As chronic stress is a significant risk factor for several cardiovascular disorders, this study investigated the hypothesis that long-term stress produced by crowding may lead to alterations in nitric oxide (NO) production and NO-dependent relaxation in the course of stress, resulting in endothelial dysfunction and hypertension in Wistar-Kyoto (WKY) rats. For this purpose, male WKY rats were divided into control (480 cm2/rat, four rats/cage, n = 8) and crowded (200 cm2/rat, five rats/cage, n = 10) groups for 8 or 12 weeks. Vasorelaxation was evaluated in vitro as a response to acetylcholine (ACh) of femoral arteries pre-contracted by serotonin, before and after NO synthase inhibition (N (G)-nitro-l-arginine methyl ester, 300 μmol/l). Crowding increased plasma corticosterone concentration but failed to affect blood pressure (determined by tail-cuff plethysmography) of rats. NO production was unchanged in the hypothalamus and left ventricle of both stressed groups; however it was significantly elevated in the aorta. Maximal ACh-induced relaxation was elevated significantly after 8-week stress, but reduced after 12 weeks. Stress elevated the NO-dependent component and reduced the NO-independent component of ACh-induced relaxation in both crowded groups. However, a reduction in the NO-independent component was more pronounced after 12-week versus 8-week stress. In conclusion, elevated endothelium-dependent relaxation was observed after 8-week stress, while the extension of stress exposure resulted in a reduction in arterial relaxation associated with a more pronounced decrease of its NO-independent component. Thus, elevation of the NO-dependent component of relaxation can be considered as an adaptation mechanism, and impairment of NO-independent relaxation might be the initial step in chronic stress-induced cardiovascular disorders.

High recurrence rate of the middle ear cholesteatoma requires regular postoperative follow-up. This study evaluated data from the patients investigated with DW MRI to ascertain (1) the strength of the technique in detecting primary, and residual recurrent cholesteatoma, and (2) its accuracy in differentiating cholesteatoma from postoperative tissue changes. The diagnostic accuracy of two different DW imaging (EPI and non-EPI) techniques was evaluated. The data have been collected prospectively from 33 consecutive patients with either primary cholesteatoma, or with suspicious symptoms for potential cholesteatoma recurrence. The findings from non-EPI (HASTE) DW MR and EPI DW MR images were blindly compared with those obtained during a primary or secondary surgery. Preoperative non-EPI (HASTE) DWI pointed to a cholesteatoma in 25 out of 33 patients. In this subgroup, cholesteatoma were confirmed also by the surgery. In five cases, the non-EPI (HASTE) DWI did not show a cholesteatoma in the temporal bone, which agreed with the surgical findings. Three misclassifications were made by non-EPI (HASTE) DWI, all in the subgroup of patients indicated for primary surgery. The resulting pooled sensitivity of non-EPI (HASTE) DW imaging for diagnosing cholesteatoma in our study amounted to 96.15% (95% confidence interval (CI) 80.36-99.9), specificity was 71.43% (95% CI 29.04-96.33). Positive predictive value was 92.59% (95% CI 75.71-99.09) and negative predictive value 83.33% (95% CI 35.88-99.58). In conclusion, we recommend the non-EPI (HASTE) DW MRI as a valid method for diagnosing cholesteatoma and follow-up after cholesteatoma surgery.

The prerequisite for a successful clinical use of autologous adipose-tissue-derived cells is the highest possible regenerative potential of the applied cell population, the stromal vascular fraction (SVF). Current isolation methods depend on high enzyme concentration, lysis buffer, long incubation steps and mechanical stress, resulting in single cell dissociation. The aim of the study was to limit cell manipulation and obtain a derivative comprising therapeutic cells (microtissue-SVF) without dissociation from their natural extracellular matrix, by employing a gentle good manufacturing practice (GMP)-grade isolation. The microtissue-SVF yielded larger numbers of viable cells as compared to the improved standard-SVF, both with low enzyme concentration and minimal dead cell content. It comprised stromal tissue compounds (collagen, glycosaminoglycans, fibroblasts), capillaries and vessel structures (CD31 + , smooth muscle actin + ). A broad range of cell types was identified by surface-marker characterisation, including mesenchymal, haematopoietic, pericytic, blood and lymphatic vascular and epithelial cells. Subpopulations such as supra-adventitial adipose-derived stromal/stem cells and endothelial progenitor cells were significantly more abundant in the microtissue-SVF, corroborated by significantly higher potency for angiogenic tube-like structure formation in vitro. The microtissue-SVF showed the characteristic phenotype and tri-lineage mesenchymal differentiation potential in vitro and an immunomodulatory and pro-angiogenic secretome. In vivo implantation of the microtissue-SVF combined with fat demonstrated successful graft integration in nude mice. The present study demonstrated a fast and gentle isolation by minor manipulation of liposuction material, achieving a therapeutically relevant cell population with high vascularisation potential and immunomodulatory properties still embedded in a fraction of its original matrix.

This study investigated the influence of chronic crowding stress on nitric oxide (NO) production, vascular function and oxidative status in young Wistar-Kyoto (WKY), borderline hypertensive (BHR) and spontaneously hypertensive (SHR) female rats. Five-week old rats were exposed to crowding for two weeks. Crowding elevated plasma corticosterone (P < 0.05) and accelerated BP (P < 0.01 versus basal) only in BHR. NO production and superoxide concentration were significantly higher in the aortas of control BHR and SHR versus WKY. Total acetylcholine (ACh)-induced relaxation in the femoral artery was reduced in control SHR versus WKY and BHR, and stress did not affect it significantly in any genotype. The attenuation of ACh-induced relaxation in SHR versus WKY was associated with reduction of its NO-independent component. Crowding elevated NO production in all strains investigated but superoxide concentration was increased only in WKY, which resulted in reduced NO-dependent relaxation in WKY. In crowded BHR and SHR, superoxide concentration was either unchanged or reduced, respectively, but NO-dependent relaxation was unchanged in both BHR and SHR versus their respective control group. This study points to genotype-related differences in stress vulnerability in young female rats. The most pronounced negative influence of stress was observed in BHR despite preserved endothelial function.

In his manifesto for the `strong programme' in the sociology of scientific knowledge (SSK), David Bloor expressed its diametric opposition to the `mentalist' or `teleological' model of `rationalist' philosophers, saying that `there can be no doubt that if the teleological model is true then the strong programme is false'. The `teleological' point of view can be seen embodied in the mentalism of contemporary interdisciplinary research under the heading of `cognitive science', and particularly in computer models of artificial intelligence (AI). In this sense, the enterprise of cognitive science, encompassing psychology, linguistics, philosophy, neuroscience and AI constitutes a massive empirical challenge to SSK's claims for the social causation of belief. Of particular interest is the AI work on scientific discovery as a special case of heuristic problem solving: the possibility of computers autonomously making fundamental scientific discoveries is providing dramatic confirmation of the `teleological' view that there are principles of rationality and a `scientific method' which are independent of social factors.

The present study was designed to evaluate the effects of vascular aging in juvenescence on endothelial function in femoral arteries and to assess differences between normotensive and hypertensive rats. The aim of the study was to determine if age affected nitric oxide- (NO-) mediated relaxations in normotensive and hypertensive rats. Juvenile (7-week-old) and young adult (22-week-old) male Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were used in this study. Femoral artery (FA) reactivity was determined by wire myograph and NO synthase activity by conversion of [3H]-L-arginine. During juvenescence systolic blood pressure (tail-cuff) increased significantly only in SHR, while NO synthesis decreased significantly in both strains. Endothelium-dependent relaxations to acetylcholine were reduced in the FA of SHR compared to age-matched WKY at both ages, yet these parameters were unchanged in adult rats compared with juvenile animals. The NO-dependent component of vasorelaxation was markedly reduced, whereas the NO-independent component was increased in adult compared to juvenile rats in both strains. The endothelial dysfunction in SHR at both ages was associated with reduction of NO-independent mechanisms. In conclusion, aging in early periods of life was associated with reduction of vascular NO production and bioavailability in both strains investigated. This reduction was however fully compensated by accentuation of NO-independent mechanisms.

One-step LINAC-based SRS with a single dose 35.0 Gy is a method to treat middle-stage posterior uveal melanoma and to preserve the eye globe or as the first step of combined methods: irradiation before endoresection or cyclectomy.

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