CAVER Analyst 1.0: graphic tool for interactive visualization and analysis of tunnels and channels in protein structures

ABSTRACT Summary: The transport of ligands, ions or solvent molecules into proteins with buried binding sites or through the membrane is enabled by protein tunnels and channels. CAVER Analyst is a software tool for calculation, analysis and real-time visualization of access tunnels and channels in static and dynamic protein structures. It provides an intuitive graphic user interface for setting up the calculation and interactive exploration of identified tunnels/channels and their characteristics. Availability and Implementation: CAVER Analyst is a multi-platform software written in JAVA. Binaries and documentation are freely available for non-commercial use at http://www.caver.cz

Bio-Sensing of Cadmium(II) Ions Using Staphylococcus aureus†

Cadmium, as a hazardous pollutant commonly present in the living environment, represents an important risk to human health due to its undesirable effects (oxidative stress, changes in activities of many enzymes, interactions with biomolecules including DNA and RNA) and consequent potential risk, making its detection very important. New and unique technological and biotechnological approaches for solving this problems are intensely sought. In this study, we used the commonly occurring potential pathogenic microorganism Staphylococcus aureus for the determination of markers which could be used for sensing of cadmium(II) ions. We were focused on monitoring the effects of different cadmium(II) ion concentrations (0, 1.25, 2.5, 5, 10, 15, 25 and 50 μg mL−1) on the growth and energetic metabolism of Staphylococcus aureus. Highly significant changes have been detected in the metabolism of thiol compounds—specifically the protein metallothionein (0.79–26.82 mmol/mg of protein), the enzyme glutathione S-transferase (190–5,827 μmol/min/mg of protein), and sulfhydryl groups (9.6–274.3 μmol cysteine/mg of protein). The ratio of reduced and oxidized glutathione indicated marked oxidative stress. In addition, dramatic changes in urease activity, which is connected with resistance of bacteria, were determined. Further, the effects of cadmium(II) ions on the metabolic pathways of arginine, β-glucosidase, phosphatase, N-acetyl β-d-glucosamine, sucrose, trehalose, mannitol, maltose, lactose, fructose and total proteins were demonstrated. A metabolomic profile of Staphylococcus aureus under cadmium(II) ion treatment conditions was completed seeking data about the possibility of cadmium(II) ion accumulation in cells. The results demonstrate potential in the application of microorganisms as modern biosensor systems based on biological components

Bio-Sensing of Cadmium(II) Ions Using Staphylococcus aureus†

Cadmium, as a hazardous pollutant commonly present in the living environment, represents an important risk to human health due to its undesirable effects (oxidative stress, changes in activities of many enzymes, interactions with biomolecules including DNA and RNA) and consequent potential risk, making its detection very important. New and unique technological and biotechnological approaches for solving this problems are intensely sought. In this study, we used the commonly occurring potential pathogenic microorganism Staphylococcus aureus for the determination of markers which could be used for sensing of cadmium(II) ions. We were focused on monitoring the effects of different cadmium(II) ion concentrations (0, 1.25, 2.5, 5, 10, 15, 25 and 50 μg mL−1) on the growth and energetic metabolism of Staphylococcus aureus. Highly significant changes have been detected in the metabolism of thiol compounds—specifically the protein metallothionein (0.79–26.82 mmol/mg of protein), the enzyme glutathione S-transferase (190–5,827 μmol/min/mg of protein), and sulfhydryl groups (9.6–274.3 μmol cysteine/mg of protein). The ratio of reduced and oxidized glutathione indicated marked oxidative stress. In addition, dramatic changes in urease activity, which is connected with resistance of bacteria, were determined. Further, the effects of cadmium(II) ions on the metabolic pathways of arginine, β-glucosidase, phosphatase, N-acetyl β-d-glucosamine, sucrose, trehalose, mannitol, maltose, lactose, fructose and total proteins were demonstrated. A metabolomic profile of Staphylococcus aureus under cadmium(II) ion treatment conditions was completed seeking data about the possibility of cadmium(II) ion accumulation in cells. The results demonstrate potential in the application of microorganisms as modern biosensor systems based on biological components

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Current and past smoking patterns in a Central European urban population: a cross-sectional study in a high-burden country

Abstract Background Many studies have examined the socioeconomic variations in smoking and quitting rates across the European region; however, data from Central and East European countries, where the tobacco burden is especially high, are sparse. This study aimed to assess the patterns in current and past smoking prevalence based on cross-sectional data from a Central European urban population sample. Methods Data from 2160 respondents aged 25–64 years in Brno, Czech Republic were collected in 2013–2014 using the Czech post-MONICA survey questionnaire to assess the prevalence of cardiovascular risk factors, including smoking status. The age- and sex-stratified randomized sample was drawn using health insurance registries. Descriptive statistics and quit ratios were calculated, and chi-square and multivariate logistic analyses conducted to examine relationships between current and past smoking and demographic (age, gender, marital status) and socioeconomic variables (education, income, occupation). Results The prevalence of current and past smoking was 23.6 and 31.3 % among men and 20.5 and 23.2 % among women, respectively. Education reliably predicted smoking and quitting rates in both genders. Among men, being unemployed was associated with greater odds of smoking (OR 3.6; 1.6–8.1) and lower likelihood of quitting (OR 0.2: 0.1–0.6); the likelihood of quitting also increased with age (OR 1.8; 1.2–2.8). Among women, marital status (being married) decreased the odds of current smoking (OR 0.6; 0.4–0.9) and increased the odds of quitting (OR 2.2; 1.2–3.9). Quit ratios were the lowest in the youngest age group (25–34 years) where quitting was more strongly associated with middle income (OR 2.7; 95 % CI 1.2–5.9) than with higher education (OR 2.9; 95 % CI 0.9–8.2). Conclusions Interventions to increase cessation rates and reduce smoking prevalence need to be gender-specific and carefully tailored to the needs of the disadvantaged groups of the population, especially the less well-off young adults. Future studies should examine the equity impact of the tobacco control policies and be inclusive of the Central and East European countries

Learning to assist smokers through encounters with standardized patients: An innovative training for physicians in an Eastern European country

Objectives: A lack of physician training is a major obstacle for effective tobacco dependence treatment. This study assessed the feasibility of an active learning training program and its effects on smoking cessation counselling skills of medical residents in Armenia, an Eastern European country with high smoking prevalence. Study design: The study used a pre-post assessment of smoking cessation counselling activities and a course evaluation survey to assess the feasibility of the intervention in a different environment. Methods: We adapted an active learning training model developed in Switzerland. Residents were trained in Yerevan, Armenia, using video-taped counselling sessions, role plays, standardized patients (actors), group discussions and immediate feedback. The training evaluation was done using a semi-structured anonymous questionnaire. The study assessed the physicians' self-reported smoking cessation counselling activities before and 6 months after the training. A non-parametric Mann-Whitney test was used to assess pre-post differences in physicians' counselling skills measured on ordinal scale. Results: Of the 37 residents trained, 75% were female, 89% aged 20-29 years and 83% were never-smokers. Twenty-eight trainees (76%) returned the course evaluation survey and 32 (86%) answered a questionnaire on skills self-assessment at 6 months follow-up. The majority agreed the course was successful in achieving its learning objectives (64%-96%) and increased their confidence in assisting their patients to quit (74%). After 6 months, the physicians were more likely than at baseline to adhere to evidence-based counselling strategies, including assessing the smoking status and dependence and matching the advice to the patient motivation. The training did not, however, improve the prescription of tobacco dependence medications. Conclusions: Six months after the training, several self-reported smoking cessation counselling activities had significantly improved compared to baseline. This training model is acceptable for medical residents in Yerevan, Armenia and offers a promising approach in addressing the lack of physician counselling skills in similar settings and populations

Association of Dietary Patterns with Metabolic Syndrome: Results from the Kardiovize Brno 2030 Study

Although metabolic syndrome (MetS) could be handled by lifestyle interventions, its relationship with dietary patterns remains unclear in populations from Central Europe. Using data from the Kardiovize Brno cohort, the present study aims to identify the main dietary patterns and to evaluate their association with MetS risk in a random urban sample from Brno, Czech Republic. In a cross-sectional study of 1934 subjects aged 25–65 years (44.3% male), dietary patterns were derived by food frequency questionnaire (FFQ) administration and principal component analysis. Metabolic syndrome was defined according to the International Diabetes Federation statement. Logistic regression models were applied. High adherence to the prudent dietary pattern was associated with lower odds of abdominal obesity, abnormal glucose concentration, and MetS. By contrast, high adherence to the western dietary pattern was associated with higher odds of abnormal glucose, triglycerides and blood pressure levels. Whilst our results confirm the deleterious effect of a western dietary pattern on several metabolic risk factors, they also indicate that the consumption of a diet rich in cereals, fish, fruit and vegetables is associated with a healthier metabolic profile. However, further prospective research is warranted to develop and validate novel potential preventive strategies against MetS and its complications