Poor patient outcome correlates with active engulfment of cytokeratin positive CTCs within cancer-associated monocyte population in lung cancer.

High rates of mortality in non-small cell lung cancer lung cancer is due to inherent and acquired resistance to systemic therapies and subsequent metastatic burden. Metastasis is supported by suppression of the immune system at secondary organs and within the circulation. Modulation of the immune system is now being exploited as a therapeutic target with immune checkpoint inhibitors. The tracking of therapeutic efficacy in a real-time can be achieved with liquid biopsy, and evaluation of circulating tumour cells and the associated immune cells. A stable liquid biopsy biomarker for non-small cell lung cancer lung cancer has yet to be approved for clinical use. We performed a cross-sectional single-site study, and collected liquid biopsies from patients diagnosed with early, locally advanced, or metastatic lung cancer, undergoing surgery, or systemic therapy (chemotherapy/checkpoint inhibitors). Evaluation of overall circulating tumour cell counts, or cluster counts did not correlate with patient outcome. Interestingly, the numbers of Pan cytokeratin positive circulating tumour cells engulfed by tumour associated monocytes correlated strongly with patient outcome independent of circulating tumour cell counts and the use of checkpoint inhibitors. We suggest that Pan cytokeratin staining within monocytes is an important indicator of tumour-associated inflammation post-therapy and an effective biomarker with strong prognostic capability for patient outcome.

Synopsis of gastropod-associated nematodes of Ciscaucasia (Russian Federation) with the description of a new species of Pellioditis Dougherty, 1953 (syn. Phasmarhabditis Andrássy, 1976).

Caucasus is known as one of the few biodiversity hotspots in Europe and is characterised by rich gastropod fauna while the nematode fauna in association with gastropods has remained largely understudied. Surveys conducted in 2019 and 2021 in the North Caucasus of the Russian Federation (Stavropol Upland and western and central parts of Krasnodar Krai) has revealed the presence of three new species of Pellioditis, a facultative parasite of land gastropods, and two species of obligate parasites, the intestinal parasite Angiostoma kimmeriense and a new, still undescribed species of a larval ectoparasite Alloionema sp. The new associations of Cruznema sp. and Rhabditophanes sp. with land gastropods were recorded for the first time in the Russian Federation. The new species of Pellioditis Dougherty, 1953 described here is based on the analysis of morphology and molecular studies of two distant and morphologically distinct strains, thermalis and sindicae. Pellioditis thermalis n. sp. was characterised by females possessing a tail of about 95-100 µm long, broadly conical in shape in the thermalis and sindicae strains, with a rounded anterior part and a subulate terminal part as long as the former; prominent phasmids located at the mid-tail, equatorial vulva position, a lateral field of three ridges (four incisions), males with spicules featuring a hole at the distal tip, ensheathed infective juveniles with average length 717 µm in the thermals strain and 771 µm in the sindicae strain, and exsheathed ones 644 µm and 682 µm, respectively. ITS-based phylogenetic analyses revealed that all Pellioditis species found in Ciscaucasia and Transcaucasia probably belong to two separate clades, with independent evolutionary histories of colonisation of this area. The entire Caucasus range area appears to serve as a biodiversity hotspot for the genus Pellioditis, presumably due to its complicated geological history and repeated isolation events for its terrestrial mollusc hosts.

[Investigation of the effect of ethylmethylhydroxypyridine succinate on the effectiveness of non-steroidal anti-inflammatory drugs for visceral and somatic pain in mice and rats]. / Izuchenie vliyaniya etilmetilgidroksipiridina suktsinata na effektivnost' nesteroidnykh protivovospalitel'nykh preparatov pri vistseral'noi i somaticheskoi boli v eksperimente na myshakh i krysakh.

OBJECTIVE: To study the effect of ethylmethylhydroxypyridine succinate (EMHPS) on the analgesic effect of the non-selective cyclooxygenase (COX) inhibitor diclofenac sodium and the selective COX-2 inhibitor etoricoxib in models of acute visceral and somatic pain and to evaluate the possibility of using EMHPS in combination with COX inhibitors to reduce their doses while maintaining analgesic efficiency. MATERIAL AND METHODS: We studied the effect of EMHPS with a single oral administration on the analgesic effects of non-steroidal anti-inflammatory drugs (NSAIDs): the non-selective COX inhibitor diclofenac sodium and the selective COX-2 inhibitor etoricoxib - on models of acute visceral (vinegar writhing test) and somatic pain (formalin test and mechanical hyperalgesia during inflammation) in an experiment on mice and rats. RESULTS: In a model of acute visceral pain in mice, EMGPS (25-100 mg/kg) does not have a significant effect on its severity, but enhances the analgesic effect of diclofenac sodium (0.5 mg/kg) and etoricoxib (1 mg/kg). In the formalin test in rats, which simulates pain during surgical incisions (trauma), EMGPS (25 mg/kg) increases the severity of the analgesic effect of COX inhibitors (1 mg/kg), primarily by reducing pain in the acute phase caused by the effect of formalin on afferent neurons. In a model of mechanical hyperalgesia in rats caused by exudative inflammation after injection of a carrageenan solution into the paw, EMHPS enhances the effect of diclofenac to a greater extent than etoricoxib. CONCLUSION: The data obtained indicate the feasibility of a clinical study of the use of EMGPS in combination with NSAIDs for visceral and somatic pain in order to assess its ability to increase the therapeutic effect of NSAIDs.

[Predictors of therapeutic efficacy of immune response checkpoint inhibitors in clear cell renal cell carcinoma].

Immunotherapy in oncologic diseases involves the use of drugs which stimulate the immune system and indirectly suppress tumor cells growth. These agents have expanded the treatment options for cancer patients. Despite the impressive success achieved in the development of immune checkpoint inhibitors (ICIs) and subsequent approval in a broader spectrum of malignant tumors, most patients are not responded the therapy. Currently available predictive markers of efficacy are nonspecific. However, microRNAs are of particular interest, which regulate gene expression and are involved in the carcinogenesis and therapy resistance. Therefore, it is clear that for the most efficient and cost-effective use of ICIs, it is important to have validated biomarkers that will accurately predict the therapeutic response. The published results on molecular genetic changes in patients with renal cell carcinoma (RCC) were analyzed and summarized in order to determine possible prognostic biomarkers when prescribing ICI therapy.

DNA methylation and gene expression changes in mouse mammary tissue during successive lactations: part I - the impact of inflammation.

Mastitis is among the main reasons women cease breastfeeding, which leads to them supplementing breast milk with artificial formula. In farm animals, mastitis results in significant economic losses and the premature culling of some animals. Nevertheless, researchers do not know enough about the effect of inflammation on the mammary gland. This article discusses the changes to DNA methylation in mouse mammary tissue caused by lipopolysaccharide-induced inflammation (4 h post-injection of lipopolysaccharide). We analysed the expression of some genes related to mammary gland function, epigenetic regulation, and the immune response. The analysis focused on three comparisons: inflammation during the first lactation, inflammation during second lactation with no history of inflammation, and inflammation during second lactation with previous inflammation. We identified differentially methylated cytosines (DMCs), differentially methylated regions (DMRs), and some differentially expressed genes (DEGs) for each comparison. The three comparisons shared some DEGs; however, few DMCs and only one DMR were shared. These observations suggest that inflammation is one of several factors affecting epigenetic regulation during successive lactations. Furthermore, the comparison between animals in second lactation with and without inflammation, with no inflammation history during first lactation showed a different pattern compared to the other conditions in this experiment. This indicates that inflammation history plays an important role in determining epigenetic changes. The data presented in this study suggest that lactation rank and previous inflammation history are equally important when explaining mammary tissue gene expression and DNA methylation changes.Abbreviations: RRBS, reduced representation bisulfite sequencing; RT-qPCR, real-time quantitative polymerase chain reaction; MEC, mammary epithelial cells; TSS, transcription start site; TTS, transcription termination site; UTR, untranslated region; SINE, short interspersed nuclear element; LINE, long interspersed nuclear element; CGI, CpG island; DEG, differentially expressed gene; DMC, differentially methylated cytosine; DMR, differentially methylated region; GO term, gene ontology term; MF, molecular function; BP, biological process.

The microbiome of buried soils demonstrates significant shifts in taxonomic structure and a general trend towards mineral horizons.

Burial mounds represent a challenge for microbiologists. Could ancient buried soils preserve microbiomes as they do archaeological artifacts? To investigate this question, we studied the soil microbiome under a burial mound dating from 2500 years ago in Western Kazakhstan. Two soil profile cuts were established: one under the burial mound and another adjacent to the mound surface steppe soil. Both soils represented the same dark chestnut soil type and had the same horizontal stratification (A, B, C horizons) with slight alterations. DNA samples isolated from all horizons were studied with molecular techniques including qPCR and high throughput sequencing of amplicon libraries of the 16S rRNA gene fragment. The taxonomic structure of the microbiome of the buried horizons demonstrated a deep divergence from ones of the surface, comparable to the variation between different soil types (representatives of the soil types were included in the survey). The cause of this divergence could be attributed to diagenetic processes characterized by the reduction of organic matter content and changes in its structure. Corresponding trends in the microbiome structure are obvious from the beta-diversity pattern: the A and B horizons of the buried soils form one cluster with the C horizons of both buried and surface soil. This trend could generally be designated as 'mineralization'. Statistically significant changes between the buried and surface soils microbiomes were detected in the number of phylogenetic clusters, the biology of which is in the line of diagenesis. The trend of 'mineralization' was also supported by PICRUSt2 functional prediction, demonstrating a higher occurrence of the processes of degradation in the buried microbiome. Our results show a profound shift in the buried microbiome relatively the "surface" microbiome, indicating the deep difference between the original and buried microbiomes.

Capturing CO2 by ceria and ceria-zirconia nanomaterials of different origin.

Ceria and ceria-zirconia nanomaterials of different origin were studied in order to elucidate the role of their structural and textural characteristics in controlling the performance towards CO2 capture. Two commercial cerias and two home-prepared samples, CeO2 and CeO2-ZrO2 (75% CeO2) mixed oxide, were investigated. The samples were characterized by a number of analytical techniques including XRD, TEM, N2-adsorption, XPS, H2-TPR, Raman and FTIR spectroscopy. Static and dynamic CO2 adsorption experiments were applied to assess the CO2 capture performance. The type of surface species formed and their thermal stability were evaluated by in situ FTIR spectroscopy and CO2-TPD analysis. The two commercial ceria samples possessed similar structural and textural characteristics, formed the same types of carbonate-like surface species upon CO2 adsorption and, consequently, demonstrated almost identical CO2 capture performance under both static and dynamic conditions. The thermal stability of the adsorbed species increased in the order bidentate (B) carbonates, hydrogen carbonates (HC) and tridentate carbonates (T-III, T-II, T-I). Reduction of CeO2 increased the relative amount of the most strongly bonded T-I tridentate carbonates. Preadsorbed water led to hydroxylation and enhanced formation of hydrogen carbonates. Although the synthesized CeO2 sample had a higher surface area (by 30%) it showed a disadvantageous long mass transfer zone in the CO2-adsorption breakthrough curves. Because of its complex pore structure, this sample probably experiences severe intraparticle CO2 diffusion resistance. Having the same surface area as the synthesized CeO2, the mixed CeO2-ZrO2 oxide exhibited the highest CO2 capture capacity of 136 µmol g-1 under dynamic conditions. This was related to the highest concentration of CO2 adsorption sites (including defects) on this sample. The CeO2-ZrO2 system showed the lowest sensitivity to the presence of water vapor in the gas stream due to the lack of dissociative water adsorption on this material.

Analysis of the Involvement of NMDA Receptors in Analgesia and Hypothermia Induced by the Activation of TRPV1 Ion Channels.

NMDA glutamate receptors play an important role in normal and pathophysiological nociception. At the periphery, they can interact with TRPV1 ion channels. The blockade of TRPV1 ion channels decreases NMDA-induced hyperalgesia, and NMDA receptor antagonists suppress the pain response to the TRPV1 agonist capsaicin. Since TRPV1 ion channels and NMDA receptors can functionally interact at the periphery, it would be interesting to investigate the possibility that they interact in the CNS. A single subcutaneous injection of 1 mg/kg of capsaicin was found to raise the thermal pain threshold in the tail flick test in mice, which reproduces the spinal flexion reflex, owing to the ability of capsaicin to cause long-term desensitization of nociceptors. Preventive administration of either noncompetitive NMDA receptor antagonists (high-affinity MK-801 20 µg/kg and 0.5 mg/kg subcutaneously; low-affinity hemantane 40 mg/kg intraperitoneally) or the selective TRPV1 antagonist BCTC (20 mg/kg intraperitoneally) inhibit the capsaicin-induced increase in the pain threshold. Capsaicin (1 mg/kg, subcutaneous injection) induces transient hypothermia in mice, which is brought about by hypothalamus-triggered vegetative reactions. This effect is prevented by BCTC but not by the noncompetitive NMDA receptor antagonists.

Evaluation of mRNA markers in differentiating human SH-SY5Y cells for estimation of developmental neurotoxicity.

Current guidelines for developmental neurotoxicity (DNT) evaluation are based on animal models. These have limitations so more relevant, efficient and robust approaches for DNT assessment are needed. We have used the human SH-SY5Y neuroblastoma cell model to evaluate a panel of 93 mRNA markers that are frequent in Neuronal diseases and functional annotations and also differentially expressed during retinoic acid-induced differentiation in the cell model. Rotenone, valproic acid (VPA), acrylamide (ACR) and methylmercury chloride (MeHg) were used as DNT positive compounds. Tolbutamide, D-mannitol and clofibrate were used as DNT negative compounds. To determine concentrations for exposure for gene expression analysis, we developed a pipeline for neurite outgrowth assessment by live-cell imaging. In addition, cell viability was measured by the resazurin assay. Gene expression was analyzed by RT-qPCR after 6 days of exposure during differentiation to concentrations of the DNT positive compounds that affected neurite outgrowth, but with no or minimal effect on cell viability. Methylmercury affected cell viability at lower concentrations than neurite outgrowth, hence the cells were exposed with the highest non-cytotoxic concentration. Rotenone (7.3 nM) induced 32 differentially expressed genes (DEGs), ACR (70 µM) 8 DEGs, and VPA (75 µM) 16 DEGs. No individual genes were significantly dysregulated by all 3 DNT positive compounds (p < 0.05), but 9 genes were differentially expressed by 2 of them. Methylmercury (0.8 nM) was used to validate the 9 DEGs. The expression of SEMA5A (encoding semaphorin 5A) and CHRNA7 (encoding nicotinic acetylcholine receptor subunit α7) was downregulated by all 4 DNT positive compounds. None of the DNT negative compounds dysregulated any of the 9 DEGs in common for the DNT positive compounds. We suggest that SEMA5A or CHRNA7 should be further evaluated as biomarkers for DNT studies in vitro since they also are involved in neurodevelopmental adverse outcomes in humans.

[The use of photodynamic therapy in the complex treatment of chronic generalized moderate periodontitis]. / Primenenie fotodinamicheskoi terapii v kompleksnom lechenii khronicheskogo generalizovannogo parodontita srednei stepeni.

OBJECTIVE: Improving the effectiveness of the treatment of chronic generalized periodontitis by photodynamic therapy (PDT) due to clinical and functional validation of the effects of a photosensitizer. MATERIAL AND METHODS: A clinical and functional study and treatment of moderate chronic generalized periodontitis was carried out in 60 people (24 males and 36 females) aged 35 to 50 years without somatic pathology with orthognathic bite. The patients were divided into 2 groups depending on the type of treatment: group 1 (main) included 30 patients (17 males and 13 females, mean age of patients was 42.5±3.3 years) who received comprehensive treatment consisting of oral sanitation, removal of dental plaque and curettage of periodontal pockets followed by PDT with 1% Geleophor gel using an AFS Spektr LED emitter with a wavelength of 660 nm and a power of 2.5 W, the course consisted of 4 procedures with exposure time of 7 minutes each; group 2 (control) included 30 patients (11 males and 19 females, mean age of patients was 43.0±2.1 years) undergoing standard treatment followed by protective capping with no active therapeutic agent. The state of microcirculation in tissues was studied by the laser Doppler flowmetry (LDF) using the LAKK-M device (Lazma, Russia). RESULTS: According to LDF data in both groups, it was found that the improvement of microcirculation in periodontal tissues after complex treatment is accompanied by an increase in blood flow and its activity, at that the level of oxygenation and specific oxygen consumption increased more pronounced after PDT, the effect persisted after 6 and 12 months. CONCLUSION: The use of PDT with LED emitter has a normalizing effect on the state of microcirculation and oxygenation in periodontal tissues.

DNA methylation and gene expression changes in mouse mammary tissue during successive lactations: part II - the impact of lactation rank.

Mastitis is among the main reasons women cease breastfeeding. In farm animals, mastitis results in significant economic losses and the premature culling of some animals. Nevertheless, the effect of inflammation on the mammary gland is not completely understood. This article discusses the changes to DNA methylation in mouse mammary tissue caused by lipopolysaccharide-induced inflammation after in vivo intramammary challenges and the differences in DNA methylation between 1st and 2nd lactations. Lactation rank induces 981 differential methylations of cytosines (DMCs) in mammary tissue. Inflammation in 1st lactation compared to inflammation in 2nd lactation results in the identification of 964 DMCs. When comparing inflammation in 1st vs. 2nd lactations with previous inflammation history, 2590 DMCs were identified. Moreover, Fluidigm PCR data show changes in the expression of several genes related to mammary function, epigenetic regulation, and the immune response. We show that the epigenetic regulation of two successive physiological lactations is not the same in terms of DNA methylation and that the effect of lactation rank on DNA methylation is stronger than that of the onset of inflammation. The conditions presented here show that few DMCs are shared between comparisons, suggesting a specific epigenetic response depending on lactation rank, the presence of inflammation, and even whether the cells had previously suffered inflammation. In the long term, this information could lead to a better understanding of the epigenetic regulation of lactation in both physiological and pathological conditions.Abbreviations: RRBS, reduced representation bisulphite sequencing; RT-qPCR, real-time quantitative polymerase chain reaction; MEC, mammary epithelial cells; MaSC, mammary stem cell; TSS, transcription start site; TTS, transcription termination site; UTR, untranslated region; SINE, short interspersed nuclear element; LINE, long interspersed nuclear element; CGI, CpG island; DEG, differentially expressed gene; DMC, differentially methylated cytosine; DMR, differentially methylated region; GO term, gene ontology term; MF, molecular function; BP, biological process.

[Correction of serum prooncogenic cytokines and metastases by 5-hydroxypyrimidine derivatives and doxorubicin after removal of a primary tumor node in mice with the Lewis lung epidermoid carcinoma]. / Korrektsiia urovnia syvorotochnykh proonkogennykh tsitokinov i metastazirovaniia proizvodnymi 5-oksipirimidina i doksorubitsinom posle udaleniia pervichnogo opukholevogo uzla u myshei s metastaziruiushchim rakom legkogo LLC.

The effect of a single injection of doxorubicin, 8-day administration of two 5-hydroxypyrimidine derivatives, SNK-411 (2-Isobutyl-4,6-dimethyl-5-hydroxypyrimidine) and SNK-578 (hydrochloride of 2-isobutyl-4,6-dimethyl-5-hydroxypyrimidine), on metastases, lifespan and serum cytokines has been investigated in С57ВL/6 mice after removal of a primary tumor node of Lewis lung carcinoma (LLC). LLC cells (1×106) were injected in the footpad of right hind feet of mice in control and experimental groups; after 14 days of tumor development the hind feet with the tumor were amputated at the ankle level. One hour before the amputation mice received a single injection of doxorubicin (4 mg/kg) and 8-day therapy with the 5-hydroxypyrimidine derivatives started. SNK-578 monotherapy was performed at a dose of 10 mg/kg administered intraperitoneally (i.p.). SNK-411 was administered per os at a dose of 25 mg/kg. In the case of combined therapy mice also received a single injection of doxorubicin (4 mg/kg; i.p.). The metastasis inhibition index in mice-treated with SNK-411 and SNK-578 were 53.3% as compared with control mice (with removed tumor). The mice-treated with SNK-411, doxorubicin, and the combination SNK-578 + doxorubicin had lifespan increased by 60.2%, 53.9%, and 42.9%, respectively. A single injection of doxorubicin, the course administration of the 5-hydroxypyrimidine derivative alone and in combination with single injection of doxorubicin completely decreased serum levels of the prooncogenic Th2-cytokines IL-4, and IL-6 and significantly decreased the level of the Th2-cytokine IL-5. Administration of doxorubicin, SNK-411 and SNK-578 did not influence serum concentration of Th1-cytokine interferon gamma (IFN-γ). These data confirm our previous findings that administration of the compounds studied decreased concentrations of prooncogenic IL-4 and IL-6 in tumor-bearing mice with LLC and had no effect on concentrations of the Th1-cytokine IFN-γ.

[The impact of dental caries prevention program on the anthropometric measurements of preschool children]. / Vliyanie programmy profilaktiki kariesa zubov, provodimoi v doshkol'nykh uchrezhdeniyakh, na rostovesovye pokazateli detei.

THE AIM OF THE STUDY: Was to compare body mass indices (BMI) of children receiving and not receiving dental caries prevention program in preschool institutions at the age of 3-6 years. MATERIAL AND METHODS: The study comprised163 children (76 boys and 87 girls) initially examined at the age of 3 years in nurseries of the Khimki city region. In one of the nurseries 54 children received dental caries prevention and educational program for 3 years. Other 109 children not receiving any special programs served as controls. Data on caries prevalence and intensity as well as weight and height were collected at baseline examination and 3 years after. BMI was calculated by standard formula and WHO criteria for weight deficiency, normal weight, overweight and obesity for children aged 2-5 and 6-17 years were applied. RESULTS: Caries prevalence in 3-years-old was 34.1% with dmft median of 1.4 teeth. After 3 years the prevalence of dental caries reached 72.5% in controls and was almost twice as low in the main group (39.3%). Caries intensity growth was also significantly higher in controls (p<0.0001). There was statistically significant difference on the rate of underweight and normal weight in children receiving and not receiving dental caries preventive program (p<0.05). The rate of normal and low BMI in the main group was 82.6% (vs. 66% in controls) and 7.7% (vs. 22%), correspondingly. The higher the caries intensity the more is the risk for being underweight (11.5% in caries-free children vs 25.7% in having DMFT+dft more than 4, p=0.034). CONCLUSION: Our study showed positive impact of dental caries prevention program on the anthropometric measurements of children aged 3-6 years which increases the significance of this type of programs in pre-school institutions.

[Investigation of the role of polymorphic loci RS2299941, RS1903858, RS10490920, RS2735343 of the PTEN gene in patients with prostate cancer].

Prostate cancer is a clinically heterogeneous disease, and accurate risk stratification of patients is becoming a key clinical task. This is the most common malignant neoplasm and the leading cause of cancer death in men worldwide. Genomic markers include tools and technologies that can predict the probability of an initial positive biopsy, reduce the number of unnecessary repeated biopsies, identify tumors with low, medium and high risk, classify the degree of disease, as well as predict and monitor the clinical response to intervention. Variants of the PTEN gene are of great interest as genetic markers of the risk of developing prostate malignancies.

The possibility of diagnosing intrauterine infection by the content of nitrite and non-thiolate nitroso compounds in maternal blood plasma.

The aim of the study is to develop a method for early diagnosis of intrauterine infection (IUI). A study of markers of inflammation in the venous blood of 60 pregnant women was conducted. The study was followed by a retrospective assessment of the outcomes of pregnancies and childbirth. Of these, 33 patients with a gestation period of more than 37 weeks (full-term pregnancy) and, accordingly, 27 patients from whom the blood sample was taken at a period of less than 37 weeks - patients with the threat of premature birth (PB). PB is the main factor contributing to the development of IUI. 27 patients were diagnosed with premature rupture of the membranes (PROM). Of these, 15 are with the threat of PB. 8 of them had a diagnosed IUI. In all cases of diagnosed PROM, including those with IUI, the concentration of nitrite and nontiolate nitroso compounds (NO2-+RNO) in the mother's blood plasma was 2.3±1.2 µM, while normally it does not exceed 0.1 µM (p<0.001). Regardless of the duration of pregnancy. The use of antibiotics in the case of PROM contributed to the normalization of the concentration (NO2-+RNO). Therefore, increasing of this indicator is result of bacterial infection. Indications of other markers of inflammation: the number of leukocytes in venous blood and in a smear of vaginal contents, the level of C-RB did not significantly change in both PROM and IUI (p>0.1). Since the concentration index (NO2-+RNO) increased in almost all cases of PREM, unlike all other clinical and biochemical indicators used in modern medicine, there is an obvious sense of its use for the current monitoring of the health of pregnant women. But it is still impossible to say unequivocally about the possibility of monitoring the fetal health by concentration (NO2-+RNO) in the mother's blood.

[Testosterone and Alzheimer's disease].

Alzheimer's disease (AD) is a neurodegenerative disease that causes dementia in half of the cases. Asthma is usually found in people over 65 years of age. The etiopathogenesis of the disease is multifactorial and includes genetic factors, nutritional disorders, mitochondrial dysfunction, oxidative stress, and aging. Sex hormones have an important influence on the development of AD, as evidenced by a higher incidence in women than in men. Considering the significant influence of T on the maintenance of normal brain function, the present study is aimed at evaluating the impact of androgen deprivation therapy (ADT), as well as testosterone therapy, on the risk of AD development and progression. Although there is some clinical inconsistency between studies, androgens have a significant effect on brain function and are beneficial for AD patients. Low levels of circulating androgens should be considered as a significant risk factor for the development of AD and memory loss. With a reduced level of T in the plasma of men, its administration improves cognitive performance and memory, treatment should be started at an early stage of the disease. In men and women with AD, androgens improve mental state and slow the progression of the disease, providing a protective effect. In the future, it is necessary to conduct studies on a large population, taking into account personality factors and a more specific approach to assessing cognitive functions and the causal relationship of T administration in AD.

Environmental Determination of Indigenous Bifidobacteria of the Human Intestine.

The environmental determination of indigenous (constantly present) bifidobacteria of the human large intestine is considered in this review. Environmental determination (from the Latin determinere, "I determine") is understood as a set of natural phenomena of a habitat (biotope) that determine the role of indigenous microorganisms in the microbiocenosis. Using the symbiotic approach, an attempt is made to identify the environmental conditions for the habitat of bifidobacteria and their physiological effects in the microsymbiocenosis. The features of indigenous bifidobacteria in terms of their nature have been established: evolutionary-genetic (phylogenetic remoteness, genome conservation, metabolic specialization), biochemical (lysozyme resistance, constitutive acetate production), and physiological (microbial "friend-foe" identification, immunoregulation), which are important in adaptation (persistence) and the provision of mutualistic effects and stability of the bifidoflora in the population.

[Testing of the Russian-language version of the Thought, Language and Communication Scale]. / Aprobatsiya russkoyazychnogo varianta shkaly Thought, Language, Communication Scale.

OBJECTIVE: To analyze the possibilities of using the Russian version of the Thought, Language and Communication Scale (TLC) for early recognition of thought disorders in patients at clinical high-risk for schizophrenia. MATERIAL AND METHODS: For the main group, the study included 30 adolescent male patients (19.2±2.2 years) hospitalized with the first depressive episode (ICD-10: F32.1, F32.2, F32.28, F32.8), who demonstrated attenuated schizophrenic symptoms (ASS) in the structure of the depression, which made it possible to attribute the patients to the group of clinical high-risk for schizophrenia. The control group consisted of 27 mentally healthy adolescent males (20.0±2.3 years). In both groups, the severity of thought impairment was assessed using the TLC scale. Psychopathological, psychometric and statistical methods were used. RESULTS: The median values of the severity of thought impairment using the TLC scale were 20 points [19.75; 26] in the main group, 10.5 points [9.25; 13] in the control group, with a high degree of statistical significance (p<0.001). The most significant differences (p<0.001) were found in following parameters: Incoherence (2 [1; 3] vs 1 [0; 1]), Tangentiality (2 [2; 2] vs 1 [0; 2]), Derailment (2 [1.25; 2] vs 1 [0.5; 2]), Illogical thinking (2 [2; 2.75] vs 0 [0; 1]), Loss of goal (1 [0; 2] vs 0 [0; 0]) and Blocking (1 [0; 1] vs 0 [0; 0] accordingly). CONCLUSION: Specific, not related to depression, disorders of thinking in patients of the clinical group, which indicates signs of disorganization of thinking and suggests the beginning of the endogenous process of the schizophrenic pole were found. The results show that the TLC scale can be used to detect early cognitive disorders in patients at risk of schizophrenia.

Quantitative method for the determination of antibiotic-resistant gut bacterial strains for the early diagnosis of chronic arthritis.

Based on the clinical and microbiological monitoring of two groups of children aged 3 to 17 years with acute (n=78) and chronic (n=46) course of reactive arthritis (ReA), a method for early diagnosis of chronic arthritis was developed by determining the number of antibiotic-resistant coprostrains in patients with ReA, characterized by the absence of the need to isolate a pure culture of the pathogen and its identification; inoculation of faeces at a dilution of 10-5 on solid 1.5% GRM-agar with an antibacterial agents used in the treatment of a particular patient, at a minimum inhibitory concentration in the resistance range, followed by incubation and counting of the colonies of microorganisms grown on the plate. A significant relationship between the number of antibiotic-resistant gut bacterial strains and the course of arthritis (acute, chronic) was revealed, and the borderline value of the number of antibiotic-resistant gut bacterial strains was determined - 5×103 CFU/g, which allows differentiating the acute course from the chronic one: in the acute course< 5×103 CFU/g, with chronic - ≥ 5×103 CFU/g. The method allows, at the stage of completion of anti-inflammatory therapy in the active phase of the disease, to identify a risk group for the development of a chronic course of arthritis among patients with ReA, which can contribute to timely therapeutic measures aimed at preventing recurrence of the disease and making the patient disabled.

[Dietary changes in males from adolescence to adulthood: results of a 28-year prospective study].

Dietary pattern usually changes with age; however, certain dietary habits may remain constant. The goal of this study was to analyze dynamic changes in the dietary pattern of males from adolescence to adulthood during a 28-year prospective follow-up. Material and methods. Initially, a representative population sample of 1,005 boys aged 11 to 12 years (mean age 11.9±0.1 years) was examined. Four visits were performed at the ages of 15, 17, 22 and 43. Assessment of actual dietary pattern was carried out by the 24-hour dietary recall method. Results. It was discovered that dietary pattern was changing with age as follows: proportions (Δ%) of meats [M (95% confidence interval)] 2.4 (-0.5-5.3), fish and seafood 1.5 (0.4-2.7), eggs 0.8 (0.1-1.5), and vegetable oils 0.3 (0.1-0.5) were increasing with age, whereas the proportions of animal fats -1.0 [-1.4…-0.6], bread and bakery -2.8 [-5.5…-0.1], sweets and confectionery -2.6 [-4.8…-0.5] were decreasing. We also observed a trend of increased consumption of fruits and fruit juices [Δ=4.9 (1.5-8.4)%]. The magnitudes of the tracking coefficients (correlation coefficients) between the initial (at the age of 15 years) values of the contributions of the main food groups to the total weight of the daily diet and their values at subsequent stages of prospective study showed that eating habits, as a certain dietary pattern, are relatively stable only in adolescence. Conclusion. Over 28 years of prospective observation of males, from adolescence to adulthood, their eating patterns underwent significant changes, which must be taken into account when developing preventive measures aimed at correcting unhealthy dietary patterns in children and adolescents, and at transition to a balanced diet.