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Purpose: Hemoconcentration during acute intense exercise is intensively investigated, while the rearrangement of hematological parameters during the recovery period is less understood. The aim of our study was to understand the mechanisms of hemodilution after short-term dynamic exercise. Methods: Twelve euhydrated male kayak athletes and 6 untrained controls were examined on a spiroergometer. In addition to the continuous recording of circulatory parameters, blood samples were taken at rest, at maximum load, and during restitution with a dense sampling frequency. Hemoglobin, hematocrit, osmolality, blood components, and core temperature were measured. Results: The hemoconcentration, independently of training status, reached its maximum (athletes Δ9.59% [4.18%] vs controls Δ11.85% [2.71%]) in the first minute of the recovery period. There was a significant increase in core temperature, reducing the viscosity of blood and promoting tissue oxygenation. High cardiac output and the increased blood flow compensate for viscosity being elevated by hemoconcentration during exercise. Hemoconcentration was maintained for 7 to 10 minutes and then diluted back to baseline 30 minutes after exercise. Temporarily higher viscosity during reduced cardiac output may result in a critical hemoconcentration zone, elevating the risk of circulatory overload. Elite athletes have a faster cardiac output decrease compared with that of hemodilution, making the circulation more vulnerable. We supposed that hemodilution was guided independently by plasma- and erythrocyte-related effectors. Conclusions: After high-intensity dynamic acute exercise, hemodilution is driven by independent factors, and a critical hemoconcentration zone may be formed during the recovery period in trained elite athletes.

In contrast to most other countries, in Hungary, suicide rates increased significantly in the first year (March to December 2020) of the COVID-19 epidemic. Worldwide, the burden of emergency health care tended to decrease in the first period of the pandemic. The main goal of the present research was to assess how the number of suicidal deliberate self-poisoning has changed in the first two years of the pandemic compared to the trend of the previous years (before March 2020) in the capital of Hungary, Budapest, and in Pest County (population approx. 3 million).In our retrospective cross-sectional study, we analyzed the results of emergency psychiatric evaluations of patients admitted to the Péterfy Hospital Emergency Department and Clinical Toxicology due to self-intoxication. From the data stored in the hospital's electronic health care system, we recorded two variables: suicidal self-poisoning, that is, suicide attempt, and the gender of the patient. Interrupted time series analysis was used, which relied on negative binomial regression estimates. In addition, the leveling in the trends was examined by changepoint detection.In males, suicide attempts decreased by 16.6% compared to the pre-pandemic period (p0.001). A similar and significant decrease was observed in females and the overall population. The trend change took place in August 2020 for women and the total population, and in October for men.It is suggested that people who have undergone a non-violent drug self-poisoning suicide attempt are less likely to call for help, such as an ambulance. Alternatively, fewer had attempted suicide because they did not want to be hospitalized. This hypothesis is supported by the fact that the change in the examined trend (August and October) coincides with the beginning of the second wave of the epidemic in Hungary.

Objective The efficacy of argon plasma coagulation (APC) on gastric antral vascular ectasia (GAVE) may be impaired over time and depends greatly on the application settings. Endoscopic band ligation (EBL) may be an alternative, but study on its efficacy is limited. This study aimed to evaluate and compare the clinical efficacy of APC and EBL in treating GAVE. Methods Changes in the need for blood transfusion, number of treatment sessions and hospitalizations were retrospectively assessed in 63 transfusion-dependent patients with GAVE (mean age: 67.1 y, 54.0% female) treated with either APC or EBL (45 and 18 patients, respectively) in four tertiary endoscopic centers. Results Both methods substantially increased hemoglobin levels and decreased patients' need for a transfusion (22.0 ± 4.0 g/L and -5.62 ± 2.30 units of packed red blood cells [RBC] with APC, and 27.4 ± 6.1 g/L and -4.79 ± 2.46 units of packed RBC with EBL), without a significant statistical difference between the methods. However, fewer EBL sessions were required both for the cessation of need for a transfusion compared with those for the resolution of GAVE lesions (0.90 ± 0.10 vs 1.69 ± 0.31, P = 0.028). Conclusions Both APC and EBL are effective in GAVE treatment. EBL may be superior in terms of number of treatment sessions, but not in its influence on hemoglobin level and need for transfusion. Further prospective studies with large, homogeneous sample size and standardized APC settings are needed.

Background: The purpose of our study was to compare the physiological effects of extreme physical and psychological stress tests in male soccer players, since these two types of stress apply to athletes with high performance requirements. Methods: A total of 63 healthy male soccer players participated in this study, all of whom underwent both of the tests. A physical stress test was carried out in an exercise physiology laboratory, where subjects completed an incremental treadmill running test to full exhaustion, and a psychological test was performed in a military tactical room, where subjects met a street offence situation. Heart rate variability (HRV) and blood pressure (BP) were recorded directly before, immediately after, and 30 min after the stress tests. Results: The majority of HRV indices changed significantly in both stress protocols. Inverse, significant changes (positive for the physical test, negative for the psychological test, p < 0.001) were found when comparing the alterations of HRV indices between the tests. Significant differences were found in the changes in systolic (p = 0.003) and diastolic (p < 0.001) BP between the test protocols, and also between the baseline and post-test measurements (p < 0.001). Conclusion: Both HRV and BP are sensitive physiological parameters to measure the impact of extreme physical and/or psychological stress

Összefoglaló. Bevezetés: A musculus cricopharyngeus flexibilis endoszkópos myotomiája a tüneteket okozó Zenker-diverticulum hatékony, biztonságos kezelési módszere. Célkitűzés és módszer: Retrospektíven elemeztük a hagyományos flexibilis endoszkópos myotomia eljárással szerzett tapasztalatainkat. Eredmények és megbeszélés: 2012. szeptember és 2020. február között 38 betegnél történt flexibilis endoszkópos myotomia tüneteket okozó Zenker-diverticulum miatt; összesen 47 myotomiát végeztünk. Betegeink többsége férfi (23/38), az átlagéletkor 71,5 év (40-88) volt. A diverticulumok átlagos mérete 3,94 (2-10) cm volt. A legtöbb esetben divertikuloszkópot alkalmaztunk, szabad kezes vágási technikára 8 esetben volt szükség. Betegeink tüneteit a kezelés előtt és azt követően a DRC- (dysphagia, regurgitatio, komplikációk) skála szerint értékeltük. A jelentősebb szövődmények előfordulása 4,2% (2/47) volt, a beavatkozással összefüggésbe hozható mortalitás nem fordult elő. Pneumomediastinum 1 betegnél alakult ki, melyet konzervatívan sikeresen kezeltünk. Beavatkozás közbeni vérzés 8 esetben (17%) jelentkezett, ezeket a beavatkozás során sikeresen megállítottuk. 1 esetben korai, kiújuló masszív vérzés miatt sürgős műtétre volt szükség. Mind a 38 beteget követtük, átlagosan 34,7 hónapig. A klinikai sikeresség 1,5 hónapnál 91,9% volt (34/37). 3 betegnek maradtak tünetei, kettőjüknél remyotomia történt, egyikük később műtétre szorult, 1 beteg pedig percutan endoszkópos gastrostomián esett át 18 hónap után. A hosszú távú követés során a teljes sikeresség (DRC2) 78,4% volt (29/37), míg lényeges klinikai javulást (DRC: 0/1/2) a betegek 89,2%-ában (33/37) sikerült elérnünk. Következtetés: Eredményeink megerősítik, hogy a hagyományos flexibilis endoszkópos myotomia biztonságos, hatékony a tüneteket okozó Zenker-diverticulum kezelésében. Orv Hetil. 2022; 163(17): 677-687.In the treatment of symptomatic Zenker's diverticulum, the flexible endoscopic myotomy of the cricopharyngeal muscle is considered to be a safe and effective technique.We retrospectively analyzed our experiences with conventional flexible endoscopic myotomy.38 patients with symptomatic Zenker's diverticulum were treated with flexible endoscopic myotomy and 47 myotomies were performed from September 2012 until February 2020. Most of our patients were male (23/38), with an average age of 71.5 (40-88) years. The mean size of diverticula was 3.94 (2-10) cm. In most cases, we used diverticuloscope, while free-hand technique was needed in 8 cases. We assessed our patients' symptoms by applying DRC (dysphagia, regurgitation, complication) score before the treatment and during follow-up. The overall rate of significant complications was 4.2% (2/47), and there was no procedure-related mortality. We observed pneumomediastinum in one patient that was treated conservatively. Intraprocedural bleeding occurred in several (8/47) cases, in all of them the bleeding was successfully stopped during intervention. In one of them, early recurrent massive bleeding required urgent surgery. All 38 patients were followed (mean 34.7 months). Clinical success at 1.5 months was 91.9% among endoscopically treated patients (34/37). 3 patients remained symptomatic, 2 of them were treated with re-myotomy, 1 of them needed surgery later on, another patient underwent percutan endoscopic gastrostomy at 18 months. Over long-term period, complete success (DRC2) was 78.4% (29/37), while clinical success (DRC: 0/1/2) reached in 89.2% (33/37).Our experiences confirmed that conventional method of flexible endoscopic myotomy is safe and effective for the treatment of Zenker's diverticulum symptoms. Orv Hetil. 2022; 163(17): 677-687.

Inadequate physical activity is currently one of the leading risk factors for mortality worldwide. University students are a high-risk group in terms of rates of obesity and lack of physical activity. In recent years, activity trackers have become increasingly popular for measuring physical activity. The aim of the present study is to examine whether university students in Hungary meet the health recommendations (10,000 steps/day) for physical activity and investigate the impact of different variables (semester-exam period, days-weekdays, days, months, sex) on the level of physical activity in free-living conditions for 3 months period. In free-living conditions, 57 healthy university students (male: 25 female: 32 mean age: 19.50 SD = 1.58) wore MiBand 1S activity tracker for 3 months. Independent sample t-tests were used to explore differences between sexes. A One-way analysis of variance (ANOVA) was used to explore differences in measures among different grouping variables and step count. A Two-way ANOVA was conducted to test for differences in the number of steps by days of the week, months, seasons and for sex differences. Tukey HSD post-hoc tests were used to examine significant differences. Students in the study achieved 10,000 steps per day on 17% of days (minimum: 0%; maximum: 76.5%; median: 11.1%). Unfortunately, 70% of the participants did not comply the 10,000 steps at least 80% of the days studied. No statistical difference were found between sexes. However, significant differences were found between BMI categories (underweight 30 kg/m2, the number of steps in the overweight category was significantly lower (F = 72.073, p < 0.001). The average daily steps were significantly higher in autumn (t = 11.457, p < 0.001) than in winter. During exam period average steps/day were significantly lower than during fall semester (t = 13.696, p < 0.001). On weekdays, steps were significantly higher than on weekends (F = 14.017, p < 0.001), and even within this, the greatest physical activity can be done by the middle of the week. Our data suggest that university students may be priority groups for future physical activity interventions. Commercial activity trackers provide huge amount of data for relatively low cost therefore it has the potential to objectively analyze physical activity and plan interventions.

Background: Variant transthyretin amyloidosis (ATTRv) is an autosomal dominant inherited disease, where the mutation of the transthyretin gene (TTR) results in the deposition of pathogenic protein fibrils in various tissues. The mutation type influences the clinical course. Until now, no data were available on the genotype, phenotype, and prevalence of Hungarian ATTRv patients. The aim of our study was to assess the prevalence, regional distribution, genotypes, and phenotypes of Hungarian patients with ATTRv. Methods: With the collaboration of Hungarian regional and university centers, we identified patients diagnosed with ATTRv. We also searched prior publications for case studies of Hungarian ATTRv patients. Results: 40 individuals in 23 families with ATTRv were identified within the borders of Hungary. At the time of the diagnosis, 24 of them were symptomatic. The two most common mutations were ATTRHis88Arg (nine families) and ATTRIle107Val (8 families). ATTRVal30Met was demonstrated in 2 families, and ATTRVal122del, ATTRPhe33Leu, ATTRIle84Ser, and ATTRAsp18Gly in one family each. The median age of the symptomatic patients at the time of clinical diagnosis was 65 years. The most common clinically significant organ involvement was restrictive cardiomyopathy, found in 24 patients. Polyneuropathy was diagnosed in 20 patients. A total of 19 patients showed a mixed phenotype. The leading symptom was heart failure in 8 cases (3 of them had only cardiac symptoms), polyneuropathy in 11 cases (all of them also had cardiac symptoms), and equally severe cardiac and neuropathy symptoms were present in 3 cases. Out of 24 symptomatic patients, 10 received targeted pharmacological therapy. The follow-up period ranged from 1 to 195 months. At the time of the retrospective analysis, 12 patients had already died, and 1 patient underwent heart transplantation. Conclusions: As TTR genotype influences the phenotype and clinical course of ATTRv, it is important to know the regional data. In Hungary, ATTRHis88Arg and ATTRIle107Val are the most common mutations in ATTRv, both presenting with mixed phenotype, but the median age at the time of the diagnosis is 9 years lower in patients with ATTRHis88Arg than in patients with ATTRIle107Val.

Levels of DNA damage represent the dynamics between damage formation and removal. Therefore, to better interpret human biomonitoring studies with DNA damage endpoints, an individual's ability to recognize and properly remove DNA damage should be characterized. Relatively few studies have included DNA repair as a biomarker and therefore, assembling and analyzing a pooled database of studies with data on base excision repair (BER) was one of the goals of hCOME T (EU-COST CA15132). A group of approximately 1911 individuals, was gathered from 8 laboratories which r u n population studies with the comet-based in vitro DNA repair assay. BER incision activity data were normalized and subsequently correlated with various host factors. BER was found to be significantly higher in women. Although it is generally accepted that age is inversely related to DNA repair , no overal l effect of age was found, but se x differences were most pronounced in the oldest quartile (> 61 years). No effect of smoking or occupational exposures was found. A body mass index (BMI) above 25 kg/m(2) was related to higher levels of BER. However, when BMI exceeded 35 kg/m(2), repair incision activity was significantly lower. Finally, higher BER incision activity was related to lower levels of DNA damage detected by the comet assay in combination with formamidopyrimidine DNA glycosylase (Fpg), which is in line with the fact that oxidatively damaged DNA is repaired by BER. These data indicate that BER plays a role in modulating the steady-state level of DNA damage that is detected in molecular epidemiological studies and should therefore be considered as a parallel endpoint in future studies.

Multiple myeloma (MM) is an incurable disease, however, novel therapeutic agents has significantly improved its prognosis. In this study we analyzed if polymorphisms in the genes of β-catenin and glutathione-S-transferase have affected the clinical course, treatment response and progression-free survival (PFS) of MM patients. Ninety-seven MM patients were involved who were administered immunomodulatory drug (Imid) or alkylating agent-based therapy. β-catenin (CTNNB1, rs4135385 A > G, rs4533622 A > C) and glutathione-S-transferase (GSTP1 105, GSTP1 114) gene polymorphisms were analyzed by Light SNiP assays. The distribution of CTNNB1 (rs4135385) AA, AG and GG genotypes were 48.4%, 47.4% and 4,1%, respectively. Patients with AA genotype were older than those who carried G allele (64.5 vs. 61.0 years of age, p

Mitochondrial DNA (mtDNA) copy number changes have been associated with various diseases. Several studies showed that mtDNA content in peripheral blood was associated with oxidative stress and cardiovascular disease. Atrial fibrillation (AF) is one of the severe cardiovascular diseases. We aimed to determine the mtDNA copy numbers in peripheral blood, in cell-free plasma and in exosomes of AF patients and healthy controls. Peripheral blood was drawn from 60 AF patients and 72 healthy controls. DNA was isolated from EDTA blood and plasma. Exosomes were isolated from cell-free plasma and then exosome encapsulated DNA (exoDNA) was extracted. Quantitative-real-time PCR was performed with Human Mitochondrial DNA (mtDNA) Monitoring Primer Set. Statistical analysis of the data was performed. We found statistically significant difference in mtDNA copy numbers in DNA isolated from peripheral whole blood, cell-free plasma and exosome samples of controls’ (44.4 ± 18.0, 27.2 ± 30.1, 11.5 ± 8.7), and patients’ group (43.4 ± 13.6, 26.2 ± 26.4, 14.5 ± 12.3). However there was no significant difference in mtDNA copy number between the two study groups either in peripheral blood, in cell-free plasma and in exosomes, and even in different sexes and ages. We found the highest copy number of mtDNA in peripheral blood, followed by plasma and exosomes. We did not find differences between patients and controls, neither age nor gender had effect on the mtDNA copy number. According to our results the mtDNA copy numbers did not differ in AF patients.

BACKGROUND Trunk prevention training, which provides the basis of several conditioning training programs, is used in sports at professional and amateur levels, taking the specifications of the given sport and the age-related characteristics of the athletes into consideration. OBJECTIVE Our aim was to examine the strength and flexibility of muscles responsible for correct posture, the lumbar motor control ability and the posture of recruitment kayak-canoe athletes. METHODS Controlled, randomized examination with 103 persons (age: 15.1 ± 3.5 years), who were divided into two groups. Fifty were in the intervention group, who took part in the 6-month trunk prevention training program (height: 162.30 cm, body weight: 49.70 ± 10.32 kg), 53 in the control group (not performing trunk prevention training) (height: 158.24 cm, body weight: 51.45 ± 11.71 kg). The strength of core muscles was measured with Kraus-Weber test, muscle flexibility with Kempf-test, lumbar motor control ability with Sitting Forward Lean and Leg Lowering test and posture with photogrammetry test before and after the program. RESULTS Static strength of abdominal muscles (p< 0.001), superficial and deep dorsal muscles (p< 0.001), flexibility of knee extensors (p< 0.001), chest muscles (p< 0.001), the lumbar motor control ability (p< 0.001) and habitual posture (p< 0.001) significantly improved in the intervention group. The post-measurements in the intervention group were significantly (p< 0.001) better than in the control group. CONCLUSIONS As a result of the trunk prevention training the strength of core stabilization muscles, the lumbar motor control ability and the posture also improved in case of recruitment athletes.

INTRODUCTION AND OBJECTIVES Cardiac resynchronization therapy (CRT) is beneficial for selected heart failure (HF) patients, although nonresponse to therapy is still prevalent. We investigated a set of novel biomarkers associated with various pathophysiological pathways of HF. Our purpose was to assess their ability to predict clinical outcomes after CRT. METHODS We studied 136 chronic HF patients undergoing CRT. We measured the plasma levels of fractalkine, pentraxin-3, hepatocyte growth factor (HGF), carbohydrate antigen-125, and matrix metalloproteinase-9 before and 6 months after CRT. The primary endpoint of the study was 5-year all-cause mortality, and we considered the absence of 6-month reverse remodelling (defined as at least a 15% decrease in end-systolic volume) as a secondary endpoint. RESULTS Fifty-eight patients died during the 5-year follow-up period and 66 patients were categorized as nonresponders. In multivariable models, only an increased HGF was an independent predictor of both mortality (HR, 1.35; 95%CI, 1.11-1.64; P=.003; per 1 standard deviation increase) and the absence of reverse remodelling (OR, 1.83; 95%CI, 1.10-3.04; P=.01; per 1 standard deviation increase). Applying HGF to the basic multivariable model of both mortality (net reclassification improvement=0.69; 95%CI, 0.39-0.99; P

Data about the functional adaptation of the right ventricle (RV) to intense exercise are limited. Our aim was to characterize the RV mechanical pattern in top-level athletes using three-dimensional echocardiography. A total of 60 elite water polo athletes (19 ± 4 yr, 17 ± 6 h of training/wk, 50% women and 50% men) and 40 healthy sedentary control subjects were enrolled. We measured the RV end-diastolic volume index (RVEDVi) and ejection fraction (RVEF) using dedicated software. Furthermore, we determined RV global longitudinal (RV GLS) and circumferential strain (RV GCS) and the relative contribution of longitudinal ejection fraction (LEF) and radial ejection fraction (REF) to RVEF using the ReVISION method. Athletes also underwent cardiopulmonary exercise testing [O2 consumption (V̇o2)/kg]. Athletes had significantly higher RVEDVi compared with control subjects (athletes vs. control subjects, 88 ± 11 vs. 65 ± 10 ml/m2, P < 0.001); however, they also demonstrated lower RVEF (56 ± 4% vs. 61 ± 5%, P < 0.001). RV GLS was comparable between the two groups (−22 ± 5% vs. −23 ± 5%, P = 0.24), whereas RV GCS was significantly lower in athletes (−21 ± 4% vs. −26 ± 7%, P < 0.001). Athletes had higher LEF and lower REF contribution to RVEF (LEF/RVEF: 0.50 ± 0.07 vs. 0.42 ± 0.07, P < 0.001; REF/RVEF: 0.33 ± 0.08 vs. 0.45 ± 0.08, P < 0.001). Moreover, the pattern of RV functional shift correlated with V̇o2/kg (LEF/RVEF: r = 0.30, P < 0.05; REF/RVEF: r = −0.27, P < 0.05). RV mechanical adaptation to long-term intense exercise implies a functional shift; the relative contribution of longitudinal motion to global function was increased, whereas the radial shortening was significantly decreased, in athletes. Moreover, this functional pattern correlates with aerobic exercise performance, representing a potential new resting marker of an athlete’s heart. NEW & NOTEWORTHY Intensive regular physical exercise results in significant changes of right ventricular morphology and function. By separate quantification of the right ventricular longitudinal and radial function, a relative dominance of longitudinal motion and a decrease in radial motion can be observed compared with sedentary controls. Moreover, this contraction pattern correlates with cardiopulmonary fitness. According to these results, this functional shift of the right ventricle may represent a novel marker of an athlete’s heart.

Impairments of theory of mind (ToM) are widely accepted underlying factors of disturbed relatedness in borderline personality disorder (BPD). The aim of this meta-analysis a was to assess the weighted mean effect sizes of ToM performances in BPD compared to healthy controls (HC), and to investigate the effect of demographic variables and comorbidities on the variability of effect sizes across the studies. Seventeen studies involving 585 BPD patients and 501 HC were selected after literature search. Effect sizes for overall ToM, mental state decoding and reasoning, cognitive and affective ToM, and for task types were calculated. BPD patients significantly underperformed HC in overall ToM, mental state reasoning, and cognitive ToM, but had no deficits in mental state decoding. Affective ToM performance was largely task dependent in BPD. Comorbid anxiety disorders had a positive moderating effect on overall and affective ToM in BPD. Our results support the notion that BPD patients' have specific ToM impairments. Further research is necessary to evaluate the role of confounding factors, especially those of clinical comorbidities, neurocognitive functions, and adverse childhood life events. Complex ToM tasks with high contextual demands seem to be the most appropriate tests to assess ToM in patients with BPD.

15 p.-8 fig.-3 tab., Haemolytic Uraemic Syndrome associated with Streptococcus pneumoniae infections (SP-HUS) is a clinically well-known entity that generally affects infants, and could have a worse prognosis than HUS associated to E. coli infections. It has been assumed that complement genetic variants associated with primary atypical HUS cases (aHUS) do not contribute to SP-HUS, which is solely attributed to the action of the pneumococcal neuraminidase on the host cellular surfaces. We previously identified complement pathogenic variants and risk polymorphisms in a few Hungarian SP-HUS patients, and have now extended these studies to a cohort of 13 Spanish SP-HUS patients. Five patients presented rare complement variants of unknown significance, but the frequency of the risk haplotypes in the CFH-CFHR3-CFHR1 region was similar to the observed in aHUS. Moreover, we observed desialylation of Factor H (FH) and the FH-Related proteins in plasma samples from 2 Spanish and 4 Hungarian SP-HUS patients. To analyze the functional relevance of this finding, we compared the ability of native and “in vitro” desialylated FH in: (a) binding to C3b-coated microtiter plates; (b) proteolysis of fluid-phase and surface-bound C3b by Factor I; (c) dissociation of surface bound-C3bBb convertase; (d) haemolytic assays on sheep erythrocytes. We found that desialylated FH had reduced capacity to control complement activation on sheep erythrocytes, suggesting a role for FH sialic acids on binding to cellular surfaces. We conclude that aHUS-risk variants in the CFH-CFHR3-CFHR1 region could also contribute to disease-predisposition to SP-HUS, and that transient desialylation of complement FH by the pneumococcal neuraminidase may have a role in disease pathogenesis., This study was funded by the Spanish Instituto de Salud Carlos III (ISCIII) and the European Regional Development Fund from the European Union (grants PI16/00723 and PI19/00970 to PS-C). IG and EA are supported by the Spanish Autonomous Region of Madrid (Complement II-CM network; S2017/BMD-3673). IG was also supported by the Spanish Fundación Senefro (http://www.senefro.org/). The study was also supported by the Higher Education Institutional Excellence Programme of the Ministry of Human Capacities in Hungary, within the framework of the molecular biology thematic programme of the Semmelweis University, by the National Office for Innovation and Research (KH130355 to ZP), and by the MSCA-ITN (Horizon 2020) CORVOS (Grant 860044 to ZP). DC was supported by the Premium Postdoctoral Fellowship Program of the Hungarian Academy of Sciences (PPD2018-016/2018).

The complement system is essential for protection against infections in oncologic patients because of the chemotherapy-induced immunosuppression. One of the key elements in the activation of the complement system via the lectin pathway is the appropriate functioning of mannose-binding lectin (MBL) and mannose-binding lectin-associated serine protease 2 (MASP2) complex. The objective of our study was to find an association between polymorphisms resulting in low MBL level and activation of the MBL-MASP2 complex. Also, we aimed at finding a connection between these abnormalities and the frequency and severity of febrile neutropenic episodes in children suffering from hemato-oncologic diseases. Ninety-seven patients had been enrolled and followed from the beginning of the therapy for 8 months, and several characteristics of febrile neutropenic episodes were recorded. Genotypes of 4 MBL2 polymorphisms (-221C/G, R52C, G54D, G57E) were determined by real-time polymerase chain reaction. Activation of the MBL-MASP2 complex was evaluated by enzyme-linked immunosorbent assay at the time of diagnosis and during an infection. The number of febrile neutropenic episodes was lower, and the time until the first episode was longer in patients with normal MBL level than in patients with low MBL level coding genotypes. The MBL-MASP2 complex activation level correlated with the MBL genotype and decreased significantly during infections in patients with low MBL level. Our results suggest that infections after immunosuppression therapy in children suffering from hemato-oncologic diseases are associated with the MBL2 genotype. Our results may contribute to the estimation of risk for infections in the future, which may modify therapeutic options for individuals.

BackgroundFactor H-related protein 5 (FHR-5) is a member of the complement Factor H protein family. Due to the homology to Factor H, the main complement regulator of the alternative pathway, it may also be implicated in the pathomechanism of kidney diseases where Factor H and alternative pathway dysregulation play a role. Here, we report the first observational study on CFHR5 variations along with serum FHR-5 levels in immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) and C3 glomerulopathy (C3G) patients together with the clinical, genetic, complement, and follow-up data.MethodsA total of 120 patients with a histologically proven diagnosis of IC-MPGN/C3G were enrolled in the study. FHR-5 serum levels were measured in ELISA, the CFHR5 gene was analyzed by Sanger sequencing, and selected variants were studied as recombinant proteins in ELISA and surface plasmon resonance (SPR).ResultsEight exonic CFHR5 variations in 14 patients (12.6%) were observed. Serum FHR-5 levels were lower in patients compared to controls. Low serum FHR-5 concentration at presentation associated with better renal survival during the follow-up period; furthermore, it showed clear association with signs of complement overactivation and clinically meaningful clusters.ConclusionsOur observations raise the possibility that the FHR-5 protein plays a fine-tuning role in the pathogenesis of IC-MPGN/C3G.

Previous studies have demonstrated that the angle of women&rsquo, s lumbar curvature affects men&rsquo, s attractiveness judgments of them. The theoretically optimal angle of lumbar curvature provides better resistance against both hyperlordosis and hypolordosis as biomechanical costs of a bipedal fetal load that could impair a woman&rsquo, s fertility. Since men find this attribute attractive, women aim to emphasize it by wearing high-heeled shoes. The primary objective of the present study was to test this evolutionary hypothesis using short videos presenting women walking by the camera. In line with previous findings based on static stimuli (photographs), dynamic stimuli (videos) presenting women walking in high-heeled shoes were expected to elicit increased attractiveness ratings as compared to women wearing flat shoes, which would be associated with the angle of lumbar curvature. Videos were taken of 52 female models walking in two conditions (i.e., wearing either high-heeled or flat shoes). A total of 108 participants (61 males, 47 females) rated the walking models&rsquo, physical attractiveness in an online setting. Each model&rsquo, s lumbar curvature was measured both in high heels and in flat shoes using photographs taken of them prior to each video recording. The results showed that wearing high heels consistently increased the models&rsquo, attractiveness, regardless of whether or not it decreased their natural difference from the theoretically optimal angle of lumbar curvature. Both male and female observers showed this positive effect. Furthermore, a negative correlation was found between the models&rsquo, body mass index (BMI) and their perceived attractiveness scores in both conditions.

Exercise elicits a systemic adaptation reaction, involving both neuroendocrine and cellular/paracrine stress responses, exemplified by the sympathoadrenergic activity and the release of cellular Hsp70 into the circulation. Regular sports training is known to result in increased fitness. In this study, we characterized the plasma norepinephrine and Hsp70 levels and modeled their relationship in response to exercise stress by bicycle ergometer in 12 trained judoka athletes and in 10 healthy controls. Resting norepinephrine was similar in both groups, whereas Hsp70 was significantly higher in controls compared to athletes. Intense exercise load induced both norepinephrine and Hsp70 elevation. However, both norepinephrine and Hsp70 were significantly lower in athletes compared to the control group. A reaction kinetic model was developed that provided a quantitative description of norepinephrine-facilitated extracellular Hsp70 release, congruent with the experimental data. Our study indicates that exercise-induced norepinephrine and extracellular Hsp70 may be coordinated responses to physiological stress, which are robustly affected by regular sports activity.

Background Endoscopic retrograde cholangiopancreatography (ERCP) is an important therapeutic modality in acute biliary pancreatitis (ABP) cases with cholangitis or ongoing common bile duct obstruction. Theoretically, inflammation of the surrounding tissues would result in a more difficult procedure. No previous studies examined this hypothesis. Objectives ABP and acute cholangitis (AC) without ABP cases were compared to assess difficulty of ERCP. Methods The rate of successful biliary access, advanced cannulation method, adverse events, cannulation and fluoroscopy time were compared in 240 ABP cases and 250 AC cases without ABP. Previous papillotomy, altered gastroduodenal anatomy, and cases with biliary stricture were excluded. Results Significantly more pancreatic guidewire manipulation (adjusted odds ratio (aOR) 1.921 [1.241–2.974]) and prophylactic pancreatic stent use (aOR 4.687 [2.415–9.098]) were seen in the ABP than in AC group. Average cannulation time in the ABP patients (248 vs. 185 s; p = 0.043) were longer than in AC cases. No difference was found between biliary cannulation and adverse events rates. Conclusion ERCP in ABP cases seem to be more challenging than in AC. Difficult biliary access is more frequent in the ABP cases which warrants the involvement of an experienced endoscopist.

Zinc finger protein 554 (ZNF554), a member of the Kr&uuml, ppel-associated box domain zinc finger protein subfamily, is predominantly expressed in the brain and placenta in humans. Recently, we unveiled that ZNF554 regulates trophoblast invasion during placentation and its decreased expression leads to the early pathogenesis of preeclampsia. Since ZNF proteins are immensely implicated in the development of several tumors including malignant tumors of the brain, here we explored the pathological role of ZNF554 in gliomas. We examined the expression of ZNF554 at mRNA and protein levels in normal brain and gliomas, and then we searched for genome-wide transcriptomic changes in U87 glioblastoma cells transiently overexpressing ZNF554. Immunohistochemistry of brain tissues in our cohort (n = 62) and analysis of large TCGA RNA-Seq data (n = 687) of control, oligodendroglioma, and astrocytoma tissues both revealed decreased expression of ZNF554 towards higher glioma grades. Furthermore, low ZNF554 expression was associated with shorter survival of grade III and IV astrocytoma patients. Overexpression of ZNF554 in U87 cells resulted in differential expression, mostly downregulation of 899 genes. The &ldquo, PI3K-Akt signaling pathway&rdquo, known to be activated during glioma development, was the most impacted among 116 dysregulated pathways. Most affected pathways were cancer-related and/or immune-related. Congruently, cell proliferation was decreased and cell cycle was arrested in ZNF554-transfected glioma cells. These data collectively suggest that ZNF554 is a potential tumor suppressor and its decreased expression may lead to the loss of oncogene suppression, activation of tumor pathways, and shorter survival of patients with malignant glioma.

BACKGROUND Maintenance of cell viability during cold storage is a key issue in organ transplantation. Methane (CH4) bioactivity has recently been recognized in ischemia/reperfusion conditions; we therefore hypothesized that cold storage in CH4-enriched preservation solution can provide an increased defense against organ dysfunction during experimental heart transplantation (HTX). METHODS The hearts of donor Lewis rats were stored for 60 minutes in cold histidine-tryptophan-ketoglutarate (Custodiol [CS]) or CH4-saturated CS solution (CS-CH4) (n = 12 each). Standard heterotopic HTX was performed, and 60 minutes later, the left ventricular (LV) pressure-volume relationships LV systolic pressure (LVSP), systolic pressure increment (dP/dtmax), diastolic pressure decrement, and coronary blood flow (CBF) were measured. Tissue samples were taken to detect proinflammatory parameters, structural damage (by light microscopy), endoplasmic reticulum (ER) stress, and apoptosis markers (CCAAT/enhancer binding protein [C/EBP] homologous protein, GRP78, glycogen synthase kinase-3β, very low-density lipoprotein receptor, caspase 3 and 9, B-cell lymphoma 2, and bcl-2-like protein 4), whereas mitochondrial functional changes were analyzed by high-resolution respirometry. RESULTS LVSP and dP/dtmax increased significantly at the largest pre-load volumes in CS-CH4 grafts as compared with the CS group (114.5 ± 16.6 mm Hg vs 82.8 ± 4.6 mm Hg and 3,133 ± 430 mm Hg/s vs 1,739 ± 169 mm Hg/s, respectively); the diastolic function and CBF (2.4 ± 0.4 ml/min/g vs 1.3 ± 0.3 ml/min/g) also improved. Mitochondrial oxidative phosphorylation capacity was more preserved (58.5 ± 9.4 pmol/s/ml vs 27.7 ± 6.6 pmol/s/ml), and cytochrome c release was reduced in CS-CH4 storage. Signs of HTX-caused myocardial damage, level of ER stress, and the transcription of proapoptotic proteins were significantly lower in CS-CH4 grafts. CONCLUSION The addition of CH4 during 1 hour of cold storage improved early in vitro graft function and reduced mitochondrial dysfunction and activation of inflammation. Evidence shows that CH4 reduced ER stress–linked proapoptotic signaling.

BACKGROUND: Equisetum arvense L., commonly known as field horsetail is a perennial fern of which extracts are rich sources of phenolic compounds, flavonoids, and phenolic acids. Activation of SIRT1 that was shown to be involved in well-known signal pathways of diabetic cardiomyopathy has a protective effect against oxidative stress, inflammatory processes, and apoptosis that are the basis of diseases such as obesity, diabetes mellitus, or cardiovascular diseases. The aim of our study was to evaluate the antidiabetic and cardioprotective effects of horsetail extract in streptozotocin induced diabetic rats. METHODS: Diabetes was induced by a single intraperitoneal injection of 45 mg/kg streptozotocin. In the control groups (healthy and diabetic), rats were administered with vehicle, whilst in the treated groups, animals were administered with 50, 100, or 200 mg/kg horsetail extract, respectively, for six weeks. Blood glucose levels, glucose tolerance, and insulin sensitivity were determined, and SIRT1 levels were measured from the cardiac muscle. RESULTS: The horsetail extract showed moderate beneficial changes in blood glucose levels and exhibited a tendency to elevate SIRT1 levels in cardiomyocytes, furthermore a 100 mg/kg dose also improved insulin sensitivity. CONCLUSIONS: Altogether our results suggest that horsetail extract might have potential in ameliorating manifested cardiomyopathy acting on SIRT1.

Acute aortic catastrophes (AAC), mainly ruptured aneurysms and dissections, lead all other vascular conditions in morbidity and mortality, even if intervention occurs. The aim of our study was to give a descriptive overview of the demographic and pathological characteristics of AAC. Between 1994 and 2013, 80,469 autopsies were performed at Semmelweis University hospitals in Budapest. After collecting the autopsy reports we were able to create the AAC database upon which we conducted our analysis. We found 567 cases of AAC. The cause of death in 120 of them was classified as a non-ruptured aorta with malperfusion or distal embolization. Of the remaining 447 cases, in 305 the cause of death was a ruptured aortic aneurysm (rAA), and in 142 it was a ruptured aortic dissection (rAD). The distribution of rAA cases was 34.4% thoracal, 4.3% thoracoabdominal, and 61.3% abdominal. We found female dominance where the rAA was thoracal. In rAD cases, 84% were Stanford A and 16% Stanford B type. In both groups we found different pathological distributions. In the prehospital group, the number of thoracal ruptures was considerable. 88% of the patients with Stanford A dissection died in the prehospital or perioperative period. The most progressive AACs were ruptures of intrapericardial aneurysms and Stanford A dissections., however survival rate can be elevated by using rapid imaging examination and immediate surgical intervention. We want to highlight that our study contains such gender differences, which are worth to be taken into consideration.

In sepsis, platelets may become activated via toll-like receptors (TLRs), causing microvascular thrombosis. Megakaryocytes (MKs) also express these receptors; thus, severe infection may modulate thrombopoiesis. To explore the relevance of altered miRNAs in platelet activation upon sepsis, we first investigated sepsis-induced miRNA expression in platelets of septic patients. The effect of abnormal Dicer level on miRNA expression was also evaluated. miRNAs were profiled in septic vs. normal platelets using TaqMan Open Array. We validated platelet miR-26b with its target SELP (P-selectin) mRNA levels and correlated them with clinical outcomes. The impact of sepsis on MK transcriptome was analyzed in MEG-01 cells after lipopolysaccharide (LPS) treatment by RNA-seq. Sepsis-reduced miR-26b was further studied using Dicer1 siRNA and calpain inhibition in MEG-01 cells. Out of 390 platelet miRNAs detected, there were 121 significantly decreased, and 61 upregulated in sepsis vs. controls. Septic platelets showed attenuated miR-26b, which were associated with disease severity and mortality. SELP mRNA level was elevated in sepsis, especially in platelets with increased mean platelet volume, causing higher P-selectin expression. Downregulation of Dicer1 generated lower miR-26b with higher SELP mRNA, while calpeptin restored miR-26b in MEG-01 cells. In conclusion, decreased miR-26b in MKs and platelets contributes to an increased level of platelet activation status in sepsis.

Aims Right- and left-side-dominant individuals reveal target-matching asymmetries between joints of the dominant and non-dominant upper limbs. However, it is unclear if such asymmetries are also present in lower limb’s joints. We hypothesized that right-side-dominant participants perform knee joint target-matching tasks more accurately with their non-dominant leg compared to left-side-dominant participants. Methods Participants performed position sense tasks using each leg by moving each limb separately and passively on an isokinetic dynamometer. Results Side-dominance affected (p Conclusions In conclusion, right-side-dominant participants tend to perform a target-matching task more accurately with the non-dominant leg compared to left-side-dominant participants. Our results extend the literature by showing that right-hemisphere specialization under proprioceptive target-matching tasks may be not evident at the lower limb joints.

Aim: Right-handed young adults perform target-matching tasks more accurately with the non-dominant (ND) compared to the dominant (D) limb, but it is unclear if age affects this disparity. We determined if age affects target-matching asymmetry in right-side dominant healthy adults. Method: Young (n = 12, age: 23.6 y, 6 females) and older (n = 12; age: 75.1 y, 7 females) adults performed a passive joint position-matching task with the D and ND leg in a randomized order. Result: Age affected absolute, constant, and variable knee JPS errors but, contrary to expectations, it did not affect target-matching asymmetries between the D and ND knees. However, older participants tended to underestimate while young subjects overestimated the target angles. Moreover, older as compared to young subjects performed the target-matching task with higher variability. Conclusion: Altogether, age seems to affect passive knee target-matching behaviour in right-side dominant healthy adults. The present data indicate that healthy aging produces age-specific modifications in passive joint position sense.

Absztrakt

Petra Hartmann,1 Edina Butt,2 Ágnes Fehér,1 Ágnes Lilla Szilágyi,1 Kurszán Dávid Jász,1 Boglárka Balázs,3 Mónika Bakonyi,3 Szilvia Berkó,3 Gábor Erős,4 Mihály Boros,1 Gyöngyi Horváth,5 Endre Varga,2 Erzsébet Csányi3 1Institute of Surgical Research, University of Szeged, Szeged, Hungary; 2Department of Traumatology, University of Szeged, Szeged, Hungary; 3Department of Pharmaceutical Technology, University of Szeged, Szeged, Hungary; 4Department of Pathology, University of Szeged, Szeged, Hungary; 5Department of Physiology, University of Szeged, Szeged, Hungary Purpose: Since electroporation (EP) can increase the permeability of biological membranes, we hypothesized that it offers an opportunity to enhance the transdermal delivery of drugs for intra-articular indications. Our aim was to compare the anti-inflammatory and analgesic efficacy of EP-combined topical administration of diclofenac sodium hydrogel (50 mg mL-1 in 230 μL volume) with that of an equivalent dose of oral (75 mg kg-1) and simple topical administration. Methods: Arthritis was induced with the injection of 2% λ-carrageenan and 4% kaolin into the right knee joints of male Sprague Dawley rats. EP was applied for 8 min with 900 V high-voltage pulses for 5 ms followed by a 20 ms break. Drug penetration into the synovial fluid and plasma was detected by high-performance liquid chromatography. Leukocyte–endothelial interactions were visualized by intravital videomicroscopy on the internal surface of the synovium. Inflammation-induced thermal and mechanical hyperalgesia reactions, knee joint edema, and inflammatory enzyme activities were assessed at 24 and 48 h after arthritis induction. Results: EP significantly increased the plasma level of diclofenac as compared with the topical controls 10 min after the 2% λ-carrageenan and 4% kaolin injection. Increased leukocyte–endothelial interactions were accompanied by joint inflammation, which was significantly reduced by oral and EP diclofenac (by 45% and by 30%, respectively) and only slightly ameliorated by simple topical diclofenac treatment (by 18%). The arthritis-related secondary hyperalgesic reactions were significantly ameliorated by oral and EP-enhanced topical diclofenac treatments. The knee cross-section area (which increased by 35%) was also reduced with both approaches. However, simple topical application did not influence the development of joint edema and secondary hyperalgesia. Conclusion: The study provides evidence for the first time of the potent anti-inflammatory and analgesic effects of EP-enhanced topical diclofenac during arthritis. The therapeutic benefit provided by EP is comparable with that of oral diclofenac; EP is a useful alternative to conventional routes of administration. Keywords: diclofenac, transdermal delivery, HPLC, intravital videomicroscopy

International audience; Background: In an era of antibiotic resistance, medical students must be prepared to prescribe antibiotics responsibly.Objectives: To assess self-reported preparedness among final-year medical students at European universities, using a comprehensive set of topics related to prudent antibiotic use.Methods: We conducted a cross-sectional, multicentre, web-based survey. All medical-degree students in their final year of studies at European universities were eligible to participate. A preparedness score was calculated for each student and mean scores were compared at medical school and country levels. Comparisons were made with national-level data on resistance among four common bacterial pathogens.Results: In total, 7328 responses were included from 179/296 eligible medical schools in 29/29 countries. Students felt at least sufficiently prepared on a mean of 71.2% of topics assessed, ranging from 54.8% (Portugal) to 84.8% (Latvia). The proportion of students wanting more education on prudent antibiotic use or general antibiotic use ranged from 20.3% (Sweden) to 94.3% (Slovakia), with a mean of 66.1%, and was strongly inversely correlated with preparedness scores (Spearman's ρ = -0.72, n = 29, P < 0.001). Higher prevalence rates of antibiotic-non-susceptible bacteria were associated with lower preparedness scores and higher self-reported needs for further education (P < 0.01).Conclusions: Most final-year European medical students feel they still need more education on antibiotic use for their future practice as junior doctors. Patterns of preparedness on specific topics were identified, were highly consistent across countries, and correlated with both perceived need for further education and levels of antibiotic resistance among common bacteria.

d-Amino acid oxidase (DAAO) is a potential target in the treatment of schizophrenia as its inhibition increases brain d-serine level and thus contributes to NMDA receptor activation. Inhibitors of DAAO were sought testing [6+5] type heterocycles and identified isatin derivatives as micromolar DAAO inhibitors. A pharmacophore and structure-activity relationship analysis of isatins and reported DAAO inhibitors led us to investigate 1H-indazol-3-ol derivatives and nanomolar inhibitors were identified. The series was further characterized by pKa and isothermal titration calorimetry measurements. Representative compounds exhibited beneficial properties in in vitro metabolic stability and PAMPA assays. 6-fluoro-1H-indazol-3-ol (37) significantly increased plasma d-serine level in an in vivo study on mice. These results show that the 1H-indazol-3-ol series represents a novel class of DAAO inhibitors with the potential to develop drug candidates.

Aims There are previous studies on quality of life (QoL) in cardiac resynchronization therapy (CRT) patients; however, there are no data with the short EuroQol-five dimensions (EQ-5D) questionnaire predicting outcomes. We aimed to assess the predictive role of baseline QoL and QoL change at 6 months after CRT with EQ-5D on 5-year mortality and response. Methods and results In our prospective follow-up study, 130 heart failure (HF) patients undergoing CRT were enrolled. Clinical evaluation, echocardiography, and EQ-5D were performed at baseline and at 6 months of follow–up, continued to 5 years. Primary endpoint was all-cause mortality at 5 years. Secondary endpoints were (i) clinical response with at least one class improvement in New York Heart Association without HF hospitalization and (ii) reverse remodelling with 15% reduction in left ventricular end-systolic volume at 6 months. Fifty-four (41.5%) patients died during 5 years, 85 (65.3%) clinical responders were identified, and 63 patients (48.5%) had reverse remodelling. Baseline issues with mobility were associated with lower response [odds ratio (OR) 0.36, 95% confidence interval (CI) 0.16–0.84; P = 0.018]. Lack of reverse remodelling correlated with self-care issues at baseline (OR 0.10, 95% CI 0.01–0.94; P = 0.04). Furthermore, self-care difficulties [hazard ratio (HR) 2.39, 95% CI 1.17–4.86; P = 0.01) or more anxiety (HR 1.51, 95% CI 1.00–2.26; P = 0.04) predicted worse long-term survival. At 6 months, mobility (HR 3.95, 95% CI 1.89–8.20; P

Aims The aim of this study was to examine the effects of gender on the relationship between Functional Movement Screen (FMS) and treadmill-based gait parameters. Methods Twenty elite junior athletes (10 women and 10 men) performed the FMS tests and gait analysis at a fixed speed. Between-gender differences were calculated for the relationship between FMS test scores and gait parameters, such as foot rotation, step length, and length of gait line. Results Gender did not affect the relationship between FMS and treadmill-based gait parameters. The nature of correlations between FMS test scores and gait parameters was different in women and men. Furthermore, different FMS test scores predicted different gait parameters in female and male athletes. FMS asymmetry and movement asymmetries measured by treadmill-based gait parameters did not correlate in either gender. Conclusion There were no interactions between FMS, gait parameters, and gender; however, correlation analyses support the idea that strength and conditioning coaches need to pay attention not only to how to score but also how to correctly use FMS.

The acquired form of idiopathic thrombotic thrombocytopenic purpura (TTP) is an autoimmune disease, in which the underlying ADAMTS13-deficiency is caused by inhibitory autoantibodies against the protease. Human leukocyte antigens (HLA), responsible for antigen presentation, play an important role in the development of antibodies. The loci coding HLA DR and DQ molecules are inherited in linkage as haplotypes. The c.1858C>T polymorphism of the PTPN22 gene, which codes a protein tyrosine phosphatase important in lymphocyte activation, predisposes to a number of autoimmune diseases. We determined the HLA-DRB1-DQB1 haplotypes and the PTPN22 c.1858C>T genotypes in 75 patients with acquired idiopathic TTP and in healthy controls, in order to assess the role of these genetic factors and their interactions in the susceptibility to TTP. We found that the carrier frequencies of the DRB1∗11-DQB1∗03 and DRB1∗15-DQB1∗06 haplotypes were higher, while those of the DRB1∗07-DQB1∗02 and DRB1∗13-DQB1∗06 haplotypes were lower in TTP patients. There was no difference in the overall frequency of the PTPN22 c.1858T allele between TTP patients and controls. In conclusion, we identified four HLA-DRB1-DQB1 haplotypes associated with an increased (DRB1∗11-DQB1∗03 and DRB1∗15-DQB1∗06) or a decreased (DRB1∗07-DQB1∗02 and DRB1∗13-DQB1∗06) susceptibility to acquired idiopathic TTP.

Background The introduction of electrocardiogram gating in computed tomography (CT) angiography imaging of aortic disease raised questions whether diameters measured on diastolic images can lead to the undersizing of aortic endografts. As previous studies suggested that young patients may have the highest risk of an unintended undersize, the aim of our study was to analyze the strain of the thoracic aorta in a young patient cohort. Methods We assessed the descending aorta of 52 patients (35 men, mean age 41.1 ± 7.3 years) who underwent coronary CT angiography (CCTA) with suspected coronary artery disease. To reduce radiation dose, native calcium score scans triggered on late systole were compared with diastolic phase CCTA images. Cross-section areas were measured, and effective diameters were derived at 3 levels of the visible segment of the descending aorta (P1, P2, and P3) in systole and diastole. Aortic pulsatility (mm, d systolic −d diastolic ) and strain (%, [d systolic −d diastolic ]/d diastolic ) were calculated at each level. All measurements were performed 3 times by 2 independent readers to evaluate interreader and intrareader reproducibility. Results A total of 936 measurements were performed. Significant differences were found between systolic and diastolic diameters at each location (all P P = 0.344). Aortic strain and pulsatility did not show significant correlation with pulse pressure ( P = 0.693), patient age ( P = 0.649), or other anamnestic data. Intraclass correlation coefficient was in the range of 0.95–0.96 for interobserver and in the range of 0.95–0.97 for intraobserver analysis. Conclusions This study shows that descending aortic strain can be measured precisely and reliably on images of routine CCTA examinations with native scans acquired during systole. We demonstrated that young adults have an aortic strain of 6.7–8.1%. As the average thoracic aortic strain was still lower than the recommended prosthesis oversize of 10%, routine use of systolic phase imaging cannot be recommended: it has no clinical benefit for the vast majority of the patients but increases the risk of motion artefacts. We also demonstrated that large interindividual differences are present in the scale of thoracic aortic strain, a phenomenon that needs further investigations to be fully understood.

Absztrakt

Zsombor Tóth-Vajna,1 Gergely Tóth-Vajna,2 Zsuzsanna Gombos,1 Brigitta Szilágyi,3 Zoltán Járai,4,5 Márton Berczeli,1 Péter Sótonyi11Heart and Vascular Center, Department of Vascular Surgery, Semmelweis University, Budapest, Hungary; 21st Department of Pediatrics, Semmelweis University, Budapest, Hungary; 3Department of Geometry, Institute of Mathematics, Budapest University of Technology and Economics, Budapest, Hungary; 4Department of Cardiology, St. Emeric University Teaching Hospital, Budapest, Hungary; 5Heart and Vascular Center, Department of Vascular Surgery, Department of Angiology, Semmelweis University, Budapest, HungaryCorrespondence: Márton BerczeliHeart and Vascular Center, Department of Vascular Surgery, Semmelweis University, 68 Városmajor Street, Budapest 1122, HungaryTel +36 20 666 3354Email marton.berczeli@gmail.comBackground and purpose: The screening tool for diagnosing lower extremity arterial disease is the assessment of the ankle-brachial index (ABI), which is widely used in general practice. However, resting ABI can easily produce a false negative result. In light of this, our goal was to determine the proportion of definitive diagnoses (peripheral arterial disease [PAD] confirmed or refuted) among patients screened in general practice, and the rate of cases in which the need for further specialized examination is necessary, with special attention to groups having non-compressible arteries and ABI negative symptomatic status. The aim of our work is to improve the efficiency of primary health care screening in PAD and reduce the extremely high domestic amputation ratio.Patients and methods: Eight hundred and sixteen patients were screened. We used the Edinburgh Questionnaire and recorded medical histories, major risk factors, current complaints, and medication. Physical examinations were performed, including ABI testing.Results: Thirty-three percent complained about lower extremity claudication; 23% had abnormal ABI values; 13% of the patients within the normal ABI range had complaints of dysbasia; and 12% were in the non-compressible artery group. The ABI-negative symptomatic group’s risk factor profile showed a close similarity to the clear PAD-positive and non-compressible artery groups.Conclusion: The percentage of PAD could be higher than the number of patients diagnosed by ABI screening. Nearly a quarter of the population fell into the non-compressible artery and ABI-negative symptomatic groups, together defined as the “murky zone”. When screening purposely for PAD, these patients deserve special attention due to the insufficient selectivity and sensitivity of measurements. If there is high clinical suspicion of PAD in spite of normal ABI values, further assessment may be considered.Keywords: peripheral arterial disease, ankle-brachial index, diabetes, screening method, ABI-negative symptomatic, non-compressible artery

There is considerable controversy regarding the vasoactive action of prostaglandin E

Levels of cardiac necroenzymes, high-sensitive troponin (hsTnT) and creatine kinase muscle-brain (CKMB) increase as a result of a myocardial damage following catheter ablation.To analyze the mid-term alteration of hsTnT and CKMB levels following radiofrequency ablation (RFCA) for atrial fibrillation (AF), atrial flutter (AFlu), AV-nodal reentry tachycardia (AVNRT) and electrophysiological studies (EPS) without ablation.Patients undergoing RFCA for various indications and EPS were consecutively enrolled in our prospective study. Concentrations of hsTnT and CKMB were measured from serial blood samples directly before and after the procedure, 4 and 20 hours later and at 3 months follow-up.Forty-seven patients (10 EPS, 12 AVNRT, 13 AFlu, 12 AF) with mean age of 55 ± 13 were included. hsTnT levels increased significantly in all groups after the procedures, while CKMB changed only in the AF group. hsTnT exceeded the reference value in all patients with ablation and in 80% of patients with EPS 4 hours post-ablation. Peak average hsTnT levels for EPS, AVNRT, AFlu were 24 ± 11, 260 ± 218 and 541 ± 233 ng/L, respectively. The highest hsTnT level was measured in the AF group (799 ± 433 ng/L). We found a positive correlation between hsTnT levels and ablation time after RFCA.The hsTnT levels significantly change after EPS and RFCA, in all patients who underwent ablation, and in 80% of those with EPS had hsTnT positivity in the early post-procedural phase. hsTnT levels depended significantly on the type of the subgroups and correlated with the ablation time. Awareness of those observations is essential to correctly interpret elevated hsTnT levels following RFCA. Orv Hetil. 2019; 160(14): 540-548.Absztrakt: Bevezetés: Ismert, hogy katéteres ablatio által okozott szívizom-károsodás következtében megnő a szívizom-specifikus nekroenzimek koncentrációja. Célkitűzés: A magas érzékenységű troponin T (hsTnT) és a szívizom-specifikus kreatin-kináz (CKMB) szintje középtávú változásának elemzése pitvarfibrilláció (PF), pitvari flutter (PFlu), AV-csomó reentry tachycardia (AVNRT) rádiófrekvenciás katéteres ablatióját követően, illetve elektrofiziológiai vizsgálat után. Módszer: Rádiófrekvenciás ablatión, illetve elektrofiziológiai vizsgálaton átesett betegeket vontunk be konszekutívan prospektív vizsgálatunkba. Sorozatvérmintákból meghatároztuk a hsTnT- és a CKMB-szinteket a procedúra előtt és után közvetlenül, majd 4 és 20 órával és 3 hónappal később. Eredmények: Negyvenhét, 55 ± 13 év átlagéletkorú beteget (10 elektrofiziológiai vizsgálat, 12 AVNRT, 13 PFlu és 12 PF) vontunk be vizsgálatunkba. A hsTnT-szintek minden csoportban szignifikánsan megemelkedtek a beavatkozást követően, a CKMB csak a PF-csoportban változott. A hsTnT-szint négy órával a beavatkozást követően az összes ablatión átesett betegnél és az elektrofiziológiai vizsgálaton átesett betegek 80%-ánál meghaladta a referenciatartományt. A legmagasabb átlagos hsTnT-koncentrációk EFV, AVNRT, PFlu esetén 24 ± 11, 260 ± 218 és 541 ± 233 ng/l-nek bizonyultak. A legmagasabb hsTnT-szint a PF-ablatiós csoportban volt kimutatható 20 órával az ablatio után (799 ± 433 ng/l). Pozitív korrelációt találtunk a rádiófrekvenciás ablatiót követő hsTnT-szint és az ablatio ideje között. Következtetések: A hsTnT alkalmas a rádiófrekvenciás ablatio és az elektrofiziológiai vizsgálat utáni myocardialis necrosis vizsgálatára, az ablatión átesett betegek mindegyikénél; elektrofiziológiai vizsgálat után 80%-ban pozitív a hsTnT. A necrosis mértéke jelentősen függ a beavatkozás típusától, és korrelál az ablatio kiterjedtségével. A fentiekben leírt megfigyelések iránymutatásként szolgálnak a rádiófrekvenciás ablatio utáni hsTnT-szint megfelelő értelmezéséhez. Orv Hetil. 2019; 160(14): 540–548.

BACKGROUND A sports therapy program in type 2 diabetes helps in glucose control, but little is known how a long-term structured exercise intervention affects the parameters in this disease. Our aim was to measure the impact of a 24-week-long sports therapy program in type 2 diabetes on the concentration of glucose in blood, body composition, and physical fitness level. METHODS In this prospective longitudinal study, 208 type II diabetic patient (80 male, 128 female, aged: 61±6.86 years) were selected and randomly assigned to a control or an intervention group. The intervention group took part in a sports therapy and recreation sports program for 6 months. Taking into account the rules of training theory and physiotherapy, fitness material of exercising (aerobics, resistance training, muscle strengthening, stretching) and outdoor elements were used during the 3-month sports program, after which it became a 3-month recreation exercise program. In the control group, there was no intervention. RESULTS The intervention group showed significant decrease in concentration of glucose in blood (mean differences [MD]:-3.23; Confidence Interval [CI] lowest: -3.50; CI highest: -2.95]; P

Background Acquired or genetic abnormalities of the complement alternative pathway are the primary cause of C3glomerulopathy(C3G) but may occur in immune-complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) as well. Less is known about the presence and role of C4nephritic factor(C4NeF) which may stabilize the classical pathway C3-convertase. Our aim was to examine the presence of C4NeF and its connection with clinical features and with other pathogenic factors. Results One hunfe IC-MPGN/C3G patients were enrolled in the study. C4NeF activity was determined by hemolytic assay utilizing sensitized sheep erythrocytes. Seventeen patients were positive for C4NeF with lower prevalence of renal impairment and lower C4d level, and higher C3 nephritic factor (C3NeF) prevalence at time of diagnosis compared to C4NeF negative patients. Patients positive for both C3NeF and C4NeF had the lowest C3 levels and highest terminal pathway activation. End-stage renal disease did not develop in any of the C4NeF positive patients during follow-up period. Positivity to other complement autoantibodies (anti-C1q, anti-C3) was also linked to the presence of nephritic factors. Unsupervised, data-driven cluster analysis identified a group of patients with high prevalence of multiple complement autoantibodies, including C4NeF. Conclusions In conclusion, C4NeF may be a possible cause of complement dysregulation in approximately 10–15% of IC-MPGN/C3G patients.

The co-occurrence in the same individual of two numerical chromosomal abnormalities (double aneuploidy) is a very rare condition, especially for autosomes. Clinical presentations are variable depending on the predominating aneuploidy. The authors present a rare case of a male infant with multiple congenital anomalies: craniofacial dysmorphism, short neck, agenesis of the corpus callosum, ventricular septal defect, bilateral broad hallux, large first interdigital space of the toes, plantar furrows, prominent calcaneus and right kidney agenesis. The karyotype identified 82% of mitosis with trisomy 8 (47,XY,+8) and 18% with trisomy 21 (47,XY,+21). The evolution was fatal because of eating difficulties, severe growth retardation and recurrent respiratory infections. He died at the age of five months. We report this case as a very rare double autosomal mosaicism, with a complete clinical and morphological description, as the first documented case in Romania.

Temporal lobe epilepsy (TLE) is characterized by changes in interneuron numbers in the hippocampus. Deep brain stimulation (DBS) is an emerging tool to treat TLE seizures, although its mechanisms are not fully deciphered. We aimed to depict the effect of amygdala DBS on the density of the most common interneuron types in the CA1 hippocampal subfield in the lithium-pilocarpine model of epilepsy. Status epilepticus was induced in male Wistar rats. Eight weeks later, a stimulation electrode was implanted to the left basolateral amygdala of both pilocarpine-treated (Pilo, n = 14) and age-matched control rats (n = 12). Ten Pilo and 4 control animals received for 10 days 4 daily packages of 50 s 4 Hz regular stimulation trains. At the end of the stimulation period, interneurons were identified by immunolabeling for parvalbumin (PV), neuropeptide Y (NPY), and neuronal nitric oxide synthase (nNOS). Cell density was determined in the CA1 subfield of the hippocampus using confocal microscopy. We found that PV+ cell density was preserved in pilocarpine-treated rats, while the NPY+/nNOS+ cell density decreased significantly. The amygdala DBS did not significantly change the cell density in healthy or in epileptic animals. We conclude that DBS with low frequency applied for 10 days does not influence interneuron cell density changes in the hippocampus of epileptic rats.

The aim of this study was to objectively assess the hand hygiene performance of medical students. Hand rubbing technique was evaluated by employing innovative UV-light-based imaging technology, identifying patterns and trends in missed areas after applying WHO's six-step protocol. This specially designed hand hygiene education and assessment program targeted 1,344 medical students at two distant sites in Central Europe. Students were introduced to a short video, presenting the basics of hand hygiene, and then received further demonstration from professional trainers, focusing on the correct execution of WHO's six-step technique. To verify the acquired skill, participants rubbed their hands with UV-marked alcohol-based solution. Digital images of the hands were recorded under UV light, followed by computer evaluation and assessment. Immediate objective visual feedback was given to the participants showing missed areas on their hands. The statistical analysis of missed spots was based on retrospective expert-driven manual evaluation. Significant difference in rubbing quality was found between female and male participants [35.3% (CI 95%: 33-38%) versus 29.0% (CI 95%: 27-31%), p 0.001], dominant and non-dominant hands [43.4% (CI 95%: 39-48%) versus 34.9% (CI 95%: 32-38%), p = 0.002], and various zones of the hands' dorsal side. Based on the participants' feedback and the evaluation of the infection control specialists, it can be stated that the identification of typically missed patterns and the instant visual feedback have a vital role in improving the hand hygiene technique of prospective medical staff.

Atypical hemolytic uremic syndrome (aHUS) is a rare disorder caused by dysregulation of the complement alternative pathway, and associated with mutations in genes of complement components and regulators. In the recent years several studies have been published describing these mutations, however, no data is available from the Central and Eastern European region. In this study we present a detailed genetic analysis of our 30 patients, hospitalized with the diagnosis of aHUS in the past 7 years. We analyzed the genetic variants of genes CFH, CFI, CD46, THBD, CFB and C3; furthermore the possible effect of mutations that may alter the function or level of factor H protein was also investigated. We identified 27 (12 novel and 15 previously described) potentially disease-causing mutations in the candidate genes in 23 patients. Genetic analysis of family members revealed that in most cases the disease develops in individuals with multiple genetic risk factors, which may explain the low penetrance of the mutations. Here we showed that two novel mutations (p.W198R, p.P1161T) and a previously reported one (p.R1215Q) in CFH caused impaired regulation as indicated by increased lysis in hemolytic test, while four CFH mutations (p.V609D, p.S722X, p.T1216del and p.C448Y) were associated with decreased factor H protein level in serum as determined by allele-specific immunoassay. These results further point to the necessity of complete genetic workup of patients with aHUS and to the importance of functional characterization of novel variations.

Electroanatomical mapping is a useful tool during the ablation of atrial fibrillation. Respiratory movement might influence the mapping accuracy and merging. This study aims to investigate the effect of respiratory gating on the accuracy of magnetic-field-based electroanatomical mapping under spontaneous respiration. Fifty-one consecutive patients (35 male, aged 30–78 years) who underwent left atrial radiofrequency catheter ablation due to atrial fibrillation were included. Electroanatomical mapping was performed with CARTO 3 System under conscious sedation. Respiratory gating was achieved with the AccuResp algorithm (Biosense Webster). Average surface match and maximum distance of the pre-acquired and electroanatomical maps, as well as left atrial volume, were recorded with and without respiratory gating after merging. The average surface match of the electroanatomical map with the left atrial reconstruction was significantly better with respiratory gating than without using the algorithm (3.81 ± 1.09 vs 4.11 ± 1.61 mm, p = 0.0119). It was not dependent of the rhythm during mapping or the image modality used for left atrial reconstruction. The maximal distance between the two maps did not depend on the use of the algorithm (19.81 ± 6.24 mm for gated and 20.87 ± 7.99 mm for non-gated, p = 0.3161). Left atrial volume of the map was significantly lower when using the respiratory compensation module (106.3 ± 31.6 vs 127.0 ± 36.4 ml, p

Antiepileptic drugs act on voltage gated sodium channels in many different ways: rufinamide is thought to influence the fast inactivation, so its anticonvulsant action could be similar to carbamazepine, whereas lacosamide enhances the slow inactivation; however some antidepressants were also described to act in the same way. Rufinamide, lacosamide, carbamazepine, fluoxetine and imipramine were tested using in vitro models of epileptiform activities. Extracellular local field potentials were recorded using hippocampal slices from immature rats and the pattern of epileptiform activities was analyzed. Seizure-like events (SLE), but not interictal bursts were sensitive to AEDs' action. Rufinamide increased interictal periods by prolonging preictal phase and reducing SLE duration, and was the only tested AED which reduced SLE frequency. Lacosamide's effect resembled that of fluoxetine in the low-Mg2+ model: both drugs reduced markedly the SLE duration, but increased their frequency. Imipramine and fluoxetine irreversibly suppressed SLE in all slices. Some proconvulsive type of action on SLEs such as increasing preictal neuronal activity by rufinamide and increasing SLE frequency by lacosamide, fluoxetine and carbamazepine, were also observed. Newer drugs were more efficient than carbamazepine, and the anticonvulsant action of antidepressants on in vitro epileptiform activities may seem somewhat surprising.

ObjectiveThe Prevention of Hospital Infections by Intervention and Training (PROHIBIT) project included a cluster-randomised, stepped wedge, controlled study to evaluate multiple strategies to prevent catheter-related bloodstream infection. We report an in-depth investigation of the main barriers, facilitators and contextual factors relevant to successfully implementing these strategies in European acute care hospitals.MethodsQualitative comparative case study in 6 of the 14 European PROHIBIT hospitals. Data were collected through interviews with key stakeholders and ethnographic observations conducted during 2-day site visits, before and 1 year into the PROHIBIT intervention. Qualitative measures of implementation success included intervention fidelity, adaptation to local context and satisfaction with the intervention programme.ResultsThree meta-themes emerged related to implementation success: ‘implementation agendas’, ‘resources’ and ‘boundary-spanning’. Hospitals established unique implementation agendas that, while not always aligned with the project goals, shaped subsequent actions. Successful implementation required having sufficient human and material resources and dedicated change agents who helped make the intervention an institutional priority. The salary provided for a dedicated study nurse was a key facilitator. Personal commitment of influential individuals and boundary spanners helped overcome resource restrictions and intrainstitutional segregation.ConclusionThis qualitative study revealed patterns across cases that were associated with successful implementation. Consideration of the intervention–context relation was indispensable to understanding the observed outcomes.

Outcome of patients undergoing catheter ablation of atrial fibrillation (AF) varies widely. We sought to investigate whether parameters derived from the spectral analysis of surface ECG and intracardiac AF electrograms can predict outcome in patients referred for pulmonary vein isolation (PVI).We performed spectral analysis on the surface ECG and intracardiac electrograms from patients referred for AF ablation. After filtering and QRST subtraction, we measured the dominant frequency (DF), regularity index (RI) and the organizational index (OI) of fibrillatory electrograms and determined their value for predicting AF recurrence after ablation. A subjective, blinded prediction based on the surface ECG was also performed.We analyzed data from 153 PVI procedures in 140 patients (67.1% with persistent or longstanding AF). In a multivariable model, DF in the right atrium (RA) and distal coronary sinus (CSd)-to-RA DF gradient predicted AF recurrence (OR, 3.52, P = 0.023 and OR, 0.2, P = 0.034, respectively). DF in RA and CSd to RA DF gradient had a good predictive value for PVI outcome (area under the curve [AUC] of 0.73, P = 0.007 and 0.74, P = 0.007, respectively). These performed better than the subjective predictions of experienced electrophysiologists ( P = 0.2).Higher RA DF, lower CSd to RA DF gradient predicted recurrence after AF ablation. These spectral measures suggest a more remodeled atrial substrate and may provide simple tools for risk stratification or predict the need for additional substrate modification in patients referred for AF ablation.

Background In patients with metastatic renal cell cancer, based on limited evidence, increased sunitinib exposure is associated with better outcome. The survival and toxicity data of patients receiving individualized dose escalated sunitinib therapy as compared to standard management were analyzed in this study. Methods From July 2013, the data of metastatic renal cell cancer patients with slight progression but still a stable disease according to RECIST 1.1 criteria treated with an escalated dose of sunitinib (first level: 62.5 mg/day in 4/2 or 2 × 2/1 scheme, second level: 75 mg/day in 4/2 or 2 × 2/1 scheme) were collected prospectively. Regarding characteristics, outcome, and toxicity data, an explorative retrospective analysis of the register was carried out, comparing treatments after and before July 1, 2013 in the study (selected patients for escalated dose) and control (standard dose) groups, respectively. Results The study involved 103 patients receiving sunitinib therapy with a median overall and progression free survival of 25.36 ± 2.62 and 14.2 ± 3.22 months, respectively. Slight progression was detected in 48.5% of them. First and second-level dose escalation were indicated in 18.2% and 4.1% of patients, respectively. The dosing scheme was modified in 22.2%. The median progression free survival (39.7 ± 5.1 vs 14.2 ± 1.3 months (p = 0.037)) and the overall survival (57.5 ± 10.7 vs 27.9 ± 2.5 months (p = 0.044)) were significantly better in the study group (with dose escalation) than in the control group. Patients with nephrectomy and lower Memorial Sloan Kettering Cancer Center (MSKCC) scores showed more favorable outcomes. After dose escalation, the most common adverse events were worsening or development of fatigue, hypertension, stomatitis, and weight loss of over 10%. Conclusions Escalation of sunitinib dosing in selected patients with metastatic renal cell cancer, especially in case of slight progression, based on tolerable toxicity is safe and improves outcome. Dose escalation in 12.5 mg steps may be recommended for properly educated patients.