Malettinin E, an antibacterial and antifungal tropolone produced by a marine Cladosporium strain

The isolation and structure elucidation of malettinins A–C (1–3) along with the new malettinin E (4) are described. The compounds were produced by the fungus Cladosporium sp. strain KF501, which was isolated from the German Wadden Sea. The malettinins are built up of tropolone/dihydropyran ring structures linked to a furan ring. The structure elucidation of the isolated compounds was achieved by means of one- and two-dimensional NMR spectroscopy supported by mass and UV data. The relative configuration of 4 was determined on the basis of single-crystal X-ray diffraction analysis. 1–4 exhibited antibacterial and antifungal activities when profiled against Xanthomonas campestris and Trichophyton rubrum. The influence of the chemical structure of the furan ring and of configurational changes on biological activities was observed

Calcarides A–E, Antibacterial Macrocyclic and Linear Polyesters from a Calcarisporium Strain

Bioactive compounds were detected in crude extracts of the fungus, Calcarisporium sp. KF525, which was isolated from German Wadden Sea water samples. Purification of the metabolites from the extracts yielded the five known polyesters, 15G256α, α-2, β, β-2 and π (1–5), and five new derivatives thereof, named calcarides A–E (6–10). The chemical structures of the isolated compounds were elucidated on the basis of one- and two-dimensional NMR spectroscopy supported by UV and HRESIMS data. The compounds exhibited inhibitory activities against Staphylococcus epidermidis, Xanthomonas campestris and Propionibacterium acnes. As the antibacterial activities were highly specific with regard to compound and test strain, a tight structure-activity relationship is assumed

Minimal residual disease - Prognostic Relevance of Treatment Response to Induction in Childhood Acute Myeloid Leukemia

Der Nachweis der minimalen Resterkrankung (MRD) im Verlauf der ersten Behandlungszyklen gilt als wesentlicher prognostischer Faktor bei der akuten myeloischen Leukämie (AML) und als ein entscheidender Parameter für eine optimierte risikoadaptierte Therapiestratifizierung. Diese Arbeit beschäftigt sich vorrangig mit der Immunphänotypisierung, da trotz einer hohen Sensitivität (10-5-10-6) der PCR-Analyse AML-spezifische Marker bisher bei einem großen Teil der Patienten nicht vorhanden sind oder nicht durchgeführt werden können. Demgegenüber kann man mit Hilfe der multiparametrischen Immunphänotypisierung bei bis zu 90% der Patienten einen leukämieassoziierten Immunphänotyp detektieren. Für den Zeitraum vom 01.07.1998 bis 31.08.2009 konnten für 791 Patienten der AML BFM Studien 1998 und 2004 die Daten hinsichtlich des Therapieansprechens an Tag 28 ausgewertet werden. Die Morphologie und die Immunphänotypisierung an Tag 28 zeigten eine sehr gute Korrelation (Spearman Korrelationskoeffizient 0.71, p 2% leukämische Blasten in der Immunphänotypisierung festgelegt. Es zeigte sich kein signifikanter Unterschied zwischen den Patienten mit > 2% Blasten und Patienten mit ≤ 2% Blasten an Tag 28 bzgl. der geschätzten Wahrscheinlichkeit für ein ereignisfreies Überleben (pEFS), der geschätzten Wahrscheinlichkeit für das Gesamtüberleben (pOS) und der kumulativen Inzidenz für das Erleiden eines Rezidivs (CI Rez.). Bei 18% der Patienten (n = 35) ließen sich an Tag 28 in der Immunphänotypisierung regenerative Blasten nachweisen. Eine Therapieanpassung erfolgte im Rahmen der AML-BFM Studie 2004 seit dem Jahr 2006. Aufgrund unzureichenden Therapieansprechens an Tag 15 und/oder an Tag 28 sowie dem Vorliegen einer prognostisch ungünstigen genetischen Aberration wurden in dem Zeitraum 2006 - 2010 30 Patienten von der Standardrisikogruppe (n = 138) in die Hochrisikogruppe stratifiziert. Von diesen Patienten erhielten 4 eine Stammzelltransplantation in erster Remission. Eine Therapieänderung erhielten 19 Patienten (8%) der Hochrisikogruppe (n = 266). 38 dieser Patienten erhielten eine Stammzelltransplantation. Durch die Therapieanpassung ab 2006 hat sich nicht nur eine Angleichung des pEFS, pOS und CI Rez. über 5 Jahre der Patienten mit oder ohne Nachweis einer MRD vollzogen, sondern es ist auch eine Annäherung der Standard- und Hochrisikogruppe in Hinblick auf das pEFS und pOS erfolgt. Die angepasste Therapiestratifizierung hat die prognostische Signifikanz der Blastenpersistenz aufgehoben und zur Verbesserung des Überlebens beigetragen.Treatment response is generally considered as prognostic factor; however, studies of minimal residual disease (MRD) did not confirm independent significance. Since 2006 the AML-BFM study group stratified poor responders after 1st and 2nd induction to intensified therapy, either by an additional element or eligibility for allogeneic matched donor stem cell transplantation (SCT). A good correlation was found between morphology and immunophenotyping (coefficientPearson 0.71). The immunophenotyping added information, especially to distinguish between regenerating blasts and leukemic blasts. We demonstrate that stratification according to morphology augmented by 4 color-immunophenotyping improved outcome significantly. This was mainly achieved by a much better event-free survival in high-risk AML. Using treatment response for stratification, EFS and OS could be improved in childhood AM

Long-Term Varicella Zoster Virus Immunity in Paediatric Liver Transplant Patients Can Be Achieved by Booster Vaccinations—A Single-Centre, Retrospective, Observational Analysis

Varicella is one of the most common vaccine-preventable infections after paediatric solid organ transplantation; thus, vaccination offers simple and cheap protection. However, children with liver disease often progress to liver transplantation (LT) before they reach the recommended vaccination age. As a live vaccine, varicella zoster virus (VZV) vaccination after transplantation is controversial; however, many case series demonstrate that vaccination may be safe and effective in paediatric liver transplant recipients. Only limited data exists describing long-term vaccination response in such immunocompromised patients. We investigated retrospectively vaccination response in paediatric patients before and after transplantation and describe long-term immunity over ten years, including the influence of booster-vaccinations. In this retrospective, single-centre study, 458 LT recipients were analysed between September 2004 and June 2021. Of these, 53 were re-transplantations. Patients with no available vaccination records and with a history of post-transplant lymphoproliferative disease, after hematopoietic stem cell transplantation and clinical chickenpox were excluded from this analysis (n = 198). In total, data on 207 children with a median annual follow-up of 6.2 years was available: 95 patients (45.9%) were unvaccinated prior to LT. Compared to healthy children, the response to vaccination, measured by seroconversion, is weaker in children with liver disease: almost 70% after one vaccination and 93% after two vaccinations. One year after transplantation, the mean titres and the number of children with protective antibody levels (VZV IgG ≥ 50 IU/L) decreased from 77.5% to 41.3%. Neither diagnosis, gender, nor age were predictors of vaccination response. Booster-vaccination was recommended for children after seroreversion using annual titre measurements and led to a significant increase in mean titre and number of protected children. Response to vaccination shows no difference from monotherapy with a calcineurin inhibitor to intensified immunosuppression by adding prednisolone or mycophenolate mofetil. Children with liver disease show weaker seroconversion rates to VZV vaccination compared to healthy children. Therefore, VZV-naïve children should receive basic immunization with two vaccine doses as well as those vaccinated only once before transplantation. An average of 2–3 vaccine doses are required in order to achieve a long-term seroconversion and protective antibody levels in 95% of children

Hepatitis A Immunity and Paediatric Liver Transplantation—A Single-Centre Analysis

Following paediatric solid organ liver transplantation, risk of infection is high, both in the short and long term. Even though an infection with hepatitis A virus (HAV) is often asymptomatic and self-limited in children, some case studies describe severe cases leading to death. Vaccinations offer simple, safe and cheap protection. However, data on vaccination rates against hepatitis A in children with liver disease are scarce. Moreover, the vaccine is only approved from the age of one year old. At the same time, up to 30% of children with liver disease are transplanted within the first year of life, so the window of opportunity for vaccination is limited. This retrospective, observational, single-centre study examines the HAV immunity in paediatric liver transplant recipients before and after the first year of transplantation. Vaccination records of 229 of 279 (82.1%) children transplanted between January 2003 and June 2021 were analysed. Of 139 eligible children aged ≥ 1 year old, only 58 (41.7%) were vaccinated at least with one HAV dose prior to transplantation. In addition, seven patients received the vaccine below one year of age. After one or two doses, 38.5% or 90.6% of 65 patients were anti-HAV-IgG positive, respectively. This percentage remained stable up to the first annual check-up. For children vaccinated only once, a shorter interval from vaccination to transplantation is a risk factor for lack of immunity. Thus, HAV immunisation should be started earlier in liver transplant candidates to improve immunity in this high-risk group

Calcaripeptides A–C, Cyclodepsipeptides from aCalcarisporiumStrain

The isolation and structure elucidation of the novel calcaripeptides A (1), B (2), and C (3) and studies on their biosynthetic origin are described. The calcaripeptides were identified from Calcarisporium sp. strain KF525, which was isolated from the German Wadden Sea. Compounds 1–3 are macrocyclic structures composed of a proline and a phenylalanine residue as well as a nonpeptidic substructure. Structure elucidation was achieved by applying one- and two-dimensional NMR spectroscopy supported by high-resolution mass spectrometry. X-ray crystallography was performed to determine the relative configuration of 1. The absolute configuration of 1 was assigned by HPLC of the amino acids after hydrolysis of the molecule and derivatization with chiral agents. Studies on the biosynthesis by feeding 13C-labeled substrates revealed that the nonpeptidic part of 1 originates from acetate and l-methionine. The involvement of a hybrid between a polyketide synthase and a nonribosomal peptide synthetase in the biosynthesis of the calcaripeptides is discussed

Balance Stability and Cervical Spine Range of Motion While Wearing a Custom-Made Mandibular Splint with Special Consideration of the Sex

Introduction: An altered dental occlusion can also affect balance stability or mobility. Thus, the aim of this study was to examine whether wearing a mandibular splint, which retains the occlusion close to the centric occlusion, can increase or decrease balance stability and the range of motion (ROM) of the cervical spine as opposed to the habitual occlusion, and if there is a difference between men and women. Material and methods: In this study, 41 male (34.7 ± 11.4 years) and 50 female subjects (29.3 ± 12.7 years) participated. Cervical spine ROM was recorded using the Zebris CMS 70P system. For balance stability, a pressure measuring platform integrated into the treadmill system (FDM-T) of the company Zebris® Medical GmbH was used. Here, the area of the ellipse and the length of the Center of Pressure (CoP) was recorded whilst in the bipedal and unipedal stance. Results: The sex comparison showed significant differences for the area of the ellipse of the right leg and ROM extension in the habitual occlusion: females showed a better balance stability and a larger ROM extension. When wearing the splint, only the CoP of the left leg was significant with a better balance stability in female subjects. Within the male subjects, the ellipse area in the bipedal and unipedal (left/right) stance showed mostly significant reductions, while the rotation left and right as well as the lateral flexion (left/right) improved when wearing the splint. Female subjects, when wearing the splint, showed a significant decrease of the ellipse area and the CoP length when standing on either leg. Flexion, rotation to the right and lateral flexion to the left/right, all increased significantly. Conclusion: Wearing a splint that keeps the jaw close to the centric relation improved balance stability and increased the ROM of the cervical spine for both male and female subjects. Women may have marginally different basic balance stability strategies than men, with regard to bipedal and unipedal standing. Nevertheless, there are scarcely any differences between the two sexes in the adaptation when wearing a splint. Changing the jaw relation in healthy adults can possibly support the release of movement potentials that simplify the performance of everyday activities or sports movements