Balance in focus: a simple observational scale to monitor the effect of exercises on static balance in case of childhood flexible flat foot

[Purpose] Childhood flexible flat foot is the most common lower limb deformity. Observational evaluation of the underlying elements of reactive balance during static positions is an accepted tool besides the timed measures. We aim to assess the effects of combined balance training on the foot function and to test the usefulness of our observational static balance score. [Participants and Methods] A total of 19 healthy primary school students with flexible flat foot deformity volunteered for the study. We evaluated the foot’s dynamic properties and static postural stability before and after a 20-week combined balance training. On the basis of the observational findings, the time vs. quality observational static balance score was developed. All data were subjected to Wilcoxon’s test and Friedman’s ANOVA to compare the effects of the training on foot trajectory and observational static balance score. [Results] Better strength and endurance in the foot extensors and improved foot function were noted after the training. Using our observational static balance score, the quality of the balance performance remarkably changed. [Conclusion] The quality domain of our new scale seems to be a useful tool in daily clinical practice and a more sensitive measure in eyes-closed situations.Key words: Balance, Foot, Movement strategy     

Hypercholesterolemia attenuates the anti-ischemic effect of preconditioning during coronary angioplasty

BACKGROUND: Cardioprotection by preconditioning is limited in some animal models of hypercholesterolemia. We studied ischemic preconditioning induced by coronary angioplasty in hypercholesterolemic and normocholesterolemic patients by means of a beat-to-beat analysis of ST segments. METHODS: Thirty coronary disease patients were classified into normocholesterolemic and hypercholesterolemic groups. Intracoronary ECG was recorded during three consecutive balloon inflations of 2-min duration with 5-min intervals. RESULTS: In normocholesterolemic patients, the ST segment was continuously elevated during the occlusions and rapidly normalized after balloon deflations. Repeated occlusions significantly attenuated ST-segment elevation from 1.28 +/- 0.67 to 0.88 +/- 0.51 mV (p < 0.001) and decreased the time to normalization of ST segment. In hypercholesterolemic patients, the ST segment was rapidly elevated in the first 30 s of the first occlusion, and normalization of the ST segment was longer on the first reperfusion. However, in these patients, repeated occlusions abolished the initial elevation of the ST segment but did not attenuate maximal ST-segment elevation (1.24 +/- 1.11 mV vs 1.21 +/- 1.09 mV) and failed to decrease the time to normalization of the ST segment. CONCLUSIONS: Hypercholesterolemia accelerates the evolution of myocardial ischemia, delays recovery on reperfusion, and deteriorates the anti-ischemic effect of preconditioning in humans.     

Reference data for ultrasound bone characteristics in Hungarian children aged 7–19 years

Backround: Osteoporosis is a common disease and physical activity (PA) has a favourable influence on bone status.

Aim: To establish normative data for calcaneal quantitative ultrasound (QUS) bone characteristics in children and to analyse the relationships between PA, anthropometric and bone parameters.

Subjects and methods: Hungarian children aged 7–19 (n?=?2674; 1325 girls, 1349 boys) provided PA, anthropometric and bone data. QUS parameters were registered with Sonost3000 densitometer (speed of sound: SOS, m/s; broadband ultrasound attenuation: BUA, dB/MHz; bone quantity index (BQI?=?αSOS?+?βBUA). Reference centiles of QUS parameters were constructed by LMS method. Multivariate linear regression models were used to analyse the relationships.

Results: QUS bone parameters increased with age. There were no gender differences, except in 11- and 19-year-old children, where boys showed higher values. SOS (1497.15?±?15.72 vs 1494.05?±?14.81?m/s) and BQI (65.31?±?16.71 vs 62.26?±?15.78) were higher in athletic children. The regression model revealed significant relations between SOS and age, relative muscle mass and PA; BUA correlated with gender, morphological age, BMI, relative muscle mass and PA.

Conclusions: Changes in the bone parameters among 7–19-year-old Hungarian children depended on age, anthropometric dimensions and the level of PA. The normative data could be used for monitoring QUS bone parameters in children, leading to more effective interventions for healthy bones.     

Loss of the nodule-specific cysteine rich peptide,NCR169, abolishes symbiotic nitrogen fixation in the Medicago truncatula dnf7 mutant

Host compatible rhizobia induce the formation of legume root nodules, symbiotic organs within which intracellular bacteria are present in plant-derived membrane compartments termed symbiosomes. In Medicago truncatula nodules, the Sinorhizobium microsymbionts undergo an irreversible differentiation process leading to the development of elongated polyploid noncultivable nitrogen fixing bacteroids that convert atmospheric dinitrogen into ammonia. This terminal differentiation is directed by the host plant and involves hundreds of nodule specific cysteine-rich peptides (NCRs). Except for certain in vitro activities of cationic peptides, the functional roles of individual NCR peptides in planta are not known. In this study, we demonstrate that the inability of M. truncatula dnf7 mutants to fix nitrogen is due to inactivation of a single NCR peptide, NCR169. In the absence of NCR169, bacterial differentiation was impaired and was associated with early senescence of the symbiotic cells. Introduction of the NCR169 gene into the dnf7-2/NCR169 deletion mutant restored symbiotic nitrogen fixation. Replacement of any of the cysteine residues in the NCR169 peptide with serine rendered it incapable of complementation, demonstrating an absolute requirement for all cysteines in planta. NCR169 was induced in the cell layers in which bacteroid elongation was most pronounced, and high expression persisted throughout the nitrogen-fixing nodule zone. Our results provide evidence for an essential role of NCR169 in the differentiation and persistence of nitrogen fixing bacteroids in M. truncatula.Legumes form endosymbiotic interactions with nitrogen-fixing soil bacteria, called rhizobia. In these symbioses, the plant provides a microaerobic environment and energy source for bacterial nitrogen fixation, and in return receives fixed nitrogen in the form of ammonium (1). Following mutual recognition, regulated developmental programs are induced in both partners leading to the formation of root nodules (2). In root hairs, host compatible rhizobia initiate the development of infection threads, along which the bacteria grow. In parallel, mitosis of cortical and pericycle cells is induced, and their proliferation leads to the formation of the nodule primordium. The infection threads grow down through the cortex and when they reach the nodule primordia, rhizobia are released and colonize nodule cells via endocytosis. Within the infected nodule cells, bacteria are surrounded by the plant-derived peribacteroid membrane, which delimits a new, facultative nitrogen-fixing organelle called the symbiosome. During nodule development, infected nodule cells also undergo differentiation; they become polyploid via multiple rounds of endoreduplication, which results in enlargement of cells that eventually become packed with thousands of symbiosomes (3, 4).Sinorhizobium (Ensifer) meliloti and S. medicae establish symbioses with Medicago truncatula leading to the formation of indeterminate nodules. This nodule type is characterized by a persistent nodule meristem and a gradient of cells in different developmental states forming specific histological zonation (5). Continuous cell proliferation in the meristem (zone I) produces cells that exit the mitotic cycle and enter cell differentiation. Zone II corresponds to the infection zone where bacteria are released from the infection threads and then these infected symbiotic cells undergo gradual differentiation. Growing, infected plant cells host more and more multiplying symbiosomes. Eventually, symbiosome proliferation ceases in older cells of Zone II, although replication of bacterial genomes continues without cell division, resulting in enlarged/elongated polyploid bacteroids. Some of the most striking changes occur in the interzone (zone II-III), a transition zone characterized by amyloplast deposition. In this zone, both rhizobia and symbiotic nodule cells complete their differentiation with the last rounds of endoreduplication and final enlargement of cells. The nitrogen-fixing zone III comprises the major part of a functional nodule wherein the differentiated bacteroids reduce atmospheric nitrogen. The developmental switches of symbiotic nodule cells are accompanied by altered size, shape and appearance of the vacuoles, which become larger in the older Zone II cells, collapse in the transition zone, and then reappear in mature nitrogen fixing cells (6). As nodule cells age, nitrogen-fixation ceases and degradation of these cells leads to formation of the senescence zone (zone IV), proximal to the root, where bacteroids are digested.The differentiation of the endosymbionts is irreversible as they are unable to resume cell proliferation and to reenter the free-living life-style (7). M. truncatula and other IRLC (Inverted Repeat-Lacking Clade) legumes possess a remarkably large number of genes encoding nodule-specific cysteine-rich (NCR) peptides (8–12). The genome of M. truncatula contains more than 600 NCR genes (13). The peptides enter the secretory pathway and the relatively conserved signal peptides are cleaved off by the signal peptidase complex in the endoplasmic reticulum (14). The mature peptides are composed of 30–50 amino acids and differ in composition and sequence, except for conserved positions of four or six cysteine residues (15). At least 138 NCR peptides are known to be targeted to the symbiosomes (16–18) and failure of their delivery to the symbiosomes impairs bacteroid differentiation in M. truncatula (16). The functions of individual NCRs as well as their combined action have remained elusive until now. Their expression at different stages of symbiotic cell development suggests distinct roles for members of this family. NCRs resemble defensin-type antimicrobial peptides in some ways. Several cationic NCR peptides display in vitro antimicrobial (bactericide and fungicide) activities (19, 20). Such NCRs expressed in the older cells of Zone II could contribute to the arrest of proliferation of bacteroids. Chemically synthesized NCR247 interacts with multiple proteins in vitro and such interactions might affect different aspects of bacteroid physiology, including gene expression, translation and arrest of cell division (17, 21). A question is whether NCR peptides function collectively or whether individual peptides might fulfill unique and essential roles. In this study, we found that loss of the NCR169 gene in the M. truncatula deletion mutant dnf7 (defective in nitrogen fixation) impairs symbiotic nitrogen-fixation. We show that the NCR169 gene fully restores the wild-type (WT) symbiotic phenotype of the dnf7 mutant and demonstrate that the in planta biological activity requires all of the cysteine residues of NCR169. In dnf7 mutant nodules, bacteroid differentiation was incomplete, although late nodulin genes and the bacterial nifA regulated genes required for the nitrogenase enzyme complex assembly were expressed. The mutant phenotype indicates that NCR169 is required for complete differentiation of bacteroids and their persistence in M. truncatula nodules.     

Citrullination under physiological and pathological conditions

Citrullination, one of the enzymatic posttranslational modifications has become a hot topic of recent research as it is involved in various physiological and pathological processes. Antibodies against citrullinated proteins called anti-citrullinated protein antibodies, are the hallmark (diagnostic and prognostic factors) of rheumatoid arthritis, and are specific for the disease. Citrullination has an important role in the normal function of the immune system, skin keratinization, the insulation of neurons and the plasticity of the central nervous system including its essential role in gene regulation. Abnormal citrullination has been proposed to play a role in multiple sclerosis and Alzheimer's disease, and recent research has drawn attention to its implication in tumorigenesis. Still, it is unclear whether citrullination is the cause or the consequence of these pathological alterations. Here, we discuss crucial aspects of citrullination during both physiological and pathological conditions.     

The role of FDG PET/CT for detecting the cause of fever of unknown origin in a clinical case

The fever of unknown origin from time to time constitutes a serious clinical problem and nearly all diagnostic methods are involved to discover urgently its cause. According to literature data (18)F-fluoro-deoxyglucose PET/CT was successful in 25-70% of cases even in patients without any positive findings with conventional diagnostic techniques. The Hungarian National Health Fund does not include fever of unknown origin in the list of reimbursed (18)F-fluoro-deoxyglucose PET/CT indications. The authors try to illustrate the clinical problem with this case report. Fever of unknown origin persisted in a patient for a year, but conventional diagnostic procedures were unsuccessful to find the cause of the fever. Finally, (18)F-fluoro-deoxyglucose PET/CT indicated a metabolically active focus between the pancreas tail and the spleen. After a long-lasting antibiotic therapy the patient became symptomfree.     

Impact of hemodialysis,left ventricular mass and FGF-23 on myocardial mechanics in end-stage renal disease: a three-dimensional speckle tracking study

Left ventricular (LV) hypertrophy and one of its inducers, the fibroblast growth factor-23 (FGF-23) were found to be associated with unfavourable outcome in end-stage renal disease (ESRD) patients. We sought to investigate the influence of hemodialysis (HD), increased LV mass and FGF-23 on LV mechanics using three-dimensional (3D) speckle tracking echocardiography. Forty-four ESRD patients on maintenance HD were examined just before and immediately after HD, and were compared to 44 normal controls (NC). Transthoracic 3D recordings were obtained using multi-beat reconstruction from 6 consecutive cardiac cycles. LV mass index (LVMi) was evaluated and 3D speckle tracking analysis was performed to calculate global longitudinal (GLS), circumferential (GCS), area (GAS) and radial (GRS) peak systolic strain. Serum FGF-23 levels were also measured. Strain values improved in all directions after HD [pre- vs. post-HD; GLS: ?20(3) vs. ?21(6), GCS: ?20(4) vs. ?22(7), GAS: ?33(5) vs. ?35(10), GRS: 50(12) vs. 53.5(20)  %, all p < 0.01]. LVMi was remarkably increased in our patients [ESRD vs. NC; 136(46) vs. 71(8) g/m², p < 0.001]. Elevated FGF-23 levels were associated with increased LV mass (ρ = 0.581, p < 0.001). LVMi was inversely related to pre-HD GCS (ρ = 0.626, p < 0.001) and post-HD GCS (ρ = 0.761, p < 0.001), GAS (ρ = 0.534, p < 0.05) and GRS (ρ = ?0.639, p < 0.01). Serum FGF-23 levels correlated with post-HD GAS (ρ = 0.513, p < 0.01) and GRS (ρ = ?0.512, p < 0.05). HD treatment results in immediate improvement in all strain directions. Besides inducing LV hypertrophy, FGF-23 may play a role in the deterioration of LV mechanics in patients with ESRD.     

Hormonal evaluation and mutation screening for steroid 21-hydroxylase deficiency in patients with unilateral and bilateral adrenal incidentalomas

OBJECTIVE: The aims of the present study were (a) to examine the occurrence of 21-hydroxylase gene (CYP21) mutations in patients with unilateral and bilateral adrenal incidentalomas and (b) to correlate the results of mutation screening with hormonal parameters of 21-hydroxylase deficiency. DESIGN: The frequency of the eight commonly occurring CYP21 mutations in blood DNA samples of 19 patients with bilateral, as well as in blood and tumoral tissue DNA samples of 31 patients with unilateral adrenal incidentalomas, was determined. In all patients, hormonal evaluation for 21-hydroxylase deficiency was performed using measurements of basal and ACTH-stimulated plasma 17-hydroxyprogesterone (17-OHP) concentrations. METHODS: Blood and tumoral DNA samples were analyzed by allele-specific PCR for the detection of the eight commonly occurring CYP21 mutations (deletion/large gene conversion, intron 2 splicing, Ile172Asn, exon 6 cluster, Val281Leu, Leu307insT, Gln318Stop and Arg356Trp mutations). Plasma 17-OHP concentrations were measured by radioimmunoassay. RESULTS: Of the 19 patients with bilateral adrenal incidentalomas, one patient had homozygous (Val281Leu) and three patients had heterozygous germline CYP21 mutations (Val281Leu in two cases and Arg356Trp in one case). Heterozygous germline CYP21 mutations were also detected in five of the 31 patients with unilateral adrenal incidentalomas (Ile172Asn in three cases and Val281Leu in two cases). Mutation screening of tumoral DNA in unilateral incidentalomas showed the presence of corresponding germline mutations but no additional somatic mutations were found. ACTH-stimulated plasma 17-OHP concentrations were above 1500 ng/dl in all patients with bilateral incidentalomas who had homozygous and heterozygous CYP21 mutations, but heterozygous carriers with unilateral incidentalomas had highly variable ACTH-stimulated plasma 17-OHP levels (between 111 and 1705 ng/dl). CONCLUSIONS: These results suggest a similar frequency of germline CYP21 mutations in patients with bilateral and unilateral adrenal incidentalomas (21.1% and 16.1% respectively). Therefore, it cannot be ruled out that, in at least some patients, CYP21 mutations may play a role in the pathomechanism of bilateral and unilateral adrenal incidentalomas. However, the lack of clear association of CYP21 mutations with increased ACTH-stimulated plasma l7-OHP response, especially in patients with unilateral incidentalomas, suggests that the effect of CYP21 mutations on adrenocortical tumor formation may also involve mechanism(s) independent of ACTH-induced changes in 17-OHP secretion.