Das lysosomale Enzym Cathepsin D als genetischer Risikofaktor für Morbus Alzheimer

100 Jahre ist es her, seitdem der Breslauer Nervenarzt Alois Alzheimer im Jahre 1907 erstmals „über eine eigenartige Erkrankung der Hirnrinde“ berichtete. Morbus Alzheimer ist ein multifaktorielles Syndrom, dem genetisch heterogene Erkrankungen zugrunde liegen. Während bei etwa 5% der Erkrankten autosomal-dominant vererbte Gendefekte ursächlich sind, wird für 95% ein komplexes Vererbungsmuster angenommen. Neben dem mittlerweile als Suszeptibilitätsgen für die Alzheimersche Krankheit etablierten Apolipoprotein E wurden weitere Risikogene, darunter auch Cathepsin D, beschrieben. Für das Cathepsin D-Gen wurde eine positive Assoziation einer CT Transition in Exon 2 (Austausch der Aminosäure Alanin zu Valin) des Profragments mit der Alzheimerschen Krankheit beschrieben. Cathepsin D ist die Hauptprotease des endosomal-lysosomalen Systems. In diesem System findet die Prozessierung des Amyloid Precursor Proteins zu -Amyloid statt, dem Hauptbestandteil der Alzheimerschen Plaques. In der vorliegenden Arbeit wurde zum einen die Assoziation zwischen dem Cathepsin D-Genotyp und Morbus Alzheimer an einer unabhängigen Stichprobe überprüft (186 Alzheimer Fälle, 247 Kontrollen). Zum anderen wurde untersucht, ob das Cathepsin D T-Allel einen erkennbaren Einfluß auf die wesentlichen neuropathologischen Veränderungen, den amyloidhaltigen Plaques, neurofibrillären Tangles und aktivierter Mikroglia aufweist. Im ersten Teil der Arbeit zeigte sich, dass der Cathepsin D-Polymorphismus das Erkrankungsrisiko für Männer signifikant um das bis zu sechsfache erhöht (OR: 2,72; 95% CI: 1,23-6,00). Bei Frauen hat es dagegen keinen signifikanten Einfluss (OR: 0,58; 95% CI: 0,30-1,13). Dieses Ergebnis stimmt mit zwei weiteren Studien überein, die ein geschlechtsspezifisches Erkrankungsrisiko von CatD für Männer berechnet haben und unterstützt die Vermutung, dass es sich bei dem Cathepsin D-Polymorphismus um einen geschlechtsspezifischen, nur bei Männern relevanten Risikofaktor für Morbus Alzheimer handeln könnte. Zudem zeigte sich, dass der APOE 4 status und das Alter keinen zusätzlichen Effekt auf das Krankheitsrisiko aufwiesen. Ausserdem zeigte sich, dass APOE 4 einen signifikanten Einfluss auf das Erkrankungsrisiko für Morbus Alzheimer aufweist (OR: 2,5; 95% CI: 1,6-3,7). Die Resultate im zweiten Teil der Arbeit lieferten keinen Anhalt für einen wesentlichen pathophysiologischen Effekt des Cathepsin D T-Allels. Interessanterweise waren -amyloidhaltige Läsionen immer in Verbindung mit CatD angefärbt, was dafür spricht, dass dieses Enzym in die Entstehung der amyloidhaltigen Plaques verwickelt ist. Das geschlechtsspezifische Risiko von Cathepsin D ist bisher kaum untersucht worden. Daher sollte dieser Aspekt zukünftig genauer beleuchtet werden. So könnten mit einer Meta-Analyse der bisher erhobenen Daten, die das Geschlecht explizit berücksichtigt, wertvolle Erkenntnisse hinsichtlich dieser Frage erzielt werden. Die vorliegenden Beobachtungen untermauern weiterhin die Ansicht, dass CatD als wesentlicher Bestandteil des lysosomalen Systems in die Pathogenese des Morbus Alzheimer involviert sein könnte

Does inhibitory control capacity in overweight and obese children and adolescents predict success in a weight-reduction program?

It has been assumed that inhibitory control capacity might influence the success of overweight or obese subjects in reducing weight. However, empirical research on this association is scarce. The present study, therefore, examines whether success in an outpatient weight-reduction program for children and adolescents can be predicted by pre-intervention inhibitory control capacity. The study sample consisted of 111 overweight and obese children and adolescents (7.5–15 years) who attended an outpatient weight-reduction program of 1 year's duration. Inhibitory control was assessed by two computerized neuropsychological procedures, a Go-NoGo and an interference task. Principal component analysis revealed "impulsivity" (fast but less valid reactions) and "inattention" (slow and highly variable reaction times) component. Those who succeeded in the intervention (losing more than 5% of BMI-SDS; n=63) scored significantly higher in the first component than those who failed, while controlling for pre-intervention BMI-SDS, age, gender, and maternal education level. The association was moderated by age. Although in younger children no effect was found, in adolescents high "impulsivity" predicted success. Our result supports the scant evidence for a role of inhibitory control. However, further studies are required to substantiate that weak inhibitory control, and thus high reactivity to external cues, entails a better outcome in behavior modification interventions

Getting science to the citizen : 'food addiction' at the British Science Festival as a case study of interactive public engagement with high profile scientific controversy

Non peer reviewedPublisher PD

The impact of impending / onset of vision loss on depression, anxiety, and vision-related quality of life in Birdshot-Retinochoroiditis and Serpiginous Choroiditis

To evaluate the impact of Birdshot-Retinochoroidopathy (BSRC) and Serpiginous Choroiditis (SC) on depression, anxiety, and vision-related quality of life. 72 individuals (BSRC: n = 28, SC: n = 8; healthy control group (HC): n = 36) completed the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and the Visual Function Questionnaire (VFQ-25). Multivariate linear regression models were used to analyze different subscales of the PHQ-9, the GAD-7 and the VFQ-25. The results showed that the mean of PHQ-9 was significantly higher while the mean of the VFQ-25 and its ' subscales were consistently lower in the disease group compared to HC. The mean of GAD-7 was not significantly lower in the disease group compared to HC. Stratification for different disease severity stages and duration of disease did not reveal any differences in sum scores of PHQ-9, GAD-7, and VFQ-25, whereas there were significant differences in some subscales of the VFQ-25. We conclude that BSRC and SC patients show higher levels of depression and a reduced visual quality of life due to imminent loss of vision. Because depression and quality of life are adversely affected by lack of social contacts and functioning, psychological treatment should enable patients to maintain their independence and ability to social interaction. Psychosomatic care should be taken in account for the treatment of BSRC and SC

Effectiveness of tranexamic acid on bleeding in conization

Objective: Bleeding is the most common complication of conization of cervix. Hemostatic sutures, intraoperative ferric subsulfate, or vasopressin can be used when intraoperative bleeding occurred, whereas oral tranexamic acid (TA) may be used for post-operative bleeding. In this study, we aimed to find out whether intraoperative cervical TA administration in patients undergoing conization caused changes in the amount of intraoperative bleeding and post-operative hemogram. Material and Methods: Patients who have undergone cervical conization between January 2019 and July 2019 in Zeynep Kamil Health Application and Research Center Gynecological Diseases and Birth Clinic were evaluated. One hundred and five patients were included to our study. One ampoule of 10% TA was applied cervically to 47 of these patients. Both groups were evaluated in terms of measuring the intraoperative amount of blood in the aspirator, changes in post-operative hb/htc/plt values compared to the pre-operative values, and the rate of post-operative bleeding. Results: In our study, the amount of intraoperative hemorrhage and pre-operative hemoglobin, hematocrit, and platelet values compared to the post-operative values were found to be similar in both groups. Conclusion: Although TA has been shown to be effective on hemorrhage in benign gynecologic operations, menorrhagia, and postpartum hemorrhages, no significant effect on hemorrhage in conization with cervical TA administration has been demonstrated

Psychometric Properties of the German Version of the Pulmonary-Specific Quality-of-Life Scale in Lung Transplant Patients

The Pulmonary-Specific Quality-of-Life Scale (PQLS) is a validated self-report questionnaire assessing health-related quality of life (HRQoL) in patients with end-stage lung disease awaiting lung transplantation. The aim of our study was to evaluate the psychometric properties of the German version of the PQLS. One hundred and forty patients awaiting lung transplantation (55% men) with a median age of 53 years [Interquartile range (IQR) 13] answered the PQLS. A group of the participants (n = 43) was evaluated again 1 year later after transplantation. A confirmatory factor analysis (CFA) of the PQLS was conducted to test the three-factor structure of the PQLS. We examined the internal consistency of the scales using Cronbach’s α. Convergent validity was explored through correlations with generic measures of HRQoL [Short-Form 8 Health Survey (SF-8), 10-item quality of life (QoL) scale], measures of depression (nine-item Patient Health Questionnaire-Depression Scale), anxiety (Generalized Anxiety Scale), and measures of lung disease severity (supplemental oxygen use, stairway steps). In the group of 43 patients assessed before and after transplantation, sensitivity to change was explored. The CFA confirmed the three-factor model with an acceptable fit. The PQLS total and the three subscale scores “task interference,” “psychological,” and “physical” showed acceptable internal consistency. The PQLS and its subscales showed a significant negative correlation with the 10-item QoL measure and the physical component score of the SF-8, whereas the mental component score of the SF-8 showed a significant negative correlation only with the PQLS subscale “psychological.” Negative correlation was found due to the opposed alignment of the PQLS compared to the 10-item QoL and the SF-8. Symptoms of depression and anxiety were significantly and positively correlated with the subscale “psychological.” Measures of lung disease severity also exhibited a significant positive correlation with the subscales “task interference” and “physical” but not “psychological.” In patients 1 year after a successful transplantation, the PQLS scores were significantly reduced by 50%. The three-factor structure of the PQLS could be replicated using CFA. The results indicate good reliability, validity, and sensitivity to change of the German version of the PQLS

Baseline Dietary Restraint Predicts Negative Treatment Outcomes after 12 Months in Children and Adolescents with Obesity Participating in a Lifestyle Intervention

Objective: Current lifestyle interventions for children and adolescents with obesity often exclude patients with an eating pathology, leaving the impact of eating pathologies on treatment outcomes largely unconsidered. We investigated the predictive value of disordered eating symptoms on BMI z-score reduction in a sample of 111 German children and adolescents with overweight (90th percentile ≤ BMI < 97th percentile) and obesity (BMI > 97th percentile) aged 7–15 years in an outpatient lifestyle intervention program. Methods: We defined a BMI z-score reduction of more than 5% after 12 months as a successful outcome. Disordered eating symptoms (i.e., dietary restraint, emotional eating, external eating, and binge eating) were assessed at baseline with the Eating Pattern Inventory (EPI-C) and the “bulimia” scale of the Eating Disorder Inventory (EDI-2). Covariates were: baseline z-BMI, age, gender, and maternal education level. Results: Multiple regression analysis revealed that dietary restraint significantly predicted change in BMI z-scores between baseline and T1. Higher levels of dietary restraint were associated with a lower BMI z-score reduction between T0 and T1. To compare non-completers with completers on the 4 eating behavior scales, we used MANCOVA. At baseline, children who subsequently dropped out of the program prematurely showed significantly higher dietary restraint scores than children who completed the intervention, irrespectively of their gender, age, and BMI z-score at baseline and their mother’s education level. Discussion: Our results provide further evidence that the analysis of treatment processes in lifestyle intervention programs for children and adolescents with overweight and obesity should take into account a broader multidimensional approach including eating and dietary habits

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good