Wie wirksam und akzeptabel ist ein Selbstbehandlungsmanual mit begleitender Kurztherapie bei Bulimia nervosa?

Zusammenfassung Je 31 DSM-III-R-Bulimia-nervosa-Kranke erhielten 8 vierzehnt?gige Therapiestunden und ein Selbstbehandlungsmanual (angeleitete Selbstver?nderung, ASV) bzw. 16 w?chentliche Einzelsitzungen kognitiver Verhaltenstherapie (KVT). Beide Modalit?ten erzielten signifikante Besserungen sowohl der E?st?rung (nach Selbsteinsch?tzung und Interviewerinnenurteil) als auch von Depressivit?t, Selbstwertgefühl, Lebensqualit?t und Wissen über Ern?hrung, Gewicht und Figur. Sie unterschieden sich nicht signifikant bezüglich Abbrecherinnenquote, Teilnahme an der Nachuntersuchung und Zahl der Patientinnen, die eine Nachbehandlung in Anspruch nahmen. Zu keinem Me?zeitpunkt ergaben sich signifikante Unterschiede zwischen ASV- und KVT-Gruppe hinsichtlich Schweregrad der Bulimia nervosa, Beck-Depressionsinventarwert, Selbstwertgefühl und Lebensqualit?t. Ein signifikant h?herer Anteil der KVT-Gruppe hatte am Ende der Behandlung mindestens eine Woche lang keine bulimischen Attacken erlebt. Drei Monate nach dem Ende der Behandlung hatte die ASV-Gruppe in dieser Hinsicht aufgeholt und war den KVT-Patientinnen im Wissen über Ern?hrung, Gewicht und Figur überlegen. Lediglich die Gesamtwerte auf einem Bulimiefragebogen zeigten sowohl bei Therapieende als auch in der Nachuntersuchung günstigere Ergebnisse für KVT. In der Nützlichkeitsbeurteilung der Behandlung und Gesamtzufriedenheit mit ihr ergaben sich keine bedeutsamen Unterschiede. Angeleitete Selbstver?nderung mit einem Selbstbehandlungsmanual kann also ohne wesentliche Qualit?tseinbu?en Therapeut(inn)enzeit sparen.      

Mendelian Randomization Study on Amino Acid Metabolism Suggests Tyrosine as Causal Trait for Type 2 Diabetes

Circulating levels of branched-chain amino acids, glycine, or aromatic amino acids have been associated with risk of type 2 diabetes. However, whether those associations reflect causal relationships or are rather driven by early processes of disease development is unclear. We selected diabetes-related amino acid ratios based on metabolic network structures and investigated causal effects of these ratios and single amino acids on the risk of type 2 diabetes in two-sample Mendelian randomization studies. Selection of genetic instruments for amino acid traits relied on genome-wide association studies in a representative sub-cohort (up to 2265 participants) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study and public data from genome-wide association studies on single amino acids. For the selected instruments, outcome associations were drawn from the DIAGRAM (DIAbetes Genetics Replication And Meta-analysis, 74,124 cases and 824,006 controls) consortium. Mendelian randomization results indicate an inverse association for a per standard deviation increase in ln-transformed tyrosine/methionine ratio with type 2 diabetes (OR = 0.87 (0.81–0.93)). Multivariable Mendelian randomization revealed inverse association for higher log₁₀-transformed tyrosine levels with type 2 diabetes (OR = 0.19 (0.04–0.88)), independent of other amino acids. Tyrosine might be a causal trait for type 2 diabetes independent of other diabetes-associated amino acids.     

Short- and Branched-Chain Fatty Acids as Fecal Markers for Microbiota Activity in Vegans and Omnivores

A vegan diet could impact microbiota composition and bacterial metabolites like short-chain (SCFA) and branched-chain fatty acids (BCFA). The aim of this study was to compare the concentrations of SCFA, BCFA, ammonia, and fecal pH between vegans and omnivores. In this cross-sectional study (vegans n = 36; omnivores n = 36), microbiota composition, fecal SCFA, BCFA, and ammonia concentrations and pH were analyzed in complete stool samples. A random forest regression (RFR) was used to identify bacteria predicting SCFA/BCFA concentrations in vegans and omnivores. No significant differences in SCFA and BCFA concentrations were observed between vegans and omnivores. Fecal pH (p = 0.005) and ammonia concentration (p = 0.01) were significantly lower in vegans than in omnivores, while fiber intake was higher (p < 0.0001). Shannon diversity was higher in omnivores compared to vegans on species level (p = 0.04) only. In vegans, a cluster of Faecalibacterium prausnitzii, Prevotella copri, Dialister spp., and Eubacterium spp. was predictive for SCFA and BCFA concentrations. In omnivores, Bacteroides spp., Clostridium spp., Ruminococcus spp., and Prevotella copri were predictive. Though SCFA and BCFA did not differ between vegans and omnivores, the results of the RFR suggest that bacterial functionality may be adapted to varying nutrient availability in these diets.     

Phase 1/1b dose escalation and expansion study of BEZ235, a dual PI3K/mTOR inhibitor,in patients with advanced solid tumors including patients with advanced breast cancer

Cancer Chemotherapy and Pharmacology - To determine the maximum tolerated dose (MTD) of BEZ235, an oral inhibitor of class I PI3K and mTOR complexes 1 and 2. We performed a phase I/Ib, multicenter,...     

Long-Term Active Surveillance of Screening Detected Subsolid Nodules is a Safe Strategy to Reduce Overtreatment

Introduction

Lung cancer presenting as subsolid nodule (SSN) can show slow growth, hence treating SSN is controversial. Our aim was to determine the long-term outcome of subjects with unresected SSNs in lung cancer screening.

Deletion of the activating NK cell receptor NKG2D accelerates rejection of cardiac allografts

It has already been shown that neutralization of the activating NK cell receptor NKG2D in combination with co‐stimulation blockade prolongs graft survival of vascularized transplants. In order to clarify the underlying cellular mechanisms, we transplanted complete MHC‐disparate BALB/c‐derived cardiac grafts into C57BL/6 wildtypes or mice deficient for NKG2D (Klrk1^?/?). Although median survival was 8 days for both recipient groups, we detected already at day 5 posttransplantation significantly greater intragraft frequencies of NKp46⁺ NK cells in Klrk1^?/? recipients than in wildtypes. This was followed by a significantly greater infiltration of CD4⁺, but a lesser infiltration of CD8⁺ T cell frequencies. Contrary to published observations, co‐stimulation blockade with CTLA4‐Ig resulted in a significant acceleration of cardiac rejection by Klrk1^?/? recipients, and this result was confirmed by applying a neutralizing antibody against NKG2D to wildtypes. In both experimental setups, grafts derived from Klrk1^?/? recipients were characterized by significantly higher levels of interferon‐γ mRNA, and both CD4⁺ and CD8⁺ T cells displayed a greater capacity for degranulation and interferon‐γ production. In summary, our results clearly illustrate that NKG2D expression in the recipient is important for cardiac allograft survival, thus supporting the hypothesis that impairment of NK cells prevents the establishment of graft acceptance.     

Ultra-sensitive troponin I is an independent predictor of incident coronary heart disease in the general population

Troponins are sensitive markers of myocardial injury and predictive of cardiovascular events, but conventional assays fail to detect slightly elevated troponins in a considerable proportion of the general population. Using a novel ultrasensitive assay, we explored the relationship of troponin levels with the incidence of coronary heart disease (CHD) in a case-cohort sample (mean age 52.5 ± 0.2 years, 51.5% women) comprising 803 CHD cases and 1942 non-cases. Ultrasensitive troponin I was detectable in 99.9% of available case-cohort samples. In an age- and sex-adjusted model, individuals in the highest quartile of the troponin distribution had a more than threefold increased risk for CHD events compared to those in the bottom quartile [hazard ratio, HR, 3.11; 95% confidence interval (CI) 2.15–4.49]. In a model adjusting for cardiovascular risk factors including C-reactive protein, cystatin C and N-terminal pro brain natriuretic peptide, individuals in the highest troponin I quartile still showed a hazard ratio of 2.58 (95% CI 1.66–4.00) for incident CHD as compared to those in the lowest quartile. Ultrasensitive troponin I was detectable in almost all individuals of a study sample reflecting middle-aged to elderly European general population. Ultrasensitive troponin concentrations exhibit an independent, graded, positive relation with incident CHD.     

Evaluation of sample work-up methods and internal standards for the determination of catecholamines in urine by HPLC with electrochemical detection

Two sample work-up methods: (I) one consisting of adsorption of the catecholamines onto alumina followed by ion pair extraction and (II) another consisting of isolation by cation exchange and subsequent adsorption onto alumina, have been evaluated for the assay of urinary catecholamines by means of HPLC with electrochemical detection. With the aim of achieving high precision, two internal standards, i.e. dihydroxybenzylamine and epinine, have been compared. The results indicate that clean HPLC chromatograms are obtained with both work-up methods and that the highest precision (RSD < 4%) is achieved with method II and with epinine as internal standard, whereas the lowest precision is obtained with method I and with dihydroxybenzylamine.     

活体牙周膜有限元仿真的可行性研究

目的　通过现代有限元方法研究牙周膜上的静平衡应力状态。方法　提出了两种用于分析牙周膜应力状态的有限元方法，把牙周膜看做是整个下颌模型的一部分，通过有限元方法来处理仿真的牙齿并加载，来研究牙周膜对牙周组织的应力应变分布的作用，计算得到的静平衡应力和牙齿根吸收状态进行比较。结果　牙周膜的最大应力发生在接近最高点位置，在中跟位置附近存在局部最大应力，而牙周膜顶点区域的应力要大于牙周膜中根附近的局部最大应力。齿槽顶部的舌侧牙周膜部位可以发现静平衡应力。静平衡应力是和位置有关的，有静平衡应力的部位就会发生牙根吸收。结论　人类切牙和单根前臼齿一样，植入物会导致其牙周膜顶点附近静平衡应力的增长，这一点同之前的发现相一致。人类切牙根吸收经常作用于牙周膜的顶点部位。