Sensitivity and identifiability analysis of COVID-19 pandemic models

The paper presents the results of sensitivity-based identif iability analysis of the COVID-19 pandemic spread models in the Novosibirsk region using the systems of differential equations and mass balance law. The algorithm is built on the sensitivity matrix analysis using the methods of differential and linear algebra. It allows one to determine the parameters that are the least and most sensitive to data changes to build a regularization for solving an identif ication problem of the most accurate pandemic spread scenarios in the region. The performed analysis has demonstrated that the virus contagiousness is identif iable from the number of daily conf irmed, critical and recovery cases. On the other hand, the predicted proportion of the admitted patients who require a ventilator and the mortality rate are determined much less consistently. It has been shown that building a more realistic forecast requires adding additional information about the process such as the number of daily hospital admissions. In our study, the problems of parameter identif ication using additional information about the number of daily conf irmed, critical and mortality cases in the region were reduced to minimizing the corresponding misf it functions. The minimization problem was solved through the differential evolution method that is widely applied for stochastic global optimization. It has been demonstrated that a more general COVID-19 spread compartmental model consisting of seven ordinary differential equations describes the main trend of the spread and is sensitive to the peaks of conf irmed cases but does not qualitatively describe small statistical datasets such as the number of daily critical cases or mortality that can lead to errors in forecasting. A more detailed agent-oriented model has been able to capture statistical data with additional noise to build scenarios of COVID-19 spread in the region

Therapeutic effect of soluble factors of M2 phenotype macrophages in children with language impairments

The aim of the present study was to assess safety and clinical efficacy of inhalation immunotherapy based on intranasal administration of bioactive factors produced by the M2 phenotype macrophages in children with language impairments, as well as to study the effect of inhalation immunotherapy on the cytokine profile in the patients' blood serum. The study was carried out according to the NCT04689282 protocol (www.ClinicalTrials.gov) and included 14 children (9 boys / 5 girls), aged 3 to 8 years, with language impairments associated with perinatal or postnatal CNS lesions of various origin. The children recruited into the study were assessed by a neurologist and speech therapist before the therapy, at the end of the course (1 month), and 6 months later. Serum samples for cytokine analysis were obtained before and 1 month after therapy. The course of intranasal inhalations by the conditioned M2 media (2 ml one time per day for 28-30 days) was safe and well tolerated. None of the 14 treated children had significant adverse reactions and severe undesirable events. Intranasal immunotherapy led to a decrease in the severity of language problems, which manifested by improved speech understanding by 45%; the sensorimotor level of speech, by 51%; word formation skills, by 72%, as well as a twofold increase in general and fine motor skills. In children with signs of autism spectrum disorders, along with a language improvement, a decrease in the severity of autistic symptoms was registered, as evidenced by statistically significant decrease in the CARS score from 42.5 to 38.5 after 1 month, and to 33 points after 6 months (p < 0.05). The clinical effect was revealed rather soon, i.e., within a month after the first procedure, being maintained or intensified during a follow-up for 6 months. At the same time, two-thirds of the children showed a clear clinical improvement, with insignificant effect in the rest of patients. Comparative analysis of the serum cytokine levels in these subgroups showed that children with a pronounced positive response to inhaled immunotherapy differed in the following parameters: (1) initially higher level of VEGF and IGF-1, and (2) decrease the level of TNFα in response to intranasal immunotherapy. In summary, we first tested a fundamentally new approach based on the use of soluble factors from M2-type macrophages and intranasal route of their administration in order to treat the children with severe language impairments, demonstrating safety and obtained preliminary data on effectiveness of such approach

Combined phlebectomy in androgenital form of varicosity veins of small pelvis

The study objective is to demonstrate the effectiveness of combined phlebectomy of varicose veins of the penis and spermatic veins in the treatment of venous erectile dysfunction of the distal type in combination with varicocele as an androgenital manifestation of small pelvic varicose disease; to demonstrate the potency of combined phlebectomy of varicose veins of the penis and spermatic veins in the treatment of venous penis of the distal type in combination with varicocele, as an androgenital manifestation of small pelvic varicose disease in men.Materials and methods. Combined phlebectomies (n = 5) were performed in patients with androgenital form of varicose small pelvic, clinically manifested by erectile dysfunction, varicose veins, varicocele.Results. Preoperative complex examination of patients included multispiral computer, magnetic resonance angio andpharmacocavernosog-raphy with ultrasonic duplex scanning of the penis, scrotum, prostatic venous plexus allowed verifying varicose disease of the small pelvic, clinically manifested by erectile, dysmorphophobic disorders in combination with varicocele. Combined phlebectomy superficial veins of the penis in combination with the operation of Marmara (phlebectomy veins of spermatic cord) with blockage of outflow into the sapheno-femo-ral anastomosis gave a positive result in all cases. The international index of erectile function increasedfrom 12 ± 2 points before the operation to 21 ± 1 pointspostoperativly (p <0.05).Conclusion. Blocking of superficial and deep venous systems of the penis by naked circumscision with phlebectomy of the superficial vein of the penis, bandaging of the retroglandular plexus in the area of the coronary sulcus of the penis, as well as high ligation in the inguinal-femoral region of the superficial vein of the penis in combination with phlebectomy of the spermatic veins (operation Marmara) allow to restore hemodynamic balance between arterial inflow and venous outflow to penis and achievement of adequate erection, sufficient for vaginal penetration

EFFECT OF PUMPKIN (CUCURBITA PEPO L.) AND MARIGOLD (TAGETES PATULA L.) EXTRACTS ON HIPPOCAMPAL MITOCHONDRIA FUNCTIONAL ACTIVITY WITHIN CONDITIONS OF EXPERIMENTAL ACUTE BRAIN HYPOMETABOLISM

The aim of the study is to evaluate the effect of pumpkin (Cucurbita pepo L.) and marigold extracts (Tagetes patula L.) on the hippocampal mitochondria functional activity within the conditions of experimental acute brain hypometabolism.Materials and methods. The work was performed on 50 male Wistar rats, which reproduced an acute brain hypometabolic state by administration of a 3M sodium azide solution in hippocampus (n = 40 and n = 10 – a group of sham-operated animals). The test extracts and the reference drug – EGb 761 – were prophylactically administered at the dose of 100 mg/kg per os for 10 days. 24 hours after the last administration, sodium azide was injected, the brain was taken, the hippocampus was isolated to obtain a supernatant and determine the parameters of mitochondrial respiration, the intensity of anaerobic processes, the concentration of the apoptosis-inducing factor, endonuclease G, and β-amyloid.Results. The carried out study established that the prophylactic administration of pumpkin and marigold extracts contributed to the restoration of a mitochondrial function and a decrease in the intensity of anaerobic processes. In the group of the rats treated with pumpkin and marigold extracts, an increase of ATP concentration in the hippocampal supernatant by 65.7% (p<0.002) was observed; it was 66.2% (p><0.002) relative to the animals deprived of pharmacological support. ,When the rats were treated with pumpkin and marigold extracts, a decrease in the concentration of apoptosis-inducing factor (by 33% (p><0.002) and 38.3% (p><0.002), respectively) and endonuclease G (by 3.6 times (p><0.002) and 4.4 times (p><0.002), respectively) was also noted. The administration of pumpkin and marigold extracts reduced the amyloid β-peptide concentration in the rats’ hippocampus by 54.4% (p><0.0002) and 54.4% (p><0.0002), respectively. The test-extracts had an equivalent therapeutic efficacy with the reference drug. Conclusion On the basis of the obtained data, it is possible to suggest the prospect of a further study of pumpkin and marigold extracts as the drugs of a targeted correction of cerebral hypometabolism. Keywords: plant extracts, hypometabolism, hippocampus, mitochondria >< 0.002) was observed; it was 66.2% (p<0.002) relative to the animals deprived of pharmacological support. ,When the rats were treated with pumpkin and marigold extracts, a decrease in the concentration of apoptosis-inducing factor (by 33% (p><0.002) and 38.3% (p><0.002), respectively) and endonuclease G (by 3.6 times (p><0.002) and 4.4 times (p><0.002), respectively) was also noted. The adm>< 0.002) relative to the animals deprived of pharmacological support. ,When the rats were treated with pumpkin and marigold extracts, a decrease in the concentration of apoptosis-inducing factor (by 33% (p<0.002) and 38.3% (p><0.002), respectively) and endonuclease G (by 3.6 times (p><0.002) and 4.4 times (p><0.002), respectively) was also noted. The administration of pumpki>< 0.002) and 38.3% (p<0.002), respectively) and endonuclease G (by 3.6 times (p><0.002) and 4.4 times (p><0.002), respectively) was also noted. The administration of pumpkin and marigold extracts reduced the amyloid β-peptide concentration in the rats’ hippocampus by 54.4% (p><0.0002) and 54.4% (p><0.0002), respectively. The test-extracts had an equivalent therapeutic efficacy with >< 0.002), respectively) and endonuclease G (by 3.6 times (p<0.002) and 4.4 times (p><0.002), respectively) was also noted. The administration of pumpkin and marigold extracts reduced the amyloid β-peptide concentration in the rats’ hippocampus by 54.4% (p><0.0002< 0.002) and 4.4 times (p<0.002), respectively) was also noted. The administration of pumpkin and marigold extracts reduced the amyloid β-peptide concentration in the rats’ hippocampus by 54.4% (p><0.0002) and 54.4% (p><0.0002), respectively. The te>< 0.002), respectively) was also noted. The administration of pumpkin and marigold extracts reduced the amyloid β-peptide concentration in the rats’ hippocampus by 54.4% (p<0.0002) and 54.4% (p><0.0002), respectively. The test-extracts had an equiva>< 0.0002) and 54.4% (p<0.0002), respectively. The test-extracts had an equivalent therapeutic efficacy with the reference drug. Conclusion On the basis of the obtained d>< 0.0002), respectively. The test-extracts had an equivalent therapeutic efficacy with the reference drug.Conclusion On the basis of the obtained data, it is possible to suggest the prospect of a further study of pumpkin and marigold extracts as the drugs of a targeted correction of cerebral hypometabolism