Explore the vast range of titles available.

Retention forestry, which retains a portion of the original stand at the time of harvesting to maintain continuity of structural and compositional diversity, has been originally developed to mitigate the impacts of clear‐cutting. Retention of habitat trees and deadwood has since become common practice also in continuous‐cover forests of Central Europe. While the use of retention in these forests is plausible, the evidence base for its application is lacking, trade‐offs have not been quantified, it is not clear what support it receives from forest owners and other stakeholders and how it is best integrated into forest management practices. The Research Training Group ConFoBi (Conservation of Forest Biodiversity in Multiple‐use Landscapes of Central Europe) focusses on the effectiveness of retention forestry, combining ecological studies on forest biodiversity with social and economic studies of biodiversity conservation across multiple spatial scales. The aim of ConFoBi is to assess whether and how structural retention measures are appropriate for the conservation of forest biodiversity in uneven‐aged and selectively harvested continuous‐cover forests of temperate Europe. The study design is based on a pool of 135 plots (1 ha) distributed along gradients of forest connectivity and structure. The main objectives are (a) to investigate the effects of structural elements and landscape context on multiple taxa, including different trophic and functional groups, to evaluate the effectiveness of retention practices for biodiversity conservation; (b) to analyze how forest biodiversity conservation is perceived and practiced, and what costs and benefits it creates; and (c) to identify how biodiversity conservation can be effectively integrated in multi‐functional forest management. ConFoBi will quantify retention levels required across the landscape, as well as the socio‐economic prerequisites for their implementation by forest owners and managers. ConFoBi's research results will provide an evidence base for integrating biodiversity conservation into forest management in temperate forests. This paper describes the background, research questions and design of the Research Training Group “ConFoBi” (Conservation of Forest Biodiversity in Multiple‐use Landscapes of Central Europe). ConFoBi focusses on the effectiveness of retention forestry, that is, retaining structural elements of old forests within a production forest matrix, and combines ecological studies on forest biodiversity with social and economic studies of biodiversity conservation across multiple spatial scales. The aim of ConFoBi is to assess whether and how structural retention measures are appropriate for the conservation of forest biodiversity in multiple‐use landscapes of temperate Europe.

Starting from a general framework for web-based e-learning systems that is based on an abstraction layer model, this paper presents a conceptual modelling approach, which captures the modelling of learners, the modelling of courses, the personalisation of courses, and the management of data in e-learning systems. Courses are modelled by outline graphs, which are further refined by some form of process algebra. The linguistic analysis of word fields referring to an application domain helps to set up these course outlines. Learners are modelled by classifying value combinations for their characteristic properties. Each learner type gives rise to intentions as well as rights and obligations in using a learning system. Intentions can be formalised as postconditions, while rights and obligations lead to deontic constraints. The intentions can be used for the personalisation of the learning system to a learner type. Finally, the management of data in an e-learning system is approached on two different levels dealing with the content of individual learning units and the integrated content of the whole system, respectively. This leads to supporting databases and views defined on them.[PUBLICATION ABSTRACT]

Melanoma arising from pigment-producing melanocytes is the deadliest form of skin cancer. Extensive ultraviolet light exposure is a major cause of melanoma and individuals with low levels of melanin are at particular risk. Humans carrying gain-of-function polymorphisms in the melanosomal/endolysosomal two-pore cation channel TPC2 present with hypopigmentation, blond hair, and albinism. Loss of TPC2 is associated with decreased cancer/melanoma proliferation, migration, invasion, tumor growth and metastasis formation, and TPC2 depleted melanoma cells show increased levels of melanin. How TPC2 activity is controlled in melanoma and the downstream molecular effects of TPC2 activation on melanoma development remain largely elusive. Here we show that the small GTPase Rab7a strongly enhances the activity of TPC2 and that effects of TPC2 on melanoma hallmarks, in vitro and in vivo strongly depend on the presence of Rab7a, which controls TPC2 activity to modulate GSK3β, β-Catenin, and MITF, a major regulator of melanoma development and progression. Direct interaction between the small GTPase Rab7a and the cation channel TPC2 has been reported but the functional regulation is less clear. Here, the authors show that Rab7a enhances the activity of TPC2 to promote melanoma progression through the GSK3β/β-Catenin/MITF axis.

The transcriptome of non-coding RNA (ncRNA) species is increasingly focused in Alzheimer’s disease (AD) research. NcRNAs comprise, among others, transfer RNAs, long non-coding RNAs and microRNAs (miRs), each with their own specific biological function. We used smallRNASeq to assess miR expression in the hippocampus of young (3 month old) and aged (eight month old) Tg4-42 mice, a model system for sporadic AD, as well as age-matched wildtype controls. Tg4-42 mice express N-truncated Aβ4-42, develop age-related neuron loss, reduced neurogenesis and behavioral deficits. Our results do not only confirm known miR-AD associations in Tg4-42 mice, but more importantly pinpoint 22 additional miRs associated to the disease. Twenty-five miRs were differentially expressed in both aged Tg4-42 and aged wildtype mice while eight miRs were differentially expressed only in aged wildtype mice, and 33 only in aged Tg4-42 mice. No significant alteration in the miRNome was detected in young mice, which indicates that the changes observed in aged mice are down-stream effects of A-induced pathology in the Tg4-42 mouse model for AD. Targets of those miRs were predicted using miRWalk. For miRs that were differentially expressed only in the Tg4-42 model, 128 targets could be identified, whereas 18 genes were targeted by miRs only differentially expressed in wildtype mice and 85 genes were targeted by miRs differentially expressed in both mouse models. Genes targeted by differentially expressed miRs in the Tg4-42 model were enriched for negative regulation of long-term synaptic potentiation, learning or memory, regulation of trans-synaptic signaling and modulation of chemical synaptic transmission obtained. This untargeted miR sequencing approach supports previous reports on the Tg4-42 mice as a valuable model for AD. Furthermore, it revealed miRs involved in AD, which can serve as biomarkers or therapeutic targets.

One of the central research questions on the etiology of Alzheimer's disease (AD) is the elucidation of the molecular signatures triggered by the amyloid cascade of pathological events. Next-generation sequencing allows the identification of genes involved in disease processes in an unbiased manner. We have combined this technique with the analysis of two AD mouse models: (1) The 5XFAD model develops early plaque formation, intraneuronal Aβ aggregation, neuron loss, and behavioral deficits. (2) The Tg4-42 model expresses N-truncated Aβ4-42 and develops neuron loss and behavioral deficits albeit without plaque formation. Our results show that learning and memory deficits in the Morris water maze and fear conditioning tasks in Tg4-42 mice at 12 months of age are similar to the deficits in 5XFAD animals. This suggested that comparative gene expression analysis between the models would allow the dissection of plaque-related and -unrelated disease relevant factors. Using deep sequencing differentially expressed genes (DEGs) were identified and subsequently verified by quantitative PCR. Nineteen DEGs were identified in pre-symptomatic young 5XFAD mice, and none in young Tg4-42 mice. In the aged cohort, 131 DEGs were found in 5XFAD and 56 DEGs in Tg4-42 mice. Many of the DEGs specific to the 5XFAD model belong to neuroinflammatory processes typically associated with plaques. Interestingly, 36 DEGs were identified in both mouse models indicating common disease pathways associated with behavioral deficits and neuron loss.

The German National Cohort (NAKO) is a multidisciplinary, population-based prospective cohort study that aims to investigate the causes of widespread diseases, identify risk factors and improve early detection and prevention of disease. Specifically, NAKO is designed to identify novel and better characterize established risk and protection factors for the development of cardiovascular diseases, cancer, diabetes, neurodegenerative and psychiatric diseases, musculoskeletal diseases, respiratory and infectious diseases in a random sample of the general population. Between 2014 and 2019, a total of 205,415 men and women aged 19–74 years were recruited and examined in 18 study centres in Germany. The baseline assessment included a face-to-face interview, self-administered questionnaires and a wide range of biomedical examinations. Biomaterials were collected from all participants including serum, EDTA plasma, buffy coats, RNA and erythrocytes, urine, saliva, nasal swabs and stool. In 56,971 participants, an intensified examination programme was implemented. Whole-body 3T magnetic resonance imaging was performed in 30,861 participants on dedicated scanners. NAKO collects follow-up information on incident diseases through a combination of active follow-up using self-report via written questionnaires at 2–3 year intervals and passive follow-up via record linkages. All study participants are invited for re-examinations at the study centres in 4–5 year intervals. Thereby, longitudinal information on changes in risk factor profiles and in vascular, cardiac, metabolic, neurocognitive, pulmonary and sensory function is collected. NAKO is a major resource for population-based epidemiology to identify new and tailored strategies for early detection, prediction, prevention and treatment of major diseases for the next 30 years.

The long-term health effects of football (soccer) have received significant attention in recent years. While brain health is currently the focus of this interest, potential long-term risks or benefits related to cardiovascular and metabolic diseases and cancer are also of interest to sports medicine professionals. However, studies assessing the overall health risks for professional football players remain scarce. We introduce ‘SoccHealth’, a satellite project to the German National Cohort (NAKO), Germany’s largest population-based cohort study. SoccHealth examined 348 former professional football players aged 40–69 using the infrastructure and comprehensive examination programme of NAKO. The German Statutory Accidental Insurance for Professional Athletes identified and invited male players, while female players were recruited among former national team members. Details of the examination programme and the sociodemographic and career-related characteristics of the participants are described. The identical examination programme for the NAKO participants provides the opportunity to draw general population controls according to various definitions and focus on the respective research question to be analysed. This report delineates one approach to evaluate the long-term health effects of football across a broad range of diseases.

IntroductionWomen with gestational diabetes mellitus (GDM) have a higher risk of developing type 2 diabetes mellitus compared with women who never had GDM. Consequently, the question of structured aftercare for GDM has emerged. In all probability, many women do not receive care according to the guidelines. In particular, the process and interaction between obstetrical, diabetic, gynaecological, paediatric and general practitioner care lacks clear definitions. Thus, our first goal is to analyse the current aftercare situation for women with GDM in Germany, for example, the participation rate in aftercare diabetes screening, as well as reasons and attitudes stated by healthcare providers to offer these services and by patients to participate (or not). Second, we want to develop an appropriate, effective and patient-centred care model.Methods and analysisThis is a population-based mixed methods study using both quantitative and qualitative research approaches. In various working packages, we evaluate data of the GestDiab register, of the Association of Statutory Health Insurance Physicians of North Rhine and the participating insurance companies (AOK Rheinland/Hamburg, BARMER, DAK Gesundheit, IKK classic, pronova BKK). In addition, quantitative (postal surveys) and qualitative (interviews) surveys will be conducted with randomly selected healthcare providers (diabetologists, gynaecologists, paediatricians and midwives) and affected women, to be subsequently analysed. All results will then be jointly examined and evaluated.Ethics and disseminationThe study was approved by the ethics committee of the Faculty of Medicine, Heinrich-Heine-University Düsseldorf (Ethics Committee No.: 2019-738). Participants of the postal surveys and interviews will be informed in detail about the study and the use of data as well as the underlying data protection regulations before voluntarily participating. The study results will be disseminated through peer-reviewed journals, conferences and public information.Trial registration numberDRKS00020283.

BackgroundThe Model for End Stage Liver Disease (MELD) predicts mortality in end stage liver disease. Incorporation of serum sodium into the MELD may improve diagnostic accuracy in decompensated patients with ascites. However, other complications of cirrhosis are not reflected. This study investigates whether quantitative liver function tests predict survival and increase prognostic accuracy of the MELD.Methods604 patients with suspected cirrhosis were staged clinically and haemodynamically. Galactose-elimination-capacity, sorbitol clearance, lidocaine metabolism and indocyanin green (ICG) half life were determined. Survival was the primary end point of the study. Prognostic effects of individual parameters were calculated using Cox regression models and ROC curves.Results321 patients on standard pharmacological and endoscopic treatment (PET) and 74 patients undergoing transjugular portosystemic shunting (TIPS) were studied. Of all quantitative liver function tests, ICG half life was the most accurate in predicting survival. Upon incorporation into the MELD, it modified the score in patients with PET up to 35 points. Clinically relevant changes to the score, however, occurred in patients with a MELD score between 10 and 30, allowing an objective prognostic discrimination of individual survival based on laboratory liver function and blood flow. The MELD-ICG was validated in the second cohort of patients undergoing TIPS implantation.ConclusionICG had the highest predictive value of the examined tests. Its incorporation into the MELD adds an estimation of liver blood flow and renders the new score MELD-ICG more accurate in predicting survival in intermediate to advanced cirrhosis than the MELD and MELD-Na.

Despite considerable improvements in oral health in recent decades, caries and periodontitis are still widespread, ranking among the most prevalent diseases worldwide and requiring future research. The German National Cohort (NAKO Gesundheitsstudie, NAKO) is a large-scaled, multidisciplinary, nationwide, multi-centre, population-based, prospective cohort study with oral examinations that aims to provide a resource to study risk factors for major diseases. The aim of the present article is to provide the methodological background, to report on the data quality, and to present initial results of the oral examinations. During baseline examinations (2014-2019), a total of 205,184 persons aged 19-74 years has been examined in 18 study centres, including, among others, a dental interview, stimulated saliva sampling, and recording of the numbers of present teeth and prostheses (standard Level 1 program). As part of the Level 2 program that was offered to 20% randomly selected participants, each study centre selected one of three modules, one of them being the Level 2 oral examination. This extended program was carried out in a subgroup of 20,828 participants, including collection of detailed information on the dental and prosthetic status as well as on periodontal, cariological and functional aspects. To ensure reliability and reproducibility, study nurses were trained and calibrated by dental experts. In addition, a reliability study was conducted among 794 Level 1 and 359 Level 2 participants, reporting intra class correlation and kappa coefficients. Intra class correlation and kappa coefficients for observer agreement and reliability were consistently above 0.7, indicating good to excellent reliability of all dental measurements. For example, intra class correlation was 0.937 for the number of present teeth (Level 1), 0.740 for mean probing depth (PD) and 0.797 for active mouth opening. An initial inspection of the data showed that the median number of present teeth was 27, of which on average 6.9 teeth were healthy and caries-free. Average mean PD was 1.92 mm. An orthodontic treatment was reported by 35.5% of participants. Overall, the dental study protocol was feasible and successfully integrated into the NAKO's overall assessment program. However, rigorous support of the study centres by dental professionals was required to ensure high quality data. In summary, high-quality data collection within the NAKO pave the way for future investigation of potential risk factors for oral diseases and links between oral and systemic diseases and conditions.