A p53-TLR3 axis ameliorates pulmonary hypertension by inducing BMPR2 via IRF3

Pulmonary arterial hypertension (PAH) features pathogenic and abnormal endothelial cells (ECs), and one potential origin is clonal selection. We studied the role of p53 and toll-like receptor 3 (TLR3) in clonal expansion and pulmonary hypertension (PH) via regulation of bone morphogenetic protein (BMPR2) signaling. ECs of PAH patients had reduced p53 expression. EC-specific p53 knockout exaggerated PH, and clonal expansion reduced p53 and TLR3 expression in rat lung CD117+ ECs. Reduced p53 degradation (Nutlin 3a) abolished clonal EC expansion, induced TLR3 and BMPR2, and ameliorated PH. Polyinosinic/polycytidylic acid [Poly(I:C)] increased BMPR2 signaling in ECs via enhanced binding of interferon regulatory factor-3 (IRF3) to the BMPR2 promoter and reduced PH in p53−/− mice but not in mice with impaired TLR3 downstream signaling. Our data show that a p53/TLR3/IRF3 axis regulates BMPR2 expression and signaling in ECs. This link can be exploited for therapy of PH

The assessment of physicians' and senior medical students’ knowledge in the field of communityacquired pneumonia: preliminary results of the KNOCAP-II project (2017-2019)

Внебольничная пневмония (ВП) относится к одной из самых актуальных проблем современной медицины. На сегодняшний день ВП занимает 4 место в структуре смертности (после сердечно-сосудистых, цереброваскулярных заболеваний и злокачественных новообразований) и 1 место среди всех смертей от инфекционных заболеваний. Цель – оценка уровня знаний врачей терапевтического профиля и студентов старших курсов медицинских вузов в вопросах ведения пациентов с ВП. В рамках многоцентрового исследования KNOCAP (полное название проекта – «The assessment of physician and students’ knowledge of community-acquired pneumonia basics») представлены результаты анонимного проспективного опроса по оценке знаний и предпочтений врачей терапевтического профиля и студентов старших медицинских курсов в вопросах ведения пациентов с ВП. По итогам первого периода проекта (2017-2019 гг.) получены и проанализированы результаты анкетирования 588 врачей терапевтического профиля и 394 студентов-медиков из 17 центров России, Украины и Кыргызстана. За основу взят метод анонимного анкетирования, для чего была разработана оригинальная анкета на основании актуальных клинических рекомендаций. Наибольшие сложности вызвали следующие вопросы: сроки проведения повторного рентгенологического исследования при положительной динамике лечения, выбор основного диагностического признака при ведении пациента с ВП, указать типовые ошибки фармакотерапии ВП и выбор стартовой антимикробной терапии у пациентов с факторами риска и без них. В целом исследование показало значимое несоответствие знаний в вопросах ведения пациентов с ВП актуальным клиническим рекомендациям 2010 г. и проектом новых клинических рекомендаций 2018-2019 гг. В настоящее время существует необходимость в повышении уровня знаний и совершенствовании профессиональной деятельности врачей терапевтического профиля и студентов старших медицинских курсов, так как проведенный многоцентровой срез знаний и предпочтений специалистов во многих вопросах выявил их недостаточный уровень для корректного ведения пациентов с ВП. Community-acquired pneumonia (CAP) is one of the most relevant problems of modern medicine. Today, CAP takes 4th place in the structure of mortality (after cardiovascular, cerebrovascular diseases and malignant neoplasms) and 1st place among all deaths from infectious diseases. The aim of the study is to assess the level of general physician’ and senior medical students’ basic knowledge in CAP treatment. The article represents the results of anonymous prospective surveys within the framework of the second stage of KNOCAP multi-centered research project (full name of the project «The assessment of physician’ and students’ knowledge of community-acquired pneumonia basics») aimed at accessing the knowledge and preferences of doctors and students on the fundamental issues in diagnosis and treatment of community-acquired pneumonia. The survey conducted in 2017-2019 involved 588 physicians and 394 students from seventeen Russian, Kyrgyzstan and Ukrainian centers. The method of anonymous questioning was used in this study, for which an original questionnaire was developed on the basis of current clinical recommendations. The following fundamental questions caused the greatest difficulties in the respondents: terms for a repeated X-ray examination in positive dynamics of CAP treatment, the choice of main diagnostic criteria of CAP, the choice of the typical mistakes of CAP treatment, the choice of the initial antimicrobial therapy. In general, the respondents’ knowledge in CAP patients’ management deviates significantly from the current clinical guidelines, as of 2010, and from the new clinical guidelines draft, 2018-2019. Currently, there is a need to increase the level of knowledge and improve the professional activities of therapists and senior medical students, as a multicenter section of the knowledge and preferences of specialists in many issues revealed their insufficient level for the correct management of patients with CAP

One-step quantitative RT-PCR assay with armored RNA controls for detection of SARS-CoV-2

Coronavirus disease 2019 (COVID-19) has become pandemic since March 11, 2020. Thus, development and integration in clinics of fast and sensitive diagnostic tools are essential. The aim of the study is a development and evaluation of a one-step quantitative reverse transcription-polymerase chain reaction (RT-qPCR) assay (COVID-19 Amp) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection with an armored positive control and internal controls constructed from synthetic MS2-phage-based RNA particles. The COVID-19 Amp assay limit of detection was 103 copies/ml, the analytical specificity was 100%. A total of 109 biological samples were examined using COVID-19 Amp and World Health Organization (WHO)-based assay. Discordance in nine samples was observed (negative by the WHO-based assay) and discordant samples were retested as positive according to the results obtained from the Vector-PCRrv-2019-nCoV-RG assay. The developed COVID-19 Amp assay has high sensitivity and specificity, includes virus particles-based controls, provides the direct definition of the SARS-CoV-2 RdRp gene partial sequence, and is suitable for any hospital and laboratory equipped for RT-qPCR. © 2020 Wiley Periodicals LL

Influence of non-motor symptoms on the Parkinson's disease features and on quality of patients' life

The main clinical symptoms of PD are well understood, but it is necessary to continue studying the changes of symptoms as it progresses. The aims of the research were: to study the structure of non-motor symptoms (NMS) at the early and last stages of PD, to determine the frequency and clinical significance of the NMS at different stages of PD, comparing the severity of NMS in PD with the severity of the same symptoms in the natural aging, to study the quality of life (QOL) of patients with the impact assessment of the NMS and the assessment of motor symptoms on this criterion. The material and methods. The study included 79 patients with PDand 25 patients without neurodegenerative disorders (control group). The degree of movement disorders severity was assessed using UPDRS scale. Cognitive function was assessed using the Montreal Cognitive Rating Scale (MoCA). To identify and assess the severity of NMS questionnaire used NMSS. Assessment of quality of life of patients was carried out by PDQ-39 questionnaire. Results. There was a significant difference between the intensity of the NMS in PD patients and the control group. Intensity of NMSs significantly correlated with disease stage, disease duration, with the points on the UPDRS scale. Conclusion. NMS significantly affect the quality of life, their severity and structure varies considerably from early to late stage PD, and they are the result of a neurodegenerative process, inherent in PD, and not the natural aging process

Computational chemistry of the silicon nitride surface. 2. Binary hydroxylamine complexes. Geometry and bond energies

In order to study the silicon nitride surface it is interesting to consider hydrogen-bonded complexes with hydroxyl and amine key groups (OH...O, OH...N, NH...O, and NH...N). To investigate the behavior of the above bonds, we considered the water, ammonia, and hydroxylamine dimers and the binary hydroxylamine complexes with water and ammonia. The results of this work are compared with the data obtained by an ab initio method. © 1996 Plenum Publishing Corporation

COMPUTATIONAL CHEMISTRY OF THE SILICON-NITRIDE SURFACE .1. WATER, AMMONIA, AND WATER-AMMONIA COMPLEX

This paper deals with computational modeling of structure and properties of the silicon nitride surface zone using combined computational and real experiments. The computational experiment implies quantum chemical calculations of structure and vibrational spectra of polyatomic clusters. The real experiment suggests measurement and analysis of vibrational spectra. For quantum chemical calculations, semiempirical methods (MNDO and AM1) were chosen. In most calculations, the MNDO/H method was preferred because of the presence of many H-bonds in the surface zone. For verification of calculations, we calculated the structures and vibrational spectra of water and ammonia molecules and the water-ammonia complex and compared the results with experimental and ab initio (extended basis) data; MNDO/H proved to be an optimal method giving reliable results

COMPUTATIONAL CHEMISTRY OF THE SILICON-NITRIDE SURFACE .1. WATER, AMMONIA, AND WATER-AMMONIA COMPLEX

This paper deals with computational modeling of structure and properties of the silicon nitride surface zone using combined computational and real experiments. The computational experiment implies quantum chemical calculations of structure and vibrational spectra of polyatomic clusters. The real experiment suggests measurement and analysis of vibrational spectra. For quantum chemical calculations, semiempirical methods (MNDO and AM1) were chosen. In most calculations, the MNDO/H method was preferred because of the presence of many H-bonds in the surface zone. For verification of calculations, we calculated the structures and vibrational spectra of water and ammonia molecules and the water-ammonia complex and compared the results with experimental and ab initio (extended basis) data; MNDO/H proved to be an optimal method giving reliable results

Peutz-Jeghers' syndrome in pediatric dermatological practice [Синдром Пейтца-Егерса в детской дерматологической практике]

Peutz-Jeghers' syndrome is a rare hereditary disease inherited by an autosomal dominant type, manifested by a characteristic clinical picture of skin lesions and hamartomas of the gastrointestinal tract. Complications of the disease include bleeding from polyps, anemia, intussusception and intestinal necrosis, as well as a high likelihood of developing malignant tumors. For the first time the syndrome was described at the beginning of the last century, and it is of interest to dermatologists, gastroenterologists, oncologists and surgeons due to the clinical heterogeneity of intestinal and skin manifestations. The article describes a clinical case of a 5-year-old girl with the Peutz-Jaegers syndrome. The patient complained of periodic dull abdominal pain that worsened after eating solid food. During the examination of the skin and mucous membranes the doctors discovered rashes on the face: perioral area, on the red border of the lips and on the mucous membrane of the lips, inside the cheeks, hard palate. Esophagogastroduodenoscopy (EGDS) revealed a polyp on a pedicle in the prepyloric part - it was removed during repeated EGDS under endotracheal anesthesia. Fibrocolonoscopy revealed hyperpigmentation of the dome of the cecum. To confirm the diagnosis, the doctors carried out DNA testing which found a mutation of the STK11 gene. Pigmentation of the perioral area is an early symptom of Peutz-Jeghers' syndrome suggesting optimal examination. Early recognition of the syndrome in children is important in the context of reducing the risk of developing intestinal obstruction, bleeding, and cancer complications in the future. © 2021 National Academy of Pediatric Science and Innovation. All rights reserved

Iron deficiencies: focus on teenage girls

T.M.&nbsp;Vasil’eva1,2, I.N. Zakharova1, A.L. Zaplatnikov1,3, N.G. Sugyan1,2, E.V. Shirdanina2, E.A. Doroshina1, L.S. Serikova1, I.D. Maykova3, O.A. Kuznetsova3, A.S.&nbsp;Vorob’eva3, E.R. Radchenko3, L.V. Goncharova3, N.V. Gavelya3 1Russian Medical Academy of Continuous Professional Education, Moscow, &nbsp;Russian Federation 2City Children Outpatient Department No. 133, Moscow, Russian Federation 3Z.A. Bashlyaeva City Children Clinical Hospital, Moscow, Russian Federation Aim: to improve the efficacy of iron deficiency treatment in teenage girls by their early diagnosis and rational treatment. Patients and Methods: complete blood count was performed in 2,303 teenage schoolgirls aged 14–17 years (mean age 16.3±0.6 years) who underwent routine annual medical examination. Whole capillary blood was tested. Reduced hemoglobin concentration (less than 120 g/l) was anemia diagnostic criterion in teenage girls. Hypochromic anemia was verified in color index less than 0.85 and mean corpuscular hemoglobin (MCH) less than 26 pg. In some girls (n=133) with verified isolated hypochromic red blood cells but in the lack of anemia and microcytosis, serum iron, total iron-binding capacity, serum ferritin, and transferrin saturation were measured. Results: hypochromic anemia was diagnosed in 8.3% of teenage girls. In 96.8% of them, anemia was mild. In 133 teenage girls with verified hypochromic red blood cells but no anemia, latent iron deficiency was diagnosed in 20.3% of cases. Preliminary results of mild iron-deficiency anemia treatment in 19 teenage girls (mean age 14.7±0.5 years) using Tardyferon demonstrate its good tolerability and high clinical laboratory efficacy. After 4 weeks of the treatment, hemoglobin concentration has increased by 10.7±0.3 g/l (р&lt;0.05). No adverse side effects were reported. Conclusions: our findings demonstrate that the algorithm described in this paper should be followed to improve the diagnosis of iron deficiencies. Keywords: anemia, hypochromic RBCs, teenage, iron deficiencies, iron-deficiency anemia, latent iron deficiency, iron preparations, Tardyferon. For citation: Vasil’eva T.M., Zakharova I.N., Zaplatnikov A.L. et al. Iron deficiencies: focus on teenage girls. Russian Journal of Woman and Child Health. 2019;2(3):206–212. <br