Production of 117mSn and 119mSn by photonuclear reactions on natural antimony.

Natural antimony targets were irradiated in a 60 MeV bremsstrahlung beam and gamma spectrometric measurements were performed. The goal was to establish the yield of 117mSn, a radionuclide with great potential for application in medicine. Considering that 117mSn is predominantly produced through a photonuclear reaction in which an charged particle is emitted (121Sb(γ,p3n)), the yield of this tin isotope is much lower than the yields of several antimony isotopes produced in (γ,xn) reactions. It has been estimated that photonuclear reactions on natural antimony could produce 117mSn activities needed for therapeutic applications, with accelerators having electron currents of the order of mA. For the used bremsstrahlung energy of 60 MeV, it was estimated how much 119mSn activity can be expected when exposing the antimony target.

[Laparoscopic distal pancreatectomy for portal annular pancreas]. / Laparoskopicheskaya distal'naya rezektsiya podzheludochnoi zhelezy pri portal'noi kol'tsevidnoi podzheludochnoi zheleze.

Portal annular pancreas is a little-known anatomical variant of annular pancreas. In these patients, pancreatic parenchyma encircles the portal vein annularly. This anomaly is associated with high risk of postoperative pancreatic fistula in pancreatic surgery. Considering small incidence of anomaly and characteristics of surgery, we describe laparoscopic distal pancreatectomy with preservation of spleen and splenic vessels in a patient with solid pseudopapillary tumor combined with portal annular pancreas. A 33-year-old woman underwent laparoscopic surgery for cystic-solid pancreatic tumor. Spleen-sparing distal pancreatectomy was performed. Portal annular pancreas was visualized intraoperatively and confirmed retrospectively after analysis of MR data. Ventral and dorsal parts of portal annular pancreas were transected using stapler device. Pancreatic fistula developed in postoperative period. The patient was discharged after 6 days with a drainage tube. Surgeons need to be aware of portal annular pancreas. This anomaly increases the risk of postoperative fistula. Transection of ventral and dorsal parts of annular pancreas using stapler device is the most acceptable option to reduce the risk of postoperative fistula.

[The medicine and blogosphere: publications review].

The article presents the review of national and foreign publications reflecting aspects of development of medical blogosphere as communication space for medical workers and patients. The methodology of content analysis was applied. The main groups of medical bloggers (doctors, patients, nurses), characteristics of the blogs content, motivation for blogosphere posting are identified. The information and communication significance of the medical blogosphere is high and topical vectors are quite diversified. The development of the medical blogosphere testifies high level of demand for information forming the content of medical blogs both in patients and in colleagues-representatives of professional community.

Prognostic significance of VEGF signaling system components and matrix metalloproteinases in blood serum of gastric cancer patients.

Analysis of long-term treatment results of 77 primary gastric cancer patients at stage I-IV of the tumor process followed during 1 - 41 months (median - 6.4 months) from the onset of specific treatment are presented depending on the basal levels of VEGF, soluble forms of its receptors (sVEGFR1, sVEGFR2) and matrix metalloproteinases (MMP-2, 7, 9) in blood serum. Overall survival assessed by Kaplan-Meyer analysis and with the help of Cox multiparametric regression model was applied as the criterion of prognostic value. It was found that at high (≥ 420 pg/ml) serum VEGF, the overall survival of patients with gastric cancer was statistically significantly lower than at the marker's levels below 420 pg/ml (p<0.011): 3-year's survival comprised 46,3±12,5% and 88,2±7,8% respectively. Median survival of patients with high VEGF level comprised 21.7 months, of those with low VEGF was not achieved during the whole follow-up period. Serum sVEGFR1, sVEGFR2, MMP-2, 7 and 9 levels were not significantly associated with the overall survival of patients included in this study. Only index M of TNM system and serum VEGF level demonstrated an independent prognostic value in multiparametric model (p=0.036). Thus, it was confirmed that VEGF signaling pathway plays an important role in gastric cancer, and its components - in the first place, VEGF A - are substantial factors of disease prognosis, and can also be useful for monitoring of treatment efficiency.

Dynamical phase transition in the first-passage probability of a Brownian motion.

We study the first-passage time distribution (FPTD) F(t_{f}|x_{0},L) for a freely diffusing particle starting at x_{0} in one dimension, to a target located at L, averaged over the initial position x_{0} drawn from a normalized distribution (1/σ)g(x_{0}/σ) of finite width σ. We show the averaged FPTD undergoes a sharp dynamical phase transition from a two-peak structure for b=L/σ>b_{c} to a single-peak structure for b

Vascular Endothelial Growth Factor and Soluble Forms of Its Receptors 1 and 2 in Gastric Cancer.

Comparative evaluation of blood content of VEGF, sVEGFR1, and sVEGFR2 in 104 primary gastric cancer patients and 65 healthy persons was performed and associations of these markers with the principal clinical and morphological characteristics of gastric cancer were analyzed. The median levels of VEGF and sVEGFR1 in gastric cancer patients significantly surpassed the control: by 1.5 (p<0.001) and 1.2 times (p<0.01), respectively. On the contrary, sVEGFR2 level in patients was below the control (p<0.001). The best sensitivity-specificity ratio (64 and 65%, respectively) was observed for VEGF at 347 pg/ml cut-off value, which is insufficient for the use of this parameter as a clinically valuable serological marker for gastric cancer. No significant associations of these markers with the disease stage, depth of primary tumor invasion, its histological type, grade, or localization were found. The serum level of VEGF in patients with metastases to more than 7 regional lymph nodes (N3) was significantly higher than in patients without lymph node metastases (N0). Blood content of sVEGFR1 in patients with distant metastases (М+) was lower than in patients without distant metastases (М0). Thus, VEGF and its receptors circulating in the peripheral blood do not play significant diagnostic role in gastric cancer, but could be useful in monitoring and prognosis of the efficiency of antiangiogenic therapy.

[Multi-component multi-stage treatment of a patient with infection of thoracic aorta prosthesis, deep sternal wound infection and soft tissue deficit of the chest]. / Mnogokomponentnoe, mnogoetapnoe lechenie patsientki s infektsiei proteza vsei grudnoi aorty, osteomielitom grudiny i defitsitom myagkikh tkanei grudnoi kletki.

We report a comorbid patient after redo Frozen Elephant Trunk procedure followed by recurrent infection of thoracic aortic prosthesis, deep sternal wound infection and extensive soft tissue defect. Closure with skin-muscle thoracodorsal flap and graft-sparing technique with omentoplasty is an alternative to total graft replacement for thoracic aortic graft infection in comorbid patients with concomitant extensive defect of the chest wall or recurrent infection in early postoperative period.

Influence of the cumulative effect of zoledronic acid on periodontal microcirculation in rats.

PURPOSE: To evaluate the effect of repeated administration of zoledronic acid (ZA) on the development and severity of osteonecrosis of the jaws. METHODS: In the experiment, 36 rats were used, which were divided into 4 groups: group 1 was injected with saline for 6 weeks, group 2 was injected with ZA once, group 3 was injected zoledronic acid for 3 weeks once a week, group 4 was injected with ZA for 6 weeks once a week. While taking medications, the tooth was removed. The volumetric blood flow rate was studied using laser and high-frequency ultrasound Doppler in the area of the periodontium of an extracted tooth in rats with the application of acetylcholine. Bone tissue was examined out using CBCT. RESULTS: In group 2, there was a violation of blood flow in the mucous membrane, bone microcirculation, but no reliable data was obtained in the bone defect in comparison with group 1. In groups 3 and 4, there was significantly disrupted blood flow. This led to an increase of the osteonecrosis (maximum at the 4th group), which was confirmed by data obtained using CBCT. An inverse relationship was observed between the blood flow of bone tissue and the size of the defect after tooth extraction. CONCLUSION: The introduction of ZA in a dose-dependent fashion resulted in impaired endothelial vasodilation and impaired blood flow to extraction sockets. These findings might explain the development of osteonecrosis of the mandible following removal of a first molar.

Disorders of microcirculation in the mechanism of bisphosphonate osteonecrosis: preliminary study in rats.

We investigated the possibilities of angioprotection and the reduction of osteonecrosis in rats that had been given bisphosphonates. In our experiment, 27 rats were divided into three groups: Group 1 was injected with saline; Group 2 was given zoledronic acid for six weeks; and Group 3 was given zoledronic acid for six weeks, with added doses of sulodexide after three weeks. After that we constructed a model of how the teeth should be extracted. The velocity of linear blood flow in the periodontal area of an extracted tooth in rats was studied using laser and high-frequency Doppler ultrasound (with the application of the vasoactive substance acetylcholine 3% for 1min). We evaluated changes in the structure of the bony tissues of the head using computed tomography, comparing the control group with the saline group. A rapid reduction in microcirculation was detected during the use of zoledronic acid for six weeks. A smaller reduction in microcirculation was detected after three weeks of treatment with sulodexide and zoledronic acid. There was a reduction in blood flow in the mucous membranes and, to a greater extent, in bony tissue. Zoledronic acid causes significant impairment of the periosteal blood flow to the mucous membranes because of a complex of disorders, which includes both the cellular component (impaired endothelium-dependent vasodilation of the mucous membrane vessels) and by reducing the intensity of microcirculation in the mucous membranes and bony tissues. Sulodexide, however, improves the restoration of blood flow and reduces the severity of osteonecrosis.

Crystal structures and vibrational spectra of L-argininium(2+) bis(tetrafluoroborate) and L-argininium(2+) bis(perchlorate).

In the present work crystal structures of (L-ArgH2)(BF4)2 (I) and (L-ArgH2)(ClO4)2 (II) isostructural salts have been determined. They crystallize in triclinic system with space group P1 and Z = 1. Structure features of the (I) and (II) were compared with respective data of previously known (L-ArgH)(BF4) and (L-ArgH)(ClO4) salts with singly charged L-argininium(+) cation. Infrared and Raman spectra of the (I) and (II) are compared with spectra of (L-ArgH)(BF4) and (L-ArgH)(ClO4) salts. The presence of cation and anions and hydrogen bonds between them are reflected in the IR and Raman spectra. The crystals (I) and (II) exhibit second harmonic generation activity.

Long-term results of isolated transmyocardial laser revascularization in combination with the intramyocardial autologous bone marrow stem cells injection.

To evaluate the long-term results of TMLR using a CO2 laser in combination with intramyocardial injection of ABMSC as an isolated procedure in patients with the end-stage coronary artery disease, the study included 20 patients (90% male), with a mean age of 58.4 ± 8.7 years. To assess the long-term results, patients were examined in a hospital. The Minnesota Living with Heart Failure Questionnaire (MLHFQ) and the Seattle Angina Questionnaire (SAQ) were used. The evolution of laboratory and instrumental indices, as well as medical therapy, was assessed. The end points of the study were death, acute myocardial infarction (AMI), repeated myocardial revascularization, recurrent hospitalizations due to coronary artery disease, and stroke. The changes in angina functional class were also evaluated. The median of follow-up period was 54 (36; 83) months, that is, 4.5 years. The analysis of the evolution of echocardiographic data showed the absence of statistically significant changes in the following parameters: left ventricular end-diastolic diameter (EDD) (p = 0.967), end-systolic diameter (ESD) (p = 0.204), end-diastolic volume (EDV) (p = 0.852), end-systolic volume (ESV) (p = 0.125), and left ventricular ejection fraction (LVEF) (p = 0.120). The patients continued to regularly take the main groups of medications. Nitrate consumption was significantly reduced (p < 0.001). Significant positive dynamics were observed in the changes in angina functional class. At the baseline, all patients had angina III FC, in the long term, 3 patients had II FC, 11 patients had I FC, and 6 patients had no angina. Clinical outcomes (mortality, recurrent myocardial infarction, stroke) were absent during the follow-up period. There were two cases of repeated myocardial revascularization. Regression analysis revealed that SYNTAX score was associated with the clinical outcome "repeated revascularization." TMLR in combination with intramyocardial injection of ABMSC is a safe method to achieve a statistically significant antianginal effect and reduce the need for "nitrates," which in turn improves the quality of life and reduces the frequency of hospitalizations due to coronary artery disease. These results can be achieved with strict adherence to the certain indications for the intervention.

Unlocking Golgi: Why Does Morphology Matter?

The mammalian Golgi apparatus is a highly dynamic organelle, which is normally localized in the juxtanuclear space and plays an essential role in the regulation of cellular homeostasis. While posttranslational modification of cargo is mediated by the resident enzymes (glycosyltransferases, glycosidases, and kinases), the ribbon structure of Golgi and its cisternal stacking mostly rely on the cooperation of coiled-coil matrix golgins. Among them, giantin, GM130, and GRASPs are unique, because they form a tripartite complex and serve as Golgi docking sites for cargo delivered from the endoplasmic reticulum (ER). Golgi undergoes significant disorganization in many pathologies associated with a block of the ER-to-Golgi or intra-Golgi transport, including cancer, different neurological diseases, alcoholic liver damage, ischemic stress, viral infections, etc. In addition, Golgi fragments during apoptosis and mitosis. Here, we summarize and analyze clinically relevant observations indicating that Golgi fragmentation is associated with the selective loss of Golgi residency for some enzymes and, conversely, with the relocation of some cytoplasmic proteins to the Golgi. The central concept is that ER and Golgi stresses impair giantin docking site but have no impact on the GM130-GRASP65 complex, thus inducing mislocalization of giantin-sensitive enzymes only. This cardinally changes the processing of proteins by eliminating the pathways controlled by the missing enzymes and by activating the processes now driven by the GM130-GRASP65-dependent proteins. This type of Golgi disorganization is different from the one induced by the cytoskeleton alteration, which despite Golgi de-centralization, neither impairs function of golgins nor alters trafficking.

[Distal duodenectomy: a new option of surgical treatment for duodenal tumors]. / Distal'naya duodenal'naya rezektsiya: novyi sposob khirurgicheskogo lecheniya pri opukholevom porazhenii dvenadtsatiperstnoi kishki.

OBJECTIVE: To assess severity, safety and functional advisability of distal pancreatectomy using original surgical technique developed in the Blokhin National Medical Research Centre of Oncology. MATERIAL AND METHODS: There were 10 patients with duodenal malignancies who have undergone distal pancreatectomy in the Blokhin National Medical Research Centre of Oncology for the period 2006-2018. Distal pancreatectomy for primary duodenal tumors was performed in 8 patients, 2 patients underwent surgery for external invasion of the duodenum. RESULTS: Postoperative complications Clavien-Dindo grade 1 and 2 occurred in 4 (40%) patients. Surgical complication grade 2 occurred in 1 (10%) patient (pancreatic fistula with effective conservative management). There were no cases of leakage of duodenal stump and duodenojejunostomy, impaired bile flow and stenosis of anastomosis with delayed stomach emptying. CONCLUSION: Distal duodenectomyis associated with low postoperative morbidity, good functionality and quality of life. This procedure is preferred for non-epithelial and neuroendocrine tumors, as well as with secondary malignant duodenal invasion.

[RESTORATION OF SYMPATHO-PARASYMPATHETIC BALANCE IN HEART RATE VARIABILITY IN THE DEVELOPMENT OF PSYCHOEMOTIONAL STRESS AGAINST THE BACKGROUND OF TAURINE IN EXPERIMENT].

In this fragment of the study, the change in the ratio of low (LF) and high frequency (HF) waves to the heart rhythmogram during prolonged immobilization (5 hours) of sexually mature white non-linear rats was studied by spectral analysis of heart rate variability, which causes psychoemotional stress and the accompanying vegetative equilibrium shift, indicating on the dysregulation of the sympatho-parasympathetic balance without and against the background of daily intraperitoneal injection of taurine (50 mg/kg) and its participation in the mechanisms of adaptive processes in the early poststress period (from 1 to 14 days). Spectral analysis of both absolute and relative indices of the I-th group (stress without taurine) revealed significant shifts in the frequency spectrum. On the first day after immobilization, the total power of the spectrum decreased by 4.3%, the HF component by 33.3%, and the level of VLF and LF-components increased by 25.5% and 25%, respectively, compared to the norm. On the 14th day after the immobilization, there is a decrease in tension, but the LF component is still above the norm by 5%. Calculations of the percentage ratios of the absolute values of the spectrum at different times of the post-stress period against the background of taurine injection showed that in the initial stage (immediately and on the first day after stress) a strong shift of activity toward sympathization occurs, and the absolute value of LF and VLF in the spectrum increased by 23,1% and 10.9% respectively. However, the complete restoration of the vago-sympathetic balance with the daily application of taurine occurs already on the 7th day after immobilization. The beneficial effect of taurine on the cardiovascular system was revealed when examining the scatterogram of the regression dependence of the heart rate, which revealed a smaller variation in heart rate and its stabilization on the 7th day after immobilization. Thus, the use of taurine immediately after stressful reactions is necessary to accelerate adaptive processes in the early post-stress period to prevent the development of stress pathology.

The bridge between transplantation and regenerative medicine: Beginning a new Banff classification of tissue engineering pathology.

The science of regenerative medicine is arguably older than transplantation-the first major textbook was published in 1901-and a major regenerative medicine meeting took place in 1988, three years before the first Banff transplant pathology meeting. However, the subject of regenerative medicine/tissue engineering pathology has never received focused attention. Defining and classifying tissue engineering pathology is long overdue. In the next decades, the field of transplantation will enlarge at least tenfold, through a hybrid of tissue engineering combined with existing approaches to lessening the organ shortage. Gradually, transplantation pathologists will become tissue-(re-) engineering pathologists with enhanced skill sets to address concerns involving the use of bioengineered organs. We outline ways of categorizing abnormalities in tissue-engineered organs through traditional light microscopy or other modalities including biomarkers. We propose creating a new Banff classification of tissue engineering pathology to standardize and assess de novo bioengineered solid organs transplantable success in vivo. We recommend constructing a framework for a classification of tissue engineering pathology now with interdisciplinary consensus discussions to further develop and finalize the classification at future Banff Transplant Pathology meetings, in collaboration with the human cell atlas project. A possible nosology of pathologic abnormalities in tissue-engineered organs is suggested.

THE IMPACT OF ALCOHOL ON PRO-METASTATIC N-GLYCOSYLATION IN PROSTATE CANCER.

Chronic alcohol abuse and alcoholism are considered risk factors for prostate cancer (PCa) progression, but the mechanism is unknown. Previously, we found that: (1) fragmentation of the Golgi complex correlates with the progression of PCa; (2) ethanol (EtOH) induces Golgi disorganization, which, in turn, alters intra-Golgi localization of some Golgi proteins. Also, progression of the prostate tumor is associated with activation of N-acetylglucosaminyltransferase-V (MGAT5)-mediated N-glycosylation of pro-metastatic proteins, including matriptase and integrins, followed by their enhanced retention at the cell surface. Here, using high-resolution microscopy, we found that alcohol effect on Golgi in low passage androgen-responsive LNCaP cells mimic the fragmented Golgi phenotype of androgen-refractory high passage LNCaP and PC-3 cells. Next, we detected that transition to androgen unresponsiveness is accompanied by downregulation of N-acetylglucosaminyltransferase-III (MGAT3), the enzyme that competes with MGAT5 for anti-metastatic N-glycan branching. Moreover, in low passage LNCaP cells, alcohol-induced Golgi fragmentation induced translocation of MGAT3 from the Golgi to the cytoplasm, while intra-Golgi localization of MGAT5 appeared unaffected. Then, the relationship between Golgi morphology, MGAT3 intracellular position, and clinicopathologic features was assessed in human PCa patient specimens with and without a history of alcohol dependence. We revealed that within the same clinical stage, the level of Golgi disorganization and the cytoplasmic shift of MGAT3 was more prominent in patients consuming alcohol. In vitro studies suggest that EtOH-induced downregulation of MGAT3 correlates with activation of MGAT5-mediated glycosylation and overexpression of both matriptase and integrins. In sum, we provide a novel insight into the alcohol-mediated tumor promotion.

Amniotic fluid stem cell-derived vesicles protect from VEGF-induced endothelial damage.

Injection of amniotic fluid stem cells (AFSC) delays the course of progression of renal fibrosis in animals with Alport Syndrome, enhancing kidney function and improving survival. The mechanisms responsible for these protective outcomes are still largely unknown. Here, we showed that vascular endothelial growth factor (VEGF) signaling within the glomeruli of Alport mice is strongly elevated early on in the disease, causing glomerular endothelial cell damage. Intraventricular injected AFSC that homed within the glomeruli showed strong modulation of the VEGF activity, particularly in glomerular endothelial cells. To investigate this phenomenon we hypothesized that extracellular vesicles (EVs) produced by the AFSC could be responsible for the observed renoprotection. AFSC derived EVs presented exosomal and stem cell markers on their surface membrane, including VEGFR1 and VEGFR2. EVs were able to modulate VEGF in glomerular endothelial cells by effectively trapping the excess VEGF through VEGFR1-binding preventing cellular damage. In contrast, VEGFR1/sVEGFR1 knockout EVs failed to show similar protection, thus indicating that VEGF trapping is a potentially viable mechanism for AFSC-EV mediated renoprotection. Taken together, our findings establish that EVs secreted by AFSC could target a specific signaling pathway within the glomerulus, thus representing a new potential glomerulus-specific targeted intervention.

[THE ROLE OF TAURINE THE PROCESS OF ADAPTATION OF VISCERAL SYSTEMS UNDER PSYCHO-EMOTIONAL STRESS IN RAT].

In recent years the identification of regulatory mechanisms of the general adaptation syndrome, manifesting itself as the response of an organism to drastic changes in the environment and leading to emotional stress, acquires a special significance. The control over visceral functions plays a particular role in stress reactions because of emerging threat of violation of neurodynamic balance of sympathetic-para- sympathetic relationships with their most sensitive element - the heart. Quick adaptation to stress helps to restore not only the sympathetic-parasympathetic homeostasis but also the energy metabolism. One of the essential components, activating metabolic processes, is taurine. This paper considers the descending influence of the paraventricular nucleus (PVN) on neuronal reactions of the solitary tract nucleus (NTS), the first linking pathways of visceral sensitivity, the mechanisms of central control over visceral reactions by mathematical model analysis of heart rate variability (MMA HRV) as well as morpho-histochemical changes in brain structures integrating and regulating the visceral sphere (PVN of the hypothalamus and the amygdala) under psycho-emotional stress without and with intraperitoneal injection of taurine (50 mg/kg). Acute and semichronic experiments were conducted on white nonlinear rats under 5-hour- long immobilization psycho-emotional stress. A highly defined centralization of vegetative HRV parame- ters (HR, IVR, INRS) was revealed, these parameters being normalized on days 7 and 14 at the background of taurine injections. The interaction and interdependence of the central regulatory mechanisms of cardiovascular reactions are shown as well as a considerable protective effect of taurine on promoting early restoration of adaptive properties of the central and peripheral segments of visceral sensitivity under development of long-term psycho-emotional stress.

Theoretical description of effective heat transfer between two viscously coupled beads.

We analytically study the role of nonconservative forces, namely viscous couplings, on the statistical properties of the energy flux between two Brownian particles kept at different temperatures. From the dynamical model describing the system, we identify an energy flow that satisfies a fluctuation theorem both in the stationary and in transient states. In particular, for the specific case of a linear nonconservative interaction, we derive an exact fluctuation theorem that holds for any measurement time in the transient regime, and which involves the energy flux alone. Moreover, in this regime the system presents an interesting asymmetry between the hot and cold particles. The theoretical predictions are in good agreement with the experimental results already presented in our previous article [Imparato et al., Phys. Rev. Lett. 116, 068301 (2016)PRLTAO0031-900710.1103/PhysRevLett.116.068301], where we investigated the thermodynamic properties of two Brownian particles, trapped with optical tweezers, interacting through a dissipative hydrodynamic coupling.

Stationary and Transient Fluctuation Theorems for Effective Heat Fluxes between Hydrodynamically Coupled Particles in Optical Traps.

We experimentally study the statistical properties of the energy fluxes between two trapped Brownian particles, interacting through dissipative hydrodynamic coupling, and submitted to an effective temperature difference ΔT, obtained by random forcing the position of one trap. We identify effective heat fluxes between the two particles and show that they satisfy an exchange fluctuation theorem in the stationary state. We also show that after the sudden application of a temperature gradient ΔT, the total hot-cold flux satisfies a transient exchange fluctuation theorem for any integration time, whereas the total cold-hot flux only does it asymptotically for long times.