Placental mosaicism and complications of pregnancy

Timely diagnosis of chromosomal aneuploidies plays an important role in determining the proper approach to the management of pregnancy. This article outlines the current ideas on the likelihood of occurrence of obstetric pathology, depending on the number of cells with genetic aberration, especially in the placenta. Such obstetric complications include fetal growth retardation, premature birth, and some forms of preeclampsia. The article describes the prenatal examination techniques, which help obtain timely information about the development of the fetus and predict pregnancy complications, more specifically, non-invasive prenatal DNA screening as a new technique with its advantages and limitations, based on the analysis of DNA of placental origin. It also highlights other latest diagnostic tools that allow to get more accurate information about placental mosaicism and the development of pathology. We have reviewed publications over the past 10 years, which are devoted to the factors responsible for the formation of placental mosaicism, the prenatal diagnostic procedures required for an accurate diagnosis, and the likelihood of obstetric pathology in case of prolonged pregnancy complicated by genetic aberrations. Foreign studies confirm the direct dependence of the likelihood of obstetric pathology on the number of cells with genetic aber ration. In accordance with the above study results, it would be only right to note that placental insufficiency can be observed in any case of genetic aberration, especially if a large volume of cells is involved in the pathological process at an early stage of differentiation. In addition, the article discusses the issue of need of thorough prenatal diagnosis to prevent the development of pregnancy pathology, including the use of the latest technologies and minimizing invasive methods

Concerning effective and safe dosages of vitamin D3: mega-analysis of clinically effective studies as a basis for actual evidence

The negative effects of hypovitaminosis D3 and vitamin D3 deficiency in 80% of Russians make eliminating vitamin D deficiency an issue of state concern. Hundreds of effective clinical studies showed realistic opportunities of vitamin D3 to help patients with disorders of carbohydrate and lipid metabolism, high levels of nonspecific inflammation, tuberculosis, and women with a higher risk of complications and pregnancy losses. Vitamin D3 supplements are essential for the prevention and treatment of a wide range of “bone” and “extraosseous” diseases. One of the most important aspects of the clinical uses of vitamin D3 is the dosage and dosage regimen of the vitamin. This paper presents the results of a “mega-analysis” of 3965 clinical studies of vitamin D3 in terms of the effectiveness of different dosages in achieving different clinical outcomes. It was shown that dosages of 2000 IU/day and 4000 IU/day correspond to the peak values of the effectiveness index, regardless of the diagnoses studied (mega-analysis of 420 randomized trials). Some effectiveness in the treatment of rickets, gestational diabetes, calcium metabolism disorders, disorders of bone density and structure, diseases of the musculoskeletal system and connective tissue can be achieved using weekly dosages of 50,000 IU/week (mega-analysis of 196 studies). It has been shown that dosages of 100,000-1,000,000 IU, intended for a single dose once a month, are almost always found only among studies with a negative result (mega-analysis of 368 studies)

Effect of immunocytotherapy on the state of the immune system of women with idiopathic habitual miscarriage

We aimed  for assessing effects of immunocytotherapy upon  the subpopulations of CD4+CD25highFoxP3+ cellswithnaturalregulatoryactivityandactivatedTh17cellswiththeCD4+CD25highRORγt+ phenotype, as well as in vitro production of cytokines in mitogen-stimulated cells from  peripheral blood  in the patients with idiopathic habitual miscarriage (IHM). The study group consisted of 33 patients with IHM who became pregnant after a pre-gestational alloimmunization. In 27 patients, the pregnancy was prolonged to the  full term  and  ended  with the  birth  of viable babies,  in six cases it was terminated before  12 weeks of gestation. Before  administration of immunocytotherapy (ICT), 19 patients were examined, of them  16 after alloimmunization outside of pregnancy, 17 at 5-6 and 8-9 weeks of pregnancy. Eleven patients were immunized at 12 weeks of pregnancy. In the control group,  12 fertile women  outside  pregnancy and 10 women  at 12 weeks of physiological pregnancy were examined. The proportion of FoxP3+ and RORγt+ cells with the CD4+CD25high phenotype was evaluated among  T-lymphocytes from peripheral blood,  as well as content of proinflammatory cytokines (IFNγ,  TNFα, IL-1β, IL-2, IL-5, IL  -6,  IL-8, IL-12p70) and  anti-inflammatory factors  (IL-4, IL-10), as well as IL-17  amounts.We have found  that,  following pre-gestational alloimmunization, the women  who lost this pregnancy, had a  low  level  of  FoxP3+Тregs that  suppress  pro-inflammatory Th17-dependent  reactions, however, without changing levels of activated Th17  cells (CD4+CD25highRORγt+   lymphocytes). These  facts,  along  with  high in vitro production of IL-17  by peripheral blood cells at the terms of 5-6 weeks of gestation, suggest that,  after pre-gestational alloimmunization in women  with miscarriage, a predilection is formed  to pro-inflammatory cytokine production. However, at the 5-6 week-period, it is realized  not in the Th1 direction of, but towards Th17 response, and a low level of CD4+CD25highRORγt+ cells may reflect an increased migration of Th17 cells from peripheral blood to the uterine endometrium.Thus,  we have shown  the  effect of immunocytotherapy upon  subpopulational composition of peripheral blood  lymphocytes and  the  cytokine profile,  as well as upon  the  course  of first trimester and  outcomes of pregnancy in women  with idiopathic habitual miscarriage

Компьютерный анализ эмоциональной модальности 20 млн публикаций в базе данных PUBMED указывает на пути повышения эффективности фармакотерапии посредством идентификации псевдонаучных публикаций, направленных на негативную эмоциональную «накачку» врачей

The search for original publications on fundamental and clinical medicine that would produce results of the highest scientific quality represents an urgent need for every medical researcher. Such publications are essential, in particular, for the development of reliable treatment standards. The Englishlanguage resources PUBMED and EMBASE are essential to help in solving this problem. However, there is an obvious problem in assessing the quality of the studies found. The paper formulates a method for analyzing the texts of biomedical publications, which is based on an algorithmic assessment of the emotional modality of medical texts (so-called sentiment analysis). The use of the topological theory of data analysis made it possible to develop a set of high-precision algorithms for identifying 16 types of sentiments (manipulative turns of speech, research without positive results, propaganda, falsification of results, negative personal attitude, aggressiveness of the text, negative emotional background, etc.). On the basis of the developed algorithms, a point scale for assessing the sentiment quality of research was obtained, which we called the "β-score": the higher the β-score, the less the evaluated text contains manipulative language constructions. As a result, the ANTIFAKE system (http://antifake-news.ru) was developed to analyze the sentiment-quality of Englishlanguage scientific texts. An analysis of ~ 20 million abstracts from PUBMED showed that publications with low sentiment quality (β-score <0, that is, that the prevalence of manipulative constructions over meaningful ones) is only 19 %. In the overwhelming majority of thematic headings (27,090 out of 27,840 headings of the MESH system PUBMED), a positive dynamics of sentiment quality of the texts of publications is shown by years). At the same time, as a result of the study, 249 headings were identified with sharply negative dynamics of sentiment quality and with a pronounced increase in manipulative sentiments characteristic of the "yellow" English-language press. These headings include tens of thousands of publications in peer-reviewed journals, which are aimed at (1) legalizing ethically unacceptable practices (euthanasia, perversions, so-called "population control", etc.), (2) discrediting psychiatry as a science, (3) media the war against micronutrients and (4) discrediting evidence-based medicine under the guise of developing the so-called "international standards of evidence-based medicine". In general, the developed system of artificial intelligence allows researchers to filter out pseudoscientific publications, the text of which is overloaded with emotional manipulation and which are published under the guise of "evidence-based standards".Поиск оригинальных публикаций по фундаментальной и клинической медицине наивысшего научного качества – насущная необходимость для каждого врача-исследователя. Такие публикации принципиально необходимы, в частности, для разработки надёжных стандартов лечения. Существенной подмогой в решении этой задачи являются англоязычные ресурсы PUBMED и EMBASE. Однако существует очевидная проблема оценки качества находимых исследований. В работе сформулирована методика анализа текстов биомедицинских публикаций, в основе которой лежит алгоритмическая оценка эмоциональной модальности медицинских текстов (т. н. сентимент-анализа). Применение топологической теории анализа данных позволило разработать комплекс высокоточных алгоритмов для выявления 16 типов сентиментов (манипулятивные обороты речи, исследования без положительных результатов, пропаганда, подделка результатов, негативное личное отношение, агрессивность текста, негативный эмоциональный фон и др.). На основе разработанных алгоритмов получена балльная шкала оценки сентимент-качества исследований, которую мы назвали «β-баллом»: чем выше β-балл, тем в меньшей степени оцениваемый текст содержит манипулятивные языковые конструкции. В результате разработана и апробирована система ANTIFAKE (http://antifake-news.ru), предназначенная для анализа сентимент-качества англоязычных научных текстов. Анализ ~20 млн абстрактов из PUBMED показал, что публикации с низким сентимент-качеством (β-балл которые направлены на (1) легализацию этически порочных практик (эвтаназия, т. н. «контроль популяций» и т. п.), (2) дискредитацию психиатрии как науки, (3) медийную войну против микронутриентов и (4) дискредитацию доказательной медицины под видом разработки т. н. «международных стандартов доказательной медицины». В целом, разработанная система искусственного интеллекта позволяет отфильтровывать псевдонаучные публикации, текст которых перегружен эмоциональной манипуляцией и которые публикуются под маской «доказательных стандартов»

Dydrogesterone in the treatment of the threatened and habitual miscarriage

The article presents the findings of the studies evaluating the efficacy of gestagens in the treatment of the threatened and habitual miscarriage. It summarizes a number of meta-analysis related to the comparative evaluation of the use of various gestagens during pregnancy. The foreign societies’ guidelines for the treatment of reproductive disorders and the management of early pregnancy in women with the threatened and habitual miscarriage are outlined

The prevention of rh-immunization in women after surgical correction of istmicocervical insufficiency

Sensitization occurs when an Rh-negative mother is exposed to Rh-positive fetal red blood cells during pregnancy in 1% of  cases and after delivery in 10% of cases, when fetal antigens enter mother’s circulation [1, 2]. A major cause of HDN is an incompatibility of the Rh blood group between the mother and fetus. The article substantiates the necessity of prophylaxis of rhesus sensitization after surgical correction of istmicocervical insufficiency

Bleeding before the 22th week of pregnancy: clinical pattern, diagnosis, haemostatic therapy

According to the national classification acting since 2012, early pregnancy loss happens before 21 weeks and 6 days of pregnancy, and premature birth is registered at 22 to 37 weeks of pregnancy. The global approach to registering perinatal mortality calls for prevention of complications starting from early pregnancy in order to avoid extremely preterm births

Systematic analysis of research on D-mannose and the prospects for its use in recurrent infections of the urinary tract in women of reproductive age

Cystitis and other urinary tract infections (UTIs) in women of reproductive age can lead to infertility, significantly complicate the course of pregnancy, and cause numerous fetal abnormalities. Antibiotic therapy during pregnancy is an extreme measure since it is associated with a high risk of fetal malformations. The use of D-mannose is an effective and safe treatment for cystitis and other UTIs, especially during pregnancy. The present systematic analysis of 32111 studies indicates a significance of D-mannose for glycosylation of human proteins and for functioning of the immune, cardiovascular, urinary and other systems. By blocking the interaction between bacterial fimbriae and the endothelium, D-mannose prevents the adsorption of bacteria (uropathogenic strains of Escherichia coli, Pseudomonas aeruginosa, Shigella, leishmania, mycobacteria, etc.) to the tissue surface, thus helping prevent recurrent UTIs. Clinical studies have confirmed both high efficacy and safety of using D-mannose and the synergistic substances (such as cranberry anthocyanins) for the treatment of cystitis and other UTIs