ПРЕДИКТИВНОЕ ЗНАЧЕНИЕ МАРКЕРОВ КЛЕТОЧНОГО ЦИКЛА ПРИ РАКЕ СЛИЗИСТОЙ ОБОЛОЧКИ ПОЛОСТИ РТА

The aim of our study was to identify the most significant biological markers characterizing the behavior of the tumor and to forecast its clinical course and to specify an individual therapy regimen for each patient.Работа посвящена выявлению наиболее значимых биологических маркеров клеточного цикла, характеризующих поведение опухоли, с целью прогноза клинического течения опухолевого процесса и индивидуализации схем лечения

Mismatch Repair–Independent Increase in Spontaneous Mutagenesis in Yeast Lacking Non-Essential Subunits of DNA Polymerase ε

Yeast DNA polymerase ε (Pol ε) is a highly accurate and processive enzyme that participates in nuclear DNA replication of the leading strand template. In addition to a large subunit (Pol2) harboring the polymerase and proofreading exonuclease active sites, Pol ε also has one essential subunit (Dpb2) and two smaller, non-essential subunits (Dpb3 and Dpb4) whose functions are not fully understood. To probe the functions of Dpb3 and Dpb4, here we investigate the consequences of their absence on the biochemical properties of Pol ε in vitro and on genome stability in vivo. The fidelity of DNA synthesis in vitro by purified Pol2/Dpb2, i.e. lacking Dpb3 and Dpb4, is comparable to the four-subunit Pol ε holoenzyme. Nonetheless, deletion of DPB3 and DPB4 elevates spontaneous frameshift and base substitution rates in vivo, to the same extent as the loss of Pol ε proofreading activity in a pol2-4 strain. In contrast to pol2-4, however, the dpb3Δdpb4Δ does not lead to a synergistic increase of mutation rates with defects in DNA mismatch repair. The increased mutation rate in dpb3Δdpb4Δ strains is partly dependent on REV3, as well as the proofreading capacity of Pol δ. Finally, biochemical studies demonstrate that the absence of Dpb3 and Dpb4 destabilizes the interaction between Pol ε and the template DNA during processive DNA synthesis and during processive 3′ to 5′exonucleolytic degradation of DNA. Collectively, these data suggest a model wherein Dpb3 and Dpb4 do not directly influence replication fidelity per se, but rather contribute to normal replication fork progression. In their absence, a defective replisome may more frequently leave gaps on the leading strand that are eventually filled by Pol ζ or Pol δ, in a post-replication process that generates errors not corrected by the DNA mismatch repair system

Free biostatistical software

This report provides information ang brief description of current freely available computer programs for statistical analysis of the results in biomedical research

CD20⁺B LYMPHOCYTES, A HIGHLY INFORMATIVE BIOMARKER FOR EARLY DIAGNOSIS OF CHRONIC ENDOMETRITIS

Plasma cells are often considered to be among important criteria in histological diagnosis of chronic endometritis (CE). Low plasma cell numbers in endometrial stroma, uneven distribution and similarity to the cells of cytogenic endometrial stroma represent difficulties with their identification by routine histological methods of study, and their absence prevents distinct diagnosis of CE. The paper presents data on comparative ROC-analysis of two immunohistochemical parameters of chronic endometritis: CD20+B lymphocytes and CD138+ plasma cells (PC). The study group included 937 women with CE, who were examined for infertility and failed IVF attempts. The control group consisted of 103 women without signs of CE who were studied for male infertility factor.The sensitivity of CD20+B cell assays for the diagnosis of CE was 98% (Se = 0.98), thus being 1.44 times higher compared to the sensitivity of CD138+PC, that was, respectively, 68% (Se = 0.68). The specificity of both indicators for the diagnosis of the absence of CE was high, i.e., 98% (Sp = 0.98), and 99% (Sp = 0.99), respectively. The threshold quantitative values for the two endometrial parameters (cutoff point) for the CE diagnosis were also determined when using CD138+PC-1 cell/5mm2 and CD20+B lymphocytes-5cell/5mm2. Analysis of linear regression showed a highly significant (p = 0.00053) relationship of CD138+ PC from CD20+B lymphocytes: With increased numbers of CD20+B lymphocytes, there is a trend for higher CD138+PC numbers which confirms their direct pathogenetic relationship. The topographic and quantitative features of CD20 B lymphocytes in the endometrium determined during immunohistochemical examination allow us to recommend this approach as a highly sensitive and significant early diagnostic indicator of chronic endometritis

Hypertension specific patient-reported outcome measure. Part II: validation survey and item selection process

Aim. Improvement of the health-related quality of life (HRQoL) is one of the basic principles of value-based medicine. HRQoL could be assessed by the patient-reported outcome measures (PROMs) also in case of arterial hypertension (HTN). However for HTN patients only generic PROMs are still used. Previously the group of experts had created the primary version of HTN-specific PROM. The purpose of the second part was to conduct a validation survey and to select the items in a statistically-based manner.Material and methods. Validation survey was conducted in a large multidisciplinary center among patients with HTN stages 1-3 and healthy volunteers. Inclusion criteria were age >18 years old, ability to understand or complete the scale themselves, absence of significant illness requiring hospitalization. The items were selected according to the principles of classical test theory (CTT) and item response theory (IRT). The criteria for CTT were sensitivity (standard deviation and coefficient of variation with corresponding confidence intervals), representativeness (item-total Pearson’s correlation coefficient), internal consistency (Cronbach’s a coefficient). In IRT analysis two methods were adopted — value of four degrees of difficulty and the discrimination estimate. Each question was evaluated according to 8 criteria. An item was considered for selection when it was retained by ≥4 criteria. The expert panel considered practical significance of each item.Results. A total of 430 questionnaires were distributed and 407 (94,7%) of them were returned completed (from 359 hypertensive patients, mean age 62,3±11,7 y.o.; 48 healthy volunteers, mean age 38,8±10,5 y.o.). The average time for PROM filling was 24±4,2 minutes. Of 163 questions, 27 met all 8 criteria and 3 questions did not match any. Of the 36 HTN-specific questions, 11 matched ≥5 criteria and in the generic part there were 87 questions (33 in the PHY domain, 35 for PSY, 8 for SOC, 11 for THER). The symmetric distribution of criteria was seen in 25 questions, of which 11 were evaluated by experts and then retained. For 40 questions, <4 eligibility criteria were recorded, of which 9 were retained after expert review. The PROM draft contained 80 questions (19 questions in the physiology domain, 22 in psychology, 6 in social, 13 in therapy, 20 items are HTN-specific).Conclusion. The methods of CTT and IRT allowed to reduce the PROM volume without losing the semantic richness and the need to reorganize the conceptual structure. The next step is the validation of the scale

APPLICATION OF MODERN STATISTICAL METHODS TO ASSESS THE INTERACTION OF THE INTERFERON STATUS OF FULL-TERM NEONATAL INFANT AND HIS MOTHER

Abstract. The analysis of the IFN-status of healthy full-term neonatal infants and their healthy mothers with modern statistical methods was conducted. It was established that the IFN status of healthy full-term neonatal infants differs from the same of their mothers with higher occurrence of IFNs and strengthened induced production of IFNα/β and IFNγ. The statistically significant interaction between indicators of the IFN status of newborns and their mothers has been revealed. The obtained data is important for assessment of nonspecific resistance in system mother–newborn

Hypertension specific patient-reported outcome measure. Part III: validation, responsiveness and reliability assessment

Aim. Health-related quality of life in patients with arterial hypertension (HTN) is still determined by only generic patient-reported outcome measures (PROMs), although disease-specific ones are more reliable and highly valid. Previously, we reported the results of development and item-selection process of the new Russian HTN-specific PROM. The purpose of this last stage was to confirm validity, reliability, responsiveness and sensitivity of the scale and to present its final version.Material and methods. Analysis was done using data from a mass survey of patients with Grades 1-3 HTN (n=359, aged 25 to 91 y. o.) and healthy volunteers (n=48, aged 23 to 65 y.o), 407 returned questionnaires. We conducted two exploratory factor analyses (EFA) with the intermediate version of the PROM (80 questions, 20 of them HTN-specific). The Cattel’s scree test was used to select the optimal number of factors. After removing the items with a low factor loadings, a confirmatory factor analysis (CFA) was performed to assess the model’s fitindexes adequacy. The core indexes to be measured were SRMR, RMSEA, CFI. Finally, the PROM’s reliability (Cronbach’s α and McDonald’s ω) and criterion validity (responsiveness) were evaluated.Results. Both EFA with oblique and varimax rotation showed 35 questions have factor loadings ≥0,5 and assigned to one of 5 factors. The basic structure of the PROM was retained for further CFA. Most of indices of fit measured met the requirements: SRMR was 0,08, RMSEA was 0,07 (90% CI (0,07-0,08)) and CFI was 0,08, which confirms the construct validity. Both Cronbach’s α and MacDonald’s ω of each of the domains were ≥0,80 and the whole scale was 0,89 confirming satisfactory reliability. Scores of the questionnaire were positively correlated with the severity of HTN (p<0,001 for Grades 1-3 HTN) and between HTN and non-HTN patients (p=0,01 and 0,04 in psychologic and social domains respectively).Conclusion. Sequentially addressing of exploratory and confirmatory factor analyses and assessment of reliability and responsiveness allowed to form the final version of the patient-reported outcome measure for arterial hypertension. The new Russian-language questionnaire is a useful and feasible tool for routine practice and clinical trials