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The giant liver fluke, Fascioloides magna, is of interest to wild-life managers, veterinarians and researchers, due to its unusual body size (3-10 cm), high pathogenic potential and because it is continuously spreading to new areas, especially in Europe. Annually, the number of cases of animal infections (mainly cervids and bovids) caused by this fluke is monitored in many European countries, including the Czech Republic (with some foci of prevalence over 90%). During the years 2009 and 2010, 1622 survey forms focused on monitoring of fascioloidosis were distributed in the community of "Czech Inspectors of Hunted Game" (CIHG), and 21.3% of forms containing positive or negative response about F. magna occurrence were returned. The administrative units monitored by particular CIHG, who answered the forms, were geographically equally distributed and therefore we believe that also the recorded distribution of F. magna in wild-life animals reflects the real situation in the Czech Republic. A significant number of cases of F. magna infection were repeatedly reported from areas in the south-west part of the Czech Republic. Moreover, our report contains also some unique records of several new F. magna foci in the western (close to the German border), northern (close to the Polish border) and central parts of the Czech Republic, supporting the assumption that the parasite is spreading further throughout Europe. In five game administrative units F. magna infection was directly confirmed by examination of dissected deer livers or by microscopic examination of coprological samples, followed by isolation of DNA from adults and eggs and further molecular analyses. Fascioloides magna intermediate host snails (Galba truncatula and Radix spp.) were collected during 2009 and 2010 from different localities of the Czech Republic, kept in aquaria, examined for shedding of F. magna cercariae, dissected and parasite/snail DNA was isolated. After PCR with specific primers for parasite/snail internal transcribed region number two (ITS-2) the obtained sequences confirmed identification of the following species: F. magna, G. truncatula, R. peregra, R. lagotis, R. labiata and R. auricularia. Although it has been demonstrated that the number of areas with positive cases of fascioloidosis is still growing, the risk of pathogenic impact of F. magna on populations of free-living animals and farming cervids/bovids is generally underestimated.

Background: Maternally inherited complex I deficiencies due to mutations in MT-ND genes represent a heterogeneous group of multisystem mitochondrial disorders (MD) with a unfavourable prognosis. The aim of the study was to characterize the impact of the mutations in MT-ND genes, including the novel m.13091 T > C variant, on the course of the disease, and to analyse the activities of respiratory chain complexes, the amount of protein subunits, and the mitochondrial energy-generating system (MEGS) in available muscle biopsies and cultivated fibroblasts., Methods: The respiratory chain complex activities were measured by spectrophotometry, MEGS were analysed using radiolabelled substrates, and protein amount by SDS-PAGE or BN-PAGE in muscle or fibroblasts., Results: In our cohort of 106 unrelated families carrying different mtDNA mutations, we found heteroplasmic mutations in the genes MT-ND1, MT-ND3, and MT-ND5, including the novel variant m.13091 T > C, in 13 patients with MD from 12 families. First symptoms developed between early childhood and adolescence and progressed to multisystem disease with a phenotype of Leigh or MELAS syndromes. MRI revealed bilateral symmetrical involvement of deep grey matter typical of Leigh syndrome in 6 children, cortical/white matter stroke-like lesions suggesting MELAS syndrome in 3 patients, and a combination of cortico-subcortical lesions and grey matter involvement in 4 patients. MEGS indicated mitochondrial disturbances in all available muscle samples, as well as a significantly decreased oxidation of [1- 14 C] pyruvate in fibroblasts. Spectrophotometric analyses revealed a low activity of complex I and/or complex I + III in all muscle samples except one, but the activities in fibroblasts were mostly normal. No correlation was found between complex I activities and mtDNA mutation load, but higher levels of heteroplasmy were generally found in more severely affected patients., Conclusions: Maternally inherited complex I deficiencies were found in 11% of families with mitochondrial diseases in our region. Six patients manifested with Leigh, three with MELAS. The remaining four patients presented with an overlap between these two syndromes. MEGS, especially the oxidation of [1- 14 C] pyruvate in fibroblasts might serve as a sensitive indicator of functional impairment due to MT-ND mutations. Early onset of the disease and higher level of mtDNA heteroplasmy were associated with a worse prognosis.

Background: Sideroblastic anemia represents a heterogeneous group of inherited or acquired diseases with disrupted erythroblast iron utilization, ineffective erythropoiesis, and variable systemic iron overload. In a cohort of 421 patients with multisystem mitochondrial diseases, refractory anemia was found in 8 children., Results: Five children had sideroblastic anemia with increased numbers of ring sideroblasts >15%. Two of the children had a fatal course of MLASA1 syndrome (mitochondrial myopathy, lactic acidosis, and sideroblastic anemia [SA]) due to a homozygous, 6-kb deletion in the PUS1 gene, part of the six-member family of pseudouridine synthases (pseudouridylases). Large homozygous deletions represent a novel cause of presumed PUS1-loss-of-function phenotype. The other three children with SA had Pearson syndrome (PS) due to mtDNA deletions of 4 to 8 kb; two of these children showed early onset of PS and died due to repeated sepsis; the other child had later onset of PS and survived as the hematological parameters normalized and the disease transitioned to Kearns-Sayre syndrome. In addition, anemia without ring sideroblasts was found in three other patients with mitochondrial disorders, including two children with later onset of PS and one child with failure to thrive, microcephaly, developmental delay, hypertrophic cardiomyopathy, and renal tubular acidosis due to the heterozygous mutations c.610A>G (p.Asn204Asp) and c.674C>T (p.Pro225Leu) in the COX10 gene encoding the cytochrome c oxidase assembly factor., Conclusions: Sideroblastic anemia was found in fewer than 1.2% of patients with multisystem mitochondrial disease, and it was usually associated with an unfavorable prognosis., (© 2018 Wiley Periodicals, Inc.)

Background: Bronchial asthma often starts in early childhood. Clinical manifestation of the disease is likely due to inflammatory processes in the airways initiated by various stimuli. Developed remodelling is regularly observed in the bronchial mucosa of adult asthmatics but we still lack information about its onset and latter development with the natural course of the disease. In this study, we analysed histological findings in bronchial biopsies obtained from very young children (under 4 yr of age). We hypothesized that initial undetectable changes in the airway epithelium of children predisposed to asthma may be one of the first mechanisms leading to morphological changes in the bronchial mucosa., Methods: We measured the thickness of the basement membrane using a light microscope and analysed the presence of its three basic structural glycoproteins: laminin, tenascin and collagen IV, using immunohistochemical techniques. We compared these findings in children predisposed to asthma according to the selected clinical criteria of the Asthma Predictive Index and in a control group of children., Results: We found a significant difference in the thickness of the basement membrane between the two groups. We also found a difference in the subepithelial deposition of laminin and collagen IV in the basement membrane but no difference in the deposition of tenascin., Conclusions: We conclude that initial changes leading to further remodelling may start at a very early age even before clinical manifestation of the disease., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Unlabelled: Chromosomal aberrations are important prognostic factors in multiple myeloma diagnosis. We evaluated the effect common high-risk chromosomal aberrations in a cohort of 102 patients with relapsed disease treated with bortezomib or thalidomide. Our results showed that patients treated with thalidomide with a gain(1)(q21) had inferior survival compared with the bortezomib group. Therefore, bortezomib-based regiments are more effective for patients with relapsed multiple myeloma with an incidence of gain in the gain(1)(q21)., Background: Prognostic impact of specific chromosomal aberrations in patients with relapsed multiple myeloma (MM) treated with the novel agents is briefly described., Patients and Methods: We analyzed the prognostic value of an extended panel of chromosomal aberrations [del(13)(q14), del(17)(p13), t(4;14)(p16;q32), gain(1)(q21), and hyperdiploidy] by using the technique of interphase fluorescence in situ hybridization in a cohort of 102 patients with relapsed MM treated with thalidomide- or bortezomib-based protocols., Results: The gain(1)(q21) had a negative impact on overall survival for patients with MM treated with thalidomide (15.7 vs. 41.3 months; P = .004). Moreover, we confirmed the negative impact of the cumulative effect of 2 or more cytogenetic changes that occur simultaneously on the overall survival in the thalidomide group (20.3 months vs. not yet reached; P = .039). We did not find any significant impact of the aberrations studied on overall survival in the bortezomib cohort of patients., Conclusion: We conclude that bortezomib-based protocols are able to partially overcome the negative prognostic impact of the tested chromosomal abnormalities in patients with relapsed MM., (Copyright © 2013 Elsevier Inc. All rights reserved.)