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Background: Disparities in school attendance exist for children with medical complexity (CMC) due to COVID-19. Longitudinal changes in family-reported school safety perceptions and predictors of full-time, in-person school attendance are unknown., Methods: This was a prospective, longitudinal cohort study with 3 survey waves (June 2021-June 2022) among English- and Spanish-speaking families of CMC aged 5 to 17 years and pre-pandemic school attendance. Changes in Health Belief Model perceptions and full-time in-person school attendance were estimated using multivariate generalized linear modeling with repeated measures., Results: Among 1601 respondents (52.9% of 3073 invited), 86.8% participated in all 3 surveys. School safety perceptions improved with time; however, perceived susceptibility to COVID-19 increased. Full-time in-person school attendance rose from 48.4% to 90.0% from wave 1 to 3 (p < .0001), and was associated with motivation, benefits, and cues. For example, families with low compared to high motivation for in-person attendance had 76% versus 98% predicted probability for child's school attendance, respectively at wave 3 (p < .0001)., Implications for School Health Policy, Practice, and Equity: Probability of full-time in-person school attendance was associated with several health belief model perceptions. School health policy and programs may benefit from promoting family motivation, benefits, and cues during future respiratory illness epidemics including COVID-19., Conclusions: In-person school attendance improved for CMC over time. Opportunities exist to continue optimizing in-person attendance and family-perceived safety for CMC at school., (© 2024 The Author(s). Journal of School Health published by Wiley Periodicals LLC on behalf of American School Health Association.)

Objective: School attendance by children with medical complexity (CMC) may be influenced by parent perceptions of their child's risk for coronavirus disease 2019 (COVID-19). The authors of this study aimed to quantify in-person school attendance and identify attendance predictors., Methods: From June to August 2021, surveys were collected from English- and Spanish-speaking parents of children aged 5 to 17 years with ≥1 complex chronic condition who received care at an academic tertiary children's hospital in the Midwestern United States and who attended school prepandemic. The outcome, in-person attendance, was defined dichotomously as any in-person attendance versus none. We evaluated parent-perceived school attendance benefits, barriers, motivation, and cues, COVID-19 severity and susceptibility using survey items derived from the health belief model (HBM). Latent HBM constructs were estimated with exploratory factor analysis. Associations between the outcome and the HBM were evaluated with multivariable logistic regression and structural equation models., Results: Among 1330 families (response rate 45%), 19% of CMC were not attending in-person school. Few demographic and clinical variables predicted school attendance. In adjusted models, family-perceived barriers, motivation, and cues predicted in-person attendance, whereas benefits, susceptibility, and severity did not. The predicted probability (95% confidence interval) of attendance ranged from 80% (70% to 87%) for high perceived barriers to 99% (95% to 99%) for low perceived barriers. Younger age (P <.01) and previous COVID-19 infection (P = .02) also predicted school attendance., Conclusions: Overall, 1 in 5 CMC did not attend school at the end of the 2020 to 2021 academic year. Family perceptions of schools' mitigation policies and encouragement of attendance may be promising avenues to address this disparity., (Copyright © 2023 by the American Academy of Pediatrics.)

Adolescent mental health and well-being have been adversely impacted by the COVID-19 pandemic. In this preregistered longitudinal study, we evaluated whether adolescents' well-being improved after playing the multiplayer serious game app Grow It! During the first lockdown (May-June 2020), 1282 Dutch adolescents played the Grow It! app (age = 16.67, SD = 3.07, 68% girls). During the second lockdown (December-May 2020 onwards), an independent cohort of 1871 adolescents participated (age = 18.66, SD = 3.70, 81% girls). Adolescents answered online questionnaires regarding affective and cognitive well-being, depressive symptoms, anxiety, and impact of COVID-19 at baseline. Three to six weeks later, the baseline questionnaire was repeated and user experience questions were asked (N = 462 and N = 733 for the first and second cohort). In both cohorts, affective and cognitive well-being increased after playing the Grow It! app (t = - 6.806, p < 0.001; t = - 6.77, p < 0.001; t = - 6.12, p < 0.001; t = - 5.93, p < 0.001; Cohen's d range 0.20-0.32). At the individual level, 41-53% of the adolescents increased in their affective or cognitive well-being. Adolescents with higher risk profiles (i.e., more depressive symptoms, lower atmosphere at home, and more COVID-19 impact) improved more strongly in their well-being. Positive user evaluations and app engagement were unrelated to changes in affective and cognitive well-being. This proof-of-concept study tentatively suggests that Grow It! supported adolescents during the pandemic., (© 2022. The Author(s).)

Adolescents are at increased risk for developing mental health problems. The Grow It! app is an mHealth intervention aimed at preventing mental health problems through improving coping by cognitive behavioral therapy (CBT)-inspired challenges as well as self-monitoring of emotions through Experience Sampling Methods (ESM). Yet, little is known about daily changes in well-being and coping during a stressful period, like the COVID-19 pandemic. The current study aimed to elucidate daily changes in positive and negative affect, and adaptive coping, and to better understand the within-person's mechanisms of the Grow It! app. The sample consisted of 12-25-year old Dutch adolescents in two independent cohorts (cohort 1: N = 476, Mage = 16.24, 76.1% female, 88.7% Dutch; cohort 2: N = 814, Mage = 18.45, 82.8% female, 97.2% Dutch). ESM were used to measure daily positive and negative affect and coping (cohort 1: 42 days, 210 assessments per person; cohort 2: 21 days, 105 assessments). The results showed that, on average, adolescents decreased in daily positive affect and adaptive coping, and increased in their experienced negative affect. A positive relation between adaptive coping and positive affect was found, although independent of the CBT-based challenges. Latent class analysis identified two heterogeneous trajectories for both positive and negative affect, indicating that the majority of participants with low to moderate-risk on developing mental health problems were likely to benefit from the Grow It! app., (© 2022. The Author(s).)

The REstarting Safe Education and Testing program for children with medical complexity was implemented in May 2021 at the University of Wisconsin to evaluate the feasibility of in-home rapid antigen COVID-19 testing among neurocognitively affected children. Parents or guardians administered BinaxNOW rapid antigen self-tests twice weekly for three months and changed to symptom and exposure testing or continued surveillance. In-home testing was feasible: nearly all (92.5%) expected tests were conducted. Symptomatic testing identified seven of nine COVID-19 cases. School safety perceptions were higher among those opting for symptom testing. Clinical Trials.gov identifier: NCT04895085. ( Am J Public Health . 2022;112(S9):S878-S882. https://doi.org/10.2105/AJPH.2022.306971).

Objective - to determine the sensitivity of Gardnerella vaginalis to fenticonazole to justify the feasibility of using this mainly antifungal drug for local treatment of BV in cases when it is a multifactorial disease caused by Gardnerella vaginalis and Candida spp. simultaneously.; We observed 98 women with infections of the urogenital tract at the ages of 20 to 49. At the first stage of the study, we analyzed the results of laboratory data on pathological discharge from the urogenital system of these patients. 36 (%) of the examined women had Gardnerella vaginalis in the vaginal discharge. At the second stage of the study, the sensitivity of Gardnerella vaginalis to fenticonazole was determined.; The resistance to fenticonazole was registered in 1 case (2.7%). In the remaining 35 patients Gardnerella vaginalis was not stable to fenticonazole. High sensitivity to this substance was found in 22 of them (61.2%). Respectively, low sensitivity was registered in 13 people from the observation group (36.1%).; Gardnerella vaginalis is the main constituent and a marker of bacterial vaginosis. The elimination of this very microorganism is of paramount importance for its treatment. In 35 studied patients (97.3%) Gardnerella vaginalis, which was isolated by culture from vaginal discharge, had sensitivity to fenticonazole. Moreover, in 22 of them (61.2%) the sensitivity was high, and low in 13 (36.1%). Candida spp. was found in 17 (47.1%) of 36 patients with bacterial vaginosis. It is appropriate to use fenticonazole as a means of local treatment during complex therapy of women with bacterial vaginosis that improves its compliance.

The aim of the work is to study the quantitative characteristics of gut microbiota (GM) in patients with arterial hypertension AH - residents of Ukraine in comparison with practically healthy individuals. 36 patients with AH stage II, 2-3 degrees against the background of normal body weight were examined. The control group consisted of 20 apparently healthy individuals. The examination included standard clinical, laboratory and instrumental methods. For determination of the quantitative composition of GM were used the method of polymerase chain reaction with hybridization-fluorescence detection of results in real time and the test system "COLONOFLOR-16 (biocenosis)" ("ALFALAB"). Statistical analysis of the results was carried out by standard methods using Microsoft Excel 17.0. The significant changes in GM quantitative characteristics were found in patients with AH (resident of Ukraine) in comparison with healthy individuals: a significant decrease in the number of Lactobacillus spp., Bifidobacterium spp. and Faecalibacterium prausnitzii. The deficiency of Lactobacillus spp., Bifidobacterium spp. and Faecalibacterium prausnitzii in patients with AH - residents of Ukraine may indicate the important role of GM disorders in the pathogenesis of hypertension.

Objectives: Throughout the COVID-19 pandemic, masking has been a widely used mitigation practice in kindergarten through 12th grade (K-12) school districts to limit within-school transmission. Prior studies attempting to quantify the impact of masking have assessed total cases within schools; however, the metric that more optimally defines effectiveness of mitigation practices is within-school transmission, or secondary cases. We estimated the impact of various masking practices on secondary transmission in a cohort of K-12 schools., Methods: We performed a multistate, prospective, observational, open cohort study from July 26, 2021 to December 13, 2021. Districts reported mitigation practices and weekly infection data. Districts that were able to perform contact tracing and adjudicate primary and secondary infections were eligible for inclusion. To estimate the impact of masking on secondary transmission, we used a quasi-Poisson regression model., Results: A total of 1 112 899 students and 157 069 staff attended 61 K-12 districts across 9 states that met inclusion criteria. The districts reported 40 601 primary and 3085 secondary infections. Six districts had optional masking policies, 9 had partial masking policies, and 46 had universal masking. In unadjusted analysis, districts that optionally masked throughout the study period had 3.6 times the rate of secondary transmission as universally masked districts; and for every 100 community-acquired cases, universally masked districts had 7.3 predicted secondary infections, whereas optionally masked districts had 26.4., Conclusions: Secondary transmission across the cohort was modest (<10% of total infections) and universal masking was associated with reduced secondary transmission compared with optional masking., (Copyright © 2022 by the American Academy of Pediatrics.)

Objectives: To establish statewide consensus priorities for safer in-person school for children with medical complexity (CMC) during the coronavirus disease 2019 (COVID-19) pandemic using a rapid, replicable, and transparent priority-setting method., Methods: We adapted the Child Health and Nutrition Research Initiative Method, which allows for crowdsourcing ideas from diverse stakeholders and engages technical experts in prioritizing these ideas using predefined scoring criteria. Crowdsourcing surveys solicited ideas from CMC families, school staff, clinicians and administrators through statewide distribution groups/listservs using the prompt: "It is safe for children with complex health issues and those around them (families, teachers, classmates, etc.) to go to school in-person during the COVID-19 pandemic if/when…" Ideas were aggregated and synthesized into a unique list of candidate priorities. Thirty-four experts then scored each candidate priority against 5 criteria (equity, impact on COVID-19, practicality, sustainability, and cost) using a 5-point Likert scale. Scores were weighted and predefined thresholds applied to identify consensus priorities., Results: From May to June 2021, 460 stakeholders contributed 1166 ideas resulting in 87 candidate priorities. After applying weighted expert scores, 10 consensus CMC-specific priorities exceeded predetermined thresholds. These priorities centered on integrating COVID-19 safety and respiratory action planning into individualized education plans, educating school communities about CMC's unique COVID-19 risks, using medical equipment safely, maintaining curricular flexibility, ensuring masking and vaccination, assigning seats during transportation, and availability of testing and medical staff at school., Conclusions: Priorities for CMC, identified by statewide stakeholders, complement and extend existing recommendations. These priorities can guide implementation efforts to support safer in-person education for CMC., Competing Interests: CONFLICT OF INTERESTS DISCLOSURES: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2022 by the American Academy of Pediatrics.)

The coronavirus disease 2019 (COVID-19) pandemic forced the suspension of in-person education in schools serving students in kindergarten through 12th grade (K-12) across the United States. As time passed, teachers, students, and parents struggled with remote education. With limited guidance at the federal level, physicians and school leaders across the country collaborated to develop local solutions for schools. This article describes the lessons learned from the development of 4 academic-community partnerships and collaboration among these partnerships to provide national leadership on managing COVID-19 mitigation in the K-12 environment. In addition, we describe a pathway forward for using academic-community partnerships to improve child health., (Copyright © 2022 by the American Academy of Pediatrics.)

Objectives: We evaluated the impact of distancing practices on secondary transmission of severe acute respiratory syndrome coronavirus 2 and the degree of sports-associated secondary transmission across a large diverse cohort of schools during spring 2021., Methods: Participating districts in North Carolina and Wisconsin and North Carolina charter schools offering in-person instruction between March 15, 2021 and June 25, 2021 reported on distancing policies, community- and school-acquired infections, quarantines, and infections associated with school-sponsored sports. We calculated the ratio of school-acquired to community-acquired infection, secondary attack rates, and the proportion of secondary transmission events associated with sports. To estimate the effect of distancing and bus practices on student secondary transmission, we used a quasi-Poisson regression model with the number of primary student cases as the denominator., Results: During the study period, 1 102 039 students and staff attended in-person instruction in 100 North Carolina school districts, 13 Wisconsin school districts, and 14 North Carolina charter schools. Students and staff had 7865 primary infections, 386 secondary infections, and 48 313 quarantines. For every 20 community-acquired infections, there was 1 within-school transmission event. Secondary transmissions associated with school sports composed 46% of secondary transmission events in middle and high schools. Relaxed distancing practices (<3 ft, 3 ft) and increased children per bus seat were not associated with increased relative risk of secondary transmission., Conclusions: With universal masking, in-person education was associated with low rates of secondary transmission, even with less stringent distancing and bus practices. Given the rates of sports-associated secondary transmission, additional mitigation may be warranted., (Copyright © 2022 by the American Academy of Pediatrics.)

We calculate the distribution probability of hexagonal six-site rings in the disordered state of a cubic or hexagonal ice lattice model with ice rules perfectly obeyed. The mean-field distribution obtained is in significant agreement with those, slightly different among them, obtained by Monte Carlo simulations of the cubic or hexagonal model. The results are discussed in connection with the equilibrium and non-equilibrium transition from disorder to ferroelectric proton order.

In review provides data on pathophysiological relationships of intestinal microbiota with body weight regulation in patients with abdominal obesity. In manuscript discusses the leading mechanisms by which the gut microbiota can contribute to obesity and metabolic diseases, analyzes its components, including gastrointestinal peptides, short-chain fatty acids, bile acids, farnesoid receptors, etc. Western diet high in salt, dysbiosis and endotoxemia can be powerful pro-inflammatory factors responsible for the development of insulin resistance and weight gain. It is promising to prescribe agonists of gastrointestinal peptides, probiotics and prebiotics, which in abdominal obesity are able to inhibit dysbiosis, regulate immune functions, and protect the organism from low-intensity chronic inflammation.

For more than 35 years after Chornobyl catastrophe, about 5 million people in Ukraine, Republic of Belarus and Russian Federation inhabit the territories that are residually contaminated with long-lived radionuclides such as 137 Cs, 90 Sr. The previous studies of the Reference Laboratory operating at RE Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology allowed specifying the effects of the protracted low dose irradiation on the state of the hematopoietic and lymphoid tissues resulting in the increased proportion of the B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma and acute myeloid leukemia among the patients referred from the contaminated areas of Ukraine. Since the beginning of 2020, these effects of radiation were superimposed by the factors associated with COVID-19 pandemic. SARS-CoV-2 infection is associated with the significant impact on hematopoiesis and immune system. Particular attention should be given to the role of such combined burden in the development of the immunodeficiency-associated lymphoid neoplasms. The extensive studies of the combined effects of low dose irradiation and COVID-19 within the large affected populations could be made a priority in future endeavors of epidemiologists and oncohematologists.

The 2017 revision of WHO Classification of tumors of hematopoietic and lymphoid tissues contains separate chapters on the immunodeficiency-associated lymphoproliferative disorders. In this mini-review, the brief description of pathological, immunophenotypical and clinical features of lymphoid neoplasms associated with primary immune disorders, HIV infection, those arising in post-transplant setting and other lymphoproliferative disorders (excluding those induced by radiation) is given. The heterogeneous spectrum of these lymphoid malignancies is specified by the nature of those factors that are capable to induce immune suppression or chronic antigenic stimulation of immune system. Taking into account the full swing of SARS-CoV-2 pandemic and our ignorance of the ability of this virus to induce the sustained stimulation of immune system, we could not exclude the high risk of autoimmune diseases and lymphoid neoplasms in the long-term post-pandemic period. In this context, the role of angiotensin-converting enzyme 2  as well as some recently reported cell receptors for SARS-CoV-2 cell entry should be considered as far as some of them (CD147, CD26) could be tumor-associated antigens.

Great attention has been paid to using biochar as soil conditioner and bio-accumulator. Nevertheless, biochar application in agriculture might cause a potential hazard to ecosystems, considering that toxic organic pollutants present in biochar may enter the environment. European Biochar Certificate (EBC) set certain criteria for biochar production. Achieving the EBC established values of the molar ratio of H/C org <0.7 and O/C org <0.4, does not ensure that biochar will not cause phytotoxicity. The results of root growth inhibition of Sinapis alba were in the range of 9% (eucalyptus wood biochar) to 82% (maize biochar). Phytotoxicity of biochar was possibly caused by the presence of water-soluble organic compounds. In total, 62 organic compounds were identified in the leachate from noncertified biochar and 35 organic compounds in the leachate from certified biochar. Biochar safety, in terms of the presence of organic compounds, can be recognised by the evaluation of the ratio of organic carbon (OC) and elemental carbon (EC). Biochar with the highest phytotoxicity showed the ratio between OC/EC > 0.1, inhibition of Sinapis alba <30% was observed with OC/EC < 0.02. To achieve Sinapis alba inhibition <20%, these parameters should be met: volatile matter (VM) <30%; concentration of OC < 4%; aromaticity ratio AL/AR < 0.35., (Copyright © 2020. Published by Elsevier B.V.)

Ordinary ice has a proton-disordered phase which is kinetically metastable, unable to reach, spontaneously, the ferroelectric (FE) ground state at low temperature where a residual Pauling entropy persists. Upon light doping with KOH at low temperature, the transition to FE ice takes place, but its microscopic mechanism still needs clarification. We introduce a lattice model based on dipolar interactions plus a competing, frustrating term that enforces the ice rule (IR). In the absence of IR-breaking defects, standard Monte Carlo (MC) simulation leaves this ice model stuck in a state of disordered proton ring configurations with the correct Pauling entropy. A replica exchange accelerated MC sampling strategy succeeds, without open path moves, interfaces, or off-lattice configurations, in equilibrating this defect-free ice, reaching its low-temperature FE order through a well-defined first-order phase transition. When proton vacancies mimicking the KOH impurities are planted into the IR-conserving lattice, they enable standard MC simulation to work, revealing the kinetics of evolution of ice from proton disorder to partial FE order below the transition temperature. Replacing ordinary nucleation, each impurity opens up a proton ring generating a linear string, an actual FE hydrogen bond wire that expands with time. Reminiscent of those described for spin ice, these impurity-induced strings are proposed to exist in doped water ice too, where IRs are even stronger. The emerging mechanism yields a dependence of the long-time FE order fraction upon dopant concentration, and upon quenching temperature, that compares favorably with that known in real-life KOH doped ice., Competing Interests: The authors declare no competing interest.

Lassa virus (LASV) is the causative agent of Lassa fever, an often-fatal hemorrhagic disease that is endemic in West Africa. Seven genetically distinct LASV lineages have been identified. As part of CEPI's (Coalition for Epidemic Preparedness Innovations) Lassa vaccine development program, we assessed the potential of the human immune system to mount cross-reactive and cross-protective humoral immune responses to antigens from the most prevalent LASV lineages, which are lineages II and III in Nigeria and lineage IV in Sierra Leone. IgG and IgM present in the blood of Lassa fever survivors from Nigeria or Sierra Leone exhibited substantial cross-reactivity for binding to LASV nucleoprotein and two engineered (linked and prefusion) versions of the glycoproteins (GP) of lineages II-IV. There was less cross-reactivity for the Zinc protein. Serum or plasma from Nigerian Lassa fever survivors neutralized LASV pseudoviruses expressing lineage II GP better than they neutralized lineage III or IV GP expressing pseudoviruses. Sierra Leonean survivors did not exhibit a lineage bias. Neutralization titres determined using LASV pseudovirus assays showed significant correlation with titres determined by plaque reduction with infectious LASV. These studies provide guidance for comparison of humoral immunity to LASV of distinct lineages following natural infection or immunization.

According to the modern concept, leukemic stem cells (LSC) in acute myeloid leukemia (AML) are distinct from the bulk of leukemic cells in bone marrow and peripheral blood of AML patients. Nevertheless, LSC are responsible for managing all the hierarchy of the bulk of leukemic blast populations. This mini-review provides brief information on the distinctive features of LSC and blast cells in cytologically recognized types of AML. The study of different phenotypes of LSC and blast cells in AML with the aid of up-to-date flow cytometric techniques is important both for the deep insight into the mechanisms of leukemogenesis and development of novel strategies of target therapy. The urgent need for extending the diagnostic panel of monoclonal antibodies used for diagnosing AML is beyond doubt.

The aim of research was to investigate the plasma microRNA (miR-133а) level in patients with essential arterial hypertension (EAH). A total of 45 patients with EAH 2-3 degrees aged 52.14 ± 8.25 years and 21 healthy individuals (control group) with comparable age and sex distributions. The following frequency of risk factors was revealed among the examined patients: overweight (53%), dyslipidaemia (73%), pre-diabetes (13%), asymptomatic hyperuricemia (29%); hypertension-mediated organ damage: increased arterial stiffness (27%), left ventricular hypertrophy (55%), atherosclerotic plaque in the carotid artery (40%), microalbuminuria (15%), moderate stage of chronic kidney disease (22%) and cardiovascular diseases: stable ischemic heart disease (11%) and heart failure with preserved ejection fraction of NYHA functional class I (18%). The plasma miR-133a level was determined by polymerase chain reaction using "CFX96 Touch" detection system (BioRad) and "TaqMan microRNA Assay" and "TaqMan® Universal PCR Master Mix" reagents (Thermo Fisher Scientific, USA). It has been established that in patients with EAH the plasma level of miR-133a was significantly lower than in practically healthy individuals (0,182 [0,102; 0,301] ), vs (0,382 [0,198; 0,474]), p <0.05). It has also been revealed a significant decrease in the level of miR-133a in the blood plasma in patients with such organs damage as LVH (0,133 [0,099;0,184]) in comparison with patients without LVH (0,238 [0,155; 0,410]), p <0.05) and also significantly lower than in healthy subjects in the control group (0,382 [0,198; 0,474]), p<0.05). There were no statistically significant differences in the plasma levels of miR-133a in the group of patients with EAH, depending on the presence of risk factors, other organ damage and cardiovascular diseases. The findings suggest the significant role of reducing of plasma levels of miR-133a in the pathogenesis of hypertension itself and in pathological remodeling of the heart.

Background: Rheumatoid arthritis (RA) is a complex, chronic autoimmune disease characterized by various inflammatory symptoms, including joint swelling, joint pain, and both structural and functional joint damage. The most commonly used animal model for studying RA is mice with collagen-induced arthritis (CIA); the wide use of this model is due primarily to many similarities with RA in human patients. Metabolomics is used increasingly in biological studies for diagnosing disease and for predicting and evaluating drug interventions, as a large number of disease-associated metabolites can be analyzed and interpreted from a biological perspective., Aim: To profile free amino acids and their biogenic metabolites in CIA mice plasma., Method: Ultra-high-performance liquid chromatography/tandem mass spectrometry coupled with multiple reaction monitoring (MRM) was used for metabolomics study., Results: Profile of 45 amine metabolites, including free amino acids and their biogenic metabolites in plasma was obtained from CIA mice. We found that the plasma levels of 20 amine metabolites were significantly decreased in the CIA group., Conclusion: The results suggest that a disordered amine response is linked to RA-associated muscle wasting and energy expenditure., (© 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

In urban environments airborne particulates (dust) must be managed to ensure that industry and community coexist in a mutually beneficial and sustainable manner. The composition of the dust is a function of the local environment and industry. In general, there is a view by many community members that a significant proportion of inhalable (PM 10 ) and respirable (PM 2.5 ) dust in these environments could be coal. Thus there is a need to have an analytical method that provides a quantitative analysis of the amount and size distribution of the different particulates that can be present in air samples. Australia's national research body, the Commonwealth Scientific and Industrial Research Organisation (CSIRO) has developed a Coal Grain Analysis (CGA) system that uses reflected light optical microscopy to provide a unique visual perspective, a qualitative feeling of the sample and quantitative information on the composition and size of the individual particles greater than 1 μm. Furthermore, semi-automated Optical Dust Marker software uses each individual particle's colour reflectance fingerprint to classify that particle. These markers can currently identify coal, combustion chars, iron, quartz/dark minerals, pyrite/bright materials and particulates of organic origin. This paper presents a case study performed using CGA to evaluate the dust composition and proportion of coal and other particulates and also their size distribution in samples collected in an urban area along a coal rail corridor in Newcastle (Australia). In coastal environments a significant proportion of dust can be water soluble (salt) particulates; the proportion of soluble particulates in those samples varied from 46% to 52.3%. The concentration of insoluble particles in samples varied from 5.9 to 15.5 μg m -3 in the PM 2.5-10 fraction and from 0.4 to 0.9 μg m -3 in the PM 1-2.5 fraction. All samples consisted predominantly of particles of organic origin (mostly plant and insect remains) - 55.3%-85.3% by mass. Dark material particles of mainly inorganic origin (low reflecting material, mainly stone dust, clay, soot, rubber and soil), combustion char and metal particles (rust and iron oxides) were present in lower concentrations - 0.0% to 19.9% by mass. The amount of coal in the water insoluble fraction of the samples ranged from 5.3% to 19.7% by mass with 2.9%-13.5% by mass of coal particles in the thoracic (2.5-10 μm) and 0.3%-1.2% by mass in the respirable (1-2.5 μm) size fraction., (Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.)

Since the cellulose used in the production of tetrapak is of very high quality, the char generated during pyrolysis should be influenced mainly by the pyrolysis temperature. This article aims to determine the chemical composition of biochar prepared at the temperatures of 400, 500, 600 and 700 °C and its environmental properties determined by the presence of organic compounds with toxicity and relatively high mobility in the environment. The analytical pyrolysis of char was used to identify the following groups of organic compounds: alkanes, cycloalkanes, alkenes, cycloalkenes, alkynes, alkadiens, ethers, alcohols, nitrogen compounds, nitrils, ketones and aldehydes, compounds containing phenols, furans, benzofurans, PAHs (polycyclic aromatic hydrocarbons), carboxylic acids, compounds containing benzenes and markers indicative of the presence of synthetic polymers (polyethylene layers, a part of dyes, antioxidants, stabilizers), and fragments of cellulose. Concerning the use of char as a soil conditioner, its ecotoxicity was monitored (Folsomia candida) by monitoring its addition to the artificial soil (char addition: 0.5, 1, 2.5, 5, 10, 15, 20, 50 and 100%). The lowest reproduction inhibition of Folsomia candida is caused by biochar prepared at the temperature of 400 °C and 700 °C, but it is not suitable for the agricultural application, the concentration of PAHs is three times higher than the EBC limit. Low-density polyethylene which is present in the aseptic box in concentration of 6%, can degrade biochar so that it cannot be used as a soil amendment. The results of the char analyses show that the pyrolysis temperature is a decisive factor in the applicability of biochar., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The peptide apelin has antihypertensive and antidiabetic properties, but its role in the processes of cardiac remodeling in patients with hypertension and type 2 diabetes (T2D) is poorly understood., Aim: The aim of the study was to investigate apelin levels in patients with hyper-tension and T2D and to determine its relations to heart structural parameters and types of cardiac remodeling., Materials and Methods: We examined 63 patients with hypertension and T2D. Investigation complex included physical examination, standard transthoracic echocardiography and determination of apelin serum levels by ELISA. Control group consisted of 16 volunteers., Results: The apelin levels in patients were significantly lower than those in volunteers (0.882(0.788; 0.924) ng/ml versus 1.097(0.944; 1.171) ng/ml, p<0.001). Negative correlation relations of apelin with septal wall thickness (r=-0.50, p<0.001), posterior wall thickness (r=-0.46, p<0.001), left ventricle (LV) mass (r=-0.39, p<0.01), LV mass index (r=-0.42, p<0.001) and left atrium size (r=-0.45, p<0.001) were found. In patients with concentric remodeling of LV apelin levels were 0.918 (0.892; 0.984) ng/ml, with concentric LV hypertrophy - 0.855(0.722; 0.899) ng/ml, with eccentric LV hypertrophy - 0.884(0.856; 0.929) ng/ml (p<0.05, p<0.001, p<0.001 versus control, respectively). Patients with concentric LV hypertrophy had significantly lower apelin levels than patients with concentric remodeling of LV (p<0.05)., Conclusion: Patients with hypertension and T2D have significant reduction of apelin blood levels, which is accompanied by cardiac remodeling development primarily concentric LV hypertrophy and have negative correlation relations of apelin with heart structural parameters that characterize LV remodeling and left atrium size.

The management of an increasing amount of municipal waste via incineration has been gaining traction. Fly ash as a by-product of incineration of municipal solid waste is considered a hazardous waste due to the elevated content of various elements. The enrichment and distribution of 24 elements in fly ash from three wastes incinerators were evaluated. Two coarse (>100 μm and <100 μm) and five sub-sieve (12-16, 16-23, 23-34, 34-49, and 49-100 μm) particle size fractions separated on a cyclosizer system were analyzed. An enhancement in the enrichment factor was observed in all samples for the majority of elements in >100 μm range compared with <100 μm range. The enrichment factor of individual elements varied considerably within the samples as well as the sub-sieve particle size ranges. These variations were attributed primarily to: (i) the vaporization and condensation mechanisms, (ii) the different design of incineration plants, (iii) incineration properties, (iv) the type of material being incinerated, and (v) the affinity of elements., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Based on the traditional Chinese medicine theory, the Chinese pharmacopeia assigns a therapeutic description of "taste" to all herbs; thus, an herb's "taste" is valued in traditional Chinese medicine as a major ethnopharmacological category and reflects the herb's therapeutic properties. These properties guide the practitioner with respect to preparing a specific herbal formula in order to provide each patient with a personalized intervention. The key challenge in evidence-based medicine is to characterize herbal therapeutic properties from a multi-target, multi-dimensional systems pharmacology perspective. Here, we used delayed luminescence (DL, the slowly decaying emission of photons following excitation with light) as a rapid, direct, highly sensitive indicator to characterize the properties of herbal medicines. The DL parameters were able to reliably identify a specific category of herbal materials with the so-called "sweet" taste. To support the DL results and provide biological relevance to the DL results, we used a murine bone marrow-derived dendritic cell-based assay to examine the immunomodulatory effects of herbal extracts from various "taste" categories. Our results indicate that DL may serve as a robust and sensitive tool for evaluating the therapeutic properties of herbs based on the traditional Chinese medicine classification of "taste". Thus, DL provides a promising technological platform for investigating the properties of Chinese herbal medicines both qualitatively and quantitatively., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The increasing prevalence of rheumatoid arthritis has driven the development of new approaches and technologies for investigating the pathophysiology of this devastating, chronic disease. From the perspective of systems biology, combining comprehensive personal data such as metabolomics profiling with ultra-weak photon emission (UPE) data may provide key information regarding the complex pathophysiology underlying rheumatoid arthritis. In this article, we integrated UPE with metabolomics-based technologies in order to investigate collagen-induced arthritis, a mouse model of rheumatoid arthritis, at the systems level, and we investigated the biological underpinnings of the complex dataset. Using correlation networks, we found that elevated inflammatory and ROS-mediated plasma metabolites are strongly correlated with a systematic reduction in amine metabolites, which is linked to muscle wasting in rheumatoid arthritis. We also found that increased UPE intensity is strongly linked to metabolic processes (with correlation co-efficiency |r| value >0.7), which may be associated with lipid oxidation that related to inflammatory and/or ROS-mediated processes. Together, these results indicate that UPE is correlated with metabolomics and may serve as a valuable tool for diagnosing chronic disease by integrating inflammatory signals at the systems level. Our correlation network analysis provides important and valuable information regarding the disease process from a system-wide perspective., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The global prevalence of type 2 diabetes is estimated to reach 4.4% by 2030, placing a significant burden on our healthcare system. Therefore, the ability to identify patients in early stages of the disease is essential for both prevention and effective management, and diagnostic methods based on traditional Chinese medicine (TCM) may be suitable for identifying patients with early-stage type 2 diabetes. Here, a panel of three physicians trained in TCM classified 44 pre-diabetic subjects into three syndrome subtypes using TCM-based diagnostics. In addition, ultra-weak photon emission (UPE) was measured at four anatomical sites in each subject. Ten properties encompassing 40 parameters were then extracted from the UPE time series. Statistical analyses, including multinomial logistic regression, were performed using the results of each parameter measured at the four sites. Sixteen UPE parameters were then selected and used to discriminate between the three subtypes of pre-diabetic subjects. Next, Spearman's correlation coefficient was used to quantify the correlation between the 16 UPE parameters and the TCM-based diagnoses. The resulting correlation networks accurately reflected the differences between the three syndrome subtypes. These results suggest that UPE is a suitable tool for detecting subtypes in early-stage type 2 diabetes. In addition, our results provide evidence that TCM may represent an important step toward personalized medicine., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Chornobyl impact on the health of adult population in Ukraine, Belarus and Russian Federation was a subject of several studies. However, the studies of the effects of Chornobyl on leukemia in adult populations in post-Soviet countries are scarce and the results are contradictory up to present. The results of the epidemiological studies of the oncohematological consequences of Chornobyl accident are briefly reviewed with particular focus on pre-Chornobyl and post-Chornobyl trends in leukemia incidence in Ukraine, Belarus and Russian Federation as well as in small territories of these countries with various levels of radionuclide contamination. This article is a part of a Special Issue entitled "The Chornobyl Nuclear Accident: Thirty Years After".

Objective: As there are pharmacological differences between males and females, and glucocorticoid (GC) treatment is associated with increased cardiovascular mortality rate in rheumatoid arthritis (RA) patients, it is important to study serum polar lipid profiles of male and female patients in response to GC therapy. Gender differences may require an adjustment to the treatment strategy for a selection of patients., Methods: Serum samples from 281 RA patients were analysed using a targeted lipidomics platform. The differences in GC use and gender on polar lipid profiles were cross sectionally examined by multiple linear regressions, while correcting for confounding factors., Results: Differences in polar lipids between GC users and non-GC users in females and males were merely restricted to lysophospholipids (lysophosphatidylcholines and lysophosphatidylethanolamines). Lysophospholipids in female patients treated with GCs were significantly higher than female patients not treated with GCs (p = 6.0 E-6), whereas no significant difference was observed in male GC users versus non-users (p = 0.397)., Conclusion: The lysophospholipid profiles in response to GCs were significantly different between male and female RA patients, which may have implications for the cardiovascular risk of GC treatment., Competing Interests: The authors have no conflicts of interest to declare.

Ultra-weak photon emission (UPE) is light emitted spontaneously by biological systems without the use of specific luminescent complexes. UPE is emitted in the near-UV/UV-Vis/near-IR spectra during oxidative metabolic reactions; however, the specific pathways involved in UPE remain poorly understood. Here, we used HL-60 cells, a human promyelocytic cell line that is often used to study respiratory burst, as a model system to measure UPE kinetics together with metabolic changes. HL-60 cells were differentiated into neutrophil-like cells by culturing in all-trans-retinoic acid for 7days. We then used a targeted metabolomics approach with capillary electrophoresis-mass spectrometry to profile intracellular metabolites in HL-60 cells and to investigate the biochemical changes based on the measured UPE profile. Our analysis revealed that the levels of specific metabolites, including putrescine, creatine, β-alanine, methionine, hydroxyproline, serine, and S-adenosylmethionine, were significantly altered in HL-60 cells after inducing respiratory burst. A comparison with recorded UPE data revealed that the changes in putrescine, glutathione, sarcosine, creatine, β-alanine, methionine, and hydroxyproline levels were inversely correlated with the change in UPE intensity. These results suggest that these metabolic pathways, particular the methionine pathway, may play a role in the observed changes in UPE in HL-60 cells and therefore demonstrate the potential for using UPE to monitor metabolic changes., (Copyright © 2016 Elsevier B.V. All rights reserved.)

In clinical practice, approximately one-third of patients with rheumatoid arthritis (RA) respond insufficiently to TNF-α inhibitors (TNFis). The aim of the study was to explore the use of a metabolomics to identify predictors for the outcome of TNFi therapy, and study the metabolomic fingerprint in active RA irrespective of patients' response. In the metabolomic profiling, lipids, oxylipins, and amines were measured in serum samples of RA patients from the observational BiOCURA cohort, before start of biological treatment. Multivariable logistic regression models were established to identify predictors for good- and non-response in patients receiving TNFi (n = 124). The added value of metabolites over prediction using clinical parameters only was determined by comparing the area under receiver operating characteristic curve (AUC-ROC), sensitivity, specificity, positive- and negative predictive value and by the net reclassification index (NRI). The models were further validated by 10-fold cross validation and tested on the complete TNFi treatment cohort including moderate responders. Additionally, metabolites were identified that cross-sectionally associated with the RA disease activity score based on a 28-joint count (DAS28), erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). Out of 139 metabolites, the best-performing predictors were sn1-LPC(18:3-ω3/ω6), sn1-LPC(15:0), ethanolamine, and lysine. The model that combined the selected metabolites with clinical parameters showed a significant larger AUC-ROC than that of the model containing only clinical parameters (p = 0.01). The combined model was able to discriminate good- and non-responders with good accuracy and to reclassify non-responders with an improvement of 30% (total NRI = 0.23) and showed a prediction error of 0.27. For the complete TNFi cohort, the NRI was 0.22. In addition, 88 metabolites were associated with DAS28, ESR or CRP (p<0.05). Our study established an accurate prediction model for response to TNFi therapy, containing metabolites and clinical parameters. Associations between metabolites and disease activity may help elucidate additional pathologic mechanisms behind RA., Competing Interests: JvL has received grants from Roche, MSD, Eli Lilly and Pfizer. JB received unrestricted grants (to his department) to conduct the BiOCURA study from Pfizer, BMS, UCB, Roche, and Schering-Plough. No other grants were received with respect to consulting fees, employment, consultancy, patents, products in development, marketed products, etc. These received grants do not alter our adherence to PLOS ONE policies on sharing data and materials. None of the other authors declared any competing interests.

To improve the quality control of herbal drugs, there has been a major shift from evaluating individual chemicals to evaluating multiple-constituent chemicals, given the multi-pharmacology nature of herbal drugs. Therefore, rapid, systematic assays are needed in order to assess the quality of medicinal herbs using a comprehensive, integrated approach. Light-induced delayed luminescence (DL) is used to measure decaying long-term ultra-weak photon emissions following excitation with light. DL is considered to be a sensitive indicator for characterizing the properties of biological systems and herbal medicines with various therapeutic properties. The aim of this study was to examine the feasibility of using DL as a novel quality-assessment tool using rhubarb material as a model system, and to establish the correlation between DL parameters and the chemical constituents of rhubarb. Raw roots and rhizomes were collected from rhubarb (Rheum palmatum L.) at various elevations in western China. HPLC analysis was used to identify fourteen bioactive constituents. Five DL parameters were calculated from the DL decay curves of the rhubarb samples. Statistical tools, including principal component analysis, were used to classify the rhubarb samples using data obtained using two different assays. Finally, Spearman's correlation coefficient was calculated to quantify the correlation between the bioactive compounds and corresponding DL parameters. We found that both the chemical analysis and DL measurements reflect variations in the quality of rhubarb due to environment factor. The DL parameters were correlated significantly with the bioactive chemical constituents. Our results indicate that DL is a promising tool for evaluating multiple constituents and for assessing the therapeutic properties of herbal medicines. Thus, DL may be used as part of a comprehensive system for assessing the quality and/or therapeutic properties of herbal medicines., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Exposure to ionizing radiation is associated with increasing risk of various types of hematological malignancies. The results of major studies on association of leukemias and radiation exposure of large populations in Japan and in Ukraine are analyzed. The patterns of different types of leukemia in 295 Chernobyl clean-up workers diagnosed according to the criteria of up-to-date World Health Organization classification within 10-25 years following Chernobyl catastrophe are summarized. In fact, a broad spectrum of radiation-related hematological malignancies has been revealed both in Life Span Study in Japan and in study of Chernobyl clean-up workers in Ukraine. The importance of the precise diagnosis of tumors of hematopoietic and lymphoid tissues according to up-to-date classifications for elucidating the role of radiation as a causative factor of leukemias is emphasized. Such studies are of high importance since according to the recent findings, radiation-associated excess risks of several types of leukemias seem to persist throughout the follow-up period up to 55 years after the radiation exposure.

Classical and up-to-date models of hematopoietic lineage determination are briefly reviewed with the focus on myeloid-based models challenging the existence of the common progenitor for T cells, B cells and NK cells. The analysis of immunophenotype of leukemic blast cells seems to be a promising approach for interpreting some controversies in the schemes of normal hematopoiesis. The literature data as well as our own findings in the patients with various types of acute leukemias are in favor of the concept postulating that common myeloid-lymphoid progenitors giving rise to T and B cell branches retain the myeloid potential. The similarity of some immunophenotypic features of blast cells in pro-B acute lymphoblastic leukemia and acute monoblastic leukemia is consistent with monocyte origin postulated in the studies of normal hematopoiesis. Study of acute leukemias may be the challenging area of research allowing for new insight into the origin of hematopoietic cell lineages.

RNA polymerase II (RNAPII) pausing/termination shortly after initiation is a hallmark of gene regulation. Here, we show that negative elongation factor (NELF) interacts with Integrator complex subunits (INTScom), RNAPII and Spt5. The interaction between NELF and INTScom subunits is RNA and DNA independent. Using both human immunodeficiency virus type 1 promoter and genome-wide analyses, we demonstrate that Integrator subunits specifically control NELF-mediated RNAPII pause/release at coding genes. The strength of RNAPII pausing is determined by the nature of the NELF-associated INTScom subunits. Interestingly, in addition to controlling RNAPII pause-release INTS11 catalytic subunit of the INTScom is required for RNAPII processivity. Finally, INTScom target genes are enriched in human immunodeficiency virus type 1 transactivation response element/NELF binding element and in a 3' box sequence required for small nuclear RNA biogenesis. Revealing these unexpected functions of INTScom in regulating RNAPII pause-release and completion of mRNA synthesis of NELF-target genes will contribute to our understanding of the gene expression cycle.

The wear performance of two types of crosslinked polyethylene (Marathon™ and XLK™, DePuy Synthes Inc., Warsaw, IN) was evaluated in a pin-on-disc wear tester, a hip wear simulator, and a knee wear simulator. Sodium azide was used as the microbial inhibitor in the calf serum-based lubricant. In the pin-on-disc wear tester, the Marathon wear rate of 5.33±0.54mm(3)/Mc was significantly lower (p=0.002) than the wear rate of 6.43±0.60mm(3)/Mc for XLK. Inversely, the Marathon wear rate of 15.07±1.03mm(3)/Mc from the hip wear simulator was 2.2-times greater than the XLK wear rate of 6.71±1.03mm(3)/Mc from the knee wear simulator. Differences in implant design, conformity, GUR type, and kinematic test conditions were suggested to account for the difference between the wear rates generated in the different types of wear testing apparati. In all wear tests, sodium azide was ineffective at inhibiting microbial growth in the lubricant. Eight different organisms were identified in the lubricant samples from the wear tests, which suggested the necessity of using an alternative, more effective microbial inhibitor. Careful sample preparation and thorough cleaning has shown to improve the consistency of the wear results. The wear rates generated in the hip and knee wear simulators closely reflected the wear behaviour of Marathon and XLK reported in published data that were tested under similar conditions., (Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.)

The issue of introduction of number of additions into actual scheme of blood formation is discussed. The long standing experience of laboratory diagnostic of oncologic hematological diseases in adults and children and the analysis of published data about normal blood formation are involved into consideration. The existence is surmised of common oligo-linear precursors for B-lymphocytes and monocytes, natural killer cells and monocytes and common cell-precursor of T-lymphocytes and dendrite cells as well. At the same time, the issue concerning the existence of human common cell-precursor of lymphization capable of differentiating into Band T-lymphocytes and natural killer cells is disputable.

Bdellovibrio and like organisms (BALO) are obligate predators of Gram-negative bacteria, belonging to the α- and δ-proteobacteria. BALO prey using either a periplasmic or an epibiotic predatory strategy, but the genetic background underlying these phenotypes is not known. Here we compare the epibiotic Bdellovibrio exovorus and Micavibrio aeruginosavorus to the periplasmic B. bacteriovorus and Bacteriovorax marinus. Electron microscopy showed that M. aeruginosavorus, but not B. exovorus, can attach to prey cells in a non-polar manner through its longitudinal side. Both these predators were resistant to a surprisingly high number of antibiotic compounds, possibly via 26 and 19 antibiotic-resistance genes, respectively, most of them encoding efflux pumps. Comparative genomic analysis of all the BALOs revealed that epibiotic predators have a much smaller genome (ca. 2.5 Mbp) than the periplasmic predators (ca. 3.5 Mbp). Additionally, periplasmic predators have, on average, 888 more proteins, at least 60% more peptidases, and one more rRNA operon. Fifteen and 219 protein families were specific to the epibiotic and the periplasmic predators, respectively, the latter clearly forming the core of the periplasmic 'predatome', which is upregulated during the growth phase. Metabolic deficiencies of epibiotic genomes include the synthesis of inosine, riboflavin, vitamin B6 and the siderophore aerobactin. The phylogeny of the epibiotic predators suggests that they evolved by convergent evolution, with M. aeruginosavorus originating from a non-predatory ancestor while B. exovorus evolved from periplasmic predators by gene loss.

Calpains are a family of cytoplasmic calcium-dependent proteinases with papain-like activity. They participate in a variety of processes in the body: age changes, functioning of endothelium and pulmonary system, regulation of apoptosis and necrosis, development of various hypometabolic states, arterial hypertension, diabetes and chronic kidney disease, tumor growth. It is concluded that calpains, causing limited proteolysis of substrates, play an important role in a wide range of biological phenomena. Their activity is associated with the response to the calcium-dependent signaling and the effects of aging. Inhibition of calpains activity contributes to inhibition of endothelial dysfunction, cardiovascular disease, formation of structural and functional changes in the kidney tissue, has neuroprotective effect, preventing sarcopenia, reduces inflammatory reactions caused by hyperventilation of the lungs.

The pressure dependences of the structural, thermoelastic and vibrational properties of SnO2 in its rutile phase are studied, as well as the pressure-induced transition to a CaCl2-type phase. These studies have been performed by means of ab initio (AI) density functional theory calculations using the localized basis code SIESTA. The results are employed to develop a shell model (SM) for application in future studies of nanostructured SnO2. A good agreement of the SM results for the pressure dependences of the above properties with the ones obtained from present and previous AI calculations as well as from experiments is achieved. The transition is characterized by a rotation of the Sn-centered oxygen octahedra around the tetragonal axis through the Sn. This rotation breaks the tetragonal symmetry of the lattice and an orthorhombic distortion appears above the critical pressure P(c). A zone-center phonon of B1g symmetry in the rutile phase involves such rotation and softens on approaching Pc. It becomes an Ag mode which stabilizes with increasing pressure in the CaCl2 phase. This behavior, together with the softening of the shear modulus (C11-C12)/2 related to the orthorhombic distortion, allows a precise determination of a value for Pc. An additional determination is provided by the splitting of the basal plane lattice parameters. Both the AI and the experimentally observed softening of the B(1g) mode are incomplete, indicating a small discontinuity at the transition. However, all results show continuous changes in volume and lattice parameters, indicating a second-order transition. All these results indicate that there should be sufficient confidence for the future employment of the shell model.

Background: Dopamine agonists could theoretically normalize the suspected central dopamine hypersensitivity in Tourette's syndrome., Methods: There was a multicenter randomized, placebo-controlled, double-blind clinical trial of pramipexole given for 6 weeks in 63 children and adolescents with Tourette's syndrome., Results: There were no significant differences in the adjusted mean change in the Total Tic Score of the Yale Global Tic Severity Scale for patients treated with pramipexole (-7.16) and placebo (-7.17). There were no significant treatment effects on change from baseline in the Global Severity score of the Yale Scale and parent- and investigator-scored Clinical Global Impression of Improvement. In patients with attention deficit hyperactivity disorder, there was improvement in DuPaul ADHD scale scores for patients receiving pramipexole compared with placebo., Conclusions: There was no evidence that pramipexole has efficacy in suppressing tics. Pramipexole may decrease symptoms of associated attention deficit hyperactivity disorder., (Copyright © 2012 Movement Disorder Society.)

Background: Genetic mechanisms that result in the development and progression of B-cell chronic lymphocytic leukemia (B-CLL) are mainly unknown. We have analyzed gene expression patterns in Ukrainian B-CLL patients with the aim of identifying B-CLL involved / associated genes in order to shed light on the biology of this pathological entity., Material and Methods: The samples of the peripheral blood and bone marrow of 44 Ukrainian B-CLL patients with no characteristics indicative of unfavorable course of the disease such as CD38 were analyzed morphologically and immunocytochemically according to the new WHO classification. Total RNA was isolated, and gene expression levels were determined by microarray method comparing with the sample from 17 healthy donors., Results: We investigated interactions using the Ingenuity Pathway Analysis (IPA) software and found 1191 network eligible up-regulated genes and 3398 Functions/Pathways eligible up-regulated genes, 1225 network eligible down-regulated genes and 2657 Functions/Pathways eligible down-regulated genes., Conclusion: In B-CLL patients, gene networks around MYC, HNF1A and HNF4A, YWHAG, NF-κB1 and SP1 are identified as up-regulated; CEBPA, YWHAG, SATB1 and RB1 -- as down-regulated. G protein coupled receptor signaling, arachidonic acid and linoleic acid metabolisms, calcium signaling, metabolism of xenobiotics by cytochrome P450 are found out as significant up-regulated pathways. EIF2 and Cdc42 signaling, regulation of eIF4 and p70S6k signaling, protein ubiquitination pathway and oxidative phosphorylation are the most significant down-regulated pathways obtained in our study. The involvement of NF-κB gene network and upregulated levels of G protein coupled receptor signaling pathway, which has an important role in transcription of NF-κB, are important and need further examination.

A study of differently polarized structures relevant to the H-bonded antiferroelectric (AFE) compound NH(4)H(2)PO(4) (ADP) is performed by first-principles calculations in the framework of the density functional theory. The calculated structures for the AFE and paraelectric (PE) phases are found in general good agreement with the available experimental data. We study the energetics and relative stability of different polarized clusters embedded in a PE matrix of ADP. We find that local ferroelectric and AFE clusters are stable and may coexist in the PE phase, which explains the coexistence of both type of microregions determined by electron spin probe measurements above the AFE-PE transition temperature. The dependency with the O-H···O bridge length of the energy barrier heights for proton transfer is studied for coordinated proton displacements along the bridges within clusters of different sizes. This dependency may have implications for the geometric isotopic effects on T(c). We analyze Mulliken orbital and bond populations which confirm the existence of a charge flow within the NH(4)(+) ion, an essential fact for the stabilization of the AFE phase over other possible polarized structures. This charge transfer is correlated with the optimization of the N-H···O bridges and with distortions of the NH(4)(+) group., (© 2011 American Institute of Physics)

Background: The complete medical consequences of the long-term exposure of population to ionizing radiation in post-Chernobyl period are still a controversial issue. The molecular biological analysis of malignant diseases of hematopoietic and lymphoid tissues in contaminated territories requires the precise diagnosis based on criteria of novel classifications., Aim: To analyze the relative gene expression of six apoptosis-related genes in different types of tumors of hematopoietic and lymphoid tissues in patients living in areas of Ukraine contaminated with radionuclides in post-Chernobyl period., Material and Methods: The samples of the peripheral blood and bone marrow of 189 Ukrainian leukemia patients and 16 patients with reactive lymphocytosis were analyzed morphologically and immunocytochemically for precise delineation of the main forms and cytological variants of hematological malignancies according to new WHO classification. Expression of six apoptosis-related genes was analyzed in the individual samples of 9 different groups of malignant diseases of hematopoietic and lymphoid tissues and one group of patients with reactive lymphocytosis by quantitative RT-PCR. Expression of genes was assessed relative to that in control group of healthy donors., Results: Up-regulation of six analyzed apoptosisrelated genes is observed in all groups of leukemia. In most groups of leukemia being analyzed, BCL-2 up-regulation level is superior to that of BAX. Prominent MYC up-regulation is observed in B-lymphoblastic leukemia/lymphoma, non-Hodgkin's lymphoma, and T-lymphoblastic leukemia/lymphoma groups. In myelodysplastic/myeloproliferative neoplasms, the striking up-regulation of Fas-1 and P38MAPK is evident. Practically all the groups of leukemia are characterized by stable high ratios of P53 up-regulation., Conclusion: In Ukrainian patients, up-regulation of six analyzed apoptosis-related genes is observed practically in all types of malignant diseases of hematopoietic and lymphoid tissues under study. Microarray-based analysis of these samples would be of great importance in terms of elucidating genomic interactions in leukemias and their possible association with ionizing radiation.

In patients with diabetic nephropathy, lowering blood pressure and reducing proteinuria by over 30% correlates with a slower progression to kidney failure. We compared two different angiotensin receptor-blockers in a double blind, prospective trial of 860 patients with type 2 diabetes whose blood pressure levels was over 130/80 mmHg or who were receiving antihypertensive medication(s) and who had a morning spot urinary protein to creatinine ratio of 700 or more. Patients were randomized to telmisartan (a highly lipophilic agent with a long half-life) or losartan (with low lipophilicity and short half-life). The primary endpoint was the difference in the urinary albumin to creatinine ratio between the groups at 52 weeks. The geometric coefficient of variation and the mean of the urinary albumin to creatinine ratio fell in both groups at 52 weeks but both were significantly greater for the telmisartan compared to the losartan cohort. Mean systolic blood pressure reductions were not significantly different between groups at trial end. We conclude that telmisartan is superior to losartan in reducing proteinuria in hypertensive patients with diabetic nephropathy, despite a similar reduction in blood pressure.

The immunophenotypic profile of hematopoietic stem cells (HSC) and hematopoietic precursor cells as well as leukemic stem cells (LSC) has been extensively studied in several laboratories worldwide. The results of our studies suggest that the standard panel for classification of acute leukemias should be supplemented with several new markers allowing us to identify more precisely the different forms of the leukemias being of the closely related origin, for example AML M6b and AML M7. The common bipotent LSC in AML M7 of low grade and AML M6b may exist analogous to precursor cell common for megakaryocytopoiesis and erythropoiesis. We have also found the similarity between blast cells in pro-B-ALL [t (4;11), 11q23] and AML M5a [t (9;11), 11q23]. Such similarity of immunophenotype and cytogenetic abnormalities in blast cells in pro-B-ALL and AML M5a may be considered as hint explaining the cases of AML M5a as a recurrence of leukemia in children with originally diagnosed pro-B-ALL.

Background: The Study of Micardis (telmisartan) in Overweight/Obese patients with Type 2 diabetes and Hypertension (SMOOTH) compared hydrochlorothiazide (HCTZ) plus telmisartan or valsartan fixed-dose combination therapies on early morning blood pressure (BP), using ambulatory BP monitoring (ABPM)., Methods: SMOOTH was a prospective, randomized, open-label, blinded-endpoint, multicentre trial. After a 2- to 4-week, single-blind, placebo run-in period, patients received once-daily telmisartan 80 mg or valsartan 160 mg for 4 weeks, with add-on HCTZ 12.5 mg for 6 weeks (T/HCTZ or V/HCTZ, respectively). At baseline and week 10, ambulatory blood pressure (ABP) was measured every 20 min and hourly means were calculated. The primary endpoint was change from baseline in mean ambulatory systolic and diastolic blood pressure (SBP; DBP) during the last 6 hours of the 24-hour dosing interval., Results: In total, 840 patients were randomized. At week 10, T/HCTZ provided significantly greater reductions versus V/HCTZ in the last 6 hours mean ABP (differences in favour of T/HCTZ: SBP 3.9 mm Hg, p < 0.0001; DBP 2.0 mm Hg, p = 0.0007). T/HCTZ also produced significantly greater reductions than V/HCTZ in 24-hour mean ABP (differences in favour of T/HCTZ: SBP 3.0 mm Hg, p = 0.0002; DBP 1.6 mm Hg, p = 0.0006) and during the morning, daytime and night-time periods (p < 0.003). Both treatments were well tolerated., Conclusion: In high-risk, overweight/obese patients with hypertension and type 2 diabetes, T/HCTZ provides significantly greater BP lowering versus V/HCTZ throughout the 24-hour dosing interval, particularly during the hazardous early morning hours.

The low-temperature antiferroelectric (AFE) phase of NH4H2PO4 corresponds to H ordering in O-H-O bridges leading to H2PO4 group polarizations perpendicular to the tetragonal c axis and alternating in chains. We determine the microscopic origin of such order by means of first-principles calculations in the framework of the density functional theory. The formation of N-Hcdots, three dots, centeredO bridges with correlated charge transfers and NH4+ group distortions turn out to be essential in stabilizing the AFE configuration against a c-polarized ferroelectric (FE) phase, as well as other FE states polarized perpendicular to the c axis. These FE states lie only a few meV above the AFE phase, which explains the observation of FE-AFE phase coexistence near the AFE transition.