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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.

Atypical hemolytic uremic syndrome (aHUS), also called complement-mediated hemolytic uremic syndrome (CM-HUS), is a rare disease caused by dysregulation in the alternative complement activation pathway. It is a life-threatening condition causing ischemia of a number of organs, and it typically causes acute kidney injury. This disorder may be triggered by various factors including viral or bacterial infections, pregnancy, surgery, and injuries. In about 60% of cases, the genetic origin of the disease can be identified—commonly mutations affecting complementary factor H and MCP protein. Eculizumab, a monoclonal antibody to the C5 component of the complement, represents the current effective treatment.We describe a case of a young woman with a previous history of polyvalent allergies, who developed atypical hemolytic uremic syndrome after vaccination with mRNA vaccine against SARS-CoV-2. The disease manifested by scleral bleeding, acute renal insufficiency, anemia, and thrombocytopenia. The patient was treated with plasma exchanges without sufficient effect; remission occurred only after starting treatment with eculizumab. Genetic examination showed that the patient is a carrier of multiple inherited risk factors (a rare pathogenic variant in CFH, MCPggaac haplotype of the CD46 gene, and the risk haplotype CFH H3). The patient is currently in hematological remission with persistent mild renal insufficiency, continuing treatment with eculizumab/ravulizumab. By this case report, we meant to point out the need for careful monitoring of people after vaccination, as it may trigger immune-mediated diseases, especially in those with predisposing factors.

Background Osteoporosis is one of the most common chronic musculoskeletal diseases. Osteoporosis-related knowledge is an important contributor in to prevent osteoporosis. There is no validated reliable questionnaire to measure the knowledge in Hungary. The aim of the study was to validate the Osteoporosis Knowledge Assessment Tool (OKAT) Hungarian version. Methods The research was a randomized validation study of a new Hungarian language instrument. The questionnaire was administered to 557 randomly selected healthy women (age between 25 and 44 years) from December 2018 to July 2019 in Baranya county, Hungary. The reliability was examined by the Flesch reading ease and McNemar’s test. We examined item discrimination and item-total correlations, inter-item consistency (Cronbach’s alpha coefficient) and principal component factor analysis. Results Significant differences (p p r = 0.25) was found between the education level and the knowledge. Significantly (p p p Conclusions The Hungarian version of the Osteoporosis Knowledge Assessment Tool is a reliable and objective questionnaire to measure women’s knowledge 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.

Preeclampsia is a syndromic disease of the mother, fetus, and placenta. The main limitation in early and accurate diagnosis of preeclampsia is rooted in the heterogeneity of this syndrome as reflected by diverse molecular pathways, symptoms and clinical outcomes. Gaps in our knowledge preclude successful early diagnosis, personalized treatment and prevention. The advent of “omics” technologies and systems biology approaches enable addressing this problem by identifying the molecular pathways associated with the underlying mechanisms and clinical phenotypes of preeclampsia. Here, we provide a brief overview on how the field has progressed, focusing on studies utilizing state-of-the-art transcriptomics and proteomics methods. Moreover, we summarize our systems biology studies involving maternal blood proteomics and placental transcriptomics, which identified early maternal and placental disease pathways, and showed that their interaction influences the clinical presentation of preeclampsia. We also present an analysis of maternal blood proteomics data which revealed distinct molecular subclasses of preeclampsia and their molecular mechanisms. Maternal and placental disease pathways behind these subclasses are similar to those recently reported in studies on the placental transcriptome. These findings may promote the development of novel diagnostic tools for the distinct subtypes of preeclampsia syndrome, enabling early detection and personalized follow-up and tailored care of patients.

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

Ovarian tumor is one of the leading causes of cancer among women. Patients are diagnosed at an advanced stage, usually. There is a need for new specific and sensitive biomarkers. Mitochondrial DNA copy number change was observed in various cancers. Our aim was to detect mitochondrial DNA copy number in whole blood (wb-mtDNA) and in plasma (cell-free and exosome encapsulated mtDNA) in patients with serous epithelial ovarian tumor. DNA was isolated from EDTA blood and plasma obtained from 24 patients and 24 healthy controls. Exosomes were isolated from cell-free plasma, and exosome encapsulated DNA (exoDNA) was extracted. Quantitative-real-time PCR was performed with Human Mitochondrial DNA (mtDNA) Monitoring Primer Set. Kruskall‑Wallis and Mann‑Whitney U test were used for data analysis. Wb-mtDNA copy number was significantly different among healthy controls and patients in multiple comparison (p = 0.0090 considering FIGO stage independently, and p = 0.0048 considering early- and late-stage cancers). There was a significant decrease among early-stage, all advanced stage and all cancer patients (FIGO I: 32.5 ± 8.3, p = 0.0061; FIGO III + IV: 37.2 ± 13.7 p = 0.0139; FIGO I + III + IV: 35.6 ± 12.2, p = 0.0017) or FIGO III patients alone (32.8 ± 5.6, p = 0.00089) compared to healthy controls. We found significant increase in copy number in exosomal mtDNA in cancer patients (236.0 ± 499.0, p = 0.0155), advanced-stage cancer patients (333.0 ± 575.0, p = 0.0095), of FIGO III (362.0 ± 609.2, p = 0.0494), and FIGO IV (304.0 ± 585.0, p = 0.0393) patients alone but not in samples of FIGO I patients (10.0 ± 3.5, p = 0.3907). In multiple comparison the increase was significant considering early- and late-stage cancers (p = 0.0253). Cell-free mtDNA copy numbers were not increased significantly. We found the highest copy number of mtDNA in exosomes, followed by plasma and peripheral blood in late-stage cancer patients. We observed significant difference in wb-mtDNA copy number between healthy controls and both early- and late-stage cancer patients.

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).

Összefoglaló. Bevezetés: A nemzetközi szakirodalomban számos betegséget illetően elérhető betegségspecifikus tudást és attitűdöt mérő kérdőív. Magyarországon az osteoporosis témakörében validált kérdőívek tárháza meglehetősen hiányos. Célkitűzés: Célunk volt a csontritkulás-specifikus magatartás és attitűd vizsgálatára alkalmas Osteoporosis Health Belief Scale (OHBS-) kérdőív magyar nyelvre történő validációja, melynek segítségével mérhetővé válna a magyar anyanyelvű nők csontritkulással kapcsolatos attitűdje. Módszer: A kérdőív magyar nyelvre validálása a 2000-ben megfogalmazott hatlépcsős irányelv szerint történt. A külső validitás vizsgálatához az Osteoporosis Knowledge Assessment Tool (OKAT-) kérdőívet használtuk. Mintánkat 600 fő alkotta; statisztikai számításaink során leíró statisztikát készítettünk, különbözőségi vizsgálatokat végeztünk, a belső konzisztencia vizsgálatára Cronbach-alfa-értéket számítottunk, a konvergens validitás és a teszt-reteszt mérések vizsgálatához Spearman-féle korrelációs koefficienst számítottunk. A kérdőív belső struktúrájának vizsgálatához faktorelemzést végeztünk. Ennek megfelelően Kaiser-Meyer-Olkin (KMO)-tesztet és Bartlett-próbát számítottunk. Eredmények: Mintánk (37,7 ± 13,15 életév) az OHBS (126,28 ± 14,85 pont) és az OKAT (8,78 ± 3,1) tekintetében egyaránt alacsony pontszámot ért el. A teljes kérdőívre kivetített Cronbach-alfa-érték 0,802 volt. A faktorelemzés (KMO = 0,886; Bartlett-próba p0,001) 7 faktort különített el, melyek megfeleltethetők az eredeti faktoroknak. A teszt-reteszt során a Spearman-féle korrelációs koefficiens 0,921 és 1,000 közötti értéket mutatott. Az OKAT- és az OHBS-dimenziók összevetésekor számos szignifikáns kapcsolatot találtunk. Megbeszélés: A vizsgálati eredmények megfelelnek az eredeti kérdőív szerinti, továbbá a más nyelvre történt validálás során kapott eredményeknek. Következtetés: Eredményeink alapján a magyar nyelvű OHBS csontritkulás-specifikus attitűdöt és magatartást vizsgáló kérdőívet megbízható és valid kérdőívnek tartjuk. Orv Hetil. 2021; 162(37): 1494-1501.In the international literature, several disease-specific questionnaires are available for many diseases. The opportunities of validated questionnaires are incomplete about osteoporosis in Hungarian language.The aim of the study was to validate the Osteoporosis Health Belief Scale (OHBS) into Hungarian that would make it possible to measure the osteoporosis-related attitude for Hungarian-speaking women.The questionnaire was validated into Hungarian according to the six-step guideline outlined in 2000. The Osteoporosis Knowledge Assessment Tool (OKAT) questionnaire was used to examine external validity. Our sample consisted of 600 women. We performed descriptive statistics; Cronbach's alpha value was calculated for internal consistency, we calculated Spearman's correlation coefficient to examine external validity. We carried out factor analysis (Kaiser-Meyer-Olkin [KMO] test, Bartlett test) to examine whether the new questionnaire is suitable for measurements in the given language the same way as the original questionnaire.Our sample (37.7 ± 13.15 years of age) achieved low score for both OHBS (126.28 ± 14.85) and OKAT (8.78 ± 3.1). The Cronbach's alpha value was 0.802. Factor analysis (KMO = 0.886; Bartlett test p0.001) identified 7 factors that can be similar to the original factors. During the test-retest, the Spearman correlation coefficient showed a value between 0.921 and 1.000. When comparing the OKAT and OHBS dimensions we found several significant relationships.The results of the study are similar to the results of the original questionnaire validation as well as to other OHBS validation studies.Based on the results, we consider that the Hungarian form of the OHBS is a reliable and valid questionnaire. Orv Hetil. 2021; 162(37): 1494-1501.

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.

CD24 is a small molecular weight cell-surface protein and an independent marker for poor prognosis in the different type of cancers. We aimed to determine the expression of CD24 in plasma, exosomes and ovarian tissue samples of serous ovarian cancer patients. We collected tissue and blood samples from 21 cases of serous ovarian cancer and eight healthy controls. We used silica adsorption method for isolation of RNA. The cDNA was synthesized using quantitative real-time PCR. We used beta-globin as a housekeeping gene for the normalization of the data. Protein-protein and miRNA networking were analyzed. There was a significant difference in the expression of CD24 in ovarian tissue between controls and patients (0.16 ± 0.32 vs. 44.97 ± 68.06; p 0.01), while CD24 did not show expression in each plasma and exosome samples. There was a correlation in the expression of CD24 and FIGO grading between controls and patients. CD24 expression was detected in exosomes in 38.1% of patients, mainly with FIGO III, and in their plasma in 9.5% of cases. Our network analysis shows LYN, SELP, FGR, and NPM1 proteins are interacting with CD24. Our study demonstrates higher expression of CD24 in ovarian cancer patients' tissue samples, and there is an association with FIGO classification. However, CD24 showed expression only in some cell-free plasma and exosome samples.

Exposure to physiological estrogens or xenoestrogens (e.g., zearalenone or bisphenol A) increases the risk for cancer. However, little information is available on their significance in ovarian cancer. We present a comprehensive study on the effect of estradiol, zearalenone and bisphenol A on the phenotype, mRNA, intracellular and cell-free miRNA expression of human epithelial ovarian cell lines. Estrogens induced a comparable effect on the rate of cell proliferation and migration as well as on the expression of estrogen-responsive genes (GREB1, CA12, DEPTOR, RBBP8) in the estrogen receptor &alpha, (ER&alpha, )-expressing PEO1 cell line, which was not observable in the absence of this receptor (in A2780 cells). The basal intracellular and cell-free expression of miR200s and miR203a was higher in PEO1, which was accompanied with low ZEB1 and high E-cadherin expression. These miRNAs showed a rapid but intermittent upregulation in response to estrogens that was diminished by an ER&alpha, specific antagonist. The role of ER&alpha, in the regulation of the MIR200B-MIR200A-MIR429 locus was further supported by publicly available ChIP-seq data. MiRNA expression of cell lysates correlated well with cell-free miRNA expression. We conclude that cell-free miR200s might be promising biomarkers to assess estrogen sensitivity of ovarian cells.

Liquid biopsy recently became a very promising diagnostic method that has several advantages over conventional invasive methods. Liquid biopsy may serve as a source of several important biomarkers including cell-free nucleic acids (cf-NAs). Cf-DNA is widely used in prenatal testing in order to characterize fetal genetic disorders. Analysis of cf-DNA may provide information about the mutation profile of tumor cells, while cell-free non-coding RNAs are promising biomarker candidates in the diagnosis and prognosis of cancer. Many of these markers have the potential to help clinicians in therapy selection and in the follow-up of patients. Thus, cf-NA-based diagnostics represent a new path in personalized medicine. Although several reviews are available in the field, most of them focus on a limited number of cf-NA types. In this review, we give an overview about all known cf-NAs including cf-DNA, cf-mtDNA and cell-free non-coding RNA (miRNA, lncRNA, circRNA, piRNA, YRNA, and vtRNA) by discussing their biogenesis, biological function and potential as biomarker candidates in liquid biopsy. We also outline possible future directions in the field.

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.

Significance Defects in development and differentiation of the placenta are associated with various pregnancy disorders such as miscarriage, stillbirth, preeclampsia, and intrauterine growth restriction. However, our knowledge on critical regulators of human placentation is scarce. In the present study, we show that the Hippo signaling-dependent transcriptional coactivator YAP plays a pivotal role in the maintenance of proliferative trophoblasts, the epithelial cells of the placenta. By binding to the transcription factor TEAD4, YAP stimulates expression of genes promoting trophoblast stemness. Additionally, YAP–TEAD4 complexes actively repress genes associated with the differentiated syncytiotrophoblast, the hormone-secreting cell type of the human placenta. Hence, YAP orchestrates a complex developmental program ensuring growth and expansion of the human placenta., Various pregnancy complications, such as severe forms of preeclampsia or intrauterine growth restriction, are thought to arise from failures in the differentiation of human placental trophoblasts. Progenitors of the latter either develop into invasive extravillous trophoblasts, remodeling the uterine vasculature, or fuse into multinuclear syncytiotrophoblasts transporting oxygen and nutrients to the growing fetus. However, key regulatory factors controlling trophoblast self-renewal and differentiation have been poorly elucidated. Using primary cells, three-dimensional organoids, and CRISPR-Cas9 genome-edited JEG-3 clones, we herein show that YAP, the transcriptional coactivator of the Hippo signaling pathway, promotes maintenance of cytotrophoblast progenitors by different genomic mechanisms. Genetic or chemical manipulation of YAP in these cellular models revealed that it stimulates proliferation and expression of cell cycle regulators and stemness-associated genes, but inhibits cell fusion and production of syncytiotrophoblast (STB)-specific proteins, such as hCG and GDF15. Genome-wide comparisons of primary villous cytotrophoblasts overexpressing constitutively active YAP-5SA with YAP KO cells and syncytializing trophoblasts revealed common target genes involved in trophoblast stemness and differentiation. ChIP-qPCR unraveled that YAP-5SA overexpression increased binding of YAP–TEAD4 complexes to promoters of proliferation-associated genes such as CCNA and CDK6. Moreover, repressive YAP–TEAD4 complexes containing the histone methyltransferase EZH2 were detected in the genomic regions of the STB-specific CGB5 and CGB7 genes. In summary, YAP plays a pivotal role in the maintenance of the human placental trophoblast epithelium. Besides activating stemness factors, it also directly represses genes promoting trophoblast cell fusion.

Introduction Placental Protein 1 (PP1), PP8, and PP22 were isolated from the placenta. Herein, we aimed to identify PP1, PP8, and PP22 proteins and their placental and trophoblastic expression patterns to reveal potential involvement in pregnancy complications. Methods We analyzed PP1, PP8, and PP22 proteins with LC-MS. We compared the placental behaviors of PP1, PP8, and PP22 to the predominantly placenta-expressed PP5/TFPI-2. Placenta-specificity scores were generated from microarray data. Trophoblasts were isolated from healthy placentas and differentiated; total RNA was isolated and subjected to microarray analysis. We assigned the placentas to the following groups: preterm controls, early-onset preeclampsia, early-onset preeclampsia with HELLP syndrome, term controls, and late-onset preeclampsia. After histopathologic examination, placentas were used for tissue microarray construction, immunostaining with anti-PP1, anti-PP5, anti-PP8, or anti-PP22 antibodies, and immunoscoring. Results PP1, PP8, and PP22 were identified as ‘nicotinate-nucleotide pyrophosphorylase’, ‘serpin B6’, and ‘protein disulfide-isomerase’, respectively. Genes encoding PP1, PP8, and PP22 are not predominantly placenta-expressed, in contrast with PP5. PP1, PP8, and PP22 mRNA expression levels did not increase during trophoblast differentiation, in contrast with PP5. PP1, PP8, and PP22 immunostaining were detected primarily in trophoblasts, while PP5 expression was restricted to the syncytiotrophoblast. The PP1 immunoscore was higher in late-onset preeclampsia, while the PP5 immunoscore was higher in early-onset preeclampsia. Discussion PP1, PP8, and PP22 are expressed primarily in trophoblasts but do not have trophoblast-specific regulation or functions. The distinct dysregulation of PP1 and PP5 expression in either late-onset or early-onset preeclampsia reflects different pathophysiological pathways in these preeclampsia subsets.

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.

The human placenta maintains pregnancy and supports the developing fetus by providing nutrition, gas-waste exchange, hormonal regulation, and an immunological barrier from the maternal immune system. The villous syncytiotrophoblast carries most of these functions and provides the interface between the maternal and fetal circulatory systems. The syncytiotrophoblast is generated by the biochemical and morphological differentiation of underlying cytotrophoblast progenitor cells. The dysfunction of the villous trophoblast development is implicated in placenta-mediated pregnancy complications. Herein, we describe gene modules and clusters involved in the dynamic differentiation of villous cytotrophoblasts into the syncytiotrophoblast. During this process, the immune defense functions are first established, followed by structural and metabolic changes, and then by peptide hormone synthesis. We describe key transcription regulatory molecules that regulate gene modules involved in placental functions. Based on transcriptomic evidence, we infer how villous trophoblast differentiation and functions are dysregulated in preterm preeclampsia, a life-threatening placenta-mediated obstetrical syndrome for the mother and fetus. In the conclusion, we uncover the blueprint for villous trophoblast development and its impairment in preterm preeclampsia, which may aid in the future development of non-invasive biomarkers for placental functions and early identification of women at risk for preterm preeclampsia as well as other placenta-mediated pregnancy complications.

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

Gene expression studies of molar pregnancy have been limited to a small number of candidate loci. We analyzed high-dimensional RNA and protein data to characterize molecular features of complete hydatidiform moles (CHMs) and corresponding pathologic pathways. CHMs and first trimester placentas were collected, histopathologically examined, then flash-frozen or paraffin-embedded. Frozen CHMs and control placentas were subjected to RNA-Seq, with resulting data and published placental RNA-Seq data subjected to bioinformatics analyses. Paraffin-embedded tissues from CHMs and control placentas were used for tissue microarray (TMA) construction, immunohistochemistry, and immunoscoring for galectin-14. Of the 14,022 protein-coding genes expressed in all samples, 3,729 were differentially expressed (DE) in CHMs, of which 72% were up-regulated. DE genes were enriched in placenta-specific genes (OR = 1.88, p = 0.0001), of which 79% were down-regulated, imprinted genes (OR = 2.38, p = 1.54 &times, 10&minus, 6), and immune genes (OR = 1.82, p = 7.34 &times, 18), of which 73% were up-regulated. DNA methylation-related enzymes and histone demethylases were dysregulated. &ldquo, Cytokine&ndash, cytokine receptor interaction&rdquo, was the most impacted of 38 dysregulated pathways, among which 17 were immune-related pathways. TMA-based immunoscoring validated the lower expression of galectin-14 in CHM. In conclusion, placental functions were down-regulated, imprinted gene expression was altered, and immune pathways were activated, indicating complex dysregulation of placental developmental and immune processes in CHMs.

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.

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

The number of women who smoke during pregnancy is significant even today. The harmful effects of smoking during pregnancy are well known but there are no data on the effects of smoking on fetal electrocardiography (ECG). The lack of data is in connection with the difficulties of recording fetal ECG through the maternal abdomen.Third trimester pregnant women who were not able to give up the harmful passion of smoking despite repeated attempts of persuasion were recruited in the study on voluntary basis. The fetal ECG was recorded non-invasively through the maternal abdomen before, during and after smoking, then the data were processed offline. The electrophysiological measurements were performed by a self developed ECG device, which allowed the examination of the morphological differences in "true-to-form" fetal ECG in addition to studying the variability of fetal heart rate. The study involved nine pregnant women. The observed changes are presented through case studies of those pregnant women who showed the most significant anomalies.Compared with the resting state fetal heart rate was increased during smoking. The short-term variability of fetal heart rate was narrowed, while the mother's heart rate did not change significantly - which was an indication of direct fetal stress. No explicit ischemic signs were detected in fetal ECG during smoking, however, in the increasing period of the fetal heart rate, the T wave morphology changed slightly, then it returned to normal.Demonstrable by the electrophysiological methods, smoking has a direct effect on fetal cardiac function. The fetal heart rate variability shows a pattern during smoking which is a typical sign of stress conditions among adults. The results may have educational consequences as well. Understanding those, hopefully will help pregnant women give up this harmful addiction.

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.

Objective The quality and quantity of sleep represent important health issues in pregnant women. Sleep disturbances could be associated, beyond alteration of quality of life, with poor pregnancy outcome. Our aim was to investigate the effect of a regular, specific, medium-term physical training program on sleep characteristics in healthy pregnant women. Materials and methods A total of 132 healthy pregnant women, with gestational age between 18 weeks and 22 weeks, were enrolled in a prospective study. They were allocated into two groups; the first group involved 79 women (average age, 29.4 years) who performed a specific gymnastics program of 10 weeks, and the second group involved 53 pregnant women (average age, 27.9 years) who did not perform gymnastics. All participants completed a comprehensive questionnaire at baseline and after 10 weeks concerning general data, sleep characteristics, and psycho-emotional status. The changes arising within a diverse set of characteristics were followed and compared for the two groups using parametric and nonparametric statistics. Results In the control group, we observed significant worsening of 12 out of the 14 studied parameters during the 10-week period. In comparison with the women who did not perform gymnastics, women who performed specific gymnastics showed the following characteristics: (1) significantly less deterioration of psycho-emotional status (stress and anxiety levels); (2) the same general pattern of decrease in sleep quality, which is related to the progression of pregnancy; and (3) a significant attenuation of the worsening of several sleep characteristics, such as restless sleep, snoring, diurnal tiredness, and excessive daytime sleepiness. Nocturnal and diurnal sleep quantity increased significantly in both groups. Conclusion The 10-week training program designed for pregnant women has an overall beneficial effect on sleep characteristics, not by improving them but by attenuating their general deterioration related to the progression of pregnancy. Our data strengthen the general recommendation regarding participation of pregnant women in specific exercise programs, mainly for maintaining their psycho-emotional and general well-being.

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.

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

Ovarian cancer is one of the most common cancer types in women characterized by a high mortality rate due to lack of early diagnosis. Circulating miRNAs besides being important regulators of cancer development could be potential biomarkers to aid diagnosis. We performed the circulating miRNA expression analysis in plasma samples obtained from ovarian cancer patients stratified into FIGO I, FIGO III, and FIGO IV stages and from healthy females using the NanoString quantitative assay. Forty-five miRNAs were differentially expressed, out of these 17 miRNAs showed significantly different expression between controls and patients, 28 were expressed only in patients, among them 19 were expressed only in FIGO I patients. Differentially expressed miRNAs were ranked by the network-based analysis to assess their importance. Target genes of the differentially expressed miRNAs were identified then functional annotation of the target genes by the GO and KEGG-based enrichment analysis was carried out. A general and an ovary-specific protein&ndash, protein interaction network was constructed from target genes. Results of our network and the functional enrichment analysis suggest that besides HSP90AA1, MYC, SP1, BRCA1, RB1, CFTR, STAT3, E2F1, ERBB2, EZH2, and MET genes, additional genes which are enriched in cell cycle regulation, FOXO, TP53, PI-3AKT, AMPK, TGF&beta, ERBB signaling pathways and in the regulation of gene expression, proliferation, cellular response to hypoxia, and negative regulation of the apoptotic process, the GO terms have central importance in ovarian cancer development. The aberrantly expressed miRNAs might be considered as potential biomarkers for the diagnosis of ovarian cancer after validation of these results in a larger cohort of ovarian cancer patients.

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

The complex effects of estradiol on non-reproductive tissues/cells, including lymphoid tissues and immunocytes, have increasingly been explored. However, the role of sex hormone binding globulin (SHBG) in the regulation of these genomic and non-genomic actions of estradiol is controversial. Moreover, the expression of SHBG and its internalization by potential receptors, as well as the influence of SHBG on estradiol uptake and signaling in lymphocytes has remained unexplored. Here, we found that human and mouse T cells expressed SHBG intrinsically. In addition, B lymphoid cell lines as well as both primary B and T lymphocytes bound and internalized external SHBG, and the amount of plasma membrane-bound SHBG decreased in B cells of pregnant compared to non-pregnant women. As potential mediators of this process, SHBG receptor candidates expressed by lymphocytes were identified in silico, including estrogen receptor (ER) alpha. Furthermore, cell surface-bound SHBG was detected in close proximity to membrane ERs while highly colocalizing with lipid rafts. The SHBG-membrane ER interaction was found functional since SHBG promoted estradiol uptake by lymphocytes and subsequently influenced Erk1/2 phosphorylation. In conclusion, the SHBG-SHBG receptor-membrane ER complex participates in the rapid estradiol signaling in lymphocytes, and this pathway may be altered in B cells in pregnant women.

Ovarian cancer is the fifth most common cause of cancer death among women that is mostly due to the difficulty of early diagnosis. Circulating miRNAs proved to be reliable biomarkers in various cancers. We screened 9 miRNAs, which are involved in epithelial-mesenchymal transition, in the plasma samples of patients with malignant (n = 28) or non-malignant (n = 12) ovarian tumors and disease-free healthy volunteers (n = 60) by qRT-PCR. The expression levels of miR200a, miR200b, miR200c, miR141, miR429, miR203a, miR34b (p 0.001) and miR34a (p 0.01) were significantly higher in the malignant samples than in healthy controls. MiR203a, miR141 (p 0.01), miR200a and miR429 (p 0.05) levels were also higher in malignant compared to non-malignant samples. ROC-AUC was the highest in the case of miR200c: 0.861 (95%CI = 0.776-0.947). Spearman's rank correlation analysis revealed positive correlation between the plasma levels of the studied miRNAs that was the highest between miR200b and miR200c (r