Different Trajectories for Diabetes Mellitus Onset and Recovery According to the Centralized Aerobic-Anaerobic Energy Balance Compensation Theory.

We recently reported that the restoration of cervical vertebral arterial blood flow access (measured as systolic peak (PS)) to the rhomboid fossa leads to the recovery of the HbA1c level in the case of patients with a pre-Diabetes Mellitus (pre-DM) condition. The theory of centralized aerobic-anaerobic energy balance compensation (TCAAEBC) provides a successful theoretical explanation for this observation. It considers the human body as a dissipative structure. Reported connections between arterial hypertension (AHT) and the level of HbA1c are linked through OABFRH. According to the TCAAEBC, this delivers incorrect information about blood oxygen availability to the cerebellum. The restoration of PS normalizes AHT in 5-6 weeks and HbA1c in 12-13 weeks. In the current study, we demonstrate the model which fits the obtained experimental data. According to the model, pathways of onset and recovery from pre-DM are different. The consequence of these differences is discussed. The great significance of the TCAAEBC for medical practice forces the creation of an appropriate mathematical model, but the required adjustment of the model needs experimental data which can only be obtained from an animal model(s). The essential part of this study is devoted to the analysis of the advantages and disadvantages of widely available common mammalian models for TCAAEBC cases.

T-Cell Immunity in COVID-19-Recovered Individuals and Individuals Vaccinated with the Combined Vector Vaccine Gam-COVID-Vac.

The COVID-19 pandemic has required extensive research on the new coronavirus SARS-CoV-2 and the creation of new highly effective vaccines. The presence of T-cells in the body that respond to virus antigens suggests adequate antiviral immunity. We investigated T-cell immunity in individuals who recovered from mild and moderate COVID-19 and in individuals vaccinated with the Gam-COVID-Vac combined vector vaccine. The ELISPOT method was used to determine the number of T-cells responding with IFN-γ synthesis to stimulation by peptides containing epitopes of the S-protein or N-, M-, ORF3, and ORF7 proteins, using peripheral blood mononuclear cells (PBMCs). At the same time, the multiplex method was used to determine the accumulation of IFN-γ and other cytokines in the culture medium. According to the data obtained, the proportion of positive conclusions about the T-cell immune response to SARS-CoV-2 antigens in control, recovered, and vaccinated individuals was 12%, 70%, and 52%, respectively. At the same time, more than half of the vaccinated individuals with a T-cell response were sensitized to the antigens of N-, M-, ORF3, and ORF7 proteins not produced by Gam-COVID-Vac, indicating a high likelihood of asymptomatic SARS-CoV-2 infection. Increased IFN-γ release by single sensitized T-cells in response to specific stimulation in recovered and vaccinated individuals did not result in the accumulation of this and other cytokines in the culture medium. These findings suggest a balance between cytokine production and utilization by immunocompetent cells as a prerequisite for providing a controlled cytokine signal and avoiding a "cytokine storm".

The Relevant Hormonal Levels and Diagnostic Features of Polycystic Ovary Syndrome in Adolescents.

RELEVANCE: The clinical picture of polycystic ovary syndrome (PCOS) is extremely polymorphic, especially in adolescence. At the same time, the diagnostic criteria of PCOS in adolescence are still under discussion, and the hormonal parameters, including anti-Mullerian hormone range and hyperandrogenism, are not determined. The aim of the present study was to characterize the pivotal clinical and hormonal features of PCOS in adolescents and to establish the age-specific thresholds of the most essential hormonal parameters. DESIGN: A case-control study. METHODS: The study included 130 girls with PCOS according to the complete Rotterdam criteria, aged 15 to 17 years. The control group consisted of 30 healthy girls with a regular menstrual cycle of the same age. A complete clinical and laboratory examination, hormonal assays, and ultrasound of the pelvic organs were performed. The serums anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH/FSH, prolactin, estradiol, 17α-OH progesterone (17α-OHP), androstenedione, testosterone (T), dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG), leptin, and free androgen index (FAI) were analyzed. The diagnostic accuracy of AMH, FAI, LH/FSH, T, and androstenedione levels in predicting PCOS in adolescents was established using a logistic regression model and calculating area under the receiver operator characteristic (ROC) curve (AUC). RESULTS: The serum levels of LH (9.0 (5.4-13.8) vs. 3.7 (2.5-4.7) IU/L; p < 0.0001), LH/FSH (1.6 (1.0-2.3) vs. 0.7 (0.5-1.1); p < 0.0001), 17α-OHP (4.1 (3.2-5.1) vs. 3.4 (2.7-3.8) nmol/L; p = 0.0071), cortisol (464.0 ± 147.6 vs. 284.0 ± 129.7 nmol/L; p < 0.0001), prolactin (266.0 (175.0-405.0) vs. 189.0 (142.0-269.0) mIU/L; p = 0.0141), T (1.9 (1.2-2.5) vs. 0.8 (0.7-1.1) nmol/L; p < 0.0001), androstenedione (15.8 (11.6-23.2) vs. 8.3 (6.5-10.8) ng/mL; p < 0.0001), AMH (9.5 (7.5-14.9) vs. 5.8 (3.8-6.9) ng/mL; p < 0.0001), FAI (5.5 (2.8-7.0) vs. 1.6 (1.1-2.3); p < 0.0001), SHBG (37.0 (24.7-55.5) vs. 52.9 (39.0-67.6) nmol/L; p = 0.0136), DHEAS (6.8 ± 3.2 vs. 5.1 ± 1.5 µmol/L; p = 0.0039), and leptin (38.7 ± 27.1 vs. 23.7 ± 14.0 ng/mL; p = 0.0178) were significantly altered in the PCOS patients compared to the controls. Multivariate analysis of all studied hormonal and instrumental parameters of PCOS in adolescents revealed as the most essential: AMH level > 7.20 ng/mL, FAI > 2.75, androstenedione > 11.45 ng/mL, total T > 1.15 nmol/L, LH/FSH ratio > 1.23, and the volume of each ovary > 10.70 cm3 (for each criterion sensitivity ≥ 75.0-93.0%, specificity ≥ 83.0-93.0%). The diagnostic accuracy of PCOS determination was 90.2-91.6% with the combined use of either four detected indexes, which was significantly higher than the use of each index separately. The accuracy of PCOS diagnostics reached 92% using AMH and leptin concentrations when the value of the logistic regression function [85.73 - (1.73 × AMH) - (0.12 × Leptin)] was less than 70.72. CONCLUSIONS: The results of the study estimate the threshold for AMH, FAI, androstenedione, testosterone, LH/FSH, and ovarian volume, which could be suggested for use in the PCOS diagnostics in adolescents with a high sensitivity and specificity. Moreover, the combination of either four determined indexes improved the diagnostic accuracy for the PCOS detection in adolescents.