Changes in haemogram of pulmоnary TB patients during positive clіnical and radiology improvement

We studied changes in the complete blood count in 48 patients with infiltrative and disseminated pulmonary tuberculosis before and after treatment against positive clinical and radiographic improvement. The haemogram of patients with tuberculosis varies during the treatment. The mean concentration of haemoglobin in red blood cells and the count of red blood cells in peripheral blood of patients with infiltrative (in 60% of cases) and disseminated (in 45% of cases) tuberculosis increased equally: Hb to 139.5 and 139.3 g/l; RBC to 4.33∙10^12/l and 4.4∙10^12/l, respectively. In 9 (36 ± 9.2%) patients with infiltrative tuberculosis, there was a reduction in the average haemoglobin content in red blood cells of patients to 117.7 g/l, while in disseminated tuberculosis, haemoglobin level did not fall below 132.7 g/l. The obtained results are explained both by a more intensive haematotoxic effect of tuberculosis infection (in case of significant infiltration) and by a toxic adverse effect of prolonged specific chemotherapy, which these patients require. In the haemogram of patients with infiltrative tuberculosis, there was a greater severity of inflammation events, and in disseminated form – of allergic and autoimmune processes. In favourable cases, quantity and quality of blood cells become normal, reflecting the cessation of bacterial excretion, toxicity, and discussion of foci and areas of infiltration. Allergenic or toxic effects of different antibacterial medicines on haematopoiesis cannot be excluded. They often caused eosinophilia, in some cases - leukocytosis, band left shift, lymphocytosis, rarely leukopenia, which may stimulate the lymphoid and reticular reaction. The results indicate the feasibility to add TB chemotherapy with cytoprotective medicines

Nucleon resonance contributions to unpolarised inclusive electron scattering

The first CLAS12 experiments will provide high-precision data on inclusive electron scattering observables at a photon virtuality $Q^2$ ranging from 0.05 GeV$^2$ to 12 GeV$^2$ and center-of-mass energies $W$ up to 4 GeV. In view of this endeavour, we present the modeling of the resonant contributions to the inclusive electron scattering observables. As input, we use the existing CLAS electrocoupling results obtained from exclusive meson electroproduction data off protons, and evaluate for the first time the resonant contributions based on the experimental results on the nucleon resonance electroexcitation. The uncertainties are given by the data and duly propagated through a Monte Carlo approach. In this way, we obtain estimates for the resonant contributions, important for insight into the nucleon parton distributions in the resonance region and for the studies of quark-hadron duality

Polarized Structure Function σ\u3csub\u3eLT\u27\u3c/sub\u3e from ⁰p Electroproduction Data in the Resonance Region at 0.2 GeV² \u3c Q² \u3c 1.0 GeV²

The first results on the σLT′ structure function in exclusive π0p electroproduction at invariant masses of the final state of 1.5GeV \u3c W \u3c 1.8 GeV and in the range of photon virtualities 0.4 GeV2 \u3c Q2 \u3c 1.0 GeV2 were obtained from data on beam spin asymmetries and differential cross sections measured with the CLAS detector at Jefferson Lab. The Legendre moments determined from the σLT′ structure function have demonstrated sensitivity to the contributions from the nucleon resonances in the second and third resonance regions. These new data on the beam spin asymmetries in π0p electroproduction extend the opportunities for the extraction of the nucleon resonance electro-excitation amplitudes in the mass range above 1.6 GeV

The Quadrupole Magnets for the LHC Injection Transfer Lines

Two injection transfer lines, each about 2.8 km long, are being built to transfer protons at 450 GeV from the Super Proton Synchrotron (SPS) to the Large Hadron Collider (LHC). A total of 180 quadrupole magnets are required; they are produced in the framework of the contribution of the Russian Federation to the construction of the LHC. The classical quadrupoles, built from laminated steel cores and copper coils, have a core length of 1.4 m, an inscribed diameter of 32 mm and a strength of 53.5 T/m at a current of 530 A. The total weight of one magnet is 1.1 ton. For obtaining the required field quality at the small inscribed diameter, great care in the stamping of the laminations and the assembly of quadrants is necessary. Special instruments have been developed to measure, with a precision of some mm, the variations of the pole gaps over the full length of the magnet and correlate them to the obtained field distribution. The design has been developed in a collaboration between BINP and CERN. Fabrication and the magnetic measurements are done at BINP and should be finished at the end of the year 2000

Experience in genetic testing of hypertrophic cardiomyopathy using nanopore DNA sequencing

Aim. To investigate the application of the Oxford Nanopore Technologies’ third generation sequencing for the genetic testing of hypertrophic cardiomyopathy.Material and methods. The study involved 12 patients with hypertrophic cardiomyopathy aged 18 to 67 years (women, 9; men, 3). Using the PCR barcoding amplicons (SQK-LSK109) protocol, DNA libraries were created which contained long-range PCR fragments of the MYH7, MYBPC3, TNNT2, TNNI3 and TPM1 genes. The sequencing was performed using the MinION system by Oxford Nanopore Technologies (UK). Bioinformatic algorithms for data analysis included Guppy v.5.0.7, Nanopolish and Clairvoyante. The identified genetic variants were confirmed by Sanger sequencing.Results. Data on the complete sequence of the five major sarcomeric genes for hypertrophic cardiomyopathy were obtained. We found eight potentially disease-causing sequence variants in MYH7, MYBPC3 and TNNT2 genes by monomolecular sequencing. However, only three mutations p.Arg243Cys, p.Tyr609Asn, p.Arg870His in the MYH7 gene, and one mutation p.Lys985Asn in the MYBPC3 were confirmed by Sanger sequencing. Cascade screening of pathogenic variant p.Arg870His in the MYH7 gene was performed. We found one asymptomatic carrier.Conclusion. It appears that monomolecular sequencing technology is a feasible approach to identify mutations in patients with hypertrophic cardiomyopathy. Although improvement in accuracy of DNA sequencing, as well as optimization and simplification of bioinformatic algorithms for identification of the genetic variants are needed

Вариабельность митохондриального генома у больных раком молочной железы в популяции якуток

Background. The Sakha (Yakutia) population, the indigenous population of Siberia living in Yakutia, has one of the lowest rates of breast cancer (BC) incidence worldwide. The low BC incidence among the indigenous population of Yakutia has been reported by several authors, but to date the reasons for this phenomenon have not been fully elucidated. It should be noted that the study of factors that reduce the risk of BC is important for its prevention. In several studies, no hereditary BC was found in the Yakuts, and no pathogenic variants of the BRCA1/2 genes associated with hereditary syndromes of breast and ovarian cancers were found. In this regard, we decided to shift the focus to studying the mitochondrial genome of Sakha BC patients using the sequencing method.The purpose of the study was to identify BC-associated mitochondrial genome variants in Sakha patients.Material and Methods. The study included 14 Sakha patients diagnosed with BC. The median age of the patients was 49 years. DNA isolation was performed using phenol-chloroform extraction. DNA libraries were prepared using the Nextera Flex kit (Illumina, USA).Whole-genome sequencing of the mitochondrial genome was performed on a MiSeq instrument (Illuminа, USA). in the Shared Use Centre of the Research Institute of Medical Genetics, Tomsk National Research Centre of the Russian Academy of Sciences. The results obtained in BC patients were compared with those of control subjects.Results. In Sakha women with BC, 159 mitochondrial genome variants that differed from the human mitochondrial DNA (mtDNA) reference sequence (rCRS) were identified. Likely pathogenic variants m.3736G>A of the MT-ND1 gene and m.7279T>C of the MT-CO1 gene were shown to be associated with BC. For the first time, variants predisposing to BC (m.10398A>G; m.14783T>C; m.15043G>A; m.15301G>A) were identified. A distinctive feature of the mitochondrial genome of populations with a low BC incidence is a high level of mtDNA variants with changes in the length of the polycytosine region in the D310 locus.Conclusion. For the first time, mtDNA variants with changes in the length of the polycytosine tract in the D310 locus and likely pathogenic variants m.3736G>A of the MT-ND1 gene and m.7279T>C of the MT-CO1 gene were identified in Sakha BC women. The data obtained indicate that further studies on the role of the identified mtDNA variants in the development of BC using a larger sample of Sakha patients are required.Введение. Популяция саха (якуты) – коренное население Сибири, проживающее на территории Якутии, отличается одним из самых низких в мире уровнем заболеваемости раком молочной железы (РМЖ). Низкий уровень заболеваемости РМЖ коренного населения Якутии отмечен в ряде публикаций, но до настоящего времени причины этого явления не до конца выяснены. Следует отметить, что изучение факторов, снижающих риск заболевания РМЖ, имеет важное значение для его профилактики. По результатам ряда исследований, у якутов не обнаружено наследственных форм РМЖ, не найдено патогенных вариантов генов BRCA1/2, ассоциированных с наследственными синдромами РМЖ и рака яичника (РЯ). В связи с этим мы приняли решение сместить акцент на исследование митохондриального генома больных РМЖ саха методом секвенирования.Цель исследования – выявить варианты митохондриального генома, ассоциированные с РМЖ, у пациенток саха.Материал и методы. В исследование включено 14 пациенток саха с диагнозом РМЖ, средний возраст составил 49 лет. Выделение ДНК осуществляли методом фенол-хлороформной экстракции. ДНК-библиотеки готовили с помощью набора Nextera Flex (Illumina, США). Полногеномное секвенирование митохондриального генома выполнялось на приборе MiSeq (Illumina, США) на базе ЦКП Томского НИМЦ. Полученные результаты у больных РМЖ сравнивались с популяционным контролем.Результаты. У женщин саха, больных РМЖ, выявлено 159 вариантов митохондриального генома, отличающихся от референсной последовательностью митохондриальной ДНК (мтДНК) человека (rCRS). Показана ассоциация вероятно патогенных вариантов m.3736G>A гена МТ-ND1 и m.7279T>C гена MT-CO1 с РМЖ. Впервые выявлены варианты, предрасполагающие к РМЖ (m.10398A>G; m.14783T>C; m.15043G>A; m.15301G>A). Особенностью митохондриального генома популяций с низким уровнем заболеваемости РМЖ является высокий уровень вариантов мтДНК с изменением длины полицитозинового участка в локусе D310.Заключение. Впервые у женщин с РМЖ из популяции саха выявлены варианты мтДНК с изменением длины полицитозинового тракта в локусе D310 и вероятно патогенные варианты m.3736G>A гена МТ-ND1 и m.7279T>C гена MT-CO1. Полученные данные свидетельствуют о целесообразности дальнейшего изучения роли выявленных вариантов мтДНК в развитии РМЖ на расширенной выборке пациентов саха

East Eurasian ancestry in the middle of Europe: Genetic footprints of Steppe nomads in the genomes of Belarusian Lipka Tatars

Medieval era encounters of nomadic groups of the Eurasian Steppe and largely sedentary East Europeans had a variety of demographic and cultural consequences. Amongst these outcomes was the emergence of the Lipka Tatars-a Slavic-speaking Sunni-Muslim minority residing in modern Belarus, Lithuania and Poland, whose ancestors arrived in these territories via several migration waves, mainly from the Golden Horde. Our results show that Belarusian Lipka Tatars share a substantial part of their gene pool with Europeans as indicated by their Y-chromosomal, mitochondrial and autosomal DNA variation. Nevertheless, Belarusian Lipkas still retain a strong genetic signal of their nomadic ancestry, witnessed by the presence of common Y-chromosomal and mitochondrial DNA variants as well as autosomal segments identical by descent between Lipkas and East Eurasians from temperate and northern regions. Hence, we document Lipka Tatars as a unique example of former Medieval migrants into Central Europe, who became sedentary, changed language to Slavic, yet preserved their faith and retained, both uni-and bi-parentally, a clear genetic echo of a complex population interplay throughout the Eurasian Steppe Belt, extending from Central Europe to northern China

First Measurement of Hard Exclusive π- Δ++ Electroproduction Beam-Spin Asymmetries off the Proton

The polarized cross-section ratio σLT′/σ0 from hard exclusive π-Δ++ electroproduction off an unpolarized hydrogen target has been extracted based on beam-spin asymmetry measurements using a 10.2 GeV/10.6 GeV incident electron beam and the CLAS12 spectrometer at Jefferson Lab. The study, which provides the first observation of this channel in the deep-inelastic regime, focuses on very forward-pion kinematics in the valence regime, and photon virtualities ranging from 1.5 GeV2 up to 7 GeV2. The reaction provides a novel access to the d-quark content of the nucleon and to p→Δ++ transition generalized parton distributions. A comparison to existing results for hard exclusive π+n and π0p electroproduction is provided, which shows a clear impact of the excitation mechanism, encoded in transition generalized parton distributions, on the asymmetry