74 research outputs found

    DAVOR MARIJAN, Borbe za Kupres 1942. Pohod proleterskih brigada i borbe za Kupres u ljeto 1942. godine., AGM - Biblioteka Povjesnica, Zagreb 1999., 279 str.

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    The \u3bc-opioid peptide (MOP) receptor is a member of the opioid receptor family and an important clinical target for analgesia. Measuring MOP receptor location and tracking its turnover traditionally used radiolabels or antibodies with attendant problems of utility of radiolabels in whole cells and poor antibody selectivity. To address these issues we have synthesized and characterised a novel ATTO488 based fluorescent Dermorphin analogue; [Cys(ATTO 488)8]Dermorphin-NH2 (DermATTO488). We initially assessed the binding profile of DermATTO488 in HEK cells expressing human MOP and CHO cells expressing human MOP, \u3bc-opioid peptide (DOP), \u3bc-opioid peptide (KOP) and Nociceptin/Orphanin FQ peptide (NOP) receptors using radioligand binding. Functional activity of the conjugated peptide was assessed by measuring (i) the ability of the ligand to engage G-protein by measuring the ability to stimulate GTP\u3b3[35S] binding and (ii) the ability to stimulate phosphorylation of ERK1/2. Receptor location was visualised using confocal scanning laser microscopy. Dermorphin and DermATTO488 bound to HEKMOP (pKi: 8.29 and 7.00; p0.05), CHOMOP (pKi: 9.26 and 8.12; p0.05) and CHODOP (pKi: 7.03 and 7.16; p0.05). Both ligands were inactive at KOP and NOP. Dermorphin and DermATTO488 stimulated the binding of GTP?[35S] with similar pEC50 (7.84 and 7.62; p0.05) and Emax (1.52 and 1.34fold p0.05) values. Moreover, Dermorphin and DermATTO488 produced a monophasic stimulation of ERK1/2 phosphorylation peaking at 5mins (6.98 and 7.64-fold; p0.05). Finally, in confocal microscopy DermATTO488 bound to recombinant MOP receptors on CHO and HEK cells in a concentration dependent manner that could be blocked by pre-incubation with unlabelled Dermorphin or Naloxone. Collectively, addition to ATTO488 to Dermorphin produced a ligand not dissimilar to Dermorphin; with ~10fold selectivity over DOP. This new ligand DermATTO488 retained functional activity and could be used to visualise MOP receptor location

    “It’s not something I chose you know”: making sense of pedophiles’ sexual interest in children and the impact on their psychosexual identity

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    Sexual interest in children is one of the most strongly predictive of the known risk factors for sexual reconviction. It is an important aspect of risk assessment to identify the presence of such interest, and an important task for treatment providers to address such a sexual interest where it is present. It has been argued that understanding pedophiles’ deviant sexual interest in children can enhance risk assessment, management, and treatment planning. This research study aims to explore the phenomenology of deviant sexual interest in children, the impact it has on pedophilic offenders’ identities, and their views on the treatability of that interest. The study used semistructured interviews and repertory grids to make sense of participants’ experiences. The results revealed three superordinate themes: “‘living’ with a deviant sexual interest,” “relational sexual self,” and “possible and feared sexual self.” The analysis unpacks these themes and repertory grid analysis is used to explore a subset of participants’ identities in more detail. The results reveal that there needs to be an acceptance from both client and therapist that their sexual interest in children may never go away. Through this acceptance, clients could work on enhancing sexual self-regulation, recognizing their triggers, and so managing their sexual thoughts, feelings, and behavior. Implications for treatment are also discussed

    Social Anxiety Modulates Subliminal Affective Priming

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    BACKGROUND: It is well established that there is anxiety-related variation between observers in the very earliest, pre-attentive stage of visual processing of images such as emotionally expressive faces, often leading to enhanced attention to threat in a variety of disorders and traits. Whether there is also variation in early-stage affective (i.e. valenced) responses resulting from such images, however, is not yet known. The present study used the subliminal affective priming paradigm to investigate whether people varying in trait social anxiety also differ in their affective responses to very briefly presented, emotionally expressive face images. METHODOLOGY/PRINCIPAL FINDINGS: Participants (n = 67) completed a subliminal affective priming task, in which briefly presented and smiling, neutral and angry faces were shown for 10 ms durations (below objective and subjective thresholds for visual discrimination), and immediately followed by a randomly selected Chinese character mask (2000 ms). Ratings of participants' liking for each Chinese character indicated the degree of valenced affective response made to the unseen emotive images. Participants' ratings of their liking for the Chinese characters were significantly influenced by the type of face image preceding them, with smiling faces generating more positive ratings than neutral and angry ones (F(2,128) = 3.107, p<0.05). Self-reported social anxiety was positively correlated with ratings of smiling relative to neutral-face primed characters (Pearson's r = .323, p<0.01). Individual variation in self-reported mood awareness was not associated with ratings. CONCLUSIONS: Trait social anxiety is associated with individual variation in affective responding, even in response to the earliest, pre-attentive stage of visual image processing. However, the fact that these priming effects are limited to smiling and not angry (i.e. threatening) images leads us to propose that the pre-attentive processes involved in generating the subliminal affective priming effect may be different from those that generate attentional biases in anxious individuals

    Hearing and dementia

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    Hearing deficits associated with cognitive impairment have attracted much recent interest, motivated by emerging evidence that impaired hearing is a risk factor for cognitive decline. However, dementia and hearing impairment present immense challenges in their own right, and their intersection in the auditory brain remains poorly understood and difficult to assess. Here, we outline a clinically oriented, symptom-based approach to the assessment of hearing in dementias, informed by recent progress in the clinical auditory neuroscience of these diseases. We consider the significance and interpretation of hearing loss and symptoms that point to a disorder of auditory cognition in patients with dementia. We identify key auditory characteristics of some important dementias and conclude with a bedside approach to assessing and managing auditory dysfunction in dementia

    Ageing, Health and Life Satisfaction of the Oldest Old: An Analysis for Germany

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    This analysis uses data from the German Socio-Economic Panel (GSOEP) and the Survey on Health, Ageing and Retirement in Europe (SHARE) to assess the effect of ageing and health on the life satisfaction of the oldest old (defined as 75 and older). We observe a U-shaped relationship between age and levels of life satisfaction for individuals aged between 16 and approximately 65. Thereafter, life satisfaction declines rapidly and the lowest absolute levels of life satisfaction are recorded for the oldest old. This decline is primarily attributable to low levels of perceived health. Once cohort effects are also controlled for, life satisfaction remains relatively constant across the lifespan

    Growth-inhibitory effects of the chemopreventive agent indole-3-carbinol are increased in combination with the polyamine putrescine in the SW480 colon tumour cell line

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    BACKGROUND: Many tumours undergo disregulation of polyamine homeostasis and upregulation of ornithine decarboxylase (ODC) activity, which can promote carcinogenesis. In animal models of colon carcinogenesis, inhibition of ODC activity by difluoromethylornithine (DFMO) has been shown to reduce the number and size of colon adenomas and carcinomas. Indole-3-carbinol (I3C) has shown promising chemopreventive activity against a range of human tumour cell types, but little is known about the effect of this agent on colon cell lines. Here, we investigated whether inhibition of ODC by I3C could contribute to a chemopreventive effect in colon cell lines. METHODS: Cell cycle progression and induction of apoptosis were assessed by flow cytometry. Ornithine decarboxylase activity was determined by liberation of CO(2 )from (14)C-labelled substrate, and polyamine levels were measured by HPLC. RESULTS: I3C inhibited proliferation of the human colon tumour cell lines HT29 and SW480, and of the normal tissue-derived HCEC line, and at higher concentrations induced apoptosis in SW480 cells. The agent also caused a decrease in ODC activity in a dose-dependent manner. While administration of exogenous putrescine reversed the growth-inhibitory effect of DFMO, it did not reverse the growth-inhibition following an I3C treatment, and in the case of the SW480 cell line, the effect was actually enhanced. In this cell line, combination treatment caused a slight increase in the proportion of cells in the G(2)/M phase of the cell cycle, and increased the proportion of cells undergoing necrosis, but did not predispose cells to apoptosis. Indole-3-carbinol also caused an increase in intracellular spermine levels, which was not modulated by putrescine co-administration. CONCLUSION: While indole-3-carbinol decreased ornithine decarboxylase activity in the colon cell lines, it appears unlikely that this constitutes a major mechanism by which the agent exerts its antiproliferative effect, although accumulation of spermine may cause cytotoxicity and contribute to cell death. The precise mechanism by which putrescine enhances the growth inhibitory effect of the agent remains to be elucidated, but does result in cells undergoing necrosis, possibly following accumulation in the G(2)/M phase of the cell cycle
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