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Up to 80% of COVID-19 survivors experience prolonged symptoms known as long COVID-19. The aim of this study was to evaluate the effects of a multidisciplinary rehabilitation program in patients with long COVID-19. The rehabilitation program was composed of physical training (aerobic, resistance, and breathing exercises), education, and group psychotherapy. After 6 weeks of rehabilitation in 97 patients with long COVID-19, body composition analysis revealed a significant decrease of abdominal fatty tissue (from 2.75 kg to 2.5 kg; p = 0.0086) with concomitant increase in skeletal muscle mass (from 23.2 kg to 24.2 kg; p = 0.0104). Almost 80% of participants reported dyspnea improvement assessed with the modified Medical Research Council scale. Patients’ physical capacity assessed with the 6 Minute Walking Test increased from 320 to 382.5 m (p < 0.0001), the number of repetitions in the 30 s Chair Stand Test improved from 13 to 16 (p < 0.0001), as well as physical fitness in the Short Physical Performance Battery Test from 14 to 16 (p < 0.0001). The impact of fatigue on everyday functioning was reduced in the Modified Fatigue Impact Scale from 37 to 27 (p < 0.0001). Cardiopulmonary exercise test did not show any change. The multidisciplinary rehabilitation program has improved body composition, dyspnea, fatigue and physical capacity in long COVID-19 patients.

In this study, novel single nucleotide polymorphisms (SNPs) were found in the 5′-regulatory regions (promoters) of the bovine glucose transporter (GT) genes SLC2A12 and SLC5A1. These polymorphisms were shown to associate with certain milk production traits in HF cows, including milk yield, milk composition, and somatic cell count. It was shown that the SNP g.-671C > G (NC_037336.1: g.72224078C > G) in the SLC2A12 gene could be an effective marker of cattle production traits and that genotypes CC and CG are associated with the best productivity. The polymorphisms found in the SLC5A1 gene promoter also influenced milk production traits in HF cows, albeit to a lesser extent, and we propose that these polymorphisms could be useful as genetic markers for milk production traits in marker-assisted selection (MAS); however, this must be confirmed on larger populations of cattle. In addition, the presence of polymorphisms within promoter regions appears to affect the expression of GT genes in the cow mammary gland and modify transcription factor (TF) binding capacity.

Background. The physical benefits of fitness for middle-aged women are well-known. Unlike the usual training sessions, aquafitness occupies a special place among the types of health-related exercise training. Its health-enhancing effect results from the activation of the body's functional systems, the gravitational unloading of the musculoskeletal system, high energy expenditures, and overall body hardening effect. The objective of this study was to evaluate the health-enhancing effects of an aquafitness program on the functional indicators and physical fitness of early adulthood women. Materials and methods. Theoretical analysis and generalization of scientific and methodological literature, anthropometric techniques, pedagogical methods, and methods of mathematical statistics were used. The functional status of the body was assessed with the indices characterizing the function of the cardiorespiratory system, which are commonly used. The study was conducted at the Sport Life fitness club, Chernivtsi. The study involved 48 women aged 21-31 with an average age of 26.3 years. The subjects took part in a six-month aquafitness program consisting of 60-min sessions, three times a week. The program was developed by the authors and included aquatic stretching, body shaping and bodybuilding exercise, aquadance, aquatic gymnastics, and aqua tae-bo. Results. After participation in the exercise program: vital capacity increased from 45.96±4.69 to 48.88±0.68; strength index increased from 35.80±1.07 to 43.26±0.71; Robinson's index increased from 85.72±12.34 to 89.63±10.11; Shtange test increased from 30.28±10.32 to 37.78±12.34; Hench test changed from 16.48±4.24 to 25.19±4.58; Kerdo index decreased from 5.23±0.74 to 0.88±0.38; and Rufier's test decreased from 12.21±4.26 to 8.03±2.14. The assessment of somatic health of the women showed a significant improvement (p

The article presents research materials relating to the study of the individual characteristics of the 2D:4D finger index in young athletes in pair female acrobatics and gymnastics. The aim of the study is to study and comparatively analyze the features of the 2D: 4D finger proportions in the "upper" and "lower" female partners in paired female acrobatics and among the female athletes involved in artistic gymnastics, referred to adolescence; confirmation of the influence of the 2D:4D finger ratio on the athletic capabilities of athletes and the formation of their sexual somatotype. It has been proved that the presence in these groups of female athletes with certain values of the inverse, andromorphic sexual somatotype indicates an increased level of testosterone in the body of these athletes and inverse adaptive changes with the formation of masculinization phenomena in them. Research methods and organization. To conduct research on the features of the 2D:4D finger proportions in the "upper" and "lower" female partner athletes in paired female acrobatics and in athletes engaged in artistic gymnastics, the following methods were used: anthropometric method to determine: IPD) and somatotyping according to the classification of J. Tanner and W. Marshall; 2) measurement and comparison of II and IV fingers of the hands of athletes using the finger ratio method according to J.T. Menning – 2D:4D Digit Ratio; 3) as well as the method of literary analysis, using available sources of information; 4) method of mathematical statistics. Organization of the study. This study was conducted in 2019-2020 with the involvement of 31 pairs of acrobats and 59 athletes involved in artistic gymnastics in Ukraine (Nikolaev and Poltava). "Lower" acrobats and gymnasts (n=90) - adolescent – 19.35±1.07 years; "Upper" acrobats (n=31) – pubertal age – 14.68±1.14 years (p≤0,01). Their experience in these sports ranged from 2.5 to 10 years. The level of sportsmanship – from I-III sports category to a candidate for master of sports, master of sports. Research results. After carrying out the study of the necessary anthropometric measurements for each participant (indicators of the width of the shoulders and pelvis, the length of the II and IV fingers of both hands) and processing the obtained anthropometric values, the values of the sexual dimorphism index (SDI) in each study group were determined by mathematical recalculation.

An increasing body of data indicates that a reduction of ticagrelor maintenance dose (MD) in stabilized patients might improve ticagrelor's safety profile and adherence to the treatment. The aim of this review was to discuss the rationale and summarize the current pharmacodynamic and clinical outcomes-based evidence from reduced MD of ticagrelor in patients with coronary artery disease (CAD).A narrative systematic review based on a literature search using the PubMed database from its inception through to June 2020. A search strategy included a combination of relevant search terms regarding ticagrelor reduced MD. The pre-determined inclusion criteria were: (1) randomized or observational trials; (2) presentation of clinical or pharmacodynamic results; (3) evaluation of any ticagrelor MD below 90 mg BID in patients with CAD.Studies evaluating the following ticagrelor reduced MD have been identified: 90 mg QD, 60 mg BID, 60 mg QD, 45 mg BID, 22.5 mg BID. Majority of trials assessing doses60 mg BID were performed in Asian patients only. Antiplatelet effect of ticagrelor in CAD decreases with the dose, however even reduced MDs provide sufficient platelet inhibition, which is greater than in clopidogrel-treated patients. De-escalation of ticagrelor dose shows a propensity towards a reduced rate of bleeding and non-bleeding adverse events.Ticagrelor doses below 90 mg BID generally show an acceptable profile of platelet inhibition. The number of studies reporting clinical outcomes in CAD patients receiving reduced MD of ticagrelor are limited, however available results indicate that in a stable setting this strategy offers improved safety with preserved efficacy in the prevention of thrombotic events.

The article deals with the individual features of language in the contemporary Polish reportage based on the text Zabójca z miasta moreli: reportaże z Turcji by Witold Szabłowski. The author presents both the statistical analysis and the stylistic peculiarities of this reportage which received a prestigious Beata Pawlak Award in 2011 and contains important components characteristic for the journalistic style. The author uses the traditional syntactic model of Zenon Klemensiewicz and takes into consideration Stanisław Jodłowski’s research achievements. According to the postulates of Anna Wierzbicka, Maria Rachwałowa, Stanisław Mikołajczak, and Marek Ruszkowski, she selects a sample of 200 utterances which are examples of such narrative constructions that strongly indicate subjectivity. In her research, firstly, she conducts a detailed analysis of the syntactic and statistical features of Szabłowski's text in comparison with the style of the contemporary Polish reportage. Secondly, she draws attention to unique stylistic features indicating the reporting syntax. As a result, the author notices the following individual features of language in Zabójca z miasta moreli: reportaże z Turcji by Witold Szabłowski: 1) simple utterances and direct and indirect objects in the developed sentences, 2) developed clauses and adverbials, 3) objective hypotaxis, and 4) adverbial hypotaxis.

Background: Contemporary antiplatelet treatment in acute myocardial infarction (AMI) is based on one of two P2Y12 receptor inhibitors, prasugrel or ticagrelor. The aim of this study was to compare diurnal variability of platelet reactivity between patients receiving prasugrel and ticagrelor during the initial phase of maintenance treatment after AMI. Methods: It was a prospective, two-center, pharmacodynamic, observational study. Blood for platelet testing was sampled at four time points on day four after AMI (8:00, 12:00, 16:00, 20:00). Diurnal variability of platelet reactivity was expressed as a coefficient of variation (CV) of the above-mentioned measurements. Results: 73 invasively-treated patients were enrolled (ticagrelor: n = 47, prasugrel: n = 26). CV was greater in patients treated with ticagrelor compared with prasugrel according to a VASP assay (47.8 [31.6–64.6]% vs. 21.3 [12.9–25.5]%, p < 0.001), while no statistical differences were detected when the CVs of platelet aggregation according to Multiplate were compared between ticagrelor- and prasugrel-treated patients. Ticagrelor-treated patients showed more pronounced platelet inhibition than prasugrel at 16:00 and 20:00 (VASP16:00: 20.6 ± 15.0 vs. 24.9 ± 12.8 PRI, p = 0.049; VASP20:00: 18.6 ± 17.7 vs. 26.0 ± 11.7 PRI, p = 0.002). Conclusions: Ticagrelor shows greater diurnal variability in platelet aggregation than prasugrel during the initial maintenance phase of AMI treatment, and this is due to the continuous increase of platelet inhibition after the morning maintenance dose. Both drugs provide an adequate antiplatelet effect early after AMI. Evaluation of the clinical significance of these findings warrants further investigation.

Excessive platelet reactivity plays a pivotal role in the pathogenesis of acute myocardial infarction. Today, the vast majority of patients presenting with acute coronary syndromes qualify for invasive treatment strategy and thus require fast and efficient platelet inhibition. Since 2008, in cases of ST-elevation myocardial infarction, the European Society of Cardiology guidelines have recommended pretreatment with a P2Y12 inhibitor. This approach has become the standard of care in the majority of centers worldwide. Nevertheless, the latest guidelines for the management of patients presenting with acute coronary syndrome without persisting ST-elevation preclude routine pretreatment with the P2Y12 receptor inhibitor. Those who oppose pretreatment support their stance with trials failing to prove the benefits of this strategy at the cost of an increased risk of major bleeding, especially in individuals inappropriately diagnosed with an acute coronary syndrome, thus having no indication for platelet inhibition. However, adequate platelet inhibition requires even up to several hours after application of a loading dose of P2Y12 receptor inhibitors. Omission of data from pharmacokinetic and pharmacodynamic studies in the absence of data from clinical studies makes generalization of the pretreatment recommendations difficult to accept. We aimed to review the scientific evidence supporting the current recommendations regarding pretreatment with P2Y12 inhibitors.

Morphine is routinely used for pain relief in patients with acute myocardial infarction. However, it was documented that morphine decreases the bioavailability and antiplatelet effect of P2Y 12 receptor inhibitors. Multiple strategies to overcome this undesirable interaction are currently under investigation; they include the follwing: administration of crushed ticagrelor tablets, co-administration of metoclopramide, bridging with intravenous antiplatelet agents, or replacement of morphine with other analgesic. Adequately powered randomised trials examining the clinical consequences of concomitant use of morphine and P2Y 12 receptor inhibitors are still lacking.

Discordant interpretations of the results of clinical trials often drive scientific disputes. Our position concerning the protocol and performance of the ISAR-REACT 5 trial have been termed as false and groundless in the recently published article. We deeply disagree with this judgement and still maintain all our opinions expressed in the previous publications, without any exceptions. As demonstrated in multiple studies, prasugrel has excellent effectiveness and predictability. In our previous publications, it was not the drug itself that we put under criticism, but rather the quality of the trial assessing the drug. As a consequence of this critical approach, we stated that taking into account the serious limitations of the ISAR-REACT 5 trial, its results should be taken with cautiousness. To summarize, we remain open to further creative scientific dispute enriching both readers and authors.

In this study, novel single nucleotide polymorphisms (SNPs) were found in the 5'-regulatory regions (promoters) of the bovine glucose transporter (GT) genes

The risk of ischemic events gradually decreases after acute coronary syndrome (ACS), reaching a stable level after 1 month, while the risk of bleeding remains steady during the whole period of dual antiplatelet treatment (DAPT). Several de-escalation strategies of antiplatelet treatment aiming to enhance safety of DAPT without depriving it of its efficacy have been evaluated so far. We hypothesized that reduction of the ticagrelor maintenance dose 1 month after ACS and its continuation until 12 months after ACS may improve adherence to antiplatelet treatment due to better tolerability compared with the standard dose of ticagrelor. Moreover, improved safety of treatment and preserved anti-ischemic benefit may also be expected with additional acetylsalicylic acid (ASA) withdrawal. To evaluate these hypotheses, we designed the Evaluating Safety and Efficacy of Two Ticagrelor-based De-escalation Antiplatelet Strategies in Acute Coronary Syndrome - a randomized clinical trial (ELECTRA-SIRIO 2), to assess the influence of ticagrelor dose reduction with or without continuation of ASA versus DAPT with standard dose ticagrelor in reducing clinically relevant bleeding and maintaining anti-ischemic efficacy in ACS patients. The study was designed as a phase III, randomized, multicenter, double-blind, investigator-initiated clinical study with a 12-month follow-up (ClinicalTrials.gov Identifier: NCT04718025; EudraCT number: 2020-005130-15).

We present a case of a 75-year-old man, who underwent a scheduled implantable cardioverter-defibrillator reoperation and has had a lung cancer found in a chest X-ray taken after the procedure, that was completely obscured by the previous device.

High platelet reactivity (HPR) is a risk factor for stent thrombosis, a potentially lethal complication of percutaneous coronary intervention. HPR is also associated with increased risk of myocardial infarction and death in invasively-treated patients with acute coronary syndrome (ACS). HPR occurs even in ACS patients treated with ticagrelor, a state-of-the-art antiplatelet agent, especially during the first hours of treatment. Patient-level pharmacodynamic data obtained from 102 ACS subjects enrolled in two prospective, pharmacodynamic trials were analysed in order to identify clinical features related with increased odds of on-ticagrelor HPR during the first two hours after ticagrelor loading dose in ACS patients. Presence of ST-segment elevation myocardial infarction (versus non-ST-segment elevation ACS) and morphine co-administration were the strongest predictors of HPR at 1 and 2 hours after ticagrelor loading dose according to linear regression analyses, multiple backward stepwise logistic regression analyses and generalized estimating equation model. By pinpointing simple to recognize clinical features, the results of this study facilitate identification of ACS patients who have the highest odds of HPR during the initial phase of treatment with ticagrelor, and who could potentially benefit from alternative treatment strategies.

Aims: Cardiac resynchronization therapy (CRT) is a treatment dedicated to patients suffering from heart failure and asynchrony of systole typically due to left bundle branch block (LBBB). The aim of this study is to analyse the safety of CRT device implantation in a large single-centre group. Methods and results: The retrospective analysis of 198 patients hospitalized in the Department of Cardiology, dr A. Jurasz University Hospital no 1 in Bydgoszcz, who underwent CRT devices implantations in two consecutive years (2015–2016) has been performed. Out of 198 patients, 136 underwent implantation of CRT de novo and 62 exchange of the device. Studied procedures included implantations of 121 (89.0%) cardiac resynchronization therapy defibrillators (CRT-D) and 15 (11.0%) cardiac resynchronization therapy pacemakers (CRT-P) de novo, as procedures of exchange were excluded from statistical analysis. Collected data included: reported complications, patients’ basic clinical characteristics, comorbidities and details of implantation procedures. Development of any complication was observed in 43 patients (31.6%), out of whom 29 (21.3%) experienced one, 10 (7.4%) two and 4 (2.9%) three complications. Most of them were minor complications. Serious complications which included pneumothorax, mediastinal hematoma and cardiac tamponade were observed in 6 (4.4%) cases, there were no perioperative deaths. The occurrence of complications was significantly more frequent in females (OR , 3.45, 95% CI 1.37–8.71, p 0.008), was associated with prolonged procedure time (OR 1.11, 95% CI 1.04–1.20, p 0.003) and prolonged hospitalization time (OR 1.16, 95% CI 1.06–1.27, p 0.001). Conclusion: Overall, implantations of CRT devices are burdened with a substantial risk of complications, although the majority of them are minor and do not require subsequent surgical intervention. The risk of developing serious complications is low, accounting for 4.4%.

Acute coronary syndromes (ACS) represent one of the most perilous presentations of ischemic heart disease. Temporal trends clearly demonstrate that ACS occur later and later in life. Elderly patients with ACS comprise a populous and growing group, with more than half of individuals presenting with myocardial infarction being 75 years or older. Nevertheless, geriatric patients are greatly underrepresented in the landmark ACS trials evaluating innovative pharmacological strategies.The authors critically summarize recently published research on contemporary and emerging antithrombotic therapy for the treatment of ACS in geriatric patients.Elderly ACS patients are characterized by simultaneously increased risk of cardiovascular events and bleeding. Very few studies assessing the efficacy and safety of novel ACS pharmacotherapy in geriatric patients are currently available. Guidelines on the treatment of ACS are based on the overall results of major randomized clinical trials (RCTs), and data supporting the recommended therapy in elderly mainly derive from subanalyses of these RCTs. Properly designed and powered RCTs are necessary to properly evaluate the net effect of current and emerging pharmacotherapy in geriatric patients. Until such data are available, elderly ACS patients should receive treatment according to the general recommendations.

The aim of this study was to provide a specific review of current medical literature regarding the lipid profile during prostate carcinoma (PCa) treatment. The main aim was to analyze the results presented by different authors and to find a commonality in the changes occurring during the treatment—hormonotherapy. The levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol were measured before and after the follow-up treatment. The manuscripts reviewed came from the period between 2008 and 2016. The size of the studies ranged from 16 participants to 310. The mean age was from 65 to 74 years in all studies. The Q test was used to attain all lipid parameters and to specify heterogeneity ( p < .0001). After 12 months of androgen deprivation therapy (ADT), the patients had a significantly higher level serum TC and TG.

Introduction. Electrocardiography (ECG) is a widely used diagnostic method for identification of patients with previous myocardial infarction (MI). The ECG manifestation of prior MI is the presence of the pathological Q waves. Patients with coronary artery disease (CAD) and diabetes are at high risk of MI. The aim of this study was to compare the prevalence and diagnostic accuracy of the pathological Q waves as an indicator of prior MI in patients with CAD and diabetes according to the present and former criteria. Methods. A cross-sectional, multi-centre study was conducted in outpatient clinics across Poland. Family physicians performed physical examinations, registered ECGs, and collected relevant information about onset of CAD and diabetes, presence and onset of hypertension, dyslipidaemia, heart failure, diabetic complications, history of MI, and pharmacotherapy. Centralised manual assessment of the obtained ECG tracings was performed. Two definitions of the pathological Q-waves were used — a present one according to the Universal Definition of MI and a former one based on the definition of MI developed by the World Health Organization. Results. We enrolled 796 patients (48.1% women, mean age 67.5 ± 10.2 years, and 51.9% men, mean age 64.3 ± 10.3 years) into the study. There were 158 patients (19.8%) — 102 men (24.7%) and 56 women (14.6%), who met the present definition of the pathological Q waves and 106 patients (13.3%) — 74 men (17.9%) and 32 women (8.4%), who met the former definition of the pathological Q waves. The prevalence of the pathological Q waves varied due to the certain group of leads. It was highest in the inferior leads — 104 and 75 according to the present and former definitions, respectively. Of note, the rate of the pathological Q waves increased up to 2.6 times in the lateral leads after the introduction of the less restrictive present definition. Sensitivity of prior MI detection by means of the present and former criteria was 26.8% and 19.8%, and specificity was 87.0% and 92.8%, respectively. The application of the present and former definitions detected prior MI with 65.6% and 71.6% positive predictive value, and with 56.3% and 55.6% negative predictive value, respectively. Conclusions. In the era of reperfusion therapy, ECG appears to be a poor diagnostic tool for detection of previous MI due to its low sensitivity. However, it may identify individuals without previous MI with rather high specificity. In diabetics with CAD, the present definition of the pathological Q waves increases sensitivity of prior MI detection by 7%, with a decrease in specificity by 6% as compared with the former definition.

Ticagrelor is a state-of-the-art antiplatelet agent used for the treatment of patients with acute coronary syndromes (ACS). Unlike remaining oral P2Y12 receptor inhibitors ticagrelor does not require metabolic activation to exert its antiplatelet action. Still, ticagrelor is extensively metabolized by hepatic CYP3A enzymes, and AR-C124910XX is its only active metabolite. A post hoc analysis of patient-level (n = 117) pharmacokinetic data pooled from two prospective studies was performed to identify clinical characteristics affecting the degree of AR-C124910XX formation during the first six hours after 180 mg ticagrelor loading dose in the setting of ACS. Both linear and multiple regression analyses indicated that ACS patients presenting with ST-elevation myocardial infarction or suffering from diabetes mellitus are more likely to have decreased rate of ticagrelor metabolism during the acute phase of ACS. Administration of morphine during ACS was found to negatively influence transformation of ticagrelor into AR-C124910XX when assessed with linear regression analysis, but not with multiple regression analysis. On the other hand, smoking appears to increase the degree of ticagrelor transformation in ACS patients. Mechanisms underlying our findings and their clinical significance warrant further research.

Statins are potent hypolipidemic drugs effectively reducing low-density lipoprotein (LDL) cholesterol serum concentration, but also exerting a wide range of pleiotropic effects. In numerous clinical trials statins were proven to substantially decrease cardiovascular morbidity and mortality both in primary and secondary prevention. However, a growing body of evidence suggests that statins, although safe and generally well-tolerated, are associated with an increased occurrence of new-onset diabetes mellitus (DM). The aim of this review is to explore the relationship between statin therapy and new-onset DM, including its clinical relevance and underlying pathomechanisms, and to discuss the concept of tailored statin therapy. According to our recently published comprehensive network meta-analysis including 113,394 patients, the high-dose statin regimens were connected with an elevated risk of new-onset DM as compared with moderate-dose statin regimens and a gradient for the risk of new-onset DM across different types and doses of statins was demonstrated. There are multiple possible mechanisms explaining the diabetogenic effect of statins (e.g., decreased insulin secretion, induction of b-cell apoptosis, increased insulin resistance or compromised glucose transport into the cells). Statins are among the most widely used drugs worldwide and physicians should be aware of the fact that there is a risk of new-onset DM across different types and doses of statins. Selection of adequate statin that suits patient’s needs remains the challenge of hypolipidemic therapy. The identification of individuals who would benefit more from smaller doses and/or use of less diabetogenic compounds could help to optimize the treatment and reduce the number of patients developing DM. The non-pharmacological approach such as adequate physical activity, weight reduction and low fat diet should not be neglected either. These actions create a chance to decrease baseline LDL-cholesterol concentration and reduce the number of both cardiovascular and DM risk factors. All in all, statins with their exceptional cardiovascular benefits will undoubtedly defend their position of a cornerstone of cardiovascular prevention because profits derived from statin therapy far exceed the potential harms connected with statin-induced impairments of glucose metabolism.

High-accuracy dispersive optical spectroscopy measurements in the visible (VIS) region have been performed on the less-abundant 12C17O isotopologue, observing high-resolution emission bands of the B1Σ+ (υ = 0) → A1Π (υ = 3, 4, and 5) Angstrom system. These are combined with high-resolution photoabsorption measurements of the 12C17O B1Σ+ (υ = 0) ← X1Σ+ (υ = 0) and C1Σ+ (υ = 0) ← X1Σ+ (υ = 0) Hopfield–Birge bands recorded with the vacuum-ultraviolet (VUV) Fourier transform spectrometer, installed on the DESIRS beamline at the SOLEIL synchrotron. The frequencies of 429 observed transitions have been determined in the 15 100–18 400 cm−1 and 86 900–92 100 cm−1 regions with an absolute accuracy of up to 0.003 cm−1 and 0.005 cm−1 for the B–A, and B–X, C–X systems, respectively. These new experimental data were combined with data from the previously analysed C → A and B → A systems. The comprehensive data set, 982 spectral lines belonging to 12 bands, was included in a deperturbation analysis of the A1Π, υ = 1–5 levels of 12C17O, taking into account interactions with levels in the d3Δi, e3Σ−, a′3Σ+, I1Σ− and D1Δ states. The A1Π and perturber states were described in terms of a set of deperturbed molecular constants, spin–orbit and L-uncoupling interaction parameters, equilibrium constants, 309 term values, as well as isotopologue-independent spin–orbit and rotation-electronic perturbation parameters.

Aims The currently available data indicate a drug–drug interaction between morphine and oral P2Y12 receptor inhibitors, when administered together. The aim of this trial was to assess the influence of infused morphine on pharmacokinetics and pharmacodynamics of ticagrelor and its active metabolite (AR-C124910XX) in patients with acute myocardial infarction. Methods and results In a single-centre, randomized, double-blind trial, patients were assigned in a 1:1 ratio to receive intravenously either morphine (5 mg) or placebo, followed by a 180 mg loading dose of ticagrelor. Pharmacokinetics was determined with liquid chromatography tandem mass spectrometry and ticagrelor antiplatelet effects were measured with up to three different platelet function tests: vasodilator-stimulated phosphoprotein phosphorylation assay, multiple electrode aggregometry and VerifyNow. The pharmacokinetic and pharmacodynamic assessment was performed in 70 patients (35 in each study group). Morphine lowered the total exposure to ticagrelor and its active metabolite by 36% (AUC(0–12): 6307 vs. 9791 ng h/mL; P = 0.003), and 37% (AUC(0–12): 1503 vs. 2388 ng h/mL; P = 0.008), respectively, with a concomitant delay in maximal plasma concentration of ticagrelor (4 vs. 2 h; P = 0.004). Multiple regression analysis showed that lower AUC(0–12) values for ticagrelor were independently associated with the administration of morphine ( P = 0.004) and the presence of ST-segment elevation myocardial infarction ( P = 0.014). All three methods of platelet reactivity assessment showed a stronger antiplatelet effect in the placebo group and a greater prevalence of high platelet reactivity in patients receiving morphine. Conclusions Morphine delays and attenuates ticagrelor exposure and action in patients with myocardial infarction. ClinicalTrials.gov Identifier: [NCT02217878][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02217878&atom=%2Fehj%2Fearly%2F2015%2F10%2F20%2Feurheartj.ehv547.atom

In the emission spectrum of the CO molecule thirteen bands of the fourth-positive ( A 1 Π → X 1 Σ + ) band system were photographed and analysed. Under high resolution and by using conventional photographic spectroscopy, the following excited bands: 7–16, 7–17, 8–18, 8–19, 9–19, 9–20, 10–20, 10–21, 11–21, 11–22, 12–22, 13–24, 14–26 and approximately 1340 molecular lines were recorded. A rotational analysis of the bands: 7–17, 8–18, 8–19, 9–20, and 11–22 were carried out for the first time, and the bands 11–21 and 14–26 were identified and analysed for the first time. After detailed rotational analysis of the bands, experimental rovibronic term values of the A 1 Π ( v = 9 –14) levels were determined for the first time. Individual and equilibrium molecular constants of the A 1 Π state as well as the Franck–Condon factors were determined for the analysed bands. Moreover, a region of analysed perturbations of the A 1 Π ( v = 7 –14) levels was extended to the J ⩾ 30 rotational levels. Also, most of theoretically predicted perturbations of the v A = 13 and 14 levels were identified for the first time.

The aim of this work was to evaluate the influence of supplementation of multiflower honey with bee products on the phenolic compound content and on antioxidant activity. Average total phenolic and flavonoids contents in the multiflower honeys were 36.06 ± 10.18 mg GAE/100 g and 4.48 ± 1.69 mg QE/100 g, respectively. The addition of royal jelly did not affect significantly the phenolic compound content and antioxidant activity. Supplementation of honey with other bee products, i.e. beebread, propolis, pollen, resulted in significant increase in the total phenolic and flavonoids contents, and in antiradical activity and reducing power, with the largest effect found for addition of beebread. Significant linear correlations between the total phenolic and flavonoids contents and antiradical activity and reducing power were found.

Water storage reservoir in the Kluczbork municipality in Ligota Zamecka is located on the Stobrawa river. In 1997 the river flooded surrounding towns and villages. It was decided to build a reservoir that during successive flood states would protect residents. The aim of this study is to analyze the possibility of using water reservoir in Kluczbork municipality for recreation and tourism purposes. The results of two surveys conducted among residents of Ligota Zamecka have been analyzed. The residents could express their opinion about the project. The first questionnaire was conducted at the time when local community was only aware of the project to build retention and recreation reservoir in Kluczbork. The second survey was conducted when the reservoir was completed and filled with water. The results indicate the change in the attitude of inhabitants towards the reservoir – the opinions were mostly positive. They think that it would be a good promotion for the Kluczbork municipality. Moreover, the physico-chemical properties of water from the reservoir were examined. The samples were collected in the autumn and spring below the inlet of Stobrawa river into the preliminary tank and at the inlet into the main tank.

Around the World, metal pollution is a major problem. Conventional practices of toxic metal removal can be ineffective and/or expensive, delaying and exacerbating the crisis. Those communities dealing with contamination must be aware of the fundamentals advances of microbe-mediated metal removal practices because these methods can be easily used and require less remedial intervention. This book describes innovations and efficient applications for metal bioremediation for environments polluted by metal contaminates.

Introduction The most common classification of acute myocardial infarction (AMI) is based on electrocardiographic findings and distinguishes ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI). Both types of AMI differ concerning their epidemiology, clinical approach and early outcomes. Ticagrelor is a P2Y12 receptor inhibitor, constituting the first-line treatment for STEMI and NSTEMI. According to available data, STEMI may be associated with lower plasma concentration of ticagrelor in the first hours of AMI, but currently there are no studies directly comparing ticagrelor pharmacokinetics or antiplatelet effect in patients with STEMI versus NSTEMI. Methods and analysis The PINPOINT study is a phase IV, single-centre, investigator-initiated, prospective, observational study designed to compare the pharmacokinetics and pharmacodynamics of ticagrelor in patients with STEMI and NSTEMI assigned to the invasive strategy of treatment. Based on an internal pilot study, the trial is expected to include at least 23 patients with each AMI type. All subjects will receive a 180 mg loading dose of ticagrelor. The primary end point of the study is the area under the plasma concentration-time curve (AUC (0–6) ) for ticagrelor during the first 6 hours after the loading dose. Secondary end points include various pharmacokinetic features of ticagrelor and its active metabolite (AR-C124910XX), and evaluation of platelet reactivity by the vasodilator-stimulated phosphoprotein assay and multiple electrode aggregometry. Blood samples for the pharmacokinetic and pharmacodynamic assessment will be obtained at pretreatment, 30 min, 1, 2, 3, 4, 6 and 12 hours post-ticagrelor loading dose. Ethics and dissemination The study received approval from the Local Ethics Committee (Komisja Bioetyczna Uniwersytetu Mikolaja Kopernika w Toruniu przy Collegium Medicum im. Ludwika Rydygiera w Bydgoszczy; approval reference number KB 617/2015). The study results will be disseminated through conference presentations and peer-reviewed journals. Trial registration number NCT02602444; Pre-results.

Contains fulltext : 135993.pdf (Publisher’s version ) (Open Access) Soon after identification of the platelet membrane glycoprotein (GP) IIb/IIIa, it has become a target of antiplatelet therapy. There are 3 intravenous GP IIb/IIIa receptor inhibitors, namely- eptifibatide, tirofiban and abciximab, used in the contemporary clinical practice, particularly in patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI). The aim of the current review is to summarize available knowledge concerning off-target effects of GP IIb/IIIa receptor inhibitors. All 3 drugs have similar antithrombotic properties, but differ with respect to pharmacodynamics, pharmacokinetics and off-target effects. Eptifibatide and tirofiban are highly specific GP IIb/IIIa receptor inhibitors, while abciximab is unselectiveand cross-reacts with integrin avb3 - a vitronectin receptor and leukocyte-associatedi ntegrin Mac-1. As a result of these interactions, abciximab seems to reduce the development of clinical restenosis, decrease infarct size, inhibit adhesion of monocytes to medical steel and modulate the inflammatory response. Intracoronary administration of abciximab provides higher drug concentration in the target area, increasing dose-dependent interactions with other integrins. Off-target effects of small molecule GP IIb/IIIa receptor inhibitors (i.e. eptifibatide and tirofiban) are predominantly connected with their suppressive influence on the inflammatory response. All in all, although GP IIb/IIIa receptor inhibitors are not recommended as a routine therapy during PCI, their antiplatelet properties and potential off-target effects may bebeneficial in certain subsets of patients.

In the isotopic 14C16O molecule eight bands of the fourth-positive (A1Π → X1Σ+) system were investigated for the first time. Under high resolution, using conventional photographic emission spectroscopy technique, highly excited 7–19, 8–20, 9–21, 10–21, 11–22, 12–23, 12–24 and 13–24 bands were recorded and spectroscopically analyzed. First individual constants of the rovibronic structure: B v ′ and D v ′ of both A1Π and X1Σ+ states as well as the equilibrium constants: Be, αe, γe, ωe, ωexe, and ωeye of the upper A1Π state were obtained. First values of band origins for all studied bands were also computed. On the basis of these parameters and the ground X1Σ+ state constants recalculated isotopically from Le Floch [1] spectroscopic constants, the first experimental rovibronic term values of the A1Π state vA = 7–13 levels were calculated. Numerous observed rotational perturbations of the A1Π state were identified and compared with the theoretically determined ones.

BACKGROUND: Data from available studies suggest that the presence of ST-elevation myocardial infarction (STEMI) may be associated with delayed and attenuated ticagrelor bioavailability and effect compared with non-ST-elevation myocardial infarction (NSTEMI). METHODS: In a single-center, prospective, observational trial 73 patients with myocardial infarction (STEMI n = 49, NSTEMI n = 24) underwent a pharmacokinetic and pharmacodynamic assessment after a 180 mg ticagrelor loading dose (LD). Ticagrelor and its active metabolite (AR-C124910XX) plasma concentrations were determined with liquid chromatography tandem mass spectrometry, and their antiplatelet effect was measured with the VASP assay and multiple electrode aggregometry. RESULTS: During the first six hours after ticagrelor LD, STEMI patients had 38% and 34% lower plasma concentration of ticagrelor and AR-C124910XX, respectively, than NSTEMI (ticagrelor AUC(0-6): 2491 [344-5587] vs. 3991 [1406-9284] ng*h/mL; p = 0.038; AR-C124910XX AUC(0-6): 473 [0-924] vs. 712 [346-1616] ng*h/mL; p = 0.027). STEMI patients also required more time to achieve maximal concentration of ticagrelor (tmax: 4.0 [3.0-12.0] vs. 2.5 [2.0-6.0] h; p = 0.012). Impaired bioavailability of ticagrelor and AR-C124910XX seen in STEMI subjects was associated with diminished platelet inhibition in this group, which was most pronounced during the initial hours of treatment. CONCLUSIONS: Plasma concentrations of ticagrelor and AR-C124910XX during the first hours after ticagrelor LD were one third lower in STEMI than in NSTEMI patients. This reduced and delayed ticagrelor bioavailability was associated with weaker antiplatelet effect in STEMI. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02602444 (November 09, 2015).

Acute coronary syndromes (ACS) are one of the leading causes of death worldwide. Several landmark trials, followed by a widespread introduction of new agents, have significantly improved ACS outcomes in recent years. However, despite the use of contemporary therapy, a substantial number of ACS patients continue to suffer from cardiovascular events. Areas covered: The aim of this review was to summarize available data on innovative drugs and pharmacological strategies that have potential to amend the current ACS therapy. We present the results of recent large clinical trials, as well as insights from ongoing phase III and phase IV studies, exploring the value of new strategies for the improvement of outcomes in ACS. Expert opinion: More potent platelet inhibition, more profound lipid reduction and possibly anti-inflammatory action are considered to have potential to further reduce the rates of adverse cardiovascular and thrombotic events in ACS patients. 'Hit fast, hit hard' approach regarding novel antiplatelet and lipid-lowering therapy seems attractive, but it has to be considered that these strategies may be associated with increased adverse events rate. Introduction of cangrelor and ezetimibe, and potentially future recognition of proprotein convertase subtilisin/kexin type 9 antibodies, are likely to alter the landscape of ACS pharmacotherapy.

SummaryAim of this study was assessment of the relationship between concentrations of ticagrelor and its active metabolite (AR-C124910XX) and results of selected platelet function tests. In a single-centre, cohort study, patients with myocardial infarction underwent blood sampling following a 180 mg ticagrelor loading dose intake (predose, 1, 2, 3, 4, 6, 12, 24 hours postdose) to perform pharmacokinetic and pharmacodynamic assessments. Platelet reactivity was evaluated using the VASP-assay, the VerifyNow device and the Multiplate analyzer. Analysis of 36 patients revealed high negative correlations between ticagrelor concentrations and platelet reactivity evaluated with all three platelet function tests (the VASP-assay: RS=-0.722; pStudy registration: ClinicalTrials.gov identifier NCT02690454.