[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.

[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.

[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.

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.

[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.

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.

[Follicular and Hurthle cell tumors of the thyroid gland. Possibilities of preoperative differential diagnosis]. / Follikuliarnye i giurtlekletochnye opukholi shchitovidnoi zhelezy. Vozmozhnosti differentsial'noi diagnostiki ha dooperatsionnom étape.

Changes suspicious for malignancy were detected in 127 patients who, according to scintigraphic examination of the thyroid, had "cold" nodules. As a consequence, all the patients were operated on and fine-needle aspiration findings were compared with the histological results. Thyroid cancer was identified in 18.9%. No differences in age between cases of benign, malignant follicular and Hurthle cell tumors were reported. Mean nodule size in patients with follicular and Hurthle cell adenoma (2.5 +/- 1.21 cm) differed from that in patients with thyroid cancer (3.35 +/- 1.86, p < 0.001). No differences in nodule size were observed in cases of micro-macrofollicular colloid goiter and thyroid cancer. The frequency of the latter was higher in Hurthle cell tumor (10 out of 23, 43.58%) than in thyroid tumor (14 out of 104, 13.56%), p = 0.002. Risk for thyroid cancer detection was higher in patients revealing nuclear atypia (10 out of 14 thyroid cancer patients, 71.4%) as compared with as low as 20 out of 79 adenoma patients, 25.32% (p = 0.03).

[Efficacy of thyroxine and potassium iodide treatment of benign nodular thyroid lesions]. / Otsenka éffektivnosti lecheniia dobrokachestvennykh uzlovykh obrazovanii shchitovidnoi zhelezy tiroksinom i kaliia iodidom.

AIM: To study efficacy of thyroxine (TX) and potassium iodide (PI) in the treatment of benign nodular thyroid lesions (BNTL). MATERIAL AND METHODS: 118 patients with BNTL (colloid or colloid hypercellular as shown by thin needle aspiration biopsy, 'cold" or "warm" by scyntigraphy findings) were randomized into two groups: 59 patients were given thyroxin and the other 59 patients PI. The day dose of TX (75-150 mcg) was prescribed according to serum concentration of TTH trying to diminish it to 0.5 mIU/l and lower. PI dose was 200 mcg/day. Most of the patients were treated for 6 months. The response was evaluated with ultrasound investigation which measured thyroid volume, the size and number of the nodes in it before and in the end of therapy. The treatment was found effective if the dominant node decreased in size by 50% and more compared to pretreatment values. RESULTS: The size of the dominant node decreased by 50% and more in 14 of 59 (23.73%) patients on TX and in 20 of 59 (33.90%) patients on PI. Both TX and PI prevented growth of the dominant node size and number of the nodes in approximately 2/3 cases. TX was more effective in young patients (40.92 +/- 3.45 years) vs older ones (47.50 +/- 1.46 years, p = 0.047) and patients with colloid nodes. PI was more effective in patients with shorter node existence (3.93 +/- 1.21 and 8.59 +/- 1.74 months, p = 0.02). TX reduced thyroid volume from 20.42 +/- 1.69 to 15.18 +/- 1.30 ml (p = 0.001), PI--from 18.34 +/- 1.57 to 15.36 +/- 1.25 ml (p = 0.001). CONCLUSION: TX and PI can inhibit or prevent the growth of thyroid benign nodes in approximately 2/3 patients especially in young patients with colloid nodes (TX) and in short existence of the node (PI).

[Functional activity of human thyrocytes in diffuse toxic goiter, autoimmune thyroiditis and thyroid nodules using nucleolar silver staining]. / Funktsional'naia aktivnost' tirotsitov cheloveka pri diffuznom toksicheskom zobe, autoimmunnom tireoldite i uzlovykh obrazovaniiakh shchitovidnoi zhelezy po dannym serebreniia iadryshek.

A comparative study of the thyrocyte nucleolar organizer region (NOR) activity was performed on silver - stained thyroid gland aspiration biopsies from controls, 39 patients with Graves' disease (GD), 15 other patients with Hashimoto thyroiditis (HT), and 71 patients with nodules which underwent surgery. Thyrocyte nucleoli from unchanged thyroid gland were round and small-sized. Their number ranged from 1.34 up to 1.96 per nucleus (mean 1.61 +/- 0.07). The average number of silver (Ag) grains ranged from 3.0 to 6.9 per nucleus (mean - 5.36 +/- 0.36). Compared to the controls the patients with GD revealed thyrocyte nucleoli with increased mean number of AG - grains per nucleus (9.84 +/- 0.24). There was a close correlation between thyrocyte NOR activity, on the one hand, and the level of T3 or T4 hormones and thyroid gland size, on the other. In patients with AT the argentophilla of thyrocyte nucleoli was intermediate between that of controls and patients with GD. This group of patients revealed an increased NOR activity of thyroid gland lymphocytes. Nucleoli of malignant thyroid cells were larger and more irregular than those of benign cells. The mean number of malignant cell nucleoli (2.55 +/- 0.22) was greater than that of the control group (1.61 +/- 0.07; p < 0.05) being identical with those of follicular adenomas (2.47 +/- 0.11) and nodular goiter (2.46 +/- 0.11). The mean number of Ag-grains in the malignant cells (14.9 +/- 0.79) was higher than that in FA (7.95 +/- 0.2; p < 0.0001) and NG (8.0 +/- 0.12; p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)