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AlphaFold changed the field of structural biology by achieving three-dimensional (3D) structure prediction from protein sequence at experimental quality. The astounding success even led to claims that the protein folding problem is "solved". However, protein folding problem is more than just structure prediction from sequence. Presently, it is unknown if the AlphaFold-triggered revolution could help to solve other problems related to protein folding. Here we assay the ability of AlphaFold to predict the impact of single mutations on protein stability (ΔΔG) and function. To study the question we extracted the pLDDT and metrics from AlphaFold predictions before and after single mutation in a protein and correlated the predicted change with the experimentally known ΔΔG values. Additionally, we correlated the same AlphaFold pLDDT metrics with the impact of a single mutation on structure using a large scale dataset of single mutations in GFP with the experimentally assayed levels of fluorescence. We found a very weak or no correlation between AlphaFold output metrics and change of protein stability or fluorescence. Our results imply that AlphaFold may not be immediately applied to other problems or applications in protein folding., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Pak et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To study the predictors of the efficacy of non-drug multimodal therapy in the treatment of mild vascular cognitive impairment., Material and Methods: Thirty patients with mild vascular cognitive impairment, under the supervision of their physician, received a 1-month non-drug treatment program including cognitive training, detailed recommendations for physical activity, and dietary planning., Results: After the end of the course of treatment, improvements in the MoCa test were achieved by 22 patients (73%), which made up Group 1. In the remaining 8 patients, the treatment had no effect (Group 2). In Group 1, the dynamics of the MoCa test averaged 1.7±0.9, in the Group 2 it was (-0.4)±0.5. Patients of Group 1 had a significantly lower level of education (10.9±2.3) compared with Group 2 (14.9±2.0), a higher initial MoCa score, and a less pronounced white matter lesion on the Fazekas scale. After the regression analysis, the level of education (B -0.999, p <0.05) and white matter damage (B -2.761, p <0.01) were significant predictors., Conclusion: When using non-drug multimodal therapy in the treatment of mild vascular cognitive impairment, lower levels of education and a lower degree of white matter vascular damage are reliable predictors of treatment efficacy.

Aim: To analyze the modes of immunosuppressive therapy as a risk factor for new-onset diabetes after transplantation (NODAT) in kidney recipients., Materials and Methods: The retrospective analysis included data from 1367 recipients (755 men and 612 women) who lived more than one year after NODAT and were observed at the Moscow City Nephrology Center from January 1989 to December 2018. NODAT was established for 178 (13%) patients based on criteria from the World Health Organization and the American Diabetes Association. The modes of immunosuppressive therapy using cyclosporin A (CSA), tacrolimus (Tac), mTOR inhibitors, glucocorticoids in patients with NODAT and without NODAT were evaluated. To assess the impact of risk factors, descriptive statistics methods were used, the odds ratio (OR) and the 95% confidence interval (CI) were calculated., Results: NODAT was diagnosed in 105 men and 73 women. The OR for men was 1.19 (95% CI 0.871.64), the OR for women was 0.84 (95% CI 0.611.15). At the time of transplantation, the average age of the kidney recipients in the NODAT group was higher than in the group without NODAT: 51 [43; 57] and 43 [32; 52] years, respectively (p=0.0001). Most patients with NODAT (82%) were older than 50 years, while in the group without NODAT, the proportion of patients of the same age was 48.5% (p=0.0001). Among patients without NODAT, transplantation of a kidney from a living donor was significantly more often compared with the group with NODAT+ (7.1% vs 1.1%;p=0.001). Among the recipients who received the regimen with CSA, diabetes developed in 75 (42.1%), those who received Tac in 102 (57.3%;p0.05). The chance (risk of development) of NODAT in patients receiving i-mTOR + Tac was 3.2 (95% CI 1.476.78;p=0.032), and for patients receiving i-mTOR + cyclosporin A, the chance of development NODAT was 1.95 (95% CI 0.884.35;p=0.044)., Conclusion: 13% of recipients developed de novo kidney diabetes after allograft. Age at the time of allotransplantation, gender, as well as the use of tacrolimus in combination with i-mTOR are the most significant risk factors for the development of NODAT.

Cognitive impairment is one of the most common consequences of brain dysfunction. Nowadays, there is an increasing interest in the diagnosis and treatment of cognitive impairment without dementia, as a stage of cognitive deficit spectrum that could be controlled. The article discusses the current approaches to the management of patients with mild cognitive impairment including non-pharmacological strategies as well as medical antioxidant treatment.

Aim: to study the impact of the autonomic nervous system on the development of renal lesion in patients with metabolic syndrome (MS)., Subjects and Methods: One hundred and nine patients (45 females and 54 males) aged 29 to 72 years who had MS were examined. Glomerular filtration rate (GFR) was estimated using the Cockroft-Gault formula, by correcting the obtained result on the body surface. According to the level of GFR, the patients were divided into 3 groups: 1) 30 MS patients with hyperfiltration (GFR > 110 ml/min/1.73 m2); 2) 55 patients with normal GFR (110-60 ml/min/1.73 m2); 3) 24patients with lower GFR ( < 60 ml/min/1.73 m2). All the patients underwent physical examination; autonomic tonus was examined by 24-hour cardiac rhythm variability (CRV) study using the Holter monitoring system, by applying the time analysis. The presence of autonomic dystonia syndrome (ADS) and its degree were determined by a questionnaire to detect autonomic nervous system (ANS) dysfunction., Results: Each of 3 groups was found to have signs of autonomic imbalance with a preponderance of sympathetic activity with decreased parasympathetic activity, these impairments being more pronounced in Group 1. The obtained regulation reflects the entire decrease in autonomic actions on the cardiovascular system in patients with MS and suggests the maximum hyperactivation of the sympathetic ANS in early-stage renal lesion--hyperfiltration, Conclusion: When the first signs of renal lesion (hyperfiltration) occur in patients with MS, there is significant hypersympaticotonia that promotes the progression of target organs, including the kidneys.

Aim: To study the time course of changes in glomerular filtration rate (GFR) in different age groups of males with metabolic syndrome (MS)., Subjects and Methods: Eighty-six male patients with MS whose age 35 to 69 years (mean age 53.6 years) were examined. The patients were divided into 3 age groups: 1) 30-50 years (mean age 43.5 years; n = 30); 2) 50-60 years (mean age 54.9 years; n = 36); 3) 60-70 (mean age 66 years; n = 20). The study included only MS patients with stages I-II chronic renal disease (CRD) (according to the NKF K/DOQI classification, 2002). GFR was determined by the Cockroft-Gault formula corrected and uncorrected for a standard body surface area (GFRst, GFRc-g). The obtained values of GFRst and GFRc-g were compared with the population-based standards determined for each formula. The authors identified an increased GFRst (> 110 ml/min/1.73 m2), a normal GFRst (60-110 ml/min/1.73 m2), and a decreased GFRst (< 60 ml/min/1.73 m2), as well as an increased GFRc-g (> 120 ml/min), a normal GFRc-g (80-120 ml/min), and a decreased GFRc-g (< 80 ml/min). GFRst < 60 ml/min/1.73 m2) was defined as CRD., Results: Each age group was found to have deviations of GFR from the normal values towards both its increase and decrease. The young age group showed a larger number of patients with increased GFR and a smaller number of patients with decreased GFR than did the old age group. This trend was seen for both GFRst and GFRc-g, but in the latter case, the spread of hyperfiltration was higher in the age group of 30-50 years and in the total group of patients., Conclusion: In the first age group, a predominance of hemofiltration precedes the development of CRD in the third age group and may reflect the trend of MS-induced renal lesion.

A steady increase in glomerular filtration rate is considered to be one of the first stages of renal lesion in essential hypertension, metabolic syndrome, and type 2 diabetes mellitus. The paper discusses methods for detection of hyperfiltration and gives their comparative characterization and indications for their use.

Granulomatosis was induced in male Wistar rats by intravenous injection of SiO(2). The course of SiO(2) granulomatosis was cyclic in animals receiving radon baths: phase 1 was characterized by an increase in the number and size of granulomas, while during phase 2 the intensity of the inflammatory process decreased and fibrosing of granulomas progressed. No trends to alleviation of the inflammatory process were noted in rats with SiO(2) granulocytosis receiving tap water baths.

Aim: To investigate involvement of patients into control of their pressure to improve quality of treatment for arterial hypertension (AH)., Materials and Methods: 134 hypertensive patients (76 females and 58 males) were interviewed. Criteria of efficacy of AH control were ability and motivation of self-measurement of blood pressure and its maintenance at the optimal level., Results: For the past year, 40% of the patients measured pressure regularly (once a day or more frequently), 34%--1-3 times a week, 9%--1-3 times a month, 17%--rarely, mostly, males. Most of the patients controlled their pressure insufficiently. This is explained by "working pressure" (high in many cases) which was registered in most of the examinees. When part of the patients reached that working pressure they discontinued treatment., Conclusion: Involvement of hypertensive patients and members of their families into control of hypertension is a feasible and valuable method of improving quality of hypertension treatment.

Data are presented on the study of BCA-09 monoclonal antibodies (MCA) produced by 2G3 hybrid cells (a new strain). The conventional method of somatic hybridization of mouse myeloma cells and splenocytes of mice immunized with peripheral blood leucocytes from a patient with acute myelomonoblastic leukemia (AMML) was used to obtain hybridomas. The study of BCA-09 MCA specificity has shown that in more than half of cases they reveal surface membrane antigen of leukemia cells in patients with AMML, and do not react with blast cells of patients with other variants of leukemia and lymphosarcoma, as well as with blood cells of normal subjects, and with some human cultural cell lines. BCA-09 MCA can be recommended for the differential diagnosis of AMML and other forms of lymphoblastoses.

A method for early immunological prognosis of acute lymphoblastic leukemia (ALL) relapses has been presented. It is based on the dynamic phenotyping of lymphoid blood cells from the patients during remission by the indirect immunofluorescence test using a specially composed panel with monoclonal antibodies (MCA) to differentiation antigens of early lymphopoiesis stages. The panel composed for monitoring the population of leukemic cells during remission, contained 6 MCA selected from 40 MCA samples with the known specificity, basing on the principle of the highest reactivity with lymphoblasts from patients, and minimal positive reactions with lymphocytes from normal subjects. Blood mononuclear cells from 10 patients with ALL were subjected to immunophenotyping in the panel with MCA during remission, before each course of polychemotherapy. A retrospective analysis of the immunophenotyping data has shown that populations of lymphoid cells carrying antigens of early differentiation stages in amounts significantly exceeding the limits of the standard values (M +/- 3 delta) appear among blood lymphocytes, practically, in all the patients, 1-4 months before the relapse of ALL has been proved.

Morphologic types L1 and L2 (FAB) of acute lymphoblastic leukemia were classified by computer morphometry of bone marrow blast cells in 57 patients. Measurements were made on MOP-Videoplan Analyser (Reichert) by means of cell image contouring. The decision rule that had been deduced by us on the basis of multidimensional analysis of variance in two-cell training sets, and the selection of the following combination of the best discriminating features [the discriminant coefficients are in brackets: maximal nuclear diameter (-0.338), nuclear perimeter (-6.145), cell area (-0.044), nuclear area (1.007), relative nucleoli eccentricity (-0.279), cytoplasmic/nuclear relation (-5.920) and integral nucleoli area (-0.640)] were used for computer classification of L1 and L2 blast cells. The threshold score for discriminant function in this case was -117.766. Complete clinical remission rates in L1 ALL appeared to be higher than in L2 but remission duration in those groups did not differ significantly. The morphometric parameters of leukemic cells seem to characterize their maturity or their position in cell cycle phases and may be used in acute leukemia patient monitoring.

The authors provide data pertaining to the immunological phenotyping in the panel of monoclonal antibodies to various differentiating antigens of the leukemic cells in 27 patients with acute lymphoblastic leukemia (ALL). Based on the composition of the differentiating antigens of the leukemic cells the following immunological variants of the disease were identified: pre-B, pre-T and T-ALL--the thymic and mature (activated) ones. The phenotype was compared with the cytochemical parameters of the lymphoblasts of the identified immunological variants of ALL and with some clinical and hematological manifestations of the disease. The comparison of the data obtained during blast cell immunophenotyping with the cytochemical parameters and some clinicohematological findings suggests the development of a more fundamental classification of ALL in order to perfect the treatment of the patients suffering from ALL.