A single-lead ECG based cardiotoxicity detection in patients on polychemotherapy.

Background: Anti-cancer treatment can be fraught with cardiovascular complications, which is the most common cause of death among oncological survivors. Without appropriate cardiomonitoring during anti-cancer treatment, it becomes challenging to detect early signs of cardiovascular complications. In order to achieve higher survival rates, it is necessary to monitor oncological patients outpatiently after anti-cancer treatment administration. In this regard, we aim to evaluate the efficacy of single-lead ECG remote monitoring to detect cardiotoxicity in cancer patients with minimal cardiovascular diseases after the first cycle of polychemotherapy. Materials and methods: The study included patients 162 patients over 18 years old with first diagnosed different types of solid tumors, planed for adjuvant (within 8 weeks after surgery) or neoadjuvant polychemotherapy. All patients were monitored, outpatiently, during 14-21 days (depending on the regimen of polychemotherapy) after polychemotherapy administration using single-lead ECG. Results: QTc > 500 mc prolongation was detected in 8 patients (6.6 %), first-diagnosed arial fibrillation was detected in 11 patients (9 %) in period after chemotherapy administration. Moreover, left ventricular diastolic dysfunction using single-lead ECG after polychemotherapy was detected in 49 (40.1 %) patients with sensitivity 80 %, specificity 95 %, AUC 0.88 (95 % CI, 0.82-0.93). Conclusions: The side effects of cancer treatment may cause life-threatening risks. Early identification of cardiotoxicity plays a vital role in the solution of this problem. Using portable devices to detect early cardiotoxicity is a simple, convenient and affordable screening method, that can be used for promptly observation of patients.

Practical Application of a New Cuffless Blood Pressure Measurement Method.

It would be useful to develop a reliable method for the cuffless measurement of blood pressure (BP), as such a method could be made available anytime and anywhere for the effective screening and monitoring of arterial hypertension. The purpose of this study is to evaluate blood pressure measurements through a CardioQVARK device in clinical practice in different patient groups. METHODS: This study involved 167 patients aged 31 to 88 years (mean 64.2 ± 7.8 years) with normal blood pressure, high blood pressure, and compensated high blood pressure. During each session, three routine blood pressure measurements with intervals of 30 s were taken using a sphygmomanometer with an appropriate cuff size, and the mean value was selected for comparison. The measurements were carried out by two observers trained at the same time with a reference sphygmomanometer using a Y-shaped connector. In the minute following the last cuff-based measurements, an electrocardiogram (ECG) with an I-lead and a photoplethysmocardiogram were recorded simultaneously for 3 min with the CardioQVARK device. We compared the systolic and diastolic BP obtained from a cuff-based mercury sphygmomanometer and smartphone-case-based BP device: the CardioQVARK monitor. A statistical analysis plan was developed using the IEEE Standard for Wearable Cuffless Blood Pressure Devices. Bland-Altman plots were used to estimate the precision of cuffless measurements. RESULTS: The mean difference between the values defined by CardioQVARK and the cuff-based sphygmomanometer for systolic blood pressure (SBP) was 0.31 ± 3.61, while that for diastolic blood pressure (DBP) was 0.44 ± 3.76. The mean absolute difference (MAD) for SBP was 3.44 ± 2.5 mm Hg, and that for DBP was 3.21 ± 2.82 mm Hg. In the subgroups, the smallest error (less than 3 mm Hg) was observed in the prehypertension group, with a slightly larger error (up to 4 mm Hg) found among patients with a normal blood pressure and stage 1 hypertension. The largest error was found in the stage 2 hypertension group (4-5.5 mm Hg). The largest error was 4.2 mm Hg in the high blood pressure group. We, therefore, did not record an error in excess of 7 mmHg, the upper boundary considered acceptable in the IEEE recommendations. We also did not reach a mean error of 5 mmHg, the upper boundary considered acceptable according to the very recent ESH recommendations. At the same time, in all groups of patients, the systolic blood pressure was determined with an error of less than 5 mm Hg in more than 80% of patients. While this study shows that the CardioQVARK device meets the standards of IEEE, the Bland-Altman analysis indicates that the cuffless measurement of diastolic blood pressure has significant bias. The difference was very small and unlikely to be of clinical relevance for the individual patient, but it may well have epidemiological relevance on a population level. Therefore, the CardioQVARK device, while being worthwhile for monitoring patients over time, may not be suitable for screening purposes. Cuffless blood pressure measurement devices are emerging as a convenient and tolerable alternative to cuff-based devices. However, there are several limitations to cuffless blood pressure measurement devices that should be considered. For instance, this study showed a high proportion of measurements with a measurement error of <5 mmHg, while detecting a small, although statistically significant, bias in the measurement of diastolic blood pressure. This suggests that this device may not be suitable for screening purposes. However, its value for monitoring BP over time is confirmed. Furthermore, and most importantly, the easy measurement method and the device portability (integrated in a smartphone) may increase the self-awareness of hypertensive patients and, potentially, lead to an improved adherence to their treatment. CONCLUSION: The cuffless blood pressure technology developed in this study was tested in accordance with the IEEE protocol and showed great precision in patient groups with different blood pressure ranges. This approach, therefore, has the potential to be applied in clinical practice.

Diabetic Retinopathy Diagnosis Based on Convolutional Neural Network in the Russian Population: A Multicenter Prospective Study.

BACKGROUND: Diabetic retinopathy is the most common complication of diabetes mellitus and is one of the leading causes of vision impairment globally, which is also relevant for the Russian Federation. OBJECTIVE: To evaluate the diagnostic efficiency of a convolutional neural network trained for the detection of diabetic retinopathy and estimation of its severity in fundus images of the Russian population. METHODS: In this cross-sectional multicenter study, the training data set was obtained from an open source and relabeled by a group of independent retina specialists; the sample size was 60,000 eyes. The test sample was recruited prospectively, 1186 fundus photographs of 593 patients were collected. The reference standard was the result of independent grading of the diabetic retinopathy stage by ophthalmologists. RESULTS: Sensitivity and specificity were 95.0% (95% CI; 90.8-96.4) and 96.8% (95% CI; 95.5- 99.0), respectively; positive predictive value - 98.8% (95% CI; 97.6-99.2); negative predictive value - 87.1% (95% CI, 83.4-96.5); accuracy - 95.9% (95% CI; 93.3-97.1); Kappa score - 0.887 (95% CI; 0.839-0.946); F1score - 0.909 (95% CI; 0.870-0.957); area under the ROC-curve - 95.9% (95% CI; 93.3-97.1). There was no statistically significant difference in diagnostic accuracy between the group with isolated diabetic retinopathy and those with hypertensive retinopathy as a concomitant diagnosis. CONCLUSION: The method for diagnosing DR presented in this article has shown its high accuracy, which is consistent with the existing world analogues, however, this method should prove its clinical efficiency in large multicenter multinational controlled randomized studies, in which the reference diagnostic method would be unified and less subjective than an ophthalmologist.

Globally invariant metabolism but density-diversity mismatch in springtails.

Soil life supports the functioning and biodiversity of terrestrial ecosystems. Springtails (Collembola) are among the most abundant soil arthropods regulating soil fertility and flow of energy through above- and belowground food webs. However, the global distribution of springtail diversity and density, and how these relate to energy fluxes remains unknown. Here, using a global dataset representing 2470 sites, we estimate the total soil springtail biomass at 27.5 megatons carbon, which is threefold higher than wild terrestrial vertebrates, and record peak densities up to 2 million individuals per square meter in the tundra. Despite a 20-fold biomass difference between the tundra and the tropics, springtail energy use (community metabolism) remains similar across the latitudinal gradient, owing to the changes in temperature with latitude. Neither springtail density nor community metabolism is predicted by local species richness, which is high in the tropics, but comparably high in some temperate forests and even tundra. Changes in springtail activity may emerge from latitudinal gradients in temperature, predation and resource limitation in soil communities. Contrasting relationships of biomass, diversity and activity of springtail communities with temperature suggest that climate warming will alter fundamental soil biodiversity metrics in different directions, potentially restructuring terrestrial food webs and affecting soil functioning.

Left Ventricular Diastolic Dysfunction Screening by a Smartphone-Case Based on Single Lead ECG.

Aims: To investigate the potential of a signal processed by smartphone-case based on single lead electrocardiogram (ECG) for left ventricular diastolic dysfunction (LVDD) determination as a screening method. Methods and Results: We included 446 subjects for sample learning and 259 patients for sample test aged 39 to 74 years for testing with 2D-echocardiography, tissue Doppler imaging and ECG using a smartphone-case based single lead ECG monitor for the assessment of LVDD. Spectral analysis of ECG signals (spECG) has been used in combination with advanced signal processing and artificial intelligence methods. Wavelengths slope, time intervals between waves, amplitudes at different points of the ECG complexes, energy of the ECG signal and asymmetry indices were analyzed. The QTc interval indicated significant diastolic dysfunction with a sensitivity of 78% and a specificity of 65%, a Tpeak parameter >590 ms with 63% and 58%, a T value off >695 ms with 63% and 74%, and QRSfi > 674 ms with 74% and 57%, respectively. A combination of the threshold values from all 4 parameters increased sensitivity to 86% and specificity to 70%, respectively (OR 11.7 [2.7-50.9], P < .001). Algorithm approbation have shown: Sensitivity-95.6%, Specificity-97.7%, Diagnostic accuracy-96.5% and Repeatability-98.8%. Conclusion: Our results indicate a great potential of a smartphone-case based on single lead ECG as novel screening tool for LVDD if spECG is used in combination with advanced signal processing and machine learning technologies.

Signaling pathways and therapeutic approaches in glioblastoma multiforme (Review).

Glioblastoma multiforme (GBM) is the most aggressive type of primary brain tumor and is associated with a poor clinical prognosis. Despite the progress in the understanding of the molecular and genetic changes that promote tumorigenesis, effective treatment options are limited. The present review intended to identify and summarize major signaling pathways and genetic abnormalities involved in the pathogenesis of GBM, as well as therapies that target these pathways. Glioblastoma remains a difficult to treat tumor; however, in the last two decades, significant improvements in the understanding of GBM biology have enabled advances in available therapeutics. Significant genomic events and signaling pathway disruptions (NF­κB, Wnt, PI3K/AKT/mTOR) involved in the formation of GBM were discussed. Current therapeutic options may only marginally prolong survival and the current standard of therapy cures only a small fraction of patients. As a result, there is an unmet requirement for further study into the processes of glioblastoma pathogenesis and the discovery of novel therapeutic targets in novel signaling pathways implicated in the evolution of glioblastoma.

Intermittent Hypoxic-Hyperoxic Exposures Effects in Patients with Metabolic Syndrome: Correction of Cardiovascular and Metabolic Profile.

The aim of this study was to evaluate efficacy and applicability of the "intermittent hypoxic-hyperoxic exposures at rest" (IHHE) protocol as an adjuvant method for metabolic syndrome (MS) cardiometabolic components. A prospective, single-center, randomized controlled clinical study was conducted on 65 patients with MS subject to optimal pharmacotherapy, who were randomly allocated to IHHE or control (CON) groups. The IHHE group completed a 3-week, 5 days/week program of IHHE, each treatment session lasting for 45 min. The CON group followed the same protocol, but was breathing room air through a facial mask instead. The data were collected 2 days before, and at day 2 after the 3-week intervention. As the primary endpoints, systolic (SBP) and diastolic (DBP) blood pressure at rest, as well as arterial stiffness and hepatic tissue elasticity parameters, were selected. After the trial, the IHHE group had a significant decrease in SBP and DBP (Cohen's d = 1.15 and 0.7, p < 0.001), which became significantly lower (p < 0.001) than in CON. We have failed to detect any pre-post IHHE changes in the arterial stiffness parameters (judging by the Cohen's d), but after the intervention, cardio-ankle vascular indexes (RCAVI and LCAVI) were significantly lowered in the IHHE group as compared with the CON. The IHHE group demonstrated a medium effect (0.68; 0.69 and 0.71 Cohen's d) in pre-post decrease of Total Cholesterol (p = 0.04), LDL (p = 0.03), and Liver Steatosis (p = 0.025). In addition, the IHHE group patients demonstrated a statistically significant decrease in pre-post differences (deltas) of RCAVI, LCAVI, all antropometric indices, NTproBNP, Liver Fibrosis, and Steatosis indices, TC, LDL, ALT, and AST in comparison with CON (p = 0.001). The pre-post shifts in SBP, DBP, and HR were significantly correlated with the reduction degree in arterial stiffness (ΔRCAVI, ΔLCAVI), liver fibrosis and steatosis severity (ΔLFibr, ΔLS), anthropometric parameters, liver enzymes, and lipid metabolism in the IHHE group only. Our results suggested that IHHE is a safe, well-tolerated intervention which could be an effective adjuvant therapy in treatment and secondary prevention of atherosclerosis, obesity, and other components of MS that improve the arterial stiffness lipid profile and liver functional state in MS patients.

Remote Screening for Atrial Fibrillation by a Federal Cardiac Monitoring System in Primary Care Patients in Russia: Results from the Prospective Interventional Multicenter FECAS-AFS Study.

Background: Screening for atrial fibrillation has the potential to significantly reduce cardiovascular morbidity and mortality. However, questions in regard to how to screen, on whom to screen, and the optimal setting of screening remain unanswered. Objective: To assess the applicability of a federal cardiac monitoring for atrial fibrillation (AF) screening and remote heart rhythm monitoring in patients at high cardiovascular risk in a mixed urban and rural population in Russia. Methods: This is a prospective multicenter cohort study including 3249 individuals with high cardiovascular risk (mean age 56 ± 12.8 years) from the larger Moscow region who were screened for AF using a smartphone-case based single-lead ECG monitor over a period of 18 month. The endpoints were considered as number of newly diagnosed AF; mean time to diagnosis; number of patients for the first time assigned to anticoagulation therapy; frequency of adverse events. Results: A trial fibrillation was diagnosed in 126 patients, 36 of them for the first time. The mean time to diagnosis was 3 ± 2 days. Of 36 patients, the CHA2DS2-VASc score was ≥1 in 34 cases, ≥2 in 29 cases. Anticoagulant therapy was first induced in 31 patients. One death in newly diagnosed group and two deaths in chronic group were registered. There were a total of eight hospitalizations: one in newly diagnosed and seven in chronic AF patients. Conclusion: Our results indicate that a Federal AF screening system in patients at high cardiovascular risk by using a smartphone-case based single lead ECG which is supported by centrally located ECG specialist and central data management is feasible and reliable when performed in a mixed urban and rural area. Further studies are needed to evaluate the full potential of this approach.

Bladder filling technique to prevent complications of the urinary system during placenta accrete surgery.

Placenta accrete spectrum (PAS) disorders are significant life-threatening nosology due to increased maternal morbidity and mortality in this condition. All surgical interventions in PAS can be accompanied by a high percentage of massive obstetric bleeding and a high frequency of urological complications, such as injuries of the ureter and bladder. To evaluate the effectiveness of the bladder filling technique during cesarean section and metroplasty in case of PAS we analyzed 41 women, that were delivered in Regional Perinatal Center (Rostov-on-Don, Russia) in the period from 2015 to 2018. Group I included 22 pregnant women who underwent a cesarean section followed by metroplasty using the method of intraoperative filling of the bladder with physiological saline. Group II (n = 19) underwent cesarean section with metroplasty without filling the bladder. In group I, one woman had a bladder injury, in group II -6 women, which is statistically significantly more often (p < .05). The total blood loss in group I (M ± σ) was 2177.8 ± 114.9 ml and was statistically significantly less (p < .05) compared with blood loss in group II -2545.7 ± 158.8 ml. Duration of surgery in group I (M ± σ) was 2-hour 45 ± 7.1 min; in group II -3-hour 31 ± 4.1 min. Thus, using the method of filling the bladder with physiological saline and mobilizing the bladder during cesarean section surgery with metroplasty in patients with PAS can reduce the frequency of bladder injury, the volume of intraoperative blood loss and duration of surgery.

Multifarious Trajectories in Plant-Based Ethnoveterinary Knowledge in Northern and Southern Eastern Europe.

Over the last century in the European context, animal production has been transformed by the dynamics of centralization and decentralization due to political and economic factors. These processes have influenced knowledge related to healing and ensuring the welfare of domestic animals. Therefore, our study aimed to document and compare current and past ethnoveterinary practices, and to identify trajectories in ethnoveterinary knowledge in study regions from both northern and southern Eastern Europe. In the summers of 2018 and 2019, we conducted 476 interviews, recording the use of 94 plant taxa, 67 of which were wild and 24 were cultivated. We documented 452 use reports, 24 of which were related to the improvement of the quality or quantity of meat and milk, while the other 428 involved ethnoveterinary practices for treating 10 domestic animal taxa. Cattle were the most mentioned target of ethnoveterinary treatments across all the study areas, representing about 70% of all use reports. Only four plant species were reported in five or more countries (Artemisia absinthium, Hypericum spp., Linum usitatissimum, Quercus robur). The four study regions located in Northern and Southern Eastern Europe did not present similar ethnoveterinary knowledge trajectories. Bukovinian mountain areas appeared to hold a living reservoir of ethnoveterinary knowledge, unlike the other regions. Setomaa (especially Estonian Setomaa) and Dzukija showed an erosion of ethnoveterinary knowledge with many uses reported in the past but no longer in use. The current richness of ethnoveterinary knowledge reported in Bukovina could have been developed and maintained through its peculiar geographical location in the Carpathian Mountains and fostered by the intrinsic relationship between the mountains and local pastoralists and by its unbroken continuity of management even during the Soviet era. Finally, our results show some patterns common to several countries and to the veterinary medicine promoted during the time of the Soviet Union. However, the Soviet Union and its centralized animal breeding system, resulted in a decline of ethnoveterinary knowledge as highly specialized veterinary doctors worked in almost every village. Future research should examine the complex networks of sources from where farmers derive their ethnoveterinary knowledge.

Effect of liraglutide on microcirculation in rat model with absolute insulin deficiency.

INTRODUCTION: The investigations of angiotropic effects of liraglutide are an issue of significant scientific and practical interest. The successful application of liraglutide has been shown in glycemic control in patients with the type 2 diabetes mellitus (DM), but the effect of liraglutide in patients with type 1 DM has not been completely studied yet in clinical practice. Therefore, the present study is aimed to investigate the effect of liraglutide which is agonist of glucagon-like peptide-1 receptors, on microcirculation in white outbred rats with the alloxan-induced diabetes. MATERIALS AND METHODS: The study was performed with 70 white outbred rats, divided into 4 groups: 1) control group (intact animals (Control)); 2) comparison group (diabetes mellitus (DM)) - animals with the alloxan-induced diabetes; 3) experimental group no. 1 (liraglutide low dose (LLD)) - animals with the alloxan-induced diabetes, which were injected by liraglutide at dosage of 0.2 mg/kg of animal weight per a day; 4) experimental group no. 2 (liraglutide high dose (LHD)) - animals with the alloxan-induced diabetes, which were injected by liraglutide at dosage of 0.4 mg/kg of animal weight per a day. The carbohydrate metabolism disorders, the microcirculation of posterior paw skin, as well as the concentration of catecholamines and markers of endothelial alteration in blood were estimated at the 42nd day of the experiment in the comparison and experimental groups. RESULTS: It was found that the correction of carbohydrate metabolism by liraglutide is succeeded by the normalization of skin perfusion of posterior paw skin of the experimental animals. Recovery of microcirculation is associated with a decrease in vascular tone and stimulation of endothelium-dependent vasodilation, caused by simultaneous decrease of catecholamines, endothelin-1 and asymmetric dimethylarginine (ADMA) concentrations in blood serum. At the same time, the administration of liraglutide on the background of insulin-deficiency results in decrease of endothelial cell alteration markers concentration in blood, such as sE-selectin, syndecan-1, and vascular endothelial growth factor (VEGF). CONCLUSION: Administration of liraglutide leads to the normalization of the carbohydrate metabolism simultaneously with the correction of microcirculation in rats with the absolute insulin deficiency. The demonstrated recovery of microcirculation by liraglutide, which represents an analogue of glucagon-like peptide-1, provides new prospects for its approval as a potential drug for pathogenetic correction of microcirculatory disorders in patients with the type 1 DM.

Cuffless Blood Pressure Measurement Using a Smartphone-Case Based ECG Monitor with Photoplethysmography in Hypertensive Patients.

The availability of simple, accurate, and affordable cuffless blood pressure (BP) devices has the potential to greatly increase the compliance with measurement recommendations and the utilization of BP measurements for BP telemonitoring. The aim of this study is to evaluate the correlation between findings from routine BP measurements using a conventional sphygmomanometer with the results from a portable ECG monitor combined with photoplethysmography (PPG) for pulse wave registration in patients with arterial hypertension. METHODS: The study included 500 patients aged 32-88 years (mean 64 ± 7.9 years). Mean values from three routine BP measurements by a sphygmomanometer with cuff were selected for comparison; within one minute after the last measurement, an electrocardiogram (ECG) was recorded for 3 min in the standard lead I using a smartphone-case based single-channel ECG monitor (CardioQVARK®-limited responsibility company "L-CARD", Moscow, Russia) simultaneously with a PPG pulse wave recording. Using a combination of the heart signal with the PPG, levels of systolic and diastolic BP were determined based on machine learning using a previously developed and validated algorithm and were compared with sphygmomanometer results. RESULTS: According to the Bland-Altman analysis, SD for systolic BP was 3.63, and bias was 0.32 for systolic BP. SD was 2.95 and bias was 0.61 for diastolic BP. The correlation between the results from the sphygmomanometer and the cuffless method was 0.89 (p = 0.001) for systolic and 0.87 (p = 0.002) for diastolic BP. CONCLUSION: Blood pressure measurements on a smartphone-case without a cuff are encouraging. However, further research is needed to improve the accuracy and reliability of clinical use in the majority of patients.

A review of Pseudachorutes Tullberg, 1871 (Collembola, Neanuridae) from the East Asia, with description of six new species.

A review of the Pseudachorutes fauna of the East Asia was performed, mainly based on fresh material from forest ecosystems of the Russian Far East and some adjoining regions. Six new species of the genus, namely P. aleksandrae sp. nov., P. armatus sp. nov., P. minimus sp. nov., P. variabilis sp. nov., P. concinnus sp. nov. and P. morulifer sp. nov., are described and extensive remarks on further six congeners, i.e. P. andrei Weiner Najt, P. hitakamiensis Tamura, P. isawaensis Tamura, P. kangchenjungae Yosii, P. longisetis Yosii and P. polychaetosus Gao Palacios-Vargas, previously known from the studied region, are given. Pseudachorutes conicus Lee Kim and P. sibiricus Rusek, are considered as probable junior synonyms of P. longisetis and P. andrei, respectively. Pseudachorutes boerneri SchÓ§tt is recorded for the first time in the eastern Palaearctic and redescribed based on materials from Yakutia, Khabarovsk Territory and Southern Primor'e. A regional key to the mentioned species and a summarizing table of diagnostic characters of all regional congeners are also provided.

Gaining momentum: Popularization of Epilobium angustifolium as food and recreational tea on the Eastern edge of Europe.

The local use of wild food plants represents a reservoir for the biocultural diversity of human diet and is therefore being extensively studied; yet the effects of the introduction of novel uses into specific biocultural conditions have been little researched. Rosebay willowherb Epilobium angustifolium L. has been intensively promoted in Europe since the mid-18th century. The expert recommendations did not provide any links to local uses thus raising the question of the legitimacy and diffusion of its food use in modern times. To understand if and to what extent those recommendations have influenced local uses, we compared them with the results of our ethnobotanical field study and the ethnographic literature in Russia, Finland, Estonia, Latvia, Lithuania, Belarus and Ukraine. Of the 599 people interviewed, nine used E. angustifolium as a food and 59 as a recreational tea. Thirty-four of those who claimed to use E. angustifolium lived in two regions of Russia. The majority of the recorded tea uses were of recent origin, following a popular trend. Few food uses of E. angustifolium were recorded in Finland, where a trend towards culinary experimentation coincides with a general trend toward the consumption of healthy wild food; yet these uses are difficult to maintain due to the problems in recognizing the plant during its early stages of growth. The popularization of E. angustifolium as a food had more effect in times of hardship, when it was seen as a means of survival and its promotion was advocated. The translation error repeatedly appeared in botanical and later popular literature, whose authors did not clearly differentiate at that time between local uses and suggestions.

Inventing a herbal tradition: The complex roots of the current popularity of Epilobium angustifolium in Eastern Europe.

ETHNOPHARMACOLOGICAL RELEVANCE: Currently various scientific and popular sources provide a wide spectrum of ethnopharmacological information on many plants, yet the sources of that information, as well as the information itself, are often not clear, potentially resulting in the erroneous use of plants among lay people or even in official medicine. Our field studies in seven countries on the Eastern edge of Europe have revealed an unusual increase in the medicinal use of Epilobium angustifolium L., especially in Estonia, where the majority of uses were specifically related to "men's problems". THE AIM OF THE CURRENT WORK IS: to understand the recent and sudden increase in the interest in the use of E. angustifolium in Estonia; to evaluate the extent of documented traditional use of E. angustifolium among sources of knowledge considered traditional; to track different sources describing (or attributed as describing) the benefits of E. angustifolium; and to detect direct and indirect influences of the written sources on the currently documented local uses of E. angustifolium on the Eastern edge of Europe. MATERIALS AND METHODS: In this study we used a variety of methods: semi-structured interviews with 599 people in 7 countries, historical data analysis and historical ethnopharmacological source analysis. We researched historical and archival sources, and academic and popular literature published on the medicinal use of E. angustifolium in the regions of our field sites as well as internationally, paying close attention to the literature that might have directly or indirectly contributed to the popularity of E. angustifolium at different times in history. RESULTS: Our results show that the sudden and recent popularity in the medical use of E. angustifolium in Estonia has been caused by local popular authors with academic medical backgrounds, relying simultaneously on "western" and Russian sources. While Russian sources have propagated (partially unpublished) results from the 1930s, "western" sources are scientific insights derived from the popularization of other Epilobium species by Austrian herbalist Maria Treben. The information Treben disseminated could have been originated from a previous peak in popularity of E. angustifolium in USA in the second half of the 19th century, caused in turn by misinterpretation of ancient herbals. The traditional uses of E. angustifolium were related to wounds and skin diseases, fever, pain (headache, sore throat, childbirth), and abdominal-related problems (constipation, stomach ache) and intestinal bleeding. Few more uses were based on the similarity principle. The main theme, however, is the fragmentation of use and its lack of consistency apart from wounds and skin diseases. CONCLUSIONS: Historical ethnobotanical investigations could help to avoid creating repeating waves of popularity of plants that have already been tried for certain diseases and later abandoned as not fully effective. There is, of course, a chance that E. angustifolium could also finally be proven to be clinically safe and cost-effective for treating benign prostatic hyperplasia, but this has not yet happened despite recent intensive research. Documented traditional use would suggest investigating the dermatological, intestinal anti-hemorrhagic and pain inhibiting properties of this plant, if any.

Phonetic Realisation and Phonemic Categorisation of the Final Reduced Corner Vowels in the Finnic Languages of Ingria.

Individual variability in sound change was explored at three stages of final vowel reduction and loss in the endangered Finnic varieties of Ingria (subdialects of Ingrian, Votic and Ingrian Finnish). The correlation between the realisation of reduced vowels and their phonemic categorisation by speakers was studied. The correlated results showed that if V was pronounced >70%, its starting loss was not yet perceived, apart from certain frequent elements, but after >70% loss, V was not perceived any more. A split of 50/50 between V and loss in production correlated with the same split in categorisation. At the beginning of a sound change, production is, therefore, more innovative, but after reanalysis, categorisation becomes more innovative and leads the change. The vowel a was the most innovative in terms of loss, u/o were the most conservative, and i was in the middle, while consonantal palatalisation was more salient than labialisation. These differences are based on acoustics, articulation and perception.

Trends and Prospects of Plant Proteases in Therapeutics.

The main function of proteases in any living organism is the cleavage of proteins resulting in the degradation of damaged, misfolded and potentially harmful proteins and therefore providing the cell with amino acids essential for the synthesis of new proteins. Besides this main function, proteases may play an important role as signal molecules and participate in numerous protein cascades to maintain the vital processes of an organism. Plant proteases are no exception to this rule. Moreover, in contrast to humanencoded enzymes, many plant proteases possess exceptional features such as higher stability, unique substrate specificity and a wide pH range for enzymatic activity. These valuable features make plant-derived proteolytic enzymes suitable for many biomedical applications, and furthermore, the plants can serve as factories for protein production. Plant proteases are already applied in the treatment of several pathological conditions in the human organism. Some of the enzymes possess antitumour, antibacterial and antifungal activity. The collagenolytic activity of plant proteases determines important medical applications such as the healing of wounds and burn debridement. Plant proteases may affect blood coagulation processes and can be applied in the treatment of digestive disorders. The present review summarizes recent advances and possible applications for plant proteases in biomedicine, and proposes further development of plant-derived proteolytic enzymes in the biotechnology and pharmaceutical industries.

Collagenolytic Enzymes and their Applications in Biomedicine.

Nowadays, enzymatic therapy is a very promising line of treatment for many different diseases. There is a group of disorders and conditions, caused by fibrotic and scar processes and associated with the excessive accumulation of collagen that needs to be catabolized to normalize the connective tissue content. The human body normally synthesizes special extracellular enzymes, matrix metalloproteases (MMPs) by itself. These enzymes can cleave components of extracellular matrix (ECM) and different types of collagen and thus maintain the balance of the connective tissue components. MMPs are multifunctional enzymes and are involved in a variety of organism processes. However, under pathological conditions, the function of MMPs is not sufficient, and these enzymes fail to deal with disease. Thus, medical intervention is required. Enzymatic therapy is a very effective way of treating such collagen-associated conditions. It involves the application of exogenous collagenolytic enzymes that catabolize excessive collagen at the affected site and lead to the successful elimination of disease. Such collagenolytic enzymes are synthesized by many organisms: bacteria, animals (especially marine organisms), plants and fungi. The most studied and commercially available are collagenases from Clostridium histolyticum and from the pancreas of the crab Paralithodes camtschatica, due to their ability to effectively hydrolyse human collagen without affecting other tissues, and their wide pH ranges of collagenolytic activity. In the present review, we summarize not only the data concerning existing collagenase-based medications and their applications in different collagen-related diseases and conditions, but we also propose collagenases from different sources for their potential application in enzymatic therapy.

Isotomidae of Japan and the Asiatic part of Russia. I. Folsomia 'inoculata' group.

The paper considers blind species of the genus Folsomia having two pairs of macrosetae on both meso- and metathorax and united in so-called 'inoculata' group, which is given a new, more laconic definition. Morphological characters important in the group's taxonomy are discussed and a further division into four subgroups is proposed. Eight new species, i.e., F. amurica Potapov & Kuznetsova, sp. n., F. breviseta Potapov & Kuznetsova, sp. n., F. calcarea Potapov, sp. n., F. imparis Potapov & Hasegawa, sp. n., F. laconica Potapov & Kuznetsova, sp. n., F. tertia Potapov, sp. n., F. trisensilla Potapov, sp. n., and F. tubulata Potapov & Babenko, sp. n., are described. F. hidakana Uchida & Tamura and F. inoculata Stach are redescribed basing on new material, for the latter species the Stach's individuals were also examined. A key to species of the group is given.

Microencapsulated Multicellular Tumor Spheroids as a Tool to Test Novel Anticancer Nanosized Drug Delivery Systems In Vitro.

In the study, MCF-7 human breast adenocarcinoma cells were used to study cytotoxicity of novel anticancer nanosized formulations, such as docetaxel-loaded nanoemulsion and liposomal formulation of a lipophilic methotrexate (MTX) prodrug. In vitro study of cytotoxicity was carried out in 2 models, namely using 3D in vitro model based on multicellular tumor spheroids (MTS) and 2D monolayer culture. MTS were generated by tumor cell cultivation within alginate-oligochitosan microcapsules. In the case of the monolayer culture, cell viability was found to be 25, 18 and 12% for the samples containing nanoemulsion at concentrations 20, 300 and 1000 nM of docetaxel, respectively, after 48 hs incubation. For MTS these values were higher, namely 33, 23 and 18%, respectively. Cytotoxicity of liposomal MTX prodrug-based formulation with final concentration of 1, 2, 10, 50, 100 and 1000 nM in both models was also studied. MTX liposomal formulation demonstrated lower cytotoxicity on MTS compared to intact MTX. Moreover, MTS were also more resistant to both liposomal formulation and intact MTX than the monolayer culture. Thus, at 1000 nM MTX in the liposomal form, cell viability in MTS was 1.4-fold higher than that in the monolayer culture. MTS could be proposed as a promising tool to test novel anticancer nanosized formulations in vitro.