EEG Sleep Slow-Wave Activity as a Mirror of Cortical Maturation

Deep (slow wave) sleep shows extensive maturational changes from childhood through adolescence, which is reflected in a decrease of sleep depth measured as the activity of electroencephalographic (EEG) slow waves. This decrease in sleep depth is paralleled by massive synaptic remodeling during adolescence as observed in anatomical studies, which supports the notion that adolescence represents a sensitive period for cortical maturation. To assess the relationship between slow-wave activity (SWA) and cortical maturation, we acquired sleep EEG and magnetic resonance imaging data in children and adolescents between 8 and 19 years. We observed a tight relationship between sleep SWA and a variety of indexes of cortical maturation derived from magnetic resonance (MR) images. Specifically, gray matter volumes in regions correlating positively with the activity of slow waves largely overlapped with brain areas exhibiting an age-dependent decrease in gray matter. The positive relationship between SWA and cortical gray matter was present also for power in other frequency ranges (theta, alpha, sigma, and beta) and other vigilance states (theta during rapid eye movement sleep). Our findings indicate a strong relationship between sleep EEG activity and cortical maturation. We propose that in particular, sleep SWA represents a good marker for structural changes in neuronal networks reflecting cortical maturation during adolescenc

Digitale Selbstlernmodule zur Stärkung fächerübergreifen-der Kompetenzen in der Lehrkräftebildung : Ein Einblick in das Lernmodul Sprache im Fach

In der Lehrkräftebildung steht der Erwerb von fachspezifischen Kompetenzen im Vordergrund. Fächerübergreifende Kompetenzen werden in der Regel vernachlässigt. Im Projekt „Fachdidaktische Unterrichtsplanung - Fachpezifisch und fachübergreifend - FaPlan" werden daher digitale Lernmodule konzipiert, die angehenden Lehrkräfte bei der Entwicklung einer fächerübergreifenden didaktische Perspektive unterstützen sollen. Am Beispiel des Lernmoduls „Sprache im Fach“ wird in diesem Beitrag exemplarisch die Gestaltung der Lernmodule und die Förderung von fächerübergreifenden Kompetenzen aufgezeigt. In teacher education, the focus is on the acquisition of subject-specific competencies. Cross-curricular competencies are usually neglected. In the project "FaPlan", digital learning modules are therefore being designed to support future teachers in the development of an interdisciplinary didactic perspective. Using the example of the learning module “Sprache im Fach", the design of the learning modules and the promotion of interdisciplinary competencies will be demonstrated

Evaluation of Sn0.9_{0.9}Fe0.1_{0.1}O2‐δ_{2‐ δ} as Potential Anode Material for Sodium‐Ion Batteries

The introduction of transition metals such as iron in oxides of alloying elements as, for instance, SnO$_2$ has been proven to enable higher capacities and superior charge storage performance when used as lithium-ion electrode materials. Herein, we report the evaluation of such electrode materials, precisely (carbon-coated) Sn$_{0.9}$Fe$_{0.1}$O$_{2−δ}$(−C), for sodium-ion battery applications. The comparison with SnO$_2$ as reference material reveals the beneficial impact of the presence of iron in the tin oxide lattice, enabling higher specific capacities and a greater reversibility of the de-/sodiation process – just like for lithium-ion battery applications. The overall achievable capacity, however, remains relatively low with about 300 mAh g$^{−1}$ and up to more than 400 mAh g$^{−1}$ for Sn$_{0.9}$Fe$_{0.1}$O$_{2-δ}$ and Sn$_{0.9}$Fe$_{0.1}$O$_{2−δ}$-C, respectively, compared to the theoretical specific capacity of more than 1,300 mAh g$^{−1}$ when assuming a completely reversible alloying and conversion reaction. The subsequently performed ex situ/operando XRD and ex situ TEM/EDX analysis unveils that this limited capacity results from an incomplete de-/sodiation reaction, thus, providing valuable insights towards an enhanced understanding of alternative reaction mechanisms for sodium-ion anode material candidates

Sperm and testicular tissue cryopreservation and assisted reproductive technology outcomes in male cancer patients: a 15-year experience

Objective: To explore the characteristics of cancer patients who cryopreserved sperm/testicular tissue samples in the Cryobank of Charite-Universitatsmedizin Berlin between 2004 and 2019, and the ART utilization rate with associated outcomes. Methods: Retrospective data were available for 506 cancer patients, of which 46 (9.1%) had used their samples for artificial reproductive technologies (ART). Corresponding cycle information was collected from external fertility centers. Results: Our cohort included 53/506 (10.5%) patients aged < 18 years at diagnosis. While adolescents and adults mainly banked sperm, adolescents showed higher rates of testicular tissue cryopreservation before (11.8%, 6/51 vs. 6.4%, 26/406) and after treatment (16.7%, 4/24 vs. 7.8%, 13/167). At study conduction, storage had been ended for 44.8% (269/601) of samples. The majority of samples used for ART were requested within the first 3 years after cryopreservation (71.5%, 28/39, range = 0-12 years). Pregnancy rate was 51.4% (19/37 cycles), resulting in 11 singleton births, 3 twin pairs, and 4 miscarriages. Conclusion: With the new advantage of public health insurance coverage of fertility preservation (FP) in Germany, an increased utilization has already been noticed in our center, emphasizing the necessity of further knowledge for individual counseling. Adolescent cancer patients need to be addressed specifically, as these patients show especially low cryopreservation rates

Hyperandrogenism and Metabolic Syndrome Are Associated With Changes in Serum-Derived microRNAs in Women With Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) remains one of the most common endocrine disorder in premenopausal women with an unfavorable metabolic risk profile. Here, we investigate whether biochemical hyperandrogenism, represented by elevated serum free testosterone, resulted in an aberrant circulating microRNA (miRNAs) expression profile and whether miRNAs can identify those PCOS women with metabolic syndrome (MetS). Accordingly, we measured serum levels of miRNAs as well as biochemical markers related to MetS in a case-control study of 42 PCOS patients and 20 Controls. Patients were diagnosed based on the Rotterdam consensus criteria and stratified based on serum free testosterone levels (≥0.034 nmol/l) into either a normoandrogenic (n = 23) or hyperandrogenic (n = 19) PCOS group. Overall, hyperandrogenic PCOS women were more insulin resistant compared to normoandrogenic PCOS women and had a higher prevalence of MetS. A total of 750 different miRNAs were analyzed using TaqMan Low-Density Arrays. Altered levels of seven miRNAs (miR-485-3p, -1290, -21-3p, -139-3p, -361-5p, -572, and -143-3p) were observed in PCOS patients when compared with healthy Controls. Stratification of PCOS women revealed that 20 miRNAs were differentially expressed between the three groups. Elevated serum free testosterone levels, adjusted for age and BMI, were significantly associated with five miRNAs (miR-1290, -20a-5p, -139-3p, -433-3p, and -361-5p). Using binary logistic regression and receiver operating characteristic curves (ROC), a combination panel of three miRNAs (miR-361-5p, -1225-3p, and -34-3p) could correctly identify all of the MetS cases within the PCOS group. This study is the first to report comprehensive miRNA profiling in different subgroups of PCOS women with respect to MetS and suggests that circulating miRNAs might be useful as diagnostic biomarkers of MetS for a different subset of PCOS

Patient-reported effects of hospital-wide implementation of shared decision-making at a university medical centre in Germany: a pre–post trial

Objectives To evaluate the feasibility and effectiveness of the SHARE TO CARE (S2C) programme, a complex intervention designed for hospital-wide implementation of shared decision-making (SDM). Design Pre–post study. Setting University Hospital Schleswig-Holstein (UKSH), Kiel Campus. Participants Healthcare professionals as well as inpatients and outpatients from 22 departments of the Kiel Campus of UKSH. Interventions The S2C programme is a comprehensive implementation strategy including four core modules: (1) physician training, (2) SDM support training for and support by nurses as decision coaches, (3) patient activation and (4) evidence-based patient decision aid development and integration into patient pathways. After full implementation, departments received the S2C certificate. Main outcome measures In this paper, we report on the feasibility and effectiveness outcomes of the implementation. Feasibility was judged by the degree of implementation of the four modules of the programme. Outcome measures for effectiveness are patient-reported experience measures (PREMs). The primary outcome measure for effectiveness is the Patient Decision Making subscale of the Perceived Involvement in Care Scale (PICS PDM ). Pre–post comparisons were done using t-tests. Results The implementation of the four components of the S2C programme was able to be completed in 18 of the 22 included departments within the time frame of the study. After completion of implementation, PICS PDM showed a statistically significant difference (p<0.01) between the means compared with baseline. This difference corresponds to a small to medium yet clinically meaningful positive effect (Hedges’ g=0.2). Consistent with this, the secondary PREMs (Preparation for Decision Making and collaboRATE) also showed statistically significant, clinically meaningful positive effects. Conclusions The hospital-wide implementation of SDM with the S2C-programme proved to be feasible and effective within the time frame of the project. The German Federal Joint Committee has recommended to make the Kiel model of SDM a national standard of care

Contribution of an Aged Microenvironment to Aging-Associated Myeloproliferative Disease

The molecular and cellular mechanisms of the age-associated increase in the incidence of acute myeloid leukemia (AML) remain poorly understood. Multiple studies support that the bone marrow (BM) microenvironment has an important influence on leukemia progression. Given that the BM niche itself undergoes extensive functional changes during lifetime, we hypothesized that one mechanism for the age-associated increase in leukemia incidence might be that an aged niche promotes leukemia progression. The most frequent genetic alteration in AML is the t(8;21) translocation, resulting in the expression of the AML1-ETO fusion protein. Expression of the fusion protein in hematopoietic cells results in mice in a myeloproliferative disorder. Testing the role of the age of the niche on leukemia progression, we performed both transplantation and in vitro co-culture experiments. Aged animals transplanted with AML1-ETO positive HSCs presented with a significant increase in the frequency of AML-ETO positive early progenitor cells in BM as well as an increased immature myeloid cell load in blood compared to young recipients. These findings suggest that an aged BM microenvironment allows a relative better expansion of pre-leukemic stem and immature myeloid cells and thus imply that the aged microenvironment plays a role in the elevated incidence of age-associated leukemia

Aging of human hematopoietic stem cells is linked to changes in Cdc42 activity

In this study, we characterize age-related phenotypes of human hematopoietic stem cells (HSC). We report increased frequencies of HSC, hematopoietic progenitor cells and lineage negative cells in the elderly but a decreased frequency of multi-lymphoid progenitors. Aged human HSC further exhibited a delay in initiating division ex vivo though without changes in their division kinetics. The activity of the small RhoGTPase Cdc42 was elevated in aged human hematopoietic cells and we identified a positive correlation between Cdc42 activity and the frequency of HSC upon aging. The frequency of human HSC polar for polarity proteins was, similar to the mouse, decreased upon aging, while inhibition of Cdc42 activity via the specific pharmacological inhibitor of Cdc42 activity, CASIN, resulted in re-polarization of aged human HSC with respect to Cdc42. Elevated activity of Cdc42 in aged HSC thus contributed to age-related changes in HSC. Xenotransplant, using NBSGW mice as recipients, showed elevated chimerism in recipients of aged compared to young HSC. Aged HSC treated with CASIN ex vivo displayed an engraftment profile similar to recipients of young HSC. Taken together, our work reveals strong evidence for a role of elevated Cdc42 activity in driving aging of human HSC, and similar to mice, this presents a likely possibility for attenuation of aging in human HSC