Behaviour patterns preceding a railway suicide: Explorative study of German Federal Police officers' experiences

<p>Abstract</p> <p>Background</p> <p>Constant high-level numbers of railway suicides indicate that prevention strategies against railway suicides are urgently needed. The main question of the present study was whether pre-crash railway suicide behaviour can be identified, using German Federal Police officers experience with suicidal events in railway related environments.</p> <p>Methods</p> <p>To collect information on pre-crash railway suicide behaviour, a questionnaire was used and made available on the German Federal Police intranet. A total of 202 subjects (mean age: 41 years, sex: 84.9% male) were included in the analysis. Multivariate logistic regression analyses were performed to predict the prevention of suicide (first model) or demand for counselling (second model) as outcomes. Sex, age, years of service, number of experienced suicides, suicides personally observed, information on suicides obtained from witnesses and finally either counselling/debriefing (first model) or whether officers had prevented a suicide (second model) were used as predictors.</p> <p>Results</p> <p>A considerable proportion of police officers reported behavioural patterns preceding a suicide. Half of them observed the dropping or leaving behind of personal belongings or the avoidance of eye contact, more than a third erratic gesture, mimic or movement. Erratic communication patterns and general confusion were each reported by about one quarter. One fifth indicated the influence of alcohol. Less frequently observed behaviour was aimlessly wandering (14.3%) and out of the ordinary clothing (4%). About one third of all railway suicide victims committed suicide in stations. Of those, 70% had chosen an eminent spot. The multivariate logistic regression model using prevented suicides as the outcome identified the number of suicides experienced, counselling/debriefing and having personally observed a suicide as variables with significant impact. The model using counselling/debriefing as the outcome identified age and having prevented a suicide as variables with a significant association.</p> <p>Conclusions</p> <p>Our results provide evidence that railway suicides are preceded by identifiable behavioural patterns. This emphasizes the importance of educational efforts, taking into account the knowledge and skills of experienced police officers.</p

In Vivo Regulation of Glycogen Synthase Kinase-3β (GSK3β) by Serotonergic Activity in Mouse Brain

The goal of this study was to determine if serotonergic activity, which is impaired in depression, regulates the phosphorylation of glycogen synthase kinase-3β (GSK3β) in mouse brain in vivo. GSK3β is inhibited by phosphorylation on serine-9 and is a target of the mood stabilizer lithium. Following administration to mice of d-fenfluramine to stimulate serotonin (5HT) release and reduce its reuptake, and clorgyline to inhibit 5HT catabolism, levels of phospho-Ser9-GSK3β were 300–400% of control levels in the prefrontal cortex, hippocampus, and striatum. Treatment with monoamine reuptake inhibitors fluoxetine and imipramine also increased the level of phospho-Ser9-GSK3β. Using receptor selective agonists and antagonists, 5HT1A receptors were found to mediate increases, and 5HT2 receptors decreases, in phospho-Ser9-GSK3β levels. This indicates that serotonergic regulation of the phosphorylation of GSK3β is achieved by a balance between the opposing actions of these 5HT receptor subtypes. These findings demonstrate for the first time that serotonergic activity regulates the phosphorylation of GSK3β and show that this regulation occurs in mammalian brain in vivo. These results raise the possibility that impaired inhibitory control of GSK3β may occur in conditions where serotonergic activity is dysregulated, such as in mood disorders

Clostridium difficile ribotypes in Austria: a multicenter, hospital-based survey

A prospective, noninterventional survey was conducted among Clostridium difficile positive patients identified in the time period of July until October 2012 in 18 hospitals distributed across all nine Austrian provinces. Participating hospitals were asked to send stool samples or isolates from ten successive patients with C.difficile infection to the National Clostridium difficile Reference Laboratory at the Austrian Agency for Health and Food Safety for PCR-ribotyping and in vitro susceptibility testing. A total of 171 eligible patients were identified, including 73 patients with toxin-positive stool specimens and 98 patients from which C. difficile isolates were provided. Of the 159 patients with known age, 127 (74.3 %) were 65 years or older, the median age was 76 years (range: 9–97 years), and the male to female ratio 2.2. Among these patients, 73 % had health care-associated and 20 % community-acquired C. difficile infection (indeterminable 7 %). The all-cause, 30-day mortality was 8.8 % (15/171). Stool samples yielded 46 different PCR-ribotypes, of which ribotypes 027 (20 %), 014 (15.8 %), 053 (10.5 %), 078 (5.3 %), and 002 (4.7 %) were the five most prevalent. Ribotype 027 was found only in the provinces Vienna, Burgenland, and Lower Austria. Severe outcome of C. difficile infection was found to be associated with ribotype 053 (prevalence ratio: 3.04; 95 % CI: 1.24, 7.44), not with the so-called hypervirulent ribotypes 027 and 078. All 027 and 053 isolates exhibited in vitro resistance against moxifloxacin. Fluoroquinolone use in the health care setting must be considered as a factor favoring the spread of these fluoroquinolone resistant C. difficile clones

Fine sediment reduces vertical migrations of Gammarus pulex (Crustacea: Amphipoda) in response to surface water loss

Surface and subsurface sediments in river ecosystems are recognized as refuges that may promote invertebrate survival during disturbances such as floods and streambed drying. Refuge use is spatiotemporally variable, with environmental factors including substrate composition, in particular the proportion of fine sediment (FS), affecting the ability of organisms to move through interstitial spaces. We conducted a laboratory experiment to examine the effects of FS on the movement of Gammarus pulex Linnaeus (Crustacea: Amphipoda) into subsurface sediments in response to surface water loss. We hypothesized that increasing volumes of FS would impede and ultimately prevent individuals from migrating into the sediments. To test this hypothesis, the proportion of FS (1–2 mm diameter) present within an open gravel matrix (4–16 mm diameter) was varied from 10 to 20% by volume in 2.5% increments. Under control conditions (0% FS), 93% of individuals moved into subsurface sediments as the water level was reduced. The proportion of individuals moving into the subsurface decreased to 74% at 10% FS, and at 20% FS no individuals entered the sediments, supporting our hypothesis. These results demonstrate the importance of reducing FS inputs into river ecosystems and restoring FS-clogged riverbeds, to promote refuge use during increasingly common instream disturbances

Elevated c-Src is linked to altered cell–matrix adhesion rather than proliferation in KM12C human colorectal cancer cells

Elevated expression and/or activity of c-Src, the prototype of the Src family of protein tyrosine kinases, is associated with the development of human colon cancer. However, despite the known pleiotropic effects of these kinases in promoting (a) cell growth downstream of growth factor receptors, and (b) the dynamic regulation of integrin adhesions in fibroblast model systems, their precise role in epithelial cancer cells is unknown. Here we addressed whether elevated expression and activity of cellular Src alters cell proliferation and/or cell–matrix adhesion in cancer cells from the Fidler model of colorectal metastasis. Although elevated Src correlates with ability to metastasise to the liver after intrasplenic injection, we found that this was not linked to enhanced growth, either in vitro or in vivo as sub-cutaneous tumours. However, elevated Src was associated with enhanced attachment to extracellular matrix. In addition, adhesion to fibronectin, was suppressed by agents that inhibited Src activity, while enforced elevation of Src in non-metastatic cells was sufficient to stimulate adhesion to fibronectin and enhanced assembly of adhesion complexes, without influencing cell growth. Thus, we conclude that one role of elevated Src in human colon cancer cells is to modulate integrin-dependent cell–matrix attachment and formation of adhesion structures, which may, in turn, influence cell motility and integrin-dependent cellular responses

Common extensor origin release in recalcitrant lateral epicondylitis - role justified?

The aim of our study was to analyse the efficacy of operative management in recalcitrant lateral epicondylitis of elbow. Forty patients included in this study were referred by general practitioners with a diagnosis of tennis elbow to the orthopaedic department at a district general hospital over a five year period. All had two or more steroid injections at the tender spot, without permanent relief of pain. All subsequently underwent simple fasciotomy of the extensor origin. Of forty patients thirty five had improvement in pain and function, two had persistent symptoms and three did not perceive any improvement. Twenty five had excellent, ten had well, two had fair and three had poor outcomes (recurrent problem; pain at rest and night). Two patients underwent revision surgery. Majority of the patients had improvement in pain and function following operative treatment. In this study, an extensor fasciotomy was demonstrated to be an effective treatment for refractory chronic lateral epicondylitis; however, further studies are warranted

P-hydroxyphenylpyruvate, an intermediate of the Phe/Tyr catabolism, improves mitochondrial oxidative metabolism under stressing conditions and prolongs survival in rats subjected to profound hemorrhagic shock

The aim of this study was to test the effect of a small volume administration of p-hydroxyphenylpyruvate (pHPP) in a rat model of profound hemorrhagic shock and to assess a possible metabolic mechanism of action of the compound. The results obtained show that hemorrhaged rats treated with 2-4% of the estimated blood volume of pHPP survived significantly longer (p<0.001) than rats treated with vehicle. In vitro analysis on cultured EA.hy 926 cells demonstrated that pHPP improved cell growth rate and promoted cell survival under stressing conditions. Moreover, pHPP stimulated mitochondria-related respiration under ATP-synthesizing conditions and exhibited antioxidant activity toward mitochondria-generated reactive oxygen species. The compound effects reported in the in vitro and in vivo analyses were obtained in the same millimolar concentration range. These data disclose pHPP as an efficient energetic substrates-supplier to the mitochondrial respiratory chain as well as an antioxidant supporting the view that the compound warrants further evaluation as a therapeutic agent. © 2014 Cotoia et al

Quantitative cross-species extrapolation between humans and fish: The case of the anti-depressant fluoxetine

This article has been made available through the Brunel Open Access Publishing Fund.Fish are an important model for the pharmacological and toxicological characterization of human pharmaceuticals in drug discovery, drug safety assessment and environmental toxicology. However, do fish respond to pharmaceuticals as humans do? To address this question, we provide a novel quantitative cross-species extrapolation approach (qCSE) based on the hypothesis that similar plasma concentrations of pharmaceuticals cause comparable target-mediated effects in both humans and fish at similar level of biological organization (Read-Across Hypothesis). To validate this hypothesis, the behavioural effects of the anti-depressant drug fluoxetine on the fish model fathead minnow (Pimephales promelas) were used as test case. Fish were exposed for 28 days to a range of measured water concentrations of fluoxetine (0.1, 1.0, 8.0, 16, 32, 64 μg/L) to produce plasma concentrations below, equal and above the range of Human Therapeutic Plasma Concentrations (HTPCs). Fluoxetine and its metabolite, norfluoxetine, were quantified in the plasma of individual fish and linked to behavioural anxiety-related endpoints. The minimum drug plasma concentrations that elicited anxiolytic responses in fish were above the upper value of the HTPC range, whereas no effects were observed at plasma concentrations below the HTPCs. In vivo metabolism of fluoxetine in humans and fish was similar, and displayed bi-phasic concentration-dependent kinetics driven by the auto-inhibitory dynamics and saturation of the enzymes that convert fluoxetine into norfluoxetine. The sensitivity of fish to fluoxetine was not so dissimilar from that of patients affected by general anxiety disorders. These results represent the first direct evidence of measured internal dose response effect of a pharmaceutical in fish, hence validating the Read-Across hypothesis applied to fluoxetine. Overall, this study demonstrates that the qCSE approach, anchored to internal drug concentrations, is a powerful tool to guide the assessment of the sensitivity of fish to pharmaceuticals, and strengthens the translational power of the cross-species extrapolation

First report of venereal and vertical transmission of canine leishmaniosis from naturally infected dogs in Germany

<p>Abstract</p> <p>Background</p> <p>Canine leishmaniosis (CanL) is a zoonotic disease caused by <it>Leishmania (L.) infantum</it>. It is endemic to several tropical and subtropical countries but also to the Mediterranean region. It is transmitted by phlebotomine sandflies but occasional non-vector transmissions have been reported, including vertical and horizontal transmission.</p> <p>Findings</p> <p>The authors report a case of CanL in a female boxer dog from Dusseldorf, Germany, that had never been in an endemic region. A serum sample from the bitch was tested positive for antibodies against <it>Leishmania </it>(IFAT 1:2,000, ELISA 72). The bitch had whelped three litters, and one puppy from the third litter was also found to be seropositive for <it>Leishmania </it>antibodies (IFAT 1:4,000, ELISA 78).</p> <p>Conclusions</p> <p>Up to now, despite intensive searching, the occurrence of sandflies could not be proved in the bitch's region of origin. Thus, vertical and horizontal transmission are to be discussed as possible ways of infection. This may be the first report of venereal and vertical transmission of <it>L. infantum </it>in naturally infected dogs in Germany.</p