Possibilities of magnetic resonance tomography in identification and diagnostics of neurosyphilis forms

Aim: To evaluate the possibilities of the magnetic resonance tomography (MRT) in diagnostics and identification of neurosyphilis. Materials and methods: A total of 1387 patients with different forms of documented neurosyphilis were examined to study the deficiency of neurological function. The diagnosis of neurosyphilis was confirmed by CSF-study. MRT was performed in 57 cases. Results: Magnetic resonance tomography (MRT) in 6 patients showed no pathology, 16 patients had arachnoid cystic changes and in 16 cases hydrocephaly occurred. Cerebral cortical atrophy was presented in 13 patients, in 12 cases — multifocal changes were visualized, 12 patients had white matter structural changes. Two cases required diagnostics. A 59-year-old man was hospitalized with epileptic seizure, progressive dementia and multifocal neurologic symptoms. A 40-year-old man was examined with recurring episodes of acute cere-brospinal accident and progressing cognitive disorders. Conclusion: MRT could be used in differential diagnostics of neurosyphilis imitating space-occupying lesions of cerebrum and spinal cord, tumors of central nervous system and could help to define the form of neurosyphili

Tyrosine Kinase Inhibitor Resistance in Patients with Chronic Myeloid Leukemia: A 10-Year Study of BCR-ABL Gene Mutation Profile in Russia (2006–2016)

Background. Kinase domain mutations of BCR-ABL gene is the most common cause of tyrosine kinase inhibitor resistance. Aim. To present the data on prognostic value of BCR-ABL mutation burden in Russian patients over the last 10 years. Materials & Methods. The study included 1885 chronic myeloid leukemia (CML) patients with tyrosine kinase inhibitor resistance who were followed up from 2006 to 2016. BCR-ABL point mutations in mRNA samples were analyzed by means of polymerase chain reaction and subsequent Sanger sequencing. Results. In 1257 CML patients with signs of tyrosine kinase inhibitor resistance BCR-ABL expression level was > 1 %. BCR–ABL mutations were detected in 31.8 % of patients. Total mutation count was 467 (70 mutation types). Total count of patients with mutation-associated tyrosine kinase inhibitor resistance decreased from 36.6 % (2006–2008) to 24.95 % (2013–2016) and to marked decrease of 23.12 % in 2014. Detection rate of imatinib-resistant mutations and F359V mutation was shown to decrease within the period from 2010–2011 to 2014–2015. F317L level, which is responsible for dasatinib resistance, considerably increased in 2015. T315I frequency was the highest in 2014, afterwards it was gradually decreasing. Mutation-associated resistance rates varied by region of the Russian Federation. Conclusion. The analysis of trends of mutation incidence in patients with CML can be of extreme significance in long-term prognosis of resistance development and in improvement of treatment planning

Prognostic Value of the PRAME Gene Expression in T-Cell Lymphoproliferative Disorders

Background. T-cell lymphomas (T-CL) represent a heterogeneous group of malignant lymphoproliferative disorders characterized by unfavorable prognosis. The cancer-testis PRAME gene is notable for its spontaneous expression in transformed cells as observed in solid tumors, B-cell lymphoproliferative and chronic myeloproliferative diseases. Activity and clinical significance of PRAME in T-CL was not studied before, which determines the relevance and provides ground for the present trial. Aim. To assess the clinical significance of the PRAME gene expression in T-CL. Materials & Methods. PRAME gene expression level was measured in samples of lymph nodes, blood, and bone marrow from 35 T-CL patients. Among them 3 patients received allogeneic hematopoietic stem cell transplantation, and 6 patients received autologous hematopoietic stem cell transplantation. A correlation was established between the PRAME expression in bone marrow and peripheral blood with morphological markers of disseminated disease with bone marrow lesions and leukemic blood. PRAME expression level was correlated with survival parameters and tumor proliferative activity (Ki-67). Results. PRAME activity was observed in 21 (60 %) patients. PRAME hyperexpression is associated with advanced stages of disease (p = 0.0734), bone marrow lesions (p = 0.0289), leukemic blood (p = 0.0187), worsening of the overall survival (OS) (p = 0.0787) and event-free survival (EFS) (p = 0.7185), also after hematopoietic stem cell transplantation (p = 0.2661 for OS and p = 0.0452 for EFS), and with a high Ki-67 expression level (p = 0.0155). Conclusion. PRAME expression in T-CL is often observed and related with unfavorable clinical prognosis

Expression of the BCR-ABL1 Gene in Patients with Chronic Myeloproliferative Diseases with Signs of Progression

Background. The V617F mutation of JAK2 is known to manifest in Ph-negative chronic myeloproliferative diseases (cMPD), such as polycythemia vera, thrombocythemia, and myelofibrosis. These diseases not infrequently advance into more aggressive forms up to acute leukemia. As the progression mechanism is still unknown, its study retains a high priority. JAK2 carrying the V617F mutation is believed to cause constant activation of V(D)J recombinase in myeloid tumor cells in cMPD patients. Aberrant activation of V(D)J recombinase in tumor cells in cMPD patients can lead to t(9;22)(q34;q11) chromosomal rearrangement. Aim. To study the expression of BCR-ABL1 resulting from translocation t(9;22)(q34;q11) in cMPD patients at the progression stage in order to test the suggested hypothesis. Materials & Methods. The BCR–ABL1 expression was assessed in peripheral blood granulocytes in cMPD patients by real-time PCR. The JAK2 V617F mutation was identified by quantitative allele-specific PCR. The JAK2 exon 12 mutations were determined using Sanger direct sequencing of PCR products. Results. The BCR-ABL1 expression was discovered in 29 % of patients with cMPD progression. The BCR-ABL1 expression in these patients correlated with hepatosplenomegaly and hyperleukocytosis. Conclusion. In a significant proportion of cMPD patients the disease progression can be associated with activation of the BCR-ABL expression

Computing Highly Correlated Positions Using Mutual Information and Graph Theory for G Protein-Coupled Receptors

G protein-coupled receptors (GPCRs) are a superfamily of seven transmembrane-spanning proteins involved in a wide array of physiological functions and are the most common targets of pharmaceuticals. This study aims to identify a cohort or clique of positions that share high mutual information. Using a multiple sequence alignment of the transmembrane (TM) domains, we calculated the mutual information between all inter-TM pairs of aligned positions and ranked the pairs by mutual information. A mutual information graph was constructed with vertices that corresponded to TM positions and edges between vertices were drawn if the mutual information exceeded a threshold of statistical significance. Positions with high degree (i.e. had significant mutual information with a large number of other positions) were found to line a well defined inter-TM ligand binding cavity for class A as well as class C GPCRs. Although the natural ligands of class C receptors bind to their extracellular N-terminal domains, the possibility of modulating their activity through ligands that bind to their helical bundle has been reported. Such positions were not found for class B GPCRs, in agreement with the observation that there are not known ligands that bind within their TM helical bundle. All identified key positions formed a clique within the MI graph of interest. For a subset of class A receptors we also considered the alignment of a portion of the second extracellular loop, and found that the two positions adjacent to the conserved Cys that bridges the loop with the TM3 qualified as key positions. Our algorithm may be useful for localizing topologically conserved regions in other protein families

Literary studies and the academy

In 1885 the University of Oxford invited applications for the newly created Merton Professorship of English Language and Literature. The holder of the chair was, according to the statutes, to ‘lecture and give instruction on the broad history and criticism of English Language and Literature, and on the works of approved English authors’. This was not in itself a particularly innovatory move, as the study of English vernacular literature had played some part in higher education in Britain for over a century. Oxford University had put English as a subject into its pass degree in 1873, had been participating since 1878 in extension teaching, of which literary study formed a significant part, and had since 1881 been setting special examinations in the subject for its non-graduating women students. What was new was the fact that this ancient university appeared to be on the verge of granting the solid academic legitimacy of an established chair to an institutionally marginal and often contentious intellectual pursuit, acknowledging the study of literary texts in English to be a fit subject not just for women and the educationally disadvantaged but also for university men

Age dependent dynamics of intima-media complex thickness in elderly patients with arterial hypertension

Aim: To estimate the dynamics of intima-media complex in elderly patients with arterial hypertension. Materials: 179 elderly patients with arterial hypertension were involved in the study. Mean intima-media wall thickness (IMT) of common carotid arteries in plaque-free sites and prevalence of plaques were evaluated by B-mode ultrasound investigation (Philips Envisor HD, USA). Results: IMT changing was of nonlinear character, remained stable up to 74 years. Mean rate of the following IMT augmentation was 0.157 mm per year. Frequency of atherosclerotic plaque revealing was significantly increased since the 7th decade. Significant correlation between IMT and systolic, diastolic, mean blood pressure levels or medication spectrum was not revealed. Conclusion: Received data proved significant influence of aging upon IMT enlargemen

Loneliness: its correlates and association with health behaviours and outcomes in nine countries of the former Soviet Union.

BACKGROUND: Research suggests that the prevalence of loneliness varies between countries and that feeling lonely may be associated with poorer health behaviours and outcomes. The aim of the current study was to examine the factors associated with loneliness, and the relationship between feeling lonely and health behaviours and outcomes in the countries of the former Soviet Union (FSU)--a region where loneliness has been little studied to date. METHODS: Using data from 18,000 respondents collected during a cross-sectional survey undertaken in nine FSU countries--Armenia, Azerbaijan, Belarus, Georgia, Kazakhstan, Kyrgyzstan, Moldova, Russia and Ukraine--in 2010/11, country-wise logistic regression analysis was conducted to determine: the factors associated with feeling lonely; the association between feeling lonely and alcohol consumption, hazardous drinking and smoking; and whether feeling lonely was linked to poorer health (i.e. poor self-rated health and psychological distress). RESULTS: The prevalence of loneliness varied widely among the countries. Being divorced/widowed and low social support were associated with loneliness in all of the countries, while other factors (e.g. living alone, low locus of control) were linked to loneliness in some of the countries. Feeling lonely was connected with hazardous drinking in Armenia, Kyrgyzstan and Russia but with smoking only in Kyrgyzstan. Loneliness was associated with psychological distress in all of the countries and poor self-rated health in every country except Kazakhstan and Moldova. CONCLUSIONS: Loneliness is associated with worse health behaviours and poorer health in the countries of the FSU. More individual country-level research is now needed to formulate effective interventions to mitigate the negative effects of loneliness on population well-being in the FSU