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Besides a therapeutic target for type 2 diabetes, dipeptidyl peptidase 4 (DPP4) is an adipokine potentially upregulated in human obesity. We aimed to explore the role of adipocyte-derived DPP4 in diet-induced obesity and insulin resistance with an adipose tissue-specific knockout (AT-DPP4-KO) mouse. Wild-type and AT-DPP4-KO mice were fed for 24 wk with a high fat diet (HFD) and characterized for body weight, glucose tolerance, insulin sensitivity by hyperinsulinemic-euglycemic clamp, and body composition and hepatic fat content. Image and molecular biology analysis of inflammation, as well as adipokine secretion, was performed in AT by immunohistochemistry, Western blot, real-time-PCR, and ELISA. Incretin levels were determined by Luminex kits. Under HFD, AT-DPP4-KO displayed markedly reduced circulating DPP4 concentrations, proving AT as a relevant source. Independently of glucose-stimulated incretin hormones, AT-DPP4-KO had improved glucose tolerance and hepatic insulin sensitivity. AT-DPP4-KO displayed smaller adipocytes and increased anti-inflammatory markers. IGF binding protein 3 (IGFBP3) levels were lower in AT and serum, whereas free IGF1 was increased. The absence of adipose DPP4 triggers beneficial AT remodeling with decreased production of IGFBP3 during HFD, likely contributing to the observed, improved hepatic insulin sensitivity.

The mechanisms underlying improved insulin sensitivity after surgically-induced weight loss are still unclear. We monitored skeletal muscle metabolism in obese individuals before and over 52 weeks after metabolic surgery. Initial weight loss occurs in parallel with a decrease in muscle oxidative capacity and respiratory control ratio. Persistent elevation of intramyocellular lipid intermediates, likely resulting from unrestrained adipose tissue lipolysis, accompanies the lack of rapid changes in insulin sensitivity. Simultaneously, alterations in skeletal muscle expression of genes involved in calcium/lipid metabolism and mitochondrial function associate with subsequent distinct DNA methylation patterns at 52 weeks after surgery. Thus, initial unfavorable metabolic changes including insulin resistance of adipose tissue and skeletal muscle precede epigenetic modifications of genes involved in muscle energy metabolism and the long-term improvement of insulin sensitivity., Surgical weight-loss interventions improve insulin sensitivity via incompletely understood mechanisms. Here the authors assess skeletal muscle epigenetic changes in individuals with obesity following metabolic surgery and compare them with data from individuals without obesity.

The use of 3d printing technology seems to be a promising way for low cost prototyping, not only of mechanical, but also of optical components or systems. It is especially useful in applications where customized equipment repeatedly is subject to immediate destruction, as in experimental detonics and the like. Due to the nature of the 3D-printing process, there is a certain inner texture and therefore inhomogeneous optical behaviour to be taken into account, which also indicates mechanical anisotropy. Recent investigations are dedicated to quantification of optical properties of such printed bodies and derivation of corresponding optimization strategies for the printing process. Beside mounting, alignment and illumination means, also refractive and reflective elements are subject to investigation. The proposed measurement methods are based on an imaging nearfield scatterometer for combined volume and surface scatter measurements as proposed in previous papers. In continuation of last year’s paper on the use of near field imaging, which basically is a reflective shadowgraph method, for characterization of glossy surfaces like printed matter or laminated material, further developments are discussed. The device has been extended for observation of photoelasticity effects and therefore homogeneity of polarization behaviour. A refined experimental set-up is introduced. Variation of plane of focus and incident angle are used for separation of various the images of the layers of the surface under test, cross and parallel polarization techniques are applied. Practical examples from current research studies are included.

The paper is understood as a continuation of a series of papers on surface metrology for application in quality control of printed matter. A stereoscopic device for extremely rugged applications, especially in quality control in printing industry, is presented. The device developed is based on variable tilted delay elements, which allow the use of a single imaging sensor and robust definition of parallax shift. Variable orthogonal delay elements were already used for variation of plane of focus in surface inspection, as described in previous papers. The method can be applied for macroscopical as well as for microscopic imaging. Beside mechanical design issues, the theoretical description, geometrical-optical approaches, and the treatment of the dispersion problem are discussed. Experimental results are included.

Tunneling cracks driven by drying in a ceramic precursor confined between two glass plates represent a simple type of three-dimensional (3D) crack pattern. They arrange themselves via mutual unloading which causes some cracks to stop whereby the remaining ones get the right spacing for further propagation. By extending a 2D-model of self-driven propagation of crack arrays, a fracture mechanical bifurcation analysis for 3D-crack patterns based on calculating the post-critical contour of the alternating bifurcation mode has been developed. Shrinkage due to drying is replaced here by a simplified thermo-mechanical model based on an effective heat flow whose related temperature field and thermal stresses drive crack propagation. By means of the finite element method, the propagation velocity and the minimum spacing between the steady-state parallel tunnelling cracks are determined. Comparison of theory and experiment suggests that propagation may be non-stationary in these experiments. The observed relation between crack spacing and layer thickness, p ~ e2/3, follows from a scaling analysis.

In der letzten Dekade wurde bei insgesamt 16 Patientinnen, die an einer Autoimmunerkrankung litten, eine ungewohnliche amikrobielle intertriginose Dermatose beschrieben. Das klinische Charakteristikum war eine sterile pustulose Dermatitis v.a. in intertriginosen Regionen, die durch lokale oder meist systemische Steroidtherapie gebessert werden konnte. Histologisch imponierten subkorneale teilweise spongiforme neutrophile Pustulationen. Die vorliegende Arbeit beschreibt eine weitere Patientin mit dieser ungewohnlichen Dermatose. In einer Literaturubersicht soll anhand der bislang beschriebenen Falle versucht werden, eine Abgrenzung von bekannten pustulosen Dermatitiden durchzufuhren.

A large number of benign melanocytic nevi is the major risk factor for malignant melanoma (MM). In a multicenter case-control study, the number of common (CN) and clinically atypical (AN) nevi were counted separately at individual sites in 278 melanoma patients and 278 age- and gender-matched non-melanoma controls. Relative risk (RR) adjusted for age and sex was calculated. In men as well as women, the number of CN on the legs was the best predictor of overall melanoma risk. In men, RR for developing MM when > or = 1 AN were present on the trunk was 4-fold (vs. none). In women, presence of AN on the arms increased RR 9.5-fold. For men and women combined, after adjusting for age and gender, the RR for developing MM on the trunk and on the legs was best predicted by counts of CN at the respective body region. However, high counts of CN on the arms were associated with high melanoma risk on the legs (somewhat lower on the trunk). For AN, no site-specificity of melanoma risk was found. Our data suggest that nevus counts of the legs are the best predictor of overall melanoma risk if total body nevus counts are not feasible. Although high counts of CN on the trunk and legs are associated with a higher risk of developing MM at the respective site than at another site, our data do not unequivocally support a direct site-specific melanoma risk.

After a survey of conception, method, and selected results of an approach to the study of the contents of media agenda-setting, this chapter develops an approach termed argumentation analysis. This approach has been used in two studies on media contents concerning the tendencies with which the daily press covered and discussed the conflict of the coexistence of the public and commercial broadcasting systems in Germany. Argumentation analysis is a contribution to the further development of agenda-setting research because it measures important aspects of the stereotyping of issue-specific conflicts by journalists and the news media. With this approach, the hypothesis that the conflict structure of media issue coverage mediates the agenda-setting effect can be tested.

Epicardial adipose tissue (Epi) is a fat depot which is closely apposed on the myocardium. Several lines of evidence suggest that it is not only a lipid-storing depot, but also an active endocrine organ which secrets inflammatory cytokines and chemolines as suggested for other types of visceral fat.We selected guinea pigs which have been shown to expand Epi with age, to investigate the expansion and properties of Epi and its impact on cardiac structure and function in detail.The amount of epicardial fat increases rapidly with age and accumulates at the aortic arch. It extends over the anterior surface of both ventricles and along the anterior and posterior branches of the coronary arteries. It also expands within the epicardium. The pattern of cytokines released by Epi is altered with age showing an up- and down-regulation of a variety of the 120 cytokines analyzed. Most prominently changed are IGFBP-4 and TIMP-2, whereas the release of adiponectin is not modified by age.The amount of Epi is closely correlated to the amount of other types of visceral fat, to insulin resistance and other features of the metabolic syndrome, but also to cardiac hypertrophy and cardiac dysfunction. The data provide evidence that the guinea pig heart is a suitable model to analyze the interactions between Epi, heart vessels and muscle tissue. It allows identifying the influence of nutritional and metabolic alterations on the complexity of the network of locally released mediators for heart structure and function. A deeper understanding of this animal model may be helpful to analyze the interactions between Epi and the myocardium in humans-where the availability of tissue and the possibilities to modify nutritional and metabolic influences on heart are restricted-and the impact of Epi on cardiovascular risk.

Thin compressive layers sandwiched between thicker tensile layers in laminar ceramics can stop unstable cracks. As shown by Lange and co-workers, the arrested crack propagates stably through the compressive layer under increasing load until a critical load or threshold strength is reached. In 4-point flexural loading tests, cracks can bifurcate after entering into the compressive layer. This paper presents finite element simulations of bifurcated crack paths and threshold strength prediction in two-dimensional approximation. In rather good agreement with experiments the calculated threshold strength increases with compression and is higher with bifurcated cracks than with straight cracks, and higher with loading axis parallel to the laminar plane than normal to it.

Perianal streptococcal dermatitis (PSD) is a superficial bacterial infection usually with group A beta-hemolytic streptococci. PSD is often misdiagnosed for long periods and patients are subjected to treatments for a variety of differential diagnoses without success. We report a 4-year-old boy with PSD who presented to our clinic with guttate psoriasis for 2 reasons: first, to make dermatologists aware of PSD and second, to emphasize the necessity to examine patients, particularly pediatric patients, with guttate psoriasis very thoroughly and swab both the pharynx and perianal and/or perigenital areas even when they are, or seem to be, asymptomatic for bacterial infections. Once PSD has been diagnosed, systemic antibiotic therapy with penicillin, erythromycin, roxithromycin, or azithromycin (probably augmented by topical mupirocin ointment) should be the treatment of choice. Therapy should be monitored by posttreatment perianal and throat swabs as well as a urine analysis to monitor for poststreptococcal glomerulonephritis. (J Am Acad Dermatol 2000;42:885-7.)

Retiform hemangioendothelioma is a rare low-grade angiosarcoma of the skin. It shares some clinical characteristics with Kaposi's sarcoma, a tumor with known human herpesvirus 8 (HHV-8) association. We report a case of retiform hemangioendothelioma in which we detected HHV-8 DNA sequences.

Publisher Summary This chapter discusses the different methods employed collect body fluid from rats, such as blood, urine, pancreatic fluid, semen. Cardiac puncture is best used for terminal blood sampling because of the risk of cardiac tamponade. Puncturing of the jugular vein in the rat without anesthesia and incision of the skin is also possible. Blood can be collected from the saphenous vein. But this method has been modified for blood collection in the smaller laboratory animal. Urine can be collected by waving a small cotton ball moistened with diethyl ether under the nose of a rat. Micturation also may be stimulated by applying gentle but firm suprapubic pressure in rat. To collect pancreatic fluid a procedure is required that separates pancreatic from biliary secretion. Further, electroejaculation allows the collection of sperm by multiple samplings over time in the same male. It is also common for the studies to collect the sperm by surgically exposing the vas deferens or cauda epididymis.

Alkaptonuric ochronosis is a rare inborn metabolic disorder. Because of the deficient activity of the enzyme homogentisic acid oxidase, homogentisic acid accumulates in plasma, is deposited in various tissues and is excreted in large amounts in urine. Dark brown discoloration of urine on exposure to air or after addition of alkaline solution is characteristic. We describe two brothers with typical alkaptonuric ochronosis with dark urine, blue pigmentation of auricles and axillae, focal brown hyperpigmentation of sclerae, and anthropathy.

The search for causes of the renaissance of right-wing extremism and of the escalation of violence against foreigners in Germany since reunification not only refers to social and institutional conditions but also includes the mass media. With respect to the mass media, two hypotheses are discussed : first, media coverage of foreigners and of political asylum since the late 1980s could have created a social climate which encourages violence against foreigners. Second, the intensity and the sensationalism of television reporting particularly on the excesses of racial violence - as for example in Hoyerswerda (in 1991) or Rostock (in 1992) - play an important role in the dynamics of the escalation in acts of violence against foreigners. The objective of this article is to sketch the public and scholarly debates on these assumptions. Against this background, the discrepancy between general public assumptions and scientific evidence of media influence in this area is discussed

PURPOSE: : To compare, in 305 patients with advanced metastatic melanoma, temozolomide and dacarbazine (DTIC) in terms of overall survival, progression-free survival (PFS), objective response, and safety, and to assess health-related quality of life (QOL) and pharmacokinetics of both drugs and their metabolite, 5-(3-methyltriazen-1-yl)imidazole-4-carboximide (MTIC). PATIENTS AND METHODS: Patients were randomized to receive either oral temozolomide at a starting dosage of 200 mg/m2/d for 5 days every 28 days or intravenous (IV) DTIC at a starting dosage of 250 mg/m2/d for 5 days every 21 days. RESULTS: In the intent-to-treat population, median survival time was 7.7 months for patients treated with temozolomide and 6.4 months for those treated with DTIC (hazards ratio, 1.18; 95% confidence interval [CI], 0.92 to 1.52). Median PFS time was significantly longer in the temozolomide-treated group (1.9 months) than in the DTIC-treated group (1.5 months) (P = .012; hazards ratio, 1.37; 95% CI, 1.07 to 1.75). No major difference in drug safety was observed. Temozolomide was well tolerated and produced a noncumulative, transient myelosuppression late in the 28-day cycle. The most common nonhematologic toxicities were mild to moderate nausea and vomiting, which were easily managed. Temozolomide therapy improved health-related QOL; more patients showed improvement or maintenance of physical functioning at week 12. Systemic exposure (area under the curve) to the parent drug and the active metabolite, MTIC, was higher after treatment with oral temozolomide than after IV administration of DTIC. CONCLUSION: Temozolomide demonstrates efficacy equal to that of DTIC and is an oral alternative for patients with advanced metastatic melanoma.

Agenda setting is the most prominent concept in the analysis of media effects in election campaigns. In a secondary analysis, contingent conditions of political agenda setting (need for orientation, interpersonal communication, issue-specific sensitivity) were tested against direct exposure and content effects of newspapers and television. The results of a series of structural equation models consistently support the audience effects model of agenda setting. Media agenda setting in an election campaign was primarily restricted by media characteristics. For an `obtrusive' issue (social security), no media effect was found. Instead, issue sensitivity is a strong (indeed the only) predictor of awareness of this issue. For an `unobtrusive' issue (foreign affairs), media agenda setting is shaped by interpersonal political communication. Newspaper agenda setting is dependent upon a high degree, television agenda setting upon a low degree, of interpersonal communication about politics.

Different pigmentary characteristics as well as different parameters of sun exposure have previously been identified as risk factors for developing cutaneous melanoma. The aim of the present study was to identify significant risk factors, de- termine the related magnitude of their estimated relative risks, and define criteria for the detection of persons at risk. Five hundred thirteen melanoma patients and 498 controls matched for age and sex underwent a whole-body examination for the number and type of melanocytic lesions and were interviewed on ultraviolet exposure and other potential risk factors. The total number of common melanocytic nevi on all body sites represented the most important risk factor in multiple logistic regression analysis with a relative risk of 7.6 for subjects with more than 100 versus no more than 10 melanocytic nevi. Other significant independent risk factors were the number of atypical melanocytic nevi (relative risk, 6.1 for at least 5 melanocytic nevi versus none), the number of actinic lentigines (relative risk, 3.5 for many versus none), hair color, skin type, and reported melanocytic nevus growth. No single parameter of sun exposure was significantly related to melanoma risk in the multivariate analysis. Groups with an estimated relative risk between 1 and 121.0 were distinguished by considering common and atypical melanocytic nevi as well as actinic lentigines as the decisive criteria. In conclusion, even without any information on the case history, whole-body examination and diagnosis of pigmented lesions was found to be an effective strategy for identifying persons at risk of developing melanoma. Furthermore, clinical recognition of at least 5 atypical melanocytic nevi without histologic examination is a key for identifying subjects at high risk.

SummaryIn malignant melanoma as in many other malignancies the process of tumorigenesis and progression appears to result from the accumulation of multiple genetic lesions. Linkage analys