The OUTREACH study: oncologists of German university hospitals in rotation on a palliative care unit-evaluation of attitude and competence in palliative care and hospice.

PURPOSE: The effect of the duration of an educational rotation presented at a palliative care unit on the palliative care knowledge gain and the increase of palliative care self-efficacy expectations are unclear. METHODS: This national prospective multicenter pre-post survey conducted at twelve German University Comprehensive Cancer Centers prospectively enrolled physicians who were assigned to training rotations in specialized palliative care units for three, six, or twelve months. Palliative care knowledge [in %] and palliative care self-efficacy expectations [max. 57 points] were evaluated before and after the rotation with a validated questionnaire. RESULTS: From March 2018 to October 2020, questionnaires of 43 physicians were analyzed. Physicians participated in a 3- (n = 3), 6- (n = 21), or 12-month (n = 19) palliative care rotation after a median of 8 (0-19) professional years. The training background of rotating physicians covered a diverse spectrum of specialties; most frequently represented were medical oncology (n = 15), and anesthesiology (n = 11). After the rotation, median palliative care knowledge increased from 81.1% to 86.5% (p < .001), and median palliative care self-efficacy expectations scores increased from 38 to 50 points (p < .001). The effect of the 12-month rotation was not significantly greater than that of the 6-month rotation. CONCLUSION: An educational rotation presented in a specialized palliative care unit for at least six months significantly improves palliative care knowledge and palliative care self-efficacy expectations of physicians from various medical backgrounds.

[Therapeutic strategy for the treatment of non-infectious uveitis proposed by an expert panel]. / Avis d'experts pour le traitement des uvéites non infectieuses.

Conventional immunosuppressive drugs, anti-TNF alpha and other biotherapies used in clinical practice are capable of controlling non-infectious anterior uveitis, posterior uveitis and panuveitis. The present work has been led by a multidisciplinary panel of experts, internists, rheumatologists and ophthalmologists and is based on a review of the literature. In case of corticodependency or sight-threatening disease, conventional immunosuppressive drugs (methotrexate, azathioprine and mycophenolate mofetil) and/or anti-TNF alpha (adalimumab, infliximab) are used to achieve and maintain remission. Interferon is an efficient immunomodulatory treatment, as a second-line therapy, for some therapeutic indications (refractory macular edema, Behçet's vascularitis). Other biologics, especially tocilizumab, are showing promising results. Local treatments (corticosteroids, sirolimus etc.) are adjuvant therapies in case of unilateral inflammatory relapse. Therapeutic response must be evaluated precisely by clinical examination and repeated complementary investigations (laser flare photometry, multimodal imaging, perimetry, electroretinography measures).

OCD-like behavior is caused by dysfunction of thalamo-amygdala circuits and upregulated TrkB/ERK-MAPK signaling as a result of SPRED2 deficiency.

Obsessive-compulsive disorder (OCD) is a common neuropsychiatric disease affecting about 2% of the general population. It is characterized by persistent intrusive thoughts and repetitive ritualized behaviors. While gene variations, malfunction of cortico-striato-thalamo-cortical (CSTC) circuits, and dysregulated synaptic transmission have been implicated in the pathogenesis of OCD, the underlying mechanisms remain largely unknown. Here we show that OCD-like behavior in mice is caused by deficiency of SPRED2, a protein expressed in various brain regions and a potent inhibitor of Ras/ERK-MAPK signaling. Excessive self-grooming, reflecting OCD-like behavior in rodents, resulted in facial skin lesions in SPRED2 knockout (KO) mice. This was alleviated by treatment with the selective serotonin reuptake inhibitor fluoxetine. In addition to the previously suggested involvement of cortico-striatal circuits, electrophysiological measurements revealed altered transmission at thalamo-amygdala synapses and morphological differences in lateral amygdala neurons of SPRED2 KO mice. Changes in synaptic function were accompanied by dysregulated expression of various pre- and postsynaptic proteins in the amygdala. This was a result of altered gene transcription and triggered upstream by upregulated tropomyosin receptor kinase B (TrkB)/ERK-MAPK signaling in the amygdala of SPRED2 KO mice. Pathway overactivation was mediated by increased activity of TrkB, Ras, and ERK as a specific result of SPRED2 deficiency and not elicited by elevated brain-derived neurotrophic factor levels. Using the MEK inhibitor selumetinib, we suppressed TrkB/ERK-MAPK pathway activity in vivo and reduced OCD-like grooming in SPRED2 KO mice. Altogether, this study identifies SPRED2 as a promising new regulator, TrkB/ERK-MAPK signaling as a novel mediating mechanism, and thalamo-amygdala synapses as critical circuitry involved in the pathogenesis of OCD.

Longitudinal changes in adipose tissue of dairy cows from late pregnancy to lactation. Part 1: The adipokines apelin and resistin and their relationship to receptors linked with lipolysis.

The transition from pregnancy to lactation is characterized by major changes in glucose and adipose tissue metabolism. Anti- and prolipolytic pathways mediated via the hydroxycarboxylic acid receptors 1 (HCAR1) and 2 (HCAR2) and tumor necrosis factor-α receptor 1 (TNFR1), as well as the adipokines apelin and resistin, are likely involved in regulating these processes. This study aimed to determine the mRNA abundance of the aforementioned receptors in both subcutaneous and visceral adipose tissue, to characterize the adipokine concentrations in serum, and to test the effects of feeding diets with either high or low portions of concentrate and a concomitant niacin supplementation from late gestation to early lactation. Twenty pluriparous German Holstein cows were all kept on the same silage-based diet until d 42 antepartum, when they were allocated to 2 feeding groups: until d 1 antepartum, 10 animals each were assigned to either a high-concentrate (60:40 concentrate-to-roughage ratio) or a low-concentrate diet (30:70). Both groups were further subdivided into a control and a niacin group, the latter receiving 24 g/d of nicotinic acid from d -42 until 24. From d 1 to 24 postpartum, the concentrate portion was increased from 30 to 50% for all cows. Biopsies of subcutaneous (SCAT) and retroperitoneal adipose tissue (RPAT) were taken at d -42, 1, 21, and 100 relative to parturition. Blood samples were drawn along with the biopsies and on d -14, 3, 7, 14, and 42. The concentrations of the adipokines apelin and resistin in serum were measured via ELISA. The mRNA of the 3 receptors in AT was quantified as well as the protein abundance of HCAR2 by Western blot. The feeding regimen did not affect the variables examined. The concentrations of apelin remained fairly constant during the observation period, whereas the resistin concentrations increased toward parturition and decreased to precalving levels within 1 wk after calving. The mRNA abundance of HCAR1, HCAR2, and TNFR1 changed in SCAT and RPAT during the considered time period. For the HCAR2 protein, time-dependent changes were restricted to SCAT. The mRNA abundance of all receptors was greater in RPAT than in SCAT. The tissue-specific correlations observed between the receptors point to a link between these factors and may indicate different regulatory roles in the respective tissues. This study provides insight into the complex metabolic adaptations during the transition period and supports a differential regulation of lipolysis among SCAT and RPAT in dairy cows.

Reduced gray matter volume in the anterior cingulate, orbitofrontal cortex and thalamus as a function of mild depressive symptoms: a voxel-based morphometric analysis.

BACKGROUND: Studies investigating structural brain abnormalities in depression have typically employed a categorical rather than dimensional approach to depression [i.e., comparing subjects with Diagnostic and Statistical Manual of Mental Disorders (DSM)-defined major depressive disorder (MDD) v. healthy controls]. The National Institute of Mental Health, through their Research Domain Criteria initiative, has encouraged a dimensional approach to the study of psychopathology as opposed to an over-reliance on categorical (e.g., DSM-based) diagnostic approaches. Moreover, subthreshold levels of depressive symptoms (i.e., severity levels below DSM criteria) have been found to be associated with a range of negative outcomes, yet have been relatively neglected in neuroimaging research. METHOD: To examine the extent to which depressive symptoms--even at subclinical levels--are linearly related to gray matter volume reductions in theoretically important brain regions, we employed whole-brain voxel-based morphometry in a sample of 54 participants. RESULTS: The severity of mild depressive symptoms, even in a subclinical population, was associated with reduced gray matter volume in the orbitofrontal cortex, anterior cingulate, thalamus, superior temporal gyrus/temporal pole and superior frontal gyrus. A conjunction analysis revealed concordance across two separate measures of depression. CONCLUSIONS: Reduced gray matter volume in theoretically important brain regions can be observed even in a sample that does not meet DSM criteria for MDD, but who nevertheless report relatively elevated levels of depressive symptoms. Overall, these findings highlight the need for additional research using dimensional conceptual and analytic approaches, as well as further investigation of subclinical populations.

The traditional Chinese medical compound Rocaglamide protects nonmalignant primary cells from DNA damage-induced toxicity by inhibition of p53 expression.

One of the main obstacles of conventional anticancer therapy is the toxicity of chemotherapeutics to normal tissues. So far, clinical approaches that aim to specifically reduce chemotherapy-mediated toxicities are rare. Recently, a number of studies have demonstrated that herbal extracts derived from traditional Chinese medicine (TCM) may reduce chemotherapy-induced side effects. Thus, we screened a panel of published cancer-inhibiting TCM compounds for their chemoprotective potential and identified the phytochemical Rocaglamide (Roc-A) as a candidate. We show that Roc-A significantly reduces apoptotic cell death induced by DNA-damaging anticancer drugs in primary human and murine cells. Investigation of the molecular mechanism of Roc-A-mediated protection revealed that Roc-A specifically blocks DNA damage-induced upregulation of the transcription factor p53 by inhibiting its protein synthesis. The essential role of p53 in Roc-A-mediated protection was confirmed by siRNA knockdown of p53 and by comparison of the effects of Roc-A on chemoprotection of splenocytes isolated from wild-type and p53-deficient mice. Importantly, Roc-A did not protect p53-deficient or -mutated cancer cells. Our data suggest that Roc-A may be used as an adjuvant to reduce the side effects of chemotherapy in patients with p53-deficient or -mutated tumors.

[Medicine from the computer]. / Medizin aus dem Computer.

Small molecules can have a significant effect on human metabolic processes. Computational drug design aims at constructing specialized small molecules that selectively and efficiently address specific proteins. The basic ideas of computational molecular design are presented and it will be shown how a virtual protein can be computer designed. This virtual protein can be used to predict the binding affinity of given small molecules without having to synthesize them in a laboratory. Modern computational drug design goes far beyond the lock and key principle. Possible future developments are discussed and a current successful example of computational drug design in the field of painkiller medication is demonstrated.

Cortico-limbic responsiveness to high-calorie food images predicts weight status among women.

OBJECTIVES: Excessive weight gain and obesity are currently among the world's major threats to health. Women show significantly higher rates of obesity and eating disorders relative to men, but the factors contributing to these gender differences remain uncertain. We examined the correlations between regional brain responses to images of high-calorie versus low-calorie foods and self-reported motivational status, including ratings of general appetite, overeating propensity, state hunger and desire for specific foods. SUBJECTS: Thirty-eight healthy right-handed adults (22 male; 16 female) ages 18-45 participated. There were no differences between males and females with regard to age or body mass index (BMI). RESULTS: Overall, motivational status correlated significantly with activation within the amygdala, insula and orbitofrontal cortex. Regional activation was then used to predict BMI, an indicator of long-term food consumption and energy expenditure. The combined model was significant, accounting for 76% of the variance in BMI for women, whereas the same regions were not predictive of weight status among men. CONCLUSIONS: Findings suggest that long-term weight status is related to visual responsiveness to calorie-dense food imagery among women.

Effects of feeding a single or sequence of beta-adrenergic agonists on cull cow meat quality.

Sixty cull cows were implanted and assigned to four treatments: C = concentrate ration only; RH = supplemented with ractopmaine-HCl (8.33 mg/kg of feed) for 25 d; ZH = supplemented with zilpaterol-HCl (ZH) (200mg head (-1)d(-1)) for the last 20 d; and RH + ZH = supplemented with RH for 25 d followed by ZH for 20 d. All cows were fed a concentrate ration for 74 d. Infraspinatus steaks from cows supplemented with RH and/or ZH had lower (P<0.05) shear force than steaks from C cows. Longissimus (LM) steaks from the 6-8th rib section of ZH and RH+ZH cows had decreased (P<0.0001) desmin degradation at 10 and 21 d postmortem compared to steaks from C and RH cows. Collagen solubility of the LM was increased (P<0.05) by ZH and RH+ZH compared to C. There were no treatment differences in 12th rib LM tenderness when enhanced with calcium lactate. Color and sensory traits of meat from RH+ZH cows were not different from C but flavor intensity was greater and off-flavor less than for C cows.

[Is the pharmacological treatment of constipation in palliative care evidence based? : a systematic literature review]. / Ist die pharmakologische therapie der obstipation in der palliativmedizin evidenzbasiert? : eine systematische Literaturübersicht.

MATERIALS AND METHODS: To evaluate the evidence for clinically established pharmacological therapies for constipation in palliative care, a systematic literature review was performed in different databases (Cochrane Library, Embase, PubMed, Ovid MEDLINE, CINAHL), textbooks, and publications. RESULTS: Whereas 130 randomized controlled trials were found with patients outside of palliative care settings, only 10 controlled studies with patients in end-of-life situations were identified: three RCTs with methylnaltrexone and one with the combination of oxycodone and naloxone showed the effect and safety of opiate antagonists for patients who are not at risk of gastrointestinal perforation. There have been no studies which test methylnaltrexone against the optimization of therapy with conventional laxatives. Six other controlled studies of limited quality in design and execution and with only few participants tested naloxone, senna, lactulose, Co-danthramer, an Ayurvedic preparation (Misrakasneham), magnesium hydroxide, fluid paraffin, sodium picosulfate and docusate without finding statistically significant differences in efficacy or side effects. Most patients in these studies had cancer. Only case studies with few patients in palliative care were found for meglumine, neostigmine, and other substances mentioned above. CONCLUSION: Evidence on medical treatment of constipation in palliative care is sparse and guidelines have to refer to evidence from outside the palliative care setting and to expert opinions. Results from studies with other patient groups can only be transferred with limitations to very ill patients at the end of life who might have a higher risk for potential side effects such as gastrointestinal perforation in case of abdominal tumor manifestation. Therefore further studies are required to evaluate the medical treatment of multiple reasons for constipation in these patients. These studies should focus on feasibility, clinical relevance and quality of life. The English full text version of this article will be available in SpringerLink as of November 2012 (under "Supplemental").

Pycnogenol® effects on skin elasticity and hydration coincide with increased gene expressions of collagen type I and hyaluronic acid synthase in women.

INTRODUCTION AND OBJECTIVES: In recent years there has been an increasing interest in the use of nutritional supplements to benefit human skin. Molecular evidence substantiating such effects, however, is scarce. In the present study we investigated whether nutritional supplementation of women with the standardized pine bark extract Pycnogenol® will improve their cosmetic appearance and relate these effects to expression of corresponding molecular markers of their skin. MATERIALS AND METHODS: For this purpose 20 healthy postmenopausal women were supplemented with Pycnogenol for 12 weeks. Before, during and after supplementation, their skin condition was assessed (i) by employing non-invasive, biophysical methods including corneometry, cutometry, visioscan and ultrasound analyses and (ii) by taking biopsies and subsequent PCR for gene expression analyses related to extracellular matrix homeostasis. RESULTS: Pycnogenol supplementation was well tolerated in all volunteers. Pycnogenol significantly improved hydration and elasticity of skin. These effects were most pronounced in women presenting with dry skin conditions prior to the start of supplementation. The skin-physiological improvement was accompanied by a significant increase in the mRNA expression of hyaluronic acid synthase-1 (HAS-1), an enzyme critically involved in the synthesis of hyaluronic acid, and a noticeable increase in gene expression involved in collagen de novo synthesis. CONCLUSIONS: This study provides skin-physiological and for the first time molecular evidence that Pycnogenol supplementation benefits human skin by increasing skin hydration and skin elasticity. These effects are most likely due to an increased synthesis of extracellular matrix molecules such as hyaluronic acid and possibly collagen. Pycnogenol supplementation may thus be useful to counteract the clinical signs of skin aging.

[Compatibility of family and medical profession]. / Vereinbarkeit von Familie und ärztlichem Beruf.

The compatibility of family and profession is especially difficult for employees in medical professions because of shift work and overtime. It seems that in the future women are going to represent the majority of medical professionals. Hence, with the manifest lack of physicians social aspects will also play a bigger role in the choice of the place of employment. In most families the classic role model prevails although women are well educated and men also set a high value on the compatibility of family and profession and would like to take parental leave and work in flexible working hours. This represents a chance, especially for radiology.

Wogonin and related natural flavones are inhibitors of CDK9 that induce apoptosis in cancer cells by transcriptional suppression of Mcl-1.

The wogonin-containing herb Scutellaria baicalensis has successfully been used for curing various diseases in traditional Chinese medicine. Wogonin has been shown to induce apoptosis in different cancer cells and to suppress growth of human cancer xenografts in vivo. However, its direct targets remain unknown. In this study, we demonstrate for the first time that wogonin and structurally related natural flavones, for example, apigenin, chrysin and luteolin, are inhibitors of cyclin-dependent kinase 9 (CDK9) and block phosphorylation of the carboxy-terminal domain of RNA polymerase II at Ser(2). This effect leads to reduced RNA synthesis and subsequently rapid downregulation of the short-lived anti-apoptotic protein myeloid cell leukemia 1 (Mcl-1) resulting in apoptosis induction in cancer cells. We show that genetic inhibition of Mcl-1 or CDK9 expression by siRNA is sufficient to mimic flavone-induced apoptosis. Pull-down and in silico docking studies demonstrate that wogonin directly binds to CDK9, presumably to the ATP-binding pocket. In contrast, wogonin does not inhibit CDK2, CDK4 and CDK6 at doses that inhibit CDK9 activity. Furthermore, we show that wogonin preferentially inhibits CDK9 in malignant compared with normal lymphocytes. Thus, our study reveals a new mechanism of anti-cancer action of natural flavones and supports CDK9 as a therapeutic target in oncology.

[Intermixture of politics and science in the GDR. The investigation of deaths at the Department of Neurology and Psychiatry at Leipzig University under Müller-Hegemann in 1963]. / Vermischung von Politik und Wissenschaft in der DDR. Die Untersuchung der Todesfälle an der Leipziger Neurologisch-Psychiatrischen Universitätsklinik unter Müller-Hegemann 1963.

This study presents archival sources that shed light on a topic still being discussed by psychiatrists in East Germany: the death of two patients at the Leipzig Department that occurred in 1960 and 1962 under the directorship of Dietfried Müller-Hegemann. These fatalities were supposed to have been induced by obsolete psychotropic drugs and were associated with Ivan Pavlov's hypnotherapy. The incidents were investigated both by highest administrative bodies and the General State Prosecutor of the former GDR. Archival sources suggest that lower party organs and the ministerial administration tried to make use of the proceedings to bring about the downfall of the head of the Leipzig Department, who had become ideologically suspicious. However, the official General State Prosecutor's investigation ascertained that both Müller-Hegemann and Christa Kohler, head of the psychotherapeutic ward, were not to be held responsible. Although the SED Central Committee at first tried to influence the outcome on the basis of ideological reservations made by the university party organisation, it finally accepted and confirmed the judgment of the General State Prosecutor. Hence, in this case, the highest party bodies followed arguments that were the result of an independent investigation and were not influenced by an individual bias or ideological motives.

[Laser acupuncture for chronic back pain. A double-blind clinical study]. / Laserakupunktur bei chronischen Rückenschmerzen. Eine klinische Doppelblinduntersuchung.

BACKGROUND: The goal of this study was to evaluate the efficacy of laser acupuncture for the clinical picture of chronic back pain under everyday conditions using a randomized, double-blind, placebo-controlled study design. A further aim was to analyze to what extent placebo effects also influence the outcome of acupuncture under these conditions. PATIENTS AND METHODS: The study included male and female patients with chronic back pain (lasting longer than 6 months) aged between 30 and 77 years with a pain score of at least 5 on a visual analog scale. The main criterion was achieving alleviation of pain by at least 50% 3 months after the start of treatment. The assessment tools used were the Von Korff questionnaire supplemented by the FFbH, FABQ, and SF-12. In addition, the participants were questioned about whether they perceived anything during the treatment and how certain they were that they had received treatment with active or inactive lasers. RESULTS: A total of 111 patients were included in the study and were treated according to the randomization list in two groups each consisting of 51 subjects. The study was completed as scheduled by 102 participants. Analysis of the primary outcome measure, improvement of the pain score by more than 50% over baseline, revealed improvements in both treatment groups between the time points used for measurement. The placebo group exhibited better levels than the group that received laser treatment. No efficacy advantage of laser acupuncture over placebo treatment could be determined. CONCLUSION: It was possible to completely blind the acupuncture forms with the study design employed. Perhaps the consistent exclusion of nonspecific treatment effects contributed to this result. It cannot be ruled out that the effects of acupuncture are based on a strong placebo effect.

5-Methoxypsoralen plus ultraviolet (UV) A is superior to medium-dose UVA1 in the treatment of severe atopic dermatitis: a randomized crossover trial.

BACKGROUND: Ultraviolet (UV) A1 and psoralen plus UVA (PUVA) are effective treatment options for severe atopic dermatitis (AD); however, their relative efficacy has not yet been determined in a head-to-head study. OBJECTIVES: To compare UVA1 and oral 5-methoxypsoralen (5-MOP) plus UVA with respect to efficacy, tolerability and duration of response in patients with severe generalized AD. METHODS: Forty patients were included in this randomized observer-blinded crossover trial. The patients received either 15 exposures to medium-dose UVA1 as the first treatment and, in cases of relapse, another 15 exposures to 5-MOP plus UVA as the second treatment, or vice versa. All patients were followed until 12 months after discontinuation of the last treatment. The SCORAD score was determined by a blinded investigator at baseline, after 10 and 15 treatments each and during the follow-up period. In addition, all adverse events were recorded during the whole study period. RESULTS: Twenty-three patients completed the crossover treatment. Both phototherapies resulted in clinical improvement; however, PUVA reduced the baseline SCORAD score to a significantly greater extent than UVA1 (mean +/- SD 54.3 +/- 25.7% vs. 37.7 +/- 22.8%; P = 0.041). The median length of remission was 4 weeks (interquartile range 4-12) after UVA1 and 12 weeks (interquartile range 4-26) after PUVA therapy (P = 0.012). CONCLUSIONS: PUVA provides a better short- and long-term response than medium-dose UVA1 in patients with severe AD.

Rocaglamide sensitizes leukemic T cells to activation-induced cell death by differential regulation of CD95L and c-FLIP expression.

Drugs with tumor selectivity may have an important benefit in chemotherapies. We have previously shown that Rocaglamide(s), derived from the medicinal plant Aglaia, kills various leukemic cells through the mitochondrial apoptosis pathway with only minor toxicities to normal lymphocytes. Here, we show further that Rocaglamide preferentially promotes activation-induced cell death in malignant T cells by differential regulation of c-FLIP and CD95L expression. Rocaglamide enhances and also prolongs activation-induced JNK activation in malignant T cells leading to downregulation of c-FLIP but upregulation of CD95L expression. We also show that malignant T cells express a significantly higher amount of Bid - the molecular linker that bridges the receptor-mediated to the mitochondria-mediated apoptosis pathway. Conversely, a substantially lower amount of c-FLIP in response to T-cell stimulation compared to normal T cells is observed. This difference may provide a therapeutic window for cancer treatment. The effect of Rocaglamide on sensitization of activation-induced cell death in malignant T cells was further demonstrated in vivo in a mouse model. Our study demonstrates that Rocaglamide may be a potential anticancer drug that simultaneously targets both c-FLIP and CD95L expressions in tumor cells. This study may also provide a new clue to design a more efficient chemotherapy by using a combination of stimuli that engage the receptor-mediated and the mitochondria-mediated death pathway.

Diversity of essential oil glands of clary sage (Salvia sclarea L., Lamiaceae).

The Lamiaceae is rich in aromatic plant species. Most of these species produce and store essential oils in specialised epidermal oil glands, which are responsible for their specific flavour. Two types of glands producing essential oil and possessing different morphological structure can be found in Salvia sclarea: peltate and capitate glands. The content of single oil glands from different positions on the plant (corolla, calyx and leaf) were sampled using an SPME fibre and analysed by gas chromatography in order to study variability of the essential oil composition. It was found that the composition of terpenoids is quite variable within an individual plant. Capitate oil glands mainly produce three essential oil compounds: the monoterpenes linalool and linalyl acetate, and the diterpene sclareol. Peltate oil glands, however, accumulate noticeable concentrations of sesquiterpenes and an unknown compound (m/z = 354). Furthermore, the oil composition varies within each gland type according to the plant organ. Linalool and linalyl acetate are characteristic substances of flowers, whereas the sesquiterpenes occur in higher proportions in leaves. Even within one gland type on a single leaf, the chemical variability is exceedingly high.

Rat strain differences in startle gating-disruptive effects of apomorphine occur with both acoustic and visual prepulses.

Prepulse inhibition of startle (PPI) is an operational measure of sensorimotor gating that is impaired in schizophrenia and is disrupted in rats by dopamine (DA) agonists like apomorphine (APO). Using acoustic prepulses and acoustic startle pulses, previous studies have demonstrated heritable strain differences between Sprague Dawley (SD) and Long Evans (LE) rats in the sensitivity to the PPI-disruptive effects of APO. As PPI deficits in schizophrenia are evident with both uni- and cross-modal stimuli, we tested whether strain differences in the gating-disruptive effects of APO occur with a cross-modal visual and acoustic stimulus combination. APO caused a dose-dependent disruption of both acoustic and visual PPI in SD rats. Compared to LE rats, SD rats were more sensitive to the PPI-disruptive effects of APO with both acoustic and visual PPI. These findings suggest that SD vs. LE strain differences in PPI APO sensitivity are mediated outside of the auditory system, within higher circuitry that regulates or processes multi-modal information. The present findings provide further validation for this heritable model of impaired sensorimotor gating in schizophrenia, which can be detected across multiple sensory modalities.

[Application of (1)H MR spectroscopic imaging in radiation oncology: choline as a marker for determining the relative probability of tumor progression after radiation of glial brain tumors]. / Einsatz der (1)H-MR-spektroskopischen Bildgebung in der Strahlentherapie: Cholin als Marker für die Bestimmung der relativen Wahrscheinlichkeit eines Tumorprogresses nach Bestrahlung glialer Hirntumoren.

PURPOSE: To determine the relative signal intensity ratios of choline (Cho), phosphocreatine (CR) and N-acetyl-aspartate (NAA) in MR spectroscopic imaging (proton-MRSI) for differentiating progressive tumors (PT) from non-progressive tumors (nPT) in follow-up and treatment planning of gliomas. Threshold values to indicate the probability of a progressive tumor were also calculated. MATERIAL AND METHODS: Thirty-four patients with histologically proven gliomas showing a suspicious brain lesion in MRI after stereotactic radiotherapy were evaluated on a 1.5 Tesla unit (Magnetom Vision, Siemens, Erlangen, Germany) using 2D proton MRSI (repetition time/echo time = 1500/135 msec, PRESS; voxel size 9 x 9 x 15 mm (3)). A total of 274 spectra were analyzed (92 voxel were localized within the suspicious brain lesion). Relative signal intensities Cho, Cr and NAA were measured and their ability to discern between PT and nPT was assessed using the linear discrimination method, logistic regression, and the cross-validation method. PT and nPT were differentiated between on the basis of clinical course and follow-up by MRI, CT and positron emission tomography. RESULTS: The Cho parameter and the relative signal intensity ratios of Cr and NAA were most effective in differentiating between PT and nPT. The logistic regression method using the parameter ln(Cho/Cr) and ln(Cho/NAA) had the best predictive results in cross-validation. A sensitivity of 93.8 % and specificity of 85.7 % were achieved in the differentiation of PT from nPT by proton-MRSI. CONCLUSION: (1)H-MRSI has a high sensitivity and specificity for differentiating between therapy-related effects and the relapse of irradiated gliomas. This method allows for assessment of the probability of radiotherapy response or failure.