[SARS-CoV-2 morbidity depending on vitamin D status].

BACKGROUND: The association between vitamin D deficiency and the severity of COVID-19 is currently being actively discussed around the world. AIM: The aim of this study was to assess the prevalence of vitamin D insufficiency and deficiency and compare it with the incidence rates of SARS-CoV-2 in eight Federal Districts of the Russian Federation. MATERIALS AND METHODS: We included 304,564 patients (234,716 women; 77,1%) with serum 25(OH)D levels results performed September 2019 through October 2020. RESULTS: Only 112,877 people (37.1%) had a normal serum 25(OH)D level, others had a deficiency. Vitamin D insufficiency and deficiency was presented with the same frequency in women and men, and no differences were found depending on the geographical location and age in subjects from 18 to 74 years old. However, subjects over 75 years more often had vitamin D deficiency, while subjects under 18 years had normal levels in over 50% cases. In addition, 21,506 patients were tested for SARS-CoV-2 by PCR with further comparison of results with serum 25(OH)D level. The SARS-CoV-2 positivity rate was detected in 3,193 subjects, negative in 18,313. There were no differences in the morbidity in a vitamin D deficiency and a normal level. Thus, 14.8% subjects had positive PCR rates among vitamin D deficiency patients (4,978 tests), 14.9% when 25(OD)D level was from 20 to 30 ng/ml (7,542 tests), 15.0% among those who had 25(OH)D 30- 50 ng/ml (6,622 tests), and 13.9% when vitamin D was more than 50 ng/ml (4,612 tests). CONCLUSION: There was no association between the COVID-19 incidence and vitamin D status in different regions of Russia. Although the nutrient deficiency persists in all regions and is most often diagnosed in people over 75 years old.

[Early postoperative measurement of growth hormone level for prognosis of surgical outcomes in acromegaly].

AIM: To investigate the value of 24 hours post-surgery measurement of growth hormone (GH) level for prognosis of surgical outcomes in acromegaly. MATERIALS AND METHODS: A prospective cohort study included 45 patients with newly diagnosed acromegaly. The degree of parasellar extension was measured on the preoperative sellar magnetic resonance imaging according to the Knosps classification. All patients underwent a transsphenoid adenomectomy performed by one neurosurgeon. Basal GH level was measured at 24 hours after surgery. The efficacy of transsphenoidal adenomectomy evaluated at 12 months after surgery. RESULTS: Acromegaly remission was achieved in 19 (42%) of 45 patients at 12 months after surgery. Pituitary microadenomas and the absence of paracellular invasion, corresponding to Knosp Grade 02, had low prognostic value for long-term remission due to low sensitivity (31.6%) and low specificity (38.5%), respectively. The highest prognostic value for acromegaly remission was showed for 24 hours post-surgery GH level with cut-off 1.30 ng/ml with sensitivity of 96.2% (95% confidence interval 81.199.8%) and specificity of 84.2% (95% confidence interval 62.494.4%). CONCLUSION: The study demonstrated the possibility of using GH level at 24 after surgery as a predictor for acromegaly remission. GH level 1.30 ng/ml at 24 hours after surgery showed better predictive value for long-term remission compared with the presence of microadenomas and Knosp Grade 02. The absence of decrease of GH level on the first day after surgery may serve as a reason for more close monitoring of patients in the postoperative period. Further studies in a larger number of observers are required to confirm our findings.

[Candida glabrata Rpn4-like Protein Complements the RPN4 Deletion in Saccharomyces cerevisiae].

Expression of Saccharomyces cerevisiae proteasomal genes is regulated in a coordinated manner by a system that includes the ScRpn4 transcription factor and its binding site known as PACE. Earlier we showed that, Rpn4-like proteins from the biotechnologically important yeast species Komagataella pfaffii (Pichia pastoris), Yarrowia lipolytica, and Debaryomyces hansenii are capable of complementing the RPN4 deletion in S. cerevisiae in spite of their low structural similarity to ScRpn4. The opportunistic yeast pathogen Candida glabrata has a gene coding for a Rpn4-like protein, which has not been characterized experimentally yet. The С. glabrata ortholog ScRpn4 was expressed heterologously and found to restore the stress resistance and expression of proteasomal genes in a mutant S. cerevisiae strain with a RPN4 deletion. This complementation required the unique N-terminal region of CgRpn4. The results indicate that CgRpn4 acts as a transcriptional activator of proteasomal genes. The S. cerevisiae model can be used for further structural and functional analyses of CgRpn4.

[Evaluation of transsphenoidal adenomectomy outcomes in acromegaly using different remission criteria]. / Otsenka rezul'tatov transsfenoidal'noi adenoméktomii pri akromegalii s primeneniem razlichnykh kriteriev remissii.

For a long time, surgical removal of somatotropinoma using the transsphenoidal approach has been the first stage of treatment in most acromegaly patients. For the past decades, the efficacy criteria for surgical treatment of acromegaly have significantly changed, which requires appropriate correction. PURPOSE: We aimed to evaluate the results of transsphenoidal adenomectomy in acromegaly patients using various criteria for disease remission. MATERIAL AND METHODS: The study included patients with newly diagnosed acromegaly who underwent transnasal transsphenoidal endoscopic adenomectomy performed by a single neurosurgeon. The surgical treatment outcomes were evaluated 6 months after operative intervention based on levels of IGF-1, OGTT, and GH. The obtained data were analyzed using different threshold values for the level of GH nadir during OGTT: criteria A <2.0 ng/ml, criteria B <1.0 ng/ml, and criteria C <0.4 ng/ml to assess acromegaly remission, along with matching of the IGF-1 level to the reference range for a given gender and age. RESULTS: The study included 70 patients (52 females and 18 males) with a mean age of 52.2±11.5 years (29 to 73 years). The baseline IGF-1 level exceeded the upper limit of the reference range 3.3±1.4 (1.1-7.3)-fold, on average. The baseline mean basal GH level was 34.2±41.7 (1.2-192.0) ng/ml. The mean pituitary adenoma size was 16.7±8.6 (4.3-46.0) mm; 18 (26%) out of 70 patients had pituitary microadenoma, and 52 (74%) patients had macroadenoma. Six months after surgery, acromegaly remission met criteria A in 47 (67%) patients, criteria B in 28 (40%) patients, and criteria C in 18 (26%) patients. CONCLUSION: Our findings demonstrate that evaluation of transsphenoidal adenomectomy outcomes in treatment of acromegaly patients depends on the criteria chosen for assessing remission. This feature should be considered when comparing outcomes of surgical treatment for acromegaly in different years. Probably, introduction of the 2010 criteria should be accompanied by revision of the previous remission indicators.

A Randomised, Controlled Study of Different Glycaemic Targets during Gestational Diabetes Treatment: Effect on the Level of Adipokines in Cord Blood and ANGPTL4 Expression in Human Umbilical Vein Endothelial Cells.

Our aim was to study the expression of adipokine-encoding genes (leptin, adiponectin, and angiopoietin-like protein 4 (ANGPTL4)) in human umbilical vein endothelial cells (HUVECs) and adipokine concentration in cord blood from women with gestational diabetes mellitus (GDM) depending on glycaemic targets. GDM patients were randomised to 2 groups per target glycaemic levels: GDM1 (tight glycaemic targets, fasting blood glucose < 5.1 mmol/L and <7.0 mmol/L postprandial, N = 20) and GDM2 (less tight glycaemic targets, <5.3 mmol/L and < 7.8 mmol/L, respectively, N = 21). The control group included 25 women with normal glucose tolerance. ANGPTL4 expression was decreased in the HUVECs from GDM patients versus the control group (23.11 ± 5.71, 21.47 ± 5.64, and 98.33 ± 20.92, for GDM1, GDM2, and controls; p < 0.001) with no difference between GDM1 and GDM2. The level of adiponectin gene expression was low and did not differ among the groups. Leptin gene expression was undetectable in HUVECs. In cord blood, leptin/adiponectin ratio (LAR) was increased in GDM2 compared to controls and GDM1 (p = 0.038) and did not differ between GDM1 and controls. Tight glycaemic targets were associated with normalisation of increased LAR in the cord blood. ANGPTL4 expression was downregulated in HUVECs of newborns from GDM mothers and was not affected by the intensity of glycaemic control.

Serum 25(OH)D and adipokines levels in people with abdominal obesity.

Abdominal obesity is a risk factor for cardiovascular disease and diabetes mellitus and has been associated with vitamin D deficiency. Some studies have suggested an association between obesity and adipokine levels as well as low serum 25-hydroxyvitamin D (25(OH)D) level but the underlying mechanisms of the interlink between vitamin D status and serum leptin and adiponectin concentrations are still disputed. We included 435 residents (132 males) from St. Petersburg, Russia into this study. All subjects had physical examination and demographics noted. Blood was collected after an overnight fast and plasma glucose, insulin, serum lipids, 25(OH)D and adipokines (adiponectin and leptin) concentrations were determined at baseline in all participants. Abdominal obesity was diagnosed in 310 (71.3%) subjects (251 females and 59 males). Vitamin D insufficiency and deficiency were found in 314 (72.2%) subjects. Mean (95% CI) age, body mass index (BMI) and serum 25(OH)D for the cohort were 47.6±11.3years; 28.7±0.2kg/m2 and 62.5±24.3nmol/l respectively. Serum 25(OH)D level inversely correlated with body weight, waist circumference (WC) and BMI in females but not in males, was lower in diabetic than non-diabetic subjects, and was not significantly different in subjects with and without MetS. WC was positively correlated with leptin and negatively correlated with adiponectin. We found correlation between leptin and serum 25(OH)D level (r=-0.15, p=0.01) but this finding was a characteristic seen only in women. Our study showed a high prevalence of abdominal obesity, vitamin D deficiency and insufficiency in residents from North-West region of Russia, close association between adipokine (leptin, adiponectin) concentrations as well as vitamin D status and body composition (WC, BMI). However in our study the interlink between leptin level and 25(OH)D was found only in females. Further investigations are required to study the relationship between serum 25(OH)D level, obesity and serum adipokine levels.

[Treatment with anti-cancer agents results in profound changes in lncRNA expression in colon cancer cells].

Using real-time RT-PCR in combination with bioinformatics, we have shown for the first time that the treatment of HCT-116 and HT-29 colon cancer cells with two anti-cancer agents (doxycycline or 3,3'-diindolylmethane) results in profound changes in the intracellular content of several lncRNAs (by up to 100 times). Since many of these RNAs are secreted by tumors into the bloodstream, the obtained results provide a basis for developing more sensitive protocols for serological monitoring of tumor relapse and metastasis, as well as for search of new anti-cancer drugs.

[Inhibition of the expression of proteasomal genes Saccharomyces cerevisiae by artificial transcriptional repressor].

26S proteasome is an ATP-dependent protease complex that takes part in cell homeostasis maintenance by the selective degradation of regulatory and damaged proteins. The proteasomal genes expression in Saccharomyces cerevisiae yeast is coordinately regulated by the system, which consists of the Rpn4 transcription factor and its binding site, called PACE. The ability to modulate proteasomal activity by changing the expression of its genes is an essential tool that can be used in fundamental studies devoted to the mechanisms of proteasome dependent cell processes, as well as in applied research for developing strategies to correct proteasome activity in some pathological processes. In this work, we present a detailed description of our SaxBricks method that allows one to construct DNA-binding domains with custom specificity from nucleotide- specific TAL domains. Having applied the SaxBricks method, we created a modular transcriptional repressor for Rpn4-dependent genes that effectively suppresses the expression of proteasomal genes.

Prevalence of Vitamin D deficiency in the North-West region of Russia: A cross-sectional study.

Russia is a country with geographic and economic preconditions for development of vitamin D deficiency. We analyzed serum 25(OH)D level in residents from North-West region (59-61° North latitude) of Russia to study the prevalence of vitamin D insufficiency and deficiency and its associations with gender, age, obesity and diet. The study population included 1664 residents (1544 adults 18-75 y.o. and 120 children/adolescents of 3-17 y.o.). Serum 25(OH)D was determined in 1226 participants by electrochemiluminescence immunoassay. We used a questionnaire to check the frequency of dairy and fish products intake as well as the use of vitamin supplements. The serum 25(OH)D level was 9.8-147.5nmol/L, mean level in adults population was 54.8±0.7nMol/L, in children/adolescents-46.8±1.6 nmol/L. We revealed that 16.8% of the study population had a 25(OH)D level more than 75nMol/L, 37.5% had insufficiency and 45.7% had vitamin D deficiency. Serum 25(OH)D level in women was lower than in men (53.9±0.8 and 67.2±2.2nmol/L; p<0.01). We did not find association between vitamin D status and age. Patients with normal BMI had higher 25(OH)D level than those with overweight and obesity (52.5±2.8 and 44.8±2.0 nmol/L, p<0.05). Negative correlations between 25(OH)D and BMI (r=-0.17, p=0.03) and WC (r=-0.15, p=0.02) were found. Questionnaire analyses showed that regular fish intake (minimum once per week) was associated with higher 25(OH)D level, while dairy products and vitamin supplements intake did not seem to have any effect on vitamin D status. This study showed high prevalence of vitamin D insufficiency and deficiency in adults and adolescent population from North-West region of Russia, and an association of low serum 25(OH)D level with female gender, obesity and low fish products diet.

Prevalence, Risk Factors, and Genetic Traits in Metabolically Healthy and Unhealthy Obese Individuals.

OBJECTIVE: To assess prevalence of metabolically healthy individuals among patients with abdominal obesity (AO) and to determine phenotype and potential genetic traits associated with a benign metabolic status. METHODS: 503 AO patients without cardiovascular diseases were examined. Waist circumference (WC), BMI, blood pressure, plasma glucose and serum insulin levels, HOMA-IR, lipid profile, and adiponectin (AN) and leptin (LEP) concentrations in serum were measured. Polymorphisms A19G and Q223R of the LEP and LEP receptor gene, and G276T and T45G of the AN gene were investigated. RESULTS: 91.3% of patients were metabolically unhealthy obese (MUO), and 8.7% metabolically healthy obese (MHO). MHO patients were younger, and had lesser BMI and WC, while duration of obesity, frequency, and duration of physical training were greater than MUO patients (p < 0.05). In MHO and MUO patients distribution of the G19G, G19A, and A19A genotypes of the LEP gene and G276G, G276T, and T276T genotypes of AN gene did not differ. The Т45Т genotype was associated with increase of metabolic disorders' risk for patients with АО (OR = 2.331; 95% CI = 1.121 ÷ 5.132). CONCLUSIONS: Prevalence of MHO individuals among patients with AO is low. Benign metabolic status was associated with younger age, lower waist circumference, and higher physical activity, shorter duration of obesity, and G45G adiponectin genotype carriage.

[Clinical features of obstructive sleep apnea syndrome in patients with acromegaly].

AIM: To investigate the incidence of sleep-related breathing disorders (SRBDs) in patients with active acromegaly (AM), to specify risk factors influencing apnea/hypopnea index (AHI), and to reveal the specific features of obstructive sleep apnea (OSA) in patients with AM versus those with OSA without AM. SUBJECTS AND METHODS: Fifty patients with active AM were examined and divided into 3 groups: control group 1 did not differ from the study group in body mass index (BMI); control group 2 did not similar in AHI from the AM group. Polysomnography was done in all the patients. RESULTS: SRBDs were detected in 40 (80%) patients. Obstructive apnea was found in all cases. Correlation analysis revealed the relationships between AHI and gender (AHI was higher in the men), BMI, disease duration, and insulin-like growth factor 1 (GF-1). There were no correlations between AHI and gender, maximum adenoma size, and growth hormone levels. Compared with control group 1, the AM group had a statistically significantly higher median AHI [16 (1-92) and 4.7 (0-31.3) episodes per hour of sleep (p < 0.001)]. In control group 2, the median BMI was considerably higher than in the control group [29.2 (19.9-44.3) and 35 (24-56) kg/m2 (p < 0.001). CONCLUSION: The detection rate of SRBDs in patients with active AM was 80%, with obstructive disorders being prevalent. There was a positive relationship between SRBD severity and BMI, AM duration, IGF-1 level. Compared to the controls, the patients with AM developed SRBDs similar in severity with lower BMI; severer SRBDs were detected in the patients with active AM with the similar BMI.

[Anxiety/depressive disorders and vitamin D status]. / Trevozhno-depressivnye rasstroistva u lits s raznym urovnem obespechennosti vitaminom D.

OBJECTIVE: To search for the association between vitamin D status and anxiety and depression. MATERIAL AND METHODS: Authors examined 310 residents of St. Petersburg (137 men and 173 women). Anxiety and depression were measured with the HADS. RESULTS AND CONCLUSION: In people with vitamin D deficiency, anxiety and depression were noted in 32.5% and 11.0%, respectively. There were negative correlations between serum 25(OH)D level and anxiety (r= -0,11, p=0.03). Symptoms of depression were not correlated with vitamin D status (r= -0.08, p=0.09) but were correlated with the age (r=0.12, p=0.02). After excluding other risk factors for psychogenic disturbances (obesity, hypertension and impaired glucose metabolism) we concluded that serum 25(OH)D could be an independent risk factor for anxiety (R2=0.02, p=0.01) in the population studied.

The new combination of risk factors determining a high risk of gestational diabetes mellitus.

AIM: The aim of this study was to identify early markers of gestational diabetes mellitus (GDM) and to reveal the most significant of them. METHODS: A total of 548 pregnant women were screened for GDM between weeks 24 and 28 of gestation, as defined by International Association of Diabetes In Pregnancy Study Groups (IADPSG) criteria, in a retrospective case-control study. First trimester maternal fasting glucose, anthropometric parameters and blood pressure were obtained from medical records. Classification Tree Method was used to identify combination of early pregnancy risk factors that predict the highest risk of the development of GDM in later pregnancy. RESULTS: The combination of Body Mass Index (BMI) >38.6 kg/m² with, abdominal circumference >91.5 cm and fasting glucose >4.5 mmol/L was associated with a 13-fold increased risk of GDM as compared to women who do not have this combination of symptoms (OR 13.2 95% CI: 2.7-63.3, P<0.001). In women with BMI less than 38,6 kg/m ² the combination of fasting glucose >4.5 mmol/L, abdominal circumference >91.5 cm with the presence of polycystic ovary syndrome (PCOS) was associated with a 6-fold increased risk of GDM as compared with women who do not have this combination of symptoms (OR=7.6, 95% CI: 1.9-30.02, P=0.003). CONCLUSION: A higher BMI, abdominal circumference, fasting glycemia in the first trimester of pregnancy and the presence of PCOS predict increased GDM risk. Taking these combinations into consideration may facilitate identification of women at particular risk for GDM.

Polymorphisms of ß 1-adrenoreceptor gene and cardiovascular complications in patients with thyrotoxicosis.

Human cardiac ß 1-AR perform a crucial role in mediating the cardiostimulating effects of norepinephrine. Gly389Arg and Ser49Gly polymorphisms of ß 1-adrenoreceptors ( ß 1-AR) can influence the cardiovascular prognosis. However, the possible effect of Gly389Arg and Ser49Gly polymorphisms on heart function in thyrotoxicosis has not been studied. We investigated the possible link between Gly389Arg and Ser49Gly polymorphisms and echocardiography parameters in 165 normotensive patients with a thyrotoxicosis without any cardiovascular disorders. Echo-CG was performed according to standard protocol before and during the thyreostatic treatment. Our data demonstrate that both Gly389Arg and Ser49Gly polymorphisms have very moderate influence on the risk of left ventricular hypertrophy and atrial fibrillation with no statistically significant effects on cardiac function and the development of cardiovascular complications.

[A new immuno-PCR format for serological diagnosis of colon cancer].

Anew immuno-PCR format is described that is based on detection of membrane protein CDH17 in serum exosomes. Format application allows distinction between sera samples of healthy donors and colon cancer patients. Obtained results open a possibility of serological colon cancer diagnosis in high risk groups.

Vitamin D deficiency is a risk factor for obesity and diabetes type 2 in women at late reproductive age.

It was suggested that glucose metabolism and body fat content depend on serum levels of 25-hydroxyvitamin D [25(OH)D]. We studied 320 healthy women at late reproductive age of 40 to 52 years old (mean age 46.1±4.5) from St. Petersburg (North-West region of Russia). 25(ОН)D levels were from 19.4 to 134.0 nMol/L (mean 52.9±22.7). Vitamin D deficiency (lower than 50 nMol/L) and insufficiency (50-75 nMol/L) was revealed in 59.1% and 27.8% of women, respectively. The study showed that low 25(OH)D levels were associated with obesity (r=-0.35, p$#X003C0.01), increased plasma glucose levels after OGTT (r=-0.31, p$#X003C0.01) and decreased insulin sensitivity index (r=-0.28, p$#X003C0.01). We found that 25(OH)D levels below 50 nMol/L were associated with obesity risk (OR 2.25[1.05-3.95], CI 95%) but not with risk of impaired glucose metabolism (1.07[0.54-2.12],CI95%). Our results showed that vitamin D insufficiency is highly prevalent in the population of healthy women. Low 25(OH)D levels correlated with high body fat, glucose levels and decreased insulin sensitivity. We conclude that vitamin D deficiency is a potential risk factor for obesity and development of insulin resistance leading to diabetes type 2.

[The effect of metformin on myocardial tolerance to ischemia in rats with diabetes mellitus type 2].

The effect of metformin on myocardial sensitivity to ischemia in rats with neonatal streptozotocin T2DM was investigated using the model of global ischemia-reperfusion in the isolated perfused heart. Metformin administration had no effect on infarct size. At the same time, infarct size in T2DM was significantly lower than in controls, which is indicative of the phenomenon of metabolic preconditioning in T2DM. The protocol of metformin administration used in this study had not afforded a significant cardioprotective effect in animals with T2DM.

[Structure and function of enteric alpha defensins in norm and pathology].

This review summarizes currently available data on enteric alpha defensins structure, their functions in the innate and adaptive immunity systems and the role in development of intestinal illnesses.

[Evaluation of methylprednisolone pulse therapy versus combined therapy with prednisolone and cyclosporine in the treatment of infiltrative ophthalmopathy in Graves' disease].

The study was undertaken to evaluate the efficiency of methylprednisolone pulse therapy versus combined therapy with prednisolone and cyclosporine in the treatment of Graves' infiltrative ophthalmopathy. Twenty-four euthyroid patients (15 females and 9 males) aged 28 to 71 years who had severe active ophthalmopathy were randomized into 2 groups. Group 1 patients received pulse therapy with methylprednisolone while Group 2 patients were treated with a combination of prednisolone and cyclosporine. The efficiency of therapy was evaluated by the changes in indices by the clinical activity score (CAS), soft tissue inflammation (STI), average exophthalmos, the dysfunction of extraocular muscles, the total diameter of extraocular muscles by the data of computed tomography 2 weeks before the initiation of therapy and 36 weeks after its discontinuation. Following 2-week therapy, the patients from both groups had lower CAS, diminished inflammatory soft tissue manifestations by the STI scale, and alleviated average exophthalmos. Thirty-six weeks after therapy discontinuation, the values returned to the baseline ones in Group 1 patients whereas the achieved positive effect is retained in Group 2 patients.

[Clinical guidelines developed by the Russian Association of Endocrinologists for the diagnosis and treatment of nodular goiter].

The guidelines presented do not pretend to be a systematic presentation of all aspects of the diagnosis and treatment of nodular goiter and are not intended to replace guidelines for various medical disciplines. In real clinical practice, situations may arise that are beyond the scope of the recommendations presented, in connection with which the final decision regarding a specific patient and responsibility for him lies with the attending physician.The recommendations presented are mainly devoted to the diagnosis and treatment of nodular (multinodular) euthyroid colloid, differently proliferating goiter in adults (over 18 years of age) and are the agreed opinion of the RAE experts who developed them. Nodular (multinodular) toxic goiter, tumors (malignant and benign), as well as other diseases that can manifest themselves by nodular formations of the thyroid gland (thyroid gland), are discussed mainly in the context of differential diagnosis. The recommendations also do not affect the features of diagnosis and treatment of nodular goiter in children and adolescents.