Impact of autoimmune gastritis on chronic urticaria in paediatric patients - pathophysiological point of views.

We would like to provide an updated comprehensive perspective and identify the components linked to chronic spontaneous urticaria (CSU) without specific triggers in autoimmune atrophic gastritis (AAG). AAG is an organ-specific autoimmune disease that affects the corpus-fundus gastric mucosa. Although we lack a unified explanation of the underlying pathways, when considering all paediatric patients reported in the literature, alterations result in gastric neuroendocrine enterochromaffin-like (ECL) cell proliferation and paracrine release of histamine. Several mechanisms have been proposed for the pathogenesis of CSU, with much evidence pointing towards AAG and ECL cell responses, which may be implicated as potential factors contributing to CSU. The excessive production/release of histamine into the bloodstream could cause or trigger exacerbations of CSU in AAG, independent of Helicobacter pylori; thus, the release of histamine from ECL cells may be the primary modulator. CONCLUSION: Considering the understanding of these interactions, recognising the respective roles of AAG in the pathogenesis of CSU may strongly impact the diagnostic workup and management of unexplained/refractory CSU and may inform future research and interventions in the paediatric population. WHAT IS KNOWN: • Autoimmune atrophic gastritis is a chronic immune-mediated inflammatory disease characterised by the destruction of the oxyntic mucosa in the gastric body and fundus, mucosal atrophy, and metaplastic changes. • Autoimmune atrophic gastritis in paediatric patients is important because of the poor outcome and risk of malignancy and possibly underestimated entities primarily reported in single-case reports. WHAT IS NEW: • Upper gastrointestinal inflammatory disorders, independent of H. pylori, have been implicated as potential inducing factors in the development of chronic spontaneous urticaria. • If a paediatric patient presents with symptoms such as anaemia, reduced vitamin B12 levels, recurrent urticaria with no other detectable aetiology, positive anti-parietal cell antibodies, and elevated gastrin levels, autoimmune atrophic gastritis should be considered a possible cause of chronic urticaria.

Bilateral versus unilateral total knee replacement - comparison of clinical and functional results in two-year follow-up.

INTRODUCTION: Total knee replacement is one of the most common surgical methods in diagnosis of end staged osteoarthritis. In this retrospective analysis, we focus on comparison of functional and clinical outcome in patients undergoing unilateral and bilateral replacement within a single surgical procedure. METHODS: 54 patients (bilateral 19, unilateral 35) underwent total knee replacement in our clinic participated in the current study. The length of hospital stay was monitored in all patients. Assessment of functional results was based on the WOMAC score, KSS 1, KSS2, range of motion and presence of complications in both groups. RESULTS: Both groups of patients were homogeneous with age, body mass index and sex. The length of hospital stay in the unilateral group was 4.7±1.3 and 5.6±2.0 in the bilateral group. Patients operated on unilaterally achieved flexion of 114.9±9.3 after one year, bilateral group 112.6±8.6, the difference was insignificant. In both groups, there is a significant improvement one year postoperatively at WOMAC, KSS1 and KSS2. Comparing WOMAC, KSS1 and KSS2 between the unilateral and bilateral groups 3, 6, 12 months postoperatively, the differences are insignificant. The revision of implants in two-year follow-up reached 1.5% in unilateral group and 1.4% in bilateral group. CONCLUSION: Unilateral and bilateral knee joint endoprosthesis implantation is a successful surgical method in orthopedic practice. With conscious selection of patients, bilateral implantation may be more advantageous alternative, as the patient undergoes one operation and the associated risks.

[Radiotherapy Indications in Patients with Hematological Malignancies During the Five Years Course of Modernized Center of Oncology and Radiotherapy Clinic in Pilsen]. / Indikace radioterapie u pacientu s hematologickými malignitami v prubehu peti let provozu modernizovaného centra Onkologické a radioterapeutické kliniky v Plzni.

Submitted: 27. 2. 2016.

Comparison of the level of physical activity after the COVID-19 pandemic in Poland, Slovakia and the Czech Republic.

BACKGROUND: The COVID-19 pandemic was associated with limited physical activity (PA) of most of the world's population. This cross-sectional prospective study aimed to assess the levels of PA of university students in Poland, Czech Republic and Slovakia after COVID-19 using the International Physical Activity Questionnaire Short Form (IPAQ-SF). METHODS: A total of 2635 students completed questionnaires regarding their PA levels using the IPAQ-SF between September and December 2022. RESULTS: PA measured by metabolic equivalent of task (MET) scores, varied between the three countries: Slovakia median MET-minutes/week score 4459.9; Czech Republic 3838.8 Poland 3567.1. The results of the post hoc analysis revealed there were significant differences in MET-minutes/week values between the Czech Republic and Poland (p < 0.035) as well as between the Czech Republic and Slovakia (p < 0.037). The analysis of energetic expenditure during walking revealed that students from the Czech Republic and Slovakia had higher median MET-min/weeks values (Czech 2284.1; Slovak 2467.1) compared to their Polish (1536.1) peers (p < 0.001). Polish cohort presented with significantly higher body mass index (BMI) (p < 0.001) than Czech and Slovak groups (BMI Czech: 22.3; Slovak 22.8; Polish 23.8). CONCLUSIONS: Significant differences in PA levels between the Czech Republic, Poland, and Slovakia university students were identified. Slovakia showed the highest median PA measured as a MET score, and Poland showed the lowest. Compared to available pre-COVID studies it seems the total level of PA in the observed cohorts has not returned to the pre-COVID levels and students remain less active.

[Identification of molecular markers in children with acute myeloid leukemia (AML)]. / Identifikácia molekulárnych markerov u detí s akútnou myeloblastovou leukémiou (AML).

BACKGROUNDS: AML is an aggressive, phenotypically and genetically heterogenous clonal disease of hematopoietic progenitor cells with a great molecular variability. New WHO classification 2008 divides de novo AML according to cytogenetic and molecular prognostic and predictive markers. Recently, it is increasingly possible to identify a subgroup of poorer prognosis patients among those with normal karyotype AML. The aim of our study was to identify prognostically important molecular markers in children with AML, to stratify patients with normal karyotype and to monitor the disease according the genetic findings. MATERIAL AND METHODS: In 2008-2010, we analyzed bone marrow and peripheral blood samples of 20 children with de novo AML by conventional cytogenetic analysis, fluorescence in situ hybridisation and molecular diagnostics. The molecular analysis was performed on the cDNA level, with the restriction analysis of PCR products (FLT3-TKD), conventional PCR (MLL-PTD, NPM1mut, FLT3-ITD) and quantification RT-PCR method (expression of fusion transcripts, BAALC, WT1). RESULTS: Samples from 20 children with AML were analyzed using the conventional cytogenetics, FISH and molecular methods. Abnormal karyotype was identified in 13 patients (65%). Further analysis revealed FLT3-ITD in 5/20 (25%), FLT3-TKD in 3/20 (15%), NPM1mut in 2/20 (10%) and MLL-PTD in 1/20 (5%), overexpression of WT1 gene in 15/20 (75%) and overexpression of BAALC in 13/20 (65%) patients. CONCLUSION: Wide cytogenetic and molecular screening helped to find at least one genetic marker in all 20 patients for later follow-up and risk stratification. 4/20 (20%) patients died of the disease progression.

Photoinduced intramolecular tryptophan oxidation and excited-state behavior of [Re(L-AA)(CO)3(α-diimine)](+) (L = pyridine or imidazole, AA = tryptophan, tyrosine, phenylalanine).

Re(I) carbonyl-diimine complexes [Re(L-AA)(CO)(3)(N,N)](+) (N,N = bpy, phen) containing an aromatic amino acid (AA), phenylalanine (Phe), tyrosine (Tyr), or tryptophan (Trp), linked to Re by a pyridine-amido or imidazole-amido ligand L have been synthesized and their excited-state properties investigated by nanosecond time-resolved IR (TRIR) and emission spectroscopy. Near-UV optical excitation populates a Re(I)(CO)(3)→N,N (3)MLCT excited state *[Re(II)(L-AA)(CO)(3)(N,N(•-))](+). Decay to the ground state (50-300 ns lifetime) is the only excited-state deactivation process observed in the case of Phe and Tyr complexes, whereas the Trp-containing species undergo a Trp(indole)→*Re(II) electron transfer (ET) producing a charge-separated (CS) state, [Re(I)(L-Trp(•+))(CO)(3)(N,N(•-))](+). The ET occurs with a 8-40 ns lifetime depending on L, N,N, and the solvent. The CS state is characterized by ν(CO) IR bands shifted to lower wavenumbers from their respective ground-state positions and two bands at 1278 and 1497 cm(-1) tentatively attributed to Trp(•+). The amido bridge is affected by both the MLCT excitation and the subsequent ET, manifested by the shifts and intensity changes of the amide-I IR band at about 1680 cm(-1). The CS state decays to the ground state by a N,N(•-)→Trp(•+) back-ET the rates of which are comparable to those of the forward ET, 30-60 ns. This study independently demonstrates that Trp can act as an electron-hopping intermediate in photodriven ET systems based on Re-labeled proteins and supramolecules. Photoinduced ET in Trp-containing Re complexes also can be used to generate Trp(•+) and investigate its spectral properties and reactivity.

Dynamic changes of high-sensitivity troponin T concentration during infancy: Clinical implications.

Cardiac troponin T determination plays a dominant role in diagnosis of myocardial pathologies. Despite generally accepted use of high-sensitive cardiac troponin T assays (hscTnT) and clearly defined cut-off limit in adults, the uncertainty persists in infants. The aim of this study was to assess plasmatic concentrations of hscTnT and describe sequential age-related dynamic changes of hscTnT in healthy infants and toddlers. Seventy-eight children (52 males/26 females) from Czech Republic aged 44 to 872 days (median, interquartile range 271; 126 to 486 days) were consecutively enrolled in the single-center, prospective observational study. Plasma concentrations of hscTnT were analyzed by the electrochemiluminescent method, age-related reference intervals were calculated using the polynominal regression model. Amongst the study population (n=78), the upper limit of hscTnT concentration defined as the 99th percentile was calculated. The 99th percentile with 95 % confidence interval at the end of 2nd, 3rd, 4th, 5th, 6th and 7th month of postnatal life were: 81 (40.6 to 63.6), 61 (36.0 to 55.3), 47 (31.9 to 48.3), 37 (28.1 to 42.3), 30 (24.7 to 37.2) and 25 (21.5 to 32.7) ng/l, respectively. Concentration of adults 99th percentile (14 ng/l) was achieved approximately at 1 year of postnatal life. Statistically significant negative correlation of hscTnT concentration with age (r=-0.81, p<0.001) was found. Significant gender differences were not found (p>0.07). The study revealed substantially increased reference intervals of hscTnT levels in infants when compared with adult population. Based on our preliminary results, the age-related interpretation of hscTnT plasmatic concentration is recommended.

Age-Related Progression of Microvascular Dysfunction in Cystic Fibrosis: New Detection Ways and Clinical Outcomes.

There are concerns about altered vascular functions that could play an important role in the pathogenesis and influence the severity of chronic disease, however, increased cardiovascular risk in paediatric cystic fibrosis (CF) has not been yet fully understood. Aim was to analyse vascular disease risk and investigate changes over times in CF and controls. We prospectively enrolled 22 CF subjects (a median age of 16.07 years), and 22 healthy demographically matched controls (a median age of 17.28 years) and determined endothelial function. We utilised a combined diagnostic approach by measuring the plethysmographic Reactive Hyperemia Index (RHI) as the post-to preocclusive endothelium-dependent changes of vascular tone, and biomarkers that are known to be related to endothelial dysfunction (ED): asymmetric dimethyl arginine (ADMA), high-sensitive CRP (hsCRP), VCAM-1 and E-selectin. RHI values were significantly lower in CF young adults (p<0.005). HsCRP (p<0.005), E-selectin (p<0.001) and VCAM-1 (p<0.001) were significantly increased in CF patients since childhood. The findings have provided a detailed account of the ongoing process of microvascular dysfunction with gradual progression with the age of CF patients, making them further at risk of advanced vascular disease. Elevations of biomarkers in CF children with not yet demonstrated RHI changes but with significantly reduced RHI in adulthood and lipid profile changes indicate the possible occurrence of ED with CF-related specific risk factors over time and will enable us to provide the best possible support.

The assessment of plasma fatty acid profiles in newly diagnosed treatment-naive paediatric Crohn's disease.

Fatty acid (FA) profiles as potentially relevant components of Crohn's disease (CD) have been insufficiently analysed. We sought to explore the plasma profiles of n-3 and n-6 polyunsa-turated fatty acids (PUFAs) in newly diagnosed untreated active CD. We included 26 consecutive CD pediatric patients (<19 years) and 14 healthy controls (HCs). Disease characteristics, including inflammatory markers, dietary histories, and the Pediatric Crohn's Disease Activity Index (PCDAI), were obtained. The profiles of plasma FAs in plasma lipid classes were analysed by gas chromatography with FID detection of methyl esters. The erythrocyte sedimentation rate, C-reactive protein level and fecal calprotectin level (all p<0.001) were significantly higher in CD patients than in HCs. Most changes were observed in plasma phospholipids (PLs), such as a higher content of n-3 and changes in n-6 long-chain PUFAs in the CD group. The CD group had a lower ratio of n-6/n-3 PUFAs in PLs (p<0.001) and triacylglycerols (TAGs) (p<0.01). Correlations of the FA content in plasma PLs with disease activity scores of CD were also observed, which were positive for the sum of monounsaturated fatty acids (MUFAs) as well as oleic acid (18:1n-9) (both p<0.05). The metabolism of PUFAs is significantly altered even in treatment-naive newly diagnosed active pediatric CD, and the content of major FAs in PLs correlates with disease activity and inflammatory markers, thus probably contributing to the still unclear early disease pathogenesis.

The effect of detergents on trimeric G-protein activity in isolated plasma membranes from rat brain cortex: correlation with studies of DPH and Laurdan fluorescence.

The effect of non-ionic detergents on baclofen (GABAB-R agonist)-stimulated G-protein activity was measured as a [(35)S]GTPgammaS binding assay in the plasma membranes (PM) isolated from the brain tissue. The effect was clearly biphasic--a decrease in the activity was followed by an activation maximum and finally, at high concentrations, drastic inhibition of the G-protein activity was noticed. Contrarily, specific radioligand binding to GABAB-receptor was inhibited in the whole range of detergent concentrations step by step, i.e. it was strictly monophasic. The magnitude of both detergent effects was decreased in the same order of potency: Brij58>Triton X-100>Digitonin. The identical order was found when comparing detergents ability to alter fluorescence anisotropy of the membrane probe 1,6-diphenyl-1,3,5-hexatriene (rDPH) incorporated into the hydrophobic PM interior. Decrease of rDPH, in the order of Brij58>Triton X-100>Digitonin, was reflected as decrease of the S-order parameter and rotation correlation time phi paralleled by an increase of diffusion wobbling constant Dw (analysis by time-resolved fluorescence according to "wobble-in-cone" model). The influence of the detergents on the membrane organization at the polar headgroup region was characterized by Laurdan generalized polarization (GP). As before, the effect of detergents on GP parameters proceeded in the order: Brij58>Triton X-100>Digitonin.

Furnace for in situ and simultaneous studies of nano-precipitates and phase transformations in steels by SANS and neutron diffraction.

Interphase precipitation occurring during solid-state phase transformations in micro-alloyed steels is generally studied through transmission electron microscopy, atom probe tomography, and ex situ measurements of Small-Angle Neutron Scattering (SANS). The advantage of SANS over the other two characterization techniques is that SANS allows for the quantitative determination of size distribution, volume fraction, and number density of a statistically significant number of precipitates within the resulting matrix at room temperature. However, the performance of ex situ SANS measurements alone does not provide information regarding the probable correlation between interphase precipitation and phase transformations. This limitation makes it necessary to perform in situ and simultaneous studies on precipitation and phase transformations in order to gain an in-depth understanding of the nucleation and growth of precipitates in relation to the evolution of austenite decomposition at high temperatures. A furnace is, thus, designed and developed for such in situ studies in which SANS measurements can be simultaneously performed with neutron diffraction measurements during the application of high-temperature thermal treatments. The furnace is capable of carrying out thermal treatments involving fast heating and cooling as well as high operation temperatures (up to 1200 °C) for a long period of time with accurate temperature control in a protective atmosphere and in a magnetic field of up to 1.5 T. The characteristics of this furnace give the possibility of developing new research studies for better insight of the relationship between phase transformations and precipitation kinetics in steels and also in other types of materials containing nano-scale microstructural features.

The diagnosis of norovirus infections in hospitalized children and adolescents with acute gastroenteritis: a study from Pilsen, Czech Republic.

BACKGROUND: Norovirus-associated sporadic gastroenteritis is an important cause of illness in Western Europe. However, at present, little information on the role of norovirus in sporadic gastroenteritis in Central Europe is available. Our study aimed at providing an assessment of their significance in hospitalized children and adolescents with acute gastroenteritis using ELISA test at the time of their introduction. METHODS: A prospective hospital based study of the etiology of acute gastroenteritis was undertaken in a total of 618 patients (mean age 39.8 months, range 0-228), who were hospitalized at the Charles University Hospital in Pilsen. All subjects were monitored in six fragmented periods during the years 2003 and 2004, 2006 and 2007. Clinical and laboratory data were processed, norovirus antigens in stools were detected using the EIA kits IDEIA Norovirus, DakoCytomation. RESULTS: A norovirus infection was confirmed in 62 cases, i.e., 10.0% of all patients with acute gastroenteritis. Vomiting was the most common symptom, recorded in 95.2 % of all the patients with norovirus infection. No severe extragastrointestinal complications were detected. The average interval between initial symptoms and the beginning of hospitalization was considerably shorter in patients with norovirus infection (1.3 days) compared with patients with rotavirus infections (2.4 days). The frequency of Salmonella spp., rotavirus, Campylobacter spp. and enteric adenovirus was 15.4%, 11.2%, 3.9%, 3.6%, respectively. CONCLUSIONS: Our findings confirm the clinical importance of noroviruses as a causative agent of acute gastroenteritis in children and teenagers in the region of a Central European country. Identification of norovirus infection should be included in the routine screenings of sporadic cases of acute gastroenteritis.

The use of solvent relaxation technique to investigate headgroup hydration and protein binding of simple and mixed phosphatidylcholine/surfactant bilayer membranes.

The subject of this report was to investigate headgroup hydration and mobility of two types of mixed lipid vesicles, containing nonionic surfactants; straight chain Brij 98, and polysorbat Tween 80, with the same number of oxyethylene units as Brij, but attached via a sorbitan ring to oleic acid. We used the fluorescence solvent relaxation (SR) approach for the purpose and revealed differences between the two systems. Fluorescent solvent relaxation probes (Prodan, Laurdan, Patman) were found to be localized in mixed lipid vesicles similarly as in pure phospholipid bilayers. The SR parameters (i.e. dynamic Stokes shift, Deltanu, and the time course of the correlation function, C(t)) of such labels are in the same range in both kinds of systems. Each type of the tested surfactants has its own impact on water organization in the bilayer headgroup region probed by Patman. Brij 98 does not modify the solvation characteristics of the dye. In contrast, Tween 80 apparently dehydrates the headgroup and decreases its mobility. The SR data measured in lipid bilayers in presence of Interferon alfa-2b reveal that this protein, a candidate for non-invasive delivery, affects the bilayer in a different way than the peptide melittin. Interferon alfa-2b binds to mixed lipid bilayers peripherally, whereas melittin is deeply inserted into lipid membranes and affects their headgroup hydration and mobility measurably.

Plethysmographic and biochemical markers in the diagnosis of endothelial dysfunction in pediatric acute lymphoblastic leukemia survivors - new applications.

Acute lymphoblastic leukemia (ALL) and its treatment are associated with endothelial dysfunction (ED) and increased cardiovascular risk in adulthood. There are no data on ED in children after successful treatment of ALL. We aimed to assess new ED in these children using the plethysmographic reactive hyperemia index (RHI) and biomarkers that are known to be related to ED. In all, 22 children (mean 15.6 years), after successful treatment of ALL, and 18 healthy subjects were included in this prospective study. RHI, plasma concentrations of asymmetric dimethyl arginine (ADMA), high-sensitive CRP (hsCRP) and E-selectin were measured in all children. RHI values were significantly lower in ALL patients when compared with healthy controls (p<0.05). hsCRP was significantly increased in ALL patients compared with the control group (p<0.001). E-selectin plasma levels were higher in ALL patients as compared to healthy controls (p=0.05). This is the first study that combines both plethysmographic and biochemical methods to assess ED in ALL survivors. Significantly decreased RHI with elevated plasma concentrations of biochemical markers imply a possible association with premature ED in ALL patients. The combined diagnostic approach seems to be a valuable tool for more accurate detection of ED and preventive cardiovascular management in these patients.

Molecular interpretation of fluorescence solvent relaxation of Patman and 2H NMR experiments in phosphatidylcholine bilayers.

The analysis of time-dependent fluorescence shifts of the bilayer probe 6-hexadecanoyl-2-(((2-(trimethylammonium)ethyl)methyl)amino)naphthalene chloride (Patman) offers valuable information on the hydration and dynamics of phospholipid headgroups. Quenching studies on vesicles composed of four phosphatidylcholines with different hydrocarbon chains (18:1c9/18:1c9, DOPC; 16:0/18:1c9, POPC; 18:1c9/16:0, OPPC; 18:1c6/18:1c6, PCDelta6) show that the chromophore of Patman is defined located at the level of the sn-1 ester-group in the phospholipid, which is invariant to the hydrocarbon chain. The so-called solvent relaxation (SR) approach as well as solid-state 2H NMR reveals that DOPC and PCDelta6 are more hydrated than POPC and OPPC. A strong dependence of SR kinetics on the position of double bond in the investigated fatty acid chains was observed. Apparently, the closer the double bond is located to the hydrated sn-1 ester-group, the more mobile this group becomes. This work demonstrates that the SR approach can report mobility changes within phospholipid bilayers with a remarkable molecular resolution.

Paucity of FOXP3+ cells in skin and peripheral blood distinguishes Sézary syndrome from other cutaneous T-cell lymphomas.

Cutaneous T-cell lymphomas (CTCL) are mainly comprised of two variants: mycosis fungoides (MF) with CD4(+) tumor cells confined to the skin and the leukemic Sézary syndrome with tumor cell spread to the blood. In this study, we investigated cutaneous expression of the regulatory T-cell (T(reg)) marker FOXP3 in 30 CTCL patients. Immunohistochemical analysis revealed significantly lower numbers of CD4(+)FOXP3(+) cells within the dermal lymphomononuclear infiltrate of Sézary patients (16% FOXP3(+) cells of CD4(+) cells) in contrast to MF (43% FOXP3(+) cells (P<0.05)) and rare types of CTCL (45% FOXP3(+) cells). Furthermore, CD4(+)FOXP3(+) T cells were also markedly reduced in the CD4(+) population within the peripheral blood of Sézary patients compared to controls as determined by fluorescence-activated cell sorter, quantitative PCR and functional analyses. The data support the conclusion that the neoplastic cells in CTCL do not express the T(reg) marker FOXP3. Our data also identify Sézary syndrome as, to our knowledge, the first reported neoplastic disease with a clear reduction in T(reg) numbers within the CD4(+) population. This lack of T(reg) might account for the more aggressive nature of Sézary syndrome compared with other CTCL.

On the generation of solar spicules and Alfvénic waves.

In the lower solar atmosphere, the chromosphere is permeated by jets known as spicules, in which plasma is propelled at speeds of 50 to 150 kilometers per second into the corona. The origin of the spicules is poorly understood, although they are expected to play a role in heating the million-degree corona and are associated with Alfvénic waves that help drive the solar wind. We compare magnetohydrodynamic simulations of spicules with observations from the Interface Region Imaging Spectrograph and the Swedish 1-m Solar Telescope. Spicules are shown to occur when magnetic tension is amplified and transported upward through interactions between ions and neutrals or ambipolar diffusion. The tension is impulsively released to drive flows, heat plasma (through ambipolar diffusion), and generate Alfvénic waves.

Right ventricular expression of extracellular matrix proteins, matrix-metalloproteinases, and their inhibitors over a period of 3 years after heart transplantation.

Fibrillar collagens I and III, nonfibrillar collagen IV, and the glycoproteins fibronectin and laminin, are elements of the myocardial extracellular matrix (ECM). Alterations in the normal concentrations and ratios of these elements may reflect remodeling in response to physiologic stress. In the case of patients' post-heart transplantation (HTx), specific patterns of alteration may herald myocardial dysfunction. Right ventricular biopsies were taken from the same 28 HTx patients before implantation and 1 week, 2 weeks, and 1, 2, and 3 years after HTx. The above-noted five ECM proteins, six matrix metalloproteinases (MMPs) and two of their tissue inhibitors (TIMPs) were detected by immunohistochemistry and scored as cells per square millimeter or semiquantitatively. The total connective tissue fibers were detected by connective tissue stain and morphometry. Variations in these ECM components were followed in the same patient cohort over 3 years. In summary, during the first 2 weeks after HTx, a predominant increase in connective tissue occurred. Increases in MMP-8 and MMP-9 were found. By 3 years after transplantation, there was a decrease of connective tissue fibers and a significant reduction of all ECM components and an increase in MMPs and TIMPs. These findings may reflect a pattern of remodeling specific to the transplanted heart.

[Current epidemiological and clinical issues regarding Helicobacter pylori infection in childhood]. / Soucasná epidemiologicko-klinická problematika infekce Helicobacter pylori v detském veku.

H. pylori infection is common worldwide, and is acquired primarily during childhood. The mechanism of acquisition is not clear. In recent years the main focus of interest has been on the transmission of infection from family members to children. The main risk factor for acquiring the infection seems to be low socioeconomic status. H. pylori is associated with gastritis, duodenal ulcers, MALT lymphoma, and gastric adenocarcinoma. Extra-intestinal clinical manifestations have also been reported. However, the infection is often asymptomatic in children and the role of H. pylori infection in gastric manifestations is the subject of conflicting reports. Methods for the diagnosis of H. pylori infection in children are subdivided into invasive and noninvasive. There is a lack of consensus on treatment. The treatment of H. pylori is hampered by high macrolide-resistance. Treatment with proton pump-based triple therapy for 1-2 weeks gives the best eradication rates when combined with supplements containing probiotics. Multinational, multicentre studies in childhood are essential to extend current knowledge to avoid long-term gastroduodenal disease sequelae.

CD95 maintains stem cell-like and non-classical EMT programs in primary human glioblastoma cells.

Glioblastoma (GBM) is one of the most aggressive types of cancer with limited therapeutic options and unfavorable prognosis. Stemness and non-classical epithelial-to-mesenchymal transition (ncEMT) features underlie the switch from normal to neoplastic states as well as resistance of tumor clones to current therapies. Therefore, identification of ligand/receptor systems maintaining this privileged state is needed to devise efficient cancer therapies. In this study, we show that the expression of CD95 associates with stemness and EMT features in GBM tumors and cells and serves as a prognostic biomarker. CD95 expression increases in tumors and with tumor relapse as compared with non-tumor tissue. Recruitment of the activating PI3K subunit, p85, to CD95 death domain is required for maintenance of EMT-related transcripts. A combination of the current GBM therapy, temozolomide, with a CD95 inhibitor dramatically abrogates tumor sphere formation. This study molecularly dissects the role of CD95 in GBM cells and contributes the rational for CD95 inhibition as a GBM therapy.