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.

Bivalent (poised or paused) chromatin comprises activating and repressing histone modifications at the same location. This combination of epigenetic marks at promoter or enhancer regions keeps genes expressed at low levels but poised for rapid activation. Typically, DNA at bivalent promoters is only lowly methylated in normal cells, but frequently shows elevated methylation levels in cancer samples. Here, we developed a universal classifier built from chromatin data that can identify cancer samples solely from hypermethylation of bivalent chromatin. Tested on over 7,000 DNA methylation data sets from several cancer types, it reaches an AUC of 0.92. Although higher levels of DNA methylation are often associated with transcriptional silencing, counter-intuitive positive statistical dependencies between DNA methylation and expression levels have been recently reported for two cancer types. Here, we re-analyze combined expression and DNA methylation data sets, comprising over 5,000 samples, and demonstrate that the conjunction of hypermethylation of bivalent chromatin and up-regulation of the corresponding genes is a general phenomenon in cancer. This up-regulation affects many developmental genes and transcription factors, including dozens of homeobox genes and other genes implicated in cancer. Thus, we reason that the disturbance of bivalent chromatin may be intimately linked to tumorigenesis.

Background: Systemic hypertension is a risk factor of age-related macular degeneration (AMD), a chronic inflammatory disease. Acute hypertension is caused by increased extracellular osmolarity after intake of dietary salt (NaCl). We determined in cultured human retinal pigment epithelial (RPE) cells whether high extracellular NaCl alters the gene expression of inflammasome-associated proteins, and whether autocrine/paracrine purinergic (P2) receptor signaling contributes to the NaCl-induced NLRP3 gene expression. Methodology/Principal Findings: Hyperosmolarity was induced by the addition of 100 mM NaCl or sucrose to the culture medium. Gene and protein expression levels were determined with real-time RT-PCR and Western blot analysis, respectively. IL-1β and IL-18 levels were evaluated with ELISA. Nuclear factor of activated T cell 5 (NFAT5) expression was knocked down with siRNA. High extracellular NaCl induced NLRP3 and pro-IL-1β gene expression, while the gene expression of further inflammasome-associated proteins (NLRP1, NLRP2, NLRP6, NLRP7, NLRP12, NLRC4, AIM2, ASC, procaspase-1, pro-IL-18) was not altered or below the detection threshold. The NaCl-induced NLRP3 gene expression was partially dependent on the activities of phospholipase C, IP3 receptors, protein kinase C, the serum and glucocorticoid-regulated kinase, p38 MAPK, ERK1/2, JNK, PI3K, and the transcription factors HIF-1 and NFAT5. Pannexin-dependent ATP release and P2Y1 receptor activation is required for the full induction of NLRP3 gene expression. High NaCl induced a transient increase of the NLRP3 protein level and a moderate NLRP3 inflammasome activation, as indicated by the transient increase of the cytosolic level of mature IL-1β. High NaCl also induced secretion of IL-18. High extracellular NaCl induces priming of the NLRP3 inflammasome in RPE cells, in part via P2Y1 receptor signaling. The inflammasome priming effect of NaCl suggests that high intake of dietary salt may promote local retinal inflammation implicated in the development of AMD.

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.

The study area is located within the Neogene-Quaternary sequences on top of the Mesozoic accreted mass at the northwest of Kazan (40 km NW of Ankara) between Karalar and Alibey villages. The research deals with the post-Miocene deformational history of an area situated at the southern edge of Galatian Volcanic Province. Two main Neogene rock sequences are cropped out / 1) Late Miocene Pazar Formation, 2) Plio-Quaternary Sinap Formation. The Pazar Formation has a succession composed mainly of clastics at the bottom and, cherts and limestones to the top of the sequence representing a fresh water lake environment. Sedimentation seems to be affected by the intense volcanism going on in the Galatian Volcanic Province. Location of a mammalian fossil found in the Pazar Formation yielded a possible time interval between MN-9 to MN-13 (Middle to Late Miocene). Sinap Formation overlies the Pazar Formation unconformably and it is dominantly represented by fluvial clastics. The post-Miocene deformational studies based on the analysis of the structural data collected from bedding planes and fault planes. Totally 213 dip-strike measurements from the Neogene units and 204 slip lineation data from the fault planes were taken. Fold analysis of dip and strike measurements taken from the Pazar Formation gave a common fold axis trending in N430E direction. Similarly fold analysis for the Sinap Formation resulted N400E striking trend for the fold axis. Stress analysis was performed by processing slip lineation data using Angelier direct inversion method. In the analysis, no reliable results for the post-Miocene compressional phase could be obtained. But the results of the post-Plio-Quaternary extensional regime are strongly reliable. It clearly gives an extension in NW-SE direction. Stress analysis together with the field observations show that the area has been structurally evolved in several phases of deformation. The NW-SE to N-S-directed post-Miocene compressional event is followed by a regional extension operating since Plio-Quaternary.

At temperatures above 0.5 Tm and in aggressive atmospheres predicting alloy performance is particularly challenging. Nickel alloys used in regimes where microstructure and properties are altered dynamically present unique requirements. Exposure may alter properties with unexpected early failure. The Gleeble is a valuable tool for investigation and simulation of thermo-mechanical properties of an alloy in various regimes up to the threshold of melting. In this study, four regimes of temperature and strain rate were simulated in an argon atmosphere to both investigate and document normal and abnormal failure modes. Commercial Inconel 601 was tested in selected regimes and in two treatments (as received and strain aged). Next two exposed conditions (TEOS and Hydride) were tested. Slow strain-rate and high temperature produced brittle intergranular fracture. Exposure at elevated temperature to process gases reduced both strength and ductility in both TEOS and Hydride. TEOS exposure reduced reduction in area in the alloy significantly more than the Hydride exposure.