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Background Dysregulation of epigenetic processes might account for alterations of the hypothalamic-pituitary-adrenal axis observed in patients with schizophrenia. Therefore, in this study, we aimed to investigate methylation of the glucocorticoid receptor (NR3C1) gene in patients with schizophrenia-spectrum disorders, individuals at familial high risk of schizophrenia (FHR-P), and healthy controls with respect to clinical manifestation and a history of psychosocial stressors. Methods We recruited 40 first-episode psychosis patients, 45 acutely relapsed schizophrenia (SCZ-AR) patients, 39 FHR-P individuals, and 56 healthy controls. The level of methylation at 9 CpG sites of the NR3C1 gene was determined using pyrosequencing. Results The level of NR3C1 methylation was significantly lower in first-episode psychosis patients and significantly higher in SCZ-AR patients compared with other subgroups of participants. Individuals with FHR-P and healthy controls had similar levels of NR3C1 methylation. A history of adverse childhood experiences was associated with significantly lower NR3C1 methylation in all subgroups of participants. Higher methylation of the NR3C1 gene was related to worse performance of attention and immediate memory as well as lower level of general functioning in patients with psychosis. Conclusions Patients with schizophrenia-spectrum disorders show altered levels of NR3C1 methylation that are significantly lower in first-episode psychosis patients and significantly higher in SCZ-AR patients. Higher methylation of the NR3C1 gene might be related to cognitive impairment observed in this clinical population. The association between a history of adverse childhood experiences and lower NR3C1 methylation is not specific to patients with psychosis. Longitudinal studies are needed to establish causal mechanisms underlying these observations.

An intra-hippocampus injection of kainic acid serves as a model of status epilepticus and the subsequent development of temporal lobe epilepsy. Matrix metalloproteinase-9 (MMP-9) is an enzyme that controls remodeling of the extracellular milieu under physiological and pathological conditions. In response to brain insult, MMP-9 contributes to pathological synaptic plasticity that may play a role in the progression of an epileptic condition. Marimastat is a metalloproteinase inhibitor that was tested in clinical trials of cancer. The present study assessed whether marimastat can impair the development of epilepsy. The inhibitory efficacy of marimastat was initially tested in neuronal cultures in vitro. As a marker substrate, we used nectin-3. Next, we investigated the blood–brain barrier penetration of marimastat using mass spectrometry and evaluated the therapeutic potential of marimastat against seizure outcomes. We found that marimastat inhibited the cleavage of nectin-3 in hippocampal neuronal cell cultures. Marimastat penetrated the blood–brain barrier and exerted an inhibitory effect on metalloproteinase activity in the brain. Finally, marimastat decreased some seizure parameters, such as seizure score and number, but did not directly affect status epilepticus. The long-term effects of marimastat were evident up to 6 weeks after kainic acid administration, in which marimastat still inhibited seizure duration.

Previous studies have reported on the relationship between gut microbiota and major depressive disorder (MDD). However, there remain gaps in literature concerning the role of the intestinal barrier and microflora in the pathogenesis of depression. This study analyzes the potential causative relationship between gut microbiota and inflammatory and gut integrity markers and clinical symptoms in inpatients with depressive episodes. Sixteen inpatients (50% females) being treated with escitalopram (5–20 mg daily) in standardized conditions were included in the study. The composition of fecal microbiota was evaluated at baseline and endpoint using 16S rRNA sequencing. A significant correlation between depression severity was found, as measured with HDRS24 (Hamilton Depression Rating Scale-24 item), and the following abundance in bacteria: positive correlation with Paraprevotella (r = 0.80, q = 0.012), strong, negative correlations with Clostridiales (r = −0.70, q = 0.016), Clostridia (r = −0.71, q = 0.026), Firmicutes (r = −0.67. q = 0.032), and the RF32 order (r = −0.70, p = 0.016) in the Alphaproteobacteria (r = −0.66, q = 0.031). After six weeks of treatment, clinical outcomes were found to have a negative correlation with levels of plasma intestinal fatty acid-binding protein (IFABP) at the beginning of the study. Still they had a positive correlation with changes in fecal calprotectin during hospitalization. In conclusion, gut microbiota was associated with the severity of depressive symptoms. However, these findings do not serve as predictors of symptomatic improvement during antidepressant treatment in inpatient treatment for MDD. In turn, intestinal integrity and inflammation markers were associated with the response to treatment of patients with MDD and symptom severity. Additional studies are needed to confirm and extend these findings.

Aim: The aim of the study was to evaluate physical fitness of rural children and adolescents on the example of pupils of the School Complex in Ołdaki, Poland. Material and method: The study covered 79 pupils of grades IV–VI of the primary school and I–III of the lower secondary school of the School Complex in Ołdaki. The study used K. Zuchora’s Index of Physical Fitness and a diagnostic survey method based on the author-prepared questionnaire. Results: The study conducted among pupils of the School Complex in Ołdaki showed that physical fitness of children and adolescents from the countryside was at a relatively good level. Of the components of the Index of Physical Fitness, the worst results were obtained for abdominal muscle strength. However, the subjects showed very good flexibility, endurance and speed. Girls and boys obtained similar test results. Striking is the fact that the oldest subjects, i.e. pupils in grade III of the lower secondary school, obtained the worst results both in the entire test and in individual exercises. Conclusions: The pupils knew how to take care of their health; they were able to indicate the benefits of being physically active, were eager to take part in physical education classes and actively spent their free time. They mostly believed that they could eat healthy. Only a small percentage of pupils admitted to have had contact with stimulants and fast-foods, which was a confirmation of the fact that they were taking good care of their health. Fitness tests proved that the pupils’ fitness was at a satisfactory level. There was no noticeable difference in the results obtained by girls and boys, which indicated similar performance in all pupils. The evaluation of the pupils’ activity in their free time proved that they were more willing to spend it actively, most often playing football and cycling 2–3 times a week.

Background Patients with ischemic heart disease (IHD) are at risk for ventricular tachycardia (VT). Catheter ablation (CA) may reduce this risk. Objective To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) of CA of VT in patients with IHD. Methods Literature searches of MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL), and the Cochrane Database of Systematic Reviews (CDSR) were performed from January 2000 through April 2018 to identify RCTs comparing a strategy of CA vs no ablation in patients with IHD and an implantable cardioverter defibrillator (ICD). Outcomes of interest included appropriate ICD therapies, appropriate ICD shocks, VT storm, recurrent VT/ventricular fibrillation (VF), cardiac hospitalizations, and all-cause mortality. Using an inverse variance random-effects model, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each endpoint. Results A total of 5 RCTs (N = 635 patients) were included, with a duration of follow-up ranging from 6 months to 27.9 months. Patients who underwent CA experienced decreased odds of appropriate ICD therapies (OR 0.49; 95% CI 0.28–0.87), appropriate ICD shocks (OR 0.52; 95% CI 0.28–0.96), VT storm (OR 0.64; 95% CI 0.43–0.95), and cardiac hospitalization (OR 0.67; 95% CI 0.46–0.97) vs those who did not undergo ablation. There was no evidence of a benefit for recurrent VT/VF (OR 0.87; 95% CI 0.41–1.85), although this endpoint was not reported in all trials, or for all-cause mortality (OR 0.89; 95% CI 0.60–1.34). Conclusion In this systematic review and meta-analysis of RCTs, CA was associated with a significant reduction in the odds of appropriate ICD therapies, appropriate ICD shocks, VT storm, and cardiac hospitalizations in patients with IHD.

The problem of eating disorders was described in literature for the first time at the end of the 17th century. Nowadays, the term eating disorders means adisturbance to eating habits for which the common denominator is, among others, a characteristic way of thinking and behaviors observed in people who are ill. Anorexia is a disorder increasingly observed among young people, but in fact the problem of eating disorders affects each age group and gender, and this aspect is presented in the following article.

We report a case of young female with remittent bilateral pulmonary embolism and thrombus in the right ventricle, who required highly specialized treatment. The coexistence of right heart thrombus with pulmonary thromboembolism is uncommon; however, significantly worsens patients prognosis. Treatment is still controversial.

Background: Atrial fibrillation (AF) is the most common clinically-significant arrhythmia in the adult population, and it is a strong independent risk factor for cerebrovascular accidents. Patients with non-valvular AF are five times more likely to suffer a stroke. Despite the clear recommendations for anticoagulant therapy, many clinicians are still reluctant to provide routine oral anticoagulation to patients with AF, despite the potential clinical benefits. Aim: To compare Polish and European populations of patients with AF and the every-day practice of stroke prevention in Poland and in the rest of Europe. Methods: We analysed the baseline data from the two first cohorts of patients enrolled in the GARFIELD-AF registry (an ongo­ing prospective, multicentre, international registry of patients newly diagnosed with AF) in Poland and in the rest of Europe. Results: Polish AF patients are generally younger (median age 67 years in both cohorts vs. 73 in cohort 1 in the rest of Eu­rope and 72 in cohort 2), but they carry a burden of more concomitant diseases. There are some noticeable differences in stroke prevention between Poland and the rest of Europe. The use of vitamin K antagonists (VKAs) is generally higher in other European countries in both cohorts (in Poland 41.7% in cohort 1 and 36.9% in cohort 2 vs. 55.5% in cohort 1 and 41.9% in cohort 2 in the rest of Europe). Meanwhile, it is generally more common in Poland to treat patients with both VKAs and antiplatelets (in cohort 1 20.4% of patients in Poland received vs. 12.0% in the rest of Europe). A total of 5.6% of patients in cohort 1 in Poland receive no antithrombotic treatment (it means: no VKA, oral factor Xa or thrombin inhibitors, antiplate­lets), meanwhile in other countries it amounts to 8.5%. The usage of non-vitamin K oral anticoagulants is growing in Poland similarly to the other European countries. Conclusions: The GARFIELD-AF registry data shows how distant everyday clinical practice is from the guidelines. It shows that still in Poland, as well as in the rest of Europe, too many patients with low stroke risk are treated with anticoagulants, while too frequently patients at high stroke risk are left with no stroke prevention. Although the tendency to use non-vitamin K oral anticoagulants is growing comparably in Poland and in the rest of Europe, the proportion of patients with intermediate and high stroke risk is not growing and more patients at low stroke risk are treated with anticoagulants.

BACKGROUND Replacement of severely stenotic aortic valve may influence cognitive and physical functioning. The aim of this study was to compare cognitive and functional status after surgical (SAVR) vs. transcatheter aortic valve replacements (TAVR) in the elderly with severe aortic stenosis (AS). METHODS It was a prospective observational study with over 6 months of follow-up. Eighty ≥70-year-old patients with AS underwent TAVR (N.=40) or SAVR (N.=40). Mini Mental State Exam (MMSE), activities daily living (ADL) score and instrumental activities daily living (IADL) score were used to assess the cognitive status, fundamental functioning and complex independent living skills, respectively. The tests were conducted at baseline and 6 months after the procedure. Additionally, MMSE was carried out at discharge. RESULTS Baseline MMSE score was lower in the TAVR vs. SAVR group (P=0.001). In the SAVR group, there was a transient in-hospital decline in mean MMSE score (P=0.020), absent in the TAVR group. Baseline ADL and IADL scores were lower in TAVR patients. Both groups experienced mild improvement. The average increase among those with improved IADL score was larger after TAVR (2.37 vs. 1.37 after SAVR; P=0.029). A systolic blood pressure (SBP) decrease

Background: Hepatocyte growth factor (HGF) concentration increases in the first few hours of myocardial infarction (MI). Aim: (1) To illustrate human HGF (hHGF) plasma concentration during the first 24 h of ST segment elevation myocardialinfarction (STEMI); (2) To estimate the odds ratio of STEMI in the context of hHGF measurements; (3) To describe the normalconcentration of hHGF in healthy subjects. Methods: The study groups consisted of 73 STEMI patients and 11 healthy volunteers. In all the patients, we took bloodsamples for hHGF twice, i.e. on admission to hospital and 24 h later. Results: The median value of hHGF in healthy volunteers was 666 pg/mL (576; 760 pg/mL). In STEMI, the highest values of hHGF were observed in the first measurement. An increase of 1 pg/mL in hHGF level increased STEMI odds ratio by 0.2%. Conclusions: In acute MI, of the known biomarkers, hHGF rises the earliest and very promptly returns to normal values.

Vascular endothelial growth factor (VEGF) is a regulator of vascular formation in physiological and pathological conditions. The aim of our study was to evaluate the value of VEGF as a surrogate marker of myocardial injury in acute ischemic conditions.In 104 consecutive patients with acute coronary syndrome (ACS) with and without ST segment elevation (STEMI and NSTEMI) the plasma and serum human VEGF (hVEGF) concentration was measured two times i.e. immediately after admission due to ACS and 24h later. According to ECG findings and coronary angiography results, patients were divided into three groups. Group A represented major myocardial injury due to ST-segment elevation in precordial leads and/or in I and aVL leads and with left anterior descending (LAD) artery responsible for STEMI symptoms or additionally with significant atherosclerotic lesions (lumen vessel narrowed50%) in other than LAD coronary arteries. Group B (medium myocardial injury) consisted of patients with ST-segment elevation in II, III and aVF leads and/or ST-segment depression in V2-V3 leads with one-vessel disease and the culprit artery was not LAD. Group C included patients with changes in ECG other than ST-segment elevation independently of the site of atherosclerotic lesions in coronary arteries.In all 104 patients with ACS the highest values of serum hVEGF were observed in second measurement (357.9 ± 346 pg/ml, p0.01). Although in the first measurement, plasma and serum hVEGF concentration did not differentiate groups, the difference between deltas for serum hVEGF was observed (p0.05). Increased number of neutrophils in the first measurement increased the OR of the high serum hVEGF concentration in the first measurement (OR=1.155; 95%CI: 1.011; 1.32) (p0.05). The number of neutrophils in the second measurement also revealed significant relationship with high serum hVEGF in the first assessment (OR=1.318, 95%CI: 1.097; 1.583) (p0.01). Increased values of triglycerides (exceeding the upper limit) were connected with decreased OR of high serum hVEGF concentrations in the first measurement (OR=0.152, 95%CI: 0.033; 0.695, p0.05).In acute coronary syndrome, serum VEGF concentrations are elevated and can serve as a surrogate marker of myocardial injury. The elevated number of neutrophils increases odds ratio of high VEGF concentrations in ACS. In patients with high concentrations of triglycerides, odds ratio of low level of hVEGF is expected.

Background: Platelet glycoprotein (GP) IIb/IIIa receptors are involved in platelet aggregation and acute thrombus formation. Changes in the expression of GP IIb/IIIa receptors are an important but little-explored aspect of antiplatelet therapy. Understanding these changes may be particularly relevant for elucidating the mechanisms and effects of GP IIb/IIIa antagonist therapy, and may help to establish methods to identify patients most likely to benefit from the use of GP IIb/IIIa blockade, or those especially prone to its thrombotic complications. The aim of this study was to evaluate the influence of common cardiovascular risk factors on the expression of GP IIb/IIIa receptors in patients with ST-segment-elevation myocardial infarction (STEMI) who received antiplatelet treatment under primary percutaneous coronary intervention (PCI). Materials and Methods: The study group consisted of 30 patients with STEMI who underwent PCI and who received antiplatelet treatment with aspirin (acetylsalicylic acid), a loading dose of clopidogrel and, if necessary, abciximab. The expression of platelet GP receptors was estimated by measuring the changes in the number of platelet antigens: CD41a (GP IIb/IIIa) and CD61 (GP IIIa). The assessments were performed in whole blood and on isolated platelets before and up to 24 hours after initiation of the antiplatelet therapy. The relationships between expression of platelet GP receptors and risk factors such as hypertension, smoking, diabetes mellitus, dyslipidemia, and family history of cardiovascular disease were examined using statistical analyses. Results: Before antiplatelet treatment, non-smokers had more receptors than smokers when antigen numbers were measured in whole blood. After treatment, the number of CD41a antigens present on isolated platelets significantly increased in non-smokers and in patients without dyslipidemia (p = 0.05). At the same time, the number of CD61 antigens increased in all patients except for those with diabetes. In patients without hypertension, the number of CD61 antigens (whole-blood measurement) increased considerably, and the difference between the patients with and without hypertension was significant (p = 0.01). The results of the study revealed that, after the treatment, the numbers of CD61 antigens were higher in patients without dyslipidemia and lower in patients with dyslipidemia compared with the results obtained from the preceding measurements. These different numbers of CD61 antigens significantly distinguished these two groups of patients from each other (p = 0.01). Conclusion: Non-smokers with STEMI have significantly higher expression of GP IIb/IIIa and IIIa receptors than do smokers. Up to 24 hours after the start of antiplatelet treatment, the number of GP IIb/IIIa receptors on the platelet surface did not depend on common cardiovascular risk factors such as hypertension, diabetes, smoking, and dyslipidemia. Patients without hypertension and without dyslipidemia tended to have more of only one component of the GP IIb/IIIa complex (i.e. GP IIIa, as represented by the antigen CD61) than the patients with these risk factors.

This study was designed to check the properties of hepatocyte growth factor (HGF) as a new marker of myocardial necrosis.In one hundred and four patients with acute coronary syndrome (ACS), plasma human HGF (hHGF) concentrations were assessed twice, i.e. just after admission to hospital and 24 h afterwards. The primary composite endpoint was assessed at three-month follow-up.The maximal concentration of hHGF (1902 pg/ml) was reached at the time of admission to hospital due to ACS with significant decrease 24 h after the first measurement (705 pg/ml p0.0001). hHGF levels in ST segment elevation myocardial infarction (STEMI) were higher than in non-ST segment elevation myocardial infarction (NSTEMI) and in patients who reached composite primary endpoint (33 patients-4211 pg/ml) vs. event-free 71 patients (1013 pg/ml p0.01). The correlation between values of hHGF and N-terminal prohormone B-type natriuretic peptide and cardiac troponin I was revealed.HGF is a very early, good marker of myocardial necrosis and a sensitive short- and long-term prognostic factor in ACS.

Hepatocyte growth factor (HGF) can be produced by various cells and elicits multiple biological responses such as motility, proliferation, morphogenesis and survival in a cell type-dependent fashion. Apart from its physiological importance, HGF may contribute to many organ diseases [1–3]. We have already shown that conversely to routinely measured biomarkers of myocardial injury, human HGF (hHGF) increases to high levels in the very early phase of acute coronary syndrome (ACS) and then decreases rapidly during the first 24 h of ACS [4]. As described in our previous article, we measured hHGF concentration only twice, namely at admission and 24 h later [4]. We decided to establish the dynamicity of hHGF level changes on the first day of myocardial injury and to determine the usefulness of its measurement in the case of untimely complications. In 4 patients with ST-segment elevation myocardial infarction (STEMI) and in 2 patients with non ST-segment elevation myocardial infarction (NSTEMI), who were eligible for coronary angiography and, possibly, primary percutaneous coronary intervention (PPCI), hHGF measurements were repeated 10 times during the first day of ACS and once at discharge from hospital (Figure 1). Each subject expressed their informed consent to participate in the study. Patients’ informed consent and the protocol of the study were approved by the Institutional Local Ethics Committee. Patients’ detailed particulars are presented in the Table I. Figure 1 Human HGF concentrations in six patients with ACS Table I Detailed description of six patients with ACS Human HGF was determined in plasma using the Quantikine Elisa kit from R&D Systems, Minneapolis, MN, USA. The mean value of hHGF evaluated in EDTA plasma using the Quantikine Elisa kit and presented in the manufacturer's brochure as a reference value was 787 pg/ml (range: 469-1113 pg/ml). In the first measurement, as illustrated in the Figure 1, a marked increase in hHGF levels was observed in STEMI patients. Very high values (maximally about 20 000 pg/ml) were reduced to almost normal values within 5 h from the first measurement. In NSTEMI patients, even in the first assessment we did not observe very high levels of hHGF, and during the first 24 h of ACS, hHGF levels were stable. Contrary to patients with an uncomplicated acute course of STEMI, 2 patients with serious cardiovascular events in the acute stage of myocardial infarction, namely cardiac arrest and early reocclusion of the coronary artery, revealed a second increase of hHGF levels during the first 24 h of ACS (Figure 1). We have already revealed that during the first 24 h of ACS HGF showed properties comparable with troponin I and N-terminal prohormone B-type natriuretic peptide (NT-proBNP), which are routinely used as markers of ischemic myocardial damage and risk stratification in patients with impaired left ventricular function [4–7]. Troponin I reached peak values and confirmed myocardial necrosis when hHGF levels were already at a normal level [4]. Now, the very high hHGF values were observed in patients admitted within the first 2 h of STEMI presentation (patients 5 and 6) (Figure 1, Table I). In this aspect, the observed changes in hHGF concentrations in the early stage of myocardial infarction are a great advantage of this diagnostic method. The time from the onset of ACS symptoms to treatment, effectiveness of reperfusion therapy measured as grade of flow in the infarct-related artery, and medical therapy applied during PPCI influence the levels of biomarkers [5, 8]. We supposed that in our study hHGF re-elevation was connected with acute complications of ACS. Due to the small number of patients we cannot definitely prove this relationship. We hope that subsequent research will confirm our preliminary observations. In conclusion, we found that: (1) in all our patients the highest hHGF values were observed at admission due to symptoms of acute coronary syndrome, (2) hHGF concentrations were reduced to normal values very quickly (within 5 h from the first measurement), (3) severe complications in the acute stage of STEMI most likely resulted in an additional increase in hHGF levels.

Thoracic aortic aneurysm is often an asymptomatic but potentially lethal disease if its most catastrophic complication – aortic dissection – occurs. Thoracic aortic dissection is associated with a high mortality rate despite ongoing improvement in its management. We report a fatal outcome of thoracic aortic aneurysm in a male patient with bicuspid aortic valve. The patient was qualified for elective surgery of the ascending aorta and aortic valve at the age of 39 but he did not agree to undergo the proposed procedure. Three years later, he experienced acute aortic dissection and died despite a prompt diagnosis and complex management.

We report the case of a 70-year-old woman with ST-segment elevation myocardial infarction of the anterior wall, complicated by ventricular septal rupture (two septal defects--VSDs) with symptoms of cardiogenic shock. After 6 weeks of conservative treatment with inotropes and intra-aortic balloon support, the patient underwent surgical repair of VSDs with good clinical outcome.

Background: Recent advances in molecular biology have made it possible to identify numerous polymorphisms of the renin-angiotensin system, which play an important role in the etiology of cardiovascular disease. Objective: The aims of the study were (i) to assess the distribution of the angiotensin II type 1 receptor (AGTR1) gene 1166A/C polymorphism and two polymorphisms of the angiotensinogen (AGT) gene (Met235Thr and Thr174Met) in patients with ST-segment-elevation myocardial infarction (STEMI) who underwent coronary angiography, compared with healthy volunteers; (ii) to determine if there was any correlation between these polymorphisms and risk of STEMI; and (iii) to assess the association of the examined polymorphisms with such classic cardiovascular risk factors as hypertension, diabetes mellitus, obesity (based on a body mass index ≥25 kg/m2), smoking, dyslipidemia, and family history of cardiovascular disease. Methods: A total of 100 patients (mean age 57 ± 10 years [range 31–76 years]; 21% women) with diagnosed STEMI and a control group consisting of 95 healthy volunteers (mean age 38 ± 11 years [range 17–60 years]; 20% women) were investigated for the AGTR1 1166A/C polymorphism and two variants of AGT (Met235Thr and Thr174Met). All patients received standard therapy for STEMI. Results: There were significant differences in the distribution of genotypes and the AGT Met174 allele for AGT Thr174Met polymorphism between patients and healthy subjects (p

We report the case of a 70-year-old woman with ST-segment elevation myocardial infarction of the anterior wall, complicated by ventricular septal rupture (two septal defects--VSDs) with symptoms of cardiogenic shock. After 6 weeks of conservative treatment with inotropes and intra-aortic balloon support, the patient underwent surgical repair of VSDs with good clinical outcome.

Activated Recombinant Factor VII (rFVIIa) in Bleeding Management after Therapy with IIb/IIIa-Inhibitor Tirofiban