Development of highly sensitive methods for drug analysis is an ongoing challenge posed by modern bioanalytical and pharmaceutical chemistry. Drug analysis is essential to monitor the quality and purity of pharmaceuticals, study the delivery vehicles for therapeutic agents, to assess the effectiveness of the substance incorporation into the drug delivery system, to estimate the kinetic parameters of reactions, catalyzed by enzymes involved in xenobiotic metabolism, and to study the mechanisms of the drug-DNA interactions from the perspective of pharmacogenomics. The study was aimed to develop an electrochemical technique for detection of a number of drugs. The method is based on electrochemical oxidation of organic molecules at positive potentials between +(0÷1.6) V. The commercially available three-contact electrodes obtained by screen printing with unmodified graphite working electrode were used for analysis. It is shown that electrochemical technique allows for simultaneous detection of several compounds at various working electrode potentials, and for detection of drugs over a wide range of the clinically meaningful drug concentrations (50 µM – 10 mМ), which could be used when working with biological fluids (blood plasma, blood serum, blood, urine), as well as when performing drug monitoring and drug–drug interaction analysis.
VIEWS 3019
Adherence to treatment is one of the major challenges posed by modern medicine. Today, cataract is the leading cause of reversible blindness and visual disability. The study was aimed to assess adherence to timely surgical treatment in individuals with cataract. The data of the cross-sectional, population-based Ural Eye and Medical Study were assessed. Among 546 participants, there were 46.3% men and 53.7% women, 59.6% urban resudents, 40.4% rural residents. Their average age was 66.36 ± 9.47 years (40–88 years). Statistical data analysis was performed using the IBM SPSS Statistic software package. The findings showed that the lack of awareness of the disorder and low interest in surgery were the main factors, affecting the patients' motivation for cataract treatment. At the same time, the frequency of ophtalmology visits was inversely related to the patients' age (OR 1.24; 95% CI 1.04–1.49) and the duration of vision loss (OR 1.08; 95% CI 0.81–1.43), and directly related to the cataract diagnosis age (OR 1.20; 95% CI 1.04–1.38), the presence of ophthalmologist in the community clinic (OR 1.71; 95% CI 1.29–2.26), trust in the doctor (OR 3.62; 95% CI 3.02–4.35), ophthalmologist's explanation of the cataract complications and advanced treatment methods (OR 1.62; 95% CI 1.34–1.97). Understanding the main factors, contributing to low treatment adherence in patients with cataracts, would make it possible to optimize the measures to improve healthcare delivery to such patients, associated with the increased coverage of surgical treatment.
VIEWS 3263
Generation and maintenance of immunity to SARS-CoV-2 is essential for  overcoming the pandemic of the novel coronavirus infection COVID-19. The study was aimed to assess the dynamic changes in the levels of IgG antibodies against the SARS-CoV-2 receptor-binding domain (RBD) with the use of the enzyme-linked immunosorbent assay (ELISA) kits, calibrated using the International Standard for anti-SARS-CoV-2 immunoglobulin (IS-SARS-CoV-2). The concentrations of anti-RBD-IgG were measured in the cohort of individuals, who had recovered from COVID-19, with an interval of a month for 6 months, and at a time point of 12 months, using the ELISA kits, calibrated with the use of IS-SARS-CoV-2; the results were expressed in binding antibody units (BAU) per 1 mL. A total of 97 blood serum samples, obtained from 20 individuals with SARS-CoV-2 infection, confirmed by PCR, were collected. The geometric mean titer (GMT) of anti-RBD-IgG was 433 BAU/mL (range 36-25,900 BAU/mL) within a month after the infection. The concentration of anti-RBD-IgG gradually decreased with time and reached the GMT value of 68 BAU/mL by the 12th month; anti-RBD-IgG persisted in 13 individuals (93%) out of 14, examined 12 months after the infection. The standardized quantitative serological data play a vital part in monitoring the immune response and make in easier to compare the studies, providing the basis for seeking the common serological correlate of the protective immunity to SARS-CoV-2.
VIEWS 2865
Gut microbiota is an essential element of maintaining the immune homeostasis, including in individuals with COVID-19. The study was aimed to assess taxonomic changes in the gut microbiota and their relationship with the disease severity and the levels of IL6, IL10, IL17, and TNFα in patients with COVID-19. A total of 110 patients with COVID-19 (index group) and 98 individuals with no COVID-19 (control group) were enrolled to the comparative cross-sectional study. The gut micribiota composition was determined by shotgun sequencing. Blood serum levels of IL6, IL10, IL17, and TNFα were assessed by enzyme-linked immunosorbent assay. The following significant changes in the gut microbiota composition were observed in patients with COVID-19 in contrast to controls: decreased abundance of B. adolescentis (p = 0.048), E. rectale (p = 0.036), F. prausnitzi (p = 0.0002), B. dorei (p < 0.001), and increased abundance of R. gnavus (p = 0.012), Сl. hathewayi (p = 0.003), E. faecium (p = 0.0003). Correlations were established between the abundance of B. dorei and the IL6 levels (r = 0.49; p = 0.034), the abundance of F. prausnitzii and the levels of IL10, IL17 (r = 0.44; p = 0.001 and r = –0.52; p < 0.001, respectively). The abundance of R. gnavus correlated with the TNFα levels, and the abundance of E. faecium was related to the levels of IL6 (r = 0.47; p = 0.002) and TNFα (r = 0.56; p = 0.001). The relationship between the abundance of B. dorei, F. prausnitzii, E. faecium and the higher SHOKS-COVID clinical assessment scale scores was also revealed (r = –0.54; p = 0.001, r = –0.60; p < 0.001 and r = 0.67; p = 0.005, respectively). Targeted correction of gut microbiota may improve the COVID-19 treatment efficacy.
VIEWS 2888
SARS-CoV-2 specific antibody response is a generally accepted measure of postinfection and vaccination-induced immunity assessment. The dynamics of avidity maturation and neutralizing activity of virus-specific immunoglobulins G during the SARS-CoV-2–associated coronavirus infection was studied in cohorts of vaccinated volunteers and COVID-19 patients. 4–6 months after vaccination, neutralization activity was low compared to hospitalized patients (medians 57.4% vs 86.4%). On the opposite, the avidity indices in vaccinated volunteers were significantly higher (median 76.7%) than among hospitalized patients (median 61.4%). During the acute phase of the disease (14–16 days PI), post-vaccination patients have also higher avidity indices than primary patients (medians 43.5% vs 20.4%). Our results suggest that in long-term perspective antibody affinity maturation rate is higher after vaccination than after a natural infection. We demonstrated that Sputnik V vaccination leads to formation of high-avidity IgG, which persists for at least 6 months of observation. These results also indicate the presence of protective efficacy markers for at least 4–6 months after the vaccination or a previous illness and gives grounds for the half-year time period chosen for booster immunization with Sputnik V in Russia.
VIEWS 3145
Microsatellite instability (MSI) characterizes a special molecular genetic subtype of malignancies and is associated with the deficiency of mismatched DNA repair. There are no reliable data on the frequency of MSI in colorectal neuroendocrine neoplasms due to the relative rarity of this cancer type. The prognostic significance of MSI is debatable. The aim of this study was to investigate the frequency of the MSI phenotype among colorectal neuroendocrine neoplasms (NENs) with different primary location, grade and stage. Twenty-nine patients (15 men and 14 women, mean age: 62.5 years) included in the study underwent surgery for colorectal neuroendocrine tumors between 2015 and 2018. The mean follow-up period was 3.8 years.  Colorectal NENs were grouped by primary location and stage. The majority of the patients (52%) had stage III cancer at diagnosis. The microsatellite stability (MSS) phenotype was confirmed in 24 patients (83%), whereas the MSI phenotype was observed in 5 patients (17%). All MSI-positive tumors were stage I well-differentiated grade G1 or G2 neuroendocrine tumors (NETs) of the rectum. Overall survival was 50% for patients with stage II MSS-positive NENs of the colon and rectum, 33% for stage III and 0% for stage IV. For patients with stage I MSI-positive NENs of the rectum, overall survival was 100%. Thus, the frequency of MSI-positive colorectal NENs was estimated.
VIEWS 2741
Despite the diversity of surgical options for slipped capital femoral epiphysis (SCFE), there is an ongoing search for the technique that would ensure a satisfactory outcome, stable fixation of bone fragments and a low rate of complications. The aim of this study was to improve the surgical technique for SCFE in patients with moderate and severe SCFE. The study included 52 children (16 girls and 36 boys) aged 10-15 years (the mean age was 13.2 years) with chronic severe (Krechmar’s stage III) stable (according to Loder’s classification) SCFE. The control group (n = 16) underwent a classic Imhauser procedure; the main group (n = 36) underwent a triplane osteotomy proposed by the authors of the study. The patients were examined prior to surgery and in the late follow-up period (the mean follow-up time was 4.7 years, ranging from 1 to 10 years). The procedure included a clinical examination, history taking, radiography to measure the slip angle and the severity of the slip, and the Harris hip score to assess hip function. After 4.7 years, both groups demonstrated an increase in the range of motion, in comparison with their preoperative results (p ≤ 0.05), good Harris hip scores (94 points in the main group and 81 points in the control group. Postoperative radiographs showed consolidation of the bone, recovery of the proximal femur anatomy. Leg length discrepancy improved significantly in both groups. The proposed technique for extraarticular osteotomy allows recovering the length of the affected leg, the anatomy and physiology of the hip joint, is simple and less traumatic.
VIEWS 2806
Differentiation between Parkinson’s disease, especially in its early stages, and essential tremor, which is a phenotypically similar movement disorder, still remains an unsolved challenge for neurology. The aim of this study was to assess the diagnostic significance of nigrosome imaging (nigrosomes are dopaminergic neuron clusters in the substantia nigra of the midbrain) using 3T high-resolution SW-MRI. The study was conducted in 20 patients with Parkinson’s disease and 10 patients with essential tremor. Visual analysis of the acquired nigrosome-1 images was performed using a 4-point ordinal rating scale. Differences in sex, age and duration of the disease were calculated using the Fisher exact test and the Mann–Whitney U test. The diagnostic value of the method was assessed using Pearson’s chisquared test.  Nigrosome-1 was bilaterally or unilaterally absent in 70% of parkinsonian patients. Less specific changes to the substantia nigra (SN) were observed in two more parkinsonian patients (10%), whose nigrosome-1 appeared reduced in size. By contrast, nigrosome-1 was bilaterally intact in all patients (100%) with essential tremor (p < 0.001). Our preliminary findings demonstrate the high potential of noninvasive nigrosome-1 imaging in the differential diagnosis of Parkinson’s disease and essential tremor.
VIEWS 3038