Depression ist auch bei Älteren eine häufige Erkrankung und kann für die Betroffenen schwere Folgen haben. Durch den Demographischen Wandel wird der Anteil älterer Menschen an der Bevölkerung in den nächsten Jahren zunehmen, wodurch das Thema Altersdepression noch wichtiger werden wird. Obwohl es etablierte und wirksame Therapiemethoden für depressive Episoden auch im hohen Alter gibt, werden Depressionen gerade in dieser Bevölkerungsgruppe häufig nicht erkannt und den Patienten somit der Zugang zu einer wirksamen Behandlung verwehrt. Deshalb wird in einigen Ländern bereits ein generelles Screening auf Depressionen empfohlen, jedoch noch nicht in Deutschland. Um Screening Methoden effektiv und ressourcenschonend einzusetzen, ist es wichtig Untergruppen von Patienten zu identifizieren, die besonders anfällig für Depressionen sind. Kenntnisse über Risikofaktoren von Depressionen im Alter sind essentiell, um solche Untergruppen eingrenzen zu können. In den letzten Jahrzehnten wurden eine große Anzahl von Studien zu Risikofaktoren von Altersdepression durchgeführt. Jedoch wiesen viele dieser Arbeiten schwerwiegende methodische Mängel auf oder es handelte sich um Querschnittstudien. Um ein tieferes Verständnis über diese Risikofaktoren zu ermöglichen, führten wir zwei Studien durch: Zunächst fasten wir alle Längsschnittstudien zu Risikofaktoren für Depressionen bei Personen im Alter von 65 Jahren oder älter in einem systematischen Review zusammen, die strenge Qualitätsstandards erfüllten. Anschließend führten wir eine hochqualitative Längsschnittstudie zu Risikofaktoren von Depressionen in einer großen Kohorte älterer Menschen im Alter von mindestens 75 Jahre durch. In die endgültige Analyse unserer systematische Übersichtsarbeit schlossen wir 30 Längsschnittstudien mit ein, in welchen multivariate Analysemethoden angewendet und strenge Einschlusskriterien erfüllt wurden. Diese Übersichtsarbeit konnte einen guten Überblick über qualitativ hochwertige Studien zu Risikofaktoren der Depression im Alter verschaffen. Jedoch konnten wir aufgrund der Heterogenität der eingeschlossenen Studien, insbesondere im Bereich der eingeschlossenen Faktoren und der verwendeten Erhebungsmethoden der Faktoren, sowie dem hohen Verzerrungsrisiko, keine Metaanalyse durchführen. In unserer prospektiven Kohortenstudie analysierten wir Risikofaktoren sowie Inzidenzraten von Depressionen in einer repräsentativen Stichprobe von 3.327 älteren Erwachsenen, die über 13 Jahre nachbeobachtet wurden. Als statistische Methode wendeten wir aufgrund der hohen Sterblichkeit der Teilnehmer die statistische Methode der Competing Risk Regression an. Die Studienteilnehmer wurden aus Hausarztpraxen rekrutiert. 2.436 Patienten ohne signifikante depressive Symptome zu Studienbeginn wurden in die endgültige Analyse miteingeschlossen. Von diesen entwickelten 543 (22,2 %) signifikante depressive Symptome (Inzidenzrate 38,8 pro 1000 Personenjahre (95 % KI 35,5–42,4)). Durch unsere Analyse, in der Versterben der Studienteilnehmer als konkurrierendem Ereignis einberechnet wurde, ergaben sich folgende Risikofaktoren für das Auftreten von depressiven Symptomen: Weibliches Geschlecht, der Beziehungsstatus ledig oder geschieden, subjektiver Gedächtnisverlust mit und ohne Sorgen über diesen, Sehstörungen, sowie Einschränkungen in der körperlichen Mobilität. Die konsistentesten Risikofaktoren in allen Studien, einschließlich unserer eigenen prospektiven Studie, waren Mobilitätseinschränkungen, gefolgt von Sehstörungen. Die meisten untersuchten Faktoren ergaben in verschiedenen Studien widersprüchliche Ergebnisse. Auch wenn diese Dissertation keine abschließenden Ergebnisse in Form einer Metaanalyse liefern konnte, zeigt sie doch mögliche Wege auf, um in zukünftigen Studien zu Risikofaktoren für Depressionen in der älteren Bevölkerung verlässlichere und konsistentere Ergebnisse zu erhalten. Auf diese Weise könnten Gruppen mit hohem Risiko für depressiven Episode in dieser unterdiagnostizierten und unterbehandelten Population identifiziert und ein Screening für Hochrisikogruppen etabliert werden. Da die Folgen einer Depression schwerwiegend sind und wirksame Behandlungsmöglichkeiten zur Verfügung stehen, lohnt es sich, die Forschung zu Risikofaktoren für Depressionen bei älteren Menschen zu verfeinern und fortzuführen.

A variety of modern software packages are available for genotype imputation relying on advanced concepts such as pre-phasing of the target dataset or utilization of admixed reference panels. In this study, we performed a comprehensive evaluation of the accuracy of modern imputation methods on the basis of the publicly available POPRES samples. Good quality genotypes were masked and re-imputed by different imputation frameworks: namely MaCH, IMPUTE2, MaCH-Minimac, SHAPEIT-IMPUTE2 and MaCH-Admix. Results were compared to evaluate the relative merit of pre-phasing and the usage of admixed references. We showed that the pre-phasing framework SHAPEIT-IMPUTE2 can overestimate the certainty of genotype distributions resulting in the lowest percentage of correctly imputed genotypes in our case. MaCH-Minimac performed better than SHAPEIT-IMPUTE2. Pre-phasing always reduced imputation accuracy. IMPUTE2 and MaCH-Admix, both relying on admixed-reference panels, showed comparable results. MaCH showed superior results if well-matched references were available (Nei’s GST ≤ 0.010). For small to medium datasets, frameworks using genetically closest reference panel are recommended if the genetic distance between target and reference data set is small. Our results are valid for small to medium data sets. As shown on a larger data set of population based German samples, the disadvantage of pre-phasing decreases for larger sample sizes.

One major approach to weight stigma reduction consists of decreasing beliefs about the personal controllability of—and responsibility for—obesity by educating about its biogenetic causes. Evidence on the efficacy of this approach is mixed, and it remains unclear whether this would create a deterministic view, potentially leading to detrimental side-effects. Two independent studies from Germany using randomized designs with delayed-intervention control groups served to (1) develop and pilot a brief, interactive stigma reduction intervention to educate N = 128 university students on gene × environment interactions in the etiology of obesity; and to (2) evaluate this intervention in the general population (N = 128) and determine mechanisms of change. The results showed (1) decreased weight stigma and controllability beliefs two weeks post-intervention in a student sample; and (2) decreased internal attributions and increased genetic attributions, knowledge, and deterministic beliefs four weeks post-intervention in a population sample. Lower weight stigma was longitudinally predicted by a decrease in controllability beliefs and an increase in the belief in genetic determinism, especially in women. The results underline the usefulness of a brief, interactive intervention promoting an interactionist view of obesity to reduce weight stigma, at least in the short term, lending support to the mechanisms of change derived from attribution theory. The increase in genetic determinism that occurred despite the intervention’s gene × environment focus had no detrimental side-effect on weight stigma, but instead contributed to its reduction. Further research is warranted on the effects of how biogenetic causal information influences weight management behavior of individuals with obesity.

Background: Internalized weight stigma has gained growing interest due to its association with multiple health impairments in individuals with obesity. Especially high internalized weight stigma is reported by individuals undergoing bariatric surgery. For assessing this concept, two different self-report questionnaires are available, but have never been compared: the Weight Self-Stigma Questionnaire (WSSQ) and the Weight Bias Internalization Scale (WBIS). The purpose of the present study was to provide and to compare reliability, convergent validity with and predictive values for psychosocial health outcomes for the WSSQ and WBIS. Methods: The WSSQ and the WBIS were used to assess internalized weight stigma in N = 78 prebariatric surgery patients. Further, body mass index (BMI) was assessed and body image, quality of life, self-esteem, depression, and anxiety were measured by well-established self-report questionnaires. Reliability, correlation, and regression analyses were conducted. Results: Internal consistency of the WSSQ was acceptable, while good internal consistency was found for the WBIS. Both measures were significantly correlated with each other and body image. While only the WSSQ was correlated with overweight preoccupation, only the WBIS was correlated with appearance evaluation. Both measures were not associated with BMI. However, correlation coefficients did not differ between the WSSQ and the WBIS for all associations with validity measures. Further, both measures significantly predicted quality of life, self-esteem, depression, and anxiety, while the WBIS explained significantly more variance than the WSSQ total score for self-esteem.

The microbiota has a strong influence on health and disease in humans. A causative shift favoring pathobionts is strongly linked to diseases. Therefore, anti-microbial agents selectively targeting potential pathogens as well as their biofilms are urgently demanded. Here we demonstrate the impact of ethyl pyruvate, so far known as ROS scavenger and antiinflammatory agent, on planktonic microbes and biofilms. Ethyl pyruvate combats preferably the growth of pathobionts belonging to bacteria and fungi independent of the genera and prevailing drug resistance. Surprisingly, this anti-microbial agent preserves symbionts like Lactobacillus species. Moreover, ethyl pyruvate prevents the formation of biofilms and promotes matured biofilms dissolution. This potentially new anti-microbial and anti-biofilm agent could have a tremendous positive impact on human, veterinary medicine and technical industry as well.

Introduction: The long-term success of non-surgical weight loss treatment in adults with obesity is limite by substantial relapse, and only a few evidence-based weight loss maintenance treatments exist. This clinical trial investigates the feasibility and efficacy of a social facilitation maintenance programme for weight loss maintenance, tailored to meet the needs of obese adults who have undergone a lifestyle weight loss intervention. Methods and analysis: In a single-centre, open feasibility trial, 72 adults currently or previously obese or overweight who have undergone a lifestyle weight loss intervention are centrally randomised to 4 months of social facilitation maintenance treatment or treatment as a usual control condition. In 16 outpatient group sessions, the social facilitation maintenance treatment, based on a socioecological model and on evidence supporting social facilitation as a key process in maintaining weight loss, focuses on promoting interpersonal relationships to build up a healthy lifestyle for long-term weight loss maintenance. Primary outcome is the amount of weight regain at 6-month follow-up, compared with pre-treatment weight, derived from measured body weight. Secondary outcomes address feasibility, including recruitment, attrition, assessment non-completion, compliance and patients’ programme evaluation; and in comparison with pre-weight loss maintenance, social and interpersonal functioning, eating behaviour and physical activity, psychological and physical symptoms, body composition and risk of comorbidity, and quality of life at post-treatment and follow-up assessments. Ethics and dissemination: The study was approved by the Ethical Committee at the University of Leipzig (165-13-15072013). The study results will be disseminated through peer-reviewed publications. Trial registration number: DRKS00005182

Clostridium difficile infection (CDI) is the most common cause of health-care-associated infectious diarrhea. Recurrence rates are as high as 20–30% after standard treatment with metronidazole or vancomycin, and appear to be reduced for patients treated with fidaxomicin. According to the literature, the risk of CDI recurrence increases after the second relapse to 30–65%. Accurate data for Germany are not yet available. Methods: Based on the research database of arvato health analytics (Munich, Germany), a secondary data analysis for the incidence, treatment characteristics and course of CDI was performed. The database included high granular accounting information of about 1.46 million medically insured patients covering the period 2006–2013, being representative for Germany. The analysis was based on new-onset CDI in 2012 in patients which either received outpatient antibiotic therapy for CDI or were hospitalized. Results: The ICD-10 coded incidence of CDI in 2012 was 83 cases per 100,000 population.

Introduction: Pulmonary Surfactant reduces surface tension in the terminal airways thus facilitating breathing and contributes to host''s innate immunity. Surfactant Proteins (SP) A, B, C and D were recently identified as inherent proteins of the CNS. Aim of the study was to investigate cerebrospinal fluid (CSF) SP levels in hydrocephalus patients compared to normal subjects. Patients and methods: CSF SP A-D levels were quantified using commercially available ELISA kits in 126 patients (0±84 years, mean 39 years). 60 patients without CNS pathologies served as a control group. Hydrocephalus patients were separated in aqueductal stenosis (AQS, n = 24), acute hydrocephalus without aqueductal stenosis (acute HC w/o AQS, n = 16) and idiopathic normal pressure hydrocephalus (NPH, n = 20). Furthermore, six patients with pseudotumor cerebri were investigated. Results: SP AÐD are present under physiological conditions in human CSF. SP-A is elevated in diseases accompanied by ventricular enlargement (AQS, acute HC w/o AQS) in a significant manner (0.67, 1.21 vs 0.38 ng/ml in control, p<0.001). SP-C is also elevated in hydrocephalic conditions (AQS, acute HC w/o AQS; 0.87, 1.71 vs. 0.48 ng/ml in controls, p<0.001) and in Pseudotumor cerebri (1.26 vs. 0.48 ng/ml in controls, p<0.01). SP-B and SP-D did not show significant alterations. Conclusion: The present study confirms the presence of SPs in human CSF. There are significant changes of SP-A and SP-C levels in diseases affecting brain water circulation and elevation of intracranial pressure. Cause of the alterations, underlying regulatory mechanisms, as well as diagnostic and therapeutic consequences of cerebral SP''s requires further thorough investigations.

Aortocoronary bypass or valve surgery usually require cardiac arrest using cardioplegic solutions. Although, in principle, in a number of cases beating heart surgery (so-called off-pump technique) is possible, aortic or valve surgery or correction of congenital heart diseases mostly require cardiopulmonary arrest. During this condition, the heart-lung machine also named cardiopulmonary bypass (CPB) has to take over the circulation. It is noteworthy that the invention of a machine bypassing the heart and lungs enabled complex cardiac operations, but possible negative effects of the CPB on other organs, especially the brain, cannot be neglected. Thus, neuroprotection during CPB is still a matter of great interest. In this review, we will describe the impact of CPB on the brain and focus on pharmacological and non-pharmacological strategies to protect the brain.

Homeostasis of hematopoietic stem cells (HSC) in the mammalian bone marrow stem cell niche is regulated by signals of the local microenvironment. Besides juxtacrine, endocrine and metabolic cues, paracrine and autocrine signals are involved in controlling quiescence, proliferation and differentiation of HSC with strong implications on expansion and differentiation ex vivo as well as in vivo transplantation. Towards this aim, a cell culture analysis on a polymer microcavity carrier platform was combined with a partial least square analysis of a mechanistic model of cell proliferation. We could demonstrate the discrimination of specific autocrine and paracrine signals from soluble factors as stimulating and inhibitory effectors in hematopoietic stem and progenitor cell culture. From that we hypothesize autocrine signals to be predominantly involved in maintaining the quiescent state of HSC in single-cell niches and advocate our analysis platform as an unprecedented option for untangling convoluted signaling mechanisms in complex cell systems being it of juxtacrine, paracrine or autocrine origin.