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Integrated analysis of epigenetic and genetic changes during MDS progression

DNA methylation is important during development of vertebrate organisms as well as for sustaining genome integrity and gene expression. Alterations of DNA methylation patterns are often associated with different diseases, for instance myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML). Consequences of aberrant DNA methylation are the silencing of tumor suppressor genes due to hypermethylation as well as the hypomethylation‐mediated weakening of transcriptional repression, reactivation of retrotransposons and genomic instability. The major aim of this thesis was the integrated analysis of epigenetic and genetic changes during disease progression to identify target genes that could be involved in development or progression of myelodysplastic syndromes. To address this issue, DNA methylation analysis was performed in pediatric and adult MDS patients using the methyl-CpG-immunoprecipitation sequencing approach (MCIp-seq) and the targeted bisulfite sequencing of the myeloid regulome, respectively. It could be demonstrated that adult MDS patients show largely private DNA methylation changes and almost no common differentially methylated regions. Identified DMRs include RUNX1, FOXO3 and ZFPM1, which show methylation sensitivity in in vitro reporter gene assays. Another observation was made in this patient cohort in which DNA methylation changes only occur with alterations in clonal architecture. In cases of a genetically stable disease, no differences in DNA methylation patterns were observed over time. In pediatric MDS patients global DNA methylation analysis revealed a correlation of DNA methylation changes with germline GATA2 mutations and refractory cytopenia (RC). In detail, a patient cluster with lower DNA methylation degree exhibited the mentioned two features, while the other cluster of patients was associated with more advanced subtypes and higher DNA methylation. DMRs identified between these two patient groups are ZIC5, VILL and TRIM45, possibly playing a role in cancer. Methylation sensitivity of these regions has to be tested with in vitro reporter gene assays and will give information about a possible role for the development or progress of MDS. Regarding longitudinal studies in pediatric MDS patients, we could show the same result like in adult patients where DNA methylation changes correlate with alterations in genetic landscape. One potential epigenetic target gene found to be methylation sensitive and already described to play an important role in AML is the VENTX promoter region. In summary, our data suggest a tight correlation of epigenetic changes with clonal architecture of the diseased hematopoiesis, but the chronological order of appearance is still an open issue

Systematische Evaluation von Pflegedokumentationssystemen - Studienprotokoll und Ergebnisse -

Seit Jahren besteht der Wunsch, im Bereich der Pflegeprozeßdokumentation Rechner einzusetzen, um so die Qualität der Pflegedokumentation zu erhöhen, Aufwände zu reduzieren, und Auswertungsmöglich-keiten zu verbessern. Aufgrund des bisher geringen Einsatzes fehlen aber kontrollierte Evaluationsstudien. Daher wurde eine solche am Universitätsklinikum Heidelberg durchgeführt. Hierfür wurde das rechnergestützte Pflegedokumentationssystem ?PIK? auf einer Modellstation der Psychiatrischen Universitätsklinik eingeführt und in einer 4-monatigen Studie (Okt. 98 - Jan. 99) evaluiert. In der Studie sollte z.B. geklärt werden, welchen Einfluß die Einführung des rechnergestützten Pflegedo-kumentationssystems auf die zeitlichen Abläufe und die Qualität der Pflegedokumentation hat und wie sich die Akzeptanz von Pflegeprozeß und Computern in der Pflege ändert. In die randomisierte, kontrollierte Studie zum Vergleich des rechnergestützten Pflegedokumentationssystems PIK mit dem bisherigen konventionellen Pflegedokumentationssystems wurde die Pflegedokumentation von insgesamt 60 Patienten aufgenommen, welche in eine der beiden Gruppen randomisiert wurden. Die Datenerhebungen erfolgten durch Fragebögen, durch Zeitmessungen, durch Interviews sowie durch Qualitätschecklisten. In der Studie konnten keine inhaltlichen Qualitätsunterschiede zwischen der Testgruppe und der Kontrollgruppe gezeigt werden. Eine deutliche Verbesserung von Lesbarkeit und Vollständigkeit war aber sichtbar. Gleichzeitig war der Zeitbedarf für die Pflegeplanung in der Testgruppe niedriger, für Pflege-dokumentation und Berichtschreibung höher. Die Akzeptanz des Pflegeprozesses sowie des Einsatzes von Computern in der Pflege stieg während der Studie an. Die Mehrheit der Benutzer wollte am Ende der Studie weiterhin mit einem rechnergestützten Pflegedokumentationssystem wie PIK arbeiten

Control of Positive and Negative Magnetoresistance in Iron Oxide : Iron Nanocomposite Thin Films for Tunable Magnetoelectric Nanodevices

The perspective of energy-efficient and tunable functional magnetic nanostructures has triggered research efforts in the fields of voltage control of magnetism and spintronics. We investigate the magnetotransport properties of nanocomposite iron oxide/iron thin films with a nominal iron thickness of 5-50 nm and find a positive magnetoresistance at small thicknesses. The highest magnetoresistance was found for 30 nm Fe with +1.1% at 3 T. This anomalous behavior is attributed to the presence of Fe3O4-Fe nanocomposite regions due to grain boundary oxidation. At the Fe3O4/Fe interfaces, spin-polarized electrons in the magnetite can be scattered and reoriented. A crossover to negative magnetoresistance (-0.11%) is achieved at a larger thickness (>40 nm) when interface scattering effects become negligible as more current flows through the iron layer. Electrolytic gating of this system induces voltage-triggered redox reactions in the Fe3O4 regions and thereby enables voltage-tuning of the magnetoresistance with the locally oxidized regions as the active tuning elements. In the low-magnetic-field region (<1 T), a crossover from positive to negative magnetoresistance is achieved by a voltage change of only 1.72 V. At 3 T, a relative change of magnetoresistance about -45% during reduction was achieved for the 30 nm Fe sample. The present low-voltage approach signifies a step forward to practical and tunable room-temperature magnetoresistance-based nanodevices, which can boost the development of nanoscale and energy-efficient magnetic field sensors with high sensitivity, magnetic memories, and magnetoelectric devices in general. Copyright © 2020 American Chemical Society

Control of positive and negative magnetoresistance in iron oxide−iron nanocomposite thin films for tunable magnetoelectric nanodevices

The perspective of energy-efficient and tunable functional magnetic nanostructures has triggered research efforts in the fields of voltage control of magnetism and spintronics. We investigate the magnetotransport properties of nanocomposite iron oxide/iron thin films with a nominal iron thickness of 5-50 nm and find a positive magnetoresistance at small thicknesses. The highest magnetoresistance was found for 30 nm Fe with +1.1% at 3 T. This anomalous behavior is attributed to the presence of Fe3O4-Fe nanocomposite regions due to grain boundary oxidation. At the Fe3O4/Fe interfaces, spin-polarized electrons in the magnetite can be scattered and reoriented. A crossover to negative magnetoresistance (−0.11%) is achieved at a larger thickness (>40 nm) when interface scattering effects become negligible as more current flows through the iron layer. Electrolytic gating of this system induces voltage-triggered redox reactions in the Fe3O4 regions and thereby enables voltage-tuning of the magnetoresistance with the locally oxidized regions as the active tuning elements. In the low-magnetic-field region (<1 T), a crossover from positive to negative magnetoresistance is achieved by a voltage change of only 1.72 V. At 3 T, a relative change of magnetoresistance about −45% during reduction was achieved for the 30 nm Fe sample. The present low-voltage approach signifies a step forward to practical and tunable room-temperature magnetoresistance-based nanodevices, which can boost the development of nanoscale and energy-efficient magnetic field sensors with high sensitivity, magnetic memories, and magnetoelectric devices in general

Prevalence and potential relevance of hyperuricemia in pediatric kidney transplant recipients—a CERTAIN registry analysis

Background: Asymptomatic hyperuricemia is frequently observed in pediatric kidney transplant recipients; symptomatic hyperuricemia, however, is a rare complication. Only few data are available in this patient population. We, therefore, investigated the prevalence of hyperuricemia and its association with kidney transplant function and blood pressure in a multicenter cohort of pediatric kidney transplant recipients. Methods: This is a retrospective, observational multicenter registry study. All pediatric kidney transplant recipients in the CERTAIN database with at least one documented serum uric acid level and a follow-up of 5 years posttransplant were eligible. We identified 151 patients with 395 measurements of serum uric acid. We calculated the prevalence of hyperuricemia, analyzed potential risk factors and clinical consequences such as elevated blood pressure and reduced estimated glomerular filtration rate (eGFR). Statistical analysis was performed using IBM SPSS Statistics 26. Results: One hundred and ten of 395 (27.8%) serum uric acid levels were above 416 µmol/L (7.0 mg/dL), defined as the upper limit of normal. Univariate analysis showed a significant (p = .026) inverse association of serum uric acid with eGFR overtime. There was no significant association of serum uric acid concentrations with body mass index (z-score), blood pressure (z-score), or sex. No episodes of gout were documented. Conclusion: This study shows that hyperuricemia is present in a considerable number of patients sometime after pediatric kidney transplantation and is associated with lower eGFR. Whether hyperuricemia contributes to faster decline of graft function or to the overall cardiovascular risk of these patients remains to be elucidated. Keywords: gout; long-term outcome; pediatric kidney transplantation; uric acid; uric acid-lowering therapy

ARSB IS REQUIRED FOR BONE REMODELING

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PORCENTAGEM DE SÓLIDOS TOTAIS EM AMOSTRAS DE LEITE DE TANQUE NO ESTADO DO PARANÁ

Avaliou - se os efeitos de meio sobre a porcentagem de sólidos totais de amostras de tanque coletadas pelas indústrias, analisadas pelo Laboratório de Qualidade do Leite do Programa de Análise de Rebanhos Leiteiros da Associação Paranaense dos Criadores de Bovinos da Raça Holandesa, Curitiba - PR. Foram analisadas 1.950.034 amostras de leite, do período de janeiro de 2005 a abril de 2012, em dez regiões do Estado do Paraná. As médias estimadas, desvios-padrão e coeficiente de variação para % de sólidos totais e idade da amostra em dias foram: 12,29 ± 0,85; 6,79% e 2,98 ± 1,57 dias, respectivamente. Todos os efeitos incluídos no modelo estatístico (mês e ano de análise, região, idade da amostra e escore da contagem de células somáticas) influenciaram significativamente (P<0,01) a variável estudada. Os maiores valores para a % de sólidos totais ocorreram no mês de maio (12,46 ± 0,0023), no ano de 2012 (12,37 ± 0,0026), na região de Curitiba (12,42 ± 0,0017), com seis dias de idade da amostra (12,27 ± 0,0030) e quando o escore da contagem de células somáticas (ECS) variou de zero a seis (zero a 1.130.000 células/ mL) a % de sólidos totais aumentou de 12,03 para 12,30%, respectivamente. A correlação de Pearson entre a % de sólidos totais com o ECS, foi baixa e positiva (0,039).