Bismuth Nanoparticles Increase Effectiveness of Proton Therapy of Ehrlich Carcinoma.

We studied the antitumor activity of the combined use of local proton irradiation in two modes (10 and 31 Gy) with preliminary intra-tumoral injection of two types of bismuth nanoparticles differing in surface coating: coated with the amphiphilic molecule Pluronic-F127 or Silane-PEG (5 kDa)-COOH polymer. Nanoparticles were used in doses of 0.75 and 1.5 mg/mouse. In two independent series on experimental tumor model (solid Ehrlich carcinoma), bismuth nanoparticles of both modifications injected directly into the tumor enhanced the antitumor effects of proton therapy. Moreover, the radiosensitizing effect of bismuth nanoparticles administered via this route increased with the increasing the doses of nanoparticles and the doses of radiation exposure. In our opinion, these promising data obtained for the first time extend the possibilities of treating malignant neoplasms.

[Therapy of mental disorders in patients with hematological malignancies]. / Terapiya nepsikhoticheskikh psikhicheskikh rasstroistv u bol'nykh s zabolevaniyami sistemy krovi.

OBJECTIVE: To assess the possibilities of therapy with minimal effective doses (MED) of psychotropic drugs for mental disorders (MD) that manifest during the treatment of hematological malignancies (HM). MATERIAL AND METHODS: A prospective study was conducted at the National Medical Research Center for Hematology of the Russian Ministry of Health (Moscow), which included 204 (39.4%) men and 314 (60.6%) women (518 patients in total), aged 17 to 83 years (median 45 years), with various HM, in which the manifestation of MD occurred during the treatment of the underlying disease. To minimize the side-effects of psychotropic drugs and given the relatively mild level of MD, psychopharmacotherapy of patients was carried out mainly at MED. The severity of MD, manifested in patients, was assessed by the illness severity scale of the Clinical Global Impression (CGI) scale, and the effectiveness of the treatment was assessed by the improvement scale (CGI-I). RESULTS: Mainly mild (188, 36%) and moderately pronounced (270, 52%) MD were noted in patients with HM during the treatment of the underlying disease. Severe psychopathological disorders (60, 12%) were observed much less often. Because of psychopharmacotherapy with MED, patients experienced a very significant (97, 19%) and significant improvement (354, 68%) of their mental state, less often the improvement was regarded as minimal (67, 13%). Therefore, almost all patients showed a stable relief of MD; in 87% (95% CI 84-90) of patients, this improvement was significant. CONCLUSION: The tactics of treatment MD that manifest in patients with HM with MED of psychotropic drugs turned out to be therapeutically effective according to the results of the assessment on CGI scales.

Compact remanence-free permanent magnet-based variable magnetic field source.

We demonstrate a simple and compact variable magnetic field source based on the permanent cube magnet array approximating a Halbach cylinder. The large air gap area accommodates standard cryostat tails while providing a high uniformity and magnetic field stability of up to 0.5 T over regions of up to about a centimeter. It eliminates magnetic remanence effects and produces reproducible fields without the need for feedback. Thanks to the low cost and exceptional energy efficiency, it provides an accessible solution for modest magnetic field requirements in a wide range of research applications.

A novel preliminary metabolomic panel for IHD diagnostics and pathogenesis.

Cardiovascular disease (CVD) represents one of the main causes of mortality worldwide and nearly a half of it is related to ischemic heart disease (IHD). The article represents a comprehensive study on the diagnostics of IHD through the targeted metabolomic profiling and machine learning techniques. A total of 112 subjects were enrolled in the study, consisting of 76 IHD patients and 36 non-CVD subjects. Metabolomic profiling was conducted, involving the quantitative analysis of 87 endogenous metabolites in plasma. A novel regression method of age-adjustment correction of metabolomics data was developed. We identified 36 significantly changed metabolites which included increased cystathionine and dimethylglycine and the decreased ADMA and arginine. Tryptophan catabolism pathways showed significant alterations with increased levels of serotonin, intermediates of the kynurenine pathway and decreased intermediates of indole pathway. Amino acid profiles indicated elevated branched-chain amino acids and increased amino acid ratios. Short-chain acylcarnitines were reduced, while long-chain acylcarnitines were elevated. Based on these metabolites data, machine learning algorithms: logistic regression, support vector machine, decision trees, random forest, and gradient boosting, were used for IHD diagnostic models. Random forest demonstrated the highest accuracy with an AUC of 0.98. The metabolites Norepinephrine; Xanthurenic acid; Anthranilic acid; Serotonin; C6-DC; C14-OH; C16; C16-OH; GSG; Phenylalanine and Methionine were found to be significant and may serve as a novel preliminary panel for IHD diagnostics. Further studies are needed to confirm these findings.

[Elimination of defects in the Schneiderian membrane during sinus lift operations]. / Ustranenie defektov membrany Shneidera vo vremya provedeniya operatsii sinus-liftinga.

PURPOSE: Evaluation of the effectiveness of a new method of plasty of an extensive defect in the mucous membrane of the Schneiderian membrane, which occurs during the sinus lift operation, using an artificial collagen membrane and a developed method for fixing it. MATERIAL AND METHODS: A total of 188 patients took part in the study, all of these patients underwent an open sinus lift operation with simultaneous or delayed implantation. Operations were performed under balanced anesthesia. Six months after the operation, according to computed tomography, the height of the formed bone regenerate was estimated. In the area of each missing tooth, the initial bone height and the resulting bone grafting were assessed. Then we compared the average values before and after the operation, the average height difference before and after the operation. RESULTS: In 19 patients during the sinus lift there was an accidental extensive rupture of the mucous membrane of the maxillary sinus. Elimination of the mucosal defect was carried out according to our patented method. All 188 patients were diagnosed with partial loss of teeth with bone tissue deficiency in the distal maxillary sinus. The height of the alveolar process in the projection of missing teeth ranged from 0.5 mm to 5 mm. Delayed dental implantation was performed when the height of the alveolar bone was less than 3 mm, direct when the presence of 3-5 mm. After 6 months, dental implants were installed in the reconstruction zone, after another 6 months - rational prosthetics. CONCLUSIONS: The proposed method of plastic surgery has the following advantages. Firstly, it allows to eliminate the defect of the mucous membrane together with an increase in the height of the alveolar ridge. Secondly, after this method, the integrity of the mucous membrane will be restored. Thirdly, with an alveolar bone height of 3 mm or more, dental implants should also be installed.

[Indocyanine green angiography in assessment of parathyroid remnant perfusion after subtotal parathyroidectomy: a case report]. / Angiografiya s indotsianinom zelenym v otsenke perfuzii ostatka tkani parashchitovidnoi zhelezy pri subtotal'noi paratireoidektomii: klinicheskoe nablyudenie.

A 72-year-old female patient with chronic kidney disease stage presented with multiple parathyroid adenomas and tertiary hyperparathyroidism. SPECT/CT with 99mTc-MIBI revealed accumulation of radiopharmaceuticals in 2 out of 4 parathyroid glands. Ultrasound established localization of all parathyroid glands. Subtotal parathyroidectomy with excision of 3 glands and resection of half of the fourth gland was performed. Intraoperative indocyanine green angiography was performed to identify all parathyroid glands and remnant perfusion. There was normal parathyroid function after 6 months.

Biological Response of Chinese Hamster B14-150 Cells to Sequential Combined Exposure to Protons and 12C Ions.

Proton and ion radiation therapy, when used both as single radiation and in mixed radiation mode, have a number of advantages over the conventional γ-therapy that are determined by physical characteristics of accelerated particles. The paper presents the results of an in vitro study of the effectiveness of sequential exposures of Chinese hamster tumor cells B14-150 to proton (p) and 12C ion beams. We used 4 irradiation schemes differing by the sequence of exposure and the contribution of each radiation to the total dose. Synergism was shown for 12C ions dose contribution of 45% (taking into account the coefficient of relative biological efficiency) and the sequence 12C→p.

Effects of Combined Exposure to Carbon Ions and Protons on the Pool of MCF-7 Breast Cancer Stem Cells In Vitro.

We studied the effects of single and combined action of protons and carbon ions 12C6+ on the pool of MCF-7 human breast cancer stem cells. Single irradiation with a beam of protons or carbon ions had no significant effects on the relative number of cancer stem cells (CSC). The effects of combined irradiation in a total equieffective dose of 4 Gy depended on the sequence of exposure to ionizing radiations: the relative number of CSC did not change after irradiation with carbon ions and then with protons, but increased in the case of the reverse sequence. The most favorable result, i.e. a decrease in the CSC pool, was observed in the case of sequential irradiation with carbon ions and protons and their equal contribution to total equieffective dose. In this case, the absolute number of CSC decreased by on average 2.1 times in comparison with the control (p<0.05). The revealed regularities are of interest for the further development of new methods of radiation therapy.

[The use of an individualized mini plate for the distalization of teeth]. / Ispol'zovanie individualizirovannoi miniplastiny dlya distalizatsii zubov.

The case of treatment of a 32-year-old patient with complaints about the aesthetics of a smile and the absence of teeth 17 and 46 is presented. During the examination, it was established: the retraction position of the teeth in the frontal part of the upper jaw, the closure of the molars according to the II class of the second subclass of Engl (distal bite), the vestibular position of the teeth 13, 23. To change the spatial position of the lower jaw, the fixation of the bracket system on the upper jaw was performed. and also an individualized mini-plate was installed in the area of the zygomatic alveolar ridge on the right and left, for distalization of the dentition of the upper jaw with the help of orthodontic traction applied from the teeth to the mini-plates. This clinical example demonstrates the possibility of using individualized mini-plates for distalization of the upper dentition, as an alternative and more stable method of treatment in such clinical cases.

[Infectious factor in transuretral surgery of benign prostate hyperplasia: a systematic review and meta-analysis].

PURPOSE: To assess postoperative bacteriuria and infectious complications in terms of antibiotic prophylaxis (ABP) regimens, preoperative urine bacterial status and total prostate-specific antigen (PSA) level in patients with benign prostate hyperplasia (BPH) undergoing transurethral prostate surgery. MATERIALS AND METHODS: The PubMed, ClinicalKey, Google Scholar and the Cochrane bibliographic databases were searched from 1992 to 2022. The Mantel-Haenszel method was used to calculate the odds ratio (OR) and inverse variance method was used to calculate mean difference (MD) with 95% confidence interval (CI). Primary outcome was the development of asymptomatic bacteriuria, secondary - development of infectious complications. RESULTS: This meta-analysis showed that ABP significantly decreased level of postoperative bacteriuria and infection complications. This meta-analysis was in favour of prolonged ABP ( more or equal 3 days) in lowering postoperative infectious complications rate compared to short regimens ( less or equal 24 hours). Preoperative bacteriuria was not significantly associated with postoperative bacteriuria level and infectious complications. Mean preoperative PSA level significantly differed in patients with and without postoperative bacteriuria. CONCLUSION: This meta-analysis demonstrated significant gaps in the knowledge of perioperative bacterial status and antibiotic prophylaxis strategies efficacy in the group of patients undergoing transurethral prostate surgery. There is no consensus on optimal ABP regimen. Most of included studies had significant heterogeneity. Further studies are required.

[Indocyanine green in liver tumor resection]. / Primenenie ICG na etapakh planirovaniya i realizatsii rezektsii pecheni po povodu opukholei.

Primary liver cancer and colorectal cancer liver metastases are among the leading causes of cancer-related mortality worldwide. Surgery is one of the main methods of treatment to achieve the best results in overall and recurrence-free survival. The main objectives in this surgery are preoperative planning, assessment of functional viability of liver parenchyma and total resection with low complication rate. Post-resection liver failure is one of the most formidable and often fatal complication following functional failure of liver remnant. Thus, preoperative assessment of liver functional reserves is a necessary step for adequate selection of patients and safe surgery. Passive liver tests, such as biochemical parameters or clinical scales, do not accurately reflect the actual functional component of liver parenchyma. The most accurate method is dynamic quantitative test of liver, such as indocyanine green clearance. The authors discuss the practical aspects of preoperative assessment of liver functional reserves using indocyanine green, as well as the concept and technical foundations of fluorescent imaging in hepatobiliary surgery.

[Indocyanine green fluorescence angiography in transoral endoscopic thyroidectomy for papillary thyroid cancer]. / Primenenie fluorestsentnoi angiografii s indotsianinom zelenym v transoral'noi endoskopicheskoi tireoidektomii pri papillyarnom rake shchitovidnoi zhelezy.

OBJECTIVE: To evaluate the effectiveness of ICG angiography in patients with papillary thyroid cancer (PTC) undergoing transoral endoscopic thyroidectomy (TOETVA) and selective neck dissection (level VI). MATERIAL AND METHODS: A retrospective analysis included 20 patients with PTC who underwent TOETVA with selective neck dissection (level VI) between September and December 2022. ICG was administered intravenously (5 mg ´ 3 times). We analyzed parathyroid glands by visual examination and ICG angiography. Fluorescence of all glands was assessed. RESULTS: Twenty patients underwent ICG angiography during TOETVA. A total of 68 parathyroid glands were identified. Only 76.5% (52/68) of parathyroid glands were identified at initial visual examination. ICG angiography additionally localized 12 glands that improved detection to 94.1% (64/68). At least one well-vascularized parathyroid gland was demonstrated by ICG angiography in 16 patients. In all these patients, serum parathyroid hormone was normal in 1 and 10 days after surgery. Two out of four patients who failed to identify a well-vascularized parathyroid gland developed transient hypoparathyroidism. There were no intraoperative and postoperative complications associated with ICG angiography. CONCLUSION: ICG angiography was simple, safe and effective for better identification and preservation of parathyroid glands in patients with PTC undergoing TOETVA. This method was valuable for assessing the viability and function of parathyroid glands and predicting postoperative hypocalcemia.

[Isolated endovascular liver chemoperfusion for liver metastases of uveal melanoma]. / Sposob izolirovannoi endovaskulyarnoi khimioperfuzii pecheni pri metastazakh uveal'noi melanomy v pechen'.

Isolated hepatic perfusion is one of the possible approaches for unresectable liver metastases of uveal melanoma. This technique is rare in modern oncology because of extremely difficult technique and high risk of intra- and postoperative complications. Thus, minimizing surgical trauma and increasing safety and reproducibility of this technique are important. There were 36 procedures of isolated «open¼ hepatic perfusion. The authors describe the first experience of endovascular hepatic perfusion. Advantages and clinical prospects of this method are shown.

Experimental Model for the Study of Reparative Bone Regeneration in the Reconstruction of the Lower Jaw.

An experimental in vivo model has been developed on the rabbit mandible to study reparative regeneration of alveolar bone after intercortical split osteotomy and the role of the periosteum in the process of reparative osteogenesis. The peculiarity of this model is fixation of the periosteum over the reconstruction zone, which allows preserving the bone block displaced during surgery and leads to the formation of an organotypic structure of the regenerate with cortical and spongy bone.

[The relationship between penile hemodynamic parameters in cavernous rteries and penile rigidity].

INTRODUCTION: Blood flow parameters in cavernous arteries during full-erection phase on Doppler ultrasonography are associated with intracavernosal pressure and, consequently, with penile rigidity. AIM: To examine the relationship between blood flow parameters in cavernous arteries and the penile rigidity. MATERIALS AND METHODS: A total of 54 healthy men and patients with erectile dysfunction of various degrees of severity, with mean age of 43,0 +/- 2,2 years ranging from 18 to 74 years, were included in the study. Erectile function was examined and 81 Doppler ultrasonography were performed after intracavernosal injection of alprostadil (10 mcg). In full-erection phase, peak systolic velocity (PSV) and systolic acceleration (SA) were measured, as well as resistive index (RI). Mean values were calculated for both cavernous arteries. Penile rigidity was assessed in three ways: clinical evaluation according to I. Goldstein, measurement of surface rigidity and evaluation of longitudinal rigidity. RESULTS: During Doppler ultrasonography a strong correlation of penile rigidity with RI (0,71-0,85) and SA (0,63-0,69) was found. Indirect assessment of penile rigidity using PSV values was less precise. With RI values close to 1,0, SA is a more reliable method for indirect rigidity assessment. CONCLUSION: Penile blood flow parameters, RI and SA, allow to evaluate a degree of rigidity and to eliminate subjectivity of the specialist performing the examination, as well as to obtain a range of penile rigidity values.

Effect of Collagen and GelMA on Preservation of the Costal Chondrocytes' Phenotype in a Scaffold in vivo.

The aim of the study was to compare type I collagen-based and methacryloyl gelatin-based (GelMA) hydrogels by their ability to form hyaline cartilage in animals after subcutaneous implantation of scaffolds. Materials and Methods: Chondrocytes were isolated from the costal cartilage of newborn rats using 0.15% collagenase solution in DMEM. The cells was characterized by glycosaminoglycan staining with alcian blue. Chondrocyte scaffolds were obtained from 4% type I porcine atelocollagen and 10% GelMA by micromolding and then implanted subcutaneously into the withers of two groups of Wistar rats. Histological and immunohistochemical studies were performed on days 12 and 26 after implantation. Tissue samples were stained with hematoxylin and eosin, alcian blue; type I and type II collagens were identified by the corresponding antibodies. Results: The implanted scaffolds induced a moderate inflammatory response in both groups when implanted in animals. By day 26 after implantation, both collagen and GelMA had almost completely resorbed. Cartilage tissue formation was observed in both animal groups. The newly formed tissue was stained intensively with alcian blue, and the cells were positive for both types of collagen. Cartilage tissue was formed among muscle fibers. Conclusion: The ability of collagen type I and GelMA hydrogels to form hyaline cartilage in animals after subcutaneous implantation of scaffolds was studied. Both collagen and GelMA contributed to formation of hyaline-like cartilage tissue type in animals, but the chondrocyte phenotype is characterized as mixed. Additional detailed studies of possible mechanisms of chondrogenesis under the influence of each of the hydrogels are needed.

[Chemotherapy-associated clinical dynamics of nosogenic reactions in breast and ovarian cancer model]. / Assotsiirovannaya s khimioterapiei klinicheskaya dinamika nozogennykh reaktsii na modeli raka molochnoi zhelezy i yaichnikov.

OBJECTIVE: To study the clinical features, dynamics and factors of nosogenic reactions (NR) development in patients with breast and ovarian cancers at the stage of chemotherapy. MATERIAL AND METHODS: The study involved 35 patients who underwent chemotherapy. Clinical-psychopathological and psychometric methods were used to assess the mental state. RESULTS: We distinguished 3 clinical types of nosogenic reactions: anxiety-phobic (n=14, 40%), anxiety-depression (n=13, 37%) and dissociative reaction (n=8, 23%). It was discovered that nosogenic reactions reflect the dynamics of psychopathological disorders associated with chemotherapy and they are connected with premorbid personality structure of the patients. When compared on the Mini-mult scales, differences were found between patients of the anxiety-phobic and dissociative groups: the score on the Anxiety and Depressive Tendencies scale was significantly higher in the group of patients with anxious-phobic NR (p<0.01), as was the score on the scale «Anxiety fixation and restrictive behavior¼, which was correlated with such personality traits as sensitivity, self-doubt, low self-esteem, obsessive fears (p<0.05). According to the results of the Spielberger-Khanin anxiety scale, in general, the sample was characterized by an increased level of anxiety compared to the norm: the average scores were 49.7 for trait anxiety and 47.7 for state anxiety. CONCLUSION: Nosogenic reactions can undergo dynamic changes at various stages of treatment. The proposed typology of nosogenies in a more detailed study can have not only scientific, but also practical significance for determining the personalized tactics of psychiatric care for cancer patients at different stages of the disease.

[Isolated liver perfusion with melphalan followed by pembrolizumab therapy for unresectable metastases of uveal melanoma to the liver]. / Sposob izolirovannoi perfuzii pecheni melfalanom s posleduyushchei terapiei pembrolizumabom v lechenii nerezektabel'nykh metastazov uveal'noi melanomy, ogranichennykh pechen'yu.

Uveal melanoma accounts for 80% of all ocular melanomas, and 30-60% of patients have metastases to the liver. A few patients are candidates for liver resection, and this disease is associated with poor prognosis. There are few data on optimal management of metastatic uveal melanoma. Isolated hepatic perfusion is a perspective method for regional treatment of inoperable metastatic liver lesions with uveal melanoma. We present a patient with uveal melanoma who underwent previous enucleation of the eye. Cancer progressed 15 years later as an isolated inoperable metastatic liver lesion. The patient underwent isolated liver perfusion with melphalan, hyperthermia and oxygenation. Subsequently, the patient received systemic therapy with pembrolizumab. Partial response was achieved 1 month after the procedure. There was no progression for 20 months after surgery under systemic therapy with pembrolizumab. Thus, isolated liver chemoperfusion with melphalan is advisable in these patients.

[Development of a Series of Neutralizing Nanobodies against SARS-CoV-2 Spike Protein].

Countering the spread of new respiratory infections and reducing the damage they cause to society requires efficient strategies for rapidly developing of targeted therapeutics, such as monoclonal antibodies. Nanobodies, defined as variable fragments of heavy-chain camelid antibodies, have a set of characteristics that make them particularly convenient for this purpose. The speed at which the SARS-CoV-2 pandemic spread confirmed that the key factor in the development of therapeutics is obtaining highly effective blocking agents as soon as possible, as well as the diversity of epitopes to which these agents bind. We have optimized the selection process of blocking nanobodies from the genetic material of camelids and obtained a panel of nanobody structures with affinity to Spike protein in the lower nanomolar and picomolar ranges and with high binding specificity. The subset of nanobodies that demonstrate the ability to block the interaction between the Spike protein and the cellular ACE2 receptor was selected in experiments in vitro and in vivo. It has been established that the epitopes bound by the nanobodies are located in the RBD domain of the Spike protein and have little overlap. The diversity of binding regions may allow a mixture of nanobodies to retain potential therapeutic efficacy towards new Spike protein variants. Furthermore, the structural features of nanobodies, particularly their compact size and high stability, indicate the possibility of their utilization in the form of aerosols.

[Immune mechanisms of complicity of somatic pathology in the pathogenesis of mental disorders]. / Immunnye mekhanizmy souchastiya somaticheskoi patologii v patogeneze psikhicheskikh rasstroistv.

Understanding the mechanisms of the relationship between the nervous and immune systems within the framework of the concept of the key role of inflammation, taking into account the involved genetic factors in the development of a wide range of combined forms of somatic and mental diseases, is of interest for research as well as for the development of new approaches to early diagnosis and more effective treatment of these diseases. This review analyzes the immune mechanisms of the development of mental disorders in patients with somatic diseases, in particular, the transmission of an inflammatory signal from the periphery to the CNS and the implementation of the influence of inflammatory factors on neurochemical systems that determine the characteristics of mental functioning. Particular attention is paid to the processes underlying the disruption of the blood-brain barrier caused by peripheral inflammation. Modulation of neurotransmission, changes in neuroplasticity, changes in regional activity of the brain in areas associated with the functions of threat recognition, cognitive processes and memory function, the effect of cytokines on the hypothalamic-pituitary-adrenal system are considered as mechanisms of action of inflammatory factors in the brain. The need to take into account variations in the genes of pro-inflammatory cytokines, which may be the cause of increased genetic vulnerability associated with the risk mental disorders in patients suffering from a certain somatic disease, is emphasized.