TY  - THES
A1  - Kunz, Jessica
T1  - Kopforthesentherapie bei Patienten mit lagerungsbedingtem Plagiozephalus: Einfluss von Alter und Schweregrad der Asymmetrie bei Therapiebeginn auf die Therapiedauer und das Therapieergebnis
T1  - Head orthosis therapy in positional plagiocephaly: 
influence of age and severity of asymmetry
on duration of therapy and treatment outcome
N2  - Zur Kopforthesentherapie in der Behandlung von Säuglingen mit lagerungsbedingten Schädelasymmetrien gibt es bisher kaum Studien, die den optimalen Behandlungsbeginn unter Berücksichtigung der Ausprägung der Asymmetrie untersuchen. Ziel der vorliegenden Studie war es daher, den Einfluss des Alters und des Schweregrades der Asymmetrie bei Therapiebeginn auf die Therapiedauer und das Therapieergebnis zu analysieren. 
Hierzu wurden 144 Patienten mit lagerungsbedingtem Plagiozephalus untersucht, die mittels Kopforthese behandelt wurden. Es erfolgte eine Einteilung in drei Altersgruppen (Altersgruppe I: < 24 Wochen mit N = 38 Säuglingen / Altersgruppe II: ≥ 24 bis < 32 Wochen mit N = 79 Säuglingen / Altersgruppe III: ≥ 32 Wochen mit N = 27 Säuglingen) und je zwei Schweregrade (mild-to-moderate: 30°-CVA >3mm bis <12mm / moderate-to-severe: 30°-CVA ≥12mm). Anhand stereophotogrammetrischer Datensätze wurden das Ausmaß und die Reduktion der Asymmetrie in den verschiedenen Untergruppen sowie die Therapiedauer miteinander verglichen.
Es zeigte sich, dass es in allen Altersgruppen zu einer signifikanten Reduktion der Asymmetrie kam, wobei sich dieser Effekt mit steigendem Alter verringerte. Ein Therapieerfolg (= CVAI <3,5%) wurde bei Patienten mit mild-to-moderate Asymmetrie in Altersgruppe I zu 83%, in Altersgruppe II zu 69% und in Altersgruppe III zu 40% erreicht. Bei Patienten mit einer schwerwiegenderen, moderate-to-severe Asymmetrie ergab sich eine symmetrische Kopfform zu 50% in Altersgruppe I, zu 30% in Altersgruppe II und nur zu 7% in Altersgruppe III. Die durchschnittliche Therapiedauer stieg von 18,6 Wochen in Altersgruppe I, 20,0 Wochen in Altersgruppe II und 25,3 Wochen in Altersgruppe III an. Das Alter bzw. der Schweregrad der Asymmetrie bei Behandlungsbeginn wurden durch die multiple Regressionsgleichung ins Verhältnis gesetzt. Dadurch kann zukünftig die zu erwartende Verbesserung der Asymmetrie durch eine Kopforthesentherapie abgeschätzt werden.
Zusammenfassend kann somit festgestellt werden, dass das Alter bei Therapiebeginn sowie der Ausprägungsgrad einer lagerungsbedingten Asymmetrie einen entscheidenden Einfluss auf Dauer und Effektivität der Kopforthesentherapie haben. Die Erfolgsrate der Therapie ist maßgeblich von diesen beiden Einflussfaktoren abhängig. Die aufgestellte Regressionsgleichung ermöglicht eine Vorhersage der Reduktion einer lagerungsbedingten Schädelasymmetrie.
N2  - Background 
Only few studies investigating the optimal time point to start head orthosis therapy for deformational plagiocephaly (DP) take into account the severity of skull asymmetry. The present study performs a 3D-analysis of the effects of age and severity of asymmetry on the final outcome.

Methods
A total of 144 patients with DP treated by molding orthosis were examined and divided into three age groups (I: <24 weeks; II: ≥24 to <32 weeks; III: ≥32 weeks) and two severity levels (mild-to-moderate: 30°-CVA ≥3mm to ≤12mm; moderate-to-severe: 30°-CVA >12mm). The extent of the reduction of asymmetry was analyzed using 3D-stereophotogrammetry. 

Results
Therapy with molding orthosis led to a significant reduction in asymmetry in all defined age groups. Efficacy of reduction decreased with increasing age. Successful treatment (=CVAI <3.5%) of patients with mild-to-moderate asymmetry was achieved in 83%, 69% and 40% (groups I, II and III), respectively, in 50%, 30% and 7% of patients with moderate-to-severe asymmetry. The average duration of treatment increased from 18.6 to 25.3 weeks (age groups I and III). 

Conclusion
Age at the beginning of treatment as well as severity of asymmetry have a definite impact on the duration and effectiveness of molding orthosis therapy.
KW  - Kopforthesentherapie
KW  - 3D-Stereophotogrammetrie
KW  - Lagerungsbedingter Plagiozephalus
KW  - Positional Plagiocephaly
KW  - Kopforthesentherapie
KW  - Head orthosis therapy
KW  - 3D-Stereophotogrammetrie
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-208446
ER  - 
TY  - JOUR
A1  - Effenberger, Madlen
A1  - Bommert, Kathryn S.
A1  - Kunz, Viktoria
A1  - Kruk, Jessica
A1  - Leich, Ellen
A1  - Rudelius, Martina
A1  - Bargou, Ralf
A1  - Bommert, Kurt
T1  - Glutaminase inhibition in multiple myeloma induces apoptosis via MYC degradation
JF  - Oncotarget
N2  - Multiple Myeloma (MM) is an incurable hematological malignancy affecting millions of people worldwide. As in all tumor cells both glucose and more recently glutamine have been identified as important for MM cellular metabolism, however there is some dispute as to the role of glutamine in MM cell survival. Here we show that the small molecule inhibitor compound 968 effectively inhibits glutaminase and that this inhibition induces apoptosis in both human multiple myeloma cell lines (HMCLs) and primary patient material. The HMCL U266 which does not express MYC was insensitive to both glutamine removal and compound 968, but ectopic expression of MYC imparted sensitivity. Finally, we show that glutamine depletion is reflected by rapid loss of MYC protein which is independent of MYC transcription and post translational modifications. However, MYC loss is dependent on proteasomal activity, and this loss was paralleled by an equally rapid induction of apoptosis. These findings are in contrast to those of glucose depletion which largely affected rates of proliferation in HMCLs, but had no effects on either MYC expression or viability. Therefore, inhibition of glutaminolysis is effective at inducing apoptosis and thus serves as a possible therapeutic target in MM.
KW  - Multiple Myeloma
KW  - glutaminase inhibition
KW  - apoptosis
KW  - MYC
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170168
VL  - 8
IS  - 49
ER  - 
TY  - JOUR
A1  - Kunz, Viktoria
A1  - Bommert, Kathryn S.
A1  - Kruk, Jessica
A1  - Schwinning, Daniel
A1  - Chatterjee, Manik
A1  - Stühmer, Thorsten
A1  - Bargou, Ralf
A1  - Bommert, Kurt
T1  - Targeting of the E3 ubiquitin-protein ligase HUWE1 impairs DNA repair capacity and tumor growth in preclinical multiple myeloma models
JF  - Scientific Reports
N2  - Experimental evidence suggests that ubiquitin-protein ligases regulate a number of cellular processes involved in tumorigenesis. We analysed the role of the E3 ubiquitin-protein ligase HUWE1 for pathobiology of multiple myeloma (MM), a still incurable blood cancer. mRNA expression analysis indicates an increase in HUWE1 expression levels correlated with advanced stages of myeloma. Pharmacologic as well as RNAi-mediated HUWE1 inhibition caused anti-proliferative effects in MM cell lines in vitro and in an MM1.S xenotransplantation mouse model. Cell cycle analysis upon HUWE1 inhibition revealed decreased S phase cell fractions. Analyses of potential HUWE1-dependent molecular functions did not show involvement in MYC-dependent gene regulation. However, HUWE1 depleted MM cells displayed increased DNA tail length by comet assay, as well as changes in the levels of DNA damage response mediators such as pBRCA1, DNA-polymerase beta, gamma H2AX and Mcl-1. Our finding that HUWE1 might thus be involved in endogenous DNA repair is further supported by strongly enhanced apoptotic effects of the DNA-damaging agent melphalan in HUWE1 depleted cells in vitro and in vivo. These data suggest that HUWE1 might contribute to tumour growth by endogenous repair of DNA, and could therefore potentially be exploitable in future treatment developments.
KW  - MYC
KW  - interacts
KW  - gene
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230632
VL  - 10
ER  - 
TY  - JOUR
A1  - Kann, Simone
A1  - Kunz, Meik
A1  - Hansen, Jessica
A1  - Sievertsen, Jürgen
A1  - Crespo, Jose J.
A1  - Loperena, Aristides
A1  - Arriens, Sandra
A1  - Dandekar, Thomas
T1  - Chagas disease: detection of Trypanosoma cruzi by a new, high-specific real time PCR
JF  - Journal of Clinical Medicine
N2  - Background: Chagas disease (CD) is a major burden in Latin America, expanding also to non-endemic countries. A gold standard to detect the CD causing pathogen Trypanosoma cruzi is currently not available. Existing real time polymerase chain reactions (RT-PCRs) lack sensitivity and/or specificity. We present a new, highly specific RT-PCR for the diagnosis and monitoring of CD. Material and Methods: We analyzed 352 serum samples from Indigenous people living in high endemic CD areas of Colombia using three leading RT-PCRs (k-DNA-, TCZ-, 18S rRNA-PCR), the newly developed one (NDO-PCR), a Rapid Test/enzyme-linked immuno sorbent assay (ELISA), and immunofluorescence. Eighty-seven PCR-products were verified by sequence analysis after plasmid vector preparation. Results: The NDO-PCR showed the highest sensitivity (92.3%), specificity (100%), and accuracy (94.3%) for T. cruzi detection in the 87 sequenced samples. Sensitivities and specificities of the kDNA-PCR were 89.2%/22.7%, 20.5%/100% for TCZ-PCR, and 1.5%/100% for the 18S rRNA-PCR. The kDNA-PCR revealed a 77.3% false positive rate, mostly due to cross-reactions with T. rangeli (NDO-PCR 0%). TCZ- and 18S rRNA-PCR showed a false negative rate of 79.5% and 98.5% (NDO-PCR 7.7%), respectively. Conclusions: The NDO-PCR demonstrated the highest specificity, sensitivity, and accuracy compared to leading PCRs. Together with serologic tests, it can be considered as a reliable tool for CD detection and can improve CD management significantly.
KW  - Chagas disease
KW  - Chagas diagnosis
KW  - Chagas monitoring
KW  - Chagas real time PCR
KW  - Trypanosoma cruzi
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-205746
SN  - 2077-0383
VL  - 9
IS  - 5
ER  -