Maternal Methyl-Enriched Diet Increases Dopaminergic Tone of the Mesolimbic Brain System in Adult Offspring of WAG/Rij Rats.

The aim of this study is to find out whether maternal methyl-enriched diet affects the content of monoamines and their metabolites in brain structures of adult WAG/Rij offspring. It has been shown for the first time that maternal methyl-enriched diet (choline, betaine, folic acid, vitamin B12, L-methionine, zink) during the perinatal period increases dopaminergic tone of the mesolimbic brain system in adult offspring of WAG/Rij rats, which is accompanied by the suppression of the symptoms of genetic absence epilepsy and comorbid depression. Results suggest that maternal methyl-enriched diet during the perinatal period may be served as a new therapeutic strategy to prevent the development of a hypofunction of the mesolimbic dopaminergic brain system and associated genetic absence epilepsy and comorbid depression in offspring.

Preoperative stereotactic ablative body radiotherapy with postoperative conventional irradiation of soft tissue sarcomas: Protocol overview with a preliminary safety report.

Preoperative radiotherapy in patients with soft tissue sarcomas is characterized by important advantages: high precision of dose delivery, reduction of tumor volume and implantation potential, induction of immunologic response. Postoperative irradiation is associated with a reduced risk of complication, and a comprehensive radiotherapy planning in accordance with the pathologic report. Combination of pre- and postoperative irradiation gives the opportunity to use the best of both methods. OBJECTIVE: To analyze feasibility and safety of radiotherapy protocol that combined pre- and postoperative radiotherapy in patients with soft tissues sarcomas of extremities. MATERIALS AND METHODS: From 06.2018 to 01.2021, 23 patients with soft tissue sarcomas of extremities were included in the protocol (NCT04330456) and 14 cases with at least 12 months follow-up were eligible for analysis. Preoperative stereotactic ablative body radiotherapy (SBRT) was performed as 5 fraction of 7 Gy with dose reduction (5 fractions of 5 Gy) on the margins of the tumor. Postoperative radiotherapy started 5-8 weeks after the surgery and was performed as standard compartmental irradiation in 25 fractions of 2 Gy. Complications were determined according to CTCAE and wound complication scales. RESULTS: Preoperative SBRT and subsequent radical resection with tumor free surgical margins were performed in all 14 cases. Primary wound closure was mentioned in all patients. Postoperative radiotherapy started 51.8 days (range 33-99 days) days after the surgery. With a relatively short follow-up of 21.5 (13-30) months, we recorded 2 cases (14%) of severe complications (Canadian sarcoma group criteria), and there were no local recurrences. CONCLUSION: Our preliminary results demonstrate that the combination of preoperative SBRT and postoperative conventional radiotherapy is feasible and does not increase the risk of postoperative complications.

Gender-Dependent Effect of Maternal Methyl-Enriched Diet on the Expression of Genetic Absence Epilepsy and Comorbid Depression in Adult Offspring of WAG/Rij Rats.

In the present study it has been shown for the first time that maternal methyl-enriched diet (choline, betaine, folic acid, vitamin B12, L-methionine, zinc) during perinatal period reduces the expression of genetic absence epilepsy and comorbid depression in adult offspring of WAG/Rij rats. This beneficial effect was more pronounced in males compared with females. It is assumed that epigenetic modifications induced by maternal methyl-enriched diet in the offspring at the early stages of ontogenesis might be a possible mechanism underlying the correction of genetically-based pathologic phenotype in WAG/Rij rats. Results suggest that methyl-enriched diet during perinatal period can be potentially used for mitigation or prevention epileptogenesis and depression-like comorbid disorders in people genetically predisposed to absence epilepsy.

Rearing by foster Wistar mother with high level of maternal care counteracts the development of genetic absence epilepsy and comorbid depression in WAG/Rij rats.

It has been shown for the first time that rearing by a foster Wistar mother with high level of maternal care (MC) counteracts the expression of genetic absence epilepsy (AE) and comorbid depression - reduces the number, duration and index of spike-wave discharges (SWDs) and immobility time in the forced swimming test, as well as exerts substantial effects on morphology and time-frequency dynamics of SWDs in WAG/Rij rats. It is supposed that increases in MC early in development might be used to counteract epileptogenesis and comorbid depression in people genetically predisposed to AE.

[Concentrations of monoamines in the brain structures and features of behavior in the two-month old WAG/Rij rats].

The first spike-wave discharges (SWDs) in WAG/Rij rats begin to appear at age of 2-3 months and are fully manifested by 5-6 months. Occurrence of SWDs in the EEG is the main indicator of absence epilepsy. Extensive absence epilepsy in 5-6 months-old WAG/Rij rats is accompanied by decreases in dopamine and its metabolites concentrations in the meso-cortico-limbic and nigro-striatal dopaminergic brain systems, resulting in the expression of depression-like behavioral symptoms. In 36 day-old WAG/Rij rats, SWDs are not manifested, deficiency of dopamine is not revealed, and symptoms of depression-like behavior are not expressed. In this study, behavior and monoamines and their metabolites concentrations were investigated in 5 brain structures (prefrontal cortex, nucleus accumbens, hypothalamus, striatum, hippocampus) in 2 month-old WAG/Rij rats in comparison with Wistar rats of the same age. Reduction of the dopamine and its metabolites concentration in 2 month-old WAG/Rij rats was found only in the prefrontal cortex, indicating rapid response of the prefrontal cortex or its high sensitivity. Rapid response of the prefrontal cortex is supposed to be a.fundamental property of this brain structure. Decreases in the dopamine and its metabolites concentration in the prefrontal cortex in 2 month-old WAG/Rij rats were associated with features of behavior which can be regarded as a state of so called pre-pathology (increased anxiety and stress reactivity) preceding the development of depression-like behavior typical for 5-6-months old rats of this strain.

[The population structure of Mycobacterium tuberculosis in Mongolia as assessed using large sequence polymorphism analysis].

112 strains of M. tuberculosis isolated from lung tuberculosis patients in Mongolia were genotyped using RD9, RD7, TbD1, RD105, and RD750 loci. The genotypes of all the strains studied were characterized using the conservation of RD7, RD9, and RD750 loci and the presence of the deletion in the locus TbD1. RD105 was detected in 65 isolates (58%). The isolate was classified into two groups--East-Asian and Euro-American.