14 research outputs found

    Preventing Suicide in Prisons, Part I Recommendations fromthe International Association for Suicide Prevention Task Force on Suicide in Prisons

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    Abstract. In 2000 the Department of Mental Health of the World Health Organization (WHO) published a guide named Preventing Suicide. A Resource for Prison Officers as part of the WHO worldwide initiative for the prevention of suicide. In 2007 there are new epidemiological data on prison suicide, a more detailed discussion of risk factors accounting for the generally higher rate of suicide in correctional settings in comparison to the general population, and several strategies for developing screening instruments. As a first step, this paper presents an update of the WHO guide by the Task Force on Suicide in Prisons, created by the International Association for Suicide Prevention. A second paper, by the same Task Force, will present some international comparisons of suicide prevention services in correctional facilities

    DN interaction from meson exchange

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    A model of the DN interaction is presented which is developed in close analogy to the meson-exchange KbarN potential of the Juelich group utilizing SU(4) symmetry constraints. The main ingredients of the interaction are provided by vector meson (rho, omega) exchange and higher-order box diagrams involving D*N, D\Delta, and D*\Delta intermediate states. The coupling of DN to the pi-Lambda_c and pi-Sigma_c channels is taken into account. The interaction model generates the Lambda_c(2595) resonance dynamically as a DN quasi-bound state. Results for DN total and differential cross sections are presented and compared with predictions of an interaction model that is based on the leading-order Weinberg-Tomozawa term. Some features of the Lambda_c(2595) resonance are discussed and the role of the near-by pi-Sigma_c threshold is emphasized. Selected predictions of the orginal KbarN model are reported too. Specifically, it is pointed out that the model generates two poles in the partial wave corresponding to the Lambda(1405) resonance.Comment: 14 pages, 8 figure

    A novel agent with histone deacetylase inhibitory activity attenuates neointimal hyperplasia

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    Purpose: Neointimal hyperplasia (NIH), a pathophysiological event identified in bypass graft and stent re-stenosis, is characterised by aberrant vascular smooth muscle cell (VSMC) migration and proliferation. Recent evidence identifies histone deacetylase modulation as a regulator of VSMC proliferation and migration and a potential therapeutic target in the treatment of NIH. The purpose of our study was to determine the in vitro and in vivo potential of a novel agent, MCT-3, to modulate VSMC migration, proliferation and NIH.\ud \ud Methods: In vitro VSMC studies utilized reverse transcriptase and real time Q-PCR gene expression analysis, western blot, elisa assay and cellular proliferation and migration scratch assay's. In vivo studies utilized the partial carotid artery ligation model of NIH together with immunohistochemistry in FVB/N mice.\ud \ud Results: MCT-3 treatment induced histone H3 and H4 acetylation and inhibited VSMC migration and proliferation in vitro and significantly attenuated NIH in vivo. MCT-3-mediated regulation of orphan nuclear receptor NUR77, Plasminogen Activator Inhibitor Type-1 (PAI-1) and cyclin dependent kinase inhibitors (CDKI) p21CIP1/WAF1 and p27KIP1 expression was also identified.\ud \ud Conclusions: Together these observations identify a novel agent, MCT-3, with histone deacetylase inhibitory activity, able to inhibit NIH and identify a potential molecular mechanism responsible for these effects. Additional pre-clinical studies may be warranted to determine the potential clinical utility of this compound

    Preventing Suicide in Prisons, Part II International Comparisons of Suicide Prevention Services in Correctional Facilities

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    The International Association for Suicide Prevention created a Task Force on Suicide in Prisons to better disseminate the information in this domain. One of its objectives was to summarize suicide-prevention activities in the prison systems. This study of the Task Force uncovered many differences between countries, although mental health professionals remain central in all suicide prevention activities. Inmate peer-support and correctional officers also play critical rotes in suicide prevention but there is great variation in the involvement of outside community workers. These differences could be explained by the availability of resources, by the structure of the correctional and community services, but mainly by the different paradigms about suicide prevention. While mere is a common and traditional paradigm mat suicide prevention services are mainly offered to individuals by mental health services, correctional systems differ in the way they include (or not) other partners of suicide prevention: correctional officers, other employees, peer inmates, chaplains/priests, and community workers. Circumstances, history, and national cultures may explain such diversity but they might also depend on the basic way we think about suicide prevention at bom individual and environmental levels. © 2007 Hogrefe & Huber Publishers

    Plasminogen activator inhibitor type-2 (PAI-2) gene transcription requires a novel NF-kappaB-like transcriptional regulatory motif

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    Induction of human plasminogen activator inhibitor type-2 (PAI-2) gene transcription is the response of macrophages to inflammatory stimuli, such as the pleiotropic cytokine, tumour necrosis factor-α (TNFα). Here we have examined whether PAI-2 gene transcription in response to TNFα may be mediated through a regulatory pathway involving the transcription factor, NF-ÎșB. We have tested the function of two potential NF-ÎșB-like sites present in the PAI-2 proximal promoter for responsiveness to TNFα using chloramphenicol acetyl transferase reporter gene deletion and mutation analyses. While no evidence was found for TNFα regulation of the PAI-2 gene through either of these two sites, one of the NF-ÎșB-like motifs, transcriptional regulatory motif (TRM), present at position −400 was found to be essential for constitutive PAI-2 transcription, as mutation of this motif abolished basal PAI-2 promoter activity in both monocyte-like U937 cells and HT1080 fibrosarcoma cells. Competition electrophoretic mobility shift assays identified four TRM-binding proteins present in U937, HT1080 and HeLa cell extracts, which bound to this motif but were not components of the NF-ÎșB regulatory complex. Expression screening of a HeLa cell cDNA library using the −400 TRM as a probe identified two cDNAs encoding partial peptides which specifically bound the TRM motif. DNA sequence analysis revealed that one cDNA was novel, and the second cDNA encoded exon 5 of the nephroblastoma overexpressed (novH) proto-oncogene, suggesting a new role for this peptide in gene regulation. Taken together, these findings identify a new regulatory element required for constitutive PAI-2 transcription, and identify potential DNA-binding proteins associated with this element that may play a role in PAI-2 gene regulation

    MicroRNA-122 and cytokeratin-18 have potential as a biomarkers of drug-induced liver injury in European and African patients on treatment for mycobacterial infection

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    Aims Patients on antituberculosis (anti‐TB) therapy are at risk of drug‐induced liver injury (DILI). MicroRNA‐122 (miR‐122) and cytokeratin‐18 (K18) are DILI biomarkers. To explore their utility in this global context, circulating miR‐122 and K18 were measured in UK and Ugandan populations on anti‐TB therapy for mycobacterial infection. Methods Healthy subjects and patients receiving anti‐TB therapy were recruited at the Royal Infirmary of Edinburgh, UK (ALISTER—ClinicalTrials.gov Identifier: NCT03211208). African patients with human immunodeficiency virus–TB coinfection were recruited at the Infectious Diseases Institute, Kampala, Uganda (SAEFRIF—NCT03982277). Serial blood samples, demographic and clinical data were collected. In ALISTER samples, MiR‐122 was quantified using polymerase chain reaction. In ALISTER and SAEFRIF samples, K18 was quantified by enzyme‐linked immunosorbent assay. Results The study had 235 participants (healthy volunteers [n = 28]; ALISTER: active TB [n = 30], latent TB [n = 88], nontuberculous mycobacterial infection [n = 25]; SAEFRIF: human immunodeficiency virus‐TB coinfection [n = 64]). In the absence of DILI, there was no difference in miR‐122 and K18 across the groups. Both miR‐122 and K18 correlated with alanine transaminase (ALT) activity (miR‐122: R = .52, 95%CI = 0.42–0.61, P < .0001. K18: R =0.42, 95%CI = 0.34–0.49, P < .0001). miR‐122 distinguished those patients with ALT>50 U/L with higher sensitivity/specificity than K18. There were 2 DILI cases: baseline ALT, 18 and 28 IU/L, peak ALT 431 and 194 IU/L; baseline K18, 58 and 219 U/L, peak K18 1247 and 3490 U/L; baseline miR‐122 4 and 17 fM, peak miR‐122 60 and 336 fM, respectively. Conclusion In patients treated with anti‐TB therapy, miR‐122 and K18 correlated with ALT and increased with DILI. Further work should determine their diagnostic and prognostic utility in this global context‐of‐use
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