described disorders and to consider the concept of clinical management of patients in this cohort

Comparative analysis of molecular RFLP and SNP markers in assessing and understanding the genetic diversity of various chicken breeds

Monitoring the genetic diversity of small populations is important with respect to conserving rare and valuable chicken breeds, as well as discovery and innovation in germplasm research and application. Restriction fragment length polymorphisms (RFLPs), the molecular markers that underlie multilocus DNA fingerprinting (MLDF), have historically been employed for this purpose, but over the past two decades, there has been an irreversible shift toward high-throughput single-nucleotide polymorphisms (SNPs). In this study, we conducted a comparative analysis of archived MLDF results and new data from whole-genome SNP genotyping (SNPg) among 18 divergently selected breeds representing a large sample of the world gene pool. As a result, we obtained data that fit the general concept of the phylogenetic distribution of the studied breeds and compared them with RFLP and SNP markers. RFLPs were found to be useful markers for retrospective assessment of changes in the genetic architecture and variability underlying the phenotypic variation in chicken populations, especially when samples from previous generations used for MLDF are unavailable for SNPg. These results can facilitate further research necessary to assess the possibility of extrapolating previous MLDF results to study the long-term dynamics of genetic diversity in various small chicken germplasm populations over time. In general, the whole-genome characterization of populations and breeds by multiple SNP loci will further form the basis for the development and implementation of genomic selection with the aim of effective use of the genetic potential of the domestic gene pool in the poultry industry

Синдром поликистозных яичников и ожирение: современная парадигма

Polycystic ovary syndrome is a heterogeneous endocrine disease that affects women of childbearing age. The pathogenesis of polycystic ovary syndrome has not been fully studied to date, its paradigm considers the genetic determinism of the manifestation of hormonal and metabolic disorders, which are considered to be criteria for the verification of the disease (hyperandrogenism, oligo/anovulation and/or polycystic ovarian transformation during ultrasound examination (ultrasound). This review discusses the main ways of interaction between hyperandrogenism, insulin resistance and obesity and their role in the pathogenesis of polycystic ovary syndrome, as well as possible methods of treatment for this category of patients. The review analyzes the role of hyperandrogenism and insulin resistance in the implementation of the genetic scenario of polycystic ovary syndrome and finds out the reasons why women with polycystic ovary syndrome often demonstrate the presence of a «metabolic trio» - hyperinsulinemia, insulin resistance and type 2 diabetes mellitus. It is noted that obesity is not included in the criteria for the diagnosis of polycystic ovary syndrome, but epidemiological data confirm the existence of a relationship between these diseases. Obesity, especially visceral, which is often found in women with polycystic ovary syndrome, enhances and worsens metabolic and reproductive outcomes with polycystic ovary syndrome, as well as increases insulin resistance and compensatory hyperinsulinemia, which, in turn, stimulates adipogenesis and suppresses lipolysis. Obesity increases the sensitivity of tech cells to luteinizing hormone stimulation and enhances functional hyperandrogenism of the ovaries, increasing the production of androgens by the ovaries. Excess body weight is associated with a large number of inflammatory adipokines, which, in turn, contribute to the growth of insulin resistance and adipogenesis. Obesity and insulin resistance exacerbate the symptoms of hyperandrogenism, forming a vicious circle that contributes to the development of polycystic ovary syndrome. These data allow us to conclude that bariatric surgery can become an alternative to drugs (metformin, thiazolidinedione analogs of glucagon-like peptide-1), which has shown positive results in the treatment of patients with polycystic ovary syndrome and obesity.Синдром поликистозных яичников представляет собой гетерогенное эндокринное заболевание, которым страдают женщины детородного возраста. Патогенез синдрома поликистозных яичников на сегодняшний день до конца не изучен, его парадигма рассматривает генетическую детерминированность манифестации гормональных и метаболических нарушений, которые принято считать критериями верификации заболевания (гиперандрогения, олиго/ановуляция и/или поликистозная трансформация яичников при ультразвуковом исследовании. В данном обзоре рассмотрены основные пути взаимодействия гиперандрогении, инсулинорезистентности и ожирения и их роль в патогенезе синдрома поликистозных яичников, а также возможные методы лечения данной категории пациенток. В обзоре анализируется роль гиперандрогении, и инсулинорезистентности в реализации генетического сценария синдрома поликистозных яичников и выясняются причины, почему женщины с синдромом поликистозных яичников часто демонстрируют наличие «метаболического трио» - гиперинсулинемии, резистентности к инсулину и сахарного диабета 2 типа. Отмечается, что ожирение не входит в критерии постановки диагноза синдрома поликистозных яичников, но эпидемиологические данные подтверждают наличие взаимосвязи между этими заболеваниями. Ожирение, особенно висцеральное, которое часто встречается у женщин с синдромом поликистозных яичников, усиливает и ухудшает метаболические и репродуктивные исходы при синдроме поликистозных яичников, а также увеличивает резистентность к инсулину и компенсаторную гиперинсулинемию, что, в свою очередь, стимулирует адипогенез и подавляет липолиз. Ожирение повышает чувствительность тека-клеток к стимуляции лютеонизирующим гормоном и усиливает функциональную гиперандрогению яичников, повышая выработку андрогенов яичниками. Избыток массы тела ассоциирован с большим количеством воспалительных адипокинов, которые, в свою очередь, способствуют росту резистентности к инсулину и адипогенез. Ожирение и инсулинорезистентность усугубляют симптомы гиперандрогении, образуя порочный круг, способствующий развитию синдрома поликистозных яичников. Приведенные данные позволяют сделать вывод, что альтернативой лекарственным средствам (метформин, тиазолидиндионоы аналоги глюкагоноподобного пептида-1) может стать бариатрическая хирургия, показавшая положительные результаты лечения пациенток с синдромом поликистозных яичников и ожирением

Poly(3-hydroxybutyrate) 3D-Scaffold–Conduit for Guided Tissue Sprouting

Scaffold biocompatibility remains an urgent problem in tissue engineering. An especially interesting problem is guided cell intergrowth and tissue sprouting using a porous scaffold with a special design. Two types of structures were obtained from poly(3-hydroxybutyrate) (PHB) using a salt leaching technique. In flat scaffolds (scaffold-1), one side was more porous (pore size 100–300 μm), while the other side was smoother (pore size 10–50 μm). Such scaffolds are suitable for the in vitro cultivation of rat mesenchymal stem cells and 3T3 fibroblasts, and, upon subcutaneous implantation to older rats, they cause moderate inflammation and the formation of a fibrous capsule. Scaffold-2s are homogeneous volumetric hard sponges (pore size 30–300 μm) with more structured pores. They were suitable for the in vitro culturing of 3T3 fibroblasts. Scaffold-2s were used to manufacture a conduit from the PHB/PHBV tube with scaffold-2 as a filler. The subcutaneous implantation of such conduits to older rats resulted in gradual soft connective tissue sprouting through the filler material of the scaffold-2 without any visible inflammatory processes. Thus, scaffold-2 can be used as a guide for connective tissue sprouting. The obtained data are advanced studies for reconstructive surgery and tissue engineering application for the elderly patients

Perspective Chapter: The Role of Interferon Gamma in Clinical Medicine

Interferon gamma (IFN-γ) is one of the key factors of both innate and adaptive immune response that promotes differentiation of naive CD4+ cells into effector Th1 T cells producing the main mediators of cellular immunity against viral and intracellular bacterial infections, and specific cytotoxic immunity through the interaction of T cells with antigen-presenting cells and macrophage activation. The clinical importance of IFN-γ includes its medical use to treat and prevent various viral and bacterial infections. IFN-γ has a direct antiviral effect on infected cells, activates local infiltrating dendritic cells, macrophages and NK cells, modulates the differentiation and maturation of T and B cells, and enhances inflammation and antiviral functions. Immunoregulatory effect of IFN-γ plays one of the essential roles in the regulation of adaptive immune response in patients with tuberculosis infection and cancer. Producing IFN-γ by T cells increases the efficiency of infiltrated phagocytic cells, by stimulating NO and maintaining local host defense during tuberculosis infection. The direct antitumor effect of IFN-γ revealed in several experimental models has numerous mechanisms for the effect of development. IFN-γ has crucial potential for enhancing any antiviral, antimycobacterial, and specific antitumor therapies

Feasibility and functional correlates of left atrial volume changes during stress echocardiography in chronic coronary syndromes

: An enlarged left atrial volume index (LAVI) at rest mirrors increased LA pressure and/or impairment of LA function. A cardiovascular stress may acutely modify left atrial volume (LAV) within minutes. Aim of this study was to assess the feasibility and functional correlates of LAV-stress echocardiography (SE) Out of 514 subjects referred to 10 quality-controlled labs, LAV-SE was completed in 490 (359 male, age 67 ± 12 years) with suspected or known chronic coronary syndromes (n = 462) or asymptomatic controls (n = 28). The utilized stress was exercise in 177, vasodilator in 167, dobutamine in 146. LAV was measured with the biplane disk summation method. SE was performed with the ABCDE protocol. The intra-observer and inter-observer LAV variability were 5% and 8%, respectively. ∆-LAVI changes (stress-rest) were negatively correlated with resting LAVI (r = - 0.271, p < 0.001) and heart rate reserve (r = -.239, p < 0.001). LAV-dilators were defined as those with stress-rest increase ≥ 6.8 ml/m2, a cutoff derived from a calculated reference change value above the biological, analytical and observer variability of LAVI. LAV dilation occurred in 56 patients (11%), more frequently with exercise (16%) and dipyridamole (13%) compared to dobutamine (4%, p < 0.01). At multivariable logistic regression analysis, B-lines ≥ 2 (OR: 2.586, 95% CI = 1.1293-5.169, p = 0.007) and abnormal contractile reserve (OR: 2.207, 95% CI = 1.111-4.386, p = 0.024) were associated with LAV dilation. In conclusion, LAV-SE is feasible with high success rate and low variability in patients with chronic coronary syndromes. LAV dilation is more likely with reduced left ventricular contractile reserve and pulmonary congestion

Stress echo 2030: The novel ABCDE-(FGLPR) protocol to define the future of imaging

With stress echo (SE) 2020 study, a new standard of practice in stress imaging was developed and disseminated: The ABCDE protocol for functional testing within and beyond CAD. ABCDE protocol was the fruit of SE 2020, and is the seed of SE 2030, which is articulated in 12 projects: 1-SE in coronary artery disease (SECAD); 2-SE in diastolic heart failure (SEDIA); 3-SE in hypertrophic cardiomyopathy (SEHCA); 4-SE post-chest radiotherapy and chemotherapy (SERA); 5-Artificial intelligence SE evaluation (AI-SEE); 6-Environmental stress echocardiography and air pollution (ESTER); 7-SE in repaired Tetralogy of Fallot (SETOF); 8-SE in post-COVID-19 (SECOV); 9: Recovery by stress echo of conventionally unfit donor good hearts (RESURGE); 10-SE for mitral ischemic regurgitation (SEMIR); 11-SE in valvular heart disease (SEVA); 12-SE for coronary vasospasm (SESPASM). The study aims to recruit in the next 5 years (2021-2025)≥10,000 patients followed for≥5 years (up to 2030) from≥20 quality-controlled laboratories from≥10 countries. In this COVID-19 era of sustainable health care delivery, SE2030 will provide the evidence to finally recommend SE as the optimal and versatile imaging modality for functional testing anywhere, any time, and in any patient