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Abstract Aims The PREPARE‐MVR study (PRediction of Early PostoperAtive Right vEntricular failure in Mitral Valve Replacement/Repair patients) sought to investigate the alterations of right ventricular (RV) contraction pattern in patients undergoing mitral valve replacement/repair (MVR) and to explore the associations between pre‐operative RV mechanics and early post‐operative RV dysfunction (RVD). Methods and results We prospectively enrolled 42 patients (63 ± 11 years, 69% men) undergoing open‐heart MVR. Transthoracic three‐dimensional (3D) echocardiography was performed pre‐operatively, at intensive care unit discharge, and 6 months after surgery. The 3D model of the RV was reconstructed, and RV ejection fraction (RVEF) was calculated. We decomposed the motion of the ventricle to compute longitudinal ejection fraction (LEF) and radial ejection fraction (REF). Pulmonary artery catheterization was performed to monitor RV stroke work index (RVSWi). RVEF was slightly decreased after MVR [52 (50–55) vs. 51 (46–54)%; P = 0.001], whereas RV contraction pattern changed notably. Before MVR, the longitudinal shortening was the main contributor to global systolic RV function [LEF/RVEF vs. REF/RVEF; 0.53 (0.47–0.58) vs. 0.33 (0.22–0.42); P

In various team sports, such as handball, referees work on the court by continuously moving with the players. Therefore, their physical fitness also has an impact on their reaction time, which could affect their professional decisions. The cardiorespiratory fitness status of healthy Hungarian elite handball referees was examined via body composition analysis and vita maxima cardiopulmonary exercise testing with lactate measurements. One hundred referees were examined (age: 29.0 ± 7.9 years; male: 64.0%; training: 4.3 ± 2.0 hours/week; ratio of former elite handball players: 39.0%; 51.0% first and 49.0% second division referees of the Hungarian National Handball Leagues). A resting heart rate (HR) of 79.0 ± 12.6 BPM was measured. On the basis of the body composition analysis the fat-free mass index proved to be 19.9 ± 2.6 kg/m2. The referees achieved a maximal oxygen uptake (V̇O2max) of 44.6 ± 6.1 ml/kg/min, with a maximal HR of 187.2 ± 11.1 BPM (which was 98.1 ± 4.6% of their calculated maximal HR) and a peak lactate of 9.2 ± 3.2 mmol/l at 557.1 ± 168.3 sec on our continuous speed, increasing slope treadmill protocol. Second division referees were younger, on a weekly average they trained more, achieved higher treadmill exercise time (respectively, 463.8 ± 131.9 vs 658.4 ± 143.9 sec, p < 0.001) and anaerobic threshold time (respectively, 265.8 ± 100.9 vs 348.2 ± 117.1 sec, p < 0.001), while the two different divisional referees had similar V̇O2max values. Regarding our physical fitness measurements, huge individual differences were observed between the referees (exercise time range: 259.0-939.0 sec, V̇O2max range: 25.3-62.4 ml/kg/min). Since it can affect their performance as referees, individual training planning, regular physical fitness measurements, and strict selection methods are suggested.

Using a curved carbon-fiber plate (CFP) in running shoes may offer notable performance benefit over flat plates, yet there is a lack of research exploring the influence of CFP geometry on internal foot loading during running. The objective of this study was to investigate the effects of CFP mechanical characteristics on forefoot biomechanics in terms of plantar pressure, bone stress distribution, and contact force transmission during a simulated impact peak moment in forefoot strike running. We employed a finite element model of the foot-shoe system, wherein various CFP configurations, including three stiffnesses (stiff, stiffer, and stiffest) and two shapes (flat plate (FCFP) and curved plate (CCFP)), were integrated into the shoe sole. Comparing the shoes with no CFP (NCFP) to those with CFP, we consistently observed a reduction in peak forefoot plantar pressure with increasing CFP stiffness. This decrease in pressure was even more notable in a CCFP demonstrating a further reduction in peak pressure ranging from 5.51 to 12.62%, compared to FCFP models. Both FCFP and CCFP designs had a negligible impact on reducing the maximum stress experienced by the 2nd and 3rd metatarsals. However, they greatly influenced the stress distribution in other metatarsal bones. These CFP designs seem to optimize the load transfer pathway, enabling a more uniform force transmission by mainly reducing contact force on the medial columns (the first three rays, measuring 0.333 times body weight for FCFP and 0.335 for CCFP in stiffest condition, compared to 0.373 in NCFP). We concluded that employing a curved CFP in running shoes could be more beneficial from an injury prevention perspective by inducing less peak pressure under the metatarsal heads while not worsening their stress state compared to flat plates., (© 2024. The Author(s).)

Background: During competition and training, exercises involving the lungs may occur throughout the sport, and fatigue is a major injury risk factor in sport, before and after fatigue studies of changes in the lungs are relatively sparse. This study is to investigate into how fatigue affects the lower limb's biomechanics during a forward lunge. Methods: 15 healthy young men participate in this study before and after to exposed to a fatigue protocol then we tested the forward lunge to obtain kinematic, kinetic changing during the task, and to estimate the corresponding muscles' strength changes in the hip, knee, and ankle joints. The measurement data before and after the fatigue protocol were compared with paired samples t-test. Results: In the sagittal and horizontal planes of the hip and knee joints, in both, the peak angles and joint range of motion (ROM) increased, whereas the moments in the sagittal plane of the knee joint smaller. The ankle joint's maximum angle smaller after fatigue. Peak vertical ground reaction force (vGRF) and peak contact both significantly smaller after completing the fatigue protocol and the quadriceps mean and maximum muscular strength significantly increased. Conclusion: After completing a fatigue protocol during lunge the hip, knee, and ankle joints become less stable in both sagittal and horizontal planes, hip and knee range of motion becomes greater. The quadriceps muscles are more susceptible to fatigue and reduced muscle force. Trainers should focus more on the thigh muscle groups., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gao, Ye, Bálint, Radak, Mao and Gu.)

A carbon-fiber plate (CFP) embedded into running shoes is a commonly applied method to improve running economy, but little is known in regard the effects of CFP design features on internal foot mechanics. This study aimed to explore how systematic changes in CFP geometrical variations (i.e., thickness and location) can alter plantar pressure and strain under the forefoot as well as metatarsal stress state through computational simulations. A foot-shoe finite element (FE) model was built and different CFP features including three thicknesses (1 mm, 2 mm, and 3 mm) and three placements (high-loaded (just below the insole), mid-loaded (in between the midsole), and low-loaded (just above the outsole)) were further modulated within the shoe sole. Simulations were conducted at the impact peak instant during forefoot strike running. Compared with the no-CFP shoe, peak plantar pressure and compressive strain under the forefoot consistently decreased when the CFP thickness increased, and the low-loaded conditions were found more effective (peak pressure decreased up to 31.91% and compressive strain decreased up to 18.61%). In terms of metatarsal stress, CFP designs resulted in varied effects and were dependent on their locations. Specifically, high-loaded CFP led to relatively higher peak metatarsal stress without the reduction trend as thickness increased (peak stress increased up to 12.91%), while low-loaded conditions showed a gradual reduction in peak stress, decreasing by 0.74%. Therefore, a low-loaded thicker CFP should be considered to achieve the pressure-relief effects of running shoes without the expense of increased metatarsal stress., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Although various sports footwear demonstrated marked changes in running biomechanical variables, few studies have yielded definitive findings on the underlying mechanisms of shoe constructions affecting running-related performance and injuries. Therefore, this study focused on examining the effect of basic shoe constructions on running biomechanics and assessing the current state of sports shoe production in terms of injury and efficiency. Relevant literature was searched on five databases using Boolean logic operation and then screened by eligibility criteria. A total of 1260 related articles were retrieved in this review, and 41 articles that met the requirements were finally included, mainly covering the influence of midsole, longitudinal bending stiffness, heel-toe drop, shoe mass, heel flare, and heel stabilizer on running-related performance and injuries. The results of this review study were: (1) The functional positioning of running shoe design and the target groups tend to influence running performance and injury risk; (2) Thickness of 15-20 mm, hardness of Asker C50-C55 of the midsole, the design of the medial or lateral heel flares of 15°, the curved carbon plate, and the 3D printed heel cup may be beneficial to optimize performance and reduce running-related injuries; (3) The update of research and development concepts in sports biomechanics may further contribute to the development of running shoes; (4) Footwear design and optimization should also consider the influences of runners' strike patterns.

Introduction: The ultrastructure and cellular composition of thrombi has a profound effect on the outcome of acute ischemic stroke (AIS), coronary (CAD) and peripheral artery disease (PAD). Activated neutrophils release a web-like structure composed mainly of DNA and citrullinated histones, called neutrophil extracellular traps (NET) that modify the stability and lysability of fibrin. Here, we investigated the NET-related structural features of thrombi retrieved from different arterial localizations and their interrelations with routinely available clinical data., Patients and Methods: Thrombi extracted from AIS (n = 78), CAD (n = 66) or PAD (n = 64) patients were processed for scanning electron microscopy, (immune)stained for fibrin, citrullinated histone H3 (cH3) and extracellular DNA. Fibrin fiber diameter, cellular components, DNA and cH3 were measured and analyzed in relation to clinical parameters., Results: DNA was least present in AIS thrombi showing a 2.5-fold lower DNA/fibrin ratio than PAD, whereas cH3 antigen was unvaryingly present at all locations. The NET content of thrombi correlated parabolically with systemic inflammatory markers and positively with patients' age. The median platelet content was lower in PAD (2.2%) than in either AIS (3.9%) or CAD (3.1%) and thrombi from smokers contained less platelets than non-smokers. Fibrin fibers were significantly thicker in male patients with CAD (median fiber diameter 76.3 nm) compared to AIS (64.1 nm) or PAD (62.1 nm) and their diameter correlated parabolically with systemic inflammatory markers., Conclusions: The observed NET-related variations in thrombus structure shed light on novel determinants of thrombus stability that eventually affect both the spontaneous progress and therapeutic outcome of ischemic arterial diseases., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Ependymomas are common pediatric brain tumors that originate from the ependyma and characterized by poor prognosis due to frequent recurrence. However, the current WHO grading system fails to accurately predict outcome. In a retrospective study, we analyzed 54 intracranial pediatric ependymomas and found a significantly higher overall survival in supratentorial cases when compared to infratentorial tumors. Next we performed region-specific immunohistochemical analysis of the ependyma in neonatal and adult ependyma from the central canal of spinal cord to the choroid plexus of lateral ventricles for components of cell-cell junctions including cadherins, claudins and occludin. We found robust claudin-5 expression in the choroid plexus epithelia but not in other compartments of the ependyma. Ultrastructural studies demonstrated distinct regional differences in cell-cell junction organization. Surprisingly, we found that 9 out of 20 supratentorial but not infratentorial ependymomas expressed high levels of the brain endothelial tight junction component claudin-5 in tumor cells. Importantly, we observed an increased overall survival in claudin-5 expressing supratentorial ependymoma. Our data indicates that claudin-5 expressing ependymomas may follow a distinct course of disease. The assessment of claudin-5 expression in ependymoma has the potential to become a useful prognostic marker in this pediatric malignancy.

Background: The two largest needle exchange programs (NEPs) in Hungary were forced to close down in the second half of 2014 due to extreme political attacks and related lack of government funding. The closures occurred against a background of rapid expansion in Hungary of injectable new psychoactive substances, which are associated with very frequent injecting episodes and syringe sharing. The aim of our analysis was to predict how the overall Hungarian NEP syringe supply was affected by the closures., Methods: We analyzed all registry data from all NEPs in Hungary for all years of standardized NEP data collection protocols currently in use (2008-2014) concerning 22 949 client enrollments, 9,211 new clients, 228,167 client contacts, 3,160,560 distributed syringes, and 2,077,676 collected syringes., Results: We found that while the combined share of the two now closed NEPs decreased over time, even in their partial year 2014 they still distributed and collected about half of all syringes, and attended to over half of all clients and client contacts in Hungary. The number of distributed syringes per PWID (WHO minimum target = 100) was 81 in 2014 in Hungary, but 39 without the two now closed NEPs., Conclusions: There is a high probability that the combination of decreased NEP coverage and the increased injection risk of new psychoactive substances may lead in Hungary to a public health disaster similar to the HIV outbreaks in Romania and Greece. This can be avoided only by an immediate change in the attitude of the Hungarian government towards harm reduction.

Aims: To assess the expression of the following cell cycle regulatory proteins in primary metastatic breast carcinomas (MBCs) and on availability in matched distant metastases (DMs): Ki67, cyclin A, geminin and aurora-kinase A (aurkA); and to compare the expression of these markers in early MBC (EMBC) and late MBC separated into groups according to median time point on metastatic event occurred (28 months)., Methods: The expression of the above mentioned markers was analysed in a total of 47 primary MBCs and 59 DMs (out of which 37 were pairs) by immunohistochemistry. Fourteen breast carcinomas with no relapse over a 10-year follow-up period were utilised as control cases (CBC)., Results: Among the MBCs, 22 metastasised to the bone, 4 to the lung and 21 to the central nervous system (CNS). Geminin (p<0.001) and Ki67 (p=0.001) were increased in the MBCs while aurkA and cyclin A showed no difference when compared with CBCs. There were no differences between aurkA, cyclin A and geminin expression in MBCs and DMs in general. Expression of Ki67 was, however, elevated (p=0.027) in DMs. In CNS metastases all markers showed elevated expression as compared to MBCs. In bone metastases, geminin was lower (p<0.001) compared with primary MBCs. In the metastases of the lung, the evaluated markers did not show different expression. According to the median follow-up until the metastatic event, Ki67 was found to be significantly elevated in EMBC (p=0.018)., Conclusions: Ki67 index and geminin distinguish a fraction of MBC with worse prognosis, showing increased levels in the latter in comparison to CBC being tumour-free over a 10-year follow-up period. Ki67 could possibly identify a group of MBCs that develop early DMs., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To examine how certain characteristics of film-presented practitioner role-models influence trainees' mentalization., Methods: In an experimental setting, psychology students watched four film clips presenting a patient-practitioner session; the clips varied in the practitioner's patient-centeredness (positive vs. negative) and gender. Participants commented on the practitioner's thoughts, emotions and intentions through the session. Analysis of 116 comments focused on the effect of patient-centeredness and gender variables on mentalization and judgment utterances., Results: Negative role-models and female role-models induced higher levels of mentalization compared to positive and male role-models. There was no gender difference in the level of mentalization; however male participants gave more judgmental responses than female participants. The patient-centeredness had a larger effect on mentalization when trainees described the opposite gender role-model., Conclusion: In a systematic comparison, students' capacity for mentalization differed according to role-models' patient-centeredness and gender, as well as the gender-match of students with role-models., Practice Implications: When working with film-presented role-models, educators should be aware of the differences in the level of mentalization elicited by positive and male role-models, as opposed to negative and female role-models. Educators should also consider the gender-match between trainees and role-models, therefore students should be exposed to both cross- and same-gender role-models., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Tumor angiogenesis and receptor tyrosine kinases (RTK) are major novel targets in anticancer molecular therapy. Accordingly, we characterized the vascular network and the expression pattern of angiogenic RTK in the most frequent pediatric brain tumors. In a retrospective collection of 44 cases (14 astrocytoma, 16 ependymoma and 14 medulloblastoma), immunohistochemistry for VEGFR1, VEGFR2, PDGFRα, PDGFRβ, and c-Kit as well as microvessel labeling with CD34 and SMA were conducted on surgical specimens. We found a significantly higher vascular density in ependymoma. Glomeruloid formations were abundant in medulloblastoma but rare or almost absent in astrocytoma and ependymoma, respectively. C-Kit and VEGFR2 labeled blood vessels were more abundant in ependymoma than in the other two types of tumors. In contrast, medulloblastoma contained higher number of PDGFRα expressing vessels. In tumor cells, we found no VEGFR2 but VEGFR1 expression in all three tumor types. PDGFRα was strongly expressed on the tumor cells in all three malignancies, while PDGFRβ tumor cell expression was present in the majority of medulloblastoma cases. Interestingly, small populations of c-Kit expressing cancer cells were found in a number of medulloblastoma and ependymoma cases. Our study suggests that different angiogenic mechanisms are present in ependymoma and medulloblastoma. Furthermore ependymoma patients may benefit from anti-angiogenic therapies based on the high vascularization as well as the endothelial expression of c-kit and VEGFR2. The expression pattern of the receptors on tumor cells also suggests the targeting of specific angiogenic tyrosine kinase receptors may have direct antitumor activity. Further preclinical and biomarker driven clinical investigations are needed to establish the application of tyrosine kinase inhibitors in the treatment of pediatric brain tumors.

Despite advances in imaging methods, the standard of diagnosis and treatment of the tumours of the nervous system remains the histological report issued by a neuropathologist. For reliable, definitive diagnosis, close collaboration with other medical professions is essential, correlation of histological findings with clinical and imaging results is necessary. Neuropathology became a subspecialty because of the specific knowledge and experience it requires. In more complex cases consultation with neuropathologists is important to ensure adequate diagnosis and subsequent treatment. In both establishing the diagnosis and treatment planning, the molecular testing of brain tumors becomes more and more important. These tests are reliably available only in larger centers. Out of the molecular markers, in current practice the investigation of codeletion at 1p/19q, IDH mutations, β-katenin nuclear positivity and MGMT methylation gained acceptance. Besides these tests already in practice, a vast array of potential diagnostic and prognostic markers are being investigated, which in the future may assist in delivering better and more individualized therapy.