Analysis of the placental tissue transcriptome of normal and preeclampsia complicated pregnancies

Preeclampsia is one of the most severe gestational complications which is one of the leading causes of maternal and perinatal morbidity and mortality. A growth in the incidence of severe and combined forms of the pathology has been observed in recent years. According to modern concepts, inadequate cytotrophoblast invasion into the spiral arteries of the uterus and development of the ischemia-reperfusion syndrome in the placental tissue play the leading role in the development of preeclampsia, which is characterized by multipleorgan failure. In this regard, our work was aimed at studying the patterns of placental tissue transcriptome that are specific to females with PE and with physiological pregnancy, as well as identifying the potential promising biomarkers and molecular mechanisms of this pathology. We have identified 63 genes whose expression proved to differ significantly in the placental tissue of females with PE and with physiological pregnancy. A cluster of differentially expressed genes (DEG) whose expression level is increased in patients with preeclampsia includes not only the known candidate genes that have been identified in many other genome-wide studies (e.g., LEP, BHLHB2, SIGLEC6, RDH13, BCL6), but also new genes (ANKRD37, SYDE1, CYBA, ITGB2, etc.), which can be considered as new biological markers of preeclampsia and are of further interest. The results of a functional annotation of DEG show that the development of preeclampsia may be related to a stress response, immune processes, the regulation of cell-cell interactions, intracellular signaling cascades, etc. In addition, the features of the differential gene expression depending on preeclampsia severity were revealed. We have found evidence of the important role of the molecular mechanisms responsible for the failure of immunological tolerance and initiation of the pro-inflammatory cascade in the development of severe preeclampsia. The results obtained elaborate the concept of the pathophysiology of preeclampsia and contain the information necessary to work out measures for targeted therapy of this disease.

Cellular internalisation, bioimaging and dark and photodynamic cytotoxicity of silica nanoparticles doped by {Mo₆I₈}⁴⁺ metal clusters

Silica nanoparticles (SNPs) doped by hexanuclear molybdenum cluster complexes [{Mo₆X₈}L₆]n (X = Cl, Br, or I; L = various inorganic or organic ligands) have been recently suggested as materials with a high potential for biomedical applications due to both the outstanding photoluminescent properties and the ability to efficiently generate singlet oxygen upon photoirradiation. However, no studies were undertaken so far to prove this concept. Therefore, here we examined the potential of photoluminescent SNPs doped by {Mo₆I₈}⁴⁺ for such applications as bioimaging and photodynamic therapy using human epidermoid larynx carcinoma (Hep-2) cell line as a model. Our results demonstrated both: (i) significant luminescence from cells with internalised molybdenum cluster doped SNPs combined with the low cytotoxicity of particles in the darkness and (ii) significant cytotoxicity of the particles upon photoirradiation. Thus, this research provides strong experimental evidence for high potential of molybdenum cluster doped materials in such biomedical applications as optical bioimaging, biolabeling and photodynamic therapy

Ribonuclease activity as a new prospective disease resistance marker in potato

Disease resistance is an important characteristic for each variety of potato, and the search for pathogen resistance markers is one of the primary tasks of plant breeding. Higher plants possess a wide spectrum of enzymes catalyzing the hydrolysis of nucleic acids; it is believed that protection against pathogens is the most probable function of the enzymes. RNases are actively involved in several immune systems of higher plants, for example, systemic acquired resistance (SAR) and genetic silencing, hence RNase activity in plant leaves, as a relatively easily measured parameter, can serve as a good marker for the selection of pathogen resistant varieties. We have analyzed sixteen varieties of potatoes permitted for use on the territory of the Russian Federation and tested the correlation of the level of variety­specifc ribonuclease (RNase) activity with such economically valuable traits as maturity and resistance to viruses, late blight and common scab. In general, the level of RNase activity was variety­specifc, which was confrmed by very small values of average squared error for the majority of tested varieties. We have detected a statistically signifcant positive correlation of RNase activity in potato leaves with increased resistance of varieties to phytopathogenic viruses, a negative correlation with resistance to scab and an absence of a signifcant connection with maturity and resistance to late blight, regardless of the organ affected by the oomycete. Thus, the level of RNase activity in potato leaves can be used as a selective marker for resistance to viruses, while varieties with increased RNase activity should be avoided when selecting resistance to scab

The study of medico-social aspects of the quality of life and the level of health care provided to children with type 1 diabetes

The article presents the results of a questionnaire-based survey of children with type 1 diabetes mellitus and their parents, analyzes medical and social aspects of the lifestyle and quality of life and the level of health care provided. Our findings indicate that the pediatric patients face significant social limitations and are at risk of developing complications (inability to attend preschool educational institutions, extracurricular and physical education classes; the need for psychological consultations; lack of conditions for controlling the level of glycemia and insulin at school; problems with school meals). The survey results helped develop recommendations for prevention of complications of diabetes mellitusВ статье представлены результаты анкетирования детей с сахарным диабетом 1 типа и их родителей, проанализированы медикосоциальные аспекты образа и качества жизни, уровень оказываемой медицинской помощи. Полученные результаты свидетельствуют о том, что у детей с данным заболеванием есть существенные социальные ограничения и присутствуют факторы риска развития осложнений (невозможность посещения дошкольных образовательных учреждений, дополнительных занятий, занятий по физической культуре, необходимость психологических консультаций, отсутствие условий для осуществления контроля уровня гликемии и постановки инсулина в образовательных учреждениях, проблемы с приемом пищи в школе). По результатам опроса были разработаны рекомендации, направленные на профилактику развития осложнений

Performance for proton anisotropic flow measurement of the CBM experiment at FAIR

The Compressed Baryonic Matter experiment (CBM) performance for proton anisotropic flow measurements is studied with Monte-Carlo simulations using collisions of gold ions at lab momentum of 12A GeV/c employing DCM-QGSM-SMM heavy-ion event generator. Realistic procedures are used for centrality estimation with the number of registered tracks and particle identification with information from Time-Of-Flight detector. Variation of directed flow estimates depending on various combinations of PSD modules is used to evaluate possible systematic biases due to collision symmetry plane estimation

Help-Seeking for Sexual Difficulties and the Potential Role of Interactive Digital Interventions: Findings From the Third British National Survey of Sexual Attitudes and Lifestyles

Sexual difficulties are common and can negatively impact health and well-being. A wide range of support is available, but there are multiple barriers to accessing help. Interactive digital interventions (IDIs) for sexual difficulties have the potential to provide a convenient, wide-reaching, and cost-effective source of support, but little is known about who might use them. We explored the potential reach of IDIs by assessing the prevalence of help-seeking among people with distressing sexual difficulties, including who seeks which sources of help. Data came from sexually active men and women, ages 16 to 74, participating in Britain's third National Survey of Sexual Attitudes and Lifestyles (Natsal-3) (N = 11,637). Help/advice was sought by less than half of those with distressing sexual difficulties, and help-seeking was associated with younger age in women but not men. The most popular sources of support were family doctor (47.5% to 54.8%), Internet (22.0% to 25.6%), and family/friend (20.7% to 41.8%), with older participants (≥ 35), particularly men, preferring to seek help from a family doctor, and younger participants (<35) preferring to seek help from the Internet or family/friend. Despite a paucity of good digital support sites for sexual function, the Internet is a common source of help. As Internet access continues to increase, so too does the potential for well-designed IDIs to support those with sexual difficulties

Sexual mixing in opposite-sex partnerships in Britain and its implications for STI risk: findings from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3)

Background: The extent to which individuals are similar to their sexual partners influences STI-transmission probabilities, yet there is a dearth of empirical data, especially those representative of the population. Methods: Analyses of data reported by 10 759 sexually active people aged 16-74 y interviewed for a British national probability survey undertaken in 2010-12. Computer-assisted self-interviews asked about partner numbers and characteristics of participants' three most recent partnerships (MRPs). Opposite-sex MRPs were weighted to represent all such partnerships in the past year (N = 16 451). Estimates of disassortative age mixing (≥±5-y difference), ethnic mixing (partner of a different ethnic group) and geographical mixing (partner from a different region/country when they first met) were calculated, stratified by gender, age group and partnership status (casual/steady). Multivariable regression examined how these disassortative mixing measures were associated with STI-risk measures: condom use at first sex together at the partnership-level and, at the participant-level, STI-risk perception and reporting STI diagnoses. Results: Disassortative age mixing occurred in around one-third of opposite-sex partnerships, with men ≥5 y older in most cases, although this proportion varied by participant's gender and age group. Ethnic mixing occurred less frequently (11.3% of men's and 8.6% of women's partnerships) as did geographical mixing (14.1 and 16.3%, respectively). Disassortative mixing was more common among casual vs steady partnerships. Condom use at first sex was less likely in women's partnerships that were age-disassortative [adjusted odds ratio (AOR): 0.79, 95% confidence interval (CI): 0.69-0.95], whereas men reporting disassortative ethnic mixing were more likely to perceive themselves at STI risk (AOR: 1.76, 95% CI: 1.23-2.52) and report STI diagnoses (AOR: 2.37, 95% CI: 1.22-4.59). Conclusions: Disassortative mixing, although uncommon among opposite-sex partnerships in Britain, is independently associated with STI risk, warranting consideration in STI-prevention efforts

Analysis of factors affecting the accuracy of 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography in case of suspected prosthetic valve infective endocarditis

Aim. To analyze the factors affecting the accuracy of 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (PET/CT) in case of suspected prosthetic valve endocarditis (PVE).Material and methods. The results of PET/CT performed in 66 patients after heart valve replacement were analyzed: 55 patients with suspected PVE (≥3 months after surgery) and 11 comparison groups without PVE (2 months after surgery). In the group with suspected PVE (n=55) at the time of the study, 27% (15/55) had a normal body temperature, 85% (47/55) — no leukocytosis. In 16% (9/55), the examination was performed from 3 to 6 months after surgery and in 67% (37/55)  — against the background of long-term antibiotic therapy (ABT). The final diagnosis of PVE was made on the basis of clinical (including 6±3 followup), laboratory, instrumental, and intraoperative (n=40) data: confirmed  — in 37 patients; ruled out — in 29 patients. In order to determine the influence of factors on obtaining false PET/CT results, the odds ratio was calculated.Results. In the group with suspected PVE (n=55), the PET/CT results made it possible to establish and rule out PVE in 92% (34/37) and 67% (12/18) of patients, respectively. In 16% (9/55) of patients, false positive (n=6) and false negative (n=3) results. Thus, the sensitivity, specificity and diagnostic accuracy of PET/CT in the diagnosis of PVE were 92%, 67% and 84%, respectively; positive and negative predictive values — 85% and 80%. The analysis of the odds ratio did not reveal the relationship of low inflammatory activity, the interval between surgery and PET/CT from 3 to 6 months, and long-term ABT before PET/CT with false PET/CT results (p&gt;0,05). In the comparison group without PVE (n=11), 91% (10/11) received false positive PET/CT results, and one patient received a true negative result.Conclusion. The data obtained indicate the high informative value of PET/CT in the diagnosis of PVE. Interval &gt;2 months between surgery and PET/CT significantly reduces the accuracy of PET/CT results. Other factors analyzed in the presented group did not affect the accuracy of PET/CT results

CYTOSTATIC ARTEMISININ ACTIVITY

Artemisinin and its derivatives are among the most important and effective antimalarial drugs. In addition to their antimalarial effect, artemisinins also have selective antitumor properties, demonstrating cytotoxic effects against various types of tumors both in vitro and in vivo.Артемизинин и его производные являются одними из самых важных и эффективных противомалярийных препаратов. Помимо их противомалярийного эффекта, артемизинины также обладают селективными противоопухолевыми свойствами, демонстрирующие цитотоксические эффекты в отношении различных типов опухолей как in vitro, так и in vivo

Identification of hub genes of preeclampsia by integrated bioinformatics analysis

Preeclampsia (PE) is a multi-factorial and multi-organ disease that affects about 5% of pregnant women. It is the main cause of maternal and perinatal morbidity and mortality. Some studies show that PE is the result of defects in trophoblast invasion and spiral artery remodeling, but the exact underlying molecular mechanism of PE remains unclear. Next generation sequencing (NGS) and analysis of differentially expressed genes (DEGs) are used for the genetic study of PE. Gene networks are an actual way of studies because biological data, we can be considered as probable predictors of the disease (hub genes).Преэклампсия (ПЭ) - это многофакторное полиорганное заболевание, поражающее около 5 % беременных женщин, является основной причиной материнской и перинатальной заболеваемости и смертности. Установлено, что плацента играет ключевую роль в развитии данной патологии беременности: некоторые исследования показывают, что ПЭ является результатом неполной инвазии трофобласта и нарушения ремоделирования спиральных артерий, но точный молекулярный механизм ПЭ остается неясным. Высокопроизводительное секвенирование (NGS)и последующий анализ дифференциально-экспрессирующихся генов (ДЭГ) являются широко используемыми в настоящее время методиками генетического исследования ПЭ, однако все большую популярность набирает анализ генных сетей, так как он позволяет рассматривать гены в совокупности взаимодействий их белковых продуктов, а также выделять наиболее функционально-активные гены (hubgenes), которые можно рассматривать в качестве вероятных предикторов заболевани