Transfer of optogenetic vectors into the brain of neonatal animals to study neuron functions during subsequent periods of development

Optogenetics, that is, the control of cell activity using light-sensitive ion channels opsins with light of a specific wavelength, is increasingly being used to study activities and functions of neurons. Expression of opsins in the cell membrane, followed by the acquisition by the cell of the sensitivity to light is achieved by means of viral vectors, often created on the basis of lentiviral or adeno-associated (AAV) viruses bearing the nucleotide sequence encoding the photo-channel proteins. Inclusion of the cell-specific promoter of interest into the transgene-expression cassette allows opsin to be produced only in the target cells. The aim of this work was to briefly describe the optogenetic method, as well as to analyze the possibility to use administration of viral vectors into the brain of neonatal animals to study the function of neurons in vivo during subsequent periods of development. In this analysis, 3-day-old rat pups received intracerebroventricular injections of optovector (pAAV-CAMKIIa-ChR2h134-YFP), coding for a photo channel, which activates neurons, and the yellow fluorescent marker protein under the CAMKIIa promoter specific for glutamatergic neurons under cold anesthesia. The peak expression of the transferred gene is usually achieved at week 3–5 after the transfer of the vector, which is what was also observed in our experiments. Stimulation of the hippocampal neurons with blue light in the 20-day-old animals, to which opto-vector was transferred at the 3rd day of life, increased the discharge activity of these neurons. This light stimulation increased expression of the recognized marker of neuronal activation protein c-Fos in these photosensitive cells too. The same experiments with older animals, 60 days after the neonatal opto-channel gene transfer, revealed no noticeable expression of this channel or photoactivation of target neurons of the hippocampus. Thus, neonatal administration of a viral vector carrying an opto-channel gene is suitable for the study of brain neurons in rats of juvenile age, and requires additional control for gene expression during subsequent periods of development

Capsule endoscopy for screening colon tumors

Department of General Surgery with a course of endoscopy of the Federal State Budgetary Educational Institution of Higher Education and Medical University of the Ministry of Health of Russia, Leningrad Regional Oncologic Dispensary, Department of Faculty Surgery. prof. A.A. Rusanov of the Federal State Budgetary Educational Institution of Higher Education and Medical University of the Ministry of Health of Russia, Sankt-Petersburg, Russia, Al XIII-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” și al III-lea Congres al Societății de Endoscopie, Chirurgie miniminvazivă și Ultrasonografie ”V.M.Guțu” din Republica MoldovaIntroduction: Most of the colon tumors are detected in the later stages. The introduction of new, minimally invasive technologies into clinical practice allows to improve the results of the diagnosis of neoplasms. Material and methods: Capsule endoscopy is a procedure for colon examination using a miniature camera, which takes more than 10,000 images of colon at a speed of 4 to 24 frames per second. For the patient, the procedure itself does not cause discomfort. On the day of the study, the patient may do his usual activities. The indications for capsular examination of the colon may be suspected tumor of the colon, a positive test of fecal occult blood test, and the patient is over 50 years old. We made a decision to launch a pilot project for screening the colon among health care workers in Oncology Dispensary of Leningrad Region. Results: In the years 2017-2018, we performed 67 capsule colon examinations for medical workers who had not previously performed a colonoscopy. A total colon investigation was performed in 58 patients (87%). Among these patients 2 malignant tumors of the colon (3.5%) were detected. Colon epithelial neoplasia was detected in 11 patients (19%). These findings contributed to perform colonoscopy with endoscopic polypectomy. Conclusion: Capsule endoscopy of the colon can be used for examination, in cases where colonoscopy is not possible. Capsule endoscopy helps to convince the patient of the need to perform colonoscopy. Capsule endoscopy is a safe method for screening colorectal cancer

Breast Cancer After Treatment of Differentiated Thyroid Cancer With Radioiodine in Young Females: What We Know and How to Investigate Open Questions. Review of the Literature and Results of a Multi-Registry Survey

Published studies on the risk of radiation-induced second primary malignancy (SPM) after radioiodine treatment (RAI) of differentiated thyroid cancer (DTC) refer mainly to patients treated as middle-aged or older adults and are not easily generalizable to those treated at a younger age. Here we review available literature on the risk of breast cancer as an SPM after RAI of DTC with a focus on females undergoing such treatment in childhood, adolescence, or young adulthood. Additionally, we report the results of a preliminary international survey of patient registries from academic tertiary referral centers specializing in pediatric DTC. The survey sought to evaluate the availability of sufficient patient data for a potential international multicenter observational case–control study of females with DTC given RAI at an early age. Our literature review identified a bi-directional association of DTC and breast cancer. The general breast cancer risk in adult DTC survivors is low, ~2%, slightly higher in females than in males, but presumably lower, not higher, in those diagnosed as children or adolescents than in those diagnosed at older ages. RAI presumably does not substantially influence breast cancer risk after DTC. However, data from patients given RAI at young ages are sparse and insufficient to make definitive conclusions regarding age dependence of the risk of breast cancer as a SPM after RAI of DTC. The preliminary analysis of data from 10 thyroid cancer registries worldwide, including altogether 6,449 patients given RAI for DTC and 1,116 controls, i.e., patients not given RAI, did not show a significant increase of breast cancer incidence after RAI. However, the numbers of cases and controls were insufficient to draw statistically reliable conclusions, and the proportion of those receiving RAI at the earliest ages was too low.In conclusion, a potential international multicenter study of female patients undergoing RAI of DTC as children, adolescents, or young adults, with a sufficient sample size, is feasible. However, breast cancer screening of a larger cohort of DTC patients is not unproblematic for ethical reasons, due to the likely, at most slightly, increased risk of breast cancer post-RAI and the expected ~10% false-positivity rate which potentially produced substantial “misdiagnosis.

Cycle-finite module categories

We describe the structure of module categories of finite dimensional algebras over an algebraically closed field for which the cycles of nonzero nonisomorphisms between indecomposable finite dimensional modules are finite (do not belong to the infinite Jacobson radical of the module category). Moreover, geometric and homological properties of these module categories are exhibited

Endoscopic treatment of patients with early forms of gastric cancer

Leningrad regional oncological dispensary, Russia, Al XIII-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” și al III-lea Congres al Societății de Endoscopie, Chirurgie miniminvazivă și Ultrasonografie ”V.M.Guțu” din Republica MoldovaBackground: Currently, most patients with gastric tumors are detected in late stages. Early diagnosis is a major factor in improving treatment outcomes. On the other hand, patients who are diagnosed on early stages often receive aggressive treatment and are not subjects to less invasive interventions. Material and Methods: In our clinic we have been using endoscopic surgery for early gastric cancer since 2009. Japanese colleagues are the most experienced in this kind of treatment that is why we follow the recommendations of Japanese Gastric Cancer Association (JGCA). The main criterion provided that endoscopic removal is possible is the depth of tumor invasion. We evaluate the depth of invasion primarily by endoscopic ultrasonography. According to our data the accuracy of this method is 94%. The main operation used for the treatment of early gastric cancer is endoscopic submucosal dissection (ESD). Its main advantages are single block resection within healthy tissues and adequate morphological assessment of the removed tumor. In the last ten years we have performed 148 ESD (145 patients) for early forms of gastric cancer. Surgeries were radical in 95% of cases. Results:There were no cases of postoperative mortality. Progression of the disease was noted only in one patient. These endoscopic surgeries have proved to be effective, safe and reasonable in treating early gastric cancer. Conclusions: Thus, endoscopic surgery significantly reduces the cost of treatment and hospital stay (average - 3.7 days), facilitates rehabilitation and improves the quality of patients’ life

Цитологические эффекты в лимфатических узлах зоны абдоминальной лимфодиссекции после интраоперационной фотодинамической терапии при злокачественных новообразованиях желудочно-кишечного тракта

Cytological studies on lymph nodes of abdominal lymphodissection zone after local intraoperative photodynamic therapy (IOPDT) of gastrointestinal cancers were carried out. As a result of the PDT, the metastatic cells are destroyed, their cytoplasmic membranes and the cytoplasm disappears, leaving behind interphase nuclei ("naked nuclei") (p<0,0001). Cytological confrmation of apoptosis (the presence of apoptotic bodies) in metastatic lymph nodes after IOPDT sessions on the lymph nodes of the abdominal lymphodissection zone is also presented.Проведены цитологические исследования материала лимфатических узлов зоны абдомининальной лимфодиссекции после интраоперационной фотодинамической терапии (ИОФДТ) при злокачественных новообразованиях желудочно‑кишечного тракта. Установлено, что в результате проведения ФДТ клетки метастатических опухолей разрушаются с исчезновением цитоплазматической мембраны и цитоплазмы, при этом остаются только интерфазные ядра («голые ядра») (р<0,0001). Также представлено цитологическое подтверждение апоптоза (наличие апоптотических телец) в лимфатических узлах с метастазами после курсов ИОФДТ в лимфатических узлах зоны абдоминальной лимфодиссекции

Autologous hematopoietic cell transplantation for T-cell prolymphocytic leukemia: a retrospective study on behalf of the Chronic Malignancies Working Party of the EBMT.

Not available

Precision of the PET activity range during irradiation with ¹⁰C, ¹¹C, and ¹²C beams

Objective. Beams of stable ions have been a well-established tool for radiotherapy for many decades. In the case of ion beam therapy with stable 12C ions, the positron emitters 10,11C are produced via projectile and target fragmentation, and their decays enable visualization of the beam via positron emission tomography (PET). However, the PET activity peak matches the Bragg peak only roughly and PET counting statistics is low. These issues can be mitigated by using a short-lived positron emitter as a therapeutic beam. Approach. An experiment studying the precision of the measurement of ranges of positron-emitting carbon isotopes by means of PET has been performed at the FRS fragment-separator facility of GSI Helmholtzzentrum für Schwerionenforschung GmbH, Germany. The PET scanner used in the experiment is a dual-panel version of a Siemens Biograph mCT PET scanner. Main results. High-quality in-beam PET images and activity distributions have been measured from the in-flight produced positron emitting isotopes 11C and 10C implanted into homogeneous PMMA phantoms. Taking advantage of the high statistics obtained in this experiment, we investigated the time evolution of the uncertainty of the range determined by means of PET during the course of irradiation, and show that the uncertainty improves with the inverse square root of the number of PET counts. The uncertainty is thus fully determined by the PET counting statistics. During the delivery of 1.6 × 107 ions in 4 spills for a total duration of 19.2 s, the PET activity range uncertainty for 10C, 11C and 12C is 0.04 mm, 0.7 mm and 1.3 mm, respectively. The gain in precision related to the PET counting statistics is thus much larger when going from 11C to 10C than when going from 12C to 11C. The much better precision for 10C is due to its much shorter half-life, which, contrary to the case of 11C, also enables to include the in-spill data in the image formation. Significance. Our results can be used to estimate the contribution from PET counting statistics to the precision of range determination in a particular carbon therapy situation, taking into account the irradiation scenario, the required dose and the PET scanner characteristics.</p

Challenges in QCD matter physics - The Compressed Baryonic Matter experiment at FAIR

Substantial experimental and theoretical efforts worldwide are devoted to explore the phase diagram of strongly interacting matter. At LHC and top RHIC energies, QCD matter is studied at very high temperatures and nearly vanishing net-baryon densities. There is evidence that a Quark-Gluon-Plasma (QGP) was created at experiments at RHIC and LHC. The transition from the QGP back to the hadron gas is found to be a smooth cross over. For larger net-baryon densities and lower temperatures, it is expected that the QCD phase diagram exhibits a rich structure, such as a first-order phase transition between hadronic and partonic matter which terminates in a critical point, or exotic phases like quarkyonic matter. The discovery of these landmarks would be a breakthrough in our understanding of the strong interaction and is therefore in the focus of various high-energy heavy-ion research programs. The Compressed Baryonic Matter (CBM) experiment at FAIR will play a unique role in the exploration of the QCD phase diagram in the region of high net-baryon densities, because it is designed to run at unprecedented interaction rates. High-rate operation is the key prerequisite for high-precision measurements of multi-differential observables and of rare diagnostic probes which are sensitive to the dense phase of the nuclear fireball. The goal of the CBM experiment at SIS100 (sqrt(s_NN) = 2.7 - 4.9 GeV) is to discover fundamental properties of QCD matter: the phase structure at large baryon-chemical potentials (mu_B > 500 MeV), effects of chiral symmetry, and the equation-of-state at high density as it is expected to occur in the core of neutron stars. In this article, we review the motivation for and the physics programme of CBM, including activities before the start of data taking in 2022, in the context of the worldwide efforts to explore high-density QCD matter.Comment: 15 pages, 11 figures. Published in European Physical Journal

Monitoring of coronavirus infection in the kyrgyz population

Purpose of the study: to study the dynamics of developing herd immunity against SARS-CoV-2 in the population of the Republic of Kyrgyzstan during COVID-19. Materials and methods. The work was carried out using the methodology for assessing population immunity developed by Rospotrebnadzor (Russia) as well as the Ministry of Health (Kypgyzstan) and the St. Petersburg Pasteur Institute. The selection of participants was carried out by questionnaire using a cloud (Internet server) service. To monitor population immunity, a cohort of 2421 subjects was formed, who participated in all stages of seromonitoring. Volunteers were randomized according to age groups (1–17, 18–29, 30–39, 40–49, 50–59, 60–69, 70+ years), regional and professional factors. Antibodies (Abs) against SARS-CoV-2 nucleocapsid (Nc) and the receptor binding domain (RBD) of S-glycoprotein were determined by qualitative and quantitative methods. The study was carried out in 3 stages according to a single scheme: 1st stage — 06/28–07/03/2021, 2nd — 21–25/02/2022 and 3rd — 31/10–04/11/2022. Since 2021, Kyrgyzstan has been vaccinating the population against SARS-CoV-2 mainly using inactivated whole-virion vaccines. Results. Population immunity against SARS-CoV-2 was predominantly accounted for by both Ab types (Nc+RBD+). By the 3rd stage, the percentage of such persons reached 99.2%, Nc–RBD– volunteers — up to 0.8%. At the 1st stage, middle-aged people dominated, but age differences were leveled out by the 2nd stage. The greatest impact on seroprevalence was found among medical workers, the smallest — among businessmen and industrial workers. Populational vaccination significantly impacted on the state of herd immunity that reached 25% by the 3rd stage. The refusals of the population in Kyrgyz Republic from vaccination noted at the 2nd and especially 3rd stages did not significantly affect level of herd immunity, which could probably be associated with asymptomatic cases of COVID-19, against which primary vaccination had a booster effect. Conclusion. The dynamics of population humoral immunity against SARS-CoV-2 included a number of changes in the level of circulating antibodies (Nc, RBD), caused by both primary infection and vaccination. The herd immunity formed in population of Kyrgyzstan allowed to reduce the incidence of COVID-19 to almost sporadic level