Cellular internalisation, bioimaging and dark and photodynamic cytotoxicity of silica nanoparticles doped by {Mo₆I₈}⁴⁺ metal clusters

Silica nanoparticles (SNPs) doped by hexanuclear molybdenum cluster complexes [{Mo₆X₈}L₆]n (X = Cl, Br, or I; L = various inorganic or organic ligands) have been recently suggested as materials with a high potential for biomedical applications due to both the outstanding photoluminescent properties and the ability to efficiently generate singlet oxygen upon photoirradiation. However, no studies were undertaken so far to prove this concept. Therefore, here we examined the potential of photoluminescent SNPs doped by {Mo₆I₈}⁴⁺ for such applications as bioimaging and photodynamic therapy using human epidermoid larynx carcinoma (Hep-2) cell line as a model. Our results demonstrated both: (i) significant luminescence from cells with internalised molybdenum cluster doped SNPs combined with the low cytotoxicity of particles in the darkness and (ii) significant cytotoxicity of the particles upon photoirradiation. Thus, this research provides strong experimental evidence for high potential of molybdenum cluster doped materials in such biomedical applications as optical bioimaging, biolabeling and photodynamic therapy

On the parasites of genus Angiostrongylus (Nematoda: Angiostrongylidae) and some cases of Angiostrongylus daskalovi in badgers from bulgaria

In the course of studies on filariid infections in wild carnivorous in Bulgaria nematodes of genus Angiostrongylus were found in the heart and pulmonary arteries of badgers. The detected specimens were examined morphologically and metrically, which allowed us to identify them as Angiostrongylusdaskalovi . A morphometrical description of the species is given in accordance with the present materials.В ходе исследования филариидных инвазий в Болгарии в сердце и легочных артериях барсуков обнаружены нематоды рода Angiostrongylus . Эти образцы исследовались морфологически и метрически, что позволило, с учетом также географического и гостального распространения, идентифицировать их как Angiostrongylus daskalovi Janchev et Genov 1988. Приводится морфометрическое описание вида по данным текущих исследований

Ribonuclease activity as a new prospective disease resistance marker in potato

Disease resistance is an important characteristic for each variety of potato, and the search for pathogen resistance markers is one of the primary tasks of plant breeding. Higher plants possess a wide spectrum of enzymes catalyzing the hydrolysis of nucleic acids; it is believed that protection against pathogens is the most probable function of the enzymes. RNases are actively involved in several immune systems of higher plants, for example, systemic acquired resistance (SAR) and genetic silencing, hence RNase activity in plant leaves, as a relatively easily measured parameter, can serve as a good marker for the selection of pathogen resistant varieties. We have analyzed sixteen varieties of potatoes permitted for use on the territory of the Russian Federation and tested the correlation of the level of variety­specifc ribonuclease (RNase) activity with such economically valuable traits as maturity and resistance to viruses, late blight and common scab. In general, the level of RNase activity was variety­specifc, which was confrmed by very small values of average squared error for the majority of tested varieties. We have detected a statistically signifcant positive correlation of RNase activity in potato leaves with increased resistance of varieties to phytopathogenic viruses, a negative correlation with resistance to scab and an absence of a signifcant connection with maturity and resistance to late blight, regardless of the organ affected by the oomycete. Thus, the level of RNase activity in potato leaves can be used as a selective marker for resistance to viruses, while varieties with increased RNase activity should be avoided when selecting resistance to scab

11C-Choline Pet/Ct in the Detection of Prostate Cancer Relapse in Patients After Radical Treatment With Psa Level < 10 Ng/Ml

Purpose: To evaluate the usefulness of 11C-Choline PET/CT in the detection of recurrent prostate cancer (PCa) in patients with biochemical relapse after radical treatment. Materials and methods: This retrospective study included 217 PCa patients who underwent 11C-Choline PET/CT in the Department of Nuclear Medicine of Bakoulev Scientific Centre. All patients had biochemical relapse 3±2 years after radical treatment for locally advanced PCa (T1–3 N0–1 M0): radical prostatectomy (n = 159) and radiation therapy (n = 58). The mean PSA value in the group was 2.1±2.5 (0.2–9.7) ng/ml, median – 1.9 ng/ml. Imaging was performed on PET/CT scanner (Biograph-64, Siemens) 10 min after injection of 11C-Choline (400–550 Mbq). Results: Overall, according to 11C-Choline PET/CT results PCa relapse was detected in 56% (121/217) of cases: in 50% (80/159) after radical prostatectomy and in 71% (41/58) after radiation therapy. The mean PSA value in PET-positive cases was 3.1±2.2 (0.2–9.7) ng/ml, while in PETnegative cases – 1.8±1.7 (0.2–4.6) ng/ml. The majority – 68% (65/96) patients with PET-negative scan had low PSA levels (&lt; 2 ng/ml). PET/CT results were positive in 43% (50/115) patients with PSA of &lt; 2 ng/ml, in 63% (45/72) with PSA of 2 to 5 ng/ml, and in 87% (26/30) with PSA of &gt; 5 ng/ml. Local relapse was detected in 51% (62/121) patients, distant metastases – in 28% (34/121) of cases, both local and distant metastases – in 21% (25/121) of cases. Lymph node metastases were detected in 38% (86/217) of all patients included in the analysis, of which 28% (24/86) had lesions in lymph node of normal size (median 7 mm). Of all PET-positive patients bone metastases were detected in 33% (40/121), of which 60% (24/40) had isolated skeletal involvement. Importantly, that 27% (11/40) of PETpositive patients with bone metastases had no structural abnormalities on CT images (CT-negative cases), corresponding to isolated involvement of bone marrow. And half of these CT-negative patients (5/11) had single lesions. The mean PSA value in patients with bone metastases was 5.0±3.7 (0.4–9.1) ng/ml, median – 3.8 ng/ml. According to 11C-Choline PET/CT results oligometastatic PCa recurrence was revealed in 38% (82/217) of all patients, of which 62% (51/82) had local relapse only. Distant oligometastatic lesions were detected in 38% (31/82), of which 13% (4/31) were presented by normal-size lymph nodes and 19% (6/31) – by early bone marrow metastases. 48% (58/121) of PET-positive results were confirmed by data of repeated PET/CT examinations. Conclusion: 11C-Choline PET/CT has been shown to be a single noninvasive accurate technique for detection of recurrent PCa in patients with rising PSA after radical treatment, which allows to differentiate patients with local and distant metastases in one study, as well as identify oligometastatic process, and therefore was useful in determining the further personalized therapeutic approach. Keywords: prostate cancer, PET/CT, 11C-Choline, biochemical recurrence, PSA

The very forward hadron calorimeter PSD for the future CBM@FAIR experiment

The Projectile Spectator Detector (PSD) of the CBM experiment at the future FAIR facility is a compensating lead-scintillator calorimeter designed to measure the energy distribution of the forward going projectile nucleons and nuclei fragments (reaction spectators) produced close to the beam rapidity. The detector performance for the centrality and reaction plane determination is re- viewed based on Monte-Carlo simulations of gold-gold collisions by means of four different heavy-ion event generators. The PSD energy resolution and the linearity of the response measured at CERN PS for the PSD supermodule consisting of 9 modules are presented. Predictions of the calorimeter radiation conditions at CBM and response measurement of one PSD module equipped with neutron irradiated MPPCs used for the light read out are discussed

Analysis of factors affecting the accuracy of 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography in case of suspected prosthetic valve infective endocarditis

Aim. To analyze the factors affecting the accuracy of 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (PET/CT) in case of suspected prosthetic valve endocarditis (PVE).Material and methods. The results of PET/CT performed in 66 patients after heart valve replacement were analyzed: 55 patients with suspected PVE (≥3 months after surgery) and 11 comparison groups without PVE (2 months after surgery). In the group with suspected PVE (n=55) at the time of the study, 27% (15/55) had a normal body temperature, 85% (47/55) — no leukocytosis. In 16% (9/55), the examination was performed from 3 to 6 months after surgery and in 67% (37/55)  — against the background of long-term antibiotic therapy (ABT). The final diagnosis of PVE was made on the basis of clinical (including 6±3 followup), laboratory, instrumental, and intraoperative (n=40) data: confirmed  — in 37 patients; ruled out — in 29 patients. In order to determine the influence of factors on obtaining false PET/CT results, the odds ratio was calculated.Results. In the group with suspected PVE (n=55), the PET/CT results made it possible to establish and rule out PVE in 92% (34/37) and 67% (12/18) of patients, respectively. In 16% (9/55) of patients, false positive (n=6) and false negative (n=3) results. Thus, the sensitivity, specificity and diagnostic accuracy of PET/CT in the diagnosis of PVE were 92%, 67% and 84%, respectively; positive and negative predictive values — 85% and 80%. The analysis of the odds ratio did not reveal the relationship of low inflammatory activity, the interval between surgery and PET/CT from 3 to 6 months, and long-term ABT before PET/CT with false PET/CT results (p&gt;0,05). In the comparison group without PVE (n=11), 91% (10/11) received false positive PET/CT results, and one patient received a true negative result.Conclusion. The data obtained indicate the high informative value of PET/CT in the diagnosis of PVE. Interval &gt;2 months between surgery and PET/CT significantly reduces the accuracy of PET/CT results. Other factors analyzed in the presented group did not affect the accuracy of PET/CT results

The problem of vaccinal prevention of newborns in Perinatal centre of third level

There was carried out a clinical and statistical analysis of the results vaccination of newborns against tuberculosis and hepatitis В in Perinatal centre (PC) of third level in 2011 year. Some of non-vaccinated children were analyzed: the group of infants, that required intensive care, and children, who were not vaccinated for other reasons. Medical and social importance of vaccination of newborns in the early period was established on the basis of cause-and-effect relations.Проведен клинико-статистический анализ результатов вакцинации новорожденных против туберкулеза и гепатита В в Перинатальном центре (ПЦ) третьего уровня в 2011 году. Среди детей, не получивших вакцинацию, анализировалась группа новорожденных, потребовавших проведения интенсивной терапии, а также дети, которые были не вакцинированы по другим причинам. На основании полученных причинно-следственных связей установлена медико-социльная значимость вакцинации новорожденных в ранние сроки

Методологический подход к формированию перечня видов высокотехнологичной медицинской помощи

Background. The implementation of individual methods of high-tech medical care (HTMC) with methods of specialized medical care within the framework of a phased transition to payment methods by diagnostic-related groups (DRGs), on the one hand, significantly expanded the availability of HTMC methods for the population. Still, it created a situation with duplication of individual treatment methods in the list of HTMC types and DRGs. Amendments to the Order of the Ministry of Health of the Russian Federation (MH RF) of August 1, 2017 No. 484n, regulating the revision of HTMC types list in terms of excluding treatment methods and (or) HTMC types in case of their duplication in the context of HTMC groups and/or DRGs, marked the beginning of large-scale work in this area and required methodological ensuring the processes of forming HTMC types list, including in terms of its revision.Objective: development of a methodological approach to the formation of HTMC types list (using the example of the list for 2023). Material and methods. An analysis of legal documents regulating the HTMC availability in the Russian Federation was carried out, including the list of medical services approved by the Order of the MH RF of October 13, 2017 No. 804n, clinical recommendations for certain nosological entities, the International Classification of Diseases (10th revision), methodological recommendations on ways to pay for medical care at the expense of the compulsory health insurance (CHI) and appendices to them (decoders of DRGs for payment of medical care provided in inpatient and daytime hospital conditions), posted on the official website of the Federal CHI Fund. The frequency of the use of certain HTMC methods and DRGs was analyzed on the basis of impersonalized information from the database of registers of bills for specialized medical care, including HTMC for 2021–2022.Results. A methodological approach to the revision of HTMC types list was developed. It included its primary analysis, expert discussion of the obtained results, consideration by the Interdepartmental Council of the MH RF of proposals agreed with experts on each HTMC method submitted for discussion, followed by a decision on the appropriateness of the proposed changes, and recalculation of the standard of financial costs for HTMC and/or basic tariff for DRGs.Conclusion. The proposed methodological approach makes it possible to unify the process of revising the HTMC types list, including the exclusion of duplicate treatment methods and/or HTMC types in the sections of HTMC list types and/or in DRGs, as well as treatment methods missing in clinical recommendations, etc. in order to bring the HTMC types list in accordance with legal documents regulating the provision of medical care in the Russian Federation.Актуальность. Инкорпорация отдельных методов высокотехнологичной медицинской помощи (ВМП) с методами специализированной медицинской помощи в рамках поэтапного перехода на способы оплаты по клинико-статистическим группам заболеваний (КСГ), с одной стороны, существенно расширила доступность ВМП для населения, а с другой – создала прецедент с дублированием отдельных методов лечения в перечне видов ВМП и КСГ. Внесение изменений в приказ Минздрава России от 1 августа 2017 г. № 484н, регламентирующий пересмотр перечня видов ВМП в части исключения методов лечения и (или) видов ВМП в случае их дублирования в разрезе групп ВМП и/или КСГ заболеваний, положило начало масштабной работе по данному направлению и потребовало методологического обеспечения процессов формирования перечня видов ВМП, в т.ч. в части его пересмотра.Цель: разработка методологического подхода к формированию перечня видов ВМП (на примере перечня на 2023 г.).Материал и методы. Выполнен анализ нормативных правовых документов, регулирующих оказание ВМП в Российской Федерации, в т.ч. номенклатуры медицинских услуг, утвержденной приказом Минздрава России от 13 октября 2017 г. № 804н, клинических рекомендаций по отдельным нозологическим формам, Международной классификации болезней 10-го пересмотра, методических рекомендаций по способам оплаты медицинской помощи за счет средств обязательного медицинского страхования (ОМС) и приложений к ним – расшифровщиков КСГ заболеваний для оплаты медицинской помощи, оказанной в стационарных условиях и в условиях дневного стационара, размещенных на официальном сайте Федерального фонда ОМС. Частоту применения тех или иных методов ВМП и КСГ заболеваний анализировали на основании обезличенных персонифицированных сведений из базы реестров счетов на оплату специализированной медицинской помощи, в т.ч. ВМП за 2021–2022 гг.Результаты. Разработан методологический подход к пересмотру перечня видов ВМП, включающий его первичный анализ, экспертное обсуждение полученных результатов, подготовку предложений, согласованных с экспертами по каждому методу ВМП для обсуждения на межведомственном совете Минздрава России в целях принятия решения о целесообразности предложенных изменений, с последующим пересчетом норматива (среднего норматива) финансовых затрат для ВМП и/или базового тарифа для КСГ заболеваний.Заключение. Предложенный методологический подход позволяет унифицировать процесс пересмотра перечня ВМП, в т.ч. в части исключения дублирующих методов лечения и/или видов ВМП в разделах перечня видов ВМП и/или КСГ, а также методов лечения, отсутствующих в клинических рекомендациях и других документах, в целях приведения перечня видов ВМП в соответствие с нормативными правовыми документами, регламентирующими оказание медицинской помощи в Российской Федерации

Совершенствование модели оплаты медицинской помощи при хроническом вирусном гепатите С в рамках реализации Программы государственных гарантий бесплатного оказания гражданам медицинской помощи на 2023 год и на плановый период 2024–2025 годов

Background. In 2021, new clinical guidelines for the treatment of chronic hepatitis C virus (HCV) in adults were published that did not contain interferon drug therapy regimens. Current therapy of chronic HCV is based on modern drugs of direct-acting antivirals (DAA). In this regard, the model of diagnosis-related groups (DRG) with the use of interferon-containing drugs as etiotropic therapy, which has been in effect until now, has lost its relevance and cannot be used to pay for cases of medical care for chronic HCV within the framework of the Program of State Guarantees of Free Medical Care to Citizens for 2023 and for the planning period of 2024–2025 (PSG). Objective: to improve the DRG model to pay for medical care for chronic HCV in a day hospital based on current clinical recommendations.Material and methods. Regulatory legal documents on the subject of the study, proposals and expert opinions of specialists, as well as feedback from public organizations, including patients, regarding the payment of medical care for chronic HCV, sent as part of a public discussion of the draft PSG, were studied. For the calculations were used: the current version of the clinical recommendations "Chronic viral hepatitis C"; impersonal personalized information of the database of registers of bills for payment for medical care for 2020–2021; the state register of manufacturers' maximum selling prices for medicines included in the list of vital and essential drugs.Results. A DRG model was developed to pay for medical care during drug therapy of chronic HCV, including for children. When calculating the model, the cost of medicines, patient days and the principles of accounting for the duration of hospitalization were updated.Conclusion. The developed DRG model to pay for medical care for chronic HCV in a day hospital with the use of drug therapy regimens with DAA recommended by clinical guidelines, including for children with HCV, contributes to improving the effectiveness of the system of payment for medical care provided as part of the implementation of the PSG and accessibility of medical care for this contingent of patients.Актуальность. В 2021 г. опубликованы новые клинические рекомендации по лечению хронического вирусного гепатита С (ХВГС) у взрослых, в которых отсутствуют интерфероновые схемы лекарственной терапии. Актуальная терапия ХВГС базируется на современных противовирусных препаратах прямого действия (ПППД). В этой связи модель клинико-статистических групп (КСГ) с применением в качестве этиотропной терапии интерфероносодержащих препаратов, действующая до настоящего времени, утратила актуальность и не может использоваться для оплаты случаев оказания медицинской помощи при ХВГС в рамках реализации Программы государственных гарантий бесплатного оказания гражданам медицинской помощи на 2023 год и на плановый период 2024–2025 годов (ПГГ).Цель: совершенствование модели КСГ заболеваний для оплаты медицинской помощи при ХВГС в условиях дневного стационара на основе действующих клинических рекомендаций.Материал и методы. Изучены нормативные правовые документы по теме исследования, предложения и экспертные мнения специалистов, а также отзывы общественных организаций, включая пациентские, в части оплаты медицинской помощи при ХВГС, направленные в рамках общественного обсуждения проекта ПГГ. Для проведения расчетов использовались: актуальная версия клинических рекомендаций «Хронический вирусный гепатит С», обезличенные персонифицированные сведения базы реестров счетов на оплату за оказание медицинской помощи за 2020–2021 гг., государственный реестр предельных отпускных цен производителей на лекарственные препараты, включенные в перечень жизненно необходимых и важнейших лекарственных препаратов.Результаты. Разработана модель КСГ заболеваний для оплаты медицинской помощи при проведении лекарственной терапии ХВГС, в т.ч. для пациентов детского возраста. При расчете модели актуализирована стоимость препаратов, пациенто-дня и принципы учета длительности госпитализации.Заключение. Разработанная модель КСГ для оплаты медицинской помощи при ХВГС в условиях дневного стационара с применением схем лекарственной терапии ПППД, предлагаемых клиническими рекомендациями, в т.ч. для детей с ХВГС, способствует повышению эффективности системы оплаты медицинской помощи, оказываемой в рамках реализации ПГГ, и доступности медицинской помощи для данного контингента больных

Высокие значения исходных объемных ПЭТ-биомаркеров как предикторы неблагоприятного прогноза классической лимфомы Ходжкина

Purpose: To analyse the prognostic value of the initial volumetric PET biomarkers – the total metabolic tumor volume (MTV) and the total lesion glycolysis (TLG) – in classic Hodgkin's lymphoma (cHL) and determine their optimal threshold values for prognosis.Material and methods. This retrospective study included 62 cHL patients with different stages who underwent staging with 18F-FGD PET/CT. The follow-up period was from 6 to 61 months after the baseline PET/CT, 41 patients remained in remission, 10 patients had refractory course, 11 relapsed. The examinations were processed with automatic (multi-foci segmentation – MFS) method to obtain MTV and TLG using two fixed absolute thresholds (SUVmax ≥ 2.5 and SUVmax ≥ 4.0) and one relative threshold (41% of SUVmax).Results. In subgroups with disease remission (n = 41) and refractory course or relapse (n = 21), statistically significant differences between MTV and TLG with the two thresholds were found – SUVmax ≥ 2.5 and 41% of SUVmax (p &lt; 0.05). When using threshold of SUVmax ≥ 4.0 statistically differences between the mean of MTV and TLG were no detected.Univariate analysis revealed correlation between progression-free survival and volumetric PET biomarkers (MTV and TLG) with three thresholds (SUVmax ≥ 2.5, SUVmax ≥ 4.0, and 41% of SUVmax).Conclusion. In cHL high values of initial volumetric PET biomarkers – MTV and TLG – calculated with three thresholds (SUVmax ≥ 2.5, SUVmax ≥ 4.0, and 41% of SUVmax) are associated with unfavourable prognosis – a high probability of refractory disease course or relapse.The optimal prognostic thresholds values of MTV and TLG in the analysed group were determined respectively: SUVmax ≥ 2.5 – 204 cm3 and 961, at 41% of SUVmax – 105 cm3 and 620.Цель исследования: анализ прогностического значения исходных объемных ПЭТ-биомаркеров – общего метаболического объема опухоли (MTV) и общего уровня гликолиза (TLG) – при классической лимфоме Ходжкина (кЛХ) и определение их оптимальных пороговых прогностических значений.Материал и методы. Ретроспективно проанализированы результаты ПЭТ/КТ-исследований 62 пациентов с впервые выявленной кЛХ. Период наблюдения составил от 6 до 61 мес после исходного ПЭТ/ КТ-исследования. В течение указанного периода у 41 (66%) пациента сохранялась ремиссия заболевания, у 10 (16%) пациентов диагностировано рефрактерное течение, у 11 (18%) – рецидив. Показатели MTV и TLG рассчитывались автоматическим методом с использованием для каждого трех значений отсечки фона: двух абсолютных – SUVmax ≥ 2,5 и SUVmax ≥ 4,0 и одного относительного – 41% от SUVmax.Результаты. Для расчета пороговых прогностических значений MTV и TLG группа была разделена на две подгруппы: 1-я – с ремиссией заболевания в течение периода наблюдения (n = 41); 2-я – с рефрактерным или рецидивирующим течением (n = 21). В указанных подгруппах были выявлены статистически значимые различия между показателями MTV и TLG при двух используемых значениях отсечки фона – SUVmax ≥ 2,5 и 41% от SUVmax (р &lt; 0,05). При использовании отсечки фона – SUVmax ≥ 4,0 – значимых различий между указанными показателями в подгруппах получено не было.При однофакторном анализе параметры MTV и TLG с использованием трех пороговых значений отсечки фона (SUVmax ≥ 2,5, SUVmax ≥ 4,0 и 41% от SUVmax) коррелировали с выживаемостью без прогрессирования.Заключение. При кЛХ высокие значения исходных объемных ПЭТ-биомаркеров MTV и TLG, рассчитанные с использованием различных порогов отсечки фона (SUVmax ≥ 2,5, SUVmax ≥ 4,0 и 41% от SUVmax), ассоциируются с неблагоприятным прогнозом – высокой вероятностью рефрактерного течения заболевания или возникновения рецидива.Оптимальные прогностические пороговые значения MTV и TLG в анализируемой группе составили: при SUVmax ≥ 2,5 – 204 см3 и 961, при 41% от SUVmax – 105 см3 и 620 соответственно