[Erratum in "Point-of-Care Blood Glucose Testing: Post-Market Performance Assessment of the Accu-Chek Inform II Hospital-Use Glucose Meter" (DOI: 10.26442/00403660.2023.12.202522)].

In the article "Point-of-care blood glucose testing: post-market performance assessment of the Accu-Chek Inform II hospital-use glucose meter," published in the Terapevticheskii Arkhiv journal, Vol. 95, No.12, 2023 (DOI: 10.26442/00403660.2023.12.202522), errors were made: the term "measurements at the place of treatment" was changed, as well as the section "Conflict of interest." At the request of the authors' team, errors in the conflict of interest and the wording of the term have been corrected, and the section "Information about the authors" has been updated. The publisher replaced the original version of the published article with the corrected one; the information on the website was also corrected. Correct text of the section "Conflict of interest": Conflict of interest. All authors are not employees or consultants of Roche Diagnostics and have not received any compensation from Roche Diagnostics. Correct wording of the term in Russian: "измерения по месту лечения". Changes were made to the title of the article in Russian: "Измерения глюкозы по месту лечения: пострегистрационное испытание госпитального глюкометра Акку-Чек Информ II", the text of the abstract, keywords, citation, in the text of the article, and abbreviations. Information of the place of work has been updated: Center for Laboratory Diagnostics of the Russian Children Clinical Hospital, a Branch of the Pirogov Russian National Research Medical University. The publisher apologizes to readers and authors for the errors and is confident that the correction of errors will ensure the correct perception and interpretation of the results of the study described in the text.

[Point-of-Care Blood Glucose Testing: Post-Market Performance Assessment of the Accu-Chek Inform II Hospital-Use Glucose Meter].

BACKGROUND: A point-of-care glucose testing (POCT) is an essential component of care in patients with hyperglycemia and hypoglycemia in inpatient and outpatient settings. In Russian medical facilities (MFs), conventional glucose meters designed for self-monitoring by patients with diabetes are commonly used for POCT. These home-use meters have two serious disadvantages: the first is large measurement bias and the second - they can't be integrated into laboratory information systems, so measurement data have to be recorded into patient charts manually. Both factors may lead to medical errors. It is reasonable to use in the MFs specialized POCT glucose meters, as they are superior to conventional ones in accuracy and may be easily connected to laboratory information systems. With this in mind, physicians at the Russian Children's Clinical Hospital decided to substitute conventional meters with the Accu-Chek Inform II POCT meter, however, after preliminary performance assessment of the model. AIM: To test the Accu-Chek Inform II performance characteristics: accuracy, linearity, repeatability, and mean absolute relative difference (MARD). MATERIALS AND METHODS: Performance of the Accu-Chek Inform II was tested by comparing the results of parallel CGL measurements with the meter and reference laboratory analyzer in capillary blood samples. Overall, 99 parallel CGL measurements were made in 45 samples. Accuracy was evaluated according to the ISO 15197-2013 and POCT12-A3 criteria. RESULTS: The Accu-Chek Inform II meter met the requirements of ISO 15197-2013 and POCT12-A3 and demonstrated high linearity (correlation coefficient, r=1,0), good repeatability (mean coefficient of variation, CV=1,38%) and acceptable MARD (4,9%). CONCLUSION: The Accu-Chek Inform II POCT glucose meter may be efficiently and safely used in inpatient and outpatient MFs and particularly in pediatric clinics.

Pure endoscopic management of epileptogenic hypothalamic hamartomas.

Hypothalamic hamartomas (HH) are rare congenital malformations located in the region of the tuber cinereum and third ventricle. Their usual clinical presentation is characterized by gelastic/dacrystic seizures which often become pharmaco-resistant and progress to secondary focal/generalized intractable epilepsy causing mostly in children cognitive and behavioral problems (particularly in cases of progressive epileptic encephalopathy) and precocious puberty. Whereas gelastic seizures can be surgically controlled either by resection of the lesion or disconnection (tissue-destructive) procedures, aimed at functionally prevent the spreading of the epileptic burst; generalized seizures tend to respond better to HH excision rather than isolated neocortical resections, which generally fail to control them. Prospective analysis of 14 consecutive patients harboring HH treated in an 8-year period; 12 patients had unilateral and two bilateral HH. All patients were managed by pure endoscopic excision of the HH. The mean operative time was 48 min and mean hospital stay was 2 days; perioperative blood loss was negligible in all cases. Two patients showed a transient diabetes insipidus (DI); no transient or permanent postoperative neurological deficit or memory impairment was recorded. Complete HH excision was achieved in 10/14 patients. At a mean follow-up of 48 months, no wound infection, meningitis, postoperative hydrocephalus, and/or mortality were recorded in this series of patients. Eight patients became seizure free (Engel class I), 2 other experienced worthwhile improvement of disabling seizures (Engel class II); 2 patients were cured from gelastic attacks while still experiencing focal dyscognitive seizures; and 2, having bilateral HH (both undergoing unilateral HH excision), did not experience significant improvement and required later on a temporal lobectomy coupled to amygdalohyppocampectomy. Overall, the followings resulted to be predictive factors for better outcomes in terms of seizure control: (1) cases of unilateral, Delalande class B, HH, (2) shorter history of epilepsy. Endoscopic resection of HH proved, in our series, to be effective in achieving complete control or in reducing the frequency of seizures. Furthermore, this approach has confirmed its minimally invasive nature with a very low morbidity rate: of note, it allowed to better preserve short-term memory and hypothalamic function.

[Nonstructural protein 1 of tick-borne encephalitis virus activates the expression of immunoproteasome subunits].

The interaction of viral proteins with host cell components plays an important role in antiviral immune response. One of the key steps of antiviral defense is the formation of immunoproteasomes. The effect of nonstructural protein 1 (NS1) of tick-borne encephalitis virus on the immunoproteasome formation was studied. It was shown that cell expression of NS1 does not reduce the efficacy of the immunoproteasome generation in response to interferon-γ stimulation and even increases the content of the immunoproteasome subunits without the interferon-γ treatment. Thus, NS1 of tick-borne encephalitis virus activates, rather than blocks the mechanisms of immune defense in the cell.

[THE VERIFICATION OF ANALYTICAL CHARACTERISTICS OF THREE MODELS OF GLUCOMETERS].

The individual portable systems of control of glucose level in blood commonly known as glucometers permit to patients with diabetes mellitus to independently correct pharmaceutical therapy. The effectiveness of this correction depends on accuracy of control of glucose level. The evaluation was implemented concerning minimal admissible accuracy and clinical accuracy of control of glucose level of devices Contour TC, Satellite Express and One Touch Select according standards expounded in GOST 15197-2011 and international standard ISO 15197-2013. It is demonstrated that Contour TC and One Touch Select meet the requirements of these standards in part of accuracy while Satellite Express does not.

[Activation of immunoproteasome subunit genes transcription in mice monocytes infected with different strains of mycobacteria].

Immunoproteasomal processing of mycobacterial antigens is necessary to control the infection and to protect the organism from development of active form of tuberculosis. Here we investigate the activation of immunoproteasome subunit genes transcription in peritoneal monocytes of C57Bl/6 mice infected with vaccine M. bovis BCG and virulent strain M. tuberculosis H37Rv. The level of transcription of LMP2, LMP7, MECL1 subunits didn't increase for one and two days after a single infection. Two rounds of infection with BCG strain M. bovis led to enhancement of the only LMP7 subunit gene transcription. However after subsequent infection of monocytes with vaccine followed by virulent strain infection the dramatic rise of all immunoproteasomal subunit genes transcription was observed. Activation of transcription of the gene coding the PA28alpha subunit of regulatory complex PA28 was observed only after a single infection of monocytes with strain M. bovis BCG. Thus, vaccination with strain M. bovis BCG promotes effective activation of immunoproteasomal genes in case of subsequent contact with virulent strain M. tuberculosis H37Rv.

[Apoptosis and neutrophils on the regulation of proliferation and differentiation ex vifo of myeloid cells with Ph-chromosome].

Human myeloid cells with Ph chromosome (Ph+ cells) from chronic myeloid leukemia (CML) in the course of proliferation and differentiation ex vivo are regulated under alternation of cell proliferation and neutrophil maturation stages by consecutive blocking and inducing apoptosis with of neutrophils participation as well bcr/abl, bax and bcl2 genes expression. Apoptosis regulation of three main Ph+ cells types from CML patients depends on alternation sequences of proliferation (1) and maturation (2) cell stages and realized by two ways. The first one is performed by consecutive blocking and inducing apoptosis under 2/1/2 stage alternation. The way is not described early. Neutrophils accumulation correlates with apoprosis blocking. Apoptosis level enhances under neutrophils exhausted. Apoptosis blockage allows cells to proliferate and, thus, to form new portion of neutrophils with consecutive regular their death as well a consequent alternation of apoptosis blocking and inducing. This way regulates proliferation efficiency indexes P/D that reflect Ph+ cells proliferating potential and performs cycle completion for proliferation and differentiation. The second way of apoptosis regulation starts from proliferation stage and performs for 1/2/1 alternations under diminished content of neutrophils and a little increase under next maturation. It leads to resistant depressed apoptosis levels that, at maximal points, are 3-8 times lower than those under alternation 2/1/2. Resistant apoptosis blocking is observed in the Ph+ cells with prolong proliferation or maturation stages, when blasts and myelosytes are accumulated under enhanced bcr/abl and bcl2 > box gene expression and remain under next maturation. Stable apoptosis blocking is accompanied by increasing amounts of blasts and myelocytes and enhancing bcr/abl and bcl 2 > bax expression. This is observed under CML progression. Ph+ cells cultivation may be useful for more distinct diagnostics of CML phases of individual CML patients and optimization of the treatment.

[DNA vaccine encoding alpha-fetoprotein with fused ornithine decarboxylase degradation signal significantly suppresses hepatocellular carcinoma growth in mice].

Hepatocellular carcinoma (HCC) is among the most frequent malignancies in humans. HCC therapy is not efficient and the usual outcome is poor. In this regard, novel approaches to treat and prevent HCC are urgently needed. The Alpha-fetoprotein (AFP) is a serological marker of HCC. Recently it has been shown, that the DNA vaccines expressing AFP are capable in generating immune response against AFP. However, both, the immunization procedures and DNA vaccines used before were complex and not always very effective. We have shown that DNA vaccine encoding HIV-1 reverse transcriptase (RT) with fused ornithine decarboxylase (ODC) degradation signal induced a strong Th-1 immune response against RT in mice. Using this approach we designed a set of novel DNA vaccines bearing AFP and ODC degradation signal. Results obtained on transfected cells demonstrated efficient expression and fast proteasomal degradation of the recombinant AFP. The anti-tumor immune response stimulation was shown in immunized animals and most importantly a notable retardation of tumor growth was observed as a result of protective vaccination.

Self-sustained non-equilibrium co-existence of fluid and solid states in a strongly coupled complex plasma system.

A complex (dusty) plasma system is well known as a paradigmatic model for studying the kinetics of solid-liquid phase transitions in inactive condensed matter. At the same time, under certain conditions a complex plasma system can also display characteristics of an active medium with the micron-sized particles converting energy of the ambient environment into motility and thereby becoming active. We present a detailed analysis of the experimental complex plasmas system that shows evidence of a non-equilibrium stationary coexistence between a cold crystalline and a hot fluid state in the structure due to the conversion of plasma energy into the motion energy of microparticles in the central region of the system. The plasma mediated non-reciprocal interaction between the dust particles is the underlying mechanism for the enormous heating of the central subsystem, and it acts as a micro-scale energy source that keeps the central subsystem in the molten state. Accurate multiscale simulations of the system based on combined molecular dynamics and particle-in-cell approaches show that strong structural nonuniformity of the system under the action of electostatic trap makes development of instabilities a local process. We present both experimental tests conducted with a complex plasmas system in a DC glow discharge plasma and a detailed theoretical analysis.

[Critical amino acids of ornitin decarboxylase degron: the presence and C-terminal arrangement is insufficient for alfa-fetoprotein degradation].

Mouse ornithine decarboxylase (ODC) degrades in proteasome in an ubiquitin-independent manner with an averagehalf-life of 2 h. The 37 amino acid long C-terminal fragment known as a degradation signal (degron) is responsible for the effective degradation of ODC. Recently, amino acids being critical for degradation in the ODC-degron have been mapped. Mutations of Cys441 and Ala442 led to protein stabilization, while a substitution of other amino acids composing ODC-degron had almost no effect on the protein turnover; whereas insertions or deletions in region between Ala442 and ODC C-terminus diminished greatly rate of protein degradation, e.g. positioning of the key amino acids from the C-terminus was shown to be crucial. Using these data we introduced both key amino acids into the alfa-fetoprotein with truncated exportation signal (deltaAFP), at the same distance from the C-terminus as they being in the ODC (deltaAFPCAG and deltaAFPLCAG). Removal of N-terminal exportation signal prevented secretion of modified proteins. Using in silico approach we demonstrated no significant difference in hydrophobicity or secondary structure between C-terminus of deltaAFP and mutated proteins. The degradation kinetics of deltaAFP, deltaAFPCAG, deltaAFPLCAG in cyloheximide-chase and proteasome inhibition assay (using MG132) was identical. Obtained results suggest that introduced substitutions are insufficient for effective recognition of mutated deltaAFP by26S proteasome. We assume thatadditional amino aci ds composing ODC-degron or their combine action could also affect degradation. Besides that, one cannot exclude that conformation of the mutated deltaAFP limits its C-terminus accessibility to proteasome.

A Simplified Streptozotocin-Induced Diabetes Model in Nude Mice.

Preclinical studies of human cellular and tissue-based products (HCT/Ps) for transplantation therapy of type 1 diabetes mellitus (T1DM) necessarily involve animal models, particularly mouse models of diabetes induced by streptozotocin (STZ). These models should mimic the clinical and metabolic manifestations of T1DM in humans (face validity) and be similar to T1DM in terms of the pathogenetic mechanism (construct validity). Furthermore, since HCT/Ps contain human cells, modeling of diabetes in immune-deficient animals is obligatory. Here we describe the most simplified diabetes model in Nude mice. Diabetes was induced in 31 males by a single intraperitoneal injection of STZ in normal saline at a medium-to-high dose of 150 mg/kg body weight. Fourteen control animals received only saline. Non-fasting plasma glucose (PG) levels were measured periodically for 50 days. All STZ-treated mice survived beyond 50 days. By day 15 after STZ administration, 22 of 31 (71%) mice developed stable diabetes based on the following criteria: (1) non-fasting PG ≥ 15 mmol/L on consecutive measurements up until day 50; (2) no diabetes remission. The mean non-fasting PG in mice with stable diabetes over the period of 35 days was equal to 25.7 mmol/L. On day 50, mean plasma insulin concentration, mean pancreatic insulin content, and the average number of ß-cells in pancreatic islets were 2.6, 8.4, and 50 times lower, respectively, than in the control animals. We consider that our Nude mouse model of diabetes meets face validity and construct validity criteria and can be used in preclinical studies of HCT/Ps.

Impact of discontinuation of antithrombotic therapy after surgery for chronic subdural hematoma.

INTRODUCTION: The management of antithrombotic therapy (AT) after surgery for chronic subdural hematoma (cSDH) requires taking account of the balance of risk between hemorrhage recurrence (HR) and the prophylactic thromboembolic effect (TE). The goal of the present study was to evaluate the prevalence of vascular events (VE: TE and/or HR) in the first 3 postoperative months after cSDH evacuation in patients previously treated by AT. The impact of AT resumption was also evaluated. PATIENTS AND METHODS: This observational prospective multicenter collaborative study (14 French neurosurgery centers) included patients with cSDH treated by AT and operated on between May 2017 and March 2018. Data collection used an e-CRF, and was principally based on an admission questionnaire and outcome/progression at 3 months. RESULTS: In this cohort of 211 patients, VE occurred in 58 patients (27.5%): HR in 47 (22.3%), TE in 17 (8%), with mixed event in 6 cases (2%). Median overall time to onset of complications 26 days±31.5, and specifically 43.5 days±29.25 for HR. Non-resumption of AT significantly increased the relative risk of VE [OR: 4.14; 95% CI: 2.08 - 8.56; P <0.001] and especially of TE [OR: 7.5; 95% CI: 1.2 - 42; P<0.001]. The relative risk of HR was significantly increased when AT was resumed at less than 30 days (P=0.015). CONCLUSION: The occurrence of VE in patients operated on for cSDH and previously treated by AT was statistically significant (27.5%). HR was the most common event (22.3%), whereas TE accounted for only the 8%, although with shorter time to onset. In order to prevent TE risk, AT should be restarted after 30 days, as HR risk is greatly decreased beyond this time.

Serum levels of interleukin 6 in recently hospitalized tick-borne encephalitis patients correlate with age, but not with disease outcome.

Infection with many encephalitic viruses is associated with the induction of the proinflammatory cytokine interleukin (IL)-6. In some situations, induction of high levels of this cytokine is associated with a protective response, but in others it can be linked to tissue damage and disease. In the studies reported here, levels of serum IL-6 and virus-specific antibodies were measured on admission to hospital and correlated with clinical outcomes. Only some patients demonstrated raised levels of serum IL-6, and there was no correlation between high levels of this cytokine and either gender or the severity of clinical disease. A statistically significant association between raised IL-6 and age was observed, with all individuals below the age of 26 showing normal levels of serum IL-6, regardless of clinical presentation. Furthermore, not all patients had detectable levels of virus-specific serum immunoglobulin G (IgG) antibodies, but an inverse and statistically significant correlation between raised IL-6 levels and IgG titre was observed. Consequently, serum levels of IL-6 cannot be used as a reliable indicator of disease outcome.

[Research and comparative characteristic of the factors determining elasticity of the human skin].

Changes in skin elasticity have been analyzed under different conditions (upon skin stretching, at different thickness of the skin, at different contents of collagen, intercellular and endocellular liquids, upon changes of venous pressure, and during contraction and relaxation of smooth muscles in skin vessels - vasomotions). Elasticity was defined by the acoustic method from the speed of diffusion of a superficial sheared acoustic wave in the skin, by the autoresonant method from the mechanical resonance frequency of skin, and from the vacuum pressure needed for skin site deformation of constant volume. It was shown that the major factors determining the elasticity of skin are it stretching, thickness, and the contents of collagen and liquids in it. The influence on elasticity of venous pressure and the contraction activity of smooth muscles in vessels is not essential. This suggests that the parameters of skin elasticity can be used as indicators of systemic and local lesions of the connective tissue.

[Experimental study of the phenomenon of antibody dependent tick-borne encephalitis virus infectivity enhancement in vitro].

Phenomenon of antibody dependent tick-borne encephalitis virus (TBEV) infectivity enhancement in the human monocytic cell culture J-96 has been studied. Three specific commercial sera that are generally used for therapy and prevention of TBE in humans were used. Results showed that enhancement of TBEV infectivity was markedly apparent following use of 2 out of 3 studied sera. Data obtained in the study prove that phenomenon of antibody dependent TBEV infectivity enhancement in monocytes cell culture may exist, but conditions for its realization in the organism are very unlikely due to the narrow range of antibodies' concentration and quantity of viral particles. A the same time, the fact of possible aggravation of TBE course after use of specific antisera for treatment and prevention of TBE in humans should not be ignored.

[Nanotechnology applications in pharmacology].

The applications of nanotechnology to pharmacology are reviewed. The potential applications of biochips, nanosensors, bioreactors, neural stem cells, immune nanoparticles, biodegradable polymers, and convection-enhanced drug delivery in the diagnostics and treatment of diseases are discussed. Specific attention is given to developments in chemotherapeutic means, including advanced drug delivery systems and targeted nanotherapy, which will form the basis of the future nanomedicine. Numerous novel medicinal forms are discussed, including polymeric nanoparticles, nanotubes, micelles, liposomes, dendrimers, fullerenes, and hydrogels. In particular, highly stable glycosphyngolipid nanotubes and nanoliposomes are proposed as drug delivery systems. For this purpose, the model of stimulation of skin vasomotor reactions by nitroglycerin application is developed. The effect of nitroglycerin is shown to increase 1.5 times when used in the form of a dispersion with nanotubes as carriers and almost 2.5 times in the case of a dispersion with nanoliposomes as carriers. Nanotechnologically manufactured biologically active substances Apiton-25 (containing apis products) and Microhydrin (containing SiO 2 nanoparticles, silicon hydrogen bonds Si-H, and free negative charges for free radical neutralization) have been studied. The results indicate that both Apiton-25 and Microhydrin upon peroral administration enhance the cyclic trial performance during prolonged submaximal exercise in endurance-trained cyclists.

[Molecular, genetic and immunohistochemical investigation of carcinosarcoma of the female reproductive tract].

Tissue precursors and genesis of female reproductive tract carcinoma vis-a-vis its carcinomatous and sarcomatous patterns remain unknown. To determine the clonal origin of 17 female reproductive tract carcinomas, such molecular, genetic and immunohistochemical techniques as PCR-SSCP and/or denaturing gel electrophoresis for K-ras, p53 and PTEN genes; D17S786, CHRNB1, TP53, BAT26 and BAT40 microsatellites and immunostaining for p53 protein were used. Carcinomatous and sarcomatous components were studied separately. Eight tumors were assumed to be monoclonal (combination or conversion tumors), while one--of an obscure origin. Our results suggest that carcinosarcomas were characterized by chromosomal instability. Moreover, it was shown that it is necessary to combine immunohistochemical techniques with a battery of methods including genetic ones to determine clonal origin of immunologically--stained carcinosarcomas.

[Synthetic fragments of the NS1 protein of the tick-borne encephalitis virus exhibiting a protective effect].

Potentially immunoactive regions of the NS1 nonstructural protein of the tick-borne encephalitis virus that can stimulate the antibody formation in vivo and protect animals from this disease were chosen on the basis of theoretical calculations. Eleven 16- to 27-aa peptides containing the chosen regions were synthesized. The ability of the free peptides (without any high-molecular-mass carrier) to stimulate the production of antipeptide antibodies in mice of three lines and ensure the formation of protective immunity was studied. Most of these peptides were shown to exhibit the immunogenic activity in a free state. Five fragments that can protect mice from the infection by a lethal dose of tick-borne encephalitis virus were found.

[Kinetics of proliferation, differentiation and transcription of genes regulating apoptosis in cultured human BCR/ABL+ Ph+-cells].

Ph+, bcr/abl+ cells arise due to t(9,22) chromosome translocation and Ph+ chromosome formation in hematopoietic stem cells. The cells show appreciable apoptosis suppression but retain their ability to differentiate and maturate. Ph chromosome, bcr/abl oncogene and Ph+, bcr/abl+ cells themselves are the hallmark of chronic myeloid leukemia. Under leukemia progression differentiating Ph+, bcr/abl+ cells transform into leukemic malignant cells with differentiation block. It is assumed to be a result of subsequent mutations or activation of proliferation of long silent Ph+ cells arisen previously in the stem cells because of the translocation. Real mechanism underlying the cell transformation remains unknown. This work was performed to develop a proper cell model allowing us to study functioning of differentiating Ph+, bcr/abl+ cells and their real transformation into malignant cells with block of differentiation. For this purpose we have investigated kinetics of Ph+, bcr/abl+ cells proliferation, differentiation, cell death and transcription of antiapoptotic genes in cultured 14-day of Ph+ mononuclear cells isolated from peripheral blood of a patient in chronic phase of chronic myeloid leukemia before treatment. The results obtained revealed that Ph+ cell differentiation proceeded in accord with characteristic scheme of chronic myeloid leukemia in vivo. Myeloid cells of hematopoietic cell lineage amounted to 3/4 of live Ph+ mononuclear cells undergoing accumulation and subsequent consumption in the course of differentiation. 95% myeloid cells were differentiating Ph+ granulocytes. The most deal of differentiating Ph+ cells was myelocytes. The rate ratio of myelocyte accumulation to its subsequent consumption showed that the rate of transformation into metamyelocytes was significantly decreased at this differentiation stage. Ph+ cells cultivation curves characterized cell death at different differentiation stages. There were observed the cell death of proliferating Ph+ cells and Ph+ myelocytes, and intensive death of mature cells as well. P/D index, that is ratio of immature Ph+ granulocytes differentiated by cell dividing (blasts, promyelocytes and myelocytes) to the cells differentiated without dividing (metamyelocytes and mature neutrofiles), revealed active of proliferation at the beginning of cultivation and unexpected new proliferative activity at the end of cultivation in the presence of growth factor. The peaks of antiapoptotic bcr/abl gene transcription activity coincided with the observed active proliferation at the beginning and at the end of cultivation. Cell proliferation, differentiation and apoptosis were noticeably accelerated by growth factor treatment. Thus, the study of the Ph+ cells cultivation kinetics is rather informative approach to investigation of continuous regulation of cellular and molecular processes in vitro in the case of chronic myeloid leukemia and allows more complete consideration of Ph+, bcr/abl+ cells hematopoiesis.