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This review generalizes results of radioecological studies implemented in Armenia in a period from the 1960s till the early 2000s. Specificity of geographical position determines the maximum of global atmospheric radioactive fallout in high mountain regions of the country. Several facilities can potentially influence the radioecological situation of Armenia: the Armenian Nuclear Power Plant, a spent nuclear fuel repository and interim storage facility for radioactive waste. Runoff of many rivers of the basin of Araks and Kura (major water arteries of South Caucasus) originates on the territory of Armenia. The aforesaid peculiarities determine the key role of Armenia in transfer and distribution of radionuclides in the region. [ABSTRACT FROM AUTHOR]

Introduction: Upon their arrival in Europe, migrants and refugees often face multiple and highly complex stressors, which risk to have a lasting impact on their mental health. These may be related to traumatisation experiences before, during and after the migration process. Mental health promotion for vulnerable migrants and refugees (VMRs) has been a neglected area of intervention in transcultural psychiatry. Objectives: MyHealth project (2017-2020) is a European initiative that aims to develop/reinforce models of increased health (and mental health) care access and improved health (and mental health) services for VMRs. Methods: Four study sites (Barcelona, Berlin, Brno and Athens) were included. Through a participatory and social innovative approach and while engaging VMRs, professionals as well as the general public of the host community, an intercultural needs assessment took place followed by a tools' development phase and a pilot testing of specific tools identified. Results: Cross-country observations conclude that the coverage of social needs may primarily determine the mental wellbeing of VMRs, and their mental health state can consequently affect their help-seeking behaviours for any experienced physical condition. The prioritization of needs and barriers as viewed by professionals may differ from how are perceived by VMRs. This gap is conditioned by professionals' bias and the intercultural contact between VMRs and host community. To overcome such barriers, specific interventions were piloted at every site (e.g. cultural competence trainings, empowerment of female refugees). Conclusions: The context-specific results allow to draw outcomes, recommendations and lessons learnt which can inform the agendas of mental health promotion strategies and European mental health policies. [ABSTRACT FROM AUTHOR]

Abstract Background Smoking cessation counseling by health professionals has been effective in increasing cessation rates. However, little is known about smoking cessation training and practices in transition countries with high smoking prevalence such as Armenia. This study identified smoking-related attitudes and behavior of physicians and nurses in a 500-bed hospital in Yerevan, Armenia, the largest cancer hospital in the country, and explored barriers to their effective participation in smoking cessation interventions. Methods This study used mixed quantitative and qualitative methods. Trained interviewers conducted a survey with physicians and nurses using a 42-item self-administered questionnaire that assessed their smoking-related attitudes and behavior and smoking cessation counseling training. Four focus group discussions with hospital physicians and nurses explored barriers to effective smoking cessation interventions. The focus group sessions were audio-taped, transcribed, and analyzed. Results The survey response rate was 58.5% (93/159) for physicians and 72.2% (122/169) for nurses. Smoking prevalence was almost five times higher in physicians compared to nurses (31.2% vs. 6.6%, p Conclusions This study was the first to explore differences in smoking-related attitudes and behavior among hospital physicians and nurses in Yerevan, Armenia. The study found substantial behavioral and attitudinal differences in these two groups. The study revealed a critical need for integrating cessation counseling training into Armenia’s medical education. As nurses had more positive attitudes toward cessation counseling compared to physicians, and more often reported having cessation training, they are an untapped resource that could be more actively engaged in smoking cessation interventions in healthcare settings.

The research aimed to determine the spatiotemporal distribution patterns of radon activity concentrations in tap water of Yerevan city and assess radon-associated hazards using both deterministic and probabilistic approaches. This was accomplished by integrating one-year monitoring data of radon in water with water consumption habits among adult population clusters, which were identified through food frequency questionnaire in Yerevan. The study findings indicated variations in radon activity levels across administrative districts. The highest average activity concentrations were detected in Davtashen (7.07 Bq/L), while the lowest average was observed in Kanaker-Zeytun (1.57 Bq/L). The overall pattern of spatiotemporal variation during monitoring period revealed higher prevalence of radon in water in the northern and western parts of the city compared to the east and south, indicating different sources of drinking water. The radon-associated hazard assessment from water, using a deterministic approach (e.g., inhalation, ingestion, radon dissolution in blood, total effective dose), revealed values below the individual dose criterion (IDC) of 0.1 mSv/y. Monte Carlo simulation revealed a probability of exceeding IDC in specific water consumption-based groups. Residents of Yerevan who drink more than 3 L water daily with the highest observed activity concentration of 11.4 Bq/L, have an 86.26 % chance of exceeding IDC. Residents consuming 2.1 L water daily have a 7.02 % chance of exceeding IDC. The study highlights the importance of applied principles and methodologies for radon monitoring, particularly considering actual water consumption data and different risk assessment approaches. Considering the worst-case scenario results, it is recommended to keep tap water consumption up to 3 L per day, keeping the tap open longer to reduce radon levels. It also emphasizes the need for continued monitoring, given the variations in radon activity. The study provides valuable insights into radon exposure assessment, mitigation, and action plans in terms of water safety and public health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Annually, approximately 200 new ovarian cancer cases are diagnosed in Armenia, which is considered an upper-middle-income country. This study aimed to summarize the survival outcomes of patients with relapsed ovarian cancer in Armenia based on the type of recurrence, risk factors, and choice of systemic treatment., Methods: This retrospective case-control study included 228 patients with relapsed ovarian cancer from three different institutions., Results: The median age of the patients was 55. The median follow-up times from relapse and primary diagnosis were 21 and 48 months, respectively. The incidence of platinum-sensitive relapse was 81.6% (186), while platinum-resistant relapse was observed in only 18.4% (42) of patients. The median post-progression survival of the platinum-sensitive group compared to the platinum-resistant group was 54 vs. 25 months ( p < 0.001), respectively, while the median survival after relapse was 25 vs. 13 months, respectively; three- and five-year post-progression survival rates in these groups were 31.2% vs. 23.8%, and 15.1% vs. 9.5%, respectively ( p = 0.113)., Conclusions: Overall, despite new therapeutic approaches, ovarian cancer continues to be one of the deadly malignant diseases affecting women, especially in developing countries with a lack of resources, where chemotherapy remains the primary available systemic treatment for the majority of patients. Low survival rates demonstrate the urgent need for more research focused on this group of patients with poor outcomes.

The present study was performed to reveal the distribution patterns and spatiotemporal changes of radionuclides in the soil of the highest mountain of Armenia: Aragats Massif. In this regard, two surveys were implemented in 2016-2018 and 2021 with an altitudinal sampling strategy. The activities of radionuclides were determined by gamma spectrometry system with HPGe detector (CANBERRA). Correlation and linear regression analysis were applied to determine the dependence of radionuclides' distribution from altitude. Classical and robust statistical methods were used to assess the local background and baseline values. In two sampling profiles, the spatiotemporal variation of radionuclides was studied. A significant correlation was revealed between 137 Cs and altitude pointing to global atmospheric migration as a primary source of 137 Cs in Armenian environment. The predicted values of regression model revealed a 0.08-Bq/kg and 0.03-Bq/kg increase of 137 Cs in each m on average, for the old and new survey, respectively. The assessment of background activities of NOR (naturally occurring radionuclides) enables setting the local background for 226 Ra, 232 Th, and 40  K in soils of Aragats Massif: 831.3 ± 20.2 Bq/kg and 540.6 ± 18.3 Bq/kg for 40  K, 85.5 ± 3.1 Bq/kg and 27.7 ± 2.6 Bq/kg for 226 Ra, and 66.8 ± 3.2 and 46.4 ± 3.0 Bq/kg for 232 Th, respectively, for the years of 2016-2018 and 2021. 137 Cs baseline activity was estimated by altitude: 350 ± 3.7 Bq/kg and 108 ± 2.5 Bq/kg, respectively, for the years of 2016-2018 and 2021., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

MyHealth European project (2017-2020) was committed to elaborate on models to engage vulnerable migrants and refugees (VMR) in their health through community involvement. Low healthcare access and poor quality of healthcare services for VMR is a common reality in many European countries. The purpose of the present study, as part of MyHealth project, was the development of an agenda for actions and consequent recommendations to tackle the issue. A qualitative research design was applied at four study sites in Barcelona, Spain; Berlin, Germany; Brno, Czech Republic and Athens, Greece. The Metaplan® group discussions allowed the collection, organization and process of ideas and opinions elaborated in the collaborative groups. In total, 14 sessions took place: 4 with health and social professionals (n = 41) and 10 with VMR (n = 77). A participatory thematic analysis was performed at every session and overall for all sessions a thematic analysis synthesized the findings. The suggested actions were divided into two levels of recommendations: (i) local authorities at destination country-related, such as the investment in health professionals' cultural competences, and (ii) VMR-related, such as adaptation of help-seeking behavior patterns. Special attention was proposed to women survivors of violence and homeless minors. The study concluded to an agenda for action in Europe. We advocate for a public health paradigm shift where, while holding a bottom-up approach, VMR as well as professionals working with them are actively and meaningfully engaged in the decision-making process of access-enhancing and health promotion strategies in a given socio-cultural context., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Pediatric palliative care (PPC) is a priority to improve pediatric hematology oncology (PHO) care in Eurasia. However, there are limited regional opportunities for PPC education. We describe the adaptation and implementation of a bilingual end-user Education in Palliative and End-of-Life Care (EPEC)-Pediatrics course for PHO clinicians in Eurasia., Methods: Due to COVID-19, this course was delivered virtually, consisting of prerecorded, asynchronous lectures, and a bilingual workshop with interactive lectures and small group sessions. A pre-postcourse design was used to evaluate the knowledge acquisition of the participants including their knowledge alignment with World Health Organization (WHO) guidance, ideal timing of palliative care, and comfort in providing palliative care to their patients. Questions were mostly quantitative with multiple choice or Likert scale options, supplemented by free-text responses., Results: A total of 44 (76%) participants from 14 countries completed all components of the course including pre- and postcourse assessments. Participant alignment with WHO guidance improved from 75% in the pre- to 90% in the postcourse assessments (p < 0.001). After participation, 93% felt more confident controlling the suffering of children at the end of life, 91% felt more confident in prescribing opioids and managing pain, and 98% better understood how to hold difficult conversations with patients and families. Most participants (98%) stated that they will change their clinical practice based on the skills and knowledge gained in this course., Conclusions: We present a successful regional adaptation of the EPEC-Pediatrics curriculum, including novel delivery of course content via a virtual bilingual format. This course resulted in significant improvement in participant attitudes and knowledge of PPC along with an understanding of the ideal timing of palliative care consultation and comfort in providing PPC to children with cancer. We plan to incorporate participant feedback to improve the course and repeat it annually to improve access to high-quality palliative care education for PHO clinicians in Eurasia., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Airway mucociliary regeneration and function are key players for airway defense and are impaired in chronic obstructive pulmonary disease (COPD). Using transcriptome analysis in COPD-derived bronchial biopsies, we observed a positive correlation between cilia-related genes and microRNA-449 ( miR449) . In vitro, miR449 was strongly increased during airway epithelial mucociliary differentiation. In vivo, miR449 was upregulated during recovery from chemical or infective insults. miR0449 -/- mice (both alleles are deleted) showed impaired ciliated epithelial regeneration after naphthalene and Haemophilus influenzae exposure, accompanied by more intense inflammation and emphysematous manifestations of COPD. The latter occurred spontaneously in aged miR449 -/- mice. We identified Aurora kinase A and its effector target HDAC6 as key mediators in miR449 -regulated ciliary homeostasis and epithelial regeneration. Aurora kinase A is downregulated upon miR449 overexpression in vitro and upregulated in miR449 -/- mouse lungs. Accordingly, imaging studies showed profoundly altered cilia length and morphology accompanied by reduced mucociliary clearance. Pharmacological inhibition of HDAC6 rescued cilia length and coverage in miR449 -/- cells, consistent with its tubulin-deacetylating function. Altogether, our study establishes a link between miR449 , ciliary dysfunction, and COPD pathogenesis.

Spatial patterns and background ranges of naturally occurring radionuclides (NORs) (i.e. U-238, Th-232, K-40) and Cs-137 were studied in the urban soils of Yerevan, the capital city of Armenia. Multifractal Inverse Distance Weighting (MIDW) was used to generate and analyze distribution patterns of radionuclide activities. Based on Fourier transformation of radioactivity data, a spectral analysis was also applied to separate, where possible, background/baseline patterns from local anomalies: two ranges of background values were found to characterise the Yerevan territory. Specifically, in the south and south-east of Yerevan, the lower background ranges of U-238, Th-232 and K-40 comprised in the intervals 2.60-36.42 Bq/kg, 4.04-30.63 Bq/kg and 147.7-396.7 Bq/kg, respectively, were observed in association with the presence of sedimentary formations. In contrast, the higher ones were found, instead, in the central and northern parts of the city where andesite-basalt lavas and ignimbrite tuffs occur. Here, the background values rise to 142.4 Bq/kg, 138.76 Bq/kg and 1502 Bq/kg, respectively. As for the distribution of artificial Cs-137, its baseline levels in Yerevan seem to depend mostly on the global radioactive fallout and some local technogenic sources. Its distribution patterns partially differ from those of NORs. In the framework of this paper, Radium equivalent activity (RaEq), outdoor absorbed dose rate in air (ODRA) and annual effective dose equivalent (AEDEs) were also determined and mapped. They show a good coincidence of their spatial variations with those of NORs. The Monte Carlo simulation was used to assess excess lifetime cancer risk from a stochastic perspective. The related sensitivity analysis revealed that, among NORs, U-238 and Th-232 give the greatest contribution to the total variance (45.7% 42.8%, respectively). In comparison, K-40 has the lowest share (11.3%). Regarding Cs-137, a highly negligible contribution to the onset of health risks (accounting for 0.02%) was observed., (Copyright © 2022. Published by Elsevier Ltd.)

Purpose: The Assessing Doctors' Attitudes on Palliative Treatment study was conducted in 11 Eurasian countries to assess physician knowledge of and structural barriers to integration of palliative care into pediatric oncology. After publication, regional collaborators identified the need to disseminate country-specific study results locally and provide policy recommendations to inform stakeholders., Methods: The Assessing Doctors' Attitudes on Palliative Treatment report was developed with Eurasian and St Jude pediatric palliative care and oncology experts to summarize study findings and deliver country-level data to local stakeholders. In parallel, an assessment was developed to explore how regional collaborators intend to use the report to improve local advocacy and dissemination of research findings. The country report and assessment were translated to English, Russian, and Mongolian., Results: Country-specific two-page reports display study findings on pediatric palliative care education, access to pediatric palliative care services, and barriers to and timing of integration with cancer care, alongside clinical and policy recommendations. These reports were distributed to collaborators in 11 countries. Assessment results (N = 30) demonstrated that regional collaborators planned to distribute the report to institutional and government stakeholders, aiming to increase access to pediatric palliative care services (77%), establish a community-based palliative care network (70%), and increase opportunities for specialization (70%)., Conclusion: We describe the development of an evidence-based advocacy tool to inform local health and education policy in Eurasia. This summary report of study findings, translated to local languages and adapted to a broader audience, is currently used to advocate for greater access and quality of palliative care for children with cancer. This work may serve as the basis for future dissemination efforts of scientific research., Competing Interests: Anna VinitskyStock and Other Ownership Interests: BioMarin, MustangBio, Baxter, Johnson & Johnson/Janssen, West PharmaceuticalResearch Funding: SpringWorks Therapeutics (Inst) Catherine G. LamStock and Other Ownership Interests: PharmaJet (I)Consulting or Advisory Role: Sanofi (I), Jazz Pharmaceuticals (I), Servier (I), BTG (I), Shire (I), EUSA Pharma (I)Speakers' Bureau: Servier (I), Sanofi (I)No other potential conflicts of interest were reported.

Purpose: The article generalizes the evolution of radioecological studies conducted by female scientists in Armenia in the period of 1950-2020. Radioecological studies were launched in 1958, prior to the construction of the ANPP and major nuclear disasters., Conclusion: The obtained results allowed the revealing peculiarities of distribution and accumulation of naturally occurring radioactive materials (NORM) and artificial radionuclides in the natural environment, urban sites and industrial centers. Series of national environmental monitoring programs were designed in order to reveal the main migration pathways of NORM and artificial radionuclides, as well as the assessment of exposure to natural and induced radiation.

The present study was conducted in mountain regions of Armenia with the aim to assess the activity concentrations of natural K-40 and artificial Cs-137 in soil and mosses and reveal the distribution similarities and differences. Most widespread moss species and surface soils were sampled concurrently from eight mountain ridges and massifs by different altitudinal belts. Statistical analysis revealed significant differences and opposite characteristics for K-40 and Cs-137. In case of K-40 the activity concentrations decreased in mosses by altitude but with no significant correlation. The mean activity concentrations of K-40 in the soils of different altitudinal belts are close, nevertheless, the higher activity concentrations are common for soils derived from ingenious rocks. For Cs-137 in mosses, the correlation with altitude is statistically insignificant, but the altitudinal dependence is noticeable within separate ridges and massifs. A significant correlation was identified between Cs-137 in soil, altitude and precipitation rate. Studying natural K-40 and artificial Cs-137 radionuclides together yielded interesting contrasting results confirming the dissimilar behaviour of radionuclides with different origins in the environment., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Spatial pattern of naturally occurring radionuclides (NOR): 226 Ra, 232 Th, 40 K, and artificial 137 Cs was studied using soil samples of the multipurpose geochemical survey of the city of Yerevan, capital of Armenia. High purity Ge detector-based gamma spectrometry system was used for the determination of radionuclides activity concentrations in urban soils. A combination of compositional data analysis, geochemical mapping and radiological assessment were applied to reveal potential factors of technologically enhanced natural radioactivity and excess lifetime cancer risk for Yerevan's population due to NOR and artificial 137 Cs in the urban environment. Statistical methods with the geochemical mapping revealed the great contribution of soil-forming rocks to NOR distribution in urban soils. The spatial distribution of calculated radiological indices and dose rates levels follows the distribution patterns of NOR. The activity concentration of fallout radionuclide 137 Cs was within the range typical for the studied altitudes. Above baseline activity of 137 Cs was observed in the north-western and western part of the city that is in typical ranges of 137 Cs content in soil derived from global radioactive fallout. Urban soils of Yerevan were found radiologically safe, however, igneous rock derived soils are a sink of NOR and the main environmental source of continuous exposure to the residents. Values of excess lifetime cancer risk were higher than mean global value., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The early integration of palliative care significantly improves quality of life for children with cancer. However, cultural, structural, and socioeconomic barriers can delay the integration of palliative care into cancer care, particularly in low-income and middle-income countries. To date, little is known regarding the timing of and barriers to palliative care integration in Eurasia., Methods: The Assessing Doctors' Attitudes on Palliative Treatment (ADAPT) survey evaluates physician perceptions regarding palliative care integration into pediatric oncology in Eurasia. This evidence-based survey was adapted to the regional context; iteratively reviewed by US and regional panelists; and piloted in English, Russian, and Mongolian. After distribution to physicians caring for children with cancer, statistical analysis was complemented by qualitative analysis of open-ended responses., Results: A total of 424 physician responses were received from 11 countries in the Eurasian region. Study findings demonstrated wide variability in access to palliative care experts across countries (18%-96%), with the majority of providers (64%) reporting that the initial palliative care consultation typically occurs when curative options are no longer available. Providers desired an earlier initial palliative care consultation than what currently occurs in their setting (P < .001). Primary barriers to timely consultation included limited access to palliative care services and specialists, lack of physician education, and perceived family resistance., Conclusions: The current study is the first to identify physician perceptions of the delayed timing of palliative care integration into childhood cancer care and associated barriers in Eurasia. These findings will inform the development of targeted interventions to mitigate local structural and cultural barriers to access and facilitate earlier palliative care integration in the region., (© 2020 American Cancer Society.)

Kv10.1 (potassium voltage-gated channel subfamily H member 1, known as EAG1 or Ether-à-go-go 1), is a voltage-gated potassium channel, prevailingly expressed in the central nervous system. The aberrant expression of Kv10.1 is detected in over 70% of all human tumor tissues and correlates with poorer prognosis. In peripheral tissues, Kv10.1 is expressed almost exclusively during the G2/M phase of the cell cycle and regulates its progression-downregulation of Kv10.1 extends the duration of the G2/M phase both in cancer and healthy cells. Here, using biochemical and imaging techniques, such as live-cell measurements of microtubule growth and of cytosolic calcium, we elucidate the mechanisms of Kv10.1-mediated regulation at the G2/M phase. We show that Kv10.1 has a dual effect on mitotic microtubule dynamics. Through the functional interaction with ORAI1 (calcium release-activated calcium channel protein 1), it modulates cytosolic calcium oscillations, thereby changing microtubule behavior. The inhibition of either Kv10.1 or ORAI1 stabilizes the microtubules. In contrast, the knockdown of Kv10.1 increases the dynamicity of mitotic microtubules, resulting in a stronger spindle assembly checkpoint, greater mitotic spindle angle, and a decrease in lagging chromosomes. Understanding of Kv10.1-mediated modulation of the microtubule architecture will help to comprehend how cancer tissue benefits from the presence of Kv10.1, and thereby increase the efficacy and safety of Kv10.1-directed therapeutic strategies.

Background: The World Health Organization (WHO) advocates for early integration of palliative care for all children with life-threatening illness. Provider awareness and misperceptions, however, can impede this imperative. In the Eurasian region, little is known about physician knowledge and perspectives on palliative care., Methods: The Assessing Doctors' Attitudes on Palliative Treatment survey was developed as an evidence-based and culturally relevant assessment of physician perceptions on palliative care integration into childhood cancer care in Eurasia. Iteratively tested by American and Eurasian palliative care experts, the survey was culturally adapted, translated, and piloted in English, Russian, and Mongolian. The survey was distributed to physicians caring for children with cancer. Fifteen statements were scored in accordance with WHO guidelines to evaluate provider knowledge. The statistical analysis was complemented by a qualitative analysis of open-ended responses., Results: This study received 424 responses from 11 countries in Eurasia. The mean alignment between provider perspectives and WHO recommendations was 70% (range, 7%-100%). Significant independent predictors of higher alignment included country, prior palliative care education, and greater experience with patient death. Respondents primarily described palliative care as end-of-life care and symptom management. Two-thirds of respondents (67%) reported not feeling confident about delivering at least 1 component of palliative care., Conclusions: This is the first study assessing physician perspectives and knowledge of palliative care in Eurasia and reveals wide variability in alignment with WHO guidelines and limited confidence in providing palliative care. Study findings will inform targeted educational interventions, which must be tailored to the local political, economic, and cultural context., (© 2020 American Cancer Society.)

We describe a modification of an established method to determine microtubule dynamics in living cells. The protocol is based on the expression of a genetically encoded marker for the positive ends of microtubules (EB3 labelled with tdTomato fluorescent protein) and high-speed, high-resolution, live-cell imaging using spinning disk confocal microscopy. Cell cycle synchronization and increased density of microtubules are achieved by inhibiting centrosomal separation in mitotic cells, and analysis of growth is performed using open-source U-Track software. The use of a bright and red-shifted fluorescent protein, in combination with the lower laser power and reduced exposure time required for spinning disk microscopy reduce phototoxicity and the probability of light-induced artifacts. This allows for imaging a larger number of cells in the same preparation while maintaining the cells in a growth medium under standard culture conditions. Because the analysis is performed in a supervised automatic fashion, the results are statistically robust and reproducible.

Obtustatin, isolated from the Levantine Viper snake venom (Macrovipera lebetina obtusa -MLO), is the shortest known monomeric disintegrin shown to specifically inhibit the binding of the α1β1 integrin to collagen IV. Its oncostatic effect is due to the inhibition of angiogenesis, likely through α1β1 integrin inhibition in endothelial cells. To explore the therapeutic potential of obtustatin, we studied its effect in S-180 sarcoma-bearing mice model in vivo as well as in human dermal microvascular endothelial cells (HMVEC-D) in vitro, and tested anti-angiogenic activity in vivo using the chick embryo chorioallantoic membrane assay (CAM assay). Our in vivo results show that obtustatin inhibits tumour growth by 33%. The expression of vascular endothelial growth factor (VEGF) increased after treatment with obtustatin, but the level of expression of caspase 8 did not change. In addition, our results demonstrate that obtustatin inhibits FGF2-induced angiogenesis in the CAM assay. Our in vitro results show that obtustatin does not exhibit cytotoxic activity in HMVEC-D cells in comparison to in vivo results. Thus, our findings disclose that obtustatin might be a potential candidate for the treatment of sarcoma in vivo with low toxicity.

Soil radioactivity levels, dose rate and radiological health risk were assessed in metal mining centers of Armenia, at the towns of Kapan and Kajaran. Archive soil samples of the multipurpose soil surveys implemented in Kapan and Kajaran were used for estimation of total alpha and total beta activity levels using gas-less iMatic™ alpha/beta cօunting system (Canberra). Ten representative soil samples per town were randomly selected from different urban zones for naturally occurring radionuclide measurements (238U, 232Th, 40 K) using high purity germanium detector. Four radiological indices: radium equivalent activity, outdoor absorbed dose rate, annual effective dose equivalent and excess lifetime cancer risk were estimated based on naturally occurring radionuclide activity concentrations in soils. Results suggest that in Kapan the soil radioactivity, although enhanced by copper and gold-polymetallic mining, are not a significant risk factor to human health. In Kajaran, the soil radioactivity levels were above the background and world average values provided by UNSCEAR, but radionuclides originated in a natural geogenic source and not from mining activities. Generally, in this region no significant radiological risks were identified in relationship with molybdenum, copper, and gold-polymetallic ore mining., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: Cardio-ankle vascular index (CAVI), a parameter of arterial stiffness, has been increasingly used for cardiovascular risk estimation. Currently used CAVI reference values are derived from the Japanese population. It is not clear whether the same reference values can be used in the white population. The aim of the present study was to describe cardiovascular risk factors influencing CAVI and to establish CAVI reference values., Methods: A total of 2160 individuals randomly selected from the Brno city population aged 25-65 years were examined. Of these, 1347 patients were free from cardiovascular disease, nondiabetic and untreated by antihypertensive or lipid-lowering drugs, forming the reference value population. CAVI was measured using the VaSera VS-1000 device (Fukuda Denshi, Tokyo, Japan)., Results: At each blood pressure (BP) level, there was a quadratic association between CAVI and age, except for a linear association in the optimal BP group. Although there was no association between BP and CAVI in younger patients, there was a linear association between CAVI and BP after 40 years of age. Reference values by age and sex were established. In each age group, except for the male 60-65-year group, reference values in our population were lower than in the Japanese one with the difference ranging from -0.29 to 0.21 for men, and from -0.38 to -0.03 for women., Conclusion: This is the first study providing CAVI reference values in a random sample of the white population. Our results suggest that the currently used values slightly overestimate CAVI in younger white, possibly underestimating cardiovascular risk.

Objective: Manual office blood pressure (BP) is still recommended for diagnosing hypertension. However, its predictive value is decreased by errors in measurement technique and the white-coat effect. The errors can be eliminated by automated office BP (AOBP) measurement taking multiple readings with the participant resting quietly alone. Therefore, use of AOBP in clinical practice requires a threshold value for hypertension diagnosis. The aim of the present study was to determine an AOBP threshold corresponding to the 140/90 mmHg manual office BP using data from a large random population sample., Methods: In 2145 participants (mean age 47.3 ± 11.3 years) randomly selected from a Brno population aged 25-64 years, BP was measured using manual mercury and automated office sphygmomanometers., Results: Manual SBP (mean difference 6.39 ± 9.76 mmHg) and DBP (mean difference 2.50 ± 6.54 mmHg) were higher than the automated BP. According to polynomial regression, automated systole of 131.06 (95% confidence interval 130.43-131.70) and diastole of 85.43 (95% confidence interval 85.03-85.82) corresponded to the manual BP of 140/90 mmHg. Using this cut-off, the white-coat hypertension was present in 24% of participants with elevated manual BP, whereas 10% had masked hypertension and 11% masked uncontrolled hypertension. In individuals with masked uncontrolled hypertension, only AOBP was associated with the urinary albumin-creatinine ratio, whereas there was no association with manual BP., Conclusion: AOBP of 131/85 mmHg corresponds to the manual BP of 140/90 mmHg. This value may be used as a threshold for diagnosing hypertension using AOBP. However, outcome-driven studies are required to confirm this threshold.

Progression of cell cycle is associated with changes in K(+) channel expression and activity. In this study, we report that Kv10.1, a K(+) channel that increases cell proliferation and tumor growth, is regulated at the transcriptional level by the pRb/E2F1 pathway. De-repression of E2F1 by HPV-E7 oncoprotein leads to increased expression of Kv10.1. In proliferating cells, E2F1 transcription factor binds directly to the Kv10.1 promoter during (or close to) G2/M, resulting in transient expression of the channel. Importantly, this happens not only in cancer cells but also in non-transformed cells. Lack of Kv10.1 in both cancer and non-transformed cells resulted in prolonged G2/M phase, as indicated by phosphorylation of Cdk1 (Y15) and sustained pRb hyperphosphorylation. Our results strongly suggest that Kv10.1 expression is coupled to cell cycle progression and facilitates G2/M progression in both healthy and tumor cells.

Objective: To develop and test an intervention to reduce children's exposure to secondhand smoke (SHS) at homes in Yerevan, Armenia., Methods: A single-blind, randomized trial in 250 households with 2- to 6-year-old children tested an intensive intervention (counseling sessions, distribution of tailored educational brochures, demonstration of home air pollution, and 2 follow-up counseling telephone calls) against minimal intervention (distribution of standard leaflets). At baseline and 4-month follow-up, researchers conducted biomonitoring (children's hair) and surveys. The study used paired t tests, McNemar's test, and linear and logistic regression analyses., Results: After adjusting for baseline hair nicotine concentration, child's age and gender, the follow-up geometric mean (GM) of hair nicotine concentration in the intervention group was 17% lower than in the control group (P = .239). The GM of hair nicotine in the intervention group significantly decreased from 0.30 ng/mg to 0.23 ng/mg (P = .024), unlike in the control group. The follow-up survey revealed an increased proportion of households with smoking restrictions and decreased exposure of children to SHS in both groups. The adjusted odds of children's less-than-daily exposure to SHS at follow-up was 1.87 times higher in the intervention group than in the control group (P = .077). The GM of mothers' knowledge scores at follow-up was 10% higher in the intervention group than in the control group (P = .006)., Conclusions: Intensive intervention is effective in decreasing children's exposure to SHS through educating mothers and promoting smoking restrictions at home. However, superiority over minimal intervention to decrease children's exposure was not statistically significant.

Unlabelled: The aggregates of amyloid beta peptides (Aβs) are regarded as one of the main pathological hallmarks of Alzheimer's disease (AD). An imbalance between the rates of synthesis and clearance of Aβs is considered to be a possible cause for the onset of AD. Dipeptidyl peptidases II and IV (DPPII and DPPIV) are serine proteases removing N-terminal dipeptides from polypeptides and proteins with proline or alanine on the penultimate position. Alanine is an N-terminal penultimate residue in Аβs, and we presumed that DPPII and DPPIV could cleave them. The results of present in vitro research demonstrate for the first time the ability of DPPIV to truncate the commercial Aβ40 and Aβ42 peptides, to hinder the fibril formation by them and to participate in the disaggregation of preformed fibrils of these peptides. The increase of absorbance at 334 nm due to complex formation between primary amines with o-phtalaldehyde was used to show cleaving of Aβ40 and Aβ42. The time-dependent increase of the quantity of primary amines during incubation of peptides in the presence of DPPIV suggested their truncation by DPPIV, but not by DPPII. The parameters of the enzymatic breakdown by DPPIV were determined for Aβ40 (Km=37.5 μM, kcat/Km=1.7×10(3)M(-1)sec(-1)) and Aβ42 (Km=138.4 μM, kcat/Km=1.90×10(2)M(-1)sec(-1)). The aggregation-disaggregation of peptides was controlled by visualization on transmission electron microscope and by Thioflavin-T fluorescence on spectrofluorimeter and fluorescent microscope. DPPIV hindered the peptide aggregation/fibrillation during 3-4 days incubation in 20mM phosphate buffer, pH 7.4, 37°C by 50-80%. Ovalbumin, BSA and DPPII did not show this effect. In the presence of DPPIV, the preformed fibrils were disaggregated by 30-40%., Conclusion: for the first time it was shown that the Aβ40 and Aβ42 are substrates of DPPIV. DPPIV prohibits the fibrillation of peptides and promotes disaggregation of their preformed aggregates., (Copyright © 2013 Elsevier Ltd. All rights reserved.)