WorldWideScience

Sample records for harmful tumour-associated proteolysis

  1. Proteolysis in hyperthermophilic microorganisms

    Donald E. Ward

    2002-01-01

    Full Text Available Proteases are found in every cell, where they recognize and break down unneeded or abnormal polypeptides or peptide-based nutrients within or outside the cell. Genome sequence data can be used to compare proteolytic enzyme inventories of different organisms as they relate to physiological needs for protein modification and hydrolysis. In this review, we exploit genome sequence data to compare hyperthermophilic microorganisms from the euryarchaeotal genus Pyrococcus, the crenarchaeote Sulfolobus solfataricus, and the bacterium Thermotoga maritima. An overview of the proteases in these organisms is given based on those proteases that have been characterized and on putative proteases that have been identified from genomic sequences, but have yet to be characterized. The analysis revealed both similarities and differences in the mechanisms utilized for proteolysis by each of these hyperthermophiles and indicated how these mechanisms relate to proteolysis in less thermophilic cells and organisms.

  2. Peptidomics for Studying Limited Proteolysis.

    Tsuchiya, Takashi; Osaki, Tsukasa; Minamino, Naoto; Sasaki, Kazuki

    2015-11-06

    Limited proteolysis is a pivotal mechanism regulating protein functions. Identifying physiologically or pathophysiologically relevant cleavage sites helps to develop molecular tools that can be used for diagnostics or therapeutics. During proteolysis of secretory and membrane proteins, part of the cleaved protein is liberated and destined to undergo degradation but should retain original cleavage sites created by proteolytic enzymes. We profiled endogenous peptides accumulated for 4 h in media conditioned by primary cultured rat cardiac fibroblasts. A total of 3916 redundant peptide sequences from 94 secretory proteins and membrane proteins served to identify limited cleavage sites, both annotated and unannotated, for signal peptide or propeptide removal, peptide hormone processing, ectodomain shedding, and regulated intramembrane proteolysis. Incorrectly predicted signal cleavage sites are found in typical proteins such as extracellular matrix proteins and the peptide hormone precursor adrenomedullin ADM. The revealed signal peptide cleavage site for ADM was experimentally verified by identifying the major molecular form of flanking proadrenomedullin N-terminal peptide. We suggest that profiling of endogenous peptides, like transcriptome sequence reads, makes sense in regular cells such as fibroblasts and that peptidomics provides insight into proteolysis-regulated protein functions.

  3. Tumour-associated osteomalacia and hypoglycaemia in a patient with prostate cancer: is Klotho involved?

    Latifyan, Sofiya Bedo; Vanhaeverbeek, Michel; Klastersky, Jean

    2014-11-17

    Tumour-associated osteomalacia is a paraneoplastic syndrome caused by renal phosphate wasting, leading to severe hypophosphataemia. Excess of circulating fibroblast growth factor 23 (FGF23) is the likely cause, acting via the FGF23/α-Klotho coreceptor, a critical regulator of phosphate metabolism. The other possible effects of that complex in humans are still under investigation. We present a case of an 84-year-old Belgian man, presenting prostate cancer with bone metastases. From June 2010 to March 2013, he presented three episodes of disease progression. From January 2012, the patient developed a progressively marked dorsal kyphosis with significant hypophosphataemia. The calculated TRP (tubular reabsorption of phosphate) was decreased and the FGF23 increased. Mid-March 2013, the patient died after a profound unconsciousness due to hypoglycaemia with hypothermia. We hypothesised that the two paraneoplastic manifestations of this patient (tumour-associated osteomalacia and refractory hypoglycaemia) were due to one cause chain with two main nodes-FGF23 and its coreceptor Klotho.. 2014 BMJ Publishing Group Ltd.

  4. Proteolysis and consistency of Meshanger cheese

    Jong, de L.

    1978-01-01

    Proteolysis in Meshanger cheese, estimated by quantitative polyacrylamide gel electrophoresis is discussed. The conversion of α s1 -casein was proportional to rennet concentration in the cheese. Changes in consistency, after a maximum, were correlated to breakdown of

  5. Protein trafficking and maturation regulate intramembrane proteolysis.

    Morohashi, Yuichi; Tomita, Taisuke

    2013-12-01

    Intramembrane-cleaving proteases (I-CLiPs) are membrane embedded proteolytic enzymes. All substrates identified so far are also membrane proteins, involving a number of critical cellular signaling as well as human diseases. After synthesis and assembly at the endoplasmic reticulum, membrane proteins are exported to the Golgi apparatus and transported to their sites of action. A number of studies have revealed the importance of the intracellular membrane trafficking in i-CLiP-mediated intramembrane proteolysis, not only for limiting the unnecessary encounter between i-CLiPs and their substrate but also for their cleavage site preference. In this review, we will discuss recent advances in our understanding of how each i-CLiP proteolysis is regulated by intracellular vesicle trafficking. This article is part of a Special Issue entitled: Intramembrane Proteases. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Taking a position on intramembrane proteolysis.

    Lemieux, M Joanne

    2018-03-30

    Decades of work have contributed to our in-depth mechanistic understanding of soluble proteases, but much less is known about the catalytic mechanism of intramembrane proteolysis due to inherent difficulties in both preparing and analyzing integral membrane enzymes and transmembrane substrates. New work from Naing et al. tackles this challenge by examining the catalytic parameters of an aspartyl intramembrane protease homologous to the enzyme that cleaves amyloid precursor protein, finding that both chemistry and register contribute to specificity in substrate cleavage. © 2018 Joanne Lemieux.

  7. Increased FOXP3 expression in tumour-associated tissues of horses affected with equine sarcoid disease.

    Mählmann, K; Hamza, E; Marti, E; Dolf, G; Klukowska, J; Gerber, V; Koch, C

    2014-12-01

    Recent studies suggest that regulatory T cells (Tregs) are associated with disease severity and progression in papilloma virus induced neoplasia. Bovine papilloma virus (BPV) is recognised as the most important aetiological factor in equine sarcoid (ES) disease. The aim of this study was to compare expression levels of Treg markers and associated cytokines in tissue samples of ES-affected equids with skin samples of healthy control horses. Eleven ES-affected, and 12 healthy horses were included in the study. Expression levels of forkhead box protein 3 (FOXP3), interleukin 10 (IL10), interleukin 4 (IL4) and interferon gamma (IFNG) mRNA in lesional and tumour-distant samples from ES-affected horses, as well as in dermal samples of healthy control horses were measured using quantitative reverse transcription polymerase chain reaction (PCR). Expression levels were compared between lesional and tumour-distant as well as between tumour-distant and control samples. Furthermore, BPV-1 E5 DNA in samples of ES-affected horses was quantified using quantitative PCR, and possible associations of viral load, disease severity and gene expression levels were evaluated. Expression levels of FOXP3, IL10 and IFNG mRNA and BPV-1 E5 copy numbers were significantly increased in lesional compared to tumour-distant samples. There was no difference in FOXP3 and cytokine expression in tumour-distant samples from ES- compared with control horses. In tumour-distant samples viral load was positively correlated with IL10 expression and severity score. The increased expression of Treg markers in tumour-associated tissues of ES-affected equids indicates a local, Treg-induced immune suppression. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Ubiquitin-mediated proteolysis in Xenopus extract.

    McDowell, Gary S; Philpott, Anna

    2016-01-01

    The small protein modifier, ubiquitin, can be covalently attached to proteins in the process of ubiquitylation, resulting in a variety of functional outcomes. In particular, the most commonly-associated and well-studied fate for proteins modified with ubiquitin is their ultimate destruction: degradation by the 26S proteasome via the ubiquitin-proteasome system, or digestion in lysosomes by proteolytic enzymes. From the earliest days of ubiquitylation research, a reliable and versatile "cell-in-a-test-tube" system has been employed in the form of cytoplasmic extracts from the eggs and embryos of the frog Xenopus laevis. Biochemical studies of ubiquitin and protein degradation using this system have led to significant advances particularly in the study of ubiquitin-mediated proteolysis, while the versatility of Xenopus as a developmental model has allowed investigation of the in vivo consequences of ubiquitylation. Here we describe the use and history of Xenopus extract in the study of ubiquitin-mediated protein degradation, and highlight the versatility of this system that has been exploited to uncover mechanisms and consequences of ubiquitylation and proteolysis.

  9. Functional Imaging of Proteolysis: Stromal and Inflammatory Cells Increase Tumor Proteolysis

    Mansoureh Sameni

    2003-07-01

    Full Text Available The underlying basement membrane is degraded during progression of breast and colon carcinoma. Thus, we imaged degradation of a quenched fluorescent derivative of basement membrane type IV collagen (DQ-collagen IV by living human breast and colon tumor spheroids. Proteolysis of DQ-collagen IV by HCT 116 and HKh-2 human colon tumor spheroids was both intracellular and pericellular. In contrast, proteolysis of DQ-collagen IV by BT20 human breast tumor spheroids was pericellular. As stromal elements can contribute to proteolytic activities associated with tumors, we also examined degradation of DQ-collagen IV by human monocytes/macrophages and colon and breast fibroblasts. Fibroblasts themselves exhibited a modest amount of pericellular degradation. Degradation was increased 4–17-fold in cocultures of fibroblasts and tumor cells as compared to either cell type alone. Inhibitors of matrix metalloproteinases, plasmin, and the cysteine protease, cathepsin B, all reduced degradation in the cocultures. Monocytes did not degrade DQ-collagen IV; however, macrophages degraded DQ-collagen IV intracellularly. In coculture of tumor cells, fibroblasts, and macrophages, degradation of DQ-collagen IV was further increased. Imaging of living tumor and stromal cells has, thus, allowed us to establish that tumor proteolysis occurs pericellularly and intracellularly and that tumor, stromal, and inflammatory cells all contribute to degradative processes.

  10. TGF-beta receptor 2 downregulation in tumour-associated stroma worsens prognosis and high-grade tumours show more tumour-associated macrophages and lower TGF-beta1 expression in colon carcinoma: a retrospective study

    Bacman, David; Merkel, Susanne; Croner, Roland; Papadopoulos, Thomas; Brueckl, Wolfgang; Dimmler, Arno

    2007-01-01

    Histological phenotype and clinical behaviour of malignant tumours are not only dependent on alterations in the epithelial cell compartment, but are affected by their interaction with inflammatory cells and tumour-associated stroma. Studies in animal models have shown influence of tumour-associated macrophages (TAM) on histological grade of differentiation in colon carcinoma. Disruption of transforming growth factor beta (TGF-beta) signalling in tumour cells is related to more aggressive clinical behaviour. Expression data of components of this pathway in tumour-associated stroma is limited. Tissue micro arrays of 310 colon carcinomas from curatively resected patients in UICC stage II and III were established. In a first step we quantified amount of CD68 positive TAMs and expression of components of TGF-beta signalling (TGF-beta1, TGF-beta receptors type 1 and 2, Smad 3 and 4) in tumour and associated stroma. Further we analyzed correlation to histological and clinical parameters (histological grade of differentiation (low-grade (i.e. grade 1 and 2) vs. high-grade (i.e. grade 3 and 4)), lymph node metastasis, distant metastasis, 5 year cancer related survival) using Chi-square or Fisher's exact test, when appropriate, to compare frequencies, Kaplan-Meier method to calculate 5-year rates of distant metastases and cancer-related survival and log rank test to compare the rates of distant metastases and survival. To identify independent prognostic factors Cox regression analysis including lymph node status and grading was performed. High-grade tumours and those with lymph node metastases showed higher rates of TAMs and lower expression of TGF-beta1. Loss of nuclear Smad4 expression in tumor was associated with presence of lymph node metastasis, but no influence on prognosis could be demonstrated. Decrease of both TGF-beta receptors in tumour-associated stroma was associated with increased lymph node metastasis and shorter survival. Stromal TGF-beta receptor 2

  11. TGF-beta receptor 2 downregulation in tumour-associated stroma worsens prognosis and high-grade tumours show more tumour-associated macrophages and lower TGF-beta1 expression in colon carcinoma: a retrospective study

    Papadopoulos Thomas

    2007-08-01

    Full Text Available Abstract Background Histological phenotype and clinical behaviour of malignant tumours are not only dependent on alterations in the epithelial cell compartment, but are affected by their interaction with inflammatory cells and tumour-associated stroma. Studies in animal models have shown influence of tumour-associated macrophages (TAM on histological grade of differentiation in colon carcinoma. Disruption of transforming growth factor beta (TGF-beta signalling in tumour cells is related to more aggressive clinical behaviour. Expression data of components of this pathway in tumour-associated stroma is limited. Methods Tissue micro arrays of 310 colon carcinomas from curatively resected patients in UICC stage II and III were established. In a first step we quantified amount of CD68 positive TAMs and expression of components of TGF-beta signalling (TGF-beta1, TGF-beta receptors type 1 and 2, Smad 3 and 4 in tumour and associated stroma. Further we analyzed correlation to histological and clinical parameters (histological grade of differentiation (low-grade (i.e. grade 1 and 2 vs. high-grade (i.e. grade 3 and 4, lymph node metastasis, distant metastasis, 5 year cancer related survival using Chi-square or Fisher's exact test, when appropriate, to compare frequencies, Kaplan-Meier method to calculate 5-year rates of distant metastases and cancer-related survival and log rank test to compare the rates of distant metastases and survival. To identify independent prognostic factors Cox regression analysis including lymph node status and grading was performed. Results High-grade tumours and those with lymph node metastases showed higher rates of TAMs and lower expression of TGF-beta1. Loss of nuclear Smad4 expression in tumor was associated with presence of lymph node metastasis, but no influence on prognosis could be demonstrated. Decrease of both TGF-beta receptors in tumour-associated stroma was associated with increased lymph node metastasis and

  12. Photodynamic treatment of a secondary vasoproliferative tumour associated with sector retinitis pigmentosa and Usher syndrome type I.

    Osman, Saatci A; Aylin, Yaman; Arikan, Gul; Celikel, Harika

    2007-03-01

    Vasoproliferative tumours may be primary or secondary and present with severe exudation leading to marked visual loss. We describe a 47-year-old man with unilateral secondary vasoproliferative tumour associated with sector retinitis pigmentosa and Usher I syndrome who was successfully treated with a single session of photodynamic treatment. Standard treatment protocol was used except that the treatment duration was doubled. A year after the treatment, the angioma-like tumour vanished and exudation was dramatically reduced. Photodynamic therapy seems to be a minimally invasive and safe technique in eyes with secondary vasoproliferative tumours.

  13. Allosteric regulation of rhomboid intramembrane proteolysis.

    Arutyunova, Elena; Panwar, Pankaj; Skiba, Pauline M; Gale, Nicola; Mak, Michelle W; Lemieux, M Joanne

    2014-09-01

    Proteolysis within the lipid bilayer is poorly understood, in particular the regulation of substrate cleavage. Rhomboids are a family of ubiquitous intramembrane serine proteases that harbour a buried active site and are known to cleave transmembrane substrates with broad specificity. In vitro gel and Förster resonance energy transfer (FRET)-based kinetic assays were developed to analyse cleavage of the transmembrane substrate psTatA (TatA from Providencia stuartii). We demonstrate significant differences in catalytic efficiency (kcat/K0.5) values for transmembrane substrate psTatA (TatA from Providencia stuartii) cleavage for three rhomboids: AarA from P. stuartii, ecGlpG from Escherichia coli and hiGlpG from Haemophilus influenzae demonstrating that rhomboids specifically recognize this substrate. Furthermore, binding of psTatA occurs with positive cooperativity. Competitive binding studies reveal an exosite-mediated mode of substrate binding, indicating allostery plays a role in substrate catalysis. We reveal that exosite formation is dependent on the oligomeric state of rhomboids, and when dimers are dissociated, allosteric substrate activation is not observed. We present a novel mechanism for specific substrate cleavage involving several dynamic processes including positive cooperativity and homotropic allostery for this interesting class of intramembrane proteases. © 2014 The Authors.

  14. Regulatory Proteolysis in Arabidopsis-Pathogen Interactions.

    Pogány, Miklós; Dankó, Tamás; Kámán-Tóth, Evelin; Schwarczinger, Ildikó; Bozsó, Zoltán

    2015-09-24

    Approximately two and a half percent of protein coding genes in Arabidopsis encode enzymes with known or putative proteolytic activity. Proteases possess not only common housekeeping functions by recycling nonfunctional proteins. By irreversibly cleaving other proteins, they regulate crucial developmental processes and control responses to environmental changes. Regulatory proteolysis is also indispensable in interactions between plants and their microbial pathogens. Proteolytic cleavage is simultaneously used both by plant cells, to recognize and inactivate invading pathogens, and by microbes, to overcome the immune system of the plant and successfully colonize host cells. In this review, we present available results on the group of proteases in the model plant Arabidopsis thaliana whose functions in microbial pathogenesis were confirmed. Pathogen-derived proteolytic factors are also discussed when they are involved in the cleavage of host metabolites. Considering the wealth of review papers available in the field of the ubiquitin-26S proteasome system results on the ubiquitin cascade are not presented. Arabidopsis and its pathogens are conferred with abundant sets of proteases. This review compiles a list of those that are apparently involved in an interaction between the plant and its pathogens, also presenting their molecular partners when available.

  15. Harmful Waste Process

    Ki, Mun Bong; Lee, Shi Jin; Park, Jun Seok; Yoon, Seok Pyo; Lee, Jae Hyo; Jo, Byeong Ryeol

    2008-08-01

    This book gives descriptions of processing harmful waste, including concerned law and definition of harmful waste, current conditions and generation of harmful waste in Korea, international condition of harmful waste, minimizing of generation of harmful waste, treatment and storage. It also tells of basic science for harmful waste disposal with physics, chemistry, combustion engineering, microbiology and technique of disposal such as physical, chemical, biological process, stabilizing and solidification, incineration and waste in landfill.

  16. Complementary methods for the identification of substrates of proteolysis.

    Pham, Victoria C; Anania, Veronica G; Phung, Qui T; Lill, Jennie R

    2014-01-01

    Proteolysis describes the cleavage of proteins into smaller components, which in vivo occurs typically to either activate or impair the functionality of cellular proteins. Proteolysis can occur during cellular homeostasis or can be induced due to external stress stimuli such as heat, biological or chemical insult, and is mediated by the activity of cellular enzymes, namely, proteases. Proteolytic cleavage of proteins can influence protein activation by exposing an active site or disrupting inhibitor binding. Conversely, proteolytic cleavage of many proteins has also been shown to lead to protein degradation resulting in inactivation of the substrate. Thousands of proteolytic events are known to take place in regulated cellular processes such as apoptosis and pyroptosis, however, their individual contribution to these processes remains poorly understood. Additionally, many cellular homeostatic processes are regulated by proteolytic events, however, in some cases, few proteolytic substrates have been identified. To gain further insight into the mechanism of action of these cellular processes, and to characterize biomarkers of cell death and other pathological indications, it is imperative to utilize a complete arsenal of tools for studying proteolysis events in vivo and in vitro. In this chapter, we focus on alternative methodologies to N-terminomics for profiling substrates of proteolysis and describe an additional suite of tools including orthogonal biophysical separation techniques such as COFRADIC or GASSP, and affinity capture tools that can enrich for newly formed C-termini (C-terminomics) generated as a result of caspase-mediated proteolysis. © 2014 Elsevier Inc. All rights reserved.

  17. The effect of different packaging materials on proteolysis, sensory ...

    In this study, tulum cheese was manufactured using raw ewe's milk and was ripened in goat's skin and plastic bags. The effect of ripening materials (skin bag or plastic) on proteolysis was investigated during 120 days of ripening. In addition, sensory scores of the cheeses were assessed at the 90th and 120th days.

  18. Physiological regulation of epithelial sodium channel by proteolysis

    Svenningsen, Per; Friis, Ulla G; Bistrup, Claus

    2011-01-01

    PURPOSE OF REVIEW: Activation of epithelial sodium channel (ENaC) by proteolysis appears to be relevant for day-to-day physiological regulation of channel activity in kidney and other epithelial tissues. Pathophysiogical, proteolytic activation of ENaC in kidney has been demonstrated in proteinuric...

  19. Perlecan and the Blood-Brain Barrier: Beneficial Proteolysis?

    Jill eRoberts

    2012-08-01

    Full Text Available The cerebral microvasculature is important for maintaining brain homeostasis. This is achieved via the blood-brain barrier (BBB, composed of endothelial cells with specialized tight junctions, astrocytes and a basement membrane. Prominent components of the basement membrane extracellular matrix (ECM include fibronectin, laminin, collagen IV and perlecan, all of which regulate cellular processes via signal transduction through various cell membrane bound ECM receptors. Expression and proteolysis of these ECM components can be rapidly altered during pathological states of the central nervous system. In particular, proteolysis of perlecan, a heparan sulfate proteoglycan, occurs within hours following ischemia induced by experimental stroke. Proteolysis of ECM components following stroke results in the degradation of the basement membrane and further disruption of the BBB. While it is clear that such proteolysis has negative consequences for the BBB, we propose that it also may lead to generation of ECM protein fragments, including the C-terminal domain V (DV of perlecan, that potentially have a positive influence on other aspects of CNS health. Indeed, perlecan DV has been shown to be persistently generated after stroke and beneficial as a neuroprotective molecule and promoter of post-stroke brain repair. This mini-review will discuss beneficial roles of perlecan protein fragment generation within the brain during stroke.

  20. Autologous monoclonal antibodies recognize tumour-associated antigens in X-irradiated C57BL/6 mice

    Artus, A; Guillemain, B; Legrand, E; Astier-Gin, T; Mamoun, R; Duplan, J -F

    1986-09-01

    X-irradiation of C57BL/6 mice induces thymic lymphosarcomas which sometimes contain retroviruses which upon injection into normal mice mimic the effect of the irradiation. We examined whether specific antigenicities, viral or cellular, were expressed by tumour cells that could be recognized by antibodies from the irradiated animals. We developed monoclonal antibodies (MAbs) using splenocytes of the diseased animal. The reactivity of such MAbs towards thymoma cell lines established in vitro was investigated by means of an ELISA. At least 10 antibody specificities were detected on the 13 tumours investigated, allowing separation of the MAbs into three classes: (i) those recognizing the autologous tumour, heterologous tumours as well as normal thymic tissue, (ii) those specific for the autologous tumour, and (iii) those specific for one tumour, but not ones of autologous origin. The last two classes corresponded to specific tumour-associated antigens. Our panel of MAbs defined each tumour by the particular pattern of antigens harboured. It is striking that most of the antigens were present in the normal thymus and that only two tumours had additional antigenicities. Additionally, quantitative variations were observed in the levels of expression of these antigens.

  1. Chemotherapy inhibits skeletal muscle ubiquitin-proteasome-dependent proteolysis.

    Tilignac, Thomas; Temparis, Sandrine; Combaret, Lydie; Taillandier, Daniel; Pouch, Marie-Noëlle; Cervek, Matjaz; Cardenas, Diana M; Le Bricon, Thierry; Debiton, Eric; Samuels, Susan E; Madelmont, Jean-Claude; Attaix, Didier

    2002-05-15

    Chemotherapy has cachectic effects, but it is unknown whether cytostatic agents alter skeletal muscle proteolysis. We hypothesized that chemotherapy-induced alterations in protein synthesis should result in the increased incidence of abnormal proteins, which in turn should stimulate ubiquitin-proteasome-dependent proteolysis. The effects of the nitrosourea cystemustine were investigated in skeletal muscles from both healthy and colon 26 adenocarcinoma-bearing mice, an appropriate model for testing the impact of cytostatic agents. Muscle wasting was seen in both groups of mice 4 days after a single cystemustine injection, and the drug further increased the loss of muscle proteins already apparent in tumor-bearing animals. Cystemustine cured the tumor-bearing mice with 100% efficacy. Surprisingly, within 11 days of treatment, rates of muscle proteolysis progressively decreased below basal levels observed in healthy control mice and contributed to the cessation of muscle wasting. Proteasome-dependent proteolysis was inhibited by mechanisms that include reduced mRNA levels for 20S and 26S proteasome subunits, decreased protein levels of 20S proteasome subunits and the S14 non-ATPase subunit of the 26S proteasome, and impaired chymotrypsin- and trypsin-like activities of the enzyme. A combination of cisplatin and ifosfamide, two drugs that are widely used in the treatment of cancer patients, also depressed the expression of proteasomal subunits in muscles from rats bearing the MatB adenocarcinoma below basal levels. Thus, a down-regulation of ubiquitin-proteasome-dependent proteolysis is observed with various cytostatic agents and contributes to reverse the chemotherapy-induced muscle wasting.

  2. Harmful Algal Blooms (HABs)

    ... toxins that may harm or kill fish and marine animals. Humans who eat shellfish contaminated with HAB toxins ... toxins that may harm or kill fish and marine animals. Humans who eat shellfish containing toxins produced by ...

  3. Self-harm

    Self-harm refers to a person's harming their own body on purpose. About 1 in 100 people hurts himself or herself in this way. More females hurt themselves than males. A person who self-harms usually does not mean to kill himself or herself. But they are at higher risk of attempting suicide if they do ...

  4. Deliberate Self Harm Behavior

    Fatma Gul Helvaci Celik

    2017-06-01

    Full Text Available The deliberate self-harm behaviour which defined as attempting to own body resulting in tisue damage without conscious desire of peolple to die, is a major public health problem worldwide. The causes of deliberate self- harm, risk factors, the relationship between mental disorders and treatment strategies are not fully known. Deliberate self- harm can be observed together with psychiatric disorders such as borderline personality disorder, histrionic personality disorder, eating disorders and mood disorders. Also, deliberate self-harm must be distinguished from suicidal behavior. Psychologi-cal trauma has been suggested as a risk factor for deliberate self- harm behavior. Trauma and traumatic events have long been associated with deliberate self- harm behavior. The aim of this review article is to investigate the etiology and epidemiology of deliberate self-harm behaviour and relationship between psychiatric disorders. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2017; 9(2.000: 209-226

  5. Dual prognostic significance of tumour-associated macrophages in human pancreatic adenocarcinoma treated or untreated with chemotherapy.

    Di Caro, Giuseppe; Cortese, Nina; Castino, Giovanni Francesco; Grizzi, Fabio; Gavazzi, Francesca; Ridolfi, Cristina; Capretti, Giovanni; Mineri, Rossana; Todoric, Jelena; Zerbi, Alessandro; Allavena, Paola; Mantovani, Alberto; Marchesi, Federica

    2016-10-01

    Tumour-associated macrophages (TAMs) play key roles in tumour progression. Recent evidence suggests that TAMs critically modulate the efficacy of anticancer therapies, raising the prospect of their targeting in human cancer. In a large retrospective cohort study involving 110 patients with pancreatic ductal adenocarcinoma (PDAC), we assessed the density of CD68-TAM immune reactive area (%IRA) at the tumour-stroma interface and addressed their prognostic relevance in relation to postsurgical adjuvant chemotherapy (CTX). In vitro, we dissected the synergism of CTX and TAMs. In human PDAC, TAMs predominantly exhibited an immunoregulatory profile, characterised by expression of scavenger receptors (CD206, CD163) and production of interleukin 10 (IL-10). Surprisingly, while the density of TAMs associated to worse prognosis and distant metastasis, CTX restrained their protumour prognostic significance. High density of TAMs at the tumour-stroma interface positively dictated prognostic responsiveness to CTX independently of T-cell density. Accordingly, in vitro, gemcitabine-treated macrophages became tumoricidal, activating a cytotoxic gene expression programme, inhibiting their protumoural effect and switching to an antitumour phenotype. In patients with human PDAC, neoadjuvant CTX was associated to a decreased density of CD206(+) and IL-10(+) TAMs at the tumour-stroma interface. Overall, our data highlight TAMs as critical determinants of prognostic responsiveness to CTX and provide clinical and in vitro evidence that CTX overall directly re-educates TAMs to restrain tumour progression. These results suggest that the quantification of TAMs could be exploited to select patients more likely to respond to CTX and provide the basis for novel strategies aimed at re-educating macrophages in the context of CTX. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  6. Increased serum levels of tumour-associated trypsin inhibitor independently predict a poor prognosis in colorectal cancer patients

    Gaber Alexander

    2010-09-01

    Full Text Available Abstract Background There is an insufficient number of reliable prognostic and response predictive biomarkers in colorectal cancer (CRC management. In a previous study, we found that high tumour tissue expression of tumour-associated trypsin inhibitor (TATI correlated with liver metastasis and an impaired prognosis in CRC. The aim of this study was to investigate the prognostic validity of serum TATI (s-TATI in CRC. We further assessed the prognostic value of carcino-embryonic antigen in serum (s-CEA and the interrelationship between s-TATI and TATI in tissue (t-TATI. Methods Using an immunofluorometric assay, s-TATI levels were analysed in 334 preoperatively collected serum samples from patients with CRC. Spearman's Rho and Chi-square test were used for analysis of correlations between s-TATI and clinicopathological parameters, s-CEA and t-TATI. Kaplan-Meier analysis and Cox uni- and multivariate regression analysis were used to estimate disease free survival (DFS and overall survival (OS according to quartiles of s-TATI and cut-offs derived from ROC-analysis of s-TATI and s-CEA. Results Increased levels of s-TATI were associated with a reduced DFS (HR = 2.00; 95% CI 1.40-2.84, P P P = 0.034 for DFS and HR = 1.78; 95% CI 1.25-2.53, P = 0.001 for OS. There was no significant association between s-TATI and t-TATI. The prognostic value of s-CEA was also evident, but somewhat weaker than for s-TATI. Conclusions High preoperative s-TATI levels predict a poor prognosis in patients with CRC, and the prognostic value is independent of established prognostic parameters and t-TATI expression. These data suggest that s-TATI might be a useful marker for prognostic stratification in CRC.

  7. Histopathology of tumour associated sarcoid-like stromal reaction in breast cancer. An analysis of 5 cases with immunohistochemical investigations.

    Bässler, R; Birke, F

    1988-01-01

    In 5 cases of invasive ductal and lobular carcinoma of the breast multiple epithelioid and giant cell containing granulomas were detected, localized mainly in circumferential regions, but also in the center of the carcinomas. These granulomas were interpreted as sarcoid-like stromal reactions, occurring as sarcoid-like lesions in uni- and bilateral primaries, in a recurrent tumour, and also in axillary lymph nodes. Histopathologically, these granulomas were not quite uniform, some of them corresponding to typical sarcoidosis, others showing marked proliferations of epithelioid or giant cells or containing fibrinoid exudate or necroses. The granulomas were surrounded by dense infiltrates of mononuclear cells. Tuberculosis and mycosis was excluded. There were no hints of generalized sarcoidosis. Pathogenetically, these are reactions in the tumour stroma of varying intensity, and are not caused by necroses of the tumour tissue nor by microbial infections. Such tumour-associated sarcoid-like stroma reactions are interpreted as a T-cell mediated immune response to an antigen expression of the carcinoma acting as the local trigger; in 2 cases they were connected with sarcoid-like lesions of the axillary lymph nodes. Their occurrence in bilateral carcinoma of the breast points to an immunological disposition for this special kind of host-versus-tumour response. The intensity of these changes in a recurrent tumour reflects an immunological hypersensitivity reaction. The pathogenetic and differential diagnostic aspects of epithelioid granulomas of the female breast in chronic granulomatous mastitis, panniculitis, foreign body reaction, rare infections, and in therapeutically induced sarcoidosis are described and discussed.

  8. [Self-harming behaviour].

    Kool, Nienke; Pollen, Wim; van Meijel, Berno

    2010-01-01

    To gain a better understanding of self-harm, a 28-year-old female patient and a 19-year-old female patient with self-harming behaviour are presented. The first patient refused treatment of cut wounds when the doctor enquired about the reason for self-harm. The second patient was referred for mental health care. These cases illustrate the complexity of this behaviour for the patient and the caregiver. Self-harm is often a symbol of underlying problems and serves multiple psychological functions. It is mostly used by patients to cope with unbearable emotions for which they have no other solution. The self-harm invokes different feelings in caregivers which tend to influence the attitude of the caregiver towards the patient. It is very important that caregivers are aware of their feelings and use them professionally. People who self-harm should not be judged, but treated respectfully and attention should be paid to their suffering.

  9. Self-harm.

    Skegg, Keren

    The term self-harm is commonly used to describe a wide range of behaviours and intentions including attempted hanging, impulsive self-poisoning, and superficial cutting in response to intolerable tension. As with suicide, rates of self-harm vary greatly between countries. 5-9% of adolescents in western countries report having self-harmed within the previous year. Risk factors include socioeconomic disadvantage, and psychiatric illness--particularly depression, substance abuse, and anxiety disorders. Cultural aspects of some societies may protect against suicide and self-harm and explain some of the international variation in rates of these events. Risk of repetition of self-harm and of later suicide is high. More than 5% of people who have been seen at a hospital after self-harm will have committed suicide within 9 years. Assessment after self-harm includes careful consideration of the patient's intent and beliefs about the lethality of the method used. Strong suicidal intent, high lethality, precautions against being discovered, and psychiatric illness are indicators of high suicide risk. Management after self-harm includes forming a trusting relationship with the patient, jointly identifying problems, ensuring support is available in a crisis, and treating psychiatric illness vigorously. Family and friends may also provide support. Large-scale studies of treatments for specific subgroups of people who self-harm might help to identify more effective treatments than are currently available. Although risk factors for self-harm are well established, aspects that protect people from engaging in self-harm need to be further explored.

  10. Inhibitors of the proteasome reduce the accelerated proteolysis in atrophying rat skeletal muscles.

    Tawa, N E; Odessey, R; Goldberg, A L

    1997-07-01

    Several observations have suggested that the enhanced proteolysis and atrophy of skeletal muscle in various pathological states is due primarily to activation of the ubiquitin-proteasome pathway. To test this idea, we investigated whether peptide aldehyde inhibitors of the proteasome, N-acetyl-leucyl-leucyl-norleucinal (LLN), or the more potent CBZ-leucyl-leucyl-leucinal (MG132) suppressed proteolysis in incubated rat skeletal muscles. These agents (e.g., MG132 at 10 microM) inhibited nonlysosomal protein breakdown by up to 50% (P protein synthesis or amino acid pools, but improved overall protein balance in the muscle. Upon treatment with MG132, ubiquitin-conjugated proteins accumulated in the muscle. The inhibition of muscle proteolysis correlated with efficacy against the proteasome, although these agents could also inhibit calpain-dependent proteolysis induced with Ca2+. These inhibitors had much larger effects on proteolysis in atrophying muscles than in controls. In the denervated soleus undergoing atrophy, the increase in ATP-dependent proteolysis was reduced 70% by MG132 (P muscle proteolysis induced by administering thyroid hormones was reduced 40-70% by the inhibitors. Finally, in rats made septic by cecal puncture, the increase in muscle proteolysis was completely blocked by MG132. Thus, the enhanced proteolysis in many catabolic states (including denervation, hyperthyroidism, and sepsis) is due to a proteasome-dependent pathway, and inhibition of proteasome function may be a useful approach to reduce muscle wasting.

  11. High expression of insulin receptor on tumour-associated blood vessels in invasive bladder cancer predicts poor overall and progression-free survival.

    Roudnicky, Filip; Dieterich, Lothar C; Poyet, Cedric; Buser, Lorenz; Wild, Peter; Tang, Dave; Camenzind, Peter; Ho, Chien Hsien; Otto, Vivianne I; Detmar, Michael

    2017-06-01

    Bladder cancer is a frequently recurring disease with a very poor prognosis once progressed to invasive stages, and tumour-associated blood vessels play a crucial role in this process. In order to identify novel biomarkers associated with progression, we isolated blood vascular endothelial cells (BECs) from human invasive bladder cancers and matched normal bladder tissue, and found that tumour-associated BECs greatly up-regulated the expression of insulin receptor (INSR). High expression of INSR on BECs of invasive bladder cancers was significantly associated with shorter progression-free and overall survival. Furthermore, increased expression of the INSR ligand IGF-2 in invasive bladder cancers was associated with reduced overall survival. INSR may therefore represent a novel biomarker to predict cancer progression. Mechanistically, we observed pronounced hypoxia in human bladder cancer tissue, and found a positive correlation between the expression of the hypoxia marker gene GLUT1 and vascular INSR expression, indicating that hypoxia drives INSR expression in tumour-associated blood vessels. In line with this, exposure of cultured BECs and human bladder cancer cell lines to hypoxia led to increased expression of INSR and IGF-2, respectively, and IGF-2 increased BEC migration through the activation of INSR in vitro. Taken together, we identified vascular INSR expression as a potential biomarker for progression in bladder cancer. Furthermore, our data suggest that IGF-2/INSR mediated paracrine crosstalk between bladder cancer cells and endothelial cells is functionally involved in tumour angiogenesis and may thus represent a new therapeutic target. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  12. Tumour-associated microglia/macrophages predict poor prognosis in high-grade gliomas and correlate with an aggressive tumour subtype

    Sørensen, M D; Dahlrot, R H; Boldt, H B

    2018-01-01

    (+) TAMs co-expressed proteins related to tumour aggressiveness including matrix metallopeptidase-14 and hypoxia-inducible factor-1α. CONCLUSIONS: This is the first study to use automated quantitative immunofluorescence to determine the prognostic impact of TAMs. Our results suggest that M2-like TAMs hold......AIMS: Glioblastomas are highly aggressive and treatment resistant. Increasing evidence suggests that tumour-associated macrophages/microglia (TAMs) facilitate tumour progression by acquiring a M2-like phenotype. Our objective was to investigate the prognostic value of TAMs in gliomas using...

  13. Harmful algal blooms

    Bhat, S.R.; PrabhaDevi; DeSouza, L.; Verlecar, X.N.; Naik, C.G.

    as harmful algal bloom. Bloom formation is a natural process and it enhances biological productivity, but turns worrisome when caused by toxic species, leading to massive fish mortalities and hazards to human health. Incidences of'red tide' are increasing...

  14. Plant senescence and proteolysis: two processes with one destiny.

    Diaz-Mendoza, Mercedes; Velasco-Arroyo, Blanca; Santamaria, M Estrella; González-Melendi, Pablo; Martinez, Manuel; Diaz, Isabel

    2016-01-01

    Senescence-associated proteolysis in plants is a complex and controlled process, essential for mobilization of nutrients from old or stressed tissues, mainly leaves, to growing or sink organs. Protein breakdown in senescing leaves involves many plastidial and nuclear proteases, regulators, different subcellular locations and dynamic protein traffic to ensure the complete transformation of proteins of high molecular weight into transportable and useful hydrolysed products. Protease activities are strictly regulated by specific inhibitors and through the activation of zymogens to develop their proteolytic activity at the right place and at the proper time. All these events associated with senescence have deep effects on the relocation of nutrients and as a consequence, on grain quality and crop yield. Thus, it can be considered that nutrient recycling is the common destiny of two processes, plant senescence and, proteolysis. This review article covers the most recent findings about leaf senescence features mediated by abiotic and biotic stresses as well as the participants and steps required in this physiological process, paying special attention to C1A cysteine proteases, their specific inhibitors, known as cystatins, and their potential targets, particularly the chloroplastic proteins as source for nitrogen recycling.

  15. Estrogen receptor of primary breast cancers: evidence for intracellular proteolysis

    Maaroufi, Younes; Lacroix, Marc; Lespagnard, Laurence; Journé, Fabrice; Larsimont, Denis; Leclercq, Guy

    2000-01-01

    Iodinated oestradiol-labeled oestrogen receptor (ER) isoforms devoid of amino-terminal ABC domains represent about two-thirds of the whole receptor population detected in cytosol samples from human breast cancers. This high frequency could not be ascribed to the expression of truncated mRNAs, or to the proteolysis of the native ER peptide at the time of homogenization or assay, suggesting an intracellular proteolysis. Free amino-terminal and ligand-binding domains maintained together within oligomeric structure(s); increase of ionic strength separated them. The amino-terminal region was consistently detected in the cell nucleus by specific immunohistochemistry leading to the concept of a potential intranuclear association between ER cleavage products and/or other regulatory proteins. We previously reported that about two-thirds of [ 125 I]oestradiol-labelled cytosolic ERs from breast cancer samples eluted as low-molecular-weight isoforms (≤ 37 kDa, size-exclusion fast pressure liquid chromatography [FPLC]). These isoforms failed to adsorb strongly to hydroxylapatite at high ionic strength, a property that was ascribed to receptors devoid of amino-terminal ABC domains. In view of recent data concerning intracellular proteolysis of several transcriptional regulators, the possibility of such behaviour for ER was assessed. The clinical significance of ER measurement in breast cancer cytosols is well established; approximately 50% of ER-positive cases respond to endocrine therapy. Whether such a poor correlation is related to a high proportion of cleaved ER is a question of prime importance. Failure of routine ER assays to discriminate between full-length and cleaved receptors led us to develop an oestradiol-binding assay based on hydroxylapatite adsorption. The aims of the present study were to demonstrate that hydroxylapatite adsorption assay easily identifies cleaved cytosolic ER forms and to assess the origin of such ER forms. Breast cancer cytosols classified as

  16. Cutting and Self-Harm

    ... Your feelings Feeling sad Cutting and self-harm Cutting and self-harm Self-harm, sometimes called self- ... There are many types of self-injury, and cutting is one type that you may have heard ...

  17. Laser-light backscattering response to water content and proteolysis in dry-cured ham

    Fulladosa, E.; Rubio-Celorio, M.; Skytte, Jacob Lercke

    2017-01-01

    on the acquisition conditions used. Laser backscattering was influenced by both dryness and proteolysis intensity showing an average light intensity decrease of 0.2 when decreasing water content (1% weight loss) and increasing proteolysis (equivalent to one-hour enzyme action). However, a decrease of scattering area...... was only detected when the water content was decreased (618 mm(2) per 1% weight loss). Changes on scattering of light profiles were only observed when the water content changed. Although there is a good correlation between water content and LBI parameters when analysing commercial samples, proteolysis...... of laser incidence) and to analyse the laser-light backscattering changes caused by additional hot air drying and proteolysis of dry-cured ham slices. The feasibility of the technology to determine water content and proteolysis (which is related to textural characteristics) of commercial sliced dry...

  18. Tumour-associated neutrophils and loss of epithelial PTEN can promote corticosteroid-insensitive MMP-9 expression in the chronically inflamed lung microenvironment.

    Vannitamby, Amanda; Seow, Huei Jiunn; Anderson, Gary; Vlahos, Ross; Thompson, Michelle; Steinfort, Daniel; Irving, Louis B; Bozinovski, Steven

    2017-12-01

    Matrix metalloproteinase-9 (MMP-9) is increased in a number of pathological lung conditions, where the proteinase contributes to deleterious remodelling of the airways. While both lung cancer and COPD are associated with increased MMP-9 expression, the cellular and molecular drivers of MMP-9 remain unresolved. In this study, MMP-9 transcript measured within the tumour region from patients with non-small-cell lung cancer (NSCLC) and coexisting COPD was found to be uniformly increased relative to adjacent tumour-free tissue. MMP-9 gene expression and immunohistochemistry identified tumour-associated neutrophils, but not macrophages, as a predominant source of this proteinase. In addition, PTEN gene expression was significantly reduced in tumour and there was evidence of epithelial MMP-9 expression. To explore whether PTEN can regulate epithelial MMP-9 expression, a small interfering (si)RNA knockdown strategy was used in Beas-2B bronchial epithelial cells. PTEN knockdown by siRNA selectively increased MMP-9 expression in response to lipopolysaccharide in a corticosteroid-insensitive manner. In summary, tumour-associated neutrophils represent an important source of MMP-9 in NSCLC, and loss of epithelial PTEN may further augment steroid-insensitive expression. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  19. Proteolysis targeting peptide (PROTAP) strategy for protein ubiquitination and degradation.

    Zheng, Jing; Tan, Chunyan; Xue, Pengcheng; Cao, Jiakun; Liu, Feng; Tan, Ying; Jiang, Yuyang

    2016-02-19

    Ubiquitination proteasome pathway (UPP) is the most important and selective way to degrade proteins in vivo. Here, a novel proteolysis targeting peptide (PROTAP) strategy, composed of a target protein binding peptide, a linker and a ubiquitin E3 ligase recognition peptide, was designed to recruit both target protein and E3 ligase and then induce polyubiquitination and degradation of the target protein through UPP. In our study, the PROTAP strategy was proved to be a general method with high specificity using Bcl-xL protein as model target in vitro and in cells, which indicates that the strategy has great potential for in vivo application. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. The Degradome database: mammalian proteases and diseases of proteolysis.

    Quesada, Víctor; Ordóñez, Gonzalo R; Sánchez, Luis M; Puente, Xose S; López-Otín, Carlos

    2009-01-01

    The degradome is defined as the complete set of proteases present in an organism. The recent availability of whole genomic sequences from multiple organisms has led us to predict the contents of the degradomes of several mammalian species. To ensure the fidelity of these predictions, our methods have included manual curation of individual sequences and, when necessary, direct cloning and sequencing experiments. The results of these studies in human, chimpanzee, mouse and rat have been incorporated into the Degradome database, which can be accessed through a web interface at http://degradome.uniovi.es. The annotations about each individual protease can be retrieved by browsing catalytic classes and families or by searching specific terms. This web site also provides detailed information about genetic diseases of proteolysis, a growing field of great importance for multiple users. Finally, the user can find additional information about protease structures, protease inhibitors, ancillary domains of proteases and differences between mammalian degradomes.

  1. Conformational changes in DNA gyrase revealed by limited proteolysis

    Kampranis, S C; Maxwell, A

    1998-01-01

    We have used limited proteolysis to identify conformational changes in DNA gyrase. Gyrase exhibits a proteolytic fingerprint dominated by two fragments, one of approximately 62 kDa, deriving from the A protein, and another of approximately 25 kDa from the B protein. Quinolone binding to the enzyme......-DNA intermediate by calcium ions does not reveal any protection, suggesting that the quinolone-induced conformational change is different from an "open-gate" state of the enzyme. A quinolone-resistant mutant of gyrase fails to give the characteristic quinolone-associated proteolytic signature. The ATP...... does not prevent dimerization since incubation of the enzyme-DNA complex with both ADPNP and quinolones gives rise to a complex whose proteolytic pattern retains the characteristic signature of dimerization but has lost the quinolone-induced protection. As a result, the quinolone-gyrase complex can...

  2. Age-related changes in factor VII proteolysis in vivo.

    Ofosu, F A; Craven, S; Dewar, L; Anvari, N; Andrew, M; Blajchman, M A

    1996-08-01

    Previous studies have reported that pre-operative plasmas of patients over the age of 40 years who developed post-operative deep vein thrombosis (DVT) had approximately twice the amount of proteolysed factor VII found in plasmas of patients in whom prophylaxis with heparin or low M(r) heparin was successful. These and other studies also reported higher concentrations of thrombin-antithrombin III in pre- and post-operative plasmas of patients who developed post-operative thrombosis than in plasmas of patients in whom prophylaxis was successful. Whether the extent of factor VII proteolysis seen in the patients who developed post-operative DVT is related to the severity of their disease or age is not known. This report investigated age-related changes in the concentrations of total factor VII protein, factor VII zymogen, factor VIIa, tissue factor pathway inhibitor, thrombin-antithrombin III, and prothrombin fragment 1 + 2 in normal plasmas and the relationships between these parameters. With the exception of thrombin-antithrombin III, statistically significant increases in the concentrations of these parameters with age were found. Additionally, the differences between the concentrations of total factor VII protein and factor VII zymogen, an index factor VII proteolysis in vivo, were statistically significant only for individuals over age 40. Using linear regression analysis, a significant correlation was found to exist between the concentrations of plasma factor VIIa and prothrombin fragment 1 + 2. Since factor VIIa-tissue factor probably initiates coagulation in vivo, we hypothesize that the elevated plasma factor VIIa (reflecting a less tightly regulated tissue factor activity and therefore increased thrombin production in vivo) accounts for the high risk for post-operative thrombosis seen in individuals over the age of 40.

  3. Cutting Class Harms Grades

    Taylor, Lewis A., III

    2012-01-01

    An accessible business school population of undergraduate students was investigated in three independent, but related studies to determine effects on grades due to cutting class and failing to take advantage of optional reviews and study quizzes. It was hypothesized that cutting classes harms exam scores, attending preexam reviews helps exam…

  4. "No Harm Done"

    Bloomfield, Kim

    2016-01-01

    It has been difficult to secure funding in Denmark to conduct research on third party harm from alcohol. The author relates her experiences in this area and challenges Danish society to examine how other societies have begun to examine this problem....

  5. The PDGF-BB-SOX7 axis-modulated IL-33 in pericytes and stromal cells promotes metastasis through tumour-associated macrophages

    Yang, Yunlong; Andersson, Patrik; Hosaka, Kayoko

    2016-01-01

    Signalling molecules and pathways that mediate crosstalk between various tumour cellular compartments in cancer metastasis remain largely unknown. We report a mechanism of the interaction between perivascular cells and tumour-associated macrophages (TAMs) in promoting metastasis through the IL-33......-ST2-dependent pathway in xenograft mouse models of cancer. IL-33 is the highest upregulated gene through activation of SOX7 transcription factor in PDGF-BB-stimulated pericytes. Gain- and loss-of-function experiments validate that IL-33 promotes metastasis through recruitment of TAMs. Pharmacological...... inhibition of the IL-33-ST2 signalling by a soluble ST2 significantly inhibits TAMs and metastasis. Genetic deletion of host IL-33 in mice also blocks PDGF-BB-induced TAM recruitment and metastasis. These findings shed light on the role of tumour stroma in promoting metastasis and have therapeutic...

  6. Tumour-associated microglia/macrophages predict poor prognosis in high-grade gliomas and correlate with an aggressive tumour subtype

    Sørensen, M D; Dahlrot, R H; Boldt, H B

    2018-01-01

    AIMS: Glioblastomas are highly aggressive and treatment resistant. Increasing evidence suggests that tumour-associated macrophages/microglia (TAMs) facilitate tumour progression by acquiring a M2-like phenotype. Our objective was to investigate the prognostic value of TAMs in gliomas using...... automated quantitative double immunofluorescence. METHODS: Samples from 240 patients with primary glioma were stained with antibodies against ionized calcium-binding adaptor molecule-1 (IBA-1) and cluster of differentiation 204 (CD204) to detect TAMs and M2-like TAMs. The expression levels were quantified...... by software-based classifiers. The associations between TAMs, gemistocytic cells and glioblastoma subtype were examined with immuno- and haematoxylin-eosin stainings. Three tissue arrays containing glioblastoma specimens were included to study IBA-1/CD204 levels in central tumour and tumour periphery...

  7. Harmful Algal Blooms

    Graham, Jennifer L.

    2007-01-01

    What are Harmful Algal Blooms (HABs)? Freshwater and marine harmful algal blooms (HABs) can occur anytime water use is impaired due to excessive accumulations of algae. HAB occurrence is affected by a complex set of physical, chemical, biological, hydrological, and meteorological conditions making it difficult to isolate specific causative environmental factors. Potential impairments include reduction in water quality, accumulation of malodorous scums in beach areas, algal production of toxins potent enough to poison both aquatic and terrestrial organisms, and algal production of taste-and-odor compounds that cause unpalatable drinking water and fish. HABs are a global problem, and toxic freshwater and (or) marine algae have been implicated in human and animal illness and death in over 45 countries worldwide and in at least 27 U.S. States (Yoo and others, 1995; Chorus and Bartram, 1999; Huisman and others, 2005).

  8. Proteolysis in model Portuguese cheeses: Effects of rennet and starter culture.

    Pereira, Cláudia I; Gomes, Eliza O; Gomes, Ana M P; Malcata, F Xavier

    2008-06-01

    To shed further light onto the mechanisms of proteolysis that prevail throughout ripening of Portuguese cheeses, model cheeses were manufactured from bovine milk, following as much as possible traditional manufacture practices - using either animal or plant rennet. The individual role upon proteolysis of two (wild) strains of lactic acid bacteria - viz. Lactococcus lactis and Lactobacillus brevis, which are normally found to high viable numbers in said cheeses, was also considered, either as single or mixed cultures. Our experimental results confirmed the influence of rennet on the proteolysis extent, but not on proteolysis depth. On the other hand, the aforementioned strains clearly improved release of medium- and small-sized peptides, and contributed as well to the free amino acid pool in cheese. Copyright © 2007 Elsevier Ltd. All rights reserved.

  9. Effects of natural plant tenderizers on proteolysis and texture of dry ...

    , and overall acceptability. From these results, it is shown that those enzymes as a raw plant juices could be used as tenderizers in dry sausage production. Keywords: Dry sausages, wild boar meat, plant enzymes, proteolysis, texture, sensory ...

  10. Islam and harm reduction.

    Kamarulzaman, A; Saifuddeen, S M

    2010-03-01

    Although drugs are haram and therefore prohibited in Islam, illicit drug use is widespread in many Islamic countries throughout the world. In the last several years increased prevalence of this problem has been observed in many of these countries which has in turn led to increasing injecting drug use driven HIV/AIDS epidemic across the Islamic world. Whilst some countries have recently responded to the threat through the implementation of harm reduction programmes, many others have been slow to respond. In Islam, The Quran and the Prophetic traditions or the Sunnah are the central sources of references for the laws and principles that guide the Muslims' way of life and by which policies and guidelines for responses including that of contemporary social and health problems can be derived. The preservation and protection of the dignity of man, and steering mankind away from harm and destruction are central to the teachings of Islam. When viewed through the Islamic principles of the preservation and protection of the faith, life, intellect, progeny and wealth, harm reduction programmes are permissible and in fact provide a practical solution to a problem that could result in far greater damage to the society at large if left unaddressed. Copyright (c) 2009. Published by Elsevier B.V.

  11. Pre-cure freezing affects proteolysis in dry-cured hams.

    Bañón, S; Cayuela, J M; Granados, M V; Garrido, M D

    1999-01-01

    Several parameters (sodium chloride, moisture, intramuscular fat, total nitrogen, non-protein nitrogen, white precipitates, free tyrosine, L* a* b* values and acceptability) related with proteolysis during the curing were compared in dry-cured hams manufactured from refrigerated and frozen/thawed raw material. Pre-cure freezing increased the proteolysis levels significantly (pcured meat, although it does not significantly affect the sensory quality of the dry-cured ham.

  12. Inhibitors of the proteasome reduce the accelerated proteolysis in atrophying rat skeletal muscles.

    Tawa, N E; Odessey, R; Goldberg, A L

    1997-01-01

    Several observations have suggested that the enhanced proteolysis and atrophy of skeletal muscle in various pathological states is due primarily to activation of the ubiquitin-proteasome pathway. To test this idea, we investigated whether peptide aldehyde inhibitors of the proteasome, N-acetyl-leucyl-leucyl-norleucinal (LLN), or the more potent CBZ-leucyl-leucyl-leucinal (MG132) suppressed proteolysis in incubated rat skeletal muscles. These agents (e.g., MG132 at 10 microM) inhibited nonlyso...

  13. 11S Storage globulin from pumpkin seeds: regularities of proteolysis by papain.

    Rudakova, A S; Rudakov, S V; Kakhovskaya, I A; Shutov, A D

    2014-08-01

    Limited proteolysis of the α- and β-chains and deep cleavage of the αβ-subunits by the cooperative (one-by-one) mechanism was observed in the course of papain hydrolysis of cucurbitin, an 11S storage globulin from seeds of the pumpkin Cucurbita maxima. An independent analysis of the kinetics of the limited and cooperative proteolyses revealed that the reaction occurs in two successive steps. In the first step, limited proteolysis consisting of detachments of short terminal peptides from the α- and β-chains was observed. The cooperative proteolysis, which occurs as a pseudo-first order reaction, started at the second step. Therefore, the limited proteolysis at the first step plays a regulatory role, impacting the rate of deep degradation of cucurbitin molecules by the cooperative mechanism. Structural alterations of cucurbitin induced by limited proteolysis are suggested to generate its susceptibility to cooperative proteolysis. These alterations are tentatively discussed on the basis of the tertiary structure of the cucurbitin subunit pdb|2EVX in comparison with previously obtained data on features of degradation of soybean 11S globulin hydrolyzed by papain.

  14. Regulation of proteolysis in Bacillus subtilis: effects of calcium ions and energy poisons

    O'Hara, M.B.; Hageman, J.H.

    1987-01-01

    Bacillus subtilis cells carry out extensive intracellular proteolysis (k = 0.15-0.23/h) during sporulation. Protein degradation was measured in cells growing in chemically defined sporulation medium, by following the release of [ 14 C]-leucine from the cells during spore formation. Sodium arsenate, carbonyl cyanide 3-chlorophenyl hydrazone, and sodium azide strongly inhibited proteolysis without altering cell viability greatly, which suggested that bulk proteolysis in B. subtilis is energy dependent. The authors have tested the hypothesis that the energy requirement may be for pumping in Ca 2+ . When [Ca 2+ ] was -6 , rates of proteolysis in sporulating cells were reduced 4-8 times that in cells in calcium ion- sufficient medium. Further, omission of Ca 2+ from the medium prevented the increase in the activity of the major intracellular serine protease. However, the presence of energy poisons in the media at levels which inhibited proteolysis, had no detectable effect on the uptake of by cells [ 45 Ca]. The authors concluded that B. subtilis cells required both metabolic energy and calcium ions for normal proteolysis

  15. Sequence analysis of PROTEOLYSIS 6 from Solanum lycopersicum

    Roslan, Nur Farhana; Chew, Bee Lyn; Goh, Hoe-Han; Isa, Nurulhikma Md

    2018-04-01

    The N-end rule pathway is a protein degradation pathway that relates the protein half-life with the identity of its N-terminal residues. A destabilizing N-terminal residues is created by enzymatic reaction or chemical modifications. This destabilized substrate will be recognized by PROTEOLYSIS 6 (PRT6) protein, which encodes an E3 ligase enzyme and resulted in substrate degradation by proteasome. PRT6 has been studied in Arabidopsis thaliana and barley but not yet been studied in fleshy fruit plants. Hence, this study was carried out in tomato that is known as the model for fleshy fruit plants. BLASTX analysis identified that Solyc09g010830 which encodes for a PRT6 gene in tomato based on its sequence similarity with PRT6 in A. thaliana. In silico gene expression analysis shows that PRT6 gene was highly expressed in tomato fruits breaker +5. Co-expression analysis shows that PRT6 may not only involved in abiotic stresses but also in biotic stresses. The objective is to analyze the sequence and characterize PRT6 gene in tomato.

  16. Acid-Mediated Tumor Proteolysis: Contribution of Cysteine Cathepsins

    Jennifer M Rothberg

    2013-10-01

    Full Text Available One of the noncellular microenvironmental factors that contribute to malignancy of solid tumors is acidic peritumoral pH. We have previously demonstrated that extracellular acidosis leads to localization of the cysteine pro-tease cathepsin B on the tumor cell membrane and its secretion. The objective of the present study was to determine if an acidic extracellular pH such as that observed in vivo (i.e., pHe 6.8 affects the activity of proteases, e.g., cathepsin B, that contribute to degradation of collagen IV by tumor cells when grown in biologically relevant three-dimensional (3D cultures. For these studies, we used 1 3D reconstituted basement membrane overlay cultures of human carcinomas, 2 live cell imaging assays to assess proteolysis, and 3 in vivo imaging of active tumor proteases. At pHe 6.8, there were increases in pericellular active cysteine cathepsins and in degradation of dye-quenched collagen IV, which was partially blocked by a cathepsin B inhibitor. Imaging probes for active cysteine cathepsins localized to tumors in vivo. The amount of bound probe decreased in tumors in bicarbonate-treated mice, a treatment previously shown to increase peritumoral pHe and reduce local invasion of the tumors. Our results are consistent with the acid-mediated invasion hypothesis and with a role for cathepsin B in promoting degradation of a basement membrane protein substrate, i.e., type IV collagen, in an acidic peritumoral environment.

  17. Proteolysis of truncated hemolysin A yields a stable dimerization interface

    Novak, Walter R.P.; Bhattacharyya, Basudeb; Grilley, Daniel P.; Weaver, Todd M. (Wabash); (UW)

    2017-02-21

    Wild-type and variant forms of HpmA265 (truncated hemolysin A) fromProteus mirabilisreveal a right-handed, parallel β-helix capped and flanked by segments of antiparallel β-strands. The low-salt crystal structures form a dimeric structureviathe implementation of on-edge main-chain hydrogen bonds donated by residues 243–263 of adjacent monomers. Surprisingly, in the high-salt structures of two variants, Y134A and Q125A-Y134A, a new dimeric interface is formedviamain-chain hydrogen bonds donated by residues 203–215 of adjacent monomers, and a previously unobserved tetramer is formed. In addition, an eight-stranded antiparallel β-sheet is formed from the flap regions of crystallographically related monomers in the high-salt structures. This new interface is possible owing to additional proteolysis of these variants after Tyr240. The interface formed in the high-salt crystal forms of hemolysin A variants may mimic the on-edge β-strand positioning used in template-assisted hemolytic activity.

  18. Imaging Proteolysis by Living Human Breast Cancer Cells

    Mansoureh Sameni

    2000-01-01

    Full Text Available Malignant progression is accompanied by degradation of extracellular matrix proteins. Here we describe a novel confocal assay in which we can observe proteolysis by living human breast cancer cells (BT20 and BT549 through the use of quenchedfluorescent protein substrates. Degradation thus was imaged, by confocal optical sectioning, as an accumulation of fluorescent products. With the BT20 cells, fluorescence was localized to pericellular focal areas that coincide with pits in the underlying matrix. In contrast, fluorescence was localized to intracellular vesicles in the BT549 cells, vesicles that also label for lysosomal markers. Neither intracellular nor pericellular fluorescence was observed in the BT549 cells in the presence of cytochalasin B, suggesting that degradation occurred intracellularly and was dependent on endocytic uptake of substrate. In the presence of a cathepsin 13-selective cysteine protease inhibitor, intracellular fluorescence was decreased ~90% and pericellular fluorescence decreased 67% to 96%, depending on the protein substrate. Matrix metallo protease inhibitors reduced pericellular fluorescence ~50%, i.e., comparably to a serine and a broad spectrum cysteine protease inhibitor. Our results suggest that: 1 a proteolytic cascade participates in pericellular digestion of matrix proteins by living human breast cancer cells, and 2 the cysteine protease cathepsin B participates in both pericellular and intracellular digestion of matrix proteins by living human breast cancer cells.

  19. Casting light on harm reduction

    Jourdan, Michael

    2009-01-01

    Background: Harm reduction is commonly regarded as complementary to other drug problem responses - as the fourth tier. Yet even core examples of harm reduction such as the provision of injection equipment and methadone treatment has over and over encountered considerable opposition, and harm redu...

  20. Alcohol harm reduction in Europe

    Herring, Rachel; Betsy, Thom; Beccaria, Franca

    2010-01-01

    The EMCDDA’s 10th scientific monograph, entitled Harm reduction: evidence, impacts and challenges provides a comprehensive overview of the harm reduction field. Part I of the monograph looks back at the emergence of harm reduction approaches and their diffusion, and explores the concept from diff...

  1. Effects of proteolysis on the adenosinetriphosphatase activities of thymus myosin

    Vu, N.D.; Wagner, P.D.

    1987-01-01

    Limited proteolysis was used to identify regions on the heavy chains of calf thymus myosin which may be involved in ATP and actin binding. Assignments of the various proteolytic fragments to different parts of the myosin heavy chain were based on solubility, gel filtration, electron microscopy, and binding of 32 P-labeled regulatory light chains. Chymotrypsin rapidly cleaved within the head of thymus myosin to give a 70,000-dalton N-terminal fragment and a 140,000-dalton C-terminal fragment. These two fragments did not dissociate under nondenaturing conditions. Cleavage within the myosin tail to give heavy meromyosin occurred more slowly. Cleavage at the site 70,000 daltons from the N-terminus of the heavy chain caused about a 30-fold decrease in the actin concentration required to achieve half-maximal stimulation of the magnesium-adenosinetriphosphatase (Mg-ATPase) activity of unphosphorylated thymus myosin. The actin-activated ATPase activity of this digested myosin was only slightly affected by light chain phosphorylation. Actin inhibited the cleavage at this site by chymotrypsin. In the presence of ATP, chymotrypsin rapidly cleaved the thymus myosin heavy chain at an additional site about 4000 daltons from the N-terminus. Cleavage at this site caused a 2-fold increase in the ethylenediaminetetraacetic acid-ATPase activity and 3-fold decreases in the Ca 2+ - and Mg-ATPase activities of thymus myosin. Thus, cleavage at the N-terminus of thymus myosin was affected by ATP, and this cleavage altered ATPase activity. Papain cleaved the thymus myosin heavy chain about 94,000 daltons from the N-terminus to give subfragment 1. Although this subfragment 1 contained intact light chains, its actin-activated ATPase activity was not affected by light chain phosphorylation

  2. Infiltration of tumour-associated macrophages in prostate biopsy specimens is predictive of disease progression after hormonal therapy for prostate cancer.

    Nonomura, Norio; Takayama, Hitoshi; Nakayama, Masashi; Nakai, Yasutomo; Kawashima, Atsunari; Mukai, Masatoshi; Nagahara, Akira; Aozasa, Katsuyuki; Tsujimura, Akira

    2011-06-01

    • To evaluate tumour-associated macrophage (TAM) infiltration in prostate biopsy specimens as a possible prognostic factor for prostate cancer (PCa) after hormonal therapy. • Immunostaining of TAMs in prostate biopsy specimens was performed using a monoclonal antibody CD68 for 71 patients having PCa treated with hormonal therapy. • Six microscopic (×400) fields around the cancer foci were selected for TAM counting. • The median value of serum prostate-specific antigen (PSA) was 50.1 ng/mL, and the median TAM count was 22. • Recurrence-free survival was significantly better in patients with fewer TAMs (<22) than in those with higher numbers of TAMs (≥22) (P < 0.001). • TAM count was higher in those with higher serum PSA (PSA), higher Gleason score, clinical T stage or those with PSA failure. Cox multivariate analysis showed that TAM count is one of the prognostic factors for PCa treated by hormonal therapy (P < 0.0001). • TAM infiltration in prostate needle biopsy specimens is a useful predictive factor for PSA failure or progression of PCa after hormonal therapy. © 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.

  3. Molecular characterization of a proteolysis-resistant lipase from Bacillus pumilus SG2

    R. Sangeetha

    2014-06-01

    Full Text Available Proteolysis-resistant lipases can be well exploited by industrial processes which employ both lipase and protease as biocatalysts. A proteolysis resistant lipase from Bacillus pumilus SG2 was isolated, purified and characterized earlier. The lipase was resistant to native and commercial proteases. In the present work, we have characterized the lip gene which encodes the proteolysis-resistant lipase from Bacillus pumilus SG2. The parameters and structural details of lipase were analysed. The lip gene consisted of 650 bp. The experimental molecular weight of SG2 lipase was nearly double that of its theoretical molecular weight, thus suggesting the existence of the functional lipase as a covalent dimer. The proteolytic cleavage sites of the lipase would have been made inaccessible by dimerisation, thus rendering the lipase resistant to protease.

  4. Effects of radiation therapy on tissue and serum concentrations of tumour associated trypsin inhibitor and their prognostic significance in rectal cancer patients

    Stenman Ulf-Håkan

    2011-08-01

    Full Text Available Abstract Background We have previously demonstrated that elevated concentrations of tumour-associated trypsin inhibitor (TATI in both tumour tissue (t-TATI and in serum (s-TATI are associated with a poor prognosis in colorectal cancer patients. It was also found that s-TATI concentrations were lower in patients with rectal cancer compared to patients with colon cancer. In this study, we investigated the effects of neoadjuvant radiotherapy (RT on concentrations of t-TATI and s-TATI in patients with rectal cancer. Methods TATI was analysed in serum, normal mucosa and tumour tissue collected at various time points in 53 rectal cancer patients enrolled in a case-control study where 12 patients received surgery alone, 20 patients 5 × 5 Gy (short-term preoperative RT and 21 patients 25 × 2 Gy (long-term preoperative RT. T-TATI was analysed by immunohistochemistry and s-TATI was determined by an immunofluorometric assay. Mann-Whitney U test and Wilcoxon Z (Z test were used to assess t-TATI and s-TATI concentrations in relation to RT. Spearman's correlation (R test was used to explore the associations between t-TATI, s-TATI and clinicopathological parameters. Overall survival (OS according to high and low t-TATI and s-TATI concentrations was estimated by classification and regression tree analysis, Kaplan-Meier analysis and the log rank test. Results RT did not affect concentrations of t-TATI or s-TATI. In patients receiving short-term but not long-term RT, s-TATI concentrations were significantly higher 4 weeks post surgery than in serum drawn prior to surgery (Z = -3.366, P Conclusions The results presented here further validate the utility of t-TATI and s-TATI as prognostic biomarkers in patients with rectal cancer, independent of neoadjuvant RT.

  5. The cachectic mediator proteolysis inducing factor activates NF-kappaB and STAT3 in human Kupffer cells and monocytes

    Watchorn, T.M.; Dowidar, N.; Dejong, C.H.; Waddell, I.D.; Garden, O.J.; Ross, J.A.

    2005-01-01

    A novel proteoglycan, proteolysis inducing factor (PIF), is capable of inducing muscle proteolysis during the process of cancer cachexia, and of inducing an acute phase response in human hepatocytes. We investigated whether PIF is able to activate pro-inflammatory pathways in human Kupffer cells,

  6. Helping Self-Harming Students

    Selekman, Matthew D.

    2009-01-01

    Approximately 14 to 17 percent of adolescents today self-harm, deliberately cutting, burning, or bruising themselves. Most self-harming adolescents use the behavior as a coping strategy to get immediate relief from emotional distress or other stressors in their lives. Stressors include fitting in with peers, activity and homework overload, fears…

  7. European rating of drug harms

    van Amsterdam, Jan; Nutt, David; Phillips, Lawrence; van den Brink, Wim

    2015-01-01

    The present paper describes the results of a rating study performed by a group of European Union (EU) drug experts using the multi-criteria decision analysis model for evaluating drug harms. Forty drug experts from throughout the EU scored 20 drugs on 16 harm criteria. The expert group also assessed

  8. Energy and calcium ion dependence of proteolysis during sporulation of Bacillus subtilis cells

    O'Hara, M.B.; Hageman, J.H.

    1990-01-01

    The authors have shown, with an optimized [ 14 C]leucine-labeling and chasing procedure, that intracellular protein degradation in sporulating cells of Bacillus subtilis 168 (trpC2) is apparently energy dependent. Sodium arsenate, sodium azide, carbonyl cyanide m-chlorophenylhydrozone, and N,N'-dicyclohexylcarbodiimide, at levels which did not induce appreciable lysis (≤ 10%) over 10-h periods of sporulation, inhibited intracellular proteolysis by 13 to 93%. Exponentially growing cells acquired arsenate resistance. In contrast to earlier reports, the authors found that chloramphenicol strongly inhibited proteolysis even when added 6 h into the sporulation process. Restricting the calcium ion concentration in the medium had no effect on rates or extent of vegetative growth, strongly inhibited sporulation, and inhibited rates of proteolysis by 60% or more. Inhibitors of energy metabolism, at the same levels which inhibited proteolysis, did not affect the rate or degree of uptake of Ca 2+ by cells. Restricting the Ca 2+ concentration in the medium reduced by threefold of the specific activity in cells of the major intracellular serine proteinase after 12 h of sporulation. finally, cells of a mutant of B. subtilis bearing an insertionally inactivated gene for the Ca 2+ -dependent intracellular proteinase-1 degraded protein in chemically defined sporulation medium at a rate indistinguishable from that of the wild-type cells for period of 8 h

  9. A primary study on texture modification and proteolysis of mao-tofu ...

    Proteolysis occurred during fermentation was evaluated by SDS-PAGE and chemical analysis. Results from Texture Profile Analysis showed that adhesiveness of mao-tofu had an increase trend while hardness, cohesiveness and springiness had a decrease trend as fermentation progressed. SEM analysis showed that the ...

  10. Characterization of linear forms of the circular enterocin AS-48 obtained by limited proteolysis

    Montalbán-López, Manuel; Spolaore, Barbara; Pinato, Odra; Martínez-Bueno, Manuel; Valdivia, Eva; Maqueda, Mercedes; Fontana, Angelo

    2008-01-01

    AS-48 is a 70-residue circular peptide from Enterococcus faecalis with a broad antibacterial activity. Here, we produced by limited proteolysis a protein species carrying a single nicking and fragments of 55 and 38 residues. Nicked AS-48 showed a lower helicity by far-ultraviolet circular dichroism

  11. Immobilization of trypsin on miniature incandescent bulbs for infrared-assisted proteolysis

    Ge, Huimin; Bao, Huimin; Zhang, Luyan; Chen, Gang, E-mail: gangchen@fudan.edu.cn

    2014-10-03

    Highlights: • Trypsin was immobilized on miniature incandescent bulbs via chitosan coating. • The bulbs acted as enzymatic reactors and the generators of infrared radiation. • The bulb bioreactors were successfully employed in infrared-assisted proteolysis. • The proteolysis could accomplish within 5 min with high sequence coverages. - Abstract: A novel efficient proteolysis approach was developed based on trypsin-immobilized miniature incandescent bulbs and infrared (IR) radiation. Trypsin was covalently immobilized in the chitosan coating on the outer surface of miniature incandescent bulbs with the aid of glutaraldehyde. When an illuminated enzyme-immobilized bulb was immersed in protein solution, the emitted IR radiation could trigger and accelerate heterogeneous protein digestion. The feasibility and performance of the novel proteolysis approach were demonstrated by the digestion of hemoglobin (HEM), cytochrome c (Cyt-c), lysozyme (LYS), and ovalbumin (OVA) and the digestion time was significantly reduced to 5 min. The obtained digests were identified by MALDI-TOF-MS with the sequence coverages of 91%, 77%, 80%, and 52% for HEM, Cyt-c, LYS, and OVA (200 ng μL{sup −1} each), respectively. The suitability of the prepared bulb bioreactors to complex proteins was demonstrated by digesting human serum.

  12. Proteolysis produced within biofilms of bacterial isolates from raw milk tankers.

    Teh, Koon Hoong; Flint, Steve; Palmer, Jon; Andrewes, Paul; Bremer, Phil; Lindsay, Denise

    2012-06-15

    In this study, six bacterial isolates that produced thermo-resistant enzymes isolated from the internal surfaces of raw milk tankers were evaluated for their ability to produce proteolysis within either single culture biofilms or co-culture biofilms. Biofilms were formed in an in vitro model system that simulated the upper internal surface of a raw milk tanker during a typical summer's day of milk collection in New Zealand. The bacterial isolates were further evaluated for their ability to form biofilms at 25, 30 and 37°C. Mutual and competitive effects were observed in some of the co-culture biofilms, with all isolates being able to form biofilms in either single culture or co-culture at the three temperatures. The proteolysis was also evaluated in both biofilms and corresponding planktonic cultures. The proteolysis per cell decreased as the temperature of incubation (20-37°C) increased. Furthermore, mutualistic interactions in terms of proteolysis were observed when cultures were grown as co-culture biofilms. This is the first study to show that proteolytic enzymes can be produced in biofilms on the internal surfaces of raw milk tankers. This has important implications for the cleaning and the temperature control of raw milk transport tankers. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Effects of radiation therapy on tissue and serum concentrations of tumour associated trypsin inhibitor and their prognostic significance in rectal cancer patients

    Gaber, Alexander; Jirström, Karin; Stene, Christina; Hotakainen, Kristina; Nodin, Björn; Palmquist, Ingrid; Bjartell, Anders; Stenman, Ulf-Håkan; Jeppsson, Bengt; Johnson, Louis B

    2011-01-01

    We have previously demonstrated that elevated concentrations of tumour-associated trypsin inhibitor (TATI) in both tumour tissue (t-TATI) and in serum (s-TATI) are associated with a poor prognosis in colorectal cancer patients. It was also found that s-TATI concentrations were lower in patients with rectal cancer compared to patients with colon cancer. In this study, we investigated the effects of neoadjuvant radiotherapy (RT) on concentrations of t-TATI and s-TATI in patients with rectal cancer. TATI was analysed in serum, normal mucosa and tumour tissue collected at various time points in 53 rectal cancer patients enrolled in a case-control study where 12 patients received surgery alone, 20 patients 5 × 5 Gy (short-term) preoperative RT and 21 patients 25 × 2 Gy (long-term) preoperative RT. T-TATI was analysed by immunohistochemistry and s-TATI was determined by an immunofluorometric assay. Mann-Whitney U test and Wilcoxon Z (Z) test were used to assess t-TATI and s-TATI concentrations in relation to RT. Spearman's correlation (R) test was used to explore the associations between t-TATI, s-TATI and clinicopathological parameters. Overall survival (OS) according to high and low t-TATI and s-TATI concentrations was estimated by classification and regression tree analysis, Kaplan-Meier analysis and the log rank test. RT did not affect concentrations of t-TATI or s-TATI. In patients receiving short-term but not long-term RT, s-TATI concentrations were significantly higher 4 weeks post surgery than in serum drawn prior to surgery (Z = -3.366, P < 0.001). T-TATI expression correlated with male gender (R = 0.406, P = 0.008). High t-TATI expression in surgical specimens was associated with a significantly shorter OS (P = 0.045). S-TATI concentrations in serum drawn at all time points were associated with an impaired OS (P = 0.035 before RT, P = 0.001 prior to surgery, P = 0.043 post surgery). At all time points, s-TATI correlated with higher age (P < 0

  14. Reducing Alcohol Harm. International Benchmark

    2008-01-01

    last 10 years.12 Apart from the cost of medical care, the cost of alcohol use can also be associated with absenteeism and property damage. Alcohol...related harms cost British industry approximately £2 billion a year13 and the NHS about £1.7 billion a year14. Alcohol affects labour and productivity...Harmful drinking, Factsheet, June (2007). 15 “ Absenteeism due to drink”, Healthcare Today Magazine, September 19th, 2007. (Accessed on 19/09/07, at

  15. Sex-work harm reduction.

    Rekart, Michael L

    2005-12-17

    Sex work is an extremely dangerous profession. The use of harm-reduction principles can help to safeguard sex workers' lives in the same way that drug users have benefited from drug-use harm reduction. Sex workers are exposed to serious harms: drug use, disease, violence, discrimination, debt, criminalisation, and exploitation (child prostitution, trafficking for sex work, and exploitation of migrants). Successful and promising harm-reduction strategies are available: education, empowerment, prevention, care, occupational health and safety, decriminalisation of sex workers, and human-rights-based approaches. Successful interventions include peer education, training in condom-negotiating skills, safety tips for street-based sex workers, male and female condoms, the prevention-care synergy, occupational health and safety guidelines for brothels, self-help organisations, and community-based child protection networks. Straightforward and achievable steps are available to improve the day-to-day lives of sex workers while they continue to work. Conceptualising and debating sex-work harm reduction as a new paradigm can hasten this process.

  16. Peptides Displayed as High Density Brush Polymers Resist Proteolysis and Retain Bioactivity

    2015-01-01

    We describe a strategy for rendering peptides resistant to proteolysis by formulating them as high-density brush polymers. The utility of this approach is demonstrated by polymerizing well-established cell-penetrating peptides (CPPs) and showing that the resulting polymers are not only resistant to proteolysis but also maintain their ability to enter cells. The scope of this design concept is explored by studying the proteolytic resistance of brush polymers composed of peptides that are substrates for either thrombin or a metalloprotease. Finally, we demonstrate that the proteolytic susceptibility of peptide brush polymers can be tuned by adjusting the density of the polymer brush and offer in silico models to rationalize this finding. We contend that this strategy offers a plausible method of preparing peptides for in vivo use, where rapid digestion by proteases has traditionally restricted their utility. PMID:25314576

  17. Harm minimization among teenage drinkers

    Jørgensen, Morten Hulvej; Curtis, Tine; Christensen, Pia Haudrup

    2007-01-01

    AIM: To examine strategies of harm minimization employed by teenage drinkers. DESIGN, SETTING AND PARTICIPANTS: Two periods of ethnographic fieldwork were conducted in a rural Danish community of approximately 2000 inhabitants. The fieldwork included 50 days of participant observation among 13....... In regulating the social context of drinking they relied on their personal experiences more than on formalized knowledge about alcohol and harm, which they had learned from prevention campaigns and educational programmes. CONCLUSIONS: In this study we found that teenagers may help each other to minimize alcohol...

  18. Autophagic dysfunction in a lysosomal storage disorder due to impaired proteolysis

    Elrick, Matthew J.; Lieberman, Andrew P.

    2013-01-01

    Alterations in macroautophagy (hereafter referred to as “autophagy”) are a common feature of lysosomal storage disorders, and have been hypothesized to play a major role in the pathogenesis of these diseases. We have recently reported multiple defects in autophagy contributing to the lysosomal storage disorder Niemann-Pick type C (NPC). These include increased formation of autophagosomes, slowed turnover of autophagosomes secondary to impaired lysosomal proteolysis, and delivery of stored lip...

  19. Extracellular proteolysis in structural and functional plasticity of mossy fiber synapses in hippocampus

    Grzegorz eWiera

    2015-11-01

    Full Text Available Brain is continuously altered in response to experience and environmental changes. One of the underlying mechanisms is synaptic plasticity, which is manifested by modification of synapse structure and function. It is becoming clear that regulated extracellular proteolysis plays a pivotal role in the structural and functional remodeling of synapses during brain development, learning and memory formation. Clearly, plasticity mechanisms may substantially differ between projections. Mossy fiber synapses onto CA3 pyramidal cells display several unique functional features, including pronounced short-term facilitation, a presynaptically expressed LTP that is independent of NMDAR activation, and NMDA-dependent metaplasticity. Moreover, structural plasticity at mossy fiber synapses ranges from the reorganization of projection topology after hippocampus-dependent learning, through intrinsically different dynamic properties of synaptic boutons to pre- and postsynaptic structural changes accompanying LTP induction. Although concomitant functional and structural plasticity in this pathway strongly suggests a role of extracellular proteolysis, its impact only starts to be investigated in this projection. In the present report, we review the role of extracellular proteolysis in various aspects of synaptic plasticity in hippocampal mossy fiber synapses. A growing body of evidence demonstrates that among perisynaptic proteases, tPA/plasmin system, β-site amyloid precursor protein-cleaving enzyme 1 (BACE1 and metalloproteinases play a crucial role in shaping plastic changes in this projection. We discuss recent advances and emerging hypotheses on the roles of proteases in mechanisms underlying mossy fiber target specific synaptic plasticity and memory formation.

  20. Collagen fibril architecture, domain organization, and triple-helical conformation govern its proteolysis.

    Perumal, Shiamalee; Antipova, Olga; Orgel, Joseph P R O

    2008-02-26

    We describe the molecular structure of the collagen fibril and how it affects collagen proteolysis or "collagenolysis." The fibril-forming collagens are major components of all mammalian connective tissues, providing the structural and organizational framework for skin, blood vessels, bone, tendon, and other tissues. The triple helix of the collagen molecule is resistant to most proteinases, and the matrix metalloproteinases that do proteolyze collagen are affected by the architecture of collagen fibrils, which are notably more resistant to collagenolysis than lone collagen monomers. Until now, there has been no molecular explanation for this. Full or limited proteolysis of the collagen fibril is known to be a key process in normal growth, development, repair, and cell differentiation, and in cancerous tumor progression and heart disease. Peptide fragments generated by collagenolysis, and the conformation of exposed sites on the fibril as a result of limited proteolysis, regulate these processes and that of cellular attachment, but it is not known how or why. Using computational and molecular visualization methods, we found that the arrangement of collagen monomers in the fibril (its architecture) protects areas vulnerable to collagenolysis and strictly governs the process. This in turn affects the accessibility of a cell interaction site located near the cleavage region. Our observations suggest that the C-terminal telopeptide must be proteolyzed before collagenase can gain access to the cleavage site. Collagenase then binds to the substrate's "interaction domain," which facilitates the triple-helix unwinding/dissociation function of the enzyme before collagenolysis.

  1. New concepts in molecular imaging: non-invasive MRI spotting of proteolysis using an Overhauser effect switch.

    Philippe Mellet

    Full Text Available Proteolysis, involved in many processes in living organisms, is tightly regulated in space and time under physiological conditions. However deregulation can occur with local persistent proteolytic activities, e.g. in inflammation, cystic fibrosis, tumors, or pancreatitis. Furthermore, little is known about the role of many proteases, hence there is a need of new imaging methods to visualize specifically normal or disease-related proteolysis in intact bodies.In this paper, a new concept for non invasive proteolysis imaging is proposed. Overhauser-enhanced Magnetic Resonance Imaging (OMRI at 0.2 Tesla was used to monitor the enzymatic hydrolysis of a nitroxide-labeled protein. In vitro, image intensity switched from 1 to 25 upon proteolysis due to the associated decrease in the motional correlation time of the substrate. The OMRI experimental device used in this study is consistent with protease imaging in mice at 0.2 T without significant heating. Simulations show that this enzymatic-driven OMRI signal switch can be obtained at lower frequencies suitable for larger animals or humans.The method is highly sensitive and makes possible proteolysis imaging in three dimensions with a good spatial resolution. Any protease could be targeted specifically through the use of taylor-made cleavable macromolecules. At short term OMRI of proteolysis may be applied to basic research as well as to evaluate therapeutic treatments in small animal models of experimental diseases.

  2. Weathering product-harm crises

    Cleeren, K.; Dekimpe, M.G.; Helsen, K.

    2008-01-01

    To counter the negative effects of a product-harm crisis, brands hope to capitalize on their equity, and often use advertising as a communication device to regain customers’ lost trust. We study how consumer characteristics and advertising influence consumers’ first-purchase decisions for two

  3. Deliberate self harm in children.

    Krishnakumar, P; Geeta, M G; Riyaz, A

    2011-05-01

    To study the nature of deliberate self-harm (DSH) in children and to identify the associated factors. Child Guidance Clinic attached to the Department of Pediatrics of a teaching hospital in South India. Children with history of deliberate self harm who were referred to the CGC for psychological evaluation during a 10 year period. Children and parents were interviewed together and separately and details regarding age, sex, family and school environment, stresses and nature of self harm were documented. Psychiatric diagnosis was made based on DSM IV diagnostic criteria. Among the 30 children included in the study, 21 were boys and 9 were girls. Majority of children were between the ages of 11 and 13 years, the youngest being 6 years old. 76%of children had history of acute stressful life events and 62%of them had chronic ongoing stress. 62%of children had stress in the family and 41%had stress at school. Stress in the family included death of a parent, conflicts with parents or siblings, mental illness in the family, parental alcoholism and parental disharmony. Stress at school included conflicts with classmates, punishment or negative comments by teachers and learning problems. Psychiatric disorders were present in 52%of children, the commonest being depressive disorder. The commonest mode of DSH was self poisoning, and rat poison (zinc phosphide) was the commonest substance used. Deliberate self harm occurs in young children and the risk factors are comparable to those in adolescents.

  4. Managing Product-Harm Crises

    H.J. van Heerde (Harald); K. Helsen; M.G. Dekimpe (Marnik)

    2005-01-01

    textabstractProduct-harm crises are among a firm’s worst nightmares. Since marketing investments may be instrumental to convince consumers to purchase the firm's products again, it is important to provide an adequate measurement of the effectiveness of these investments, especially after the crisis.

  5. The lumbrical muscle: a novel in situ system to evaluate adult skeletal muscle proteolysis and anticatabolic drugs for therapeutic purposes.

    Bergantin, Leandro Bueno; Figueiredo, Leonardo Bruno; Godinho, Rosely Oliveira

    2011-12-01

    The molecular regulation of skeletal muscle proteolysis and the pharmacological screening of anticatabolic drugs have been addressed by measuring tyrosine release from prepubertal rat skeletal muscles, which are thin enough to allow adequate in vitro diffusion of oxygen and substrates. However, the use of muscle at accelerated prepubertal growth has limited the analysis of adult muscle proteolysis or that associated with aging and neurodegenerative diseases. Here we established the adult rat lumbrical muscle (4/hindpaw; 8/rat) as a new in situ experimental model for dynamic measurement of skeletal muscle proteolysis. By incubating lumbrical muscles attached to their individual metatarsal bones in Tyrode solution, we showed that the muscle proteolysis rate of adult and aged rats (3-4 to 24 mo old) is 45-25% of that in prepubertal animals (1 mo old), which makes questionable the usual extrapolation of proteolysis from prepubertal to adult/senile muscles. While acute mechanical injury or 1- to 7-day denervation increased tyrosine release from adult lumbrical muscle by up to 60%, it was reduced by 20-28% after 2-h incubation with β-adrenoceptor agonists, forskolin or phosphodiesterase inhibitor IBMX. Using inhibitors of 26S-proteasome (MG132), lysosome (methylamine), or calpain (E64/leupeptin) systems, we showed that ubiquitin-proteasome is accountable for 40-50% of total lumbrical proteolysis of adult, middle-aged, and aged rats. In conclusion, the lumbrical model allows the analysis of muscle proteolysis rate from prepubertal to senile rats. By permitting eight simultaneous matched measurements per rat, the new model improves similar protocols performed in paired extensor digitorum longus (EDL) muscles from prepubertal rats, optimizing the pharmacological screening of drugs for anticatabolic purposes.

  6. cAMP-dependent proteolysis of GATA-6 is linked to JNK-signaling pathway

    Ushijima, Hironori [Department of Molecular Biology, School of Pharmacy, Iwate Medical University, 2-1-1, Nishitokuta, Yahaba, Shiwagun, Iwate 028-3694 (Japan); Maeda, Masatomo, E-mail: mmaeda@iwate-med.ac.jp [Department of Molecular Biology, School of Pharmacy, Iwate Medical University, 2-1-1, Nishitokuta, Yahaba, Shiwagun, Iwate 028-3694 (Japan)

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer A JNK inhibitor SP600125 inhibited cAMP-dependent proteolysis of GATA-6. Black-Right-Pointing-Pointer Effect of a JNK activator anisomycin on the proteolysis was examined. Black-Right-Pointing-Pointer Anisomycin stimulated the export of nuclear GATA-6 into the cytoplasm. Black-Right-Pointing-Pointer JNK activated the CRM1 mediated nuclear export of GATA-6. Black-Right-Pointing-Pointer JNK further stimulated slowly the degradation of GATA-6 by cytoplasmic proteasomes. -- Abstract: A JNK inhibitor SP600125 inhibited cAMP-dependent proteolysis of GATA-6 by proteasomes around its IC50. We further examined the effects of SP600125 on the degradation of GATA-6 in detail, since an activator of JNK (anisomycin) is available. Interestingly, anisomycin immediately stimulated the export of nuclear GATA-6 into the cytoplasm, and then the cytoplasmic content of GATA-6 decreased slowly through degradation by proteasomes. Such an effect of anisomycin was inhibited by SP600125, indicating that the observed phenomenon might be linked to the JNK signaling pathway. The inhibitory effect of SP600125 could not be ascribed to the inhibition of PKA, since phosphorylation of CREB occurred in the presence of dbcAMP and SP600125. The nuclear export of GATA-6 was inhibited by leptomycin B, suggesting that CRM1-mediated export could be activated by anisomycin. Furthermore, it seems likely that the JNK activated by anisomycin may stimulate not only the nuclear export of GATA-6 through CRM1 but also the degradation of GATA-6 by cytoplasmic proteasomes. In contrast, A-kinase might activate only the latter process through JNK.

  7. Pregnancy Cravings Can Harm Your Oral Health

    ... 2018 About | Contact InfoBites Quick Reference Learn more Oral Health and Overal Health Gum Disease and Cardiovascular Health ... your desktop! more... Pregnancy Cravings Can Harm Your Oral Health Article Chapters Pregnancy Cravings Can Harm Your Oral ...

  8. Use of high-gradient magnetic fishing for reducing proteolysis during fermentation

    Maury, Trine Lütken; Ottow, Kim Ekelund; Brask, Jesper

    2012-01-01

    Proteolysis during fermentation may have a severe impact on the yield and quality of a secreted product. In the current study, we demonstrate the use of high-gradient magnetic fishing (HGMF) as an efficient alternative to the more conventional methods of preventing proteolytic degradation....... Bacitracin-linked magnetic affinity adsorbents were employed directly in a fermenter during Bacillus licheniformis cultivation to remove trace amounts of unwanted proteases. The constructed magnetic adsorbents had excellent, highly specific binding characteristics in the fermentation broth (K(d) = 1...

  9. Autophagic dysfunction in a lysosomal storage disorder due to impaired proteolysis.

    Elrick, Matthew J; Lieberman, Andrew P

    2013-02-01

    Alterations in macroautophagy (hereafter referred to as "autophagy") are a common feature of lysosomal storage disorders, and have been hypothesized to play a major role in the pathogenesis of these diseases. We have recently reported multiple defects in autophagy contributing to the lysosomal storage disorder Niemann-Pick type C (NPC). These include increased formation of autophagosomes, slowed turnover of autophagosomes secondary to impaired lysosomal proteolysis, and delivery of stored lipids to the lysosome via autophagy. The study summarized here describes novel methods for the interrogation of individual stages of the autophagic pathway, and suggests mechanisms by which lipid storage may result in broader lysosomal dysfunction.

  10. Histopathological growth pattern, proteolysis and angiogenesis in chemonaive patients resected for multiple colorectal liver metastases

    Eefsen, Rikke Løvendahl; Van den Eynden, Gert G; Høyer-Hansen, Gunilla

    2012-01-01

    The purpose of this study was to characterise growth patterns, proteolysis, and angiogenesis in colorectal liver metastases from chemonaive patients with multiple liver metastases. Twenty-four patients were included in the study, resected for a median of 2.6 metastases. The growth pattern......-type plasminogen activator receptor (P = 0.0008). Angiogenesis was most pronounced in metastases with a pushing growth pattern in comparison to those with desmoplastic (P = 0.0007) and replacement growth pattern (P = 0.021). Although a minor fraction of the patients harboured metastases with different growth...

  11. Bituminization of biologically harmful wastes

    Freund, M.; Magyar, M.; Mozes, G.; Csikos, R.; Kristof, M.; Toth, L.; Hima, G.

    1977-01-01

    The invention claims the bitumenization of biologically harmful wastes, such as industrial wastes containing radioactive materials. These wastes containing water are transported from sludge basins, this either by gravity or by mechanical stirrino. into a suitably adapted absorption zone or to several parallel zones filled with bitumen heated to 100 to 250 degC. An inert gas is forced into the system foaming the zone contents. The foam phase is decomposed by the action of heat while water is evaporated and condensed. Bitumen containing dry matter of the radioactive wastes is discharged from the bottom part of the absorption zone and stored in a tank. (Kr)

  12. [Dutch parliament legitimizes harmful quackery].

    van Dam, Frits S A M; Renckens, Cees N M

    2010-01-01

    The Dutch parliament has recently accepted a tax law in which certain groups of alternative therapists can be exempt from VAT. To be eligible for this VAT exemption, the disciplines to which the therapists belong have to meet certain training requirements. In this article it is contended, in agreement with the Royal College of Physicians in the UK, that statutory regulation is inappropriate for disciplines whose therapies are neither of proved benefit nor appropriately tested. It legitimizes harmful therapies. This is illustrated by two serious accidents, previously described in this journal, caused by a chiropractor and a craniosacral therapist.

  13. Nonsuicidal Self-Harm among Community Adolescents: Understanding the "Whats" and "Whys" of Self-Harm

    Laye-Gindhu, Aviva; Schonert-Reichl, Kimberly A.

    2005-01-01

    This study examines self-harm in a community sample of adolescents. More specifically, the study identifies the prevalence and types of self-harm, elucidates the nature and underlying function of self-harm, and evaluates the relation of psychological adjustment, sociodemographic, and health-risk variables to self-harm. Self-report questionnaires…

  14. Overexpression of the essential Sis1 chaperone reduces TDP-43 effects on toxicity and proteolysis

    Park, Sei-Kyoung; Hong, Joo Y.; Arslan, Fatih; Tietsort, Alex; Tank, Elizabeth M. H.; Li, Xingli

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by selective loss of motor neurons with inclusions frequently containing the RNA/DNA binding protein TDP-43. Using a yeast model of ALS exhibiting TDP-43 dependent toxicity, we now show that TDP-43 overexpression dramatically alters cell shape and reduces ubiquitin dependent proteolysis of a reporter construct. Furthermore, we show that an excess of the Hsp40 chaperone, Sis1, reduced TDP-43’s effect on toxicity, cell shape and proteolysis. The strength of these effects was influenced by the presence of the endogenous yeast prion, [PIN+]. Although overexpression of Sis1 altered the TDP-43 aggregation pattern, we did not detect physical association of Sis1 with TDP-43, suggesting the possibility of indirect effects on TDP-43 aggregation. Furthermore, overexpression of the mammalian Sis1 homologue, DNAJB1, relieves TDP-43 mediated toxicity in primary rodent cortical neurons, suggesting that Sis1 and its homologues may have neuroprotective effects in ALS. PMID:28531192

  15. Proteolysis of proBDNF is a key regulator in the formation of memory.

    Philip Barnes

    2008-09-01

    Full Text Available It is essential to understand the molecular processes underlying long-term memory to provide therapeutic targets of aberrant memory that produce pathological behaviour in humans. Under conditions of recall, fully-consolidated memories can undergo reconsolidation or extinction. These retrieval-mediated memory processes may rely on distinct molecular processes. The cellular mechanisms initiating the signature molecular events are not known. Using infusions of protein synthesis inhibitors, antisense oligonucleotide targeting brain-derived neurotrophic factor (BDNF mRNA or tPA-STOP (an inhibitor of the proteolysis of BDNF protein into the hippocampus of the awake rat, we show that acquisition and extinction of contextual fear memory depended on the increased and decreased proteolysis of proBDNF (precursor BDNF in the hippocampus, respectively. Conditions of retrieval that are known to initiate the reconsolidation of contextual fear memory, a BDNF-independent memory process, were not correlated with altered proBDNF cleavage. Thus, the processing of BDNF was associated with the acquisition of new information and the updating of information about a salient stimulus. Furthermore, the differential requirement for the processing of proBDNF by tPA in distinct memory processes suggest that the molecular events actively engaged to support the storage and/or the successful retrieval of memory depends on the integration of ongoing experience with past learning.

  16. Proteolysis of Sardine (Sardina pilchardus and Anchovy (Stolephorus commersonii by Commercial Enzymes in Saline Solutions

    Chau Minh Le

    2015-01-01

    Full Text Available Fish sauce production is a very long process and there is a great interest in shortening it. Among the different strategies to speed up this process, the addition of external proteases could be a solution. This study focuses on the eff ect of two commercial enzymes (Protamex and Protex 51FP on the proteolysis of two fish species traditionally converted into fish sauce: sardine and anchovy, by comparison with classical autolysis. Hydrolysis reactions were conducted with fresh fish at a temperature of 30 °C and under different saline conditions (from 0 to 30 % NaCl. Hydrolysis degree and liquefaction of the raw material were used to follow the process. As expected, the proteolysis decreased with increasing amount of salt. Regarding the fi sh species, higher rate of liquefaction and higher hydrolysis degree were obtained with anchovy. Between the two proteases, Protex 51FP gave better results with both fi sh types. This study demonstrates that the addition of commercial proteases could be helpful for the liquefaction of fi sh and cleavage of peptide bonds that occur during fi sh sauce production and thus speed up the production process.

  17. The role of extracellular proteolysis in synaptic plasticity of the central nervous system 

    Anna Konopka

    2012-11-01

    Full Text Available The extracellular matrix (ECM of the central nervous system has a specific structure and protein composition that are different from those in other organs. Today we know that the ECM not only provides physical scaffolding for the neurons and glia, but also actively modifies their functions. Over the last two decades, a growing body of research evidence has been collected, suggesting an important role of ECM proteolysis in synaptic plasticity of the brain. So far the majority of data concern two large families of proteases: the serine proteases and the matrix metalloproteinases. The members of these families are localized at the synapses, and are secreted into the extracellular space in an activity-dependent manner. The proteases remodel the local environment as well as influencing synapse structure and function. The structural modifications induced by proteases include shape and size changes, as well as synapse elimination, and synaptogenesis. The functional changes include modifications of receptor function in the postsynaptic part of the synapse, as well as the potentiation or depression of neurotransmitter secretion by the presynaptic site. The present review summarizes the current view on the role of extracellular proteolysis in the physiological synaptic plasticity underlying the phenomena of learning and memory, as well as in the pathological plasticity occurring during epileptogenesis or development of drug addiction. 

  18. Increased intracellular proteolysis reduces disease severity in an ER stress-associated dwarfism.

    Mullan, Lorna A; Mularczyk, Ewa J; Kung, Louise H; Forouhan, Mitra; Wragg, Jordan Ma; Goodacre, Royston; Bateman, John F; Swanton, Eileithyia; Briggs, Michael D; Boot-Handford, Raymond P

    2017-10-02

    The short-limbed dwarfism metaphyseal chondrodysplasia type Schmid (MCDS) is linked to mutations in type X collagen, which increase ER stress by inducing misfolding of the mutant protein and subsequently disrupting hypertrophic chondrocyte differentiation. Here, we show that carbamazepine (CBZ), an autophagy-stimulating drug that is clinically approved for the treatment of seizures and bipolar disease, reduced the ER stress induced by 4 different MCDS-causing mutant forms of collagen X in human cell culture. Depending on the nature of the mutation, CBZ application stimulated proteolysis of misfolded collagen X by either autophagy or proteasomal degradation, thereby reducing intracellular accumulation of mutant collagen. In MCDS mice expressing the Col10a1.pN617K mutation, CBZ reduced the MCDS-associated expansion of the growth plate hypertrophic zone, attenuated enhanced expression of ER stress markers such as Bip and Atf4, increased bone growth, and reduced skeletal dysplasia. CBZ produced these beneficial effects by reducing the MCDS-associated abnormalities in hypertrophic chondrocyte differentiation. Stimulation of intracellular proteolysis using CBZ treatment may therefore be a clinically viable way of treating the ER stress-associated dwarfism MCDS.

  19. The use of in situ proteolysis in the crystallization of murine CstF-77

    Bai, Yun; Auperin, Thierry C.; Tong, Liang

    2007-01-01

    In situ proteolysis with fungal protease or subtilisin is crucial for the crystallization of murine CstF-77. The cleavage-stimulation factor (CstF) is required for the cleavage of the 3′-end of messenger RNA precursors in eukaryotes. During structure determination of the 77 kDa subunit of the murine CstF complex (CstF-77), it was serendipitously discovered that a solution infected by a fungus was crucial for the crystallization of this protein. CstF-77 was partially proteolyzed during crystallization; this was very likely to have been catalyzed by a protease secreted by the fungus. It was found that the fungal protease can be replaced by subtilisin and this in situ proteolysis protocol produced crystals of sufficient size for structural studies. After an extensive search, it was found that 55% glucose can be used as a cryoprotectant while maintaining the diffraction quality of the crystals; most other commonly used cryoprotectants were detrimental to the diffraction quality

  20. Bystander protein protects potential vaccine-targeting ligands against intestinal proteolysis.

    Reuter, Fabian; Bade, Steffen; Hirst, Timothy R; Frey, Andreas

    2009-07-20

    Endowing mucosal vaccines with ligands that target antigen to mucosal lymphoid tissues may improve immunization efficacy provided that the ligands withstand the proteolytic environment of the gastro-intestinal tract until they reach their destination. Our aim was to investigate whether and how three renowned ligands - Ulex europaeus agglutinin I and the B subunits of cholera toxin and E. coli heat-labile enterotoxin - master this challenge. We assessed the digestive power of natural murine intestinal fluid (natIF) using assays for trypsin, chymotrypsin and pancreatic elastase along with a test for nonspecific proteolysis. The natIF was compared with simulated murine intestinal fluid (simIF) that resembled the trypsin, chymotrypsin and elastase activities of its natural counterpart but lacked or contained albumins as additional protease substrates. The ligands were exposed to the digestive fluids and degradation was determined. The studies revealed that (i) the three pancreatic endoproteases constitute only one third of the total protease activity of natIF and (ii) the ligands resist proteolysis in natIF and protein-enriched simIF over 3 h but (iii) are partially destroyed in simIF that lacks additional protease substrate. We assume that the proteins of natIF are preferred substrates for the intestinal proteases and thus can protect vaccine-targeting ligands from destruction.

  1. Calpain-mediated proteolysis of tropomodulin isoforms leads to thin filament elongation in dystrophic skeletal muscle.

    Gokhin, David S; Tierney, Matthew T; Sui, Zhenhua; Sacco, Alessandra; Fowler, Velia M

    2014-03-01

    Duchenne muscular dystrophy (DMD) induces sarcolemmal mechanical instability and rupture, hyperactivity of intracellular calpains, and proteolytic breakdown of muscle structural proteins. Here we identify the two sarcomeric tropomodulin (Tmod) isoforms, Tmod1 and Tmod4, as novel proteolytic targets of m-calpain, with Tmod1 exhibiting ∼10-fold greater sensitivity to calpain-mediated cleavage than Tmod4 in situ. In mdx mice, increased m-calpain levels in dystrophic soleus muscle are associated with loss of Tmod1 from the thin filament pointed ends, resulting in ∼11% increase in thin filament lengths. In mdx/mTR mice, a more severe model of DMD, Tmod1 disappears from the thin filament pointed ends in both tibialis anterior (TA) and soleus muscles, whereas Tmod4 additionally disappears from soleus muscle, resulting in thin filament length increases of ∼10 and ∼12% in TA and soleus muscles, respectively. In both mdx and mdx/mTR mice, both TA and soleus muscles exhibit normal localization of α-actinin, the nebulin M1M2M3 domain, Tmod3, and cytoplasmic γ-actin, indicating that m-calpain does not cause wholesale proteolysis of other sarcomeric and actin cytoskeletal proteins in dystrophic skeletal muscle. These results implicate Tmod proteolysis and resultant thin filament length misspecification as novel mechanisms that may contribute to DMD pathology, affecting muscles in a use- and disease severity-dependent manner.

  2. Excess alpha chains are lost from beta-thalassemic reticulocytes by proteolysis

    Testa, U.; Hinard, N.; Beuzard, Y.; Tsapis, A.; Galacteros, F.; Thomopoulos, P.; Rosa, J.

    1981-01-01

    During incubation of reticulocytes from patients with beta-thalassemia, after labeling of the hemoglobin with radioactive amino acids, the excess alpha chains are gradually lost from the cells. The aim of this study was to investigate the mechanism of this phenomenon. A system was developed in which reticulocytes from beta-thalassemia patients are labeled with [3H]leucine, washed several times in nonradioactive medium, and then incubated in the same medium containing puromycin added in order to stop further protein synthesis. The results have clearly shown that excess alpha chains are gradually degraded by proteolysis. N-ethylmaleimide or epsilon-aminocaproic acid inhibited the proteolysis of free alpha chains. The addition of either ATP or hemin did not change the rate of alpha chain degradation. The time required to degrade 50% of the pool of free alpha chains was directly dependent on the initial value of this pool. This finding suggests the absence of a significant individual variation in the ability to proteolyse free alpha chains

  3. Hepatic steatosis inhibits autophagic proteolysis via impairment of autophagosomal acidification and cathepsin expression

    Inami, Yoshihiro; Yamashina, Shunhei; Izumi, Kousuke; Ueno, Takashi; Tanida, Isei; Ikejima, Kenichi; Watanabe, Sumio

    2011-01-01

    Highlights: → Acidification of autophagosome was blunted in steatotic hepatocytes. → Hepatic steatosis did not disturb fusion of isolated autophagosome and lysosome. → Proteinase activity of cathepsin B and L in autolysosomes was inhibited by steatosis. → Hepatic expression of cathepsin B and L was suppressed by steatosis. -- Abstract: Autophagy, one of protein degradation system, contributes to maintain cellular homeostasis and cell defense. Recently, some evidences indicated that autophagy and lipid metabolism are interrelated. Here, we demonstrate that hepatic steatosis impairs autophagic proteolysis. Though accumulation of autophagosome is observed in hepatocytes from ob/ob mice, expression of p62 was augmented in liver from ob/ob mice more than control mice. Moreover, degradation of the long-lived protein leucine was significantly suppressed in hepatocytes isolated from ob/ob mice. More than 80% of autophagosomes were stained by LysoTracker Red (LTR) in hepatocytes from control mice; however, rate of LTR-stained autophagosomes in hepatocytes were suppressed in ob/ob mice. On the other hand, clearance of autolysosomes loaded with LTR was blunted in hepatocytes from ob/ob mice. Although fusion of isolated autophagosome and lysosome was not disturbed, proteinase activity of cathepsin B and L in autolysosomes and cathepsin B and L expression of liver were suppressed in ob/ob mice. These results indicate that lipid accumulation blunts autophagic proteolysis via impairment of autophagosomal acidification and cathepsin expression.

  4. Hepatic steatosis inhibits autophagic proteolysis via impairment of autophagosomal acidification and cathepsin expression

    Inami, Yoshihiro [Department of Gastroenterology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421 (Japan); Yamashina, Shunhei, E-mail: syamashi@juntendo.ac.jp [Department of Gastroenterology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421 (Japan); Izumi, Kousuke [Department of Gastroenterology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421 (Japan); Ueno, Takashi [Department of Biochemistry, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421 (Japan); Tanida, Isei [Department of Biochemistry and Cell Biology, Laboratory of Biomembranes, National Institute of Infectious Disease, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640 (Japan); Ikejima, Kenichi; Watanabe, Sumio [Department of Gastroenterology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421 (Japan)

    2011-09-09

    Highlights: {yields} Acidification of autophagosome was blunted in steatotic hepatocytes. {yields} Hepatic steatosis did not disturb fusion of isolated autophagosome and lysosome. {yields} Proteinase activity of cathepsin B and L in autolysosomes was inhibited by steatosis. {yields} Hepatic expression of cathepsin B and L was suppressed by steatosis. -- Abstract: Autophagy, one of protein degradation system, contributes to maintain cellular homeostasis and cell defense. Recently, some evidences indicated that autophagy and lipid metabolism are interrelated. Here, we demonstrate that hepatic steatosis impairs autophagic proteolysis. Though accumulation of autophagosome is observed in hepatocytes from ob/ob mice, expression of p62 was augmented in liver from ob/ob mice more than control mice. Moreover, degradation of the long-lived protein leucine was significantly suppressed in hepatocytes isolated from ob/ob mice. More than 80% of autophagosomes were stained by LysoTracker Red (LTR) in hepatocytes from control mice; however, rate of LTR-stained autophagosomes in hepatocytes were suppressed in ob/ob mice. On the other hand, clearance of autolysosomes loaded with LTR was blunted in hepatocytes from ob/ob mice. Although fusion of isolated autophagosome and lysosome was not disturbed, proteinase activity of cathepsin B and L in autolysosomes and cathepsin B and L expression of liver were suppressed in ob/ob mice. These results indicate that lipid accumulation blunts autophagic proteolysis via impairment of autophagosomal acidification and cathepsin expression.

  5. Impact of microencapsulated peptidase (Aspergillus oryzae) on cheddar cheese proteolysis and its biologically active peptide profile.

    Seneweera, Saman; Kailasapathy, Kaila

    2011-07-01

    We investigated the delivery of calcium-alginate encapsulated peptidase (Flavourzyme(®), Aspergillus oryzae) on proteolysis of Cheddar cheese. Physical and chemical characteristics such as moisture, pH and fat content were measured, and no differences were found between control and experimental cheese at day 0. SDS-PAGE analysis clearly showed that proteolysis of α and k casein was significantly accelerated after three months of maturity in the experimental cheese. A large number of low molecular weight peptides were found in the water soluble fraction of the experimental cheeses and some of these peptides were new. N-terminal amino acid sequence analysis identified these as P(1), Leu-Thu-Glu; P(3), Asp-Val-Pro-Ser-Glu) and relatively abundant stable peptides P(2), P(4), Arg-Pro-Lys-His-Pro-Ile; P(5), Arg-Pro-Lys-His-Pro-Ile-Lys and P(6). These peptides were mainly originated from αs1-CN and β-CN. Three of the identified peptides (P(1), P(2), P(3) and P(4)) are known to biologically active and P(1) and P(3) were only present in experimental cheese suggesting that experimental cheese has improved health benefits.

  6. Proteolysis inside the membrane is a rate-governed reaction not driven by substrate affinity.

    Dickey, Seth W; Baker, Rosanna P; Cho, Sangwoo; Urban, Siniša

    2013-12-05

    Enzymatic cleavage of transmembrane anchors to release proteins from the membrane controls diverse signaling pathways and is implicated in more than a dozen diseases. How catalysis works within the viscous, water-excluding, two-dimensional membrane is unknown. We developed an inducible reconstitution system to interrogate rhomboid proteolysis quantitatively within the membrane in real time. Remarkably, rhomboid proteases displayed no physiological affinity for substrates (K(d) ~190 μM/0.1 mol%). Instead, ~10,000-fold differences in proteolytic efficiency with substrate mutants and diverse rhomboid proteases were reflected in k(cat) values alone. Analysis of gate-open mutant and solvent isotope effects revealed that substrate gating, not hydrolysis, is rate limiting. Ultimately, a single proteolytic event within the membrane normally takes minutes. Rhomboid intramembrane proteolysis is thus a slow, kinetically controlled reaction not driven by transmembrane protein-protein affinity. These properties are unlike those of other studied proteases or membrane proteins but are strikingly reminiscent of one subset of DNA-repair enzymes, raising important mechanistic and drug-design implications. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Harm reduction principles for healthcare settings

    Mary Hawk

    2017-10-01

    Full Text Available Abstract Background Harm reduction refers to interventions aimed at reducing the negative effects of health behaviors without necessarily extinguishing the problematic health behaviors completely. The vast majority of the harm reduction literature focuses on the harms of drug use and on specific harm reduction strategies, such as syringe exchange, rather than on the harm reduction philosophy as a whole. Given that a harm reduction approach can address other risk behaviors that often occur alongside drug use and that harm reduction principles have been applied to harms such as sex work, eating disorders, and tobacco use, a natural evolution of the harm reduction philosophy is to extend it to other health risk behaviors and to a broader healthcare audience. Methods Building on the extant literature, we used data from in-depth qualitative interviews with 23 patients and 17 staff members from an HIV clinic in the USA to describe harm reduction principles for use in healthcare settings. Results We defined six principles of harm reduction and generalized them for use in healthcare settings with patients beyond those who use illicit substances. The principles include humanism, pragmatism, individualism, autonomy, incrementalism, and accountability without termination. For each of these principles, we present a definition, a description of how healthcare providers can deliver interventions informed by the principle, and examples of how each principle may be applied in the healthcare setting. Conclusion This paper is one of the firsts to provide a comprehensive set of principles for universal harm reduction as a conceptual approach for healthcare provision. Applying harm reduction principles in healthcare settings may improve clinical care outcomes given that the quality of the provider-patient relationship is known to impact health outcomes and treatment adherence. Harm reduction can be a universal precaution applied to all individuals regardless of

  8. Harm reduction principles for healthcare settings.

    Hawk, Mary; Coulter, Robert W S; Egan, James E; Fisk, Stuart; Reuel Friedman, M; Tula, Monique; Kinsky, Suzanne

    2017-10-24

    Harm reduction refers to interventions aimed at reducing the negative effects of health behaviors without necessarily extinguishing the problematic health behaviors completely. The vast majority of the harm reduction literature focuses on the harms of drug use and on specific harm reduction strategies, such as syringe exchange, rather than on the harm reduction philosophy as a whole. Given that a harm reduction approach can address other risk behaviors that often occur alongside drug use and that harm reduction principles have been applied to harms such as sex work, eating disorders, and tobacco use, a natural evolution of the harm reduction philosophy is to extend it to other health risk behaviors and to a broader healthcare audience. Building on the extant literature, we used data from in-depth qualitative interviews with 23 patients and 17 staff members from an HIV clinic in the USA to describe harm reduction principles for use in healthcare settings. We defined six principles of harm reduction and generalized them for use in healthcare settings with patients beyond those who use illicit substances. The principles include humanism, pragmatism, individualism, autonomy, incrementalism, and accountability without termination. For each of these principles, we present a definition, a description of how healthcare providers can deliver interventions informed by the principle, and examples of how each principle may be applied in the healthcare setting. This paper is one of the firsts to provide a comprehensive set of principles for universal harm reduction as a conceptual approach for healthcare provision. Applying harm reduction principles in healthcare settings may improve clinical care outcomes given that the quality of the provider-patient relationship is known to impact health outcomes and treatment adherence. Harm reduction can be a universal precaution applied to all individuals regardless of their disclosure of negative health behaviors, given that health

  9. Enzymatically structured emulsions in simulated gastrointestinal environment: impact on interfacial proteolysis and diffusion in intestinal mucus.

    Macierzanka, Adam; Böttger, Franziska; Rigby, Neil M; Lille, Martina; Poutanen, Kaisa; Mills, E N Clare; Mackie, Alan R

    2012-12-18

    Fundamental knowledge of physicochemical interactions in the gastrointestinal environment is required in order to support rational designing of protein-stabilized colloidal food and pharmaceutical delivery systems with controlled behavior. In this paper, we report on the colloidal behavior of emulsions stabilized with the milk protein sodium caseinate (Na-Cas), and exposed to conditions simulating the human upper gastrointestinal tract. In particular, we looked at how the kinetics of proteolysis was affected by adsorption to an oil-water interface in emulsion and whether the proteolysis and the emulsion stability could be manipulated by enzymatic structuring of the interface. After cross-linking with the enzyme transglutaminase, the protein was digested with use of an in vitro model of gastro-duodenal proteolysis in the presence or absence of physiologically relevant surfactants (phosphatidylcholine, PC; bile salts, BS). Significant differences were found between the rates of digestion of Na-Cas cross-linked in emulsion (adsorbed protein) and in solution. In emulsion, the digestion of a population of polypeptides of M(r) ca. 50-100 kDa was significantly retarded through the gastric digestion. The persistent interfacial polypeptides maintained the original emulsion droplet size and prevented the system from phase separating. Rapid pepsinolysis of adsorbed, non-cross-linked Na-Cas and its displacement by PC led to emulsion destabilization. These results suggest that structuring of emulsions by enzymatic cross-linking of the interfacial protein may affect the phase behavior of emulsion in the stomach and the gastric digestion rate in vivo. Measurements of ζ-potential revealed that BS displaced the remaining protein from the oil droplets during the simulated duodenal phase of digestion. Diffusion of the postdigestion emulsion droplets through ex vivo porcine intestinal mucus was only significant in the presence of BS due to the high negative charge these

  10. The ATPase and protease domains of yeast mitochondrial Lon : Roles in proteolysis and respiration-dependent growth

    van Dijl, JM; Kutejova, E; Suda, K; Perecko, D; Schatz, G; Suzuki, CK

    1998-01-01

    The ATP-dependent Lon protease of Saccharomyces cerevisiae mitochondria is required for selective proteolysis in the matrix, maintenance of mitochondrial DNA, and respiration-dependent growth. Lon may also possess a chaperone-like function that facilitates protein degradation and protein-complex

  11. Chemical and proteolysis-derived changes during long-term storage of lactose-hydrolyzed ultrahigh-temperature (UHT) milk.

    Jansson, Therese; Jensen, Hanne B; Sundekilde, Ulrik K; Clausen, Morten R; Eggers, Nina; Larsen, Lotte B; Ray, Colin; Andersen, Henrik J; Bertram, Hanne C

    2014-11-19

    Proteolytic activity in milk may release bitter-tasting peptides and generate free amino terminals that react with carbohydrates, which initiate Maillard reaction. Ultrahigh temperature (UHT) heat treatment inactivates the majority of proteolytic enzymes in milk. In lactose-hydrolyzed milk a β-galactosidase preparation is applied to the milk after heat treatment, which has proteolytic side activities that may induce quality deterioration of long-term-stored milk. In the present study proteolysis, glycation, and volatile compound formation were investigated in conventional (100% lactose), filtered (60% lactose), and lactose-hydrolyzed (<1% lactose) UHT milk using reverse phase high-pressure liquid chromatography-mass spectrometry, proton nuclear magnetic resonance, and gas chromatography-mass spectrometry. Proteolysis was observed in all milk types. However, the degree of proteolysis was significantly higher in the lactose-hydrolyzed milk compared to the conventional and filtered milk. The proteins most prone to proteolysis were β-CN and αs1-CN, which were clearly hydrolyzed after approximately 90 days of storage in the lactose-hydrolyzed milk.

  12. A model of proteolysis and amino acid biosynthesis for Lactobacillus delbrueckii subsp. bulgaricus in whey.

    Liu, Enuo; Zheng, Huajun; Hao, Pei; Konno, Tomonobu; Yu, Yao; Kume, Hisae; Oda, Munehiro; Ji, Zai-Si

    2012-12-01

    Lactobacillus delbrueckii subsp. bulgaricus 2038 (L. bulgaricus 2038) is a bacterium that is used as a starter for dairy products by Meiji Co., Ltd of Japan. Culturing L. bulgaricus 2038 with whey as the sole nitrogen source results in a shorter lag phase than other milk proteins under the same conditions (carbon source, minerals, and vitamins). Microarray results of gene expression revealed characteristics of amino acid anabolism with whey as the nitrogen source and established a model of proteolysis and amino acid biosynthesis for L. bulgaricus. Whey peptides and free amino acids are readily metabolized, enabling rapid entry into the logarithmic growth phase. The oligopeptide transport system is the primary pathway for obtaining amino acids. Amino acid biosynthesis maintains the balance between amino acids required for cell growth and the amount obtained from environment. The interconversion of amino acids is also important for L. bulgaricus 2038 growth.

  13. MBTPS2 mutations cause defective regulated intramembrane proteolysis in X-linked osteogenesis imperfecta

    Lindert, Uschi; Cabral, Wayne A.; Ausavarat, Surasawadee; Tongkobpetch, Siraprapa; Ludin, Katja; Barnes, Aileen M.; Yeetong, Patra; Weis, Maryann; Krabichler, Birgit; Srichomthong, Chalurmpon; Makareeva, Elena N.; Janecke, Andreas R.; Leikin, Sergey; Röthlisberger, Benno; Rohrbach, Marianne; Kennerknecht, Ingo; Eyre, David R.; Suphapeetiporn, Kanya; Giunta, Cecilia; Marini, Joan C.; Shotelersuk, Vorasuk

    2016-01-01

    Osteogenesis imperfecta (OI) is a collagen-related bone dysplasia. We identified an X-linked recessive form of OI caused by defects in MBTPS2, which encodes site-2 metalloprotease (S2P). MBTPS2 missense mutations in two independent kindreds with moderate/severe OI cause substitutions at highly conserved S2P residues. Mutant S2P has normal stability, but impaired functioning in regulated intramembrane proteolysis (RIP) of OASIS, ATF6 and SREBP transcription factors, consistent with decreased proband secretion of type I collagen. Further, hydroxylation of the collagen lysine residue (K87) critical for crosslinking is reduced in proband bone tissue, consistent with decreased lysyl hydroxylase 1 in proband osteoblasts. Reduced collagen crosslinks presumptively undermine bone strength. Also, proband osteoblasts have broadly defective differentiation. These mutations provide evidence that RIP plays a fundamental role in normal bone development. PMID:27380894

  14. VEGFR2 Trafficking, Signaling and Proteolysis is Regulated by the Ubiquitin Isopeptidase USP8.

    Smith, Gina A; Fearnley, Gareth W; Abdul-Zani, Izma; Wheatcroft, Stephen B; Tomlinson, Darren C; Harrison, Michael A; Ponnambalam, Sreenivasan

    2016-01-01

    Vascular endothelial growth factor A (VEGF-A) regulates many aspects of vascular function. VEGF-A binding to vascular endothelial growth factor receptor 2 (VEGFR2) stimulates endothelial signal transduction and regulates multiple cellular responses. Activated VEGFR2 undergoes ubiquitination but the enzymes that regulate this post-translational modification are unclear. In this study, the de-ubiquitinating enzyme, USP8, is shown to regulate VEGFR2 trafficking, de-ubiquitination, proteolysis and signal transduction. USP8-depleted endothelial cells displayed altered VEGFR2 ubiquitination and production of a unique VEGFR2 extracellular domain proteolytic fragment caused by VEGFR2 accumulation in the endosome-lysosome system. In addition, perturbed VEGFR2 trafficking impaired VEGF-A-stimulated signal transduction in USP8-depleted cells. Thus, regulation of VEGFR2 ubiquitination and de-ubiquitination has important consequences for the endothelial cell response and vascular physiology. © 2015 The Authors. Traffic published by John Wiley & Sons Ltd.

  15. Cross-system excision of chaperone-mediated proteolysis in chaperone-assisted recombinant protein production

    Martínez-Alonso, Mónica; Villaverde, Antonio

    2010-01-01

    Main Escherichia coli cytosolic chaperones such as DnaK are key components of the control quality network designed to minimize the prevalence of polypeptides with aberrant conformations. This is achieved by both favoring refolding activities but also stimulating proteolytic degradation of folding reluctant species. This last activity is responsible for the decrease of the proteolytic stability of recombinant proteins when co-produced along with DnaK, where an increase in solubility might be associated to a decrease in protein yield. However, when DnaK and its co-chaperone DnaJ are co-produced in cultured insect cells or whole insect larvae (and expectedly, in other heterologous hosts), only positive, folding-related effects of these chaperones are observed, in absence of proteolysis-mediated reduction of recombinant protein yield. PMID:21326941

  16. Harm reduction through a social justice lens.

    Pauly, Bernadette

    2008-02-01

    People who are street involved such as those experiencing homelessness and drug use face multiple inequities in health and access to health care. Morbidity and mortality are significantly increased among those who are street involved. Incorporation of a harm reduction philosophy in health care has the potential to shift the moral context of health care delivery and enhance access to health care services. However, harm reduction with a primary focus on reducing the harms of drug use fails focus on the harms associated with the context of drug use such as homelessness, violence and poverty. Ethical analysis of the underlying values of harm reduction and examination of different conceptions of justice are discussed as a basis for action that addresses a broad range of harms associated with drug use. Theories of distributive justice that focus primarily on the distribution of material goods are limited as theoretical frameworks for addressing the root causes of harm associated with drug use. Social justice, reconceptualised and interpreted through a critical lens as described by Iris Marion Young, is presented as a promising alternative ethical framework. A critical reinterpretation of social justice leads to insights that can illuminate structural inequities that contribute to the harms associated with the context of drug use. Such an approach provides promise as means of informing policy that aims to reduce a broad range of harms associated with drug use such as homelessness and poverty.

  17. Implications of the Maillard reaction on bovine alpha-lactalbumin and its proteolysis during in vitro infant digestion.

    Joubran, Yousef; Moscovici, Alice; Portmann, Reto; Lesmes, Uri

    2017-06-21

    This study investigated the functionality and digestibility of Maillard reaction products (MRPs) of alpha-lactalbumin (α-la), a major whey protein and component of infant formulas. The impact of different carbohydrates (glucose, galactose or galacto-oligosaccharides (GOS)) and heating duration was studied. SDS-PAGE, UV and color measurements monitored reaction extent, which varied between carbohydrates whereby galactose reacted more readily than glucose. Surface hydrophobicity and antioxidant capacity were found to be significantly (p Maillard conjugation, with GOS-based MRPs elevating antioxidant capacity ∼50-fold compared to α-la. In addition, the digestive proteolysis of MRPs was evaluated using an infant in vitro gastro-duodenal model. SDS-PAGE analyses of digesta revealed Maillard conjugation generally increased α-la's susceptibility to proteolysis. Interestingly, GOS-based MRPs presented an optimization challenge, since heating for 12 h delayed proteolysis, while extended heating resulted in the highest susceptibility to proteolysis. Proteomic analyses further demonstrated the differences in enzymatic cleavage patterns and helped identify bioactive peptides rendered bioaccessible during the digestion of α-la or its MRPs. Bioinformatic mining of the proteomic data using PeptideRanker also gave rise to two potentially novel bioactive peptides, FQINNKIW and GINYWLAHKALCS. Finally, antioxidant capacity of luminal contents, measured by DPPH, revealed Maillard conjugation increased the antioxidant capacity of both gastric and duodenal digesta. Overall, this work draws a link between the Maillard reaction, digestive proteolysis and the bioaccessibility of bioactive peptides and antioxidant species in the infant alimentary canal. This could help rationally process infant formulas towards improved nutritional and extra-nutritional benefits.

  18. Harmful effects of ultraviolet radiation

    Anon.

    1989-01-01

    Tanning for cosmetic purposes by sunbathing or by using artificial tanning devices is widespread. The hazards associated with exposure to ultraviolet radiation are of concern to the medical profession. Depending on the amount and form of the radiation, as well as on the skin type of the individual exposed, ultraviolet radiation causes erythema, sunburn, photodamage (photoaging), photocarcinogenesis, damage to the eyes, alteration of the immune system of the skin, and chemical hypersensitivity. Skin cancers most commonly produced by ultraviolet radiation are basal and squamous cell carcinomas. There also is much circumstantial evidence that the increase in the incidence of cutaneous malignant melanoma during the past half century is related to increased sun exposure, but this has not been proved. Effective and cosmetically acceptable sunscreen preparations have been developed that can do much to prevent or reduce most harmful effects to ultraviolet radiation if they are applied properly and consistently. Other safety measures include (1) minimizing exposure to ultraviolet radiation, (2) being aware of reflective surfaces while in the sun, (3) wearing protective clothing, (4) avoiding use of artificial tanning devices, and (5) protecting infants and children

  19. Gambling Harm and Crime Careers.

    May-Chahal, Corinne; Humphreys, Leslie; Clifton, Alison; Francis, Brian; Reith, Gerda

    2017-03-01

    Incarcerated populations across the world have been found to be consistently and significantly more vulnerable to problem gambling than general populations in the same countries. In an effort to gain a more specific understanding of this vulnerability the present study applied latent class analysis and criminal career theory to gambling data collected from a sample of English and Scottish, male and female prisoners (N = 1057). Theoretical links between gambling and crime were tested through three hypotheses: (1) that prisoners in the UK would have higher rates of problem gambling behaviour than the national population; (2) that if the link between gambling and crime is coincidental, gambling behaviour would be highly prevalent in an offending population, and (3) if connections between gambling behaviour and offending are co-symptomatic a mediating factor would show a strong association. The first of these was supported, the second was not supported and the third was partially supported. Latent class analysis found six gambling behaviour clusters measured by responses to the Problem Gambling Severity Index, primarily distinguished by loss chasing behaviour. Longitudinal offending data drawn from the Police National Computer database found four criminal career types, distinguished by frequency and persistence over time. A significant association was found between higher level loss chasing and high rate offending in criminal careers suggesting that impulse control may be a mediating factor for both gambling harm and criminal careers.

  20. Adolescent self-harm and risk factors.

    Zhang, Jixiang; Song, Jianwei; Wang, Jing

    2016-12-01

    This study aims to define the characteristics of adolescents who have engaged in self-harm behavior and ascertain the risk factors. From January 2013 to January 2014, 4,176 adolescents from senior middle schools in Linyi, China, were administered four questionnaire surveys to ascertain the following: incidence of self-harm behavior regarding the frequency of different self-harm behaviors by group (never/one to five times/greater than five times in the last 6 months) and then comparing the self-harm behavior of the different subgroups; symptom self-check, comparing the differences between the adolescents with self-harm behavior and without in nine subscales (somatization, obsessive-compulsive symptoms, interpersonal sensitivity, depression, anxiety, hostility, fear, paranoid, and psychosis); Adolescent Self-Rating Life Events Check List scores; and Egna Minnenav Barndoms Uppfostran (EMBU) scores. Multivariate logistic regression analysis was used to determine the risk factors of self-harm in adolescents. The incidence of adolescent self-harm was 27.60%; the occurrence of adolescent self-harm was closely related to their mental health status, stressful life events, and EMBU. Being female, an urban student, or an only child; having poor school performance or experiences of stressful life events, harsh parenting styles, or excessive interference; and poor mental health were the risk factors for adolescent self-harm. The incidence of adolescent self-harm was high, and their mental health status, stressful life events, and EMBU affected the occurrence of adolescent self-harm, which is an issue that needs greater attention. © 2016 John Wiley & Sons Australia, Ltd.

  1. What’s the Harm? Harms in Research with Adults with Intellectual Disability

    McDonald, Katherine E.; Conroy, Nicole E.; Olick, Robert S.

    2017-01-01

    Scientific advances can improve the lives of adults with intellectual disability, yet concerns that research participation may impose harm impede scientific progress. What counts as harmful can be subjective and perceptions of harm may vary among stakeholders. We studied perspectives on the harmfulness of research events among adults with intellectual disability, family members and friends, disability service providers, researchers, and Institutional Review Board members. We found considerable variance. For example, adults with intellectual disability see exclusion from research as more harmful, but most psychosocial harms as less significant than others. All stakeholders agree that having someone else make the participation decision is harmful. Findings provide insights into the concept of harm and ethical research with adults with intellectual disability. PMID:28095059

  2. Mammography screening. Benefits, harms, and informed choice

    Jørgensen, Karsten Juhl

    2013-01-01

    exaggerates benefits, participation is directly recommended, and the harms are downplayed or left out, despite agreement that the objective is informed choice. This raises an ethical discussion concerning autonomy versus paternalism, and the difficulty in weighing benefits against harms. Finally, financial...

  3. Alcohol and self-harm in Anuradhapura

    Sørensen, Jane Brandt; Jayasena, Chandima; Agampodi, Thilini Chanchala

    the personal network of the drinker and lead to secondary traumatization. This can appear as emotional distress, financial difficulties and lead to domestic violence and in some cases self-harm and suicide. This interplay between alcohol and self-harm was investigated in individuals, families and communities...

  4. Harm and the Boundaries of Disease.

    McGivern, Patrick; Sorial, Sarah

    2017-08-01

    What is the relationship between harm and disease? Discussions of the relationship between harm and disease typically suffer from two shortcomings. First, they offer relatively little analysis of the concept of harm itself, focusing instead on examples of clear cases of harm such as death and dismemberment. This makes it difficult to evaluate such accounts in borderline cases, where the putative harms are less severe. Second, they assume that harm-based accounts of disease must be understood normatively rather than naturalistically, in the sense that they are inherently value based. This makes such accounts vulnerable to more general objections of normative accounts of disease. Here we draw on an influential account of harm from the philosophy of law to develop a harm-based account of disease that overcomes both of these shortcomings. © The Author 2017. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Physical harm due to chronic substance use

    van Amsterdam, Jan; Pennings, Ed; Brunt, Tibor; van den Brink, Wim

    2013-01-01

    Chronic use at high dose of illicit drugs, alcohol and tobacco is associated with physical disease. The relative physical harm of these substances has not been described before, but will benefit the guiding of policy measures about licit and illicit substances. The physical harm of 19 addictive

  6. Proteolysis of bovine beta-lactoglobulin during thermal treatment in subdenaturing conditions highlights some structural features of the temperature-modified protein and yields fragments with low immunoreactivity

    Iametti, S.; Rasmussen, P.; Frøkiær, Hanne

    2002-01-01

    Bovine beta-lactoglobulin was hydrolyzed with trypsin or chymotrypsin in the course of heat treatment at 55, 60 and 65 C at neutral pH. At these temperatures beta-lactoglobulin undergoes significant but reversible structural changes. In the conditions used in the present study, beta......-lactoglobulin was virtually insensitive to proteolysis by either enzyme at room temperature, but underwent extensive proteolysis when either protease was present during the heat treatment. High-temperature proteolysis occurs in a progressive manner. Mass spectrometry analysis of some large-sized breakdown intermediates...

  7. [Harmful practices affecting women's health].

    1990-07-01

    The harmful practices discussed in this article are based on case histories form the Central Maternity in Niamey, yet these practices universally affect women throughout Africa. Nutritional taboos are aimed at certain diseases such as measles, diarrhea, dysentery, malnutrition and anemia and consumption of foods rich in proteins and lipids are forbidden. Children are forbidden from eating eggs; pregnant women are forbidden from eating fruits and vegetables because of the fear of hemorrhaging from the sugar content in the fruit; camel meat is forbidden for fear of extending the pregnancy. Female circumcision, a dangerous practice, especially during childbirth, causes many medical problems that remain permanent. Adolescent pregnancy and marriages are practiced to avoid delinquency among children; yet such practices take place because of arranged marriages for a dowry to young men or to older rich men and these forced marriages to adolescents are the causes of increases in divorce, prostitution and desertion. These young marriages have serious consequences on the health status of the mother and the infant, often leading to maternal and infant death. The high level of fertility in Niger is a response to the social structure of the family. It is a patrilineal system that encourages women to have many children, especially sons. In Niger, pregnancy is surrounded by supernatural and mysterious forces, where a child is the intervention for ancestral spirits. In Islam a child is considered a "Gift of God". A woman is expected to work until the delivery of her baby otherwise she is jeered by her neighbors. During delivery women are not expected to cry or show any pain for fear of dishonoring her family irregardless of any medical compilations she faces. Women in Africa are exploited as free labor, deteriorate and age rapidly, are generally illiterate and are not protected under any laws.

  8. Deprivation as un-experienced harm?

    Keerus, Külli; Gjerris, Mickey; Röcklinsberg, Helena

    2017-01-01

    Tom Regan encapsulated his principle of harm as a prima facie direct duty not to harm experiencing subjects of a life. However, his consideration of harm as deprivation, one example of which is loss of freedom, can easily be interpreted as a harm, which may not be experienced by its subject....... This creates a gap between Regan’s criterion for moral status and his account of what our duties are. However, in comparison with three basic paradigms of welfare known in nonhuman animal welfare science, Regan’s understanding coheres with a modified version of a feelings-based paradigm: not only the immediate...... feelings of satisfaction, but also future opportunities to have such feelings, must be taken into account. Such an interpretation is compatible with Regan’s understanding of harm as deprivation. The potential source of confusion, however, lies in Regan’s own possible argumentative mistakes....

  9. Digital Self-Harm Among Adolescents.

    Patchin, Justin W; Hinduja, Sameer

    2017-12-01

    Despite increased media and scholarly attention to digital forms of aggression directed toward adolescents by their peers (e.g., cyberbullying), very little research has explored digital aggression directed toward oneself. "Digital self-harm" is the anonymous online posting, sending, or otherwise sharing of hurtful content about oneself. The current study examined the extent of digital self-harm among adolescents. Survey data were obtained in 2016 from a nationally representative sample of 5,593 American middle and high school students (12-17 years old). Logistic regression analysis was used to identify correlates of participation in digital self-harm. Qualitative responses were also reviewed to better understand motivations for digital self-harm. About 6% of students have anonymously posted something online about themselves that was mean. Males were significantly more likely to report participation (7.1% compared to 5.3%). Several statistically significant correlates of involvement in digital self-harm were identified, including sexual orientation, experience with school bullying and cyberbullying, drug use, participation in various forms of adolescent deviance, and depressive symptoms. Digital self-harm is a new problem that demands additional scholarly attention. A deeper inquiry as to the motivations behind this behavior, and how it correlates to offline self-harm and suicidal ideation, can help direct mental health professionals toward informed prevention approaches. Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  10. Discovery of Anti-Hypertensive Oligopeptides from Adlay Based on In Silico Proteolysis and Virtual Screening

    Liansheng Qiao

    2016-12-01

    Full Text Available Adlay (Coix larchryma-jobi L. was the commonly used Traditional Chinese Medicine (TCM with high content of seed storage protein. The hydrolyzed bioactive oligopeptides of adlay have been proven to be anti-hypertensive effective components. However, the structures and anti-hypertensive mechanism of bioactive oligopeptides from adlay were not clear. To discover the definite anti-hypertensive oligopeptides from adlay, in silico proteolysis and virtual screening were implemented to obtain potential oligopeptides, which were further identified by biochemistry assay and molecular dynamics simulation. In this paper, ten sequences of adlay prolamins were collected and in silico hydrolyzed to construct the oligopeptide library with 134 oligopeptides. This library was reverse screened by anti-hypertensive pharmacophore database, which was constructed by our research team and contained ten anti-hypertensive targets. Angiotensin-I converting enzyme (ACE was identified as the main potential target for the anti-hypertensive activity of adlay oligopeptides. Three crystal structures of ACE were utilized for docking studies and 19 oligopeptides were finally identified with potential ACE inhibitory activity. According to mapping features and evaluation indexes of pharmacophore and docking, three oligopeptides were selected for biochemistry assay. An oligopeptide sequence, NPATY (IC50 = 61.88 ± 2.77 µM, was identified as the ACE inhibitor by reverse-phase high performance liquid chromatography (RP-HPLC assay. Molecular dynamics simulation of NPATY was further utilized to analyze interactive bonds and key residues. ALA354 was identified as a key residue of ACE inhibitors. Hydrophobic effect of VAL518 and electrostatic effects of HIS383, HIS387, HIS513 and Zn2+ were also regarded as playing a key role in inhibiting ACE activities. This study provides a research strategy to explore the pharmacological mechanism of Traditional Chinese Medicine (TCM proteins based on

  11. Suicide Following Deliberate Self-Harm.

    Olfson, Mark; Wall, Melanie; Wang, Shuai; Crystal, Stephen; Gerhard, Tobias; Blanco, Carlos

    2017-08-01

    The authors sought to identify risk factors for repeat self-harm and completed suicide over the following year among adults with deliberate self-harm. A national cohort of Medicaid-financed adults clinically diagnosed with deliberate self-harm (N=61,297) was followed for up to 1 year. Repeat self-harm per 1,000 person-years and suicide rates per 100,000 person-years (based on cause of death information from the National Death Index) were determined. Hazard ratios of repeat self-harm and suicide were estimated by Cox proportional hazard models. During the 12 months after nonfatal self-harm, the rate of repeat self-harm was 263.2 per 1,000 person-years and the rate of completed suicide was 439.1 per 100,000 person-years, or 37.2 times higher than in a matched general population cohort. The hazard of suicide was higher after initial self-harm events involving violent as compared with nonviolent methods (hazard ratio=7.5, 95% CI=5.5-10.1), especially firearms (hazard ratio=15.86, 95% CI=10.7-23.4; computed with poisoning as reference), and to a lesser extent after events of patients who had recently received outpatient mental health care (hazard ratio=1.6, 95% CI=1.2-2.0). Compared with self-harm patients using nonviolent methods, those who used violent methods were at significantly increased risk of suicide during the first 30 days after the initial event (hazard ratio=17.5, 95% CI=11.2-27.3), but not during the following 335 days. Adults treated for deliberate self-harm frequently repeat self-harm in the following year. Patients who use a violent method for their initial self-harm, especially firearms, have an exceptionally high risk of suicide, particularly right after the initial event, which highlights the importance of careful assessment and close follow-up of this group.

  12. Effect of pulp preconditioning on acidification, proteolysis, sugars and free fatty acids concentration during fermentation of cocoa (Theobroma cacao) beans.

    Afoakwa, Emmanuel Ohene; Quao, Jennifer; Budu, Agnes Simpson; Takrama, Jemmy; Saalia, Firibu Kwesi

    2011-11-01

    Changes in acidification, proteolysis, sugars and free fatty acids (FFAs) concentrations of Ghanaian cocoa beans as affected by pulp preconditioning (pod storage or PS) and fermentation were investigated. Non-volatile acidity, pH, proteolysis, sugars (total, reducing and non-reducing) and FFAs concentrations were analysed using standard methods. Increasing PS consistently decreased the non-volatile acidity with concomitant increase in pH during fermentation of the beans. Fermentation decreased the pH of the unstored beans from 6.7 to 4.9 within the first 4 days and then increased slightly again to 5.3 by the sixth day. Protein, total sugars and non-reducing sugars decreased significantly (p cocoa beans was largely affected by fermentation than by PS.

  13. Cell cycle- and cell growth-regulated proteolysis of mammalian CDC6 is dependent on APC-CDH1

    Petersen, B O; Wagener, C; Marinoni, F

    2000-01-01

    is targeted for ubiquitin-mediated proteolysis by the anaphase promoting complex (APC)/cyclosome in G(1). A combination of point mutations in the destruction box and KEN-box motifs in CDC6 stabilizes the protein in G(1) and in quiescent cells. Furthermore, APC, in association with CDH1, ubiquitinates CDC6...... in vitro, and both APC and CDH1 are required and limiting for CDC6 proteolysis in vivo. Although a stable mutant of CDC6 is biologically active, overexpression of this mutant or wild-type CDC6 is not sufficient to induce multiple rounds of DNA replication in the same cell cycle. The APC-CDH1-dependent...

  14. Perennial peanut (Arachis glabrata Benth.) contains polyphenol oxidase (PPO) and PPO substrates that can reduce post-harvest proteolysis.

    Sullivan, Michael L; Foster, Jamie L

    2013-08-15

    Studies of perennial peanut (Arachis glabrata Benth.) suggest its hay and haylage have greater levels of rumen undegraded protein (RUP) than other legume forages such as alfalfa (Medicago sativa L.). Greater RUP can result in more efficient nitrogen utilization by ruminant animals with positive economic and environmental effects. We sought to determine whether, like red clover (Trifolium pretense L.), perennial peanut contains polyphenol oxidase (PPO) and PPO substrates that might be responsible for increased RUP. Perennial peanut extracts contain immunologically detectible PPO protein and high levels of PPO activity (>100 nkatal mg(-1) protein). Addition of caffeic acid (PPO substrate) to perennial peanut extracts depleted of endogenous substrates reduced proteolysis by 90%. Addition of phenolics prepared from perennial peanut leaves to extracts of either transgenic PPO-expressing or control (non-expressing) alfalfa showed peanut phenolics could reduce proteolysis >70% in a PPO-dependent manner. Two abundant likely PPO substrates are present in perennial peanut leaves including caftaric acid. Perennial peanut contains PPO and PPO substrates that together are capable of inhibiting post-harvest proteolysis, suggesting a possible mechanism for increased RUP in this forage. Research related to optimizing the PPO system in other forage crops will likely be applicable to perennial peanut. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

  15. Granzyme B-dependent proteolysis acts as a switch to enhance the proinflammatory activity of IL-1α.

    Afonina, Inna S

    2011-10-21

    Granzyme B is a cytotoxic lymphocyte-derived protease that plays a central role in promoting apoptosis of virus-infected target cells, through direct proteolysis and activation of constituents of the cell death machinery. However, previous studies have also implicated granzymes A and B in the production of proinflammatory cytokines, via a mechanism that remains undefined. Here we show that IL-1α is a substrate for granzyme B and that proteolysis potently enhanced the biological activity of this cytokine in vitro as well as in vivo. Consistent with this, compared with full-length IL-1α, granzyme B-processed IL-1α exhibited more potent activity as an immunoadjuvant in vivo. Furthermore, proteolysis of IL-1α within the same region, by proteases such as calpain and elastase, was also found to enhance its biological potency. Thus, IL-1α processing by multiple immune-related proteases, including granzyme B, acts as a switch to enhance the proinflammatory properties of this cytokine.

  16. Yak milk casein as potential precursor of angiotensin I-converting enzyme inhibitory peptides based on in silico proteolysis.

    Lin, Kai; Zhang, Lan-Wei; Han, Xue; Xin, Liang; Meng, Zhao-Xu; Gong, Pi-Min; Cheng, Da-You

    2018-07-15

    Yak milk casein was selected as a potential precursor of bioactive peptides based on in silico analysis. Most notable among these are the angiotensin I-converting enzyme (ACE) inhibitory peptides. First, yak milk casein has high homology with cow milk casein by homologous analysis. The potential of yak milk casein for the releasing bioactive peptides was evaluated by determining the frequency of occurrence of fragments with a given activity. Through the BIOPEP database analysis, there are many bioactive peptides in yak milk casein sequences. Then, an in silico proteolysis using single or combined enzymes to obtained ACE inhibitory peptides was investigated. Cytotoxicity analysis using the online toxic prediction tool ToxinPred revealed that all in silico proteolysis derived ACE inhibitory peptides are non-cytotoxic. Overall, the present study highlights a in silico proteolysis approach to assist the yak milk casein releasing ACE inhibitory peptides and provides a guidance for the actual hydrolysis of proteins for the production of bioactive peptides. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. [Pharmacological mechanism analysis of oligopeptide from Pinctada fucata based on in silico proteolysis and protein interaction network].

    Chen, Yan-Kun; Qiao, Lian-Sheng; Huo, Xiao-Qian; Zhang, Xu; Han, Na; Zhang, Yan-Ling

    2017-09-01

    Pinctada fucata oligopeptide is one of key pharmaceutical effective constituents of P. fucata. It is significant to analyze its pharmacological effect and mechanism. This study aims to discover the potential oligopeptides from P. fucata and analyze the mechanism of P. fucata oligopeptide based on in silico technologies and protein interaction network(PIN). First, main protein sequences of P. fucata were collected, and oligopeptides were obtained using in silico gastrointestinal tract proteolysis. Then, key potential targets of P. fucata oligopeptides were obtained through pharmacophore screening. The protein-protein interaction(PPI) of targets was achieved and implemented to construct PIN and analyze the mechanism of P. fucata oligopeptides. P. fucata oligopeptide database was constructed based on in silico technologies, including 458 oligopeptides. Twelve modules were identified from PIN by a graph theoretic clustering algorithm Molecular Complex Detection(MCODE) and analyzed by Gene ontology(GO) enrichment. The results indicated that P. fucata oligopeptides have an effect in treating neurological diseases, such as Alzheimer's disease. In silico proteolysis could be used to analyze the protein sequences of traditional Chinese medicine(TCM). According to the combination of in silico proteolysis and PIN, the biological activity of oligopeptides could be interpreted rapidly based on the known TCM protein sequence. The study provides the methodology basis for rapidly and efficiently implementing the mechanism analysis of TCM oligopeptides. Copyright© by the Chinese Pharmaceutical Association.

  18. Involvement of μ/m-calpain in the proteolysis and meat quality changes during postmortem storage of chicken breast muscle.

    Zhao, Liang; Xing, Tong; Huang, Jichao; Qiao, Yan; Chen, Yulian; Huang, Ming

    2018-02-01

    The objective of this study was to investigate the role of calpain isotypes, especially poultry-specific μ/m-calpain in the proteolysis and meat quality changes of chicken breast muscle during postmortem storage. Calpain activity was detected by casein zymography, while the degradation of titin, desmin and Troponin-T was analyzed by sodium dodecyl sulfate - polyacrylamide gel electrophoresis and western blot. Meat quality indicators such as water holding capacity and tenderness were also studied. The correlation analysis between calpain activity, proteolysis and the changes in meat quality indicators indicated that there were strong correlations for μ-calpain during the first 12 h of storage, while such strong correlations for μ/m-calpain were only found in samples stored from 12 h to 7 days. Our study suggested that μ-calpain played a major role in meat quality changes while μ/m-calpain could also be involved but played a limited role in the proteolysis and meat quality changes during 12 h to 7 days postmortem storage of chicken breast muscle. © 2017 Japanese Society of Animal Science.

  19. Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations.

    Lee, Ju-Hyun; Yu, W Haung; Kumar, Asok; Lee, Sooyeon; Mohan, Panaiyur S; Peterhoff, Corrinne M; Wolfe, Devin M; Martinez-Vicente, Marta; Massey, Ashish C; Sovak, Guy; Uchiyama, Yasuo; Westaway, David; Cuervo, Ana Maria; Nixon, Ralph A

    2010-06-25

    Macroautophagy is a lysosomal degradative pathway essential for neuron survival. Here, we show that macroautophagy requires the Alzheimer's disease (AD)-related protein presenilin-1 (PS1). In PS1 null blastocysts, neurons from mice hypomorphic for PS1 or conditionally depleted of PS1, substrate proteolysis and autophagosome clearance during macroautophagy are prevented as a result of a selective impairment of autolysosome acidification and cathepsin activation. These deficits are caused by failed PS1-dependent targeting of the v-ATPase V0a1 subunit to lysosomes. N-glycosylation of the V0a1 subunit, essential for its efficient ER-to-lysosome delivery, requires the selective binding of PS1 holoprotein to the unglycosylated subunit and the Sec61alpha/oligosaccharyltransferase complex. PS1 mutations causing early-onset AD produce a similar lysosomal/autophagy phenotype in fibroblasts from AD patients. PS1 is therefore essential for v-ATPase targeting to lysosomes, lysosome acidification, and proteolysis during autophagy. Defective lysosomal proteolysis represents a basis for pathogenic protein accumulations and neuronal cell death in AD and suggests previously unidentified therapeutic targets.

  20. Climate Adaptation and Harmful Algal Blooms

    EPA supports local, state and tribal efforts to maintain water quality. A key element of its efforts is to reduce excess nutrient pollution and the resulting adverse impacts, including harmful algal blooms.

  1. Hurtful Emotions: Understanding Self-Harm

    ... Issues Subscribe September 2017 Print this issue Hurtful Emotions Understanding Self-Harm En español Send us your ... help you learn new ways to cope with emotion. See the Wise Choices box for tips on ...

  2. Reducing the harms associated with risk assessments

    Montague, Peter

    2004-01-01

    Risk assessments are the intellectual products of dedicated public health and environmental professionals. Like many other products, risk assessments carry with them the potential for both good and harm. This paper briefly examines some of the harms to which risk assessments have contributed, and then suggests that the legal 'duty to warn' doctrine offers a logical and practical way to reduce some of these harms. The paper suggests concepts that could be incorporated into warnings accompanying every formal risk assessment as routine 'boiler plate' addenda, just as other potentially harmful products, such as lawn mowers and cook stoves, are accompanied by warnings. Finally, the paper briefly examines the 'Code of Ethics and Standards of Practice for Environmental Professionals' (promulgated by the National Association of Environmental Professionals) and shows that the suggested warnings are consistent with recommended practices for environmental professionals

  3. Detecting the Killer Toxin (Harmful Algal Blooms)

    Quevenco, Rodolfo

    2011-01-01

    IAEA is stepping up efforts to help countries understand the phenomenon and use more reliable methods for early detection and monitoring so as to limit harmful algal blooms (HABs) adverse effects on coastal communities everywhere.

  4. Thalassiosira mala (Bacillariophyta), a potentially harmful, marine ...

    Thalassiosira malaitalic> (Bacillariophyta), a potentially harmful, marine diatom from Chilka Lake and other coastal localities of Odisha, India: Nomenclature, ... Department of Biological Science, Florida State University, Tallahassee, FL 32306–4370, USA; Department of Biology, Valdosta State University, Valdosta, GA ...

  5. Harm reduction-the cannabis paradox

    Melamede Robert

    2005-09-01

    Full Text Available Abstract This article examines harm reduction from a novel perspective. Its central thesis is that harm reduction is not only a social concept, but also a biological one. More specifically, evolution does not make moral distinctions in the selection process, but utilizes a cannabis-based approach to harm reduction in order to promote survival of the fittest. Evidence will be provided from peer-reviewed scientific literature that supports the hypothesis that humans, and all animals, make and use internally produced cannabis-like products (endocannabinoids as part of the evolutionary harm reduction program. More specifically, endocannabinoids homeostatically regulate all body systems (cardiovascular, digestive, endocrine, excretory, immune, nervous, musculo-skeletal, reproductive. Therefore, the health of each individual is dependant on this system working appropriately.

  6. Proteolysis of milk fat globule membrane proteins during in vitro gastric digestion of milk.

    Ye, A; Cui, J; Singh, H

    2011-06-01

    The influence of gastric proteolysis on the physicochemical characteristics of milk fat globules and the proteins of the milk fat globule membrane (MFGM) in raw milk and cream was examined in vitro in simulated gastric fluid (SGF) containing various pepsin concentrations at pH 1.6 for up to 2h. Apparent flocculation of the milk fat globules occurred in raw milk samples incubated in SGF containing pepsin, but no coalescence was observed in either raw milk samples or cream samples. The changes in the particle size of the fat globules as a result of the flocculation were dependent on the pepsin concentration. Correspondingly, the physical characteristics of the fat globules and the composition of the MFGM proteins in raw milk changed during incubation in SGF containing pepsin. The major MFGM proteins were hydrolyzed at different rates by the pepsin in the SGF; butyrophilin was more resistant than xanthine oxidase, PAS 6, or PAS 7. Peptides with various molecular weights, which altered with the time of incubation and the pepsin concentration, were present at the surfaces of the fat globules. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  7. Rapid and efficient proteolysis through laser-assisted immobilized enzyme reactors.

    Zhang, Peng; Gao, Mingxia; Zhu, Shaochun; Lei, Jie; Zhang, Xiangmin

    2011-11-25

    In this report, laser radiation (808nm) for the first time was employed to enhance the efficiency of proteolysis through immobilized enzyme reactor (IMER). IMER based monolithic support was prepared in the fused-silica capillary via a simple two-step procedure including acryloylation on trypsin surface and in situ aqueous polymerization/immobilization. The feasibility and high efficiency of the laser-assisted IMER were demonstrated by the digestion of bovine serum albumin (BSA), cytochrome c (Cyt-c) and β-casein. The digestion process was achieved in 60s. The peptides were identified by MALDI-TOF-MS, yielding the sequence coverage of 33% for BSA, 73% for Cyt-c and 22% for β-casein. The comparisons between the in-solution digestion and on IMER reaction with/without laser assistance were made. To further confirm its efficiency in proteome analysis, the laser-assisted IMER was also applied to the analysis of one fraction of human serum sample through two-dimensional (2-D) separation of strong anion exchange/reversed-phase liquid chromatography (SAX/RPLC). After a database search, 49 unique peptides corresponding to 5 proteins were identified. The results showed that the laser-assisted IMER provides a promising platform for the high-throughput protein identification. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. PMA Induces SnoN Proteolysis and CD61 Expression through an Autocrine Mechanism

    Li, Chonghua; Peart, Natoya; Xuan, Zhenyu; Lewis, Dorothy E; Xia, Yang; Jin, Jianping

    2014-01-01

    Phorbol-12-myristate-13-acetate, also called PMA, is a small molecule that activates protein kinase C and functions to differentiate hematologic lineage cells. However, the mechanism of PMA-induced cellular differentiation is not fully understood. We found that PMA triggers global enhancement of protein ubiquitination in K562, a myelogenous leukemia cell line and one of the enhanced-ubiquitination targets is SnoN, an inhibitor of the Smad signaling pathway. Our data indicated that PMA stimulated the production of Activin A, a cytokine of the TGF-β family. Activin A then activated the phosphorylation of both Smad2 and Smad3. In consequence, SnoN is ubiquitinated by the APCCdh1 ubiquitin ligase with the help of phosphorylated Smad2. Furthermore, we found that SnoN proteolysis is important for the expression of CD61, a marker of megakaryocyte. These results indicate that protein ubiquitination promotes megakaryopoiesis via degrading SnoN, an inhibitor of CD61 expression, strengths the roles of ubiquitination in cellular differentiation. PMID:24637302

  9. Structural Basis for Regulated Proteolysis by the α-Secretase ADAM10.

    Seegar, Tom C M; Killingsworth, Lauren B; Saha, Nayanendu; Meyer, Peter A; Patra, Dhabaleswar; Zimmerman, Brandon; Janes, Peter W; Rubinstein, Eric; Nikolov, Dimitar B; Skiniotis, Georgios; Kruse, Andrew C; Blacklow, Stephen C

    2017-12-14

    Cleavage of membrane-anchored proteins by ADAM (a disintegrin and metalloproteinase) endopeptidases plays a key role in a wide variety of biological signal transduction and protein turnover processes. Among ADAM family members, ADAM10 stands out as particularly important because it is both responsible for regulated proteolysis of Notch receptors and catalyzes the non-amyloidogenic α-secretase cleavage of the Alzheimer's precursor protein (APP). We present here the X-ray crystal structure of the ADAM10 ectodomain, which, together with biochemical and cellular studies, reveals how access to the enzyme active site is regulated. The enzyme adopts an unanticipated architecture in which the C-terminal cysteine-rich domain partially occludes the enzyme active site, preventing unfettered substrate access. Binding of a modulatory antibody to the cysteine-rich domain liberates the catalytic domain from autoinhibition, enhancing enzymatic activity toward a peptide substrate. Together, these studies reveal a mechanism for regulation of ADAM activity and offer a roadmap for its modulation. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Preventing mutant huntingtin proteolysis and intermittent fasting promote autophagy in models of Huntington disease.

    Ehrnhoefer, Dagmar E; Martin, Dale D O; Schmidt, Mandi E; Qiu, Xiaofan; Ladha, Safia; Caron, Nicholas S; Skotte, Niels H; Nguyen, Yen T N; Vaid, Kuljeet; Southwell, Amber L; Engemann, Sabine; Franciosi, Sonia; Hayden, Michael R

    2018-03-06

    Huntington disease (HD) is caused by the expression of mutant huntingtin (mHTT) bearing a polyglutamine expansion. In HD, mHTT accumulation is accompanied by a dysfunction in basal autophagy, which manifests as specific defects in cargo loading during selective autophagy. Here we show that the expression of mHTT resistant to proteolysis at the caspase cleavage site D586 (C6R mHTT) increases autophagy, which may be due to its increased binding to the autophagy adapter p62. This is accompanied by faster degradation of C6R mHTT in vitro and a lack of mHTT accumulation the C6R mouse model with age. These findings may explain the previously observed neuroprotective properties of C6R mHTT. As the C6R mutation cannot be easily translated into a therapeutic approach, we show that a scheduled feeding paradigm is sufficient to lower mHTT levels in YAC128 mice expressing cleavable mHTT. This is consistent with a previous model, where the presence of cleavable mHTT impairs basal autophagy, while fasting-induced autophagy remains functional. In HD, mHTT clearance and autophagy may become increasingly impaired as a function of age and disease stage, because of gradually increased activity of mHTT-processing enzymes. Our findings imply that mHTT clearance could be enhanced by a regulated dietary schedule that promotes autophagy.

  11. Activation-induced proteolysis of cytoplasmic domain of zeta in T cell receptors and Fc receptors.

    Taupin, J L; Anderson, P

    1994-12-01

    The CD3-T cell receptor (TCR) complex on T cells and the Fc gamma receptor type III (Fc gamma RIII)-zeta-gamma complex on natural killer cells are functionally analogous activation receptors that associate with a family of disulfide-linked dimers composed of the related subunits zeta and gamma. Immunochemical analysis of receptor complexes separated on two-dimensional diagonal gels allowed the identification of a previously uncharacterized zeta-p14 heterodimer. zeta-p14 is a component of both CD3-TCR and Fc gamma RIII-zeta-gamma. Peptide mapping analysis shows that p14 is structurally related to zeta, suggesting that it is either: (i) derived from zeta proteolytically or (ii) the product of an alternatively spliced mRNA. The observation that COS cells transformed with a cDNA encoding zeta express zeta-p14 supports the former possibility. The expression of CD3-TCR complexes including zeta-p14 increases following activation with phorbol 12-myristate 13-acetate or concanavalin A, suggesting that proteolysis of zeta may contribute to receptor modulation or desensitization.

  12. Locked and proteolysis-based transcription activator-like effector (TALE) regulation.

    Lonzarić, Jan; Lebar, Tina; Majerle, Andreja; Manček-Keber, Mateja; Jerala, Roman

    2016-02-18

    Development of orthogonal, designable and adjustable transcriptional regulators is an important goal of synthetic biology. Their activity has been typically modulated through stimulus-induced oligomerization or interaction between the DNA-binding and activation/repression domain. We exploited a feature of the designable Transcription activator-like effector (TALE) DNA-binding domain that it winds around the DNA which allows to topologically prevent it from binding by intramolecular cyclization. This new approach was investigated through noncovalent ligand-induced cyclization or through a covalent split intein cyclization strategy, where the topological inhibition of DNA binding by cyclization and its restoration by a proteolytic release of the topologic constraint was expected. We show that locked TALEs indeed have diminished DNA binding and regain full transcriptional activity by stimulation with the rapamycin ligand or site-specific proteolysis of the peptide linker, with much higher level of activation than rapamycin-induced heterodimerization. Additionally, we demonstrated reversibility, activation of genomic targets and implemented logic gates based on combinations of protein cyclization, proteolytic cleavage and ligand-induced dimerization, where the strongest fold induction was achieved by the proteolytic cleavage of a repression domain from a linear TALE. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  13. Region-specific proteolysis differentially regulates type 1 inositol 1,4,5-trisphosphate receptor activity.

    Wang, Liwei; Wagner, Larry E; Alzayady, Kamil J; Yule, David I

    2017-07-14

    The inositol 1,4,5 trisphosphate receptor (IP 3 R) is an intracellular Ca 2+ release channel expressed predominately on the membranes of the endoplasmic reticulum. IP 3 R1 can be cleaved by caspase or calpain into at least two receptor fragments. However, the functional consequences of receptor fragmentation are poorly understood. Our previous work has demonstrated that IP 3 R1 channels, formed following either enzymatic fragmentation or expression of the corresponding complementary polypeptide chains, retain tetrameric architecture and are still activated by IP 3 binding despite the loss of peptide continuity. In this study, we demonstrate that region-specific receptor fragmentation modifies channel regulation. Specifically, the agonist-evoked temporal Ca 2+ release profile and protein kinase A modulation of Ca 2+ release are markedly altered. Moreover, we also demonstrate that activation of fragmented IP 3 R1 can result in a distinct functional outcome. Our work suggests that proteolysis of IP 3 R1 may represent a novel form of modulation of IP 3 R1 channel function and increases the repertoire of Ca 2+ signals achievable through this channel. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. VEGF-A isoforms program differential VEGFR2 signal transduction, trafficking and proteolysis

    Gareth W. Fearnley

    2016-05-01

    Full Text Available Vascular endothelial growth factor A (VEGF-A binding to the receptor tyrosine kinase VEGFR2 triggers multiple signal transduction pathways, which regulate endothelial cell responses that control vascular development. Multiple isoforms of VEGF-A can elicit differential signal transduction and endothelial responses. However, it is unclear how such cellular responses are controlled by isoform-specific VEGF-A–VEGFR2 complexes. Increasingly, there is the realization that the membrane trafficking of receptor–ligand complexes influences signal transduction and protein turnover. By building on these concepts, our study shows for the first time that three different VEGF-A isoforms (VEGF-A165, VEGF-A121 and VEGF-A145 promote distinct patterns of VEGFR2 endocytosis for delivery into early endosomes. This differential VEGFR2 endocytosis and trafficking is linked to VEGF-A isoform-specific signal transduction events. Disruption of clathrin-dependent endocytosis blocked VEGF-A isoform-specific VEGFR2 activation, signal transduction and caused substantial depletion in membrane-bound VEGFR1 and VEGFR2 levels. Furthermore, such VEGF-A isoforms promoted differential patterns of VEGFR2 ubiquitylation, proteolysis and terminal degradation. Our study now provides novel insights into how different VEGF-A isoforms can bind the same receptor tyrosine kinase and elicit diverse cellular outcomes.

  15. VEGF-A isoforms program differential VEGFR2 signal transduction, trafficking and proteolysis.

    Fearnley, Gareth W; Smith, Gina A; Abdul-Zani, Izma; Yuldasheva, Nadira; Mughal, Nadeem A; Homer-Vanniasinkam, Shervanthi; Kearney, Mark T; Zachary, Ian C; Tomlinson, Darren C; Harrison, Michael A; Wheatcroft, Stephen B; Ponnambalam, Sreenivasan

    2016-05-15

    Vascular endothelial growth factor A (VEGF-A) binding to the receptor tyrosine kinase VEGFR2 triggers multiple signal transduction pathways, which regulate endothelial cell responses that control vascular development. Multiple isoforms of VEGF-A can elicit differential signal transduction and endothelial responses. However, it is unclear how such cellular responses are controlled by isoform-specific VEGF-A-VEGFR2 complexes. Increasingly, there is the realization that the membrane trafficking of receptor-ligand complexes influences signal transduction and protein turnover. By building on these concepts, our study shows for the first time that three different VEGF-A isoforms (VEGF-A165, VEGF-A121 and VEGF-A145) promote distinct patterns of VEGFR2 endocytosis for delivery into early endosomes. This differential VEGFR2 endocytosis and trafficking is linked to VEGF-A isoform-specific signal transduction events. Disruption of clathrin-dependent endocytosis blocked VEGF-A isoform-specific VEGFR2 activation, signal transduction and caused substantial depletion in membrane-bound VEGFR1 and VEGFR2 levels. Furthermore, such VEGF-A isoforms promoted differential patterns of VEGFR2 ubiquitylation, proteolysis and terminal degradation. Our study now provides novel insights into how different VEGF-A isoforms can bind the same receptor tyrosine kinase and elicit diverse cellular outcomes. © 2016. Published by The Company of Biologists Ltd.

  16. Quantitative proteomics and terminomics to elucidate the role of ubiquitination and proteolysis in adaptive immunity.

    Klein, Theo; Viner, Rosa I; Overall, Christopher M

    2016-10-28

    Adaptive immunity is the specialized defence mechanism in vertebrates that evolved to eliminate pathogens. Specialized lymphocytes recognize specific protein epitopes through antigen receptors to mount potent immune responses, many of which are initiated by nuclear factor-kappa B activation and gene transcription. Most, if not all, pathways in adaptive immunity are further regulated by post-translational modification (PTM) of signalling proteins, e.g. phosphorylation, citrullination, ubiquitination and proteolytic processing. The importance of PTMs is reflected by genetic or acquired defects in these pathways that lead to a dysfunctional immune response. Here we discuss the state of the art in targeted proteomics and systems biology approaches to dissect the PTM landscape specifically regarding ubiquitination and proteolysis in B- and T-cell activation. Recent advances have occurred in methods for specific enrichment and targeted quantitation. Together with improved instrument sensitivity, these advances enable the accurate analysis of often rare PTM events that are opaque to conventional proteomics approaches, now rendering in-depth analysis and pathway dissection possible. We discuss published approaches, including as a case study the profiling of the N-terminome of lymphocytes of a rare patient with a genetic defect in the paracaspase protease MALT1, a key regulator protease in antigen-driven signalling, which was manifested by elevated linear ubiquitination.This article is part of the themed issue 'Quantitative mass spectrometry'. © 2016 The Authors.

  17. Liberal egalitarianism and the harm principle

    Lombardi, Michele; Veneziani, Roberto

    2009-01-01

    This paper analyses Rawls's celebrated difference principle, and its lexicographic extension, in societies with a finite and an infinite number of agents. A unified framework of analysis is set up, which allows one to characterise Rawlsian egalitarian principles by means of a weaker version of a new axiom - the Harm Principle - recently proposed by marven09. This is quite surprising, because the Harm principle is meant to capture a liberal requirement of noninterference and it incorporates no...

  18. Authority dependence and judgments of utilitarian harm.

    Piazza, Jared; Sousa, Paulo; Holbrook, Colin

    2013-09-01

    Three studies tested the conditions under which people judge utilitarian harm to be authority dependent (i.e., whether its right or wrongness depends on the ruling of an authority). In Study 1, participants judged the right or wrongness of physical abuse when used as an interrogation method anticipated to yield useful information for preventing future terrorist attacks. The ruling of the military authority towards the harm was manipulated (prohibited vs. prescribed) and found to significantly influence judgments of the right or wrongness of inflicting harm. Study 2 established a boundary condition with regards to the influence of authority, which was eliminated when the utility of the harm was definitely obtained rather than forecasted. Finally, Study 3 replicated the findings of Studies 1-2 in a completely different context-an expert committee's ruling about the harming of chimpanzees for biomedical research. These results are discussed as they inform ongoing debates regarding the role of authority in moderating judgments of complex and simple harm. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Harm mediates the disgust-immorality link.

    Schein, Chelsea; Ritter, Ryan S; Gray, Kurt

    2016-09-01

    Many acts are disgusting, but only some of these acts are immoral. Dyadic morality predicts that disgusting acts should be judged as immoral to the extent that they seem harmful. Consistent with this prediction, 3 studies reveal that perceived harm mediates the link between feelings of disgust and moral condemnation-even for ostensibly harmless "purity" violations. In many cases, accounting for perceived harm completely eliminates the link between disgust and moral condemnation. Analyses also reveal the predictive power of anger and typicality/weirdness in moral judgments of disgusting acts. The mediation of disgust by harm holds across diverse acts including gay marriage, sex acts, and religious blasphemy. Revealing the endogenous presence and moral relevance of harm within disgusting-but-ostensibly harmless acts argues against modular accounts of moral cognition such as moral foundations theory. Instead, these data support pluralistic conceptions of harm and constructionist accounts of morality and emotion. Implications for moral cognition and the concept of "purity" are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  20. Phenylbutyric acid rescues endoplasmic reticulum stress-induced suppression of APP proteolysis and prevents apoptosis in neuronal cells.

    Jesse C Wiley

    Full Text Available BACKGROUND: The familial and sporadic forms of Alzheimer's disease (AD have an identical pathology with a severe disparity in the time of onset [1]. The pathological similarity suggests that epigenetic processes may phenocopy the Familial Alzheimer's disease (FAD mutations within sporadic AD. Numerous groups have demonstrated that FAD mutations in presenilin result in 'loss of function' of gamma-secretase mediated APP cleavage [2], [3], [4], [5]. Accordingly, ER stress is prominent within the pathologically impacted brain regions in AD patients [6] and is reported to inhibit APP trafficking through the secretory pathway [7], [8]. As the maturation of APP and the cleaving secretases requires trafficking through the secretory pathway [9], [10], [11], we hypothesized that ER stress may block trafficking requisite for normal levels of APP cleavage and that the small molecular chaperone 4-phenylbutyrate (PBA may rescue the proteolytic deficit. METHODOLOGY/PRINCIPAL FINDINGS: The APP-Gal4VP16/Gal4-reporter screen was stably incorporated into neuroblastoma cells in order to assay gamma-secretase mediated APP proteolysis under normal and pharmacologically induced ER stress conditions. Three unrelated pharmacological agents (tunicamycin, thapsigargin and brefeldin A all repressed APP proteolysis in parallel with activation of unfolded protein response (UPR signaling-a biochemical marker of ER stress. Co-treatment of the gamma-secretase reporter cells with PBA blocked the repressive effects of tunicamycin and thapsigargin upon APP proteolysis, UPR activation, and apoptosis. In unstressed cells, PBA stimulated gamma-secretase mediated cleavage of APP by 8-10 fold, in the absence of any significant effects upon amyloid production, by promoting APP trafficking through the secretory pathway and the stimulation of the non-pathogenic alpha/gamma-cleavage. CONCLUSIONS/SIGNIFICANCE: ER stress represses gamma-secretase mediated APP proteolysis, which replicates

  1. Radiation sterilization of harmful algae in water

    Byung Chull An; Jae-Sung Kim; Seung Sik Lee; Shyamkumar Barampuram; Eun Mi Lee; Byung Yeoup Chung

    2007-01-01

    Complete text of publication follows. Objective: Drinking water, water used in food production and for irrigation, water for fish farming, waste water, surface water, and recreational water have been recently recognized as a vector for the transmission of harmful micro-organisms. The human and animal harmful algae is a waterborne risk to public health and economy because the algae are ubiquitous and persistent in water and wastewater, not completely removed by physical-chemical treatment processes, and relatively resistant to chemical disinfection. Gamma and electron beam radiation technology is of growing in the water industry since it was demonstrated that gamma and electron beam radiation is very effective against harmful algae. Materials and Methods: Harmful algae (Scenedesmus quadricauda(Turpin) Brebisson 1835 (AG10003), Chlorella vulgaris Beijerinck 1896 (AG30007) and Chlamydomonas sp. (AG10061)) were distributed from Korean collection for type cultures (KCTC). Strains were cultured aerobically in Allen's medium at 25□ and 300 umol/m2s for 1 week using bioreactor. We investigated the disinfection efficiency of harmful algae irradiated with gamma (0.05 to 10 kGy for 30 min) and electron beam (1 to 19 kGy for 5 sec) rays. Results and Conclusion: We investigated the disinfection efficiency of harmful algae irradiated with gamma and electron beam rays of 50 to 19000 Gy. We established the optimum sterilization condition which use the gamma and electron beam radiation. Gamma ray disinfected harmful algae at 400 Gy for 30 min. Also, electron beam disinfected at 1000 Gy for 5 sec. This alternative disinfection practice had powerful disinfection efficiency. Hence, the multi-barrier approach for drinking water treatment in which a combination of various disinfectants and filtration technologies are applied for removal and inactivation of different microbial pathogens will guarantee a lower risk of microbial contamination.

  2. Assessing harmful effects in systematic Reviews

    Woolacott Nerys F

    2004-07-01

    Full Text Available Abstract Background Balanced decisions about health care interventions require reliable evidence on harms as well as benefits. Most systematic reviews focus on efficacy and randomised trials, for which the methodology is well established. Methods to systematically review harmful effects are less well developed and there are few sources of guidance for researchers. We present our own recent experience of conducting systematic reviews of harmful effects and make suggestions for future practice and further research. Methods We described and compared the methods used in three systematic reviews. Our evaluation focused on the review question, study designs and quality assessment. Results One review question focused on providing information on specific harmful effects to furnish an economic model, the other two addressed much broader questions. All three reviews included randomised and observational data, although each defined the inclusion criteria differently. Standard methods were used to assess study quality. Various practical problems were encountered in applying the study design inclusion criteria and assessing quality, mainly because of poor study design, inadequate reporting and the limitations of existing tools. All three reviews generated a large volume of work that did not yield much useful information for health care decision makers. The key areas for improvement we identified were focusing the review question and developing methods for quality assessment of studies of harmful effects. Conclusions Systematic reviews of harmful effects are more likely to yield information pertinent to clinical decision-making if they address a focused question. This will enable clear decisions to be made about the type of research to include in the review. The methodology for assessing the quality of harmful effects data in systematic reviews requires further development.

  3. Harm avoidance and disability in old age.

    Wilson, Robert S; Buchman, Aron S; Arnold, Steven E; Shah, Raj C; Tang, Yuxiao; Bennett, David A

    2006-01-01

    The relation of personality to disability in old age is not well understood. The authors examined the relation of harm avoidance, a trait indicating a tendency to worry, fear uncertainty, be shy, and tire easily, to disability in a group of 474 older persons without dementia. Participants completed the 35-item Harm Avoidance scale. Disability was assessed with the Rosow-Breslau scale, a self-report measure of physical mobility. Performance-based tests of lower limb functions were also administered from which composite measures of gait, balance, and strength were derived. In a logistic regression model controlled for age, sex, education, and lower limb function, persons with high levels of harm avoidance were nearly three times as likely to report mobility limitations as persons with low levels, and these effects largely reflected fatigability and fear of uncertainty. The association of harm avoidance with disability was not explained or modified by frailty, physical activity, depressive symptoms, neuroticism, extraversion, or cognition. The results suggest that harm avoidance is associated with disability in old age.

  4. Metal ion release from metallothioneins: proteolysis as an alternative to oxidation.

    Peroza, Estevão A; dos Santos Cabral, Augusto; Wan, Xiaoqiong; Freisinger, Eva

    2013-09-01

    Metallothioneins (MTs) are among others involved in the cellular regulation of essential Zn(II) and Cu(I) ions. However, the high binding affinity of these proteins requires additional factors to promote metal ion release under physiological conditions. The mechanisms and efficiencies of these processes leave many open questions. We report here a comprehensive analysis of the Zn(II)-release properties of various MTs with special focus on members of the four main subfamilies of plant MTs. Zn(II) competition experiments with the metal ion chelator 4-(2-pyridylazo)resorcinol (PAR) in the presence of the cellular redox pair glutathione (GSH)/glutathione disulfide (GSSG) show that plant MTs from the subfamilies MT1, MT2, and MT3 are remarkably more affected by oxidative stress than those from the Ec subfamily and the well-characterized human MT2 form. In addition, we evaluated proteolytic digestion with trypsin and proteinase K as an alternative mechanism for selective promotion of metal ion release from MTs. Also here the observed percentage of liberated metal ions depends strongly on the MT form evaluated. Closer evaluation of the data additionally allowed deducing the thermodynamic and kinetic properties of the Zn(II) release processes. The Cu(I)-form of chickpea MT2 was used to exemplify that both oxidation and proteolysis are also effective ways to increase the transfer of copper ions to other molecules. Zn(II) release experiments with the individual metal-binding domains of Ec-1 from wheat grain reveal distinct differences from the full-length protein. This triggers the question about the roles of the long cysteine-free peptide stretches typical for plant MTs.

  5. Matriptase activation connects tissue factor-dependent coagulation initiation to epithelial proteolysis and signaling.

    Le Gall, Sylvain M; Szabo, Roman; Lee, Melody; Kirchhofer, Daniel; Craik, Charles S; Bugge, Thomas H; Camerer, Eric

    2016-06-23

    The coagulation cascade is designed to sense tissue injury by physical separation of the membrane-anchored cofactor tissue factor (TF) from inactive precursors of coagulation proteases circulating in plasma. Once TF on epithelial and other extravascular cells is exposed to plasma, sequential activation of coagulation proteases coordinates hemostasis and contributes to host defense and tissue repair. Membrane-anchored serine proteases (MASPs) play critical roles in the development and homeostasis of epithelial barrier tissues; how MASPs are activated in mature epithelia is unknown. We here report that proteases of the extrinsic pathway of blood coagulation transactivate the MASP matriptase, thus connecting coagulation initiation to epithelial proteolysis and signaling. Exposure of TF-expressing cells to factors (F) VIIa and Xa triggered the conversion of latent pro-matriptase to an active protease, which in turn cleaved the pericellular substrates protease-activated receptor-2 (PAR2) and pro-urokinase. An activation pathway-selective PAR2 mutant resistant to direct cleavage by TF:FVIIa and FXa was activated by these proteases when cells co-expressed pro-matriptase, and matriptase transactivation was necessary for efficient cleavage and activation of wild-type PAR2 by physiological concentrations of TF:FVIIa and FXa. The coagulation initiation complex induced rapid and prolonged enhancement of the barrier function of epithelial monolayers that was dependent on matriptase transactivation and PAR2 signaling. These observations suggest that the coagulation cascade engages matriptase to help coordinate epithelial defense and repair programs after injury or infection, and that matriptase may contribute to TF-driven pathogenesis in cancer and inflammation.

  6. Protein translation, proteolysis and autophagy in human skeletal muscle atrophy after spinal cord injury.

    Lundell, L S; Savikj, M; Kostovski, E; Iversen, P O; Zierath, J R; Krook, A; Chibalin, A V; Widegren, U

    2018-02-08

    Spinal cord injury-induced loss of skeletal muscle mass does not progress linearly. In humans, peak muscle loss occurs during the first 6 weeks postinjury, and gradually continues thereafter. The aim of this study was to delineate the regulatory events underlying skeletal muscle atrophy during the first year following spinal cord injury. Key translational, autophagic and proteolytic proteins were analysed by immunoblotting of human vastus lateralis muscle obtained 1, 3 and 12 months following spinal cord injury. Age-matched able-bodied control subjects were also studied. Several downstream targets of Akt signalling decreased after spinal cord injury in skeletal muscle, without changes in resting Akt Ser 473 and Akt Thr 308 phosphorylation or total Akt protein. Abundance of mTOR protein and mTOR Ser 2448 phosphorylation, as well as FOXO1 Ser 256 phosphorylation and FOXO3 protein, decreased in response to spinal cord injury, coincident with attenuated protein abundance of E3 ubiquitin ligases, MuRF1 and MAFbx. S6 protein and Ser 235/236 phosphorylation, as well as 4E-BP1 Thr 37/46 phosphorylation, increased transiently after spinal cord injury, indicating higher levels of protein translation early after injury. Protein abundance of LC3-I and LC3-II decreased 3 months postinjury as compared with 1 month postinjury, but not compared to able-bodied control subjects, indicating lower levels of autophagy. Proteins regulating proteasomal degradation were stably increased in response to spinal cord injury. Together, these data provide indirect evidence suggesting that protein translation and autophagy transiently increase, while whole proteolysis remains stably higher in skeletal muscle within the first year after spinal cord injury. © 2018 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  7. Multiple functions of the von Willebrand Factor A domain in matrilins: secretion, assembly, and proteolysis

    Kanbe Katsuaki

    2008-06-01

    Full Text Available Abstract The von Willebrand Factor A (vWF A domain is one of the most widely distributed structural modules in cell-matrix adhesive molecules such as intergrins and extracellular matrix proteins. Mutations in the vWF A domain of matrilin-3 cause multiple epiphyseal dysplasia (MED, however the pathological mechanism remains to be determined. Previously we showed that the vWF A domain in matrilin-1 mediates formation of a filamentous matrix network through metal-ion dependent adhesion sites in the domain. Here we show two new functions of the vWF A domain in cartilage-specific matrilins (1 and 3. First, vWF A domain regulates oligomerization of matrilins. Insertion of a vWF A domain into matrilin-3 converts the formation of a mixture of matrilin-3 tetramer, trimer, and dimer into a tetramer only, while deletion of a vWF A domain from matrilin-1 converts the formation of the native matrilin-1 trimer into a mixture of trimer and dimer. Second, the vWF A domain protects matrilin-1 from proteolysis. We identified a latent proteolytic site next to the vWF A2 domain in matrilin-1, which is sensitive to the inhibitors of matrix proteases. Deletion of the abutting vWF A domain results in degradation of matrilin-1, presumably by exposing the adjacent proteolytic site. In addition, we also confirmed the vWF A domain is vital for the secretion of matrilin-3. Secretion of the mutant matrilin-3 harbouring a point mutation within the vWF A domain, as occurred in MED patients, is markedly reduced and delayed, resulting from intracellular retention of the mutant matrilin-3. Taken together, our data suggest that different mutations/deletions of the vWF A domain in matrilins may lead to distinct pathological mechanisms due to the multiple functions of the vWF A domain.

  8. Structural inferences for the native skeletal muscle sodium channel as derived from patterns of endogenous proteolysis

    Kraner, S.; Yang, J.; Barchi, R.

    1989-01-01

    The alpha subunit (Mr approximately 260,000) of the rat skeletal muscle sodium channel is sensitive to cleavage by endogenous proteases during the isolation of muscle surface membrane. Antisera against synthetic oligopeptides were used to map the resultant fragments in order to identify protease-sensitive regions of the channel's structure in its native membrane environment. Antibodies to the amino terminus labeled major fragments of Mr approximately 130,000 and 90,000 and lesser amounts of other peptides as small as Mr approximately 12,000. Antisera to epitopes within the carboxyl-terminal half of the primary sequence recognized two fragments of Mr approximately 110,000 and 78,000. Individual antisera also selectively labeled smaller polypeptides in the most extensively cleaved preparations. The immunoreactivity patterns of monoclonal antibodies previously raised against the purified channel were then surveyed. The binding sites for one group of monoclonals, including several that recognize subtype-specific epitopes in the channel structure, were localized within a 12-kDa fragment near the amino terminus. The distribution of carbohydrate along the primary structure of the channel was also assessed by quantitating 125 I-wheat germ agglutinin and 125I-concanavalin A binding to the proteolytic peptides. Most of the carbohydrate detected by these lectins was located between 22 and 90 kDa from the amino terminus of the protein. No lectin binding was detected to fragments arising from carboxyl-terminal half of the protein. These results were analyzed in terms of current models of sodium channel tertiary structure. In its normal membrane environment, the skeletal muscle sodium channel appears sensitive to cleavage by endogenous proteases in regions predicted to link the four repeat domains on the cytoplasmic side of the membrane while the repeat domains themselves are resistant to proteolysis

  9. A SIMPLE FLUORESCENT LABELING METHOD FOR STUDIES OF PROTEIN OXIDATION, PROTEIN MODIFICATION, AND PROTEOLYSIS

    Pickering, Andrew. M.; Davies, Kelvin. J. A.

    2014-01-01

    Proteins are sensitive to oxidation, and oxidized proteins are excellent substrates for degradation by proteolytic enzymes such as the Proteasome and the mitochondrial Lon protease. Protein labeling is required for studies of protein turnover. Unfortunately, most labeling techniques involve 3H or 14C methylation which is expensive, exposes researchers to radioactivity, generates large amounts of radioactive waste, and allows only single-point assays because samples require acid-precipitation. Alternative labeling methods, have largely proven unsuitable, either because the probe itself is modified by the oxidant(s) being studied, or because the alternative labeling techniques are too complex or too costly for routine use. What is needed is a simple, quick, and cheap labeling technique that uses a non-radioactive marker, that binds strongly to proteins, is resistant to oxidative modification, and emits a strong signal. We have devised a new reductive method for labeling free carboxyl groups of proteins with the small fluorophore 7-amino-4-methycoumarin (AMC). When bound to target proteins, AMC fluoresces very weakly but when AMC is released by proteinases, proteases, or peptidases, it fluoresces strongly. Thus, without acid-precipitation, the proteolysis of any target protein can be studied continuously, in multiwell plates. In direct comparisons, 3H-labeled proteins and AMC-labeled proteins exhibited essentially identical degradation patterns during incubation with trypsin, cell extracts, and purified proteasome. AMC-labeled proteins are well-suited to study increased proteolytic susceptibility following protein modification, since the AMC-protein bond is resistant to oxidizing agents such as hydrogen peroxide and peroxynitrite, and is stable over time and to extremes of pH, temperature (even boiling), freeze-thawing, mercaptoethanol, and methanol. PMID:21988844

  10. LSD1 demethylase and the methyl-binding protein PHF20L1 prevent SET7 methyltransferase-dependent proteolysis of the stem-cell protein SOX2.

    Zhang, Chunxiao; Hoang, Nam; Leng, Feng; Saxena, Lovely; Lee, Logan; Alejo, Salvador; Qi, Dandan; Khal, Anthony; Sun, Hong; Lu, Fei; Zhang, Hui

    2018-03-09

    The pluripotency-controlling stem-cell protein SRY-box 2 (SOX2) plays a pivotal role in maintaining the self-renewal and pluripotency of embryonic stem cells and also of teratocarcinoma or embryonic carcinoma cells. SOX2 is monomethylated at lysine 119 (Lys-119) in mouse embryonic stem cells by the SET7 methyltransferase, and this methylation triggers ubiquitin-dependent SOX2 proteolysis. However, the molecular regulators and mechanisms controlling SET7-induced SOX2 proteolysis are unknown. Here, we report that in human ovarian teratocarcinoma PA-1 cells, methylation-dependent SOX2 proteolysis is dynamically regulated by the LSD1 lysine demethylase and a methyl-binding protein, PHD finger protein 20-like 1 (PHF20L1). We found that LSD1 not only removes the methyl group from monomethylated Lys-117 (equivalent to Lys-119 in mouse SOX2), but it also demethylates monomethylated Lys-42 in SOX2, a reaction that SET7 also regulated and that also triggered SOX2 proteolysis. Our studies further revealed that PHF20L1 binds both monomethylated Lys-42 and Lys-117 in SOX2 and thereby prevents SOX2 proteolysis. Down-regulation of either LSD1 or PHF20L1 promoted SOX2 proteolysis, which was prevented by SET7 inactivation in both PA-1 and mouse embryonic stem cells. Our studies also disclosed that LSD1 and PHF20L1 normally regulate the growth of pluripotent mouse embryonic stem cells and PA-1 cells by preventing methylation-dependent SOX2 proteolysis. In conclusion, our findings reveal an important mechanism by which the stability of the pluripotency-controlling stem-cell protein SOX2 is dynamically regulated by the activities of SET7, LSD1, and PHF20L1 in pluripotent stem cells. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. [Self-harm vs. harming others: the lived experiences of a dysfunctional family].

    Wu, Hsiu-Chin; Lin, Mei-Feng; Yu, Shu-Hua

    2007-10-01

    The purpose of this study was to explore the lived experiences of self-harm and harm to others from the perspective of two adult offspring and a father, the latter of whom was prone to alcohol abuse and domestic violence and had attempted suicide. Written informed consents were obtained from the subjects after a detailed explanation of the research aims and procedures. A qualitative, phenomenological method was applied for the study. Three subjects were interviewed using a semi-structured interview guide designed by the researchers and based on the aims of the study over a six-month period of home care. A qualitative content analysis based on a phenomenological method was used to identify themes in the data. Two main categories emerged: (1) the mutual harm to the couple subsystem, (2) the misplaced parental-child subsystem. Subsequently, two to four themes were identified from each category. These results provide a better analysis and understanding of the perceived experiences of the harm to the spouse, parental, and sibling subsystems. They should also help health professionals to improve awareness of the lived experiences associated with the issues of self-harm and threats of harm to others. This study could serve as a valuable reference in promoting possible prevention strategies aiming at the reduction of self-harm and harm to others in dysfunctional families within the community.

  12. Characteristics of Self-Harm Behaviour among Identified Self-Harming Youth in Care

    Grenville, Jeffrey; Goodman, Deborah; Macpherson, Alison K.

    2012-01-01

    The objective of this study was to describe deliberate self-harming (DSH) characteristics in a child-welfare population identified as having threatened or completed self-harm. Secondary data from 621 serious occurrence reports (SOR) that documented 2004-2007 DSH incidents and DSH threats with 252 Canadian youth in care (Y-INC) of the Children's…

  13. Regulation of progranulin expression in human microglia and proteolysis of progranulin by matrix metalloproteinase-12 (MMP-12.

    Hyeon-Sook Suh

    Full Text Available The essential role of progranulin (PGRN as a neurotrophic factor has been demonstrated by the discovery that haploinsufficiency due to GRN gene mutations causes frontotemporal lobar dementia. In addition to neurons, microglia in vivo express PGRN, but little is known about the regulation of PGRN expression by microglia.In the current study, we examined the regulation of expression and function of PGRN, its proteolytic enzyme macrophage elastase (MMP-12, as well as the inhibitor of PGRN proteolysis, secretory leukocyte protease inhibitor (SLPI, in human CNS cells.Cultures of primary human microglia and astrocytes were stimulated with the TLR ligands (LPS or poly IC, Th1 cytokines (IL-1/IFNγ, or Th2 cytokines (IL-4, IL-13. Results were analyzed by Q-PCR, immunoblotting or ELISA. The roles of MMP-12 and SLPI in PGRN cleavage were also examined.Unstimulated microglia produced nanogram levels of PGRN, and PGRN release from microglia was suppressed by the TLR ligands or IL-1/IFNγ, but increased by IL-4 or IL-13. Unexpectedly, while astrocytes stimulated with proinflammatory factors released large amounts of SLPI, none were detected in microglial cultures. We also identified MMP-12 as a PGRN proteolytic enzyme, and SLPI as an inhibitor of MMP-12-induced PGRN proteolysis. Experiments employing PGRN siRNA demonstrated that microglial PGRN was involved in the cytokine and chemokine production following TLR3/4 activation, with its effect on TNFα being the most conspicuous.Our study is the first detailed examination of PGRN in human microglia. Our results establish microglia as a significant source of PGRN, and MMP-12 and SLPI as modulators of PGRN proteolysis. Negative and positive regulation of microglial PGRN release by the proinflammatory/Th1 and the Th2 stimuli, respectively, suggests a fundamentally different aspect of PGRN regulation compared to other known microglial activation products. Microglial PGRN appears to function as an endogenous

  14. Proteolysis of virulence regulator ToxR is associated with entry of Vibrio cholerae into a dormant state.

    Salvador Almagro-Moreno

    2015-04-01

    Full Text Available Vibrio cholerae O1 is a natural inhabitant of aquatic environments and causes the diarrheal disease, cholera. Two of its primary virulence regulators, TcpP and ToxR, are localized in the inner membrane. TcpP is encoded on the Vibrio Pathogenicity Island (VPI, a horizontally acquired mobile genetic element, and functions primarily in virulence gene regulation. TcpP has been shown to undergo regulated intramembrane proteolysis (RIP in response to environmental conditions that are unfavorable for virulence gene expression. ToxR is encoded in the ancestral genome and is present in non-pathogenic strains of V. cholerae, indicating it has roles outside of the human host. In this study, we show that ToxR undergoes RIP in V. cholerae in response to nutrient limitation at alkaline pH, a condition that occurs during the stationary phase of growth. This process involves the site-2 protease RseP (YaeL, and is dependent upon the RpoE-mediated periplasmic stress response, as deletion mutants for the genes encoding these two proteins cannot proteolyze ToxR under nutrient limitation at alkaline pH. We determined that the loss of ToxR, genetically or by proteolysis, is associated with entry of V. cholerae into a dormant state in which the bacterium is normally found in the aquatic environment called viable but nonculturable (VBNC. Strains that can proteolyze ToxR, or do not encode it, lose culturability, experience a change in morphology associated with cells in VBNC, yet remain viable under nutrient limitation at alkaline pH. On the other hand, mutant strains that cannot proteolyze ToxR remain culturable and maintain the morphology of cells in an active state of growth. Overall, our findings provide a link between the proteolysis of a virulence regulator and the entry of a pathogen into an environmentally persistent state.

  15. Time-Course of Muscle Mass Loss, Damage, and Proteolysis in Gastrocnemius following Unloading and Reloading: Implications in Chronic Diseases

    Chacon-Cabrera, Alba; Lund-Palau, Helena; Gea, Joaquim; Barreiro, Esther

    2016-01-01

    Background Disuse muscle atrophy is a major comorbidity in patients with chronic diseases including cancer. We sought to explore the kinetics of molecular mechanisms shown to be involved in muscle mass loss throughout time in a mouse model of disuse muscle atrophy and recovery following immobilization. Methods Body and muscle weights, grip strength, muscle phenotype (fiber type composition and morphometry and muscle structural alterations), proteolysis, contractile proteins, systemic troponin I, and mitochondrial content were assessed in gastrocnemius of mice exposed to periods (1, 2, 3, 7, 15 and 30 days) of non-invasive hindlimb immobilization (plastic splint, I cohorts) and in those exposed to reloading for different time-points (1, 3, 7, 15, and 30 days, R cohorts) following a seven-day period of immobilization. Groups of control animals were also used. Results Compared to non-exposed controls, muscle weight, limb strength, slow- and fast-twitch cross-sectional areas, mtDNA/nDNA, and myosin content were decreased in mice of I cohorts, whereas tyrosine release, ubiquitin-proteasome activity, muscle injury and systemic troponin I levels were increased. Gastrocnemius reloading following splint removal improved muscle mass loss, strength, fiber atrophy, injury, myosin content, and mtDNA/nDNA, while reducing ubiquitin-proteasome activity and proteolysis. Conclusions A consistent program of molecular and cellular events leading to reduced gastrocnemius muscle mass and mitochondrial content and reduced strength, enhanced proteolysis, and injury, was seen in this non-invasive mouse model of disuse muscle atrophy. Unloading of the muscle following removal of the splint significantly improved the alterations seen during unloading, characterized by a specific kinetic profile of molecular events involved in muscle regeneration. These findings have implications in patients with chronic diseases including cancer in whom physical activity may be severely compromised. PMID

  16. Summer heatwaves promote blooms of harmful cyanobacteria

    K.D Joehnk; J. Huisman; J. Sharples; B.P. Sommeijer (Ben); P.M. Visser (Petra); J.M. Stroom

    2008-01-01

    htmlabstractDense surface blooms of toxic cyanobacteria in eutrophic lakes may lead to mass mortalities of fish and birds, and provide a serious health threat for cattle, pets, and humans. It has been argued that global warming may increase the incidence of harmful algal blooms. Here, we report on a

  17. Summer heatwaves promote blooms of harmful cyanobacteria

    Jöhnk, K.D.; Huisman, J.; Sharples, J.; Sommeijer, B.; Visser, P.M.; Stroom, J.M.

    2008-01-01

    Dense surface blooms of toxic cyanobacteria in eutrophic lakes may lead to mass mortalities of fish and birds, and provide a serious health threat for cattle, pets, and humans. It has been argued that global warming may increase the incidence of harmful algal blooms. Here, we report on a lake

  18. Harmful traditional practices in a newborn

    PROF. EZECHUKWU

    2014-11-17

    Nov 17, 2014 ... impact of harmful traditional home care practices on ... She was initially on breast milk and water until the tenth day of life ... and zygomatic bone as well as loss of subcutaneous fat. (fig 1). .... ity and protection during the neo-.

  19. Moral Distress, Workplace Health, and Intrinsic Harm.

    Weber, Elijah

    2016-05-01

    Moral distress is now being recognized as a frequent experience for many health care providers, and there's good evidence that it has a negative impact on the health care work environment. However, contemporary discussions of moral distress have several problems. First, they tend to rely on inadequate characterizations of moral distress. As a result, subsequent investigations regarding the frequency and consequences of moral distress often proceed without a clear understanding of the phenomenon being discussed, and thereby risk substantially misrepresenting the nature, frequency, and possible consequences of moral distress. These discussions also minimize the intrinsically harmful aspects of moral distress. This is a serious omission. Moral distress doesn't just have a negative impact on the health care work environment; it also directly harms the one who experiences it. In this paper, I claim that these problems can be addressed by first clarifying our understanding of moral distress, and then identifying what makes moral distress intrinsically harmful. I begin by identifying three common mistakes that characterizations of moral distress tend to make, and explaining why these mistakes are problematic. Next, I offer an account of moral distress that avoids these mistakes. Then, I defend the claim that moral distress is intrinsically harmful to the subject who experiences it. I conclude by explaining how acknowledging this aspect of moral distress should reshape our discussions about how best to deal with this phenomenon. © 2015 John Wiley & Sons Ltd.

  20. Mitigating the Harmful Effects of Violent Television

    Rosenkoetter, Lawrence I.; Rosenkoetter, Sharon E.; Ozretich, Rachel A.; Acock, Alan C.

    2004-01-01

    In an effort to minimize the harmful effects of violent TV, a yearlong intervention was undertaken with children in Grades 1 through 3 (N = 177). The classroom-based intervention consisted of 31 brief lessons that emphasized the many ways in which television distorts violence. As hypothesized, the intervention resulted in a reduction in children's…

  1. How Teacher Turnover Harms Student Achievement

    Ronfeldt, Matthew; Loeb, Susanna; Wyckoff, James

    2013-01-01

    Researchers and policymakers often assume that teacher turnover harms student achievement, though recent studies suggest this may not be the case. Using a unique identification strategy that employs school-by-grade level turnover and two classes of fixed-effects models, this study estimates the effects of teacher turnover on over 850,000 New York…

  2. Dynamic assembly, localization and proteolysis of the Bacillus subtilis SMC complex

    Rinn Cornelia

    2005-06-01

    Full Text Available Abstract Background SMC proteins are key components of several protein complexes that perform vital tasks in different chromosome dynamics. Bacterial SMC forms a complex with ScpA and ScpB that is essential for chromosome arrangement and segregation. The complex localizes to discrete centres on the nucleoids that during most of the time of the cell cycle localize in a bipolar manner. The complex binds to DNA and condenses DNA in an as yet unknown manner. Results We show that in vitro, ScpA and ScpB form different complexes with each other, among which the level of the putative 2 ScpA/4 ScpB complex showed a pronounced decrease in level upon addition of SMC protein. Different mutations of the ATPase-binding pocket of SMC reduced, but did not abolish interaction of mutant SMC with ScpA and ScpB. The loss of SMC ATPase activity led to a loss of function in vivo, and abolished proper localization of the SMC complex. The formation of bipolar SMC centres was also lost after repression of gyrase activity, and was abnormal during inhibition of replication, resulting in single central clusters. Resumption of replication quickly re-established bipolar SMC centres, showing that proper localization depends on ongoing replication. We also found that the SMC protein is subject to induced proteolysis, most strikingly as cells enter stationary phase, which is partly achieved by ClpX and LonA proteases. Atomic force microscopy revealed the existence of high order rosette-like SMC structures in vitro, which might explain the formation of the SMC centres in vivo. Conclusion Our data suggest that a ScpA/ScpB sub-complex is directly recruited into the SMC complex. This process does not require SMC ATPase activity, which, however, appears to facilitate loading of ScpA and ScpB. Thus, the activity of SMC could be regulated through binding and release of ScpA and ScpB, which has been shown to affect SMC ATPase activity. The proper bipolar localization of the SMC

  3. Role of calpain in eccentric contraction-induced proteolysis of Ca2+-regulatory proteins and force depression in rat fast-twitch skeletal muscle.

    Kanzaki, Keita; Watanabe, Daiki; Kuratani, Mai; Yamada, Takashi; Matsunaga, Satoshi; Wada, Masanobu

    2017-02-01

    The aim of this study was to examine the in vivo effects of eccentric contraction (ECC) on calpain-dependent proteolysis of Ca 2+ -regulatory proteins and force production in fast-twitch skeletal muscles. Rat extensor digitorum longus muscles were exposed to 200 repeated ECC in situ and excised immediately [recovery 0 (REC0)] or 3 days [recovery 3 (REC3)] after cessation of ECC. Calpain inhibitor (CI)-treated rats were intraperitoneally injected with MDL-28170 before ECC and during REC3. Tetanic force was markedly reduced at REC0 and remained reduced at REC3. CI treatment ameliorated the ECC-induced force decline but only at REC3. No evidence was found for proteolysis of dihydropyridine receptor (DHPR), junctophilin (JP)1, JP2, ryanodine receptor (RyR), sarcoplasmic reticulum Ca 2+ -ATPase (SERCA)1a, or junctional face protein-45 at REC0. At REC3, ECC resulted in decreases in DHPR, JP1, JP2, RyR, and SERCA1a. CI treatment prevented the decreases in DHPR, JP1, and JP2, whereas it had little effect on RyR and SERCA1a. These findings suggest that DHPR, JP1, and JP2, but not RyR and SERCA1a, undergo calpain-dependent proteolysis in in vivo muscles subjected to ECC and that impaired function of DHPR and/or JP might cause prolonged force deficits with ECC. NEW & NOTEWORTHY Calpain-dependent proteolysis is one of the contributing factors to muscle damage that occurs with eccentric contraction (ECC). It is unclear, however, whether calpains account for proteolysis of Ca 2+ -regulatory proteins in in vivo muscles subjected to ECC. Here, we provide evidence that dihydropyridine receptor and junctophilin, but not ryanodine receptor and sarcoplasmic reticulum Ca 2+ -ATPase, undergo calpain-dependent proteolysis. Copyright © 2017 the American Physiological Society.

  4. Effect of monoclonal antibodies on limited proteolysis of native glycoprotein gD of herpes simplex virus type 1

    Eisenberg, R.J.; Long, D.; Pereira, L.; Hampar, B.; Zweig, M.; Cohen, G.H.

    1982-01-01

    We examined the properties of 17 monoclonal antibodies to glycoprotein gD of herpes simplex type 1 (HSV-1) (gD-1) and HSV-2 (gD-2). The antibodies recognized eight separate determinants of gD, based on differences in radioimmuno-precipitation and neutralization assays. The determinants were distributed as follows: three were gD-1 specific, one was gD-2 specific, and four were type common. Several type-specific and type-common determinants appeared to be involved in neutralization. We developed a procedure for examining the effect that binding of monoclonal antibody has on proteolysis of native gD-1 by Staphylococcus aureus protease V8. We showed that several different patterns of protease V8 cleavage were obtained, depending on the monoclonal antibody used. The proteolysis patterns were generally consistent with the immunological groupings. With four groups of antibodies, we found that fragments of gD-1 remained bound to antibody after V8 treatment. A 38,000-dalton fragment remained bound to antibodies in three different groups of monoclonal antibodies. This fragment appeared to contain one type-common and two type-specific determinants. A 12,000-dalton fragment remained bound to antibodies belonging to one type-common group of monoclonal antibodies. Tryptic peptide analysis revealed that the 12,000-dalton fragment represented a portion of the 38,000-dalton fragment and was enriched in a type-common arginine tryptic peptide

  5. Effect of pulsed electric field on the proteolysis of cold boned beef M. Longissimus lumborum and M. Semimembranosus.

    Suwandy, Via; Carne, Alan; van de Ven, Remy; Bekhit, Alaa El-Din A; Hopkins, David L

    2015-02-01

    The effects of pulsed electric field (PEF) and ageing (3, 7, 14 and 21 days) on the shear force, protein profile, and post-mortem proteolysis of beef loins (M. Longissimus lumborum, LL) and topsides (M. Semimembranosus, SM) were investigated using a range of pulsed electric field treatments [voltages (5 and 10 kV) and frequencies (20, 50, and 90 Hz)]. PEF treatment decreased the shear force of beef LL and SM muscles by up to 19%. The reduction in the shear force in the LL was not affected by the treatment intensity whereas the reduction in the SM was dependent on PEF frequency. PEF treated beef loins showed increased proteolysis, both early post-mortem and during subsequent post-mortem storage reflected by increased degradation of troponin-T and desmin. The most prominent troponin-T degradation was found in samples treated with 5 kV-90 Hz, 10 kV-20 Hz at day 3 and day 7 post-treatment in addition to 10 kV-50 Hz in subsequent post-treatment times. The degradation of desmin in PEF treated beef loins increased with ageing time.

  6. The Vip3Ag4 Insecticidal Protoxin from Bacillus thuringiensis Adopts A Tetrameric Configuration That Is Maintained on Proteolysis

    Leopoldo Palma

    2017-05-01

    Full Text Available The Vip3 proteins produced during vegetative growth by strains of the bacterium Bacillus thuringiensis show insecticidal activity against lepidopteran insects with a mechanism of action that may involve pore formation and apoptosis. These proteins are promising supplements to our arsenal of insecticidal proteins, but the molecular details of their activity are not understood. As a first step in the structural characterisation of these proteins, we have analysed their secondary structure and resolved the surface topology of a tetrameric complex of the Vip3Ag4 protein by transmission electron microscopy. Sites sensitive to proteolysis by trypsin are identified and the trypsin-cleaved protein appears to retain a similar structure as an octomeric complex comprising four copies each of the ~65 kDa and ~21 kDa products of proteolysis. This processed form of the toxin may represent the active toxin. The quality and monodispersity of the protein produced in this study make Vip3Ag4 a candidate for more detailed structural analysis using cryo-electron microscopy.

  7. Mammography screening. Benefits, harms, and informed choice.

    Jørgensen, Karsten Juhl

    2013-04-01

    The rationale for breast cancer screening with mammography is deceptively simple: catch it early and reduce mortality from the disease and the need for mastectomies. But breast cancer is a complex problem, and complex problems rarely have simple solutions. Breast screening brings forward the time of diagnosis only slightly compared to the lifetime of a tumour, and screen-detected tumours have a size where metastases are possible. A key question is if screening can prevent metastases, and if the screen-detected tumours are small enough to allow breast conserving surgery rather than mastectomy. A mortality reduction can never justify a medical intervention in its own right, but must be weighed against the harms. Overdiagnosis is the most important harm of breast screening, but has gained wider recognition only in recent years. Screening leads to the detection and treatment of breast cancers that would otherwise never have been detected because they grow very slowly or not at all and would not have been detected in the woman's lifetime in the absence of screening. Screening therefore turns women into cancer patients unnecessarily, with life-long physical and psychological harms. The debate about the justification of breast screening is therefore not a simple question of whether screening reduces breast cancer mortality. This dissertation quantifies the primary benefits and harms of screening mammography. Denmark has an unscreened "control group" because only two geographical regions offered screening over a long time-period, which is unique in an international context. This was used to study breast cancer mortality, overdiagnosis, and the use of mastectomies. Also, a systematic review of overdiagnosis in five other countries allowed us to show that about half of the screen-detected breast cancers are overdiagnosed. An effect on breast cancer mortality is doubtful in today's setting, and overdiagnosis causes an increase in the use of mastectomies. These findings are

  8. Protecting air basins from harmful discharges

    Yankovskiy, S S

    1983-01-01

    The work is a brief description of the content of the reports delivered at the seminar entitled Protecting the Air Basin from Harmful Discharges of the Machine Building Enterprises, which took place at the All Union Exhibit of the Achievements of the National Economy of the USSR (VDNKh) in 1982. Representatives of different ministries and agencies, scientific research institutes (NII), planning and design and other specialized organizations, institutes of higher learning (vuz) and enterprises from different branches of industry took part in the work of the seminar. The seminar noted measures to eliminate deficiencies which occur in individual enterprises of the branch and measures to improve the work to improve protection of the air basin from harmful discharges of machine building enterprises.

  9. Harmful effects on plants. 2. rev. ed.

    Hock, B.; Elstner, E.F.

    1988-01-01

    The book deals with accidentally or purposefully induced harmful effects on plants, i.e. eukariyotes and fungi, with emphasis being placed on chemicals as the main pollutants. After discussing the quantification of damage as a prerequisite for detecting, defining, and possibly preventing, damage to plants by toxic substances in the environment, the second part of the book deals with the harmful effects that are purposefully induced, for example in agriculture or horticulture, by employment of pesticides (herbicides or fungicides). In this context, all aspects of uptake, metabolism, and detoxication are discussed, especially referring to the molecular conditions of relevance to a selective elimination of metabolic or developmental processes in the plants, which is explained by the effects of pesticides and antibiotics. Injuries caused by autogenous substances in the plants, upon exceeding a certain amount or dose are also explained, together with effects of physical factors (as e.g. ionizing radiation), or biogenic factors (as e.g. parasites). (ECB) [de

  10. Boundaries between Fair and Harmful Tax Competition

    Paweł Szwajdler

    2016-12-01

    Full Text Available The aim of this paper is to show boundaries between fair and harmful tax competition. The author analyses OECD’s reports and literature related to the tax competition. In the beginning, the author presents the notion of tax competition and its division into fair and unfair tax competition. Differences between tax heaven and preferential tax regime are also discussed. In the summary, the author highlights that boundaries between fair and harmful tax competition are not obvious, but there are well-known guidelines, which let distinguish above-mentioned issues. The author considers that there are real tax burden, effective exchange of tax information and transparency in the fair tax regime. The author states that taxpayer can do justified tax planning in such tax system.

  11. Party drugs - use and harm reduction.

    Frei, Matthew

    2010-08-01

    Party drug use, the intermittent use of stimulants, ecstasy and so-called 'designer drugs' at dance parties or 'raves', is now part of the culture of many young Australians. This article discusses the risks associated with the use of 'party drugs' and describes an useful approach to general practitioner assessment and management of patients who may be using party drugs. Party drug use is associated with a range of harms, including risks associated with behaviour while drug affected, toxicity and overdose, mental health complications and physical morbidity. Multiple substance use, particularly combining sedatives, further amplifies risk. If GPs have some understanding of these drugs and their effects, they are well placed to provide an effective intervention in party drug users by supporting the reduction of harm.

  12. Harmful organisms in urban green areas

    Hanousková, Irena; Boháč, Jaroslav; Sedláček, František; Šerá, Božena; Lepšová, A.; Zacharda, Miloslav

    -, č. 23 (2004), s. 58-68 ISSN 1335-342X R&D Projects: GA MŠk(CZ) OC C11.001 Grant - others:ÚEK AV ČR(CZ) OC C11.001 Program:OC Institutional research plan: CEZ:AV0Z6087904 Keywords : urban green areas, harmful organisms, management, * planning Subject RIV: AP - Urban, Regional and Transport Planning

  13. Is Personality Associated with Secondhand Harm from Drinking?

    Davis MacNevin, Parnell; Thompson, Kara; Teehan, Michael; Stuart, Heather; Stewart, Sherry

    2017-09-01

    Prior research suggests more than 70% of undergraduates have experienced harm from other students' drinking. This study built on the literature by, first, investigating whether secondhand harm cluster into latent factors that reflect distinct but related types of harm. Second, given the paucity of research examining factors that increase students' vulnerability to secondhand harm, we examined dimensions from Castellanos-Ryan and Conrod's 4-factor personality model for alcohol disorders (impulsivity [IMP], sensation seeking [SS], hopelessness [HOP], anxiety sensitivity [AS]) as predictors of secondhand harm exposure. We also investigated the possible mediating role of students' own problematic alcohol use in explaining personality-secondhand harm relationships. An online survey was administered to 1,537 first-year Canadian undergraduates (68% women). Problematic alcohol use was measured by the Alcohol Use Disorders Identification Test, and personality was measured by the Substance Use Risk Profile Scale. Eleven secondhand harm items were included. The secondhand harm clustered into 3 distinct but related factors: "strains" (e.g., interruption of sleep or study), "threats" (e.g., harassment or assault), and "interpersonal harm" (e.g., arguments with peers). Sixty-eight percent of respondents reported strains, 44% threats, and 64% interpersonal harm, and 35% reported experiencing all 3 types of harm, in the last term. All 4 personality dimensions were independently associated with greater secondhand harm exposure. HOP was directly associated with threats and interpersonal harm, and AS was directly associated with all 3 types of harm. SS and IMP were both indirectly associated with all 3 types of harm through students' own problematic alcohol use. In addition, IMP was directly related to threats. The prevalence of secondhand harm from alcohol is high among undergraduates. Findings suggest that distinct personality risks may predispose students to experience secondhand

  14. Révision du genre Eurypetalum Harms (Fabaceae, Caesalpinioideae)

    Obiang-Mbomio, D.; Breteler, F.J.

    2007-01-01

    Revision of the genus Eurypetalum Harms (Fabaceae, Caesalpinioideae). Th e African genus Eurypetalum Harms (Fabaceae, Caesalpinioideae) of Lower Guinea is revised. Two species, E. tessmannii and E. unijugum, are recognized. Th ey are illustrated and their distributions are mapped. Eurypetalum

  15. Characterisation of cysteine proteinases responsible for digestive proteolysis in guts of larval Western corn rootworm (Diabrotica virgifera) by expression in the yeast Pichia pastoris

    Bown, D.P.; Wilkinson, H.S.; Jongsma, M.A.; Gatehouse, J.A.

    2004-01-01

    Cysteine proteinases are the major class of enzymes responsible for digestive proteolysis in western corn rootworm (Diabrotica virgifera), a serious pest of maize. A larval gut extract hydrolysed typical cathepsin substrates, such as Z-phe-arg-AMC and Z-arg-arg-AMC, and hydrolysis was inhibited by

  16. PROTEOLYSIS DURING MANUFACTURE AND RIPENING/STORING OF “OLOMOUCKÉ TVARŮŽKY” CHEESE (PGI

    Vendula Pachlová

    2015-02-01

    Full Text Available Twenty-two free amino acid (FAA concentrations were observed during manufacture (1st, 3rd and 7th days of production and ripening period (42 days storing at 8°C of “Olomoucké tvarůžky” (PGI, smear acid cheese. Sensory attributes were also analysed during ripening period. The free amino acids were determined by means of ion-exchange chromatography. The development of the individual FAA content positively correlated with the ripening period (r = 0.7734–0.9229; P < 0.01.The results gave information about the development precursors (FAA of typically sensory active compound in “Olomoucké tvarůžky” (PGI during its production and especially ripening. In conclusion, we found that free amino acid concentration as finally products of proteolysis are positive with improved flavour.

  17. Cloning and expression of the receptor for human urokinase plasminogen activator, a central molecule in cell surface, plasmin dependent proteolysis

    Roldan, A.L.; Cubellis, M.V.; Masucci, M.T.

    1990-01-01

    , and therefore the capacity of cells to migrate and invade neighboring tissues. We have isolated a 1.4 kb cDNA clone coding for the entire human uPAR. An oligonucleotide synthesized on the basis of the N-terminal sequence of the purified protein was used to screen a cDNA library made from SV40 transformed human......, a size very close to that of the cloned cDNA. Expression of the uPAR cDNA in mouse cells confirms that the clone is complete and expresses a functional uPA binding protein, located on the cell surface and with properties similar to the human uPAR. Caseinolytic plaque assay, immunofluorescence analysis......The surface receptor for urokinase plasminogen activator (uPAR) has been recognized in recent years as a key molecule in regulating plasminogen mediated extracellular proteolysis. Surface plasminogen activation controls the connections between cells, basement membrane and extracellular matrix...

  18. Initiation of proteolysis of yeast fructose-1,6-bisphosphatase by pH-control of adenylate cyclase

    Holzer, H.; Purwin, C.; Pohlig, G.; Scheffers, W.A.; Nicolay, K.

    1986-01-01

    Addition of fermentable sugars or uncouplers such as CCCP to resting yeast cells grown on glucose initiates phosphorylation of fructose-1,6-bisphosphatase (FBPase). There is good evidence that phosphorylation marks FBPase for proteolytic degradation. 31 P-NMR measurements of the cytosolic pH of yeast cells demonstrated a decrease of the cytosolic pH from 7.0 to 6.5 after addition of glucose or CCCP to starved yeast. Activity of adenylate cyclase in permeabilized yeast cells increases 2-3-fold when the pH is lowered from 7.0 to 6.5. It is concluded that pH controlled activation of adenylate cyclase causes the previously described increase in cyclic AMP which leads to phosphorylation of FBPase and finally to proteolysis of FBPase

  19. Proteolysis of His-Phe-Arg-Trp-Pro-Gly-Pro in the blood and brain of rats in vivo.

    Shevchenko, K V; Nagaev, I Yu; Babakov, V N; Andreeva, L A; Shevchenko, V P; Radilov, A S; Myasoedov, N F

    2015-01-01

    The kinetics of the content of His-Phe-Arg-Trp-Pro-Gly-Pro (ACTH (6-9)PGP) and its hydrolysis products in the blood and brain of rats in the case of intranasal administration and intravenous injection of tritiated ACTH(6-9)PGP was studied. The parameters of bioavailability of ACTH(6-9)PGP administered intranasally were higher, indicating certain prospects in the intranasal application in clinical practice. We also found that the factor that determines ACTH(6-9)PGP proteolysis in experiments both in vivo and in vitro is aminopeptidases. The main products of ACTH(6-9)PGP during its metabolism in rats are short peptides and amino acids.

  20. Impact of pasteurization of human milk on preterm newborn in vitro digestion: Gastrointestinal disintegration, lipolysis and proteolysis.

    de Oliveira, Samira C; Bourlieu, Claire; Ménard, Olivia; Bellanger, Amandine; Henry, Gwénaële; Rousseau, Florence; Dirson, Emelyne; Carrière, Frédéric; Dupont, Didier; Deglaire, Amélie

    2016-11-15

    Human milk feeding is an important recommendation for preterm newborns considering their vulnerability and digestive immaturity. Holder pasteurization (62.5°C, 30min) applied in milk banks modifies its biological quality and its microstructure. We investigated the impact of pasteurization of preterm human milk on its gastrointestinal kinetics of lipolysis, proteolysis and structural disintegration. An in vitro dynamic system was set up to simulate the gastrointestinal digestion of preterm newborns. A pool of preterm human milk was digested as raw or after Holder pasteurization. Pasteurization impacted the microstructure of undigested human milk, its gastrointestinal disintegration and tended to limit the intestinal lipolysis. Furthermore, the gastrointestinal bioaccessibility of some fatty acids was decreased by pasteurization, while the intestinal bioaccessibility of some amino acids was selectively modulated. The impact of pasteurization on the digestion of human milk may have nutritional relevance in vivo and potentially modulates preterm development and growth. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Measuring emergency department nurses' attitudes towards deliberate self-harm using the Self-Harm Antipathy Scale.

    Conlon, Mary

    2012-01-31

    The emergency department is an important gateway for the treatment of self-harm patients. Nurses\\' attitudes towards patients who self-harm can be negative and often nurses experience frustration, helplessness, ambivalence and antipathy. Patients are often dissatisfied with the care provided, and meeting with positive or negative attitudes greatly influences whether they seek additional help. A quantitative design was utilised to measure emergency department nurses\\' attitudes towards deliberate self-harm. The \\'Self-Harm Antipathy Scale\\

  2. Ascorbate attenuates pulmonary emphysema by inhibiting tobacco smoke and Rtp801-triggered lung protein modification and proteolysis.

    Gupta, Indranil; Ganguly, Souradipta; Rozanas, Christine R; Stuehr, Dennis J; Panda, Koustubh

    2016-07-19

    Cigarette smoking causes emphysema, a fatal disease involving extensive structural and functional damage of the lung. Using a guinea pig model and human lung cells, we show that oxidant(s) present in tobacco smoke not only cause direct oxidative damage of lung proteins, contributing to the major share of lung injury, but also activate Rtp801, a key proinflammatory cellular factor involved in tobacco smoke-induced lung damage. Rtp801 triggers nuclear factor κB and consequent inducible NOS (iNOS)-mediated overproduction of NO, which in combination with excess superoxide produced during Rtp801 activation, contribute to increased oxido-nitrosative stress and lung protein nitration. However, lung-specific inhibition of iNOS with a iNOS-specific inhibitor, N6-(1-iminoethyl)-L-lysine, dihydrochloride (L-NIL) solely restricts lung protein nitration but fails to prevent or reverse the major tobacco smoke-induced oxidative lung injury. In comparison, the dietary antioxidant, ascorbate or vitamin C, can substantially prevent such damage by inhibiting both tobacco smoke-induced lung protein oxidation as well as activation of pulmonary Rtp801 and consequent iNOS/NO-induced nitration of lung proteins, that otherwise lead to increased proteolysis of such oxidized or nitrated proteins by endogenous lung proteases, resulting in emphysematous lung damage. Vitamin C also restricts the up-regulation of matrix-metalloproteinase-9, the major lung protease involved in the proteolysis of such modified lung proteins during tobacco smoke-induced emphysema. Overall, our findings implicate tobacco-smoke oxidant(s) as the primary etiopathogenic factor behind both the noncellular and cellular damage mechanisms governing emphysematous lung injury and demonstrate the potential of vitamin C to accomplish holistic prevention of such damage.

  3. MMP-13 regulates growth of wound granulation tissue and modulates gene expression signatures involved in inflammation, proteolysis, and cell viability.

    Mervi Toriseva

    Full Text Available Proteinases play a pivotal role in wound healing by regulating cell-matrix interactions and availability of bioactive molecules. The role of matrix metalloproteinase-13 (MMP-13 in granulation tissue growth was studied in subcutaneously implanted viscose cellulose sponge in MMP-13 knockout (Mmp13(-/- and wild type (WT mice. The tissue samples were harvested at time points day 7, 14 and 21 and subjected to histological analysis and gene expression profiling. Granulation tissue growth was significantly reduced (42% at day 21 in Mmp13(-/- mice. Granulation tissue in Mmp13(-/- mice showed delayed organization of myofibroblasts, increased microvascular density at day 14, and virtual absence of large vessels at day 21. Gene expression profiling identified differentially expressed genes in Mmp13(-/- mouse granulation tissue involved in biological functions including inflammatory response, angiogenesis, cellular movement, cellular growth and proliferation and proteolysis. Among genes linked to angiogenesis, Adamts4 and Npy were significantly upregulated in early granulation tissue in Mmp13(-/- mice, and a set of genes involved in leukocyte motility including Il6 were systematically downregulated at day 14. The expression of Pdgfd was downregulated in Mmp13(-/- granulation tissue in all time points. The expression of matrix metalloproteinases Mmp2, Mmp3, Mmp9 was also significantly downregulated in granulation tissue of Mmp13(-/- mice compared to WT mice. Mmp13(-/- mouse skin fibroblasts displayed altered cell morphology and impaired ability to contract collagen gel and decreased production of MMP-2. These results provide evidence for an important role for MMP-13 in wound healing by coordinating cellular activities important in the growth and maturation of granulation tissue, including myofibroblast function, inflammation, angiogenesis, and proteolysis.

  4. Recombinant PrPSc shares structural features with brain-derived PrPSc: Insights from limited proteolysis.

    Sevillano, Alejandro M; Fernández-Borges, Natalia; Younas, Neelam; Wang, Fei; R Elezgarai, Saioa; Bravo, Susana; Vázquez-Fernández, Ester; Rosa, Isaac; Eraña, Hasier; Gil, David; Veiga, Sonia; Vidal, Enric; Erickson-Beltran, Melissa L; Guitián, Esteban; Silva, Christopher J; Nonno, Romolo; Ma, Jiyan; Castilla, Joaquín; R Requena, Jesús

    2018-01-01

    Very solid evidence suggests that the core of full length PrPSc is a 4-rung β-solenoid, and that individual PrPSc subunits stack to form amyloid fibers. We recently used limited proteolysis to map the β-strands and connecting loops that make up the PrPSc solenoid. Using high resolution SDS-PAGE followed by epitope analysis, and mass spectrometry, we identified positions ~116/118, 133-134, 141, 152-153, 162, 169 and 179 (murine numbering) as Proteinase K (PK) cleavage sites in PrPSc. Such sites likely define loops and/or borders of β-strands, helping us to predict the threading of the β-solenoid. We have now extended this approach to recombinant PrPSc (recPrPSc). The term recPrPSc refers to bona fide recombinant prions prepared by PMCA, exhibiting infectivity with attack rates of ~100%. Limited proteolysis of mouse and bank vole recPrPSc species yielded N-terminally truncated PK-resistant fragments similar to those seen in brain-derived PrPSc, albeit with varying relative yields. Along with these fragments, doubly N- and C-terminally truncated fragments, in particular ~89/97-152, were detected in some recPrPSc preparations; similar fragments are characteristic of atypical strains of brain-derived PrPSc. Our results suggest a shared architecture of recPrPSc and brain PrPSc prions. The observed differences, in particular the distinct yields of specific PK-resistant fragments, are likely due to differences in threading which result in the specific biochemical characteristics of recPrPSc. Furthermore, recombinant PrPSc offers exciting opportunities for structural studies unachievable with brain-derived PrPSc.

  5. Andrographolide alleviates imiquimod-induced psoriasis in mice via inducing autophagic proteolysis of MyD88.

    Shao, Fenli; Tan, Tao; Tan, Yang; Sun, Yang; Wu, Xingxin; Xu, Qiang

    2016-09-01

    Psoriasis is a chronic inflammatory skin disease with excessive activation of toll-like receptors (TLRs), which play important roles in developing psoriasis. Targeting TLR signaling remains a challenge for treating psoriasis. Here, we found that andrographolide (Andro), a small-molecule natural product, alleviated imiquimod- but not interleukin 23 (IL-23)-induced psoriasis in mice with reducing expressions of IL-23 and IL-1β in the skin. The improvement in imiquimod-induced psoriasis by Andro was not observed in microtubule-associated protein 1 light chain 3 beta (MAP1LC3B) knockout mice. Furthermore, Andro inhibited mRNA expressions of IL-23, IL-6 and IL-1β but not CD80 and CD86 in bone-marrow derived dendritic cells (BMDCs) treated with lipopolysaccharide (LPS) in a MAP1LC3B-dependent manner. In addition, Andro inhibited imiquimod-induced mRNA expressions of IL-23, IL-6, IL-1β, CD80 and CD86 in BMDCs from mice. Interestingly, Andro induced a degradation of myeloid differentiation factor 88 (MyD88) and blocked the recruitment of TNF receptor-associated factor 6 (TRAF6) to MyD88 upon LPS stimulation in BMDCs from mice. Blockade of autophagic proteolysis using NH4Cl or MAP1LC3B(-/-) BMDCs abolished the Andro-induced MyD88 degradation. In conclusion, Andro controls activation of MyD88-dependent cytokines and alleviates psoriasis in mice via inducing autophagic proteolysis of MyD88, which could be a novel strategy to treat psoriasis. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. In vivo effect of an antilipolytic drug (3,5'-dimethylpyrazole) on autophagic proteolysis and autophagy-related gene expression in rat liver

    Donati, Alessio; Ventruti, Annamaria; Cavallini, Gabriella; Masini, Matilde; Vittorini, Simona; Chantret, Isabelle; Codogno, Patrice; Bergamini, Ettore

    2008-01-01

    Autophagy is an intracellular pathway induced by starvation, inhibited by nutrients, that is responsible for degradation of long-lived proteins and altered cell organelles. This process is involved in cell maintenance could be induced by antilipolytic drugs and may have anti-aging effects [A. Donati, The involvement of macroautophagy in aging and anti-aging interventions, Mol. Aspects Med. 27 (2006) 455-470]. We analyzed the effect of an intraperitoneal injection of an antilipolytic agent (3,5'-dimethylpyrazole, DMP, 12 mg/kg b.w.), that mimics nutrient shortage on autophagy and expression of autophagic genes in the liver of male 3-month-old Sprague-Dawley albino rats. Autophagy was evaluated by observing electron micrographs of the liver autophagosomal compartment and by monitoring protein degradation assessed by the release of valine into the bloodstream. LC3 gene expression, whose product is one of the best known markers of autophagy, was also monitored. As expected, DMP decreased the plasma levels of free fatty acids, glucose, and insulin and increased autophagic vacuoles and proteolysis. DMP treatment caused an increase in the expression of the LC3 gene although this occurred later than the induction of authophagic proteolysis caused by DMP. Glucose treatment rescued the effects caused by DMP on glucose and insulin plasma levels and negatively affected the rate of autophagic proteolysis, but did not suppress the positive regulatory effect on LC3 mRNA levels. In conclusion, antilipolytic drugs may induce both autophagic proteolysis and higher expression of an autophagy-related gene and the effect on autophagy gene expression might not be secondary to the stimulation of autophagic proteolysis

  7. Brief Report: The Self Harm Questionnaire--A New Tool Designed to Improve Identification of Self Harm in Adolescents

    Ougrin, Dennis; Boege, Isabel

    2013-01-01

    The Self Harm Questionnaire (SHQ) aiming at identification of self-harm in adolescents has been developed and piloted in a sample of 12-17 year olds (n = 100). The adolescents were recruited from both in- and outpatient psychiatric services. Concurrent validity of the SHQ was evaluated by comparing the SHQ results with recorded self harm in the…

  8. Harmfulness of smoking among high school students

    Iwona Rotter

    2013-03-01

    Full Text Available Introduction: The aim of the study was to assess the level of awareness of smoking and non smoking students on harmful impact of nicotine and cigarette smoke on human body. Material and methods: The study was carried out in March 2011 in high schools in Szczecin. Own elaborated questionnaire was used. 288 students from high school, technical college and vocational school were tested. Results: The majority of responders (95,1% claimed that cigarette smoke is harmful both for passive and active smokers. They most often pinpoint the direct cause connected with smoking to pulmonary diseases (264 persons and cancers (240 persons. Almost 90% of students found negative impact of tobacco products on development of fetus of pregnant women. Overwhelming majority of respondents (83,2% feels anxious if it comes to stay in a room filled with smoke. Conclusions: The awareness of high school students on negative influence of smoking on human body is quite satisfactory, but there is still a need for more education in the range of diseases and symptoms connected with smoking.

  9. FACEBOOK AND WHATSAPP: BENEFICIAL OR HARMFUL?

    Sankalp Raj

    2015-04-01

    Full Text Available New innovations and advances in science and technology in the present day have made considerable and significant changes in the lifestyle of people all around the globe. Communication from one part of the world to another is possible at the hit of a button . Social networking is being rampantly used everywhere and by everybody, be it youngsters or the older generation. Facebook and Whatsapp are the most commonly used means of communication in social networking at present. Smart phones functioning as minicomp uters with fast internet connectivity in the pockets of today’s technosavy generation have made them create and spend most of their time interacting with people in a virtual world. There is an urgent need to understand the dynamics of social media and its effects on the lifestyle of people. Studies documenting the same have been very few. This study was conducted to understand the benefits and harms towards health and academics of MBBS students. This cross - sectional study on 147 MBBS students revealed inter esting findings and opinions of the students. Effects of Facebook and What Sapp on productivity and sleep disturbances due to it were the significant findings of the study. Facebook and Whatsapp can be considered both beneficial and harmful and it solely d epends on how it is being put to use

  10. Trichloroacetic Acid Ingestion: Self-Harm Attempt

    E. R. Black

    2017-01-01

    Full Text Available Objective. Trichloroacetic acid (TCAA, or trichloroethanoic acid, is a chemical analogue of acetic acid where three methyl group hydrogen atoms are replaced by chlorine. TCAAs are also abbreviated and referred to as TCAs, causing confusion with the psychiatric antidepressant drug class, especially among patients. TCAAs exist in dermatological treatments such as chemical peels or wart chemoablation medication. TCAA ingestion or overdose can cause gastric irritation symptoms including vomiting, diarrhea, or lassitude. This symptomatology is less severe than TCA overdose, where symptoms may include elevated body temperature, blurred vision, dilated pupils, sleepiness, confusion, seizures, rapid heart rate, and cardiac arrest. Owing to the vast difference in symptoms, the need for clinical intervention differs greatly. While overdose of either in a self-harm attempt can warrant psychiatric hospital admission, the risk of death in TCAA ingestion is far less. Case Report. A patient ingested TCAA in the form of a commercially available dermatological chemical peel as a self-harm attempt, thinking that it was a more injurious TCA. Conclusion. Awareness among physicians, particularly psychiatrists, regarding this relatively obscure chemical compound (TCAA and its use by suicidal patients mistakenly believing it to be a substance that can be significantly more lethal (TCA, is imperative.

  11. Perceived harmfulness of substance use: A pilot study

    Siddharth Sarkar

    2014-01-01

    Full Text Available Background: Harm ratings of substances help in understanding the perception toward substance use and formulating policies. Evidence of such harm ratings by substance users and their caregivers provides a clearer perspective of those who experience and observe such harm closely. Materials and Methods: Substance users and their caregivers were recruited from the Drug De-addiction and Treatment Centre of PGIMER, Chandigarh. Sociodemographic details of the subjects were noted. The subjects were then asked to rate a list of psychoactive preparations according to the harms they thought the preparation caused. The list of substances was developed taking into consideration substance commonly encountered in the geographical area. The harm ratings were transformed on a scale of 0-100. Results: All subjects were males and majority of them were educated above 10 th standard, were not employed and belonged to urban background. Most of them had taken psychoactive substances in their lifetimes but were currently abstinent. Most of the subjects endorsed intravenous drugs as the most harmful, followed by heroin. Beer and chewable tobacco considered the least harmful substances. Greater degree of education was associated with lower harm rankings for heroin, cannabis, dextropropoxyphene, and raw opium; while urban residence was associated with greater harm ratings for cannabis and raw opium. Differences in the harms were perceived for different preparations of the same active compound for alcohol and nicotine. Conclusion: Harm ratings of substances can be a useful guide while formulating policies and allocating resources. Need for further research extending this pilot study is emphasized.

  12. Can harmful tax competition be curbed at the international level?

    Gjersti, Per O. [Finans- og Tolldepartementet, Oslo (Norway)

    1998-07-01

    This presentation discusses the following issues: (1) Good vs harmful tax competition?, (2) How to identify harmful competition?, (3) What is the economic and social impact of harmful tax competition?, (4) What can be done about harmful tax competition? There are three levels, the EU level, the OECD level and the global level. Existing measures to counteract harmful tax practices are insufficient because action by one country merely shifts activity to another country and puts its tax payers at a competitive disadvantage and because coordination action eases political pressure. The EU code of good conduct and the OECD guidelines for dealing with harmful preferential tax regimes are compared, with respect to general features, with respect to key factors to identify harmful measures, and with respect to general scope.

  13. No harm done? Assessing risk of harm under the federal breach notification rule.

    Dimick, Chris

    2010-08-01

    Provisions within the HITECH Act require that covered entities notify individuals if their protected health information is breached. However, the current regulation allows an exemption if the risk of harm is slight. Assessing risk can be subjective, and privacy officers have been working to create methods to conduct and document their analyses.

  14. Harming High Performers : A Social Comparison Perspective on Interpersonal Harming in Work Teams

    Lam, Catherine K.; Van der Vegt, Gerben S.; Walter, Frank; Huang, Xu; Huang, Xin

    This study developed a multilevel model of the interpersonal harming behavior associated with social comparison processes in work teams. We tested this model using temporally lagged data from a sample of student teams (Study 1) and cross-sectional data from a sample of work teams in a

  15. Harmful Algal Blooms and Public Health.

    Grattan, Lynn M; Holobaugh, Sailor; Morris, J Glenn

    2016-07-01

    The five most commonly recognized Harmful Algal Bloom related illnesses include Ciguatera poisoning, Paralytic Shellfish poisoning, Neurotoxin Shellfish poisoning, Diarrheic Shellfish Poisoning and Amnesic Shellfish poisoning. Although they are each the product of different toxins, toxin assemblages or HAB precursors these clinical syndromes have much in common. Exposure occurs through the consumption of fish or shellfish; routine clinical tests are not available for diagnosis; there is no known antidote for exposure; and the risk of these illnesses can negatively impact local fishing and tourism industries. Thus, illness prevention is of paramount importance to minimize human and public health risks. To accomplish this, close communication and collaboration is needed among HAB scientists, public health researchers and local, state and tribal health departments at academic, community outreach, and policy levels.

  16. Harmful Effects of Nanoparticles on Animals

    Jean-Marie Exbrayat

    2015-01-01

    Full Text Available Since several years nanoparticles (NPs are produced by industries and used in several fields of activities. They are finally found in aquatic and terrestrial environments, where they are ingested by living organisms in which they accumulate, before being eliminated. In organisms, NPs represent foreign elements with their own physicochemical properties due to their small size. So NPs may interfere with the normal physiological mechanisms of the embryos, growing animals, and adults, and it is indispensable to understand their potentially direct or indirect harmful effects on living organisms. It has been already shown that NPs could be toxic to bacteria, algae, invertebrates, and vertebrates. In this review, several examples of recent studies are given. We will examine successively the effects of NPs on terrestrial and semiaquatic and aquatic vertebrate and invertebrate animals.

  17. Harmful Algal Blooms and Public Health

    Grattan, Lynn M.; Holobaugh, Sailor; Morris, J. Glenn

    2015-01-01

    The five most commonly recognized Harmful Algal Bloom related illnesses include Ciguatera poisoning, Paralytic Shellfish poisoning, Neurotoxin Shellfish poisoning, Diarrheic Shellfish Poisoning and Amnesic Shellfish poisoning. Although they are each the product of different toxins, toxin assemblages or HAB precursors these clinical syndromes have much in common. Exposure occurs through the consumption of fish or shellfish; routine clinical tests are not available for diagnosis; there is no known antidote for exposure; and the risk of these illnesses can negatively impact local fishing and tourism industries. Thus, illness prevention is of paramount importance to minimize human and public health risks. To accomplish this, close communication and collaboration is needed among HAB scientists, public health researchers and local, state and tribal health departments at academic, community outreach, and policy levels. PMID:27616971

  18. Potentially harmful excipients in neonatal medicines

    Nellis, Georgi; Metsvaht, Tuuli; Varendi, Heili

    2015-01-01

    OBJECTIVES: We aimed to describe administration of eight potentially harmful excipients of interest (EOI)-parabens, polysorbate 80, propylene glycol, benzoates, saccharin sodium, sorbitol, ethanol and benzalkonium chloride-to hospitalised neonates in Europe and to identify risk factors for exposure....... METHODS: All medicines administered to neonates during 1 day with individual prescription and demographic data were registered in a web-based point prevalence study. Excipients were identified from the Summaries of Product Characteristics. Determinants of EOI administration (geographical region......, gestational age (GA), active pharmaceutical ingredient, unit level and hospital teaching status) were identified using multivariable logistical regression analysis. RESULTS: Overall 89 neonatal units from 21 countries participated. Altogether 2095 prescriptions for 530 products administered to 726 neonates...

  19. Protective role of plants against harmful radiation

    Gautam, Shreesh Kumar; Kumar, Pawan; Singh, Abhishek; Kumar, Vikas; Bharti, Navaldey [Department of Applied Plant Science-Horticulture, Babasaheb Bhimrao Ambedkar University, Lucknow (India)

    2012-07-01

    The rapid technological advancement has increased human exposure to ionizing radiations enormously. Ionizing radiations produces deleterious effects in the living organisms. Widespread use of radiation in diagnosis therapy, industry, energy sector and inadvertent exposure during air and space travel, nuclear accidents and nuclear terror attacks requires safeguard against human exposures. Lead shielding and other physical measures can be used in such situations but with difficulty to manage; thus pharmacological intervention could be the most prudent strategy to protect humans against the harmful effect of ionizing radiations. These pharmacological agents are radioprotectives; The development of radioprotective agents has been the subject of intense research in view of their potential for use within a radiation environment. However, no ideal, safe synthetic radio protectors are available to date, so the search for alternative sources including plants has been ongoing. In Ayurveda, the traditional Indian system of medicine, several plants have been used to treat free radical-mediated ailments and, therefore, it is logical to expect that such plants may also render some protection against radiation damage. This all is due to antioxidant enzymes, nitroxides, and melatonin, antiemetic, anti-inflammatory. haemopoitic and immunostimulant compounds. Some of the plants which are found to be radioprotective are Centella asiatica, Ginkgo biloba, Hippophae rhamnoides, Ocimum sanctum, Podophyllurn hexandrum, Tinospora cordifolia, Emblica officinalis, Phyllanthus amarus, etc. So there is an urgent need to identify and characterize the many of the plants in relation to the radioprotection. Besides these medicinal plants there are also some fruits and vegetables which are having good response against harmful radiations such as Kiwifruit Actinidia deliciosa (Actinidaceae), Cape Gooseberry Physalis peruviana (Solanaceae). They protect against the radiation-induced damage by

  20. [Harmful biological agents at museum workposts].

    Skóra, Justyna; Zduniak, Katarzyna; Gutarowska, Beata; Rembisz, Daria

    2012-01-01

    The aim of the studies was to determine the level and kind of microbiological contamination of air and surfaces in museum premises with various collection specificities. In addition, the criteria for selecting indicators of contamination with harmful biological agents at museum workposts are proposed. The analysis of microbial contamination was carried out in 14 museum premises (storehouses, restoration workshops, exhibition hall). Microbiological air purity was measured with a MAS-100 Eco Air Sampler. Surface samples were collected using contact plates RODAC Envirocheck. Biochemical API tests were used to identify bacteria and yeasts. Fungi were diagnosed with taxonomic keys, based on macro- and microscopic mycelia assessment. The levels of microbiological contamination in museums varied and ranged from 2.1 x 10(2) to 7.0 x 10(3) cfu/m3 in the air and from 1.4 x 10(2) to 1.7 x 10(4) cfu/100 cm2 on surfaces. The dominant microorganisms were fungi, which accounted respectively for 18-98% and 23-100% of all isolates from tested sites and surfaces. It was found that the amount of fungi in the indoor air of the Museum of Archeology and Ethnography and the Museum of Independence Traditions equaled respectively 4.2 x 10(2) cfu/m3 and 1.4 x 10(4) cfu/m3, which means that they exceeded the recommended reference value of 2.0 x 10(2) cfu/m3. Having analyzed the frequency of strain isolation, the source of microorganisms and the hazard to human health, 10 fungal species were isolated, which may be regarded as indicators of contamination with harmful biological agents at museum workposts. They are: Aspergillus (A. niger, A. versicolor), Cladosporium (C. herbarum, C. macrocarpum), Penicillium (P. carneum, P. digitatum, P. italicum, P. paneum, P. polonicum), Rhizopus nigricans.

  1. Geoengineering, Climate Harm, and Business as Usual

    Jankunis, F. J.; Peacock, K.

    2014-12-01

    We define geoengineering (GE) as the intentional use of technology to change the planet's climate. Many people believe GE is different in kind rather than degree from any other organized activity in human history. In fact, humans caused changes in the planet's climate long before the industrial age, and all organisms engineer their environments directly or indirectly. The relevant difference between this cumulative and generally inadvertent activity and GE is the presence of intention. Now that science has revealed the extent to which humans can change the climate, however, even the continuance of Business as Usual (BAU) is, in effect, a form of intentional GE, albeit one that will cause significant climate harm, defined as effects such as sea level rise that will impact human well-being. But as with all forms of engineering, the devil is in the details: what forms of GE should be tried first? Some methods, such as large-scale afforestation, are low risk but have long-term payoffs; others, such as aerosol injection into the stratosphere, could help buy time in a warming crisis but have unknown side-effects and little long-term future. Climate change is a world-wide, inter-generational tragedy of the commons. Rational choice theory, the spatial and temporal extension of the problem, poorly fitted moral frameworks, and political maneuvering are all factors that inhibit solutions to the climate tragedy of the commons. The longer that such factors are allowed to dominate decision-making (or the lack thereof) the more likely it is that humanity will be forced to resort to riskier and more drastic forms of GE. We argue that this fact brings an additional measure of urgency to the search for ways to engineer the climate differently so as to avoid climate harm in the most lasting and least risky way.

  2. Protective role of plants against harmful radiation

    Gautam, Shreesh Kumar; Kumar, Pawan; Singh, Abhishek; Kumar, Vikas; Bharti, Navaldey

    2012-01-01

    The rapid technological advancement has increased human exposure to ionizing radiations enormously. Ionizing radiations produces deleterious effects in the living organisms. Widespread use of radiation in diagnosis therapy, industry, energy sector and inadvertent exposure during air and space travel, nuclear accidents and nuclear terror attacks requires safeguard against human exposures. Lead shielding and other physical measures can be used in such situations but with difficulty to manage; thus pharmacological intervention could be the most prudent strategy to protect humans against the harmful effect of ionizing radiations. These pharmacological agents are radioprotectives; The development of radioprotective agents has been the subject of intense research in view of their potential for use within a radiation environment. However, no ideal, safe synthetic radio protectors are available to date, so the search for alternative sources including plants has been ongoing. In Ayurveda, the traditional Indian system of medicine, several plants have been used to treat free radical-mediated ailments and, therefore, it is logical to expect that such plants may also render some protection against radiation damage. This all is due to antioxidant enzymes, nitroxides, and melatonin, antiemetic, anti-inflammatory. haemopoitic and immunostimulant compounds. Some of the plants which are found to be radioprotective are Centella asiatica, Ginkgo biloba, Hippophae rhamnoides, Ocimum sanctum, Podophyllurn hexandrum, Tinospora cordifolia, Emblica officinalis, Phyllanthus amarus, etc. So there is an urgent need to identify and characterize the many of the plants in relation to the radioprotection. Besides these medicinal plants there are also some fruits and vegetables which are having good response against harmful radiations such as Kiwifruit Actinidia deliciosa (Actinidaceae), Cape Gooseberry Physalis peruviana (Solanaceae). They protect against the radiation-induced damage by

  3. Potentially Harmful Therapy and Multicultural Counseling: Bridging Two Disciplinary Discourses

    Wendt, Dennis C.; Gone, Joseph P.; Nagata, Donna K.

    2015-01-01

    In recent years psychologists have been increasingly concerned about potentially harmful therapy, yet this recent discourse has not addressed issues that have long been voiced by the multicultural counseling and psychotherapy movement. We aim to begin to bring these seemingly disparate discourses of harm into greater conversation with one another, in the service of placing the discipline on a firmer foothold in its considerations of potentially harmful therapy. After reviewing the two discourses and exploring reasons for their divergence, we argue that they operate according to differing assumptions pertaining to the sources, objects, and scope of harm. We then argue that these differences reveal the discipline’s need to better appreciate that harm is a social construct, that psychotherapy may be inherently ethnocentric, and that strategies for collecting evidence of harm should be integrated with a social justice agenda. PMID:26339075

  4. Self-harm in patients with schizophrenia spectrum disorders.

    Mork, Erlend; Mehlum, Lars; Barrett, Elizabeth A; Agartz, Ingrid; Harkavy-Friedman, Jill M; Lorentzen, Steinar; Melle, Ingrid; Andreassen, Ole A; Walby, Fredrik A

    2012-01-01

    This study describes the prevalence, clinical characteristics, and gender profile of self-harm in a cross-sectional sample of 388 patients with schizophrenia spectrum disorders. All patients were interviewed and assessed with respect to lifetime self-harm and relevant clinical variables. An overall of 49% of the patients reported self-harm which was associated with female gender, having had a depressive episode, younger age at psychosis onset, alcohol abuse or dependence, current suicidality, awareness of illness, and low adherence to prescribed medication. Higher awareness of having a mental disorder was associated with self-harm in men only, while emotional dysregulation was associated with self-harm in women only. We conclude that while self-harm in patients with schizophrenia spectrum disorders is highly prevalent in both genders, risk factors in men and women differ in several important ways.

  5. Predictors for repeat self-harm and suicide among older people within 12 months of a self-harm presentation.

    Cheung, Gary; Foster, Gisele; de Beer, Wayne; Gee, Susan; Hawkes, Tracey; Rimkeit, Sally; Tan, Yu Mwee; Merry, Sally; Sundram, Frederick

    2017-08-01

    A past history of self-harm is a significant risk factor for suicide in older people. The aims of this study are to (i) characterize older people who present with self-harm to emergency departments (EDs); and (ii) determine the predictors for repeat self-harm and suicide. Demographic and clinical data were retrospectively collected on older people (age 65+ years), who presented to seven EDs in New Zealand following an episode of self-harm between 1st July 2010 and 30th June 2013. In addition, 12-month follow-up information on repeat self-harm and suicide was collected. The sample included 339 older people (55.2% female) with an age range of 65-96 years (mean age = 75.0; SD = 7.6). Overdose (68.7%) was the most common method of self-harm. 76.4% of the self-harm cases were classified as suicide attempts. Perceived physical illness (47.8%) and family discord (34.5%) were the most common stressors. 12.7% of older people repeated self-harm and 2.1% died by suicide within 12 months. Older people who had a positive blood alcohol reading (OR = 3.87, 95% Cl = 1.35-11.12, p = 0.012) and were already with mental health services at the index self-harm (OR = 2.73, 95% Cl = 1.20-6.25, p = 0.047) were more likely to repeat self-harm/suicide within 12 months. Older people who self-harm are at very high risk of repeat self-harm and suicide. Screening and assessment for alcohol use disorders should be routinely performed following a self-harm presentation, along with providing structured psychological treatment as an adjunct to pharmacological treatment for depression and interventions to improve the person's resilience resources.

  6. Myocardial overexpression of TIMP3 after myocardial infarction exerts beneficial effects by promoting angiogenesis and suppressing early proteolysis.

    Takawale, Abhijit; Zhang, Pu; Azad, Abul; Wang, Wang; Wang, Xiuhua; Murray, Allan G; Kassiri, Zamaneh

    2017-08-01

    Myocardial infarction (MI) results in loss of cardiomyocytes, adverse extracellular matrix (ECM) and structural remodeling, and left ventricular (LV) dilation and dysfunction. Tissue inhibitors of metalloproteinase (TIMPs) inhibit matrix metalloproteinases (MMPs), the main regulators of ECM turnover. TIMPs also have MMP-independent functions. TIMP3 levels are reduced in the heart within 24 h of MI in mice. We investigated if overexpression of TIMP3 post-MI limits adverse remodeling and LV dilation and dysfunction. MI was induced by left anterior descending coronary artery ligation in 10- to 12-wk-old male C57BL/6J mice, and adenoviral constructs expressing human (h)TIMP3 (Ad-hTIMP3) or no TIMP (Ad-Null) were injected in the peri-infarct zone (5.4 × 10 7 plaque-forming units/heart, 5 injections/heart). Cardiac function assessed by echocardiography showed improved LV physiology and reduced LV dilation after TIMP3 overexpression compared with the Ad-Null-MI group. Post-MI adverse remodeling was attenuated in the Ad-hTIMP3-MI group, as assessed by greater cardiomyocyte density, less infarct expansion, and ECM disruption. TIMP3 overexpression blunted the early rise in proteolytic activities post-MI. A higher density of coronary arteries and a greater number of proliferating endothelial cells were detected in the infarct and peri-infarct regions in the Ad-hTIMP3-MI group compared with the Ad-Null-MI group. In vitro three-dimensional angiogenesis assay confirmed that recombinant TIMP3 promotes angiogenesis in human endothelial cells, although biphasically and in a dose-dependent manner. Intriguingly, overexpression of Ad-hTIMP3 at 10-fold higher concentration had no beneficial effects, consistent with antiangiogenic effects of TIMP3 at higher doses. In conclusion, optimal overexpression of TIMP3 can be a promising therapeutic approach to limit adverse post-MI remodeling by dually inhibiting early proteolysis and promoting angiogenesis. NEW & NOTEWORTHY Here, we report

  7. Impulsivity and self-harm in adolescence: a systematic review.

    Lockwood, Joanna; Daley, David; Townsend, Ellen; Sayal, Kapil

    2017-04-01

    Research supports an association between impulsivity and self-harm, yet inconsistencies in methodology across studies have complicated understanding of this relationship. This systematic review examines the association between impulsivity and self-harm in community-based adolescents aged 11-25 years and aims to integrate findings according to differing concepts and methods. Electronic searches of EMBASE, MEDLINE, PsychINFO, CINAHL, PubMed and The Cochrane Library, and manual searches of reference lists of relevant reviews identified 4496 articles published up to July 2015, of which 28 met inclusion criteria. Twenty-four of the studies reported an association between broadly specified impulsivity and self-harm. However, findings varied according to the conception and measurement of impulsivity and the precision with which self-harm behaviours were specified. Specifically, lifetime non-suicidal self-injury was most consistently associated with mood-based impulsivity-related traits. However, cognitive facets of impulsivity (relating to difficulties maintaining focus or acting without forethought) differentiated current self-harm from past self-harm. These facets also distinguished those with thoughts of self-harm (ideation) from those who acted on thoughts (enaction). The findings suggested that mood-based impulsivity is related to the initiation of self-harm, while cognitive facets of impulsivity are associated with the maintenance of self-harm. In addition, behavioural impulsivity is most relevant to self-harm under conditions of negative affect. Collectively, the findings indicate that distinct impulsivity facets confer unique risks across the life-course of self-harm. From a clinical perspective, the review suggests that interventions focusing on reducing rash reactivity to emotions or improving self-regulation and decision making may offer most benefit in supporting those who self-harm.

  8. Intrapersonal factors of adolescents self-harming behaviour

    Volodko, Liubov

    2014-01-01

    Researches often differentiate two groups of self-harming adolescents: those who attempters a suicide, and those who are harming themselves in a non-suicidal way, and they don‘t seek the death. However just a few community-based research, which would directly compare these groups, were done so far, and therefore information about the differences of the psychological peculiarity and self-harming behavior‘s internal factors between the groups is ambivalent. Lifestyle and Coping Skills Questionn...

  9. Repetition of self-harm and suicide following self-harm in children and adolescents: findings from the Multicentre Study of Self-harm in England.

    Hawton, Keith; Bergen, Helen; Kapur, Navneet; Cooper, Jayne; Steeg, Sarah; Ness, Jennifer; Waters, Keith

    2012-12-01

    Self-harm (intentional self-poisoning and self-injury) in children and adolescents is often repeated and is associated with increased risk of future suicide. We have investigated factors associated with these outcomes. We used data collected in the Multicentre Study of Self-harm in England on all self-harm hospital presentations by individuals aged 10-18 years between 2000 and 2007, and national death information on these individuals to the end of 2010. Cox hazard proportional models were used to identify independent and multivariable predictors of repetition of self-harm and of suicide. Repetition of self-harm occurred in 27.3% of individuals (N = 3920) who presented between 2000 and 2005 and were followed up until 2007. Multivariate analysis showed that repetition was associated with age, self-cutting, and previous self-harm and psychiatric treatment. Of 51 deaths in individuals who presented between 2000 and 2007 and were followed up to 2010 (N = 5133) half (49.0%) were suicides. The method used was usually different to that used for self-harm. Multivariate analysis showed that suicide was associated with male gender [Hazard ratio (HR) = 2.4, 95% CI 1.2-4.8], self-cutting (HR = 2.1, 95% CI 1.1-3.7) and prior psychiatric treatment at initial presentation (HR = 4.2, 95% CI 1.7-10.5). It was also associated with self-cutting and history of psychiatric treatment at the last episode before death, and history of previous self harm. Self-cutting as a method of self-harm in children and adolescents conveys greater risk of suicide (and repetition) than self-poisoning although different methods are usually used for suicide. The findings underline the need for psychosocial assessment in all cases. © 2012 The Authors. Journal of Child Psychology and Psychiatry © 2012 Association for Child and Adolescent Mental Health.

  10. Self-harm and ethnicity: A systematic review.

    Al-Sharifi, Ali; Krynicki, Carl R; Upthegrove, Rachel

    2015-09-01

    This review will focus on the rates, clinical characteristics, risk factors and methods of self-harm and suicide in different ethnic groups in the United Kingdom, providing an update synthesis of recent literature. Studies that met the inclusion criteria between 2003 and 2013 were reviewed using the following databases: MEDLINE, PsycINFO, EMBASE and CINAHL. The methodological quality of each study was then assessed using a structured scoring system. A total of 2,362 articles were retrieved, 10 of which matched the inclusion criteria were reviewed. Significant differences were found in the rates of self-harm between ethnic groups with Asian males being least likely to self-harm and Black females being most likely to self-harm. Also, Black and South Asian people were less likely to repeat self-harm. Factors that may help protect or predispose individuals to self-harm or attempt suicide (such as religion, mental health and coping styles) also differ between ethnic groups. There are clear ethnic differences in self-harm and suicide, which may be affected by factors such as cultural pressures and prevalence of mental illness. An awareness of these differences is vital to help prevent further attempts of self-harm and suicide. Further research into differences between ethnic and cultural groups and self-harm continues to be important. © The Author(s) 2015.

  11. Caring for self-harming patients in general practice.

    Rowe, Joanne; Jaye, Chrystal

    2017-12-01

    INTRODUCTION Intentional self-harm is an international public health issue with high personal, social and financial costs to society. Poor relationship dynamics are known to have a negative influence on the psyche of people who self-harm, and this can increase anxiety and decrease self-esteem, both shown to be significant contributors to self-harm behaviours. Positive and functional social supports have been proposed as a cost-effective and constructive approach in diminishing self-harming behaviours. AIM This qualitative study investigated the aspects of professional, social, familial and romantic relationships that people who have self-harmed identified as having a positive and constructive effect on their self-harm behaviour. METHODS Twelve participants with a history of self-harming behaviours were recruited through free press advertising in primary care and interviewed. The participants ranged in age from 19 to 70 years, and represented New Zealand (NZ) European and Māori from across the Southern region of NZ. RESULTS This study shows that constructive relationships that inhibit self-harm behaviours are characterised by participants' perceptions of authenticity in their relationships, and knowing that other people genuinely care. Feeling cared for within an authentic therapeutic relationship enabled participants to overcome their perception of being damaged selves and gave them the skills and confidence to develop functional relationships within their communities. A relationship-centred care approach may be useful for general practitioners seeking to develop more effective therapeutic relationships with patients who deliberately self-harm.

  12. [Influence of delta-sleep inducing peptide on the state of lysosomal membranes and intensity of lysosomal proteolysis in different rat tissues during physiological aging of the organism].

    Kutilin, D S; Bondarenko, T I; Mikhaleva, I I

    2014-01-01

    It is shown that subcutaneous injection of exogenous delta-sleep inducing peptide (DSIP) to rats aged 2-24 months in a dose of 100 μg/kg animal body weight by courses of 5 consecutive days per month has a stabilizing effect on the state of lysosomal membranes in rat tissues (brain, heart muscle and liver) at different ontogenetic stages, and this effect is accompanied by increasing intensity of lysosomal proteolysis in these tissues.

  13. Effect of protein degradation on spot Mr distribution in 2-D gels – a case study of proteolysis during development of Streptomyces coelicolor cultures

    Vohradský, Jiří; Branny, Pavel; Li, X.-M.; Thompson, CH. J.

    2008-01-01

    Roč. 8, č. 12 (2008), s. 2371-2375 ISSN 1615-9853 R&D Projects: GA ČR GA310/07/1009 Grant - others:AT(AT) EC Integrated Project ActinoGEN, LSHM-CT-2004-005224 Institutional research plan: CEZ:AV0Z50200510 Keywords : 2-de * proteolysis * streptomyces Subject RIV: EE - Microbiology, Virology Impact factor: 4.586, year: 2008

  14. Activated thrombin-activatable fibrinolysis inhibitor (TAFIa) attenuates breast cancer cell metastatic behaviors through inhibition of plasminogen activation and extracellular proteolysis

    Bazzi, Zainab A.; Lanoue, Danielle; El-Youssef, Mouhanned; Romagnuolo, Rocco; Tubman, Janice; Cavallo-Medved, Dora; Porter, Lisa A.; Boffa, Michael B.

    2016-01-01

    Thrombin activatable fibrinolysis inhibitor (TAFI) is a plasma zymogen, which can be converted to activated TAFI (TAFIa) through proteolytic cleavage by thrombin, plasmin, and most effectively thrombin in complex with the endothelial cofactor thrombomodulin (TM). TAFIa is a carboxypeptidase that cleaves carboxyl terminal lysine and arginine residues from protein and peptide substrates, including plasminogen-binding sites on cell surface receptors. Carboxyl terminal lysine residues play a pivotal role in enhancing cell surface plasminogen activation to plasmin. Plasmin has many critical functions including cleaving components of the extracellular matrix (ECM), which enhances invasion and migration of cancer cells. We therefore hypothesized that TAFIa could act to attenuate metastasis. To assess the role of TAFIa in breast cancer metastasis, in vitro migration and invasion assays, live cell proteolysis and cell proliferation using MDA-MB-231 and SUM149 cells were carried out in the presence of a TAFIa inhibitor, recombinant TAFI variants, or soluble TM. Inhibition of TAFIa with potato tuber carboxypeptidase inhibitor increased cell invasion, migration and proteolysis of both cell lines, whereas addition of TM resulted in a decrease in all these parameters. A stable variant of TAFIa, TAFIa-CIIYQ, showed enhanced inhibitory effects on cell invasion, migration and proteolysis. Furthermore, pericellular plasminogen activation was significantly decreased on the surface of MDA-MB-231 and SUM149 cells following treatment with various concentrations of TAFIa. Taken together, these results indicate a vital role for TAFIa in regulating pericellular plasminogen activation and ultimately ECM proteolysis in the breast cancer microenvironment. Enhancement of TAFI activation in this microenvironment may be a therapeutic strategy to inhibit invasion and prevent metastasis of breast cancer cells

  15. Continuous fast Fourier transforms cyclic voltammetry as a new approach for investigation of skim milk k-casein proteolysis, a comparative study.

    Shayeh, Javad Shabani; Sefidbakht, Yahya; Siadat, Seyed Omid Ranaei; Niknam, Kaveh

    2017-10-01

    Cheese production is relied upon the action of Rennet on the casein micelles of milk. Chymosin assay methods are usually time consuming and offline. Herein, we report a new electrochemical technique for studying the proteolysis of K-casein. The interaction of rennet and its substrate was studied by fast Fourier transform continuous cyclic voltammetry (FFTCCV) based on a determination of k-casein in aqueous solution. FFTCCV technique is a very useful method for studying the enzymatic procedures. Fast response, no need of modified electrodes or complex equipment is some of FFTCCV advantages. Various concentrations of enzyme and substrate were selected and the increase in the appearance of charged species in solution as a result of the addition of rennet was studied. Data obtained using FFTCCV technique were also confirmed by turbidity analysis. The results show that rennet proteolysis activity occurs in much shorter time scales compare with its aggregation. Hence, following the appearance of charged segments as a result of proteolysis could be under consideration as a rapid and online method. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Effect of Aloe vera (Aloe barbadensis Miller) on survivability, extent of proteolysis and ACE inhibition of potential probiotic cultures in fermented milk.

    Basannavar, Santosh; Pothuraju, Ramesh; Sharma, Raj Kumar

    2014-10-01

    In the present investigation, the effect of Aloe vera gel powder on angiotensin-converting enzyme (ACE) inhibitory activity, extent of proteolysis during fermentation and survival of Lactobacillus casei NCDC19 during storage of fermented milk was studied. Among the different cultures screened for ACE inhibitory activity, Lactobacillus casei NCDC 19 exhibited the highest ACE inhibition (approx. 40%) as well as extent of proteolysis (0.37, Abs₃₄₀). In the presence of Aloe vera (0.5% and 1% w/v) an increase in extent of proteolysis (0.460 ± 0.047 and 0.480 ± 0.027) and percent ACE inhibitory activity (44.32 ± 2.83 and 47.52 ± 1.83) was observed in comparison to control. Aloe vera powder addition also led to an increase in viable counts (>11 log cfu mL⁻¹) of L. casei NCDC 19 in fermented milk during storage for 7 days and the counts were maintained in sufficiently higher numbers. The study suggests Aloe vera to be a good functional ingredient which can be further explored for different health attributes. © 2014 Society of Chemical Industry.

  17. Do Austerity Measures Harm International Trade?

    Dorin Iulian CHIRIŢOIU

    2015-06-01

    Full Text Available This paper focuses on the trade relations between Romania and the PIIGS (Portugal, Italy, Ireland, Greece, and Spain in order to verify whether the exports of Romania have been positively or negatively affected by the austerity measures adopted by these Eurozone periphery countries, thus diminishing Romania’s export performance in such markets. Hence, our main research question is whether austerity measures harm or affect in any way the inflows and outflows of international trade in the studied countries. To assess this hypothesis, we focused on the external trade relations, and their linkages with the macroeconomic environment, rather than the competitiveness of a state explained by a detailed sectoral analysis. In this respect, we use comparative and descriptive statistics in order to observe the consequences of the internal devaluation, and implicitly austerity measures, on the PIIGS-Romanian trade relations. Our findings suggest that the effects of austerity measures are not homogenous because they depend on the scale of trade exchanges and on the way in which the austerity measures were applied.

  18. Evaluation of Harmful Algal Bloom Outreach Activities

    Richard Weisman

    2007-12-01

    Full Text Available With an apparent increase of harmful algal blooms (HABs worldwide,healthcare providers, public health personnel and coastal managers are struggling toprovide scientifically-based appropriately-targeted HAB outreach and education. Since1998, the Florida Poison Information Center-Miami, with its 24 hour/365 day/year freeAquatic Toxins Hotline (1-888-232-8635 available in several languages, has received over 25,000 HAB-related calls. As part of HAB surveillance, all possible cases of HAB-relatedillness among callers are reported to the Florida Health Department. This pilot studyevaluated an automated call processing menu system that allows callers to access bilingualHAB information, and to speak directly with a trained Poison Information Specialist. Themajority (68% of callers reported satisfaction with the information, and many provided specific suggestions for improvement. This pilot study, the first known evaluation of use and satisfaction with HAB educational outreach materials, demonstrated that the automated system provided useful HAB-related information for the majority of callers, and decreased the routine informational call workload for the Poison Information Specialists, allowing them to focus on callers needing immediate assistance and their healthcare providers. These results will lead to improvement of this valuable HAB outreach, education and surveillance tool. Formal evaluation is recommended for future HAB outreach and educational materials.

  19. Energy drinks and adolescents: what's the harm?

    Harris, Jennifer L; Munsell, Christina R

    2015-04-01

    Concerns about potential dangers from energy drink consumption by youth have been raised by health experts, whereas energy drink manufacturers claim these products are safe and suitable for marketing to teens. This review summarizes the evidence used to support both sides of the debate. Unlike most beverage categories, sales of energy drinks and other highly caffeinated products continue to grow, and marketing is often targeted to youth under the age of 18 years. These products pose a risk of caffeine toxicity when consumed by some young people, and there is evidence of other troubling physiological and behavioral effects associated with their consumption by youth. The US Food and Drug Administration has indicated it will reexamine the safety of caffeine in the food supply; however, more research is needed to better understand youth consumption of energy drinks and caffeine in general, as well as the long-term effects on health. Meanwhile, policymakers and physician groups have called on energy drink manufacturers to take voluntary action to reduce the potential harm of their products, including placing restrictions on marketing to youth under the age of 18 years. Additional regulatory and legislative options are also being discussed. © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  20. Calcium supplementation in osteoporosis: useful or harmful?

    Chiodini, Iacopo; Bolland, Mark J

    2018-04-01

    Osteoporosis and fragility fractures are important social and economic problems worldwide and are due to both the loss of bone mineral density and sarcopenia. Indeed, fragility fractures are associated with increased disability, morbidity and mortality. It is known that a normal calcium balance together with a normal vitamin D status is important for maintaining well-balanced bone metabolism, and for many years, calcium and vitamin D have been considered crucial in the prevention and treatment of osteoporosis. However, recently, the usefulness of calcium supplementation (alone or with concomitant vitamin D) has been questioned, since some studies reported only weak efficacy of these supplementations in reducing fragility fracture risk. On the other hand, besides the gastrointestinal side effects of calcium supplements and the risk of kidney stones related to use of co-administered calcium and vitamin D supplements, other recent data suggested potential adverse cardiovascular effects from calcium supplementation. This debate article is focused on the evidence regarding both the possible usefulness for bone health and the potential harmful effects of calcium and/or calcium with vitamin D supplementation. © 2018 European Society of Endocrinology.

  1. Satellite monitoring of cyanobacterial harmful algal bloom ...

    Cyanobacterial harmful algal blooms (cyanoHABs) cause extensive problems in lakes worldwide, including human and ecological health risks, anoxia and fish kills, and taste and odor problems. CyanoHABs are a particular concern because of their dense biomass and the risk of exposure to toxins in both recreational waters and drinking source waters. Successful cyanoHAB assessment by satellites may provide a first-line of defense indicator for human and ecological health protection. In this study, assessment methods were developed to determine the utility of satellite technology for detecting cyanoHAB occurrence frequency at locations of potential management interest. The European Space Agency's MEdium Resolution Imaging Spectrometer (MERIS) was evaluated to prepare for the equivalent Sentinel-3 Ocean and Land Colour Imager (OLCI) launched in 2016. Based on the 2012 National Lakes Assessment site evaluation guidelines and National Hydrography Dataset, there were 275,897 lakes and reservoirs greater than 1 hectare in the 48 U.S. states. Results from this evaluation show that 5.6 % of waterbodies were resolvable by satellites with 300 m single pixel resolution and 0.7 % of waterbodies were resolvable when a 3x3 pixel array was applied based on minimum Euclidian distance from shore. Satellite data was also spatially joined to US public water surface intake (PWSI) locations, where single pixel resolution resolved 57% of PWSI and a 3x3 pixel array resolved 33% of

  2. Regulated proteolysis of Trop2 drives epithelial hyperplasia and stem cell self-renewal via β-catenin signaling.

    Stoyanova, Tanya; Goldstein, Andrew S; Cai, Houjian; Drake, Justin M; Huang, Jiaoti; Witte, Owen N

    2012-10-15

    The cell surface protein Trop2 is expressed on immature stem/progenitor-like cells and is overexpressed in many epithelial cancers. However the biological function of Trop2 in tissue maintenance and tumorigenesis remains unclear. In this study, we demonstrate that Trop2 is a regulator of self-renewal, proliferation, and transformation. Trop2 controls these processes through a mechanism of regulated intramembrane proteolysis that leads to cleavage of Trop2, creating two products: the extracellular domain and the intracellular domain. The intracellular domain of Trop2 is released from the membrane and accumulates in the nucleus. Heightened expression of the Trop2 intracellular domain promotes stem/progenitor self-renewal through signaling via β-catenin and is sufficient to initiate precursor lesions to prostate cancer in vivo. Importantly, we demonstrate that loss of β-catenin or Trop2 loss-of-function cleavage mutants abrogates Trop2-driven self-renewal and hyperplasia in the prostate. These findings suggest that heightened expression of Trop2 is selected for in epithelial cancers to enhance the stem-like properties of self-renewal and proliferation. Defining the mechanism of Trop2 function in self-renewal and transformation is essential to identify new therapeutic strategies to block Trop2 activation in cancer.

  3. Bacillus licheniformis BlaR1 L3 Loop Is a Zinc Metalloprotease Activated by Self-Proteolysis

    Sépulchre, Jérémy; Amoroso, Ana; Joris, Bernard

    2012-01-01

    In Bacillus licheniformis 749/I, BlaP β-lactamase is induced by the presence of a β-lactam antibiotic outside the cell. The first step in the induction mechanism is the detection of the antibiotic by the membrane-bound penicillin receptor BlaR1 that is composed of two functional domains: a carboxy-terminal domain exposed outside the cell, which acts as a penicillin sensor, and an amino-terminal domain anchored to the cytoplasmic membrane, which works as a transducer-transmitter. The acylation of BlaR1 sensor domain by the antibiotic generates an intramolecular signal that leads to the activation of the L3 cytoplasmic loop of the transmitter by a single-point cleavage. The exact mechanism of L3 activation and the nature of the secondary cytoplasmic signal launched by the activated transmitter remain unknown. However, these two events seem to be linked to the presence of a HEXXH zinc binding motif of neutral zinc metallopeptidases. By different experimental approaches, we demonstrated that the L3 loop binds zinc ion, belongs to Gluzincin metallopeptidase superfamily and is activated by self-proteolysis. PMID:22623956

  4. Therapeutic effects of remediating autophagy failure in a mouse model of Alzheimer disease by enhancing lysosomal proteolysis.

    Yang, Dun-Sheng; Stavrides, Philip; Mohan, Panaiyur S; Kaushik, Susmita; Kumar, Asok; Ohno, Masuo; Schmidt, Stephen D; Wesson, Daniel W; Bandyopadhyay, Urmi; Jiang, Ying; Pawlik, Monika; Peterhoff, Corrinne M; Yang, Austin J; Wilson, Donald A; St George-Hyslop, Peter; Westaway, David; Mathews, Paul M; Levy, Efrat; Cuervo, Ana M; Nixon, Ralph A

    2011-07-01

    The extensive autophagic-lysosomal pathology in Alzheimer disease (AD) brain has revealed a major defect: in the proteolytic clearance of autophagy substrates. Autophagy failure contributes on several levels to AD pathogenesis and has become an important therapeutic target for AD and other neurodegenerative diseases. We recently observed broad therapeutic effects of stimulating autophagic-lysosomal proteolysis in the TgCRND8 mouse model of AD that exhibits defective proteolytic clearance of autophagic substrates, robust intralysosomal amyloid-β peptide (Aβ) accumulation, extracellular β-amyloid deposition and cognitive deficits. By genetically deleting the lysosomal cysteine protease inhibitor, cystatin B (CstB), to selectively restore depressed cathepsin activities, we substantially cleared Aβ, ubiquitinated proteins and other autophagic substrates from autolysosomes/lysosomes and rescued autophagic-lysosomal pathology, as well as reduced total Aβ40/42 levels and extracellular amyloid deposition, highlighting the underappreciated importance of the lysosomal system for Aβ clearance. Most importantly, lysosomal remediation prevented the marked learning and memory deficits in TgCRND8 mice. Our findings underscore the pathogenic significance of autophagic-lysosomal dysfunction in AD and demonstrate the value of reversing this dysfunction as an innovative therapeautic strategy for AD.

  5. The cellular response to vascular endothelial growth factors requires co-ordinated signal transduction, trafficking and proteolysis.

    Smith, Gina A; Fearnley, Gareth W; Tomlinson, Darren C; Harrison, Michael A; Ponnambalam, Sreenivasan

    2015-08-18

    VEGFs (vascular endothelial growth factors) are a family of conserved disulfide-linked soluble secretory glycoproteins found in higher eukaryotes. VEGFs mediate a wide range of responses in different tissues including metabolic homoeostasis, cell proliferation, migration and tubulogenesis. Such responses are initiated by VEGF binding to soluble and membrane-bound VEGFRs (VEGF receptor tyrosine kinases) and co-receptors. VEGF and receptor splice isoform diversity further enhances complexity of membrane protein assembly and function in signal transduction pathways that control multiple cellular responses. Different signal transduction pathways are simultaneously activated by VEGFR-VEGF complexes with membrane trafficking along the endosome-lysosome network further modulating signal output from multiple enzymatic events associated with such pathways. Balancing VEGFR-VEGF signal transduction with trafficking and proteolysis is essential in controlling the intensity and duration of different intracellular signalling events. Dysfunction in VEGF-regulated signal transduction is important in chronic disease states including cancer, atherosclerosis and blindness. This family of growth factors and receptors is an important model system for understanding human disease pathology and developing new therapeutics for treating such ailments. © 2015 Authors.

  6. Defining and redefining harm reduction in the Lao context

    Sychareun Vanphanom

    2012-07-01

    Full Text Available Abstract The response to drug use in Laos has focused on reducing opium supply (supply reduction and rates of drug use (demand reduction. However, recently there is increased interest among government counterparts to discuss and develop broader responses to injecting drug use (IDU including the introduction of harm reduction programs. The concept of harm reduction has just been introduced to Lao PDR and as yet there is no agreement on a definition of the concept. We highlight here a range of issues that remain controversial in Lao PDR in the HIV, drug use and harm reduction discourse, the definition of 'harm reduction' and related terms; and the scope of harm reduction. This was a qualitative study, consisting of in-depth interviews with 27 law enforcement and 8 health officers who work in the fields of HIV and/or drug control about their understanding of HIV related to drug use, and concepts of harm reduction. Content analysis was performed to identify the coding, categories and themes. We found that law enforcement officers in particular had limited understanding about harm reduction and the feasibility and appropriateness of harm reduction services in the Lao context. Harm reduction should be a core element of a public health response to HIV where drug use and IDU exists. Recommendations include the necessity of increasing the awareness of harm reduction among law enforcement officers and providing appropriate evidence to support the needs of harm reduction policy and programs. HIV prevention and treatment strategies should be integrated within existing social and cultural frameworks, working with the task force for HIV/IDU and other government counterparts.

  7. The role of interpersonal harm in distinguishing regret from guilt.

    Zeelenberg, Marcel; Breugelmans, Seger M

    2008-10-01

    Regret and guilt are emotions that are produced by negative outcomes for which one is responsible. Both emotions have received ample attention in the psychological literature; however, it is still unclear to what extent regret and guilt represent distinct psychological processes. We examined the extent to which the distinction between interpersonal harm (negative outcomes for others) and intrapersonal harm (negative outcomes for self) is crucial in differentiating these two emotions. In a series of 3 studies we found that guilt is predominantly felt in situations of interpersonal harm, whereas regret is felt in both situations of interpersonal harm and intrapersonal harm. Moreover, the results show that in situations of interpersonal harm the phenomenology of regret shares many, but not all features with the phenomenology of guilt. We conclude that the emotion processes resulting from interpersonal and intrapersonal harm are clearly distinct, but that regret as an emotion label is applied to both types of processes whereas the emotion label guilt is primarily used to refer to experiences of interpersonal harm. Implications for emotion research are discussed. (c) 2008 APA, all rights reserved

  8. Managing Sexually Harmful Behaviour in a Residential Special School

    Pritchard, Duncan; Graham, Nicola; Ikin, Annette; Penney, Heather; Kovacs, Lisa; Mercer, Dawn; Edwards, Richard; Jones, Dylan; Mace, Floyd Charles

    2012-01-01

    Children and young people with learning disabilities who present sexually harmful behaviour are marginalised and do not always participate in community activities. This case study describes a multi-component intervention that successfully reduced the sexually harmful behaviour of a 16-year-old boy with a mild learning disability. The intervention…

  9. Harmful algal blooms of the Southern Benguela current: A review ...

    Harmful algal blooms of the Southern Benguela current: A review and appraisal of monitoring from 1989 to 1997. ... The Benguela upwelling system is subjected to blooms of harmful and toxic algae, the incidence and consequences of which are documented here. Red tides are common and usually attributed to members of ...

  10. Monitoring of harmful algal blooms along the Norwegian coast using ...

    A Norwegian monitoring system for harmful algal blooms, consisting of an Observer Network, the State Food Hygiene Control Agency, the Oceanographic Company of Norway, the Institute of Marine Research and the Directorate for Fisheries, is reviewed. Potentially harmful algae on the Norwegian coast are found primarily ...

  11. Self-Harm and Conventional Gender Roles in Women

    Straiton, Melanie L.; Hjelmeland, Heidi; Grimholt, Tine K.; Dieserud, Gudrun

    2013-01-01

    A total of thirty-two women admitted to a general hospital for medical treatment after self-harming completed measures of conventional positive and negative masculinity and femininity. Comparisons were made with two control groups with no self-harm history; 33 women receiving psychiatric outpatient treatment and a nonclinical sample of 206 women.…

  12. 47 CFR 76.1203 - Incidence of harm.

    2010-10-01

    ... 47 Telecommunication 4 2010-10-01 2010-10-01 false Incidence of harm. 76.1203 Section 76.1203 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Competitive Availability of Navigation Devices § 76.1203 Incidence of harm. A...

  13. Nurses’ attitudes towards self-harm: a literature review

    P. Karman; prof Berno van Meijel; I.E. Poslawsky; Nienke Kool

    2014-01-01

    Self-harm is a growing health problem. Nurses in a variety of healthcare settings play a central role in the care of people who self-harm. Their professional attitudes towards these people are essential for high-quality care. This review aims to develop insight into nurses’ attitudes towards

  14. Nurses' attitudes towards self-harm: a literature review

    Karman, P.; Kool, N.; Poslawsky, I.E.; van Meijel, B.

    2015-01-01

    Accessible summary: People who self-harm experience many problems and needs related to management of emotional and practical stress. A positive attitude among nurses is especially important given the close contact they have with people who self-harm. This article is based on a review of the

  15. What's the Harm? The Coverage of Ethics and Harm Avoidance in Research Methods Textbooks

    Dixon, Shane; Quirke, Linda

    2018-01-01

    Methods textbooks play a role in socializing a new generation of researchers about ethical research. How do undergraduate social research methods textbooks portray harm, its prevalence, and ways to mitigate harm to participants? We conducted a content analysis of ethics chapters in the 18 highest-selling undergraduate textbooks used in sociology…

  16. 76 FR 5387 - Guidance for Industry and Food and Drug Administration Staff; “`Harmful and Potentially Harmful...

    2011-01-31

    ... of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville... harmful constituents, including smoke constituents, to health in each tobacco product by brand and by quantity in each brand and subbrand.'' The guidance discusses the meaning of the term ``harmful and...

  17. [Harm reduction strategy in tobacco control].

    Gorini, Giuseppe

    2011-01-01

    .Thus, California Department of Health Services prohibits promotion of snus and medicinal nicotine as a harm reduction strategy. However, the US Federal Family Smoking Prevention and Tobacco Control Act, signed by President Obama in 2009, places tobacco products under FDA jurisdiction: FDA must define criteria for lowering carcinogens and toxicants in tobacco products, making more available medicinal nicotine, evaluating PREPs, creating a federal Tobacco Control Agency.Which approaches is Italy going to follow?

  18. Harmed patients gaining voice: challenging dominant perspectives in the construction of medical harm and patient safety reforms.

    Ocloo, Josephine Enyonam

    2010-08-01

    Patient safety is a central issue in healthcare. In the United Kingdom, where there is more accurate information on National Health Service (NHS) hospitals than on primary care or the private sector, the evidence on adverse incidents shows that avoidable medical harm is a major concern. This paper looks at the occurrence of medical harm and argues that in the construction of patient safety reforms, it is important to be aware of alternative narratives about issues of power and accountability from harmed patients and self-help groups, that challenge dominant perspectives on the issues. The paper draws upon evidence from two sources. First, the paper draws on experiences of self-help groups set up as a result of medical harm and part of a campaigning network, where evidence was gathered from 14 groups over more than 2 years. In addition, data were obtained from 21 individuals affected by harm that attended a residential workshop called the Break Through Programme; 18 questionnaires were completed from participants and a written narrative account of their experiences and observational data were gathered from a range of workshop sessions. Looking at the issues from harmed patients' perspectives, the research illustrates that a model of medical harm focussing predominantly upon the clinical markers and individual agency associated with a medical model operates to obscure a range of social processes. These social processes, connected to the power and dominance of the medical profession and the activities of a wider state, are seen to be a major part of the construction of harm that impacts upon patients, which is further compounded by its concealment. Understanding the experiences of harmed patients is therefore seen as an important way of generating knowledge about the medical and social processes involved in harm, that can lead to a broader framework for addressing patient safety. Copyright 2010 Elsevier Ltd. All rights reserved.

  19. Lipolysis and proteolysis profiles of fresh artisanal goat cheese made with raw milk with 3 different fat contents.

    Sánchez-Macías, D; Morales-Delanuez, A; Moreno-Indias, I; Hernández-Castellano, L E; Mendoza-Grimón, V; Castro, N; Argüello, A

    2011-12-01

    The objective of this study was to describe the proteolysis and lipolysis profiles in goat cheese made in the Canary Islands (Spain) using raw milk with 3 different fat contents (0.5, 1.5, and 5%) and ripened for 1, 7, 14, and 28 d. β-Casein was the most abundant protein in all cheeses and at all ripening times. Quantitative analysis showed a general decrease in caseins as ripening progressed, and degradation rates were higher for α(S1)-casein than for β-casein and α(S2)-casein. Furthermore, the degradation rate during the experimental time decreased with lower fat contents. The α(S2)-casein and α(S1)-casein levels that remained in full-fat and reduced-fat cheeses were less than those in low-fat cheese. In contrast, β-casein also showed degradation along with ripening, but differences in degradation among the 3 cheese types were not significant at 28 d. The degradation products increased with the ripening time in all cheeses, but they were higher in full-fat cheese than in reduced-fat and low-fat cheeses. The free fatty acid concentration per 100g of cheese was higher in full-fat cheese than in reduced- and low-fat cheese; however, when the results were expressed as milligrams of free fatty acids per gram of fat in cheese, then lipolysis occurred more rapidly in low-fat cheese than in reduced- and full-fat cheeses. These results may explain the atypical texture and off-flavors found in low-fat goat cheeses, likely the main causes of non-acceptance. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  20. Overview of harm reduction in prisons in seven European countries.

    Sander, Gen; Scandurra, Alessio; Kamenska, Anhelita; MacNamara, Catherine; Kalpaki, Christina; Bessa, Cristina Fernandez; Laso, Gemma Nicolás; Parisi, Grazia; Varley, Lorraine; Wolny, Marcin; Moudatsou, Maria; Pontes, Nuno Henrique; Mannix-McNamara, Patricia; Libianchi, Sandro; Antypas, Tzanetos

    2016-10-07

    While the last decade has seen a growth of support for harm reduction around the world, the availability and accessibility of quality harm reduction services in prison settings is uneven and continues to be inadequate compared to the progress achieved in the broader community. This article provides a brief overview of harm reduction in prisons in Catalonia (Spain), Greece, Ireland, Italy, Latvia, Poland, and Portugal. While each country provides a wide range of harm reduction services in the broader community, the majority fail to provide these same services or the same quality of these services, in prison settings, in clear violation of international human rights law and minimum standards on the treatment of prisoners. Where harm reduction services have been available and easily accessible in prison settings for some time, better health outcomes have been observed, including significantly reduced rates of HIV and HCV incidence. While the provision of harm reduction in each of these countries' prisons varies considerably, certain key themes and lessons can be distilled, including around features of an enabling environment for harm reduction, resource allocation, collection of disaggregated data, and accessibility of services.

  1. Psychological characteristics of self-harming behavior in Korean adolescents.

    Lee, Woo Kyeong

    2016-10-01

    Recently, self-injury is drawing the attention of researchers and clinicians. The purpose of this study was to investigate the prevalence and psychological characteristics of adolescents who engage in self-harm and to examine the risk factors for engaging in this harmful behavior among Korean mid-adolescents. Participants were 784 adolescents aged 13-15 years. They completed self-report questionnaires that assessed (1) Non-Suicidal Self-Injury: the Self-Harm Questionnaire, Toronto Alexithymia Scale; (2) depression: Children's Depression Inventory; (3) adolescent-parent relationship: Parental Bonding Instrument; (4) peer attachment: Inventory of Parent and Peer Attachment; and (5) academic stress. Overall, 12.4% (n=97) of participants reported engaging in self-destructive behavior at least once in their lives. The primary reason for engaging in self-harm was to regulate negative emotions such as anger and sadness. As expected, the self-harm group showed statistically significant higher levels of academic stress, alexithymia, depression, and poor relationships with their parents and peers. Stepwise multiple regression analysis showed that alexithymia, depression, and peer relations were significant predictors of self-harming behavior. Given that the primary reason for engaging in self-harm is to cope with negative emotions, mental health professionals in school settings should regularly evaluate self-injurious behavior and provide prevention programs for adolescents at risk. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Subsidies which are harmful to the environment, a complex reality

    Pourquier, Francois-Xavier; Monnoyer-Smith, Laurence; Demeulenaere, Laurence

    2017-12-01

    As the reduction of public supports which are harmful to the environment is a major stake in terms of struggle against pollutions and greenhouse gases, this publication proposes a discussion of these subsidies which are still important in France despite recent improvements, notably regarding wastes and fuels. The author first discusses how these harmful subsidies are defined by international or research bodies. He outlines that some subsidies have been suppressed since 2013, that important reforms have been initiated, and that, however, the level of harmful subsidies remains high. Then, he discusses the necessary reconciliation of different objectives, and briefly evokes the German and Italian assessment examples

  3. Learning-Based Detection of Harmful Data in Mobile Devices

    Seok-Woo Jang

    2016-01-01

    Full Text Available The Internet has supported diverse types of multimedia content flowing freely on smart phones and tablet PCs based on its easy accessibility. However, multimedia content that can be emotionally harmful for children is also easily spread, causing many social problems. This paper proposes a method to assess the harmfulness of input images automatically based on an artificial neural network. The proposed method first detects human face areas based on the MCT features from the input images. Next, based on color characteristics, this study identifies human skin color areas along with the candidate areas of nipples, one of the human body parts representing harmfulness. Finally, the method removes nonnipple areas among the detected candidate areas using the artificial neural network. The experimental results show that the suggested neural network learning-based method can determine the harmfulness of various types of images more effectively by detecting nipple regions from input images robustly.

  4. Research on the Ordered Mesoporous Silica for Tobacco Harm Reduction

    Wang, Y.; Y Li, Z.; Ding, J. X.; Hu, Z. J.; Liu, Z.; Zhou, G.; Huang, T. H.

    2017-12-01

    For reducting tobacco harm, this paper prepared an ordered mesoporous silica by using triblock copolymer Pluronic P123 as template. The property of this material was characterized by the X-ray scattering spectrum(XRD), Transmission electron microscopy(TEM), Scanning electron microscopy (SEM) and Nitrogen adsorption/desorption. Then this ordered mesoporous silica was added into the cigarette filter in order to researching its effect of cigarette harm index. The result shows that the feature of SBA-15 was grain morphology, ordered arrangement, tubular porous 2-D hexagonal structure. The application of SBA-15 in cigarette filter can selectively reduce harmful components in cigarette smoke such as crotonaldehyde, hydrogen cyanide, benzo pyrene and tar. The synthesized SBA-15 could properly reduce cigarette harm index.

  5. Differentiating drugs by harm potential: the rational versus the feasible.

    Kalant, H

    1999-01-01

    In an ideal harm reduction model, drugs would be ranked according to their potential to cause harm, with varying implications for control policies and interventions. In such a public health oriented approach, the maximum protection of the public from harm would be balanced with the least possible restriction of freedom. In reality, however, the accuracy and completeness of the necessary information for such a ranking is highly limited. Many other factors not readily incorporated in a rational model, such as values, beliefs, and traditions, also affect drug policy decisions. Thus, rather than relying on acquisition of the necessary knowledge, it may be preferable to focus efforts on developing effective nonlegal measures to reduce drug use and harm. [Translations are provided in the International Abstracts Section of this issue.

  6. Population dynamics of potentially harmful algal blooms in Bizerte ...

    These were numerically dominated by potentially toxic species of the diatom genus Pseudo-nitzschia, which were present year-round at all stations. ... Canonical correspondence analyses revealed significant relationships between the harmful phytoplankton species monitored and the environmental conditions.

  7. Problems of harmful habits and dependences of students.

    Gorobey Nikolaj Petrovich

    2011-11-01

    Full Text Available The analysis of data of modern scientific literature is conducted on issue of harmful habits and dependences of students. It is shown that considerable part of student young people have harmful habits and dependences. Negative influence of harmful habits and dependences of students is exposed on the state of their health. Importance of delivering is well-proven from addiction behavior in practice of healthy way of life of students. It is set that one of foreground jobs of present time there is an increase of level of education of student young people on questions abandonment from harmful habits and dependences. The ways of decision of problem of addiction behavior of students are offered as an effective condition of improvement of the state of their health.

  8. Mental health nurses' attitudes toward self-harm: Curricular implications

    David G. Shaw

    2016-12-01

    Conclusion: The FASH Model may inform future curriculum innovation. Adopting a holistic approach to education of nurses about self-harm may assist in developing attitudes and skills to make care provision more effective in secure mental health settings.

  9. Harmful situations, impure people: an attribution asymmetry across moral domains.

    Chakroff, Alek; Young, Liane

    2015-03-01

    People make inferences about the actions of others, assessing whether an act is best explained by person-based versus situation-based accounts. Here we examine people's explanations for norm violations in different domains: harmful acts (e.g., assault) and impure acts (e.g., incest). Across four studies, we find evidence for an attribution asymmetry: people endorse more person-based attributions for impure versus harmful acts. This attribution asymmetry is partly explained by the abnormality of impure versus harmful acts, but not by differences in the moral wrongness or the statistical frequency of these acts. Finally, this asymmetry persists even when the situational factors that lead an agent to act impurely are stipulated. These results suggest that, relative to harmful acts, impure acts are linked to person-based attributions. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. A novel Meloidogyne graminicola effector, MgGPP, is secreted into host cells and undergoes glycosylation in concert with proteolysis to suppress plant defenses and promote parasitism.

    Jiansong Chen

    2017-04-01

    Full Text Available Plant pathogen effectors can recruit the host post-translational machinery to mediate their post-translational modification (PTM and regulate their activity to facilitate parasitism, but few studies have focused on this phenomenon in the field of plant-parasitic nematodes. In this study, we show that the plant-parasitic nematode Meloidogyne graminicola has evolved a novel effector, MgGPP, that is exclusively expressed within the nematode subventral esophageal gland cells and up-regulated in the early parasitic stage of M. graminicola. The effector MgGPP plays a role in nematode parasitism. Transgenic rice lines expressing MgGPP become significantly more susceptible to M. graminicola infection than wild-type control plants, and conversely, in planta, the silencing of MgGPP through RNAi technology substantially increases the resistance of rice to M. graminicola. Significantly, we show that MgGPP is secreted into host plants and targeted to the ER, where the N-glycosylation and C-terminal proteolysis of MgGPP occur. C-terminal proteolysis promotes MgGPP to leave the ER, after which it is transported to the nucleus. In addition, N-glycosylation of MgGPP is required for suppressing the host response. The research data provide an intriguing example of in planta glycosylation in concert with proteolysis of a pathogen effector, which depict a novel mechanism by which parasitic nematodes could subjugate plant immunity and promote parasitism and may present a promising target for developing new strategies against nematode infections.

  11. Toxoplasma gondii infection shifts dendritic cells into an amoeboid rapid migration mode encompassing podosome dissolution, secretion of TIMP-1, and reduced proteolysis of extracellular matrix.

    Ólafsson, Einar B; Varas-Godoy, Manuel; Barragan, Antonio

    2018-03-01

    Dendritic cells (DCs) infected by Toxoplasma gondii rapidly acquire a hypermigratory phenotype that promotes systemic parasite dissemination by a "Trojan horse" mechanism in mice. Recent paradigms of leukocyte migration have identified the amoeboid migration mode of DCs as particularly suited for rapid locomotion in extracellular matrix and tissues. Here, we have developed a microscopy-based high-throughput approach to assess motility and matrix degradation by Toxoplasma-challenged murine and human DCs. DCs challenged with T. gondii exhibited dependency on metalloproteinase activity for hypermotility and transmigration but, strikingly, also dramatically reduced pericellular proteolysis. Toxoplasma-challenged DCs up-regulated expression and secretion of tissue inhibitor of metalloproteinases-1 (TIMP-1) and their supernatants impaired matrix degradation by naïve DCs and by-stander DCs dose dependently. Gene silencing of TIMP-1 by short hairpin RNA restored matrix degradation activity in Toxoplasma-infected DCs. Additionally, dissolution of podosome structures in parasitised DCs coincided with abrogated matrix degradation. Toxoplasma lysates inhibited pericellular proteolysis in a MyD88-dependent fashion whereas abrogated proteolysis persevered in Toxoplasma-infected MyD88-deficient DCs. This indicated that both TLR/MyD88-dependent and TLR/MyD88-independent signalling pathways mediated podosome dissolution and the abrogated matrix degradation. We report that increased TIMP-1 secretion and cytoskeletal rearrangements encompassing podosome dissolution are features of Toxoplasma-induced hypermigration of DCs with an impact on matrix degradation. Jointly, the data highlight how an obligate intracellular parasite orchestrates key regulatory cellular processes consistent with non-proteolytic amoeboid migration of the vehicle cells that facilitate its dissemination. © 2017 John Wiley & Sons Ltd.

  12. Probing the 3-D Structure, Dynamics, and Stability of Bacterial Collagenase Collagen Binding Domain (apo- versus holo-) by Limited Proteolysis MALDI-TOF MS

    Sides, Cynthia R.; Liyanage, Rohana; Lay, Jackson O.; Philominathan, Sagaya Theresa Leena; Matsushita, Osamu; Sakon, Joshua

    2012-03-01

    Pairing limited proteolysis and matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) to probe clostridial collagenase collagen binding domain (CBD) reveals the solution dynamics and stability of the protein, as these factors are crucial to CBD effectiveness as a drug-delivery vehicle. MS analysis of proteolytic digests indicates initial cleavage sites, thereby specifying the less stable and highly accessible regions of CBD. Modulation of protein structure and stability upon metal binding is shown through MS analysis of calcium-bound and cobalt-bound CBD proteolytic digests. Previously determined X-ray crystal structures illustrate that calcium binding induces secondary structure transformation in the highly mobile N-terminal arm and increases protein stability. MS-based detection of exposed residues confirms protein flexibility, accentuates N-terminal dynamics, and demonstrates increased global protein stability exported by calcium binding. Additionally, apo- and calcium-bound CBD proteolysis sites correlate well with crystallographic B-factors, accessibility, and enzyme specificity. MS-observed cleavage sites with no clear correlations are explained either by crystal contacts of the X-ray crystal structures or by observed differences between Molecules A and B in the X-ray crystal structures. The study newly reveals the absence of the βA strand and thus the very dynamic N-terminal linker, as corroborated by the solution X-ray scattering results. Cobalt binding has a regional effect on the solution phase stability of CBD, as limited proteolysis data implies the capture of an intermediate-CBD solution structure when cobalt is bound.

  13. Marine harmful algal blooms, human health and wellbeing

    Berdalet, Elisa; Fleming, Lora E.; Gowen, Richard

    2016-01-01

    cause harm to humans and other organisms. These harmful algal blooms (HABs) have direct impacts on human health and negative influences on human wellbeing, mainly through their consequences to coastal ecosystem services (fisheries, tourism and recreation) and other marine organisms and environments...... maintaining intensive, multidisciplinary and collaborative scientific research, and strengthening the coordination with stakeholders, policymakers and the general public. Here we provide an overview of different aspects of the HABs phenomena, an important element of the intrinsic links between oceans...

  14. Deliberate Self-Harm in Adolescence: A Challenge for Schools

    Best, Ron

    2006-01-01

    Acts of deliberate self-harm (DSH) by adolescents are thought to be on the increase. Many of those who self-harm are of school age and it is to be expected that schools (and their teachers) will be aware of the problem and will respond appropriately as part of their pastoral-care provision. However, a recent survey of research in pastoral care and…

  15. Global Fund investments in harm reduction from 2002 to 2009

    Bridge, Jamie; Hunter, Benjamin M; Atun, Rifat

    2012-01-01

    Injecting drug use has been documented in 158 countries and is a major contributor to HIV epidemics. People who inject drugs have poor and inequitable access to HIV services. The Global Fund to Fight AIDS, Tuberculosis and Malaria is the leading multilateral donor for HIV programmes and encourage...... applicants to include harm reduction interventions in their proposals. This study is the first detailed analysis of Global Fund investments in harm reduction interventions....

  16. Harm reduction as a strategy for supporting people who self-harm on mental health wards : the views and experiences of practitioners

    James, Karen; Samuels, Isaac; Moran, Paul; Stewart, Duncan

    2017-01-01

    Background: Harm reduction has had positive outcomes for people using sexual health and substance misuse services. Clinical guidance recommends these approaches may be appropriately adopted by mental health practitioners when managing some people who self-harm. There has, however, been very little research in this area. Methods: We explored practitioners’ views of harm reduction as a strategy for supporting people who self-harm. The Self Harm Antipathy Scale (SHAS) was administered to a rando...

  17. Age-related differences in lean mass, protein synthesis and skeletal muscle markers of proteolysis after bed rest and exercise rehabilitation

    Tanner, Ruth E; Brunker, Lucille B; Agergaard, Jakob

    2015-01-01

    during a constant stable isotope infusion in the postabsorptive state and after essential amino acid (EAA) ingestion on three occasions: before (PRE), after bed rest and after rehabilitation. Samples were assessed for protein synthesis, mTORC1 signalling, REDD1/2 expression and molecular markers related...... to muscle proteolysis (MURF1, MAFBX, AMPKα, LC3II/I, Beclin1). We found that leg lean mass and strength decreased in older but not younger adults after bedrest (P protein synthesis increased before bed rest in both age groups...... (P protein synthesis rates and increased MAFBX mRNA, p-AMPKα and the LC3II/I ratio (P

  18. Drug policy, harm and human rights: a rationalist approach.

    Stevens, Alex

    2011-05-01

    It has recently been argued that drug-related harms cannot be compared, so making it impossible to choose rationally between various drug policy options. Attempts to apply international human rights law to this area are valid, but have found it difficult to overcome the problems in applying codified human rights to issues of drug policy. This article applies the rationalist ethical argument of Gewirth (1978) to this issue. It outlines his argument to the 'principle of generic consistency' and the hierarchy of basic, nonsubtractive and additive rights that it entails. It then applies these ideas to drug policy issues, such as whether there is a right to use drugs, whether the rights of drug 'addicts' can be limited, and how different harms can be compared in choosing between policies. There is an additive right to use drugs, but only insofar as this right does not conflict with the basic and nonsubtractive rights of others. People whose freedom to choose whether to use drugs is compromised by compulsion have a right to receive treatment. They retain enforceable duties not to inflict harms on others. Policies which reduce harms to basic and nonsubtractive rights should be pursued, even if they lead to harms to additive rights. There exists a sound, rational, extra-legal basis for the discussion of drug policy and related harms which enables commensurable discussion of drug policy options. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. HARMFUL ENTOMOPHAUNA IMPACTS ON QUALITY OF MERCANTILE WHEAT AND FLOUR

    Stanislav Milošević

    2005-06-01

    Full Text Available Presence of harmful insects and mites is almost inevitable in mercantile wheat stored in warehouses. They cause significant damages and therefore it is necessary to perform pest control and chemical treatment. Study of harmful and destructive entomophauna impacts on quality of mercantile wheat and flour has been presented. Mercantile wheat stored in silos has been used in the study. Testing of quality of rheological properties and presence of harmful entomophauna were done in the labs within the silos «Žitoprerada d.o.o. Valpovo « and Department of Plant Protection on Faculty of Agriculture in Osijek. Presence of harmful entomophauna, quality of mercantile wheat stored in a warehouse and rheological flour properties were determined. The following harmful entomophauna were found: mites (Acarinae, primary pests of order Coleoptera and Lepidoptera, secondary pests of order Coleoptera and other insects found belong to Coleoptera, Psocoptera and useful insects of Hymenoptera orders. Influence of harmful entomophauna on quality of mercantile wheat is manifested by reduced quality of stored wheat due to decrease of water content and hectoliter mass. Lower quality of flour obtained by milling of infected wheat is manifested by change in rheological properties: dough stability, water absorption, growth, resistance, energy, extensibility, maximum resistance, start of puffing up, and viscosity.

  20. Harm expectancy violation during exposure therapy for posttraumatic stress disorder.

    de Kleine, Rianne A; Hendriks, Lotte; Becker, Eni S; Broekman, Theo G; van Minnen, Agnes

    2017-06-01

    Exposure therapy has proven efficacy in the treatment of posttraumatic stress disorder (PTSD). Emotional processing theory proposes that fear habituation is a central mechanism in symptom reduction, but the empirical evidence supporting this is mixed. Recently it has been proposed that violation of harm expectancies is a crucial mechanism of action in exposure therapy. But to date, changes in harm expectancies have not been examined during exposure therapy in PTSD. The goal of the current study was to examine harm expectancy violation as mechanism of change in exposure therapy for posttraumatic stress disorder (PTSD). Patients (N=50, 44 female) with a primary diagnosis of chronic PTSD received intensive exposure therapy. Harm expectancies, harm experiences and subjective units of distress (SUDs) were assessed at each imaginal exposure session, and PTSD symptoms were assessed pre- and posttreatment with the Clinician Administered PTSD Scale (CAPS). Results showed that harm expectancies were violated within and strongly declined in-between exposure therapy sessions. However, expectancy violation was not related to PTSD symptom change. Fear habituation measures were moderately related to PTSD symptom reductions. In line with theory, exposure therapy promotes expectancy violation in PTSD patients, but this is not related to exposure therapy outcome. More work is warranted to investigate mechanisms of change during exposure therapy in PTSD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Do no harm: a defense of markets in healthcare.

    Kline, William

    2010-09-01

    This paper argues that the rules that constitute a market protect autonomy and increase welfare in healthcare. Markets do the former through protecting rights to self-ownership and a cluster of rights that protect its exercise. Markets protect welfare by organizing and protecting trades. In contrast, prohibition destroys legitimate markets, giving rise to so-called black markets that harm both the autonomy and well-being of agents. For example, a fee-for-service medical system is a highly developed and specialized market. It is individuals working together, through the division of labor, to provide mutual insurance. This coordination, and the benefits it makes possible, is not possible without injunctions against harm. Prohibitions on harm are not mere ethical niceties, they are practice rules for both healthcare and markets. Placing the doctor within a healthcare market actually reinforces the doctor's moral obligation, and the legal enforcement of that obligation, not to harm. Similarly, markets reinforce patient rights to self-determination through legal and institutional enforcement of the harm principle in the form of the protection of certain basic welfare rights to life, bodily integrity, property, trade, and contract. Since the establishment of markets protects agent autonomy and welfare, and prohibition directly harms the same, there are strong reasons for establishing markets to protect trade in precisely those areas where autonomy and well-being are most vulnerable to exploitation, for example, the trade in human kidneys.

  2. Why Suicide? The Analysis of Motives for Self-Harm.

    Abbas, Mohammed J; Mohanna, Mostafa A; Diab, Tarig A; Chikoore, Millicent; Wang, Michael

    2018-03-01

    There is a gap in understanding the meaning and motives behind suicidal behaviour. Using the Ideal Type methodology, Jean Baechler systematically examined the internal logic of suicidal and self-harming behaviours. He developed a typology of eleven typical meanings/motives: Flight, Grief, Self-punishment, Vengeance, Crime, Blackmail, Appeal, Sacrifice, Transfiguration, Ordeal and Game. To develop and validate a standardized instrument to measure the motives/meanings of suicidal and self-harming behaviours, using Baechler's typology. We developed a self-fill Likert questionnaire (Ideal Typical Meaning Questionnaire, ITMQ) covering ten of Baechler's eleven types. The questionnaire was completed by 147 patients within four weeks of attempting suicide or self-harm. The Death Attitude Profile-Revised (DAP-R) questionnaire was used to examine the concurrent validity of the Flight and the Transfiguration types and to explore the association between suicidal/self-harming motives and views about death. The final 25-item ITMQ has an eight-factor structure (Appeal/Blackmail, Ordeal/Game, Vengeance, Self-punishment, Sacrifice, Flight, Grief and Transfiguration) supporting Baechler's theory. The types have adequate reliability. Correlations with the DAP-R gave some support for the concurrent validity of the Flight and Transfiguration types. The ITMQ is a measure of suicidal and self-harming motives/meanings based on a sound conceptual framework and could significantly contribute to the understanding of suicidal and self-harming behaviour in research and clinical settings.

  3. Surface expression and limited proteolysis of ADAM10 are increased by a dominant negative inhibitor of dynamin

    Slack Barbara E

    2011-05-01

    Full Text Available Abstract Background The amyloid precursor protein (APP is cleaved by β- and γ-secretases to generate toxic amyloid β (Aβ peptides. Alternatively, α-secretases cleave APP within the Aβ domain, precluding Aβ formation and releasing the soluble ectodomain, sAPPα. We previously showed that inhibition of the GTPase dynamin reduced APP internalization and increased release of sAPPα, apparently by prolonging the interaction between APP and α-secretases at the plasma membrane. This was accompanied by a reduction in Aβ generation. In the present study, we investigated whether surface expression of the α-secretase ADAM (a disintegrin and metalloprotease10 is also regulated by dynamin-dependent endocytosis. Results Transfection of human embryonic kidney (HEK cells stably expressing M3 muscarinic receptors with a dominant negative dynamin I mutant (dyn I K44A, increased surface expression of both immature, and mature, catalytically active forms of co-expressed ADAM10. Surface levels of ADAM10 were unaffected by activation of protein kinase C (PKC or M3 receptors, indicating that receptor-coupled shedding of the ADAM substrate APP is unlikely to be mediated by inhibition of ADAM10 endocytosis in this cell line. Dyn I K44A strongly increased the formation of a C-terminal fragment of ADAM10, consistent with earlier reports that the ADAM10 ectodomain is itself a target for sheddases. The abundance of this fragment was increased in the presence of a γ-secretase inhibitor, but was not affected by M3 receptor activation. The dynamin mutant did not affect the distribution of ADAM10 and its C-terminal fragment between raft and non-raft membrane compartments. Conclusions Surface expression and limited proteolysis of ADAM10 are regulated by dynamin-dependent endocytosis, but are unaffected by activation of signaling pathways that upregulate shedding of ADAM substrates such as APP. Modulation of ADAM10 internalization could affect cellular behavior in two

  4. Determination of protein-carbonyls and ubiquitin-mediated proteolysis as biomarkers of oxidative-stress in bivalvia and anthozoa

    Walker, Stephen Thomas

    2002-01-01

    blotting and immunohistochemistry in host and zooxanthellae tissues of A. agaricites, depth-dependant differential expression is suggested. These data suggest that differential capacities to mitigate oxidative-stress play a role in setting species distribution limits and that selective proteolysis can be considered an important defence against free-radical mediated protein oxidation. (author)

  5. Determination of protein-carbonyls and ubiquitin-mediated proteolysis as biomarkers of oxidative-stress in bivalvia and anthozoa

    Walker, Stephen Thomas

    2002-07-01

    between species. PC=Os can be detected by DNPH-reactivity/Western blotting assay in host A. agaricites. UPCs can be assayed via Western blotting and immunohistochemistry in host and zooxanthellae tissues of A. agaricites, depth-dependant differential expression is suggested. These data suggest that differential capacities to mitigate oxidative-stress play a role in setting species distribution limits and that selective proteolysis can be considered an important defence against free-radical mediated protein oxidation. (author)

  6. Concomitant external pneumatic compression treatment with consecutive days of high intensity interval training reduces markers of proteolysis.

    Haun, Cody T; Roberts, Michael D; Romero, Matthew A; Osburn, Shelby C; Healy, James C; Moore, Angelique N; Mobley, Christopher B; Roberson, Paul A; Kephart, Wesley C; Mumford, Petey W; Goodlett, Michael D; Pascoe, David D; Martin, Jeffrey S

    2017-12-01

    To compare the effects of external pneumatic compression (EPC) and sham when used concurrently with high intensity interval training (HIIT) on performance-related outcomes and recovery-related molecular measures. Eighteen recreationally endurance-trained male participants (age: 21.6 ± 2.4 years, BMI: 25.7 ± 0.5 kg/m 2 , VO 2peak : 51.3 ± 0.9 mL/kg/min) were randomized to balanced sham and EPC treatment groups. Three consecutive days of HIIT followed by EPC/sham treatment (Days 2-4) and 3 consecutive days of recovery (Days 5-7) with EPC/sham only on Days 5-6 were employed. Venipuncture, flexibility and pressure-to-pain threshold (PPT) measurements were made throughout. Vastus lateralis muscle was biopsied at PRE (i.e., Day 1), 1-h post-EPC/sham treatment on Day 2 (POST1), and 24-h post-EPC/sham treatment on Day 7 (POST2). 6-km run time trial performance was tested at PRE and POST2. No group × time interaction was observed for flexibility, PPT, or serum measures of creatine kinase (CK), hsCRP, and 8-isoprostane. However, there was a main effect of time for serum CK (p = 0.005). Change from PRE in 6-km run times at POST2 were not significantly different between groups. Significant between-groups differences existed for change from PRE in atrogin-1 mRNA (p = 0.018) at the POST1 time point (EPC: - 19.7 ± 8.1%, sham: + 7.7 ± 5.9%) and atrogin-1 protein concentration (p = 0.013) at the POST2 time point (EPC: - 31.8 ± 7.5%, sham: + 96.0 ± 34.7%). In addition, change from PRE in poly-Ub proteins was significantly different between groups at both the POST1 (EPC: - 26.0 ± 10.3%, sham: + 34.8 ± 28.5%; p = 0.046) and POST2 (EPC: - 33.7 ± 17.2%, sham: + 21.4 ± 14.9%; p = 0.037) time points. EPC when used concurrently with HIIT and in subsequent recovery days reduces skeletal muscle markers of proteolysis.

  7. Responsible and controlled use: Older cannabis users and harm reduction

    Lau, Nicholas; Sales, Paloma; Averill, Sheigla; Murphy, Fiona; Sato, Sye-Ok; Murphy, Sheigla

    2015-01-01

    Background Cannabis use is becoming more accepted in mainstream society. In this paper, we use Zinberg’s classic theoretical framework of drug, set, and setting to elucidate how older adult cannabis users managed health, social and legal risks in a context of normalized cannabis use. Methods We present selected findings from our qualitative study of Baby Boomer (born 1946–1964) cannabis users in the San Francisco Bay Area. Data collection consisted of a recorded, in-depth life history interview followed by a questionnaire and health survey. Qualitative interviews were analyzed to discover the factors of cannabis harm reduction from the users’ perspectives. Results Interviewees made harm reduction choices based on preferred cannabis derivatives and routes of administration, as well as why, when, where, and with whom to use. Most interviewees minimized cannabis-related harms so they could maintain social functioning in their everyday lives. Responsible and controlled use was described as moderation of quantity and frequency of cannabis used, using in appropriate settings, and respect for non-users. Users contributed to the normalization of cannabis use through normification. Conclusion Participants followed rituals or cultural practices, characterized by sanctions that helped define “normal” or “acceptable” cannabis use. Users contributed to cannabis normalization through their harm reduction methods. These cultural practices may prove to be more effective than formal legal prohibitions in reducing cannabis-related harms. Findings also suggest that users with access to a regulated market (medical cannabis dispensaries) were better equipped to practice harm reduction. More research is needed on both cannabis culture and alternative routes of administration as harm reduction methods. PMID:25911027

  8. Association Between Deliberate Self-harm and Violent Criminality.

    Sahlin, Hanna; Kuja-Halkola, Ralf; Bjureberg, Johan; Lichtenstein, Paul; Molero, Yasmina; Rydell, Mina; Hedman, Erik; Runeson, Bo; Jokinen, Jussi; Ljótsson, Brjánn; Hellner, Clara

    2017-06-01

    Individuals who self-harm may have an increased risk of aggression toward others, but this association has been insufficiently investigated. More conclusive evidence may affect assessment, treatment interventions, and clinical guidelines. To investigate the association between nonfatal self-harm and violent crime. This population-based longitudinal cohort study, conducted from January 1, 1997, through December 31, 2013, studied all Swedish citizens born between 1982 and 1998 who were 15 years and older (N = 1 850 252). Individuals who emigrated from Sweden before the age of 15 years (n = 104 051) or immigrated to Sweden after the age of 13 years (ie, crime according to the Swedish penal code. The study cohort consisted of 1 850 525 individuals (950 382 males and 900 143 females), and the mean (SD) follow-up time was 8.1 (4.7) years (range, 0-17.0 years; minimum age, 15 years; maximum age, 32 years). During a mean follow-up period of 8.1 years, 55 185 individuals (3.0%) received clinical care for self-harm. The crude hazard ratio was 4.9 (95% CI, 4.8-5.0) for violent crime conviction in exposed individuals compared with the unexposed group. Women who self-harm were at particularly high risk for expressing violent behaviors. After adjustment for relevant psychiatric comorbidities and socioeconomic status, an almost doubled hazard of violent offense remained (hazard ratio, 1.8; 95% CI, 1.8-1.9). Self-harm is associated with an increased risk of conviction for a violent offense in both sexes. The risk of violence, as well as the risk of suicide and self-harm, should be assessed among offending and self-harming individuals.

  9. Harm reduction - a historical view from the left.

    Friedman, S R.; Southwell, M; Bueno, R; Paone, D; Byrne, J; Crofts, N

    2001-04-01

    The harm reduction movement formed during a period in which social movements of the working class and the excluded were weak, neo-liberalism ideologically triumphant, and potential opposition movements were viewed as offering "tinkering" with the system rather than a total social alternative. This climate shaped and limited the perspectives, strategies, and tactics of harm reductionists almost everywhere. In many countries, this period was also marked by a "political economy of scapegoating" that often targeted drug users as the cause of social woes. This scapegoating took the form of "divide and rule" political initiatives by business and political leaderships to prevent social unrest in a long period of worldwide economic trends toward lowered profit rates and toward increasing income inequality. However, times have changed. Mass strikes and other labor struggles, opposition to the World Trade Organisation and other agencies of neo-liberalism, community-based protests against belt-tightening, and other forms of social unrest have been increasing in many countries. This opens up the possibility of new allies for the harm reduction movement, but also poses difficult problems for which we need to develop answers. On-the-ground experience in alliance formation needs to be combined with careful discussion of and research about what approaches work to convince other movements to work for and with harm reduction, and which approaches do not. Class differences within the harm reduction movement are likely to become more salient in terms of (a) creating internal tensions, (b) increasingly, opening up new ways in which working class harm reductionists can organize within their own communities and workplaces, and (c) producing different strategic orientations that will need to be discussed and debated. As a movement, we will need to find ways to accommodate and discuss differing perspectives, needs, and assessments of opportunities and threats without paralyzing harm

  10. Responsible and controlled use: Older cannabis users and harm reduction.

    Lau, Nicholas; Sales, Paloma; Averill, Sheigla; Murphy, Fiona; Sato, Sye-Ok; Murphy, Sheigla

    2015-08-01

    Cannabis use is becoming more accepted in mainstream society. In this paper, we use Zinberg's classic theoretical framework of drug, set, and setting to elucidate how older adult cannabis users managed health, social and legal risks in a context of normalized cannabis use. We present selected findings from our qualitative study of Baby Boomer (born 1946-1964) cannabis users in the San Francisco Bay Area. Data collection consisted of a recorded, in-depth life history interview followed by a questionnaire and health survey. Qualitative interviews were analyzed to discover the factors of cannabis harm reduction from the users' perspectives. Interviewees made harm reduction choices based on preferred cannabis derivatives and routes of administration, as well as why, when, where, and with whom to use. Most interviewees minimized cannabis-related harms so they could maintain social functioning in their everyday lives. Responsible and controlled use was described as moderation of quantity and frequency of cannabis used, using in appropriate settings, and respect for non-users. Users contributed to the normalization of cannabis use through normification. Participants followed rituals or cultural practices, characterized by sanctions that helped define "normal" or "acceptable" cannabis use. Users contributed to cannabis normalization through their harm reduction methods. These cultural practices may prove to be more effective than formal legal prohibitions in reducing cannabis-related harms. Findings also suggest that users with access to a regulated market (medical cannabis dispensaries) were better equipped to practice harm reduction. More research is needed on both cannabis culture and alternative routes of administration as harm reduction methods. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Decreased rate of protein synthesis, caspase-3 activity, and ubiquitin-proteasome proteolysis in soleus muscles from growing rats fed a low-protein, high-carbohydrate diet.

    Batistela, Emanuele; Pereira, Mayara Peron; Siqueira, Juliany Torres; Paula-Gomes, Silvia; Zanon, Neusa Maria; Oliveira, Eduardo Brandt; Navegantes, Luiz Carlos Carvalho; Kettelhut, Isis C; Andrade, Claudia Marlise Balbinotti; Kawashita, Nair Honda; Baviera, Amanda Martins

    2014-06-01

    The aim of this study was to investigate the changes in the rates of both protein synthesis and breakdown, and the activation of intracellular effectors that control these processes in soleus muscles from growing rats fed a low-protein, high-carbohydrate (LPHC) diet for 15 days. The mass and the protein content, as well as the rate of protein synthesis, were decreased in the soleus from LPHC-fed rats. The availability of amino acids was diminished, since the levels of various essential amino acids were decreased in the plasma of LPHC-fed rats. Overall rate of proteolysis was also decreased, explained by reductions in the mRNA levels of atrogin-1 and MuRF-1, ubiquitin conjugates, proteasome activity, and in the activity of caspase-3. Soleus muscles from LPHC-fed rats showed increased insulin sensitivity, with increased levels of insulin receptor and phosphorylation levels of AKT, which probably explains the inhibition of both the caspase-3 activity and the ubiquitin-proteasome system. The fall of muscle proteolysis seems to represent an adaptive response that contributes to spare proteins in a condition of diminished availability of dietary amino acids. Furthermore, the decreased rate of protein synthesis may be the driving factor to the lower muscle mass gain in growing rats fed the LPHC diet.

  12. JNK signaling pathway regulates sorbitol-induced Tau proteolysis and apoptosis in SH-SY5Y cells by targeting caspase-3.

    Olivera Santa-Catalina, Marta; Caballero Bermejo, Montaña; Argent, Ricardo; Alonso, Juan C; Centeno, Francisco; Lorenzo, María J

    2017-12-15

    Growing evidence suggests that Diabetes Mellitus increases the risk of developing Alzheimer's disease. It is well known that hyperglycemia, a key feature of Diabetes Mellitus, may induce plasma osmolarity disturbances. Both hyperglycemia and hyperosmolarity promote the altered post-translational regulation of microtubule-associated protein Tau. Interestingly, abnormal hyperphosphorylation and cleavage of Tau have been proven to lead to the genesis of filamentous structures referred to as neurofibrillary tangles, the main pathological hallmark of Alzheimer's disease. We have previously described that hyperosmotic stress induced by sorbitol promotes Tau proteolysis and apoptosis in SH-SY5Y cells via caspase-3 activation. In order to gain insights into the regulatory mechanisms of such processes, in this work we explored the intracellular signaling pathways that regulate these events. We found that sorbitol treatment significantly enhanced the activation of conventional families of MAPK in SH-SY5Y cells. Tau proteolysis was completely prevented by JNK inhibition but not affected by either ERK1/2 or p38 MAPK blockade. Moreover, inhibition of JNK, but not ERK1/2 or p38 MAPK, efficiently prevented sorbitol-induced apoptosis and caspase-3 activation. In summary, we provide evidence that JNK signaling pathway is an upstream regulator of hyperosmotic stress-induced Tau cleavage and apoptosis in SH-SY5Y through the control of caspase-3 activation. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Metabolic and morphological alterations induced by proteolysis-inducing factor from Walker tumour-bearing rats in C2C12 myotubes

    Yano, Claudia L; Ventrucci, Gislaine; Field, William N; Tisdale, Michael J; Gomes-Marcondes, Maria Cristina C

    2008-01-01

    Patients with advanced cancer suffer from cachexia, which is characterised by a marked weight loss, and is invariably associated with the presence of tumoral and humoral factors which are mainly responsible for the depletion of fat stores and muscular tissue. In this work, we used cytotoxicity and enzymatic assays and morphological analysis to examine the effects of a proteolysis-inducing factor (PIF)-like molecule purified from ascitic fluid of Walker tumour-bearing rats (WF), which has been suggested to be responsible for muscle atrophy, on cultured C 2 C 12 muscle cells. WF decreased the viability of C 2 C 12 myotubes, especially at concentrations of 20–25 μg.mL -1 . There was an increase in the content of the pro-oxidant malondialdehyde, and a decrease in antioxidant enzyme activity. Myotubes protein synthesis decreased and protein degradation increased together with an enhanced in the chymotrypsin-like enzyme activity, a measure of functional proteasome activity, after treatment with WF. Morphological alterations such as cell retraction and the presence of numerous cells in suspension were observed, particularly at high WF concentrations. These results indicate that WF has similar effects to those of proteolysis-inducing factor, but is less potent than the latter. Further studies are required to determine the precise role of WF in this experimental model

  14. Metabolic and morphological alterations induced by proteolysis-inducing factor from Walker tumour-bearing rats in C2C12 myotubes

    Tisdale Michael J

    2008-01-01

    Full Text Available Abstract Background Patients with advanced cancer suffer from cachexia, which is characterised by a marked weight loss, and is invariably associated with the presence of tumoral and humoral factors which are mainly responsible for the depletion of fat stores and muscular tissue. Methods In this work, we used cytotoxicity and enzymatic assays and morphological analysis to examine the effects of a proteolysis-inducing factor (PIF-like molecule purified from ascitic fluid of Walker tumour-bearing rats (WF, which has been suggested to be responsible for muscle atrophy, on cultured C2C12 muscle cells. Results WF decreased the viability of C2C12 myotubes, especially at concentrations of 20–25 μg.mL-1. There was an increase in the content of the pro-oxidant malondialdehyde, and a decrease in antioxidant enzyme activity. Myotubes protein synthesis decreased and protein degradation increased together with an enhanced in the chymotrypsin-like enzyme activity, a measure of functional proteasome activity, after treatment with WF. Morphological alterations such as cell retraction and the presence of numerous cells in suspension were observed, particularly at high WF concentrations. Conclusion These results indicate that WF has similar effects to those of proteolysis-inducing factor, but is less potent than the latter. Further studies are required to determine the precise role of WF in this experimental model.

  15. Metabolic and morphological alterations induced by proteolysis-inducing factor from Walker tumour-bearing rats in C{sub 2}C{sub 12} myotubes

    Yano, Claudia L; Ventrucci, Gislaine [Departamento de Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), CP 6109, 13083-970, Campinas, São Paulo (Brazil); Field, William N; Tisdale, Michael J [Cancer Research Laboratory, Pharmaceutical Sciences Research Institute, Aston University, Birmingham, B4 7ET (United Kingdom); Gomes-Marcondes, Maria Cristina C [Departamento de Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), CP 6109, 13083-970, Campinas, São Paulo (Brazil)

    2008-01-28

    Patients with advanced cancer suffer from cachexia, which is characterised by a marked weight loss, and is invariably associated with the presence of tumoral and humoral factors which are mainly responsible for the depletion of fat stores and muscular tissue. In this work, we used cytotoxicity and enzymatic assays and morphological analysis to examine the effects of a proteolysis-inducing factor (PIF)-like molecule purified from ascitic fluid of Walker tumour-bearing rats (WF), which has been suggested to be responsible for muscle atrophy, on cultured C{sub 2}C{sub 12} muscle cells. WF decreased the viability of C{sub 2}C{sub 12} myotubes, especially at concentrations of 20–25 μg.mL{sup -1}. There was an increase in the content of the pro-oxidant malondialdehyde, and a decrease in antioxidant enzyme activity. Myotubes protein synthesis decreased and protein degradation increased together with an enhanced in the chymotrypsin-like enzyme activity, a measure of functional proteasome activity, after treatment with WF. Morphological alterations such as cell retraction and the presence of numerous cells in suspension were observed, particularly at high WF concentrations. These results indicate that WF has similar effects to those of proteolysis-inducing factor, but is less potent than the latter. Further studies are required to determine the precise role of WF in this experimental model.

  16. [Harm reduction interventions in drug users: current situation and recommendations].

    Bosque-Prous, Marina; Brugal, María Teresa

    2016-11-01

    Harm reduction encompasses interventions, programmes and policies that seek to reduce the negative consequences of the consumption of both legal and illegal drugs on the individual and public health. Harm reduction looks to mitigate the harm suffered by drug users through drug use monitoring and prevention, and promotes initiatives that respect and protect the human rights of this population. The harm reduction policies that have proven effective and efficient are: opioid substitution maintenance therapy (methadone); needle and syringe exchange programmes; supervised drug consumption rooms; and overdose prevention through peer-based naloxone distribution. In order to be effective, these policies must have comprehensive coverage and be implemented in areas where the target population is prevalent. Resident-based opposition to the implementation of these policies is known as the NIMBY (Not In My Back Yard) phenomenon, which is characterised by being against the implementation of new measures in a particular place, but does not question their usefulness. Given that any NIMBY phenomenon is a complex social, cultural and political phenomenon, it is important to conduct a thorough analysis of the situation prior to implementing any of these measures. Harm reduction policies must be extended to other substances such as alcohol and tobacco, as well as to other conditions beyond infectious/contagious diseases and overdose. Copyright © 2016 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. PREP advertisement features affect smokers' beliefs regarding potential harm.

    Strasser, A A; Tang, K Z; Tuller, M D; Cappella, J N

    2008-09-01

    The Institute of Medicine report on potential reduced exposure products (PREPs) recommends that advertising and labelling be regulated to prevent explicitly or implicitly false or misleading claims. Belief that a product is less harmful may increase use or prevent smoking cessation. To determine the effect of altering advertisement features on smokers' beliefs of the harm exposure from a PREP. A Quest advertisement was digitally altered using computer software and presented to participants using web-based television recruitment contracted through a survey company. 500 current smokers completed demographic and smoking history questions, were randomised to view one of three advertisement conditions, then completed eight items assessing their beliefs of the harmfulness of the product. Advertisement conditions included the original, unaltered advertisement; a "red" condition where the cigarette packages were digitally altered to the colour red, implying increased harm potential; and a "no text" condition where all text was removed to reduce explicit product information. Polytomous logistic regression, using "incorrect," "unsure" and "correct" as outcomes, and advertisement type and covariates as predictors, was used for analyses. Participants randomised to the "no text" advertisement were less likely to be incorrect in their beliefs that Quest cigarettes are lower in tar, less addictive, less likely to cause cancer, have fewer chemicals, are healthier and make smoking safer. Smokers can form false beliefs about the harmfulness of PREP products based on how the PREPs are marketed. Careful examination must be undertaken to provide empirical evidence to better formulate regulatory principles of PREP advertising.

  18. Local competition increases people’s willingness to harm others

    Barker, Jessie; Barclay, Pat

    2016-01-01

    Why should organisms incur a cost in order to inflict a (usually greater) cost on others? Such costly harming behavior may be favored when competition for resources occurs locally, because it increases individuals' fitness relative to close competitors. However, there is no explicit experimental...... evidence supporting the prediction that people are more willing to harm others under local versus global competition. We illustrate this prediction with a game theoretic model, and then test it in a series of economic games. In these experiments, players could spend money to make others lose more. We...... manipulated the scale of competition by awarding cash prizes to the players with the highest payoffs per set of social partners (local competition) or in all the participants in a session (global competition). We found that, as predicted, people were more harmful to others when competition was local (study 1...

  19. Self-harm and overcrowding among prisoners in Geneva, Switzerland.

    Wolff, Hans; Casillas, Alejandra; Perneger, Thomas; Heller, Patrick; Golay, Diane; Mouton, Elisabeth; Bodenmann, Patrick; Getaz, Laurent

    2016-01-01

    Prison institutional conditions affect risk for self-harm among detainees. In particular, prison overcrowding may increase the likelihood of self-harm by creating competition for resources, space, and enhancing a "deprivation state." The purpose of this paper is to examine the association between overcrowding and prisoner acts of self-harm. This cross-sectional study took place at Geneva's pre-trial prison (capacity:376) between 2006 and 2014. Outcomes were acts of self-harm that required medical attention, and self-strangulation/hanging events (combined into one group, as these are difficult to differentiate). Dichotomous predictors were overcrowding index- annual mean daily population divided by capacity ( > 200 percent vs prison change in gender, area of origin, foreign residency, religion, or psychiatric treatment. The present study is limited by the definition and identification of self-harm. The distinction between self-strangulation and self-hanging, and the precise classification of an intent to die is difficult to make in practice, especially with limited prison data records available. The relevant literature addresses the complexity of the association between non-suicidal and suicidal behavior. Despite this, the combined category self-strangulations/hangings gives some indication of severe self-harm events, especially since the methodology of categorization employed was consistent throughout the entire period of the study. Other limitations include the small sample size and the lack of individual patient data and prison data to help control for confounding factors. Despite these drawbacks, pertinent data (socio-demographics and number of prisoners treated for mental health and drug abuse) remained stable over the years. Thus, there are no apparent changes in the inmate population that could be linked to an increase in self-harm. High-security placements and mean prisoner stay have increased over time, with a decrease in staff to prisoner ratio - and these

  20. Emergency staff reactions to suicidal and self-harming patients.

    Pompili, Maurizio; Girardi, Paolo; Ruberto, Amedeo; Kotzalidis, Giorgio D; Tatarelli, Roberto

    2005-08-01

    Staff in the emergency departments of hospitals are reported as being negative or ambivalent toward suicidal or self-harming individuals. According to the literature, these patients are subjected to stigmatization and lack of empathy. This phenomenon has been linked to a decreased quality of care offered to these individuals and to missing an important opportunity to prevent further suicidal behavior or repetition of deliberate self-harm. Also, protocols, proper guidelines and education for the emergency staff call for a revision and an implementation. In this paper, evidence suggesting staff attitudes toward suicidal and self-harming patients is reviewed. An overview of related issues such as clinical judgment, the use of scales and nurses' role is also included in this report.

  1. Harmful Tax Competition in the EU with Reference to Croatia

    Saša Drezgić

    2005-08-01

    Full Text Available The process of globalisation has led, among other things, to harmful tax competition. This paper considers the efforts within the EU in combating harmful tax competition (Code of Conduct on Business Taxation and their effects when taking into account the EU regulations in relation to state aids. Considering a number of problems in the implementation of the Code, and the numerous criticisms with regard to the validity of the combat against harmful tax competition – it is difficult to give a final answer about its success. Croatian tax system, and the corporation tax in particular, are analysed in the light of the aforementioned problems. The advantages of the equal treatment of domestic and foreign investors, as well as the certain elements of state aids in tax benefits, are pointed out.

  2. The cost of harmful alcohol use in South Africa.

    Matzopoulos, R G; Truen, S; Bowman, B; Corrigall, J

    2014-02-01

    The economic, social and health costs associated with alcohol-related harms are important measures with which to inform alcohol management policies and laws. This analysis builds on previous cost estimates for South Africa. We reviewed existing international best-practice costing frameworks to provide the costing definitions and dimensions. We sourced data from South African costing literature or, if unavailable, estimated costs using socio-economic and health data from secondary sources. Care was taken to avoid possible causes of cost overestimation, in particular double counting and, as far as possible, second-round effects of alcohol abuse. The combined total tangible and intangible costs of alcohol harm to the economy were estimated at 10 - 12% of the 2009 gross domestic product (GDP). The tangible financial cost of harmful alcohol use alone was estimated at R37.9 billion, or 1.6% of the 2009 GDP. The costs of alcohol-related harms provide a substantial counterbalance to the economic benefits highlighted by the alcohol industry to counter stricter regulation. Curtailing these costs by regulatory and policy interventions contributes directly and indirectly to social well-being and the economy. CONCLUSIONS; Existing frameworks that guide the regulation and distribution of alcohol frequently focus on maximising the contribution of the alcohol sector to the economy, but should also take into account the associated economic, social and health costs. Current interventions do not systematically address the most important causes of harm from alcohol, and need to be informed by reliable evidence of the ongoing costs of alcohol-related harms.

  3. Informed choice requires information about both benefits and harms

    Jørgensen, K J; Brodersen, J; Hartling, O J

    2009-01-01

    women is seriously biased in favour of participation. Women are not informed about the major harms of screening, and the decision to attend has already been made for them by a public authority. This short-circuits informed decision-making and the legislation on informed consent, and violates...... the autonomy of the women. Screening invitations must present both benefits and harms in a balanced fashion, and should offer, not encourage, participation. It should be stated clearly that the choice not to participate is as sensible as the choice to do so. To allow this to happen, the responsibility...

  4. The concept of "harm" in Internet gaming disorder.

    King, Daniel L; Delfabbro, Paul H

    2018-05-23

    Internet gaming disorder (IGD) is a proposed condition that refers to persistent gaming leading to clinically significant impairment. However, there have been few attempts to study the different types and degrees of harm caused by IGD. This commentary describes some of the negative intrapersonal and interpersonal effects of an extreme time investment in gaming activities in the context of IGD. Future research should examine the way in which IGD harms may occur at different levels and degrees. This may enhance the screening of individuals whose behavior is suspected to meet the definition of the proposed IGD criteria.

  5. Embodied harms: gender, shame, and technology-facilitated sexual violence.

    Henry, Nicola; Powell, Anastasia

    2015-06-01

    Criminality in cyberspace has been the subject of much debate since the 1990s, yet comparatively little attention has been paid to technology-facilitated sexual violence and harassment (TFSV). The aim of this article is to explore the ways in which retraditionalized gender hierarchies and inequalities are manifested in online contexts, and to conceptualize the cause and effects of TFSV as "embodied harms." We argue that problematic mind/body and online/off-line dualisms result in a failure to grasp the unique nature of embodied harms, precluding an adequate understanding and theorization of TFSV. © The Author(s) 2015.

  6. Fasting: Benefits and probable health harmfulness from the Islamic perspective

    Mahdi Ebrahimi

    2015-06-01

    Medical science can determine the effects and consequences of thirst and hunger during the month of Ramadan. In the religious perspective, it has been emphasized that fasting is for achieving the divine virtue, and this shouldn’t be in conflict with maintaining man’s health. Therefore, the conditions in which there is the probability of harmfulness to man’s health due to fasting, man shouldn’t fast. As a result, medical science could recognize the conditions in which there is probable harmfulness to man’s health.

  7. Double Jeopardy: Insurance, Animal Harm, and Domestic Violence.

    Signal, Tania; Taylor, Nik; Burke, Karena J; Brownlow, Luke

    2018-05-01

    Although the role of companion animals within the dynamic of domestic violence (DV) is increasingly recognized, the overlap of animal harm and insurance discrimination for victims/survivors of DV has not been considered. Prompted by a case study presented in a National Link Coalition LINK-Letter, this research note examines "Pet Insurance" policies available in Australia and whether nonaccidental injury caused by an intimate partner would be covered. We discuss the implications of exclusion criteria for victims/survivors of DV, shelters providing places for animals within a DV dynamic, and, more broadly, for cross- or mandatory-reporting (of animal harm) initiatives.

  8. Disseminated transmissible venereal tumour associated with Leishmaniasis in a dog.

    Trevizan, J T; Carreira, J T; Souza, N C; Carvalho, I R; Gomes, P B C; Lima, V M F; Orlandi, C M B; Rozza, D B; Koivisto, M B

    2012-12-01

    This report addresses an atypical transmissible venereal tumour in an 8-year-old bitch that was pluriparous and seropositive for leishmaniasis. There were ascites and a serosanguineous discharge from the vulva, but no lesions on the external genital mucosa. An aspirate of the peritoneal fluid showed mononuclear round cells characteristic of transmissible venereal tumour (TVT). Exploratory laparotomy revealed light red, granulomatous structures in the peritoneum, omentum, spleen, liver and uterine horns. Cytological and histopathological tests confirmed the diagnosis of intra-abdominal TVT. Dissemination of the TVT to several organs inside the abdominal cavity probably resulted from immunosuppression caused by leishmaniasis, which favoured the presence and aggressiveness of TVT. © 2012 Blackwell Verlag GmbH.

  9. Malignant Peripheral Nerve Sheath Tumour Associated With Von ...

    Examination revealed a middle aged woman with generalized subcutaneous nodules of various sizes (3mm - 2.5cm), multiple café-au-lait spots (2cm-4.5cm), a plexiform neurofibroma on the left side of the forehead measuring 6cm x 5cm x 5cm. There was a firm, non-pulsatile and non-tender mass (11.5cm x 9cm x 5cm) on ...

  10. Environmentally harmful subventions in the Federal Republic of Germany. Updating for the year 2016

    Koeder, Lea; Burger, Andreas

    2016-12-01

    The contribution on environmentally harmful subventions in the Federal Republic of Germany (Updating for the year 2016) includes the following issues: Why the reduction of environmentally harmful subventions is necessary; subventions and related processes; international initiatives for the reduction of environmentally harmful subventions, routes for the reduction of environmentally harmful subventions.

  11. Harm reduction as a strategy for supporting people who self-harm on mental health wards: the views and experiences of practitioners.

    James, Karen; Samuels, Isaac; Moran, Paul; Stewart, Duncan

    2017-05-01

    Harm reduction has had positive outcomes for people using sexual health and substance misuse services. Clinical guidance recommends these approaches may be appropriately adopted by mental health practitioners when managing some people who self-harm. There has, however, been very little research in this area. We explored practitioners' views of harm reduction as a strategy for supporting people who self-harm. The Self Harm Antipathy Scale (SHAS) was administered to a random sample of 395 mental health practitioners working on 31 wards in England, semi-structured interviews were then conducted with 18 survey respondents. Practitioners who had implemented the approach reported positive outcomes including a reduction in incidence and severity of self-harm and a perceived increase in empowerment of service users. Practitioners with no experience of using harm reduction were concerned that self-harm would increase in severity, and were unsure how to assess and manage risk in people under a harm reduction care plan. Some fundamentally disagreed with the principle of harm reduction for self-harm because it challenged their core beliefs about the morality of self-harm, or the ethical and potential legal ramifications of allowing individuals to harm themselves. This study was conducted solely with practitioners working on inpatient units. The majority of staff interviewed had no experience of harm reduction and so their concerns may not reflect challenges encountered by practitioners in clinical practice. Harm reduction is being used to support people who self-harm within inpatient psychiatry and some practitioners report potential benefits of this approach. However, this raises particularly complex practical, ethical and legal issues and further research is needed to assess the safety, acceptability and efficacy of the approach. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  12. Inhibition of post-traumatic septic proteolysis and ureagenesis and stimulation of hepatic acute-phase protein production by branched-chain amino acid TPN.

    Chiarla, C; Siegel, J H; Kidd, S; Coleman, B; Mora, R; Tacchino, R; Placko, R; Gum, M; Wiles, C E; Belzberg, H

    1988-08-01

    Previous studies have shown that severe sepsis after major trauma results in the reprioritization of release of hepatic acute-phase proteins (APP). They suggest competition for leucine for nutritional utilization may be responsible. To test this hypothesis, a branched-chain enriched (46.6%) amino acid mixture (BCAA) was administered on a prospective randomized basis with standard TPN therapy to 16 septic post-trauma patients. After sepsis was diagnosed, a randomized therapy (control-TPN or BCAA-TPN) was given for 12 days, or until death occurred. Total calories and amino acid nitrogen (N) administered were not different in the two groups (t-test) and q 8 h (347 study periods) amino acid clearances, urinary urea nitrogen excretion, muscle proteolysis from 3-methyl-histidine (3-MH) excretion, and standard indices of sepsis severity and hepatic function were measured, as well as platelets (PLAT), leucocytes (WBC), albumin (ALB), and six acute-phase proteins: C-reactive protein (CRP), alpha-1-antitrypsin (A1TRIP), fibrinogen (FIBRIN), alpha-2-macroglobulin (AMACRO), ceruloplasmin (CERUL), and transferrin (TRANS). Using Scheffé analysis of all contrasts the data showed: BCAA resulted in a fall in 24-hour urea N excretion (24.0 to 20.0 gm/24 hr) and in proteolysis (138 to 126 gm/24 hr) (p less than 0.0001). Prestudy CRP levels were all elevated, but compared to control where APP reprioritization occurred, over the initial 10 days of therapy BCAA patients had a more rapid fall in CRP with a more rapid rise in FIBRIN, TRANS, CERUL, ALBUMIN, AMACRO, and A1TRIP (all p less than 0.0001) relative to CRP. Also, the sepsis-reduced clearances of glutamine and glutamate, alanine, and proline were increased (p less than 0.0001) during BCAA even though urea nitrogen production was reduced (p less than 0.0001). The increase in leucine clearance with BCAA-enriched TPN was positively correlated (r2 = 0.601; p less than 0.0001) with the increase in the sum of all APP and ALB and was

  13. Primary School Children and Self Harm: The Emotional Impact upon Education Professionals, and Their Understandings of Why Children Self Harm and How This Is Managed

    Simm, Rebecca; Roen, Katrina; Daiches, Anna

    2010-01-01

    There is evidence suggesting that self harm among young people is beginning earlier, in childhood and adolescent years. This paper reports on a qualitative study of primary school staff responses to self harm among children. Some studies with adolescents show self harm presents challenges to education professionals who may lack training or…

  14. First Episode of Self-Harm in Older Age : A Report From the 10-Year Prospective Manchester Self-Harm Project

    Voshaar, Richard C. Oude; Cooper, Jayne; Murphy, Elizabeth; Steeg, Sarah; Kapur, Nay; Purandare, Nitin B.

    Objective: Self-harm is closely related to completed suicide, especially in older age. As empirical research of self-harm in older age is scarce, with no studies confined to first-ever episodes in older age, we examined the clinical characteristics and the risk of repetition in first-ever self-harm

  15. First episode of self-harm in older age: a report from the 10-year prospective Manchester Self-Harm project

    Oude Voshaar, R.C.; Cooper, J.; Murphy, E.; Steeg, S.; Kapur, N.; Purandare, N.B.

    2011-01-01

    OBJECTIVE: Self-harm is closely related to completed suicide, especially in older age. As empirical research of self-harm in older age is scarce, with no studies confined to first-ever episodes in older age, we examined the clinical characteristics and the risk of repetition in first-ever self-harm

  16. Physical processes contributing to harmful algal blooms in Saldanha ...

    Since 1994, disruption of harvesting as a result of the presence of harmful algal species has been a regular late-summer phenomenon. Toxic blooms that are ultimately advected into the bay develop on the continental shelf to the north between 32°S and St Helena Bay, a region characterized by favourable conditions for ...

  17. The character of harms: operational challenges in control

    Sparrow, Malcolm K

    2008-01-01

    ... approach which he terms "the sabotage of harms." The book explores the institutional arrangements and decision-frameworks necessary to support this emerging operational model. Written for reflective practitioners charged with risk-control responsibilities across the public, private, and non-governmental sectors, The Character ...

  18. Harms of unsuccessful donation after circulatory death: An exploratory study.

    Taylor, Lauren J; Buffington, Anne; Scalea, Joseph R; Fost, Norman; Croes, Kenneth D; Mezrich, Joshua D; Schwarze, Margaret L

    2018-02-01

    While donation after circulatory death (DCD) has expanded options for organ donation, many who wish to donate are still unable to do so. We conducted face-to-face interviews with family members (N = 15) who had direct experience with unsuccessful DCD and 5 focus groups with professionals involved in the donation process. We used qualitative content analysis to characterize the harms of nondonation as perceived by participants. Participants reported a broad spectrum of harms affecting organ recipients, donors, and donor families. Harms included waste of precious life-giving organs and hospital resources, inability to honor the donor's memory and character, and impaired ability for families to make sense of tragedy and cope with loss. Donor families empathized with the initial hope and ultimate despair of potential recipients who must continue their wait on the transplant list. Focus group members reinforced these findings and highlighted the struggle of families to navigate the uncertainty regarding the timing of death during the donation process. While families reported significant harm, many appreciated the donation attempt. These findings highlight the importance of organ donation to donor families and the difficult experiences associated with current processes that could inform development of alternative donation strategies. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

  19. Benefits, harms and evidence - reflections from UK primary healthcare.

    McCartney, Margaret

    2018-01-01

    In this paper I examine the relationship between benefits, harms and evidence-based medicine in the context of British primary healthcare. First, I will examine: 'What is a benefit and what is a harm?' Second, what should we know about where the balance of risk and benefit appear to lie? Third, what should we do with this knowledge, particularly in the context of the biopsychosocial gaze of primary care? I conclude that even perfect knowledge about benefits and harms requires to be translated in the context of the individual patient: it also requires to be interpreted according to what that persons' wishes are. By reiterating again and again how biases are stacked in favour of recommending treatments and interventions well beyond their rational evidence, my hope is that more honest medicine will result in less but higher value medicine. Stopping doing things that don't work, or work rarely, or come with an unacceptable burden of side effects or appointments should make room for the pleasure of practicing medicine. •Even perfect knowledge about benefits and harms requires to be translated in the context of the individual patient: it also requires to be interpreted according to what that persons' wishes are.•In the real, messy frontline world of general practice, we will always have uncertainty about where the balance of risk and benefit might lie.

  20. Fibre optic microarrays for the detection and enumeration of harmful ...

    Harmful algal blooms (HABs) are a serious threat to coastal resources, causing impacts ranging from the contamination of seafood products with potent toxins to mortalities of wild and farmed fish and other marine animals. As the threat from HABs has expanded, new approaches have become necessary, including ...

  1. Does Income Inequality Harm Health? New Cross-National Evidence

    Beckfield, Jason

    2004-01-01

    The provocative hypothesis that income inequality harms population health has sparked a large body of research, some of which has reported strong associations between income inequality and population health. Cross-national evidence is frequently cited in support of this important hypothesis, but the hypothesis remains controversial, and the…

  2. Evolution of helping and harming in heterogeneous groups.

    Rodrigues, António M M; Gardner, Andy

    2013-08-01

    Social groups are often composed of individuals who differ in many respects. Theoretical studies on the evolution of helping and harming behaviors have largely focused upon genetic differences between individuals. However, nongenetic variation between group members is widespread in natural populations, and may mediate differences in individuals' social behavior. Here, we develop a framework to study how variation in individual quality mediates the evolution of unconditional and conditional social traits. We investigate the scope for the evolution of social traits that are conditional on the quality of the actor and/or recipients. We find that asymmetries in individual quality can lead to the evolution of plastic traits with different individuals expressing helping and harming traits within the same group. In this context, population viscosity can mediate the evolution of social traits, and local competition can promote both helping and harming behaviors. Furthermore, asymmetries in individual quality can lead to the evolution of competition-like traits between clonal individuals. Overall, we highlight the importance of asymmetries in individual quality, including differences in reproductive value and the ability to engage in successful social interactions, in mediating the evolution of helping and harming behaviors. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

  3. Immigration Enforcement Practices Harm Refugee Children and Citizen-Children

    Zayas, Luis H.

    2018-01-01

    Aggressive immigration enforcement hurts the very youngest children. Refugee and U.S.-born children of undocumented immigrants experience many childhood adversities, compromising their development and health. Refugee children flee traumatizing violence in their home countries, face grueling migrations, and are harmed further by being held in…

  4. Harmful cyanobacteria and their cyanotoxins in Egyptian fresh waters

    Cyanobacterial blooms have increased in freshwater ecosystems worldwide in the last century, mostly resulting from eutrophication and climate change. These blooms represent serious threats to environmental and human health because of the production of harmful metabolites, called cyanotoxins. Like many countries ...

  5. Harm to patients and others caused by impaired junior doctors ...

    Creative Commons licence CC-BY-NC 4.0. Harm to patients and ... enjoining doctors to 'self-report' impairment, the HPCSA Handbook on Internship .... e.g. where doctors have car accidents while driving home because they are not provided ...

  6. Cognitive-behavioural therapy for deliberate self-harm

    Slee, Nadja

    2008-01-01

    This thesis describes the outcomes of a randomized controlled trial of a Cognitive Behavioural Therapy (CBT) intervention for patients who engage in Deliberate Self-Harm (DSH). The CBT intervention was designed to supplement usual care following an episode of DSH. The study involved 90 people (95%

  7. Effects of rising CO₂ on the harmful cyanobacterium Microcystis

    Sandrini, G.

    2016-01-01

    The waters of our planet are full with cyanobacteria that use CO₂, water and light for photosynthesis. Cyanobacteria form the base of the food web and have a strong impact on all life on Earth. Yet, not all cyanobacteria are beneficial. Harmful cyanobacteria (also known as ‘blue-green algae’) can

  8. Risk management and liability for environmental harm caused by ...

    This calls for the existence of a liability regime that will place some legal responsibility on the party responsible for the harm. This paper assesses the South African regulatory framework of relevance to GMOs, which is composed of a fragmented set of laws that deals with risk assessment, risk management and liability for ...

  9. 30 CFR 75.322 - Harmful quantities of noxious gases.

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Harmful quantities of noxious gases. 75.322... quantities of noxious gases. Concentrations of noxious or poisonous gases, other than carbon dioxide, shall... Governmental Industrial Hygienists in “Threshold Limit Values for Substance in Workroom Air” (1972). Detectors...

  10. Vaginismus : Heightened Harm Avoidance and Pain Catastrophizing Cognitions

    Borg, Charmaine; Peters, Madelon L.; Schultz, Willibrord Weijmar; de Jong, Peter J.

    Introduction. Catastrophic appraisal of experienced pain may promote hypervigilance and intense pain, while the personality trait of harm avoidance (HA) might prevent the occurrence of correcting such experiences. Women inflicted with vaginismus may enter a self-perpetuating downward spiral of

  11. Harming others : universal subjectivism and the expanding moral circle

    Berg, Floris van den

    2011-01-01

    Harming Others expounds what the author calls universal subjectivism, which is a cosmopolitan theory of political philosophy that deals with global justice, non-human animals and future generations. Although its main focus is political philosophy, the theory has wide applications to contemporary

  12. Synthesis of Porous Inorganic Hollow Fibers without Harmful Solvents

    Shukla, Sushumna; de Wit, Patrick; Luiten-Olieman, Maria W.J.; Kappert, Emiel; Nijmeijer, Arian; Benes, Nieck Edwin

    2015-01-01

    A route for the fabrication of porous inorganic hollow fibers with high surface-area-to-volume ratio that avoids harmful solvents is presented. The approach is based on bio-ionic gelation of an aqueous mixture of inorganic particles and sodium alginate during wet spinning. In a subsequent thermal

  13. Building Face Composites Can Harm Lineup Identification Performance

    Wells, Gary L.; Charman, Steve D.; Olson, Elizabeth A.

    2005-01-01

    Face composite programs permit eyewitnesses to build likenesses of target faces by selecting facial features and combining them into an intact face. Research has shown that these composites are generally poor likenesses of the target face. Two experiments tested the proposition that this composite-building process could harm the builder's memory…

  14. Mull it over: cannabis vaporizers and harm reduction.

    Gartner, Coral E

    2015-11-01

    Legalization of cannabis is likely to lead to greater use. Balanced regulation of potentially less harmful modes of administration, such as vaporizers, is needed. Further research is warranted not only on the direct health effects of vaping cannabis, but also on its potential to decrease co-administration of tobacco with cannabis.

  15. Suicide and Self-Harm Related Internet Use.

    Padmanathan, Prianka; Biddle, Lucy; Carroll, Robert; Derges, Jane; Potokar, John; Gunnell, David

    2018-05-31

    The rise in Internet use adds a new dimension to suicide prevention. We investigated suicide/self-harm (S/Sh)-related Internet use among patients presenting to hospital with self-harm. We asked 1,198 adult and 315 child and adolescent patients presenting to hospital following self-harm in a city in South West England about Internet use associated with their hospital presentation. Associations between Internet use and sociodemographic and clinical characteristics were investigated using multivariable logistic regression models. Focus groups with clinicians explored the acceptability and utility of asking about Internet use. The prevalence of S/Sh-related Internet use was 8.4% (95% CI: 6.8-10.1%) among adult hospital presentations and 26.0% (95% CI = 21.3-31.2%) among children's hospital presentations. In both samples, S/Sh-related Internet use was associated with higher levels of suicidal intent. Mostly, clinicians found it acceptable to ask about Internet use during psychosocial assessments and believed this could inform perceptions of risk and decision-making. It is unclear whether the findings in this study are applicable to the general self-harm patient population because only those who had psychosocial assessments were included. S/Sh-related Internet use is likely to become increasingly relevant as the Internet-native generation matures. Furthermore, Internet use may be a proxy marker for intent.

  16. 40 CFR Appendix C to Part 112 - Substantial Harm Criteria

    2010-07-01

    ... to Part 112 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS OIL POLLUTION PREVENTION Pt. 112, App. C Appendix C to Part 112—Substantial Harm Criteria 1.0Introduction The..., except in the Gulf of Mexico. In the Gulf of Mexico, it means the area shoreward of the lines of...

  17. Mobile phone social harms (mobile phone, communicative device or ...

    One of the human inventions created in order to facilitate life but it became scourge for him is mobile phone. Ignorance on quality of using mobile phone and conscious use of it in inappropriate way will have consequences that it seems that it gradually becomes as social problem and harm. Author of this paper aims to warns ...

  18. The distribution of harm in price-fixing cases

    Boone, J.; Müller, W.

    2012-01-01

    We consider a vertically related industry and analyze how the total harm due to a price increase upstream is distributed over downstream firms and final consumers. For this purpose, we develop a general model without making specific assumptions regarding demand, costs, or the mode of competition. We

  19. The Distribution of Harm in Price-Fixing Cases

    Boone, J.; Müller, W.

    2008-01-01

    Abstract: We consider a vertically related industry and analyze how the total harm due to a price increase upstream is distributed over downstream firms and final consumers. For this purpose, we develop a general model without making specific assumptions regarding demand, costs, or the mode of

  20. The distribution of harm in price-fixing cases

    Boone, J.; Müller, W.

    2008-01-01

    We consider a vertically related industry and analyze how the total harm due to a price increase upstream is distributed over downstream firms and final consumers. For this purpose, we develop a general model without making specific assumptions regarding demand, costs, or the mode of competition. We

  1. Harming ourselves and defiling others: what determines a moral domain?

    Alek Chakroff

    Full Text Available Recent work has distinguished "harm" from "purity" violations, but how does an act get classified as belonging to a domain in the first place? We demonstrate the impact of not only the kind of action (e.g., harmful versus impure but also its target (e.g., oneself versus another. Across two experiments, common signatures of harm and purity tracked with other-directed and self-directed actions, respectively. First, participants judged self-directed acts as primarily impure and other-directed acts as primarily harmful. Second, conservatism predicted harsher judgments of self-directed but not other-directed acts. Third, while participants delivered harsher judgments of intentional versus accidental acts, this effect was smaller for self-directed than other-directed acts. Finally, participants judged self-directed acts more harshly when focusing on the actor's character versus the action itself; other-directed acts elicited the opposite pattern. These findings suggest that moral domains are defined not only by the kind of action but also by the target of the action.

  2. Mental health nurses' attitudes toward self-harm: Curricular implications

    David G. Shaw

    2016-10-01

    Methods: The study aimed to explore the attitudes of mental health nurses toward service users who self-harm in secure environments, and to inform mental health curriculum development. It was conducted in a large forensic mental health unit, containing medium and low secure facilities, to the west of London, UK. A qualitative multi-method approach was adopted, underpinned by interpretative phenomenological analysis. Data were obtained from mental health nurses using individual interviews and focus groups, and analysis followed a step-by-step thematic approach using interpretative phenomenological analysis. Results: Nurses' attitudes toward self-harm varied but were mainly negative, and this was usually related to limited knowledge and skills. The results of the study, framed by the Theory of Planned Behaviour, led to the development of a proposed educational model entitled ‘Factors Affecting Self-Harming Behaviours’ (FASH. Conclusion: The FASH Model may inform future curriculum innovation. Adopting a holistic approach to education of nurses about self-harm may assist in developing attitudes and skills to make care provision more effective in secure mental health settings.

  3. Biological control of Microcystis dominated harmful algal blooms ...

    Freshwater resources are now threatened by the presence and increase of harmful algal blooms (HAB) all over the world. The HABs are sometimes a direct result of anthropogenic pollution entering water bodies, such as partially treated nutrient-rich effluents and the leaching of fertilisers and animal wastes. The impact of ...

  4. Benefits and harms of perioperative beta-blockade

    Wetterslev, Jørn; Juul, Anne Benedicte

    2006-01-01

    randomized trials. However, confidence intervals of the intervention effects in the meta-analyses are wide, leaving room for both benefits and harms. The largest observational study performed suggests that perioperative beta-blockade is associated with higher mortality in patients with low cardiac risk...

  5. A safer alternative: Cannabis substitution as harm reduction.

    Lau, Nicholas; Sales, Paloma; Averill, Sheigla; Murphy, Fiona; Sato, Sye-Ok; Murphy, Sheigla

    2015-11-01

    Substitution is operationalised as a conscious choice made by users to use one drug instead of, or in conjunction with another based on: perceived safety, level of addiction potential, effectiveness in relieving symptoms, access and level of acceptance. Harm reduction is a set of strategies that aim to minimise problems associated with drug use while recognising that for some users, abstinence may be neither a realistic nor a desirable goal. In this paper, we aim for deeper understandings of older adult cannabis users' beliefs and substitution practices as part of the harm reduction framework. We present selected findings from our qualitative study of Baby Boomer (born 1946-1964) marijuana users in the San Francisco Bay Area. Although the sample consisted of primary cannabis users, many had personal experience with other drugs throughout their lifetimes. Data collection consisted of an audio-recorded, semi-structured in-depth life history interview followed by a questionnaire and health survey. Qualitative interviews were analysed to discover users' harm reduction beliefs and cannabis substitution practices. Study participants described using cannabis as a safer alternative for alcohol, illicit drugs and pharmaceuticals based on their perceptions of less adverse side effects, low-risk for addiction and greater effectiveness at relieving symptoms, such as chronic pain. Cannabis substitution can be an effective harm reduction method for those who are unable or unwilling to stop using drugs completely. More research is needed on cannabis as a safer alternative. © 2015 Australasian Professional Society on Alcohol and other Drugs.

  6. 47 CFR 68.108 - Incidence of harm.

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Incidence of harm. 68.108 Section 68.108 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) CONNECTION OF TERMINAL EQUIPMENT TO THE TELEPHONE NETWORK Conditions on Use of Terminal Equipment § 68.108 Incidence of...

  7. Mental health nurses' attitudes toward self-harm: Curricular ...

    David G. Shaw

    Mental health curriculum. Interpretative phenomenological analysis. Nurses ... This paper reports on a qualitative study into the attitudes of ... There are a couple of published accounts based on ... the stimulus is self-harm and the health professional (nurse) ... iours, including sex and exercise (Connor & Norman, 2005).

  8. Crystalline methamphetamine use and methamphetamine-related harms in Australia.

    Degenhardt, Louisa; Sara, Grant; McKetin, Rebecca; Roxburgh, Amanda; Dobbins, Timothy; Farrell, Michael; Burns, Lucinda; Hall, Wayne D

    2017-03-01

    Concerns about crystal methamphetamine use and harm have increased in multiple countries. This paper describes how changes in the availability and use of crystal methamphetamine have impacted on methamphetamine-related harms in Australia. Data on methamphetamine use were obtained from population-level surveys, health service data and surveys of drug use among sentinel groups of ecstasy users and people who inject drugs. Data were obtained on seizures, arrests, clandestine laboratory detections, hospital separations, mental health unit admissions, drug telephone helpline calls and drug treatment episodes. Segmented linear regression models were fitted to identify changes in these series using log-transformed data where appropriate. The availability of crystal methamphetamine has increased as evidenced by increased laboratory detections, domestic seizures and purity of the seized drug. Population surveys do not report an increase in the number of people who used at least once in the past year. However, more users report using crystal methamphetamine rather than lower-purity powder methamphetamine and more regular use. Indicators of methamphetamine-related harms have increased in parallel with this change. Amphetamine-related helpline calls, drug treatment, arrests and hospital admissions for amphetamine disorders and psychosis all peaked in the mid-2000s, declined for several years and have increased steeply since 2010. The increased availability and use of crystal methamphetamine have been associated with increased regular use and harms. Treatment is required for those experiencing problems and the capacity of health services to provide care needs to be enhanced.[Degenhardt L, Sara G, Connor JP, McKetin R, Roxburgh A, Dobbins T, Farrell M, Burns L, Hall WD. Crystalline methamphetamine use and methamphetamine-related harms in Australia. Drug Alcohol Rev 2017;36:160-170]. © 2016 Australasian Professional Society on Alcohol and other Drugs.

  9. Specific Emissions of Harmful Substances from Small Boilers

    Horák Jiøí

    1998-09-01

    Full Text Available Coal is on of the most important energy source and its significance will increase in a future. In Czech republic coal is except else widely used as a fuel for combustion in a small boilers (up to 50 kW. Low efficiency of the small boilers which is often below 50% together with high emissions of the harmful substances into near surroundings cause in average 40 – 70% of total local air pollution. The research was performed in a scope of the Grant no. 101/98/0820 of Grant Agency of Czech Republic was focused on quality of combustion process related to combustion efficiency and creation of harmful substances at combustion of domestic fuels. Experiments were performed to compare combustion of brown coal, clack coal, coke and black coal slurry. Extremely high creation of harmful substances (CO, NOX, solid particles and organic substances was measured when the black coal slurry was used as a fuel, measured in kg of emissions per GJ of burned fuel. Combustion of brown coal produced significant emissions of solid particles which bond harmful substances as metals, polyaromatic hydrocarbons and others together with high emissions of SO2 . Strong dependence between emissions of CO and low quality of combustion given by low combustion temperature, shortage of combustion air, not suitable design of after-combustion chamber and short duration of fuel presence in a combustion area was found out. Emissions of wide range of metals were investigated. The results of the research grant project describe and explain the combustion process and creation of harmful substances in small boilers plus give suggestions and recommendations leading to rational operation of the small boilers and lowering their negative impact to environment.

  10. PREP advertisement features affect smokers’ beliefs regarding potential harm

    Strasser, Andrew A; Tang, Kathy Z; Tuller, Michael D; Cappella, Joseph N

    2014-01-01

    Background The Institute of Medicine report on potential reduced exposure products (PREPs) recommends that advertising and labelling be regulated to prevent explicitly or implicitly false or misleading claims. Belief that a product is less harmful may increase use or prevent smoking cessation. Objective To determine the effect of altering advertisement features on smokers’ beliefs of the harm exposure from a PREP. Methods A Quest advertisement was digitally altered using computer software and presented to participants using web-based television recruitment contracted through a survey company. 500 current smokers completed demographic and smoking history questions, were randomised to view one of three advertisement conditions, then completed eight items assessing their beliefs of the harmfulness of the product. Advertisement conditions included the original, unaltered advertisement; a “red” condition where the cigarette packages were digitally altered to the colour red, implying increased harm potential; and a “no text” condition where all text was removed to reduce explicit product information. Polytomous logistic regression, using “incorrect,” “unsure” and “correct” as outcomes, and advertisement type and covariates as predictors, was used for analyses. Results Participants randomised to the “no text” advertisement were less likely to be incorrect in their beliefs that Quest cigarettes are lower in tar, less addictive, less likely to cause cancer, have fewer chemicals, healthier and make smoking safer. Conclusions Smokers can form false beliefs about the harmfulness of PREP products based on how the PREPs are marketed. Careful examination must be undertaken to provide empirical evidence to better formulate regulatory principles of PREP advertising. PMID:18768457

  11. Effect of processing on proteolysis and biogenic amines formation in a Portuguese traditional dry-fermented ripened sausage "Chouriço Grosso de Estremoz e Borba PGI".

    Roseiro, L C; Gomes, A; Gonçalves, H; Sol, M; Cercas, R; Santos, C

    2010-01-01

    The influence of alternative drying environmental conditions on the proteolysis of a traditional Portuguese fermented sausage was evaluated, in relation to different ripening periods. Traditional sausages (batch T) had lower pH than counterparts (batch M), with differences (Palanine>taurine>serine>valine and taurine>alanine>leucine>serine>valine sequences in the former product from batches T and M, respectively, and, coincidently, the same sequence for both batches in the later (serine>leucine>alanine>proline>valine). Such effect on FAA concentrations led to a distinct (Psweet, bitter, acidic and aged sensorial attributes between batches, in S8 and S9 products. BA typical quantitative sequences varied between batches according to the ripening stage, with differences in S6 and S7 end products also reflecting the distinct microbial development rates and profiles observed. Overall, the total BA mean concentration was higher (P<0.05) in products from batch T.

  12. Expression, limited proteolysis and preliminary crystallographic analysis of IpaD, a component of the Shigella flexneri type III secretion system

    Johnson, Steven [Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford (United Kingdom); Sir William Dunn School of Pathology, University of Oxford (United Kingdom); Roversi, Pietro [Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford (United Kingdom); Espina, Marianela [Department of Molecular Biosciences, University of Kansas (United States); Deane, Janet E. [Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford (United Kingdom); Birket, Susan; Picking, William D. [Department of Molecular Biosciences, University of Kansas (United States); Blocker, Ariel [Sir William Dunn School of Pathology, University of Oxford (United Kingdom); Picking, Wendy L. [Department of Molecular Biosciences, University of Kansas (United States); Lea, Susan M., E-mail: susan.lea@path.ox.ac.uk [Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford (United Kingdom); Sir William Dunn School of Pathology, University of Oxford (United Kingdom)

    2006-09-01

    IpaD, the putative needle-tip protein of the S. flexneri type III secretion system, has been crystallized in a variety of crystal forms using in-drop proteolysis. Native and selenomethionine-labelled data collection and preliminary analyses are reported. IpaD, the putative needle-tip protein of the Shigella flexneri type III secretion system, has been overexpressed and purified. Crystals were grown of the native protein in space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 55.9, b = 100.7, c = 112.0 Å, and data were collected to 2.9 Å resolution. Analysis of the native Patterson map revealed a peak at 50% of the origin on the Harker section v = 0.5, suggesting twofold non-crystallographic symmetry parallel to the b crystallographic axis. As attempts to derivatize or grow selenomethionine-labelled protein crystals failed, in-drop proteolysis was used to produce new crystal forms. A trace amount of subtilisin Carlsberg was added to IpaD before sparse-matrix screening, resulting in the production of several new crystal forms. This approach produced SeMet-labelled crystals and diffraction data were collected to 3.2 Å resolution. The SeMet crystals belong to space group C2, with unit-cell parameters a = 139.4, b = 45.0, c = 99.5 Å, β = 107.9°. An anomalous difference Patterson map revealed peaks on the Harker section v = 0, while the self-rotation function indicates the presence of a twofold noncrystallographic symmetry axis, which is consistent with two molecules per asymmetric unit.

  13. Expression, limited proteolysis and preliminary crystallographic analysis of IpaD, a component of the Shigella flexneri type III secretion system

    Johnson, Steven; Roversi, Pietro; Espina, Marianela; Deane, Janet E.; Birket, Susan; Picking, William D.; Blocker, Ariel; Picking, Wendy L.; Lea, Susan M.

    2006-01-01

    IpaD, the putative needle-tip protein of the S. flexneri type III secretion system, has been crystallized in a variety of crystal forms using in-drop proteolysis. Native and selenomethionine-labelled data collection and preliminary analyses are reported. IpaD, the putative needle-tip protein of the Shigella flexneri type III secretion system, has been overexpressed and purified. Crystals were grown of the native protein in space group P2 1 2 1 2 1 , with unit-cell parameters a = 55.9, b = 100.7, c = 112.0 Å, and data were collected to 2.9 Å resolution. Analysis of the native Patterson map revealed a peak at 50% of the origin on the Harker section v = 0.5, suggesting twofold non-crystallographic symmetry parallel to the b crystallographic axis. As attempts to derivatize or grow selenomethionine-labelled protein crystals failed, in-drop proteolysis was used to produce new crystal forms. A trace amount of subtilisin Carlsberg was added to IpaD before sparse-matrix screening, resulting in the production of several new crystal forms. This approach produced SeMet-labelled crystals and diffraction data were collected to 3.2 Å resolution. The SeMet crystals belong to space group C2, with unit-cell parameters a = 139.4, b = 45.0, c = 99.5 Å, β = 107.9°. An anomalous difference Patterson map revealed peaks on the Harker section v = 0, while the self-rotation function indicates the presence of a twofold noncrystallographic symmetry axis, which is consistent with two molecules per asymmetric unit

  14. Arsenite reduces insulin secretion in rat pancreatic β-cells by decreasing the calcium-dependent calpain-10 proteolysis of SNAP-25

    Diaz-Villasenor, Andrea; Burns, Anna L.; Salazar, Ana Maria; Sordo, Monserrat; Hiriart, Marcia; Cebrian, Mariano E.; Ostrosky-Wegman, Patricia

    2008-01-01

    An increase in the prevalence of type 2 diabetes has been consistently observed among residents of high arsenic exposure areas. We have previously shown that in rat pancreatic β-cells, low arsenite doses impair the secretion of insulin without altering its synthesis. To further study the mechanism by which arsenite reduces insulin secretion, we evaluated the effects of arsenite on the calcium-calpain pathway that triggers insulin exocytosis in RINm5F cells. Cell cycle and proliferation analysis were also performed to complement the characterization. Free [Ca 2+ ]i oscillations needed for glucose-stimulated insulin secretion were abated in the presence of subchronic low arsenite doses (0.5-2 μM). The global activity of calpains increased with 2 μM arsenite. However, during the secretion of insulin stimulated with glucose (15.6 mM), 1 μM arsenite decreased the activity of calpain-10, measured as SNAP-25 proteolysis. Both proteins are needed to fuse insulin granules with the membrane to produce insulin exocytosis. Arsenite also induced a slowdown in the β cell line proliferation in a dose-dependent manner, reflected by a reduction of dividing cells and in their arrest in G2/M. Data obtained showed that one of the mechanisms by which arsenite impairs insulin secretion is by decreasing the oscillations of free [Ca 2+ ]i, thus reducing calcium-dependent calpain-10 partial proteolysis of SNAP-25. The effects in cell division and proliferation observed with arsenite exposure can be an indirect consequence of the decrease in insulin secretion

  15. In-capillary enrichment, proteolysis and separation using capillary electrophoresis with discontinuous buffers: application on proteins with moderately acidic and basic isoelectric points.

    Nesbitt, Chandra A; Yeung, Ken K-C

    2009-01-01

    Advances in mass spectrometry and capillary-format separation continue to improve the sensitivity of protein analysis. Of equal importance is the miniaturization of sample pretreatment such as enrichment and proteolysis. In a previous report (Nesbitt et al., Electrophoresis, 2008, 29, 466-474), nanoliter-volume protein enrichment, tryptic digestion, and partial separation was demonstrated in capillary electrophoresis followed by MALDI mass spectral analysis. A discontinuous buffer system, consisting of ammonium (pH 10) and acetate (pH 4), was used to create a pH junction inside the capillary, trapping a protein with a neutral isoelectric point, myoglobin (pI 7.2). Moreover, co-enrichment of myoglobin with trypsin led to an in-capillary digestion. In this paper, the ability of this discontinuous buffer system to perform similar in-capillary sample pretreatment on proteins with moderately acidic and basic pI was studied and reported. Lentil lectin (pI 8.6) and a multi-phosphorylated protein, beta-casein (pI 5.1), were selected as model proteins. In addition to the previously shown tryptic digestion, proteolysis with endoproteinase Asp-N was also performed. Digestion of these acidic and basic pI proteins produced a few peptides with extreme pI values lying outside the trapping range of the discontinuous buffer. An alteration in the peptide trapping procedure was made to accommodate these analytes. Offline MALDI mass spectral analysis confirmed the presence of the expected peptides. The presented miniaturized sample pretreatment methodology was proven to be applicable on proteins with a moderately wide range of pI. Flexibility in the choice of protease was also evident.

  16. Harmful algal bloom smart device application: using image analysis and machine learning techniques for classification of harmful algal blooms

    Northern Kentucky University and the U.S. EPA Office of Research Development in Cincinnati Agency are collaborating to develop a harmful algal bloom detection algorithm that estimates the presence of cyanobacteria in freshwater systems by image analysis. Green and blue-green alg...

  17. Evaluation of strategies to communicate harmful and potentially harmful constituent (HPHC) information through cigarette package inserts: a discrete choice experiment.

    Salloum, Ramzi G; Louviere, Jordan J; Getz, Kayla R; Islam, Farahnaz; Anshari, Dien; Cho, Yoojin; O'Connor, Richard J; Hammond, David; Thrasher, James F

    2017-07-13

    The US Food and Drug Administration (FDA) has regulatory authority to use inserts to communicate with consumers about harmful and potentially harmful constituents (HPHCs) in tobacco products; however, little is known about the most effective manner for presenting HPHC information. In a discrete choice experiment, participants evaluated eight choice sets, each of which showed two cigarette packages from four different brands and tar levels (high vs low), accompanied by an insert that included between-subject manipulations (ie, listing of HPHCs vs grouping by disease outcome and numeric values ascribed to HPHCs vs no numbers) and within-subject manipulations (ie, 1 of 4 warning topics; statement linking an HPHC with disease vs statement with no HPHC link). For each choice set, participants were asked: (1) which package is more harmful and (2) which motivates them to not smoke; each with a 'no difference' option. Alternative-specific logit models regressed choice on attribute levels. 1212 participants were recruited from an online consumer panel (725 18-29-year-old smokers and susceptible non-smokers and 487 30-64-year-old smokers). Participants were more likely to endorse high-tar products as more harmful than low-tar products, with a greater effect when numeric HPHC information was present. Compared with a simple warning statement, the statement linking HPHCs with disease encouraged quit motivation. Numeric HPHC information on inserts appears to produce misunderstandings that some cigarettes are less harmful than others. Furthermore, brief narratives that link HPHCs to smoking-related disease may promote cessation versus communications that do not explicitly link HPHCs to disease. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  18. Does clinical management improve outcomes following self-harm? Results from the multicentre study of self-harm in England.

    Nav Kapur

    Full Text Available Evidence to guide clinical management of self-harm is sparse, trials have recruited selected samples, and psychological treatments that are suggested in guidelines may not be available in routine practice.To examine how the management that patients receive in hospital relates to subsequent outcome.We identified episodes of self-harm presenting to three UK centres (Derby, Manchester, Oxford over a 10 year period (2000 to 2009. We used established data collection systems to investigate the relationship between four aspects of management (psychosocial assessment, medical admission, psychiatric admission, referral for specialist mental health follow up and repetition of self-harm within 12 months, adjusted for differences in baseline demographic and clinical characteristics.35,938 individuals presented with self-harm during the study period. In two of the three centres, receiving a psychosocial assessment was associated with a 40% lower risk of repetition, Hazard Ratios (95% CIs: Centre A 0.99 (0.90-1.09; Centre B 0.59 (0.48-0.74; Centre C 0.59 (0.52-0.68. There was little indication that the apparent protective effects were mediated through referral and follow up arrangements. The association between psychosocial assessment and a reduced risk of repetition appeared to be least evident in those from the most deprived areas.These findings add to the growing body of evidence that thorough assessment is central to the management of self-harm, but further work is needed to elucidate the possible mechanisms and explore the effects in different clinical subgroups.

  19. The harm argument against surrogacy revisited: two versions not to forget.

    Agnafors, Marcus

    2014-08-01

    It has been a common claim that surrogacy is morally problematic since it involves harm to the child or the surrogate-the harm argument. Due to a growing body of empirical research, the harm argument has seen a decrease in popularity, as there seems to be little evidence of harmful consequences of surrogacy. In this article, two revised versions of the harm argument are developed. It is argued that the two suggested versions of the harm argument survive the current criticism against the standard harm argument. The first version argues that the child is harmed by being separated from the gestational mother. The second version directs attention to the fact that surrogacy involves great incentives to keep the gestational mother's level of maternal-fetal attachment low, which tend to increase the risk of harm to the child. While neither of the two arguments is conclusive regarding the moral status of surrogacy, both constitute important considerations that are often ignored.

  20. An index of harm for comparing occupational risks

    Schaaf, E.; Hennig, J.; Schnadt, H.; Becker, G.

    1986-03-01

    An index of harm is presented describing the health hazards of persons occupationally exposed to ionizing radiation, for comparison with occupational risks in conventional working areas. The criterion for evaluating injuries is the remaining lifetime affected by chronic damage. The affected years of life themselves are evaluated in a scheme considering the degree of reduced ability to work. The index of harm is based on an evaluation of a data pool collected by all F.R.G. associations for social insurance against occupational accidents, which recorded all data of first compensation for accidents. The index can be taken into consideration for assessment of risks emanating from ionizing radiation, and for evaluating the radiation protection currently provided by maximum permissible limits, etc. (DG) [de

  1. Oceans and Human Health: Microplastics and Harmful Algal Bloom

    Sombrito, Elvira Z.

    2015-01-01

    Traditionally the focus of research and concern of environmental studies in the marine system is the impact of human activities in the ocean: the sources, distribution and fate of pollutants resulting from human activities. More recently, there has been recognition of the potential direct impact health can come from eating contaminated seafood, swimming in polluted water, and exposure to toxins from harmful algal blooms. This paper will present two areas of concern that illustrates the fact that the health of the oceans and the health of humans go hand in hand: chemical pollution from plastics in the ocean and harmful alga bloom. The nuclear methodologies than can be useful in these areas will also be introduced. It is hoped that through the recognition of the inter-dependence of the health of both humans and the oceans, efforts will be made to restore and preserve the oceans. (author)

  2. The flaws and human harms of animal experimentation.

    Akhtar, Aysha

    2015-10-01

    Nonhuman animal ("animal") experimentation is typically defended by arguments that it is reliable, that animals provide sufficiently good models of human biology and diseases to yield relevant information, and that, consequently, its use provides major human health benefits. I demonstrate that a growing body of scientific literature critically assessing the validity of animal experimentation generally (and animal modeling specifically) raises important concerns about its reliability and predictive value for human outcomes and for understanding human physiology. The unreliability of animal experimentation across a wide range of areas undermines scientific arguments in favor of the practice. Additionally, I show how animal experimentation often significantly harms humans through misleading safety studies, potential abandonment of effective therapeutics, and direction of resources away from more effective testing methods. The resulting evidence suggests that the collective harms and costs to humans from animal experimentation outweigh potential benefits and that resources would be better invested in developing human-based testing methods.

  3. Investigating the "self" in deliberate self-harm.

    Adams, Joanna; Rodham, Karen; Gavin, Jeff

    2005-12-01

    In this study, the authors explored how a group of young people aged 16 to 26 years (who identified themselves as having engaged in deliberate self-harm) made sense of the self by conducting two online focus groups and four e-mail interviews. They analyzed data using interpretive phenomenological analysis. The concept of validation was the primary means of making sense of the self and concerned the desire to be considered legitimate and of worth. This desire was clearly evident across three realms of conflict: (a) the intrinsic or extrinsic self, which marked the distinction between objective fact and subjective opinion; (b) the accepted or denied self; and (c) the notion of normality. It is possible that having one's denied self validated online might lead to an exacerbation of an individual's self-harming behavior. Further work is needed to explore the effects of online discussion forums on such taboo forms of behavior.

  4. Trends in self-harm in Kuala Lumpur, 2005–2011

    Armitage, Christopher J.; Abdul Rahim, Wirda; Rowe, Richard; O'Connor, Rory C.

    2016-01-01

    Acts of self-harm are not routinely tracked in Malaysia. The present study investigates the prevalence of self-harm in Kuala Lumpur, Malaysia, over a 7-year period. The aims were to: (a) assess the prevalence of self-harm; (b) examine any changes over a period of 7 years, and (c) identify correlates of methods of self-harm. Data were extracted from the hospital records of Kuala Lumpur Hospital to review trends in self-harm between 2005 and 2011. There were 918 episodes of self-harm across the...

  5. Beneficial and Harmful Agile Practices for Product Quality

    Theobald, Sven; Diebold, Philipp

    2017-01-01

    There is the widespread belief that Agile neglects the product quality. This lack of understanding how Agile processes assure the quality of the product prevents especially companies from regulated domains from an adoption of Agile. This work aims to identify which Agile Practices contribute towards product quality. Hence, data from a survey study is analyzed to identify Ag-ile Practices which are beneficial or harmful for the quality of the product. From 49 practices that were used in the su...

  6. Optimal Advertising When Envisioning a Product-Harm Crisis

    Olivier Rubel; Prasad A. Naik; Shuba Srinivasan

    2011-01-01

    How should forward-looking managers plan advertising if they envision a product-harm crisis in the future? To address this question, we propose a dynamic model of brand advertising in which, at each instant, a nonzero probability exists for the occurrence of a crisis event that damages the brand's baseline sales and may enhance or erode marketing effectiveness when the crisis occurs. Because managers do not know when the crisis will occur, its random time of occurrence induces a stochastic co...

  7. Students as effective harm reductionists and needle exchange organizers.

    Barbour, Kyle; McQuade, Miriam; Brown, Brandon

    2017-03-17

    Needle exchange programs are safe, highly effective programs for promoting health among people who inject drugs. However, they remain poorly funded, and often illegal, in many places worldwide due to fear and stigma surrounding drug use. Continued advocacy, education, and implementation of new needle exchanges are thus essential to improve public health and reduce structural inequality. We argue that students, and especially professional and graduate students, have the potential to play an important role in advancing harm reduction. Students benefit from the respect given to the professions they are training to enter, which gives them leverage to navigate the political hurdles often faced by needle exchange organizers, especially in areas that presently lack services. In addition, due to their relative simplicity, needle exchanges do not require much of the licensing, clinical knowledge, and infrastructure associated with more traditional student programs, such as student-run free medical clinics. Students are capable of learning harm reduction cultural approaches and techniques if they remain humble, open-minded, and seek the help of the harm reduction community. Consequently, students can generate tremendous benefits to their community without performing beyond their appropriate clinical limitations. Students benefit from organizing needle exchanges by gaining applied experience in advocacy, organization-building, and political finesse. Working in a needle exchange significantly helps erode stigma against multiple marginalized populations. Students in health-related professions additionally learn clinically-relevant knowledge that is often lacking from their formal training, such as an understanding of structural violence and inequality, root causes of substance use, client-centered approaches to health services, and interacting with clients as peers, rather than through the standard hierarchical medical interaction. We therefore encourage students to learn about

  8. Analysis and control of harmful emissions from combustion processes

    Jafari, Ahmad

    2000-01-01

    This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University. The harmful effects of air pollutants on human beings and environment have been the major reason for efforts in sampling, analysis and control of their sources. The major pollutants emitted to atmosphere from stationary combustion processes are nitrogen oxides, inorganic acids, carbon dioxide, carbon monoxide, hydrocarbon and soot. In the current work two methods are developed for sampl...

  9. Fighting Harmful Tax Competition Generated by Offshore Jurisdictions

    Dan Drosu Saguna

    2015-03-01

    Full Text Available Harmful tax competition is not just tax system, but can also undermine the interests of local communities and the environment. Tax havens are a huge drain of resources from other countries (basic non tax haven to offshore areas. To operate, tax havens are supported economically, politically, and socially by high tax states. Also, by encouraging savings, it boosts investment and capital formation. Because they are low tax jurisdictions, they exert a higher tax on tax rates worldwide.

  10. The cost of harmful alcohol use in South Africa

    Matzopoulos, R G; Truen, S; Bowman, B; Corrigall, J

    2014-01-01

    BACKGROUND: The economic, social and health costs associated with alcohol-related harms are important measures with which to inform alcohol management policies and laws. This analysis builds on previous cost estimates for South Africa. METHODS: We reviewed existing international best-practice costing frameworks to provide the costing definitions and dimensions. We sourced data from South African costing literature or, if unavailable, estimated costs using socio-economic and health data from s...

  11. The scientific foundation for tobacco harm reduction, 2006-2011

    Rodu, Brad

    2011-01-01

    Abstract Over the past five years there has been exponential expansion of interest in tobacco harm reduction (THR), with a concomitant increase in the number of published studies. The purpose of this manuscript is to review and analyze influential contributions to the scientific and medical literature relating to THR, and to discuss issues that continue to stimulate debate. Numerous epidemiologic studies and subsequent meta-analyses confirm that smokeless tobacco (ST) use is associated with m...

  12. SELF-HARM AS A SIGN OF STAGING CRIMINAL EVENTS

    Vitaly Fadeev

    2015-12-01

    Full Text Available The article considers the problems of conducting investigative activities related to the dramatization of a criminal event, characterized by the application of self-harm to induce the employee of a consequence of misconceptions about the criminal event. At the same time, there is a need to study places of alleged crimes with the help of modern techniques and information technologies that enable more detail to model events.

  13. ICHTHYOLOGICAL ASPECTS OF THE MATERIALITITY HARM TO FISHERIES DETERMINING

    І. Нrytsyniak; А. Chuklin; І. Buzevych

    2013-01-01

    Purpose. Definition and analysis of biological criteria for qualified materiality harm caused by the fishing industry as a result of illegal extraction of water biological resources. Methodology. The calculations were carried out for the top of the Kanev reservoir and were based on data from the Water of Life reserves the Kanev reservoir identified Institute of Fisheries NAAS within acceptable elaboration of industrial catches for 2013 year. Index of an average natural mortality were dete...

  14. Fasting: Benefits and probable health harmfulness from the Islamic perspective

    Mahdi Ebrahimi; Saeedeh Behrooznia

    2015-01-01

    Fasting is a form of Islamic worship to approach God.  There is a direct relationship between fasting, abstaining from eating and drinking, and an individual’s health as well as his ill-health. Therefore, it is of utmost importance in the Islamic perspective to weigh the spiritual benefits achieved through fasting against its probable harmfulness to an individual’s health. Regarding fasting, the Islamic perspective is based on spiritual and social goals whose achievement centers around fas...

  15. Youth Justice staff attitudes towards screening for self-harm.

    Knowles, Sarah E; Townsend, Ellen; Anderson, Martin P

    2012-09-01

    Young offenders are recognised as a high-risk group for suicidal behaviour. It is essential that the screening used to identify those at risk and refer them to mental health services is effective, especially in community settings where service utilisation is low. Staff attitudes towards screening for suicide and self-harm are likely to influence how a young offender engages with the screening process. Our study is the first to explore community youth justice staff attitudes towards, and perceptions of, screening for self-harmful behaviour. Eight semi-structured interviews were conducted at an English Youth Offending Team in June 2006 with staff who had used the suicide screening tool with young offenders. Data were analysed using Interpretative Phenomenological Analysis. Staff attitudes towards working within the screening system varied along two dimensions. The first 'active/passive' dimension related to perceived confidence in dealing with self-harm. The second 'positive/negative' dimension related to perceptions of the benefits of screening and the effectiveness of mental health provision for young offenders. Results indicate that barriers to effective screening must be tackled at both individual and organisational levels. The model of attitudes presented here could be used to increase understanding of how staff can be supported to engage effectively with the screening system. © 2012 Blackwell Publishing Ltd.

  16. The politics of harm reduction in federal prisons.

    Watson, Tara Marie

    2014-09-01

    We need to understand better the political barriers to prison-based harm reduction programs. In this paper, I examine the situation in the Correctional Service of Canada (CSC), a federal prison agency with a zero-tolerance drug policy and general opposition to prison needle and syringe programs (PNSPs) and safer tattooing initiatives. This study draws on 16 interviews with former CSC senior officials, former frontline staff, and external stakeholders; CSC policy and practice documents; and testimony from a House of Commons Standing Committee public study. Thematic coding and comparison of texts were used to examine emergent themes of interest. Four interrelated issues were central for understanding the political barriers: a narrower definition of harm reduction used in corrections, both in principle and practice; the Conservative government's tough-on-crime agenda; strong union opposition; and stakeholder perceptions that political constraints will likely persist, including the view that litigation may offer the only way to introduce PNSPs. The system is at an impasse and key questions remain about the importability of harm reduction services into federal prisons. Despite a highly challenging policy environment, moving forward will demand asking new, critical questions and devising more strategic ways of entering the political-operational dialogue that opposes evidence-based programs. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Income inequality and alcohol attributable harm in Australia

    Chikritzhs Tanya N

    2009-02-01

    Full Text Available Abstract Background There is little research on the relationship between key socioeconomic variables and alcohol related harms in Australia. The aim of this research was to examine the relationship between income inequality and the rates of alcohol-attributable hospitalisation and death at a local-area level in Australia. Method We conducted a cross sectional ecological analysis at a Local Government Area (LGA level of associations between data on alcohol caused harms and income inequality data after adjusting for socioeconomic disadvantage and remoteness of LGAs. The main outcome measures used were matched rate ratios for four measures of alcohol caused harm; acute (primarily related to the short term consequences of drinking and chronic (primarily related to the long term consequences of drinking alcohol-attributable hospitalisation and acute and chronic alcohol-attributable death. Matching was undertaken using control conditions (non-alcohol-attributable at an LGA level. Results A total of 885 alcohol-attributable deaths and 19467 alcohol-attributable hospitalisations across all LGAs were available for analysis. After weighting by the total number of cases in each LGA, the matched rate ratios of acute and chronic alcohol-attributable hospitalisation and chronic alcohol-attributable death were associated with the squared centred Gini coefficients of LGAs. This relationship was evident after adjusting for socioeconomic disadvantage and remoteness of LGAs. For both measures of hospitalisation the relationship was curvilinear; increases in income inequality were initially associated with declining rates of hospitalisation followed by large increases as the Gini coefficient increased beyond 0.15. The pattern for chronic alcohol-attributable death was similar, but without the initial decrease. There was no association between income inequality and acute alcohol-attributable death, probably due to the relatively small number of these types of death

  18. Self-harm - an overview of the tools used to assess non-suicidal self-harming behaviors

    Drzał-Fiałkiewcz Ewelina

    2017-12-01

    Full Text Available Introduction: Non-Suicidal Self-Injury (NSSI is the deliberate injury to one’s own body intended to cause mental or physical harm to oneself. In view of the growing scale of the NSSI, especially among young people without identifying any other psychiatric disorders, the disorder was included in both DSM-5 and ICD10 as independent diagnostic entity. Many etiopathogenetic hypotheses and research tools assessing various aspects of NSSI have been developed.

  19. Small Area Estimate Maps: Is a Hookah Less Harmful? - Small Area Estimates

    This metric is defined as a person 18 years of age or older who must have reported that he/she thinks that smoking tobacco using a hookah is less harmful or much less harmful compared to smoking cigarettes.

  20. Children's Moral Judgments as a Function of Intention, Damage, and an Actor's Physical Harm.

    Suls, Jerry; Kalle, Robert J.

    1979-01-01

    Examines children's moral judgments of story characters who accidently harm themselves. Children in kindergarten and in grades 3 and 5 rated actors in stories which varied in terms of intention, damage, and harm to the actor. (SS)

  1. Recommended next care following hospital-treated self-harm: Patterns and trends over time.

    Arensman, Ella

    2018-01-01

    The specific objectives of this study were to examine variation in the care of self-harm patients in hospital settings and to identify the factors that predict recommended next care following self-harm.

  2. Self harm and attempted suicide in adults: 10 practical questions and answers for emergency department staff

    Mitchell, A J; Dennis, M

    2006-01-01

    Self harm is a complex behaviour that can be best thought of as a maladaptive response to acute and chronic stress, often but not exclusively linked with thoughts of dying. Patients presenting with self harm usually have current psychosocial difficulties, are likely to be suffering from mental health problems, and are at significant risk of further self harm and suicide. Recent guidelines suggest that all self harm attendees should receive an initial risk assessment at triage in the emergency...

  3. Integrative harm reduction psychotherapy: a case of substance use, multiple trauma, and suicidality.

    Tatarsky, Andrew; Kellogg, Scott

    2010-02-01

    Harm reduction is a new paradigm that seeks to reduce the harmful consequences of substance use and other risky behaviors without requiring abstinence. This article discusses integrative harm reduction psychotherapy, one application of harm reduction principles to psychotherapy. Seven therapeutic tasks are described with attention to clinical process, skills, and strategies. A case is presented that illustrates the application of this approach with life-threatening substance use that was related to multiple trauma and suicidal depression. (c) 2010 Wiley Periodicals, Inc.

  4. Two sides to the story: Adolescent and parent views on harmful intention in defining school bullying.

    Thomas, Hannah J; Connor, Jason P; Baguley, Chantelle M; Scott, James G

    2017-07-01

    Bullying is defined as repeated negative actions involving a power differential, and intention to harm. There is limited research on harmful intention as a definitional component. This study explored the role of the perpetrator's harmful intention and the target's perception of harmful intention. Some 209 students (M = 14.5 years; 66.5% female) and 447 parents (M = 46.4 years; 86.4% female) were randomly assigned in an online survey. Participants assessed the likelihood of bullying in five hypothetical scenarios (physical, verbal, rumor, exclusion, and cyber) across five intention conditions, that also involved repetition and a power differential. The five intention conditions were: 1) harm intended by perpetrator (I) and perceived as intended to harm by target (I) [II condition]; 2) harm not intended by perpetrator (N) but perceived as intended to harm by target (I) [NI condition]; 3) harm intended by perpetrator (I) but not perceived as intended to harm by target (N) [IN condition]; 4) harm not intended by perpetrator (N) and not perceived as intended to harm by target N [NN condition]; and 5) a control which did not state any actual or perceived harmful intention [C condition]. For students and parents, the perpetrator's harmful intention and the target's perception of harmful intention were important when considering whether a peer interaction constituted bullying. These findings confirm the applicability of the three-part definition of bullying, and highlight the importance of assessing these two dimensions of harmful intention when determining whether a problematic peer interaction should be regarded as bullying. Aggr. Behav. 43:352-363, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. Psychological characteristics, stressful life events and deliberate self-harm: findings from the Child & Adolescent Self-harm in Europe (CASE) Study.

    Madge, Nicola; Hawton, Keith; McMahon, Elaine M; Corcoran, Paul; De Leo, Diego; de Wilde, Erik Jan; Fekete, Sandor; van Heeringen, Kees; Ystgaard, Mette; Arensman, Ella

    2011-10-01

    There is evidence to suggest that both psychological characteristics and stressful life events are contributory factors in deliberate self-harm among young people. These links, and the possibility of a dose-response relationship between self-harm and both psychological health and life events, were investigated in the context of a seven-country school-based study. Over 30,000, mainly 15 and 16 year olds, completed anonymous questionnaires at secondary schools in Belgium, England, Hungary, Ireland, the Netherlands, Norway and Australia. Pupils were asked to report on thoughts and episodes of self-harm, complete scales on depression and anxiety symptoms, impulsivity and self-esteem and indicate stressful events in their lives. Level and frequency of self-harm was judged according to whether they had thought about harming themselves or reported single or multiple self-harm episodes. Multinomial logistic regression assessed the extent to which psychological characteristics and stressful life events distinguished between adolescents with different self-harm histories. Increased severity of self-harm history was associated with greater depression, anxiety and impulsivity and lower self-esteem and an increased prevalence of all ten life event categories. Female gender, higher impulsivity and experiencing the suicide or self-harm of others, physical or sexual abuse and worries about sexual orientation independently differentiated single-episode self-harmers from adolescents with self-harm thoughts only. Female gender, higher depression, lower self-esteem, experiencing the suicide or self-harm of others, and trouble with the police independently distinguished multiple- from single-episode self-harmers. The findings reinforce the importance of psychological characteristics and stressful life events in adolescent self-harm but nonetheless suggest that some factors are more likely than others to be implicated.

  6. Environments, risk and health harms: a qualitative investigation into the illicit use of anabolic steroids among people using harm reduction services in the UK

    Kimergård, Andreas; McVeigh, Jim

    2014-01-01

    Objectives The illicit use of anabolic steroids among the gym population continues to rise, along with the number of steroid using clients attending harm reduction services in the UK. This presents serious challenges to public health. Study objectives were to account for the experiences of anabolic steroid users and investigate how ‘risk environments’ produce harm. Methods Qualitative face-to-face interviews with 24 users of anabolic steroids engaged with harm reduction services in the UK. Re...

  7. Impact of the recent recession on self-harm: Longitudinal ecological and patient-level investigation from the Multicentre Study of Self-harm in England.

    Hawton, Keith; Bergen, Helen; Geulayov, Galit; Waters, Keith; Ness, Jennifer; Cooper, Jayne; Kapur, Navneet

    2016-02-01

    Economic recessions are associated with increases in suicide rates but there is little information for non-fatal self-harm. To investigate the impact of the recent recession on rates of self-harm in England and problems faced by patients who self-harm. Analysis of data from the Multicentre Study of Self-harm in England for 2001-2010 and local employment statistics for Oxford, Manchester and Derby, including interrupted time series analyses to estimate the effect of the recession on rates of self-harm. Rates of self-harm increased in both genders in Derby and in males in Manchester in 2008-2010, but not in either gender in Oxford, results which largely followed changes in general population unemployment. More patients who self-harm were unemployed in 2008-10 compared to before the recession. The proportion in receipt of sickness or disability allowances decreased. More patients of both genders had employment and financial problems in 2008-2010 and more females also had housing problems, changes which were also largely found in employed patients. We have assumed that the recession began in 2008 and information on problems was only available for patients having a psychosocial assessment. Increased rates of self-harm were found in areas where there were greater rises in rates of unemployment. Work, financial and housing problems increased in people who self-harmed. Changes in welfare benefits may have contributed. None. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. 46 CFR 4.03-65 - Significant harm to the environment.

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Significant harm to the environment. 4.03-65 Section 4... MARINE CASUALTIES AND INVESTIGATIONS Definitions § 4.03-65 Significant harm to the environment. Significant harm to the environment means— (a) In the navigable waters of the United States, a discharge of...

  9. Children's Impact on Adults' Substance Use Problem Awareness and Treatment Optimism: The Role of Harm

    Droege, Jocelyn R.; Stevens, Edward B.; Jason, Leonard A.

    2015-01-01

    Substance abuse is associated with a host of harmful consequences to the substance user as well as other individuals and society as a whole. Although harm is an integral component of substance abuse, there is a dearth of research that investigates the relationship between harm and substance use problems. The goal of this study was to explore…

  10. Applying Dialectical Behavior Therapy to Self-Harm in College-Age Men: A Case Study

    Cannon, Jennifer L.; Umstead, Lindsey K.

    2018-01-01

    Researchers suggest an increase in self-harm among men. Specifically, college-age men appear to be at risk for self-harming behaviors, and counselors often overlook these behaviors in treatment. In this article, the authors describe the issue of self-harm and illustrate the use of dialectical behavior therapy (DBT; Linehan, 2014) with male college…

  11. Explaining Self-Harm: Youth Cybertalk and Marginalized Sexualities and Genders

    McDermott, Elizabeth; Roen, Katrina; Piela, Anna

    2015-01-01

    This study investigates self-harm among young lesbian, gay, bisexual, and trans (LGBT) people. Using qualitative virtual methods, we examined online forums to explore young LGBT people's cybertalk about emotional distress and self-harming. We investigated how youth explained the relationship between self-harm and sexuality and gender. We found…

  12. Negative Intrusive Thoughts and Dissociation as Risk Factors for Self-Harm

    Batey, Helen; May, Jon; Andrade, Jackie

    2010-01-01

    Relationships between self-harm and vulnerability factors were studied in a general population of 432 participants, of whom 30% reported some experience of self-harm. This group scored higher on dissociation and childhood trauma, had lower self-worth, and reported more negative intrusive thoughts. Among the non-harming group, 10% scored similarly…

  13. Ranking the harm of non-medically used prescription opioids in the UK

    van Amsterdam, Jan; Phillips, Lawrence; Henderson, Graeme; Bell, James; Bowden-Jones, Owen; Hammersley, Richard; Ramsey, John; Taylor, Polly; Dale-Perera, Annette; Melichar, Jan; van den Brink, Wim; Nutt, David

    2015-01-01

    A panel of nine experts applied multi-criteria decision analysis (MCDA) to determine the relative overall harm to users and harms to others of street heroin (injected and smoked) and eleven non-medically used prescription opioids. The experts assessed harm scores for each of the 13 opioids on each

  14. Assessing the tobacco harm reduction (THR debate: a systematic review

    Yogi Hendlin

    2018-03-01

    Full Text Available Background Tobacco Harm Reduction (THR has become synonymous with substituting alternative tobacco products for cigarettes. However, there exists much dissension among tobacco control professionals regarding accepting harm reduction methods prolonging nicotine addiction and profiting the tobacco, e-cigarette and pharmaceutical industries. We evaluate the influence of these industries on the academic THR literature and debate. Methods We undertook a comprehensive review of all peer-review papers published on the topic of tobacco harm reduction between 1992 and July 2016. Our initial search yielded 5,172 relevant hits, and after screening, we double-coded 1,067 full-text articles. Codes include the article's stand on THR (weakly or strongly pro-, anti-, or neutral/mixed, major themes, product type, country of author origin, article type (letter/commentary, RTC, longitudinal study, etc., journal quality, and funding source. These results were analyzed in STATA. Results Of the 498 articles we have coded so far, 379 were included. The results show that six percent of all articles are editorials, 36% letters or commentaries, and 21% are non-empirical articles while only 31% are original research and 6% reviews. Thirty-three percent of pro-THR articles disclosed some sort of industry funding. Of these, 30% were funded by the tobacco industry, 22% by the E-cigarette industry and 48% were funded by pharmaceutical industries. Conclusions The THR debate has been influenced by scientists funded by tobacco, electronic-cigarette and surprisingly pharmaceutical industries in the favor of product substitution. Moreover, the majority of this debate is occurring over 'opinion pieces' rather than on the basis of empirical research. Thus, more robust and unbiased scientific evidence is needed to evaluate these alternative products before endorsing them for the public.

  15. Harms of prescription opioid use in the United States.

    Imtiaz, Sameer; Shield, Kevin D; Fischer, Benedikt; Rehm, Jürgen

    2014-10-27

    Consumption levels of prescription opioids (POs) have increased substantially worldwide, particularly the United States. An emerging perspective implicates increasing consumption levels of POs as the primary system level driving factor behind the observed PO-related harms. As such, the present study aimed to assess the correlations between consumption levels of POs and PO-related harms, including non-medical prescription opioid use (NMPOU), PO-related morbidity and PO-related mortality. Pearson's product-moment correlations were computed using published data from the United States (2001 - 2010). Consumption levels of POs were extracted from the technical reports published by the International Narcotics Control Board, while data for NMPOU was utilized from the National Survey on Drug Use and Health. Additionally, data for PO-related morbidity (substance abuse treatment admissions per 10,000 people) and PO-related mortality (PO overdose deaths per 100,000 people) were obtained from published studies. Consumption levels of POs were significantly correlated with prevalence of NMPOU in the past month (r =0.741, 95% CI =0.208-0.935), past year (r =0.638, 95% CI =0.014-0.904) and lifetime (r =0.753, 95% CI =0.235-0.938), as well as average number of days per person per year of NMPOU among the general population (r =0.900, 95% CI =0.625-0.976) and NMPOU users (r =0.720, 95% CI =0.165-0.929). Similar results were also obtained for PO-related morbidity and PO-related mortality measures. These findings suggest that reducing consumption levels of POs at the population level may be an effective strategy to limit PO-related harms.

  16. E-cigarettes in pregnancy: reducing or introducing harm?

    Weighall, Jaydene; Wilbraham, Susan

    2016-01-01

    Electronic cigarettes use has become increasingly prevalent with around 17.6% of population using these products. The serious harm to health caused by cigarette smoke is well publicised, and government advice has promoted the message that e-cigarettes are 95% safer; however e-cigarettes are not risk free. Given the high prevalence of e-cigarette usage, pregnant women are likely to look to midwives for guidance on whether e-cigarettes are safe, however advice to midwives is inconsistent. The c...

  17. Managing young people with self-harming or suicidal behaviour.

    Fisher, Gemma

    2016-02-01

    This literature review aimed to determine the risk factors being used to identify children and young people who are at increased risk of engaging in self-harm and suicidal behaviour, so that optimal care can be provided for this patient group in children's medical ward settings. The two main themes that emerged were mental and neurodevelopmental disorders, and external factors. Management strategies to aid healthcare professionals in caring for this patient group were also identified. The review concludes by highlighting the need to provide healthcare professionals with continuing education about the mental health problems of children and young people, including risk factors and management strategies.

  18. Intensification of sewage treatment processes from harmful substances

    Asadov, S.M.

    2007-01-01

    Full text: Intensive development of power, chemical, oil, machine-building and other industries results in increase of industrial toxic emissions. Local pollutions as a result of emissions of the industrial enterprises in many cases surpass the maximum permissible sanitary norms. E.g. works connected to an oil recovery, have led to pollution of huge territories of the Azerbaijan Republic, including Caspian Sea. Development of scientific bases of optimization of operating practices of industrial sewage treatment will allow to liquidate the harmful impurities. It is necessary for preservation of the environment to increase the clearing and sewage quality degree. During modeling a real process of sewage treatment from polluting impurities we need to build more and more complex models. It demands in return the application of applied mathematics methods for process of clearing of liquids. General theory and technology of sewage treatment, in particular, from heavy metals, radioactive nuclides now are absent. Achievement of an object provides for solution of the following problems: a) Research of laws of influence of various technological and physical and chemical parameters on efficiency of waste treatment from heavy metals and radioactive nuclides; b) Development of the effective reagents, allowing to remove from sewage cations of toxic heavy metals and radioactive nuclides; c) Construction of statistical models of an experimental material on clearing concrete sewage; d) Modeling of searches of optimum modes of sewage treatment processes from heavy metals ions; e) Development of optimum processes of sewage treatment from toxic heavy metals ions. The mentioned above problems are scantily studied both in experimental, and in the theoretical point of view. Expected scientific novelty of the offered project can be made in the following: Technological modes of carrying out of deep clearing processes of real sewage from toxic impurities, in particular from heavy metals ions

  19. Tobacco harm reduction: an alternative cessation strategy for inveterate smokers

    Godshall William T

    2006-12-01

    Full Text Available Abstract According to the Centers for Disease Control and Prevention, about 45 million Americans continue to smoke, even after one of the most intense public health campaigns in history, now over 40 years old. Each year some 438,000 smokers die from smoking-related diseases, including lung and other cancers, cardiovascular disorders and pulmonary diseases. Many smokers are unable – or at least unwilling – to achieve cessation through complete nicotine and tobacco abstinence; they continue smoking despite the very real and obvious adverse health consequences. Conventional smoking cessation policies and programs generally present smokers with two unpleasant alternatives: quit, or die. A third approach to smoking cessation, tobacco harm reduction, involves the use of alternative sources of nicotine, including modern smokeless tobacco products. A substantial body of research, much of it produced over the past decade, establishes the scientific and medical foundation for tobacco harm reduction using smokeless tobacco products. This report provides a description of traditional and modern smokeless tobacco products, and of the prevalence of their use in the United States and Sweden. It reviews the epidemiologic evidence for low health risks associated with smokeless use, both in absolute terms and in comparison to the much higher risks of smoking. The report also describes evidence that smokeless tobacco has served as an effective substitute for cigarettes among Swedish men, who consequently have among the lowest smoking-related mortality rates in the developed world. The report documents the fact that extensive misinformation about ST products is widely available from ostensibly reputable sources, including governmental health agencies and major health organizations. The American Council on Science and Health believes that strong support of tobacco harm reduction is fully consistent with its mission to promote sound science in regulation and in

  20. Self-harm in British South Asian women: psychosocial correlates and strategies for prevention

    Waheed W; Husain MI; Husain Nusrat

    2006-01-01

    Abstract Objective To review the rates of self-harm in British South Asian women, look into the factors that contribute to these high rates of self-harm and discuss possible strategies for prevention and provision of culturally sensitive service for South Asian women who harm themselves. Method Review. Results South Asian women are significantly more likely to self harm between ages 16–24 years than white women. Across all age groups the rates of self harm are lower in South Asian men as comp...

  1. Harm reduction psychotherapy: extending the reach of traditional substance use treatment.

    Tatarsky, Andrew

    2003-12-01

    Harm reduction is a paradigm-shifting idea that has the potential to significantly improve the treatment of problem substance users. The essence of harm reduction is the recognition that treatment must start from the client's needs and personal goals and that all change that reduces the harms associated with substance use can be regarded as valuable. The paper presents harm reduction's rationale, principles, treatment implications, and application to psychotherapy. The author describes his model of Integrative Harm Reduction Psychotherapy, an approach that integrates a strategic skills-building focus with an exploration of the multiple meanings of substance use and the importance of the therapeutic alliance.

  2. Insulin does not stimulate muscle protein synthesis during increased plasma branched-chain amino acids alone but still decreases whole body proteolysis in humans.

    Everman, Sarah; Meyer, Christian; Tran, Lee; Hoffman, Nyssa; Carroll, Chad C; Dedmon, William L; Katsanos, Christos S

    2016-10-01

    Insulin stimulates muscle protein synthesis when the levels of total amino acids, or at least the essential amino acids, are at or above their postabsorptive concentrations. Among the essential amino acids, branched-chain amino acids (BCAA) have the primary role in stimulating muscle protein synthesis and are commonly sought alone to stimulate muscle protein synthesis in humans. Fourteen healthy young subjects were studied before and after insulin infusion to examine whether insulin stimulates muscle protein synthesis in relation to the availability of BCAA alone. One half of the subjects were studied in the presence of postabsorptive BCAA concentrations (control) and the other half in the presence of increased plasma BCAA (BCAA). Compared with that prior to the initiation of the insulin infusion, fractional synthesis rate of muscle protein (%/h) did not change (P > 0.05) during insulin in either the control (0.04 ± 0.01 vs 0.05 ± 0.01) or the BCAA (0.05 ± 0.02 vs. 0.05 ± 0.01) experiments. Insulin decreased (P BCAA (0.89 ± 0.07 vs 0.61 ± 0.03) experiments, but the change was not different between the two experiments (P > 0.05). In conclusion, insulin does not stimulate muscle protein synthesis in the presence of increased circulating levels of plasma BCAA alone. Insulin's suppressive effect on proteolysis is observed independently of the levels of circulating plasma BCAA. Copyright © 2016 the American Physiological Society.

  3. Spatiotemporally regulated proteolysis to dissect the role of vegetative proteins during Bacillus subtilis sporulation: cell-specific requirement of σH and σA.

    Riley, Eammon P; Trinquier, Aude; Reilly, Madeline L; Durchon, Marine; Perera, Varahenage R; Pogliano, Kit; Lopez-Garrido, Javier

    2018-04-01

    Sporulation in Bacillus subtilis is a paradigm of bacterial development, which involves the interaction between a larger mother cell and a smaller forespore. The mother cell and the forespore activate different genetic programs, leading to the production of sporulation-specific proteins. A critical gap in our understanding of sporulation is how vegetative proteins, made before sporulation initiation, contribute to spore formation. Here we present a system, spatiotemporally regulated proteolysis (STRP), which enables the rapid, developmentally regulated degradation of target proteins, thereby providing a suitable method to dissect the cell- and developmental stage-specific role of vegetative proteins. STRP has been used to dissect the role of two major vegetative sigma factors, σ H and σ A , during sporulation. The results suggest that σ H is only required in predivisional cells, where it is essential for sporulation initiation, but that it is dispensable during subsequent steps of spore formation. However, evidence has been provided that σ A plays different roles in the mother cell, where it replenishes housekeeping functions, and in the forespore, where it plays an unexpected role in promoting spore germination and outgrowth. Altogether, the results demonstrate that STRP has the potential to provide a comprehensive molecular dissection of every stage of sporulation, germination and outgrowth. © 2018 John Wiley & Sons Ltd.

  4. Age-related differences in lean mass, protein synthesis and skeletal muscle markers of proteolysis after bed rest and exercise rehabilitation.

    Tanner, Ruth E; Brunker, Lucille B; Agergaard, Jakob; Barrows, Katherine M; Briggs, Robert A; Kwon, Oh Sung; Young, Laura M; Hopkins, Paul N; Volpi, Elena; Marcus, Robin L; LaStayo, Paul C; Drummond, Micah J

    2015-09-15

    Bed rest-induced muscle loss and impaired muscle recovery may contribute to age-related sarcopenia. It is unknown if there are age-related differences in muscle mass and muscle anabolic and catabolic responses to bed rest. A secondary objective was to determine if rehabilitation could reverse bed rest responses. Nine older and fourteen young adults participated in a 5-day bed rest challenge (BED REST). This was followed by 8 weeks of high intensity resistance exercise (REHAB). Leg lean mass (via dual-energy X-ray absorptiometry; DXA) and strength were determined. Muscle biopsies were collected during a constant stable isotope infusion in the postabsorptive state and after essential amino acid (EAA) ingestion on three occasions: before (PRE), after bed rest and after rehabilitation. Samples were assessed for protein synthesis, mTORC1 signalling, REDD1/2 expression and molecular markers related to muscle proteolysis (MURF1, MAFBX, AMPKα, LC3II/I, Beclin1). We found that leg lean mass and strength decreased in older but not younger adults after bedrest (P protein synthesis increased before bed rest in both age groups (P protein synthesis rates and increased MAFBX mRNA, p-AMPKα and the LC3II/I ratio (P protein synthesis and a marginal increase in proteolytic markers. Finally, rehabilitation restored bed rest-induced deficits in lean mass and strength in older adults. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  5. Limited proteolysis combined with isotope labeling and quantitative LC-MALDI MS for monitoring protein conformational changes: a study on calcium-binding sites of cardiac Troponin C

    McDonald, Chris; Li Liang

    2005-01-01

    Studies of protein-protein and protein-ligand interactions are important for understanding biological functions of proteins. A new technique based on the partial proteolysis of proteins combined with quantitative mass spectrometry is developed as a means of tracking structural changes after the formation of a protein-ligand complex. In this technique, a protein of interest with and without the binding of a ligand is digested with an enzyme to generate a set of peptides, followed by separation of the peptides by liquid chromatography. Matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS) is used to identify chromatographically separated peptides, and locate their sequence alignments in the parent protein. Using an isotopically labeled protein as a sample against an unlabeled protein standard, quantitative information can be gathered. This overcomes the inherent lack of quantitative capability of MALDI MS. The utility of the technique to investigate protein-ligand interactions is demonstrated in a model system involving calcium binding to cardiac Troponin C (cTnC). Using this technique, the general location of the three calcium-binding sites of cTnC can be determined by using several different enzymes to generate overlapping peptide maps of cTnC

  6. The Role of G-Protein-Coupled Receptor Proteolysis Site Cleavage of Polycystin-1 in Renal Physiology and Polycystic Kidney Disease

    Marie Trudel

    2016-01-01

    Full Text Available Polycystin-1 (PC1 plays an essential role in renal tubular morphogenesis, and PC1 dysfunction causes human autosomal dominant polycystic kidney disease. A fundamental characteristic of PC1 is post-translational modification via cleavage at the juxtamembrane GPCR proteolysis site (GPS motif that is part of the larger GAIN domain. Given the considerable biochemical complexity of PC1 molecules generated in vivo by this process, GPS cleavage has several profound implications on the intracellular trafficking and localization in association with their particular function. The critical nature of GPS cleavage is further emphasized by the increasing numbers of PKD1 mutations that significantly affect this cleavage process. The GAIN domain with the GPS motif therefore represents the key structural element with fundamental importance for PC1 and might be polycystic kidney disease’s (PKD Achilles’ heel in a large spectrum of PKD1 missense mutations. We highlight the central roles of PC1 cleavage for the regulation of its biogenesis, intracellular trafficking and function, as well as its significance in polycystic kidney disease.

  7. Proteolysis of complement factors iC3b and C5 by the serine protease prostate-specific antigen in prostatic fluid and seminal plasma.

    Manning, Michael L; Williams, Simon A; Jelinek, Christine A; Kostova, Maya B; Denmeade, Samuel R

    2013-03-15

    Prostate-specific Ag (PSA) is a serine protease that is expressed exclusively by normal and malignant prostate epithelial cells. The continued high-level expression of PSA by the majority of men with both high- and low-grade prostate cancer throughout the course of disease progression, even in the androgen-ablated state, suggests that PSA has a role in the pathogenesis of disease. Current experimental and clinical evidence suggests that chronic inflammation, regardless of the cause, may predispose men to prostate cancer. The responsibility of the immune system in immune surveillance and eventually tumor progression is well appreciated but not completely understood. In this study, we used a mass spectrometry-based evaluation of prostatic fluid obtained from diseased prostates after removal by radical prostatectomy to identify potential immunoregulatory proteins. This analysis revealed the presence of Igs and the complement system proteins C3, factor B, and clusterin. Verification of these findings by Western blot confirmed the high-level expression of C3 in the prostatic fluid and the presence of a previously uncharacterized C-terminal C3 cleavage product. Biochemical analysis of this C3 cleavage fragment revealed a putative PSA cleavage site after tyrosine-1348. Purified PSA was able to cleave iC3b and the related complement protein C5. These results suggest a previously uncharacterized function of PSA as an immunoregulatory protease that could help to create an environment hospitable to malignancy through proteolysis of the complement system.

  8. Enhancement of 9α-Hydroxy-4-androstene-3,17-dione Production from Soybean Phytosterols by Deficiency of a Regulated Intramembrane Proteolysis Metalloprotease in Mycobacterium neoaurum.

    Xiong, Liang-Bin; Sun, Wan-Ju; Liu, Yong-Jun; Wang, Feng-Qing; Wei, Dong-Zhi

    2017-12-06

    Modification of the sterol catabolism pathway in mycobacteria may result in the accumulation of some valuable steroid pharmaceutical intermediates, such as 9α-hydroxy-4-androstene-3,17-dione (9-OHAD). In previous work, sigma factor D (SigD) was identified as a negative factor of the 9-OHAD production in Mycobacterium neoaurum. Here, the deficiency of rip1 putatively coding for a regulated intramembrane proteolysis metalloprotease (Rip1), which could cleave the negative regulator of SigD (anti-SigD), enhanced the transcription of some key genes (choM1, kshA, and hsd4A) in the sterol catabolic pathway. Furthermore, the deletion of rip1 increased the consumption of phytosterols by 37.8% after 96 h of growth in M. neoaurum. The production of 9-OHAD in the engineered M. neoaurumΔkstD1ΔkstD2ΔkstD3Δrip1 (MnΔk123Δrip1) strain was ultimately increased by 27.3% compared to that in its parental strain M. neoaurumΔkstD1ΔkstD2ΔkstD3 (MnΔk123). This study further confirms the important role of SigD-related factors in the catabolism of sterols.

  9. Methylated DNMT1 and E2F1 are targeted for proteolysis by L3MBTL3 and CRL4DCAF5 ubiquitin ligase.

    Leng, Feng; Yu, Jiekai; Zhang, Chunxiao; Alejo, Salvador; Hoang, Nam; Sun, Hong; Lu, Fei; Zhang, Hui

    2018-04-24

    Many non-histone proteins are lysine methylated and a novel function of this modification is to trigger the proteolysis of methylated proteins. Here, we report that the methylated lysine 142 of DNMT1, a major DNA methyltransferase that preserves epigenetic inheritance of DNA methylation patterns during DNA replication, is demethylated by LSD1. A novel methyl-binding protein, L3MBTL3, binds the K142-methylated DNMT1 and recruits a novel CRL4 DCAF5 ubiquitin ligase to degrade DNMT1. Both LSD1 and PHF20L1 act primarily in S phase to prevent DNMT1 degradation by L3MBTL3-CRL4 DCAF5 . Mouse L3MBTL3/MBT-1 deletion causes accumulation of DNMT1 protein, increased genomic DNA methylation, and late embryonic lethality. DNMT1 contains a consensus methylation motif shared by many non-histone proteins including E2F1, a key transcription factor for S phase. We show that the methylation-dependent E2F1 degradation is also controlled by L3MBTL3-CRL4 DCAF5 . Our studies elucidate for the first time a novel mechanism by which the stability of many methylated non-histone proteins are regulated.

  10. In Situ Proteolysis for Crystallization of Membrane Bound Cytochrome P450 17A1 and 17A2 Proteins from Zebrafish.

    Lei, Li; Egli, Martin

    2016-04-01

    Fish and human cytochrome P450 (P450) 17A1 catalyze both steroid 17α-hydroxylation and 17α,20-lyase reactions. Fish P450 17A2 catalyzes only 17α-hydroxylation. Both enzymes are microsomal-type P450s, integral membrane proteins that bind to the membrane through their N-terminal hydrophobic segment, the signal anchor sequence. The presence of this N-terminal region renders expression of full-length proteins challenging or impossible. For some proteins, variable truncation of the signal anchor sequence precludes expression or results in poor expression levels. To crystallize P450 17A1 and 17A2 in order to gain insight into their different activities, we used an alternative N-terminal sequence to boost expression together with in situ proteolysis. Key features of our approach to identify crystallizable P450 fragments were the use of an N-terminal leader sequence, a screen composed of 12 proteases to establish optimal cleavage, variations of protease concentration in combination with an SDS-PAGE assay, and analysis of the resulting fragments using Edman sequencing. Described in this unit are protocols for vector preparation, expression, purification, and in situ proteolytic crystallization of two membrane-bound P450 proteins. Copyright © 2016 John Wiley & Sons, Inc.

  11. Are long physician working hours harmful to patient safety?

    Ehara, Akira

    2008-04-01

    Pediatricians of Japanese hospitals including not only residents but also attending physicians work long hours, and 8% work for >79 h per week. Most of them work consecutively for >or=32 h when they are on call. The aim of the present study was to evaluate the effect of long work hours on patient safety. The electronic databases MEDLINE and EMBASE to searched identify the English- and Japanese-language literature for studies on work hours, medical errors, patient safety, and malpractice for years 1966-2005. Studies that analyzed the relationship between physician work hours and outcomes directly related to patient safety were selected. Seven studies met the criteria. Four studies suggest that reduction of work hours has a favorable effect on patient safety indicators. In the other three studies no significant changes of the indicators were observed, but no report found that shorter work hours were harmful to patient safety. Decrease of physician work hours is not harmful but favorable to patient safety.

  12. Ethics of tobacco harm reduction from a liberal perspective.

    van der Eijk, Yvette

    2016-05-01

    Mixed evidence on the possible harms, benefits and usage patterns of electronic nicotine delivery systems (ENDS, or 'e-cigarettes'), has led to vigorous and ongoing debates on the issue. The ethical trade-off often represented is that, though smokers should be permitted access to ENDS as a less harmful alternative to smoking, this comes at the expense of non-smokers and children who may experiment with ENDS, become addicted to them, or experience health issues from long-term exposure to passive ENDS vapour. Lacking from many debates is a balanced analysis based on sound ethical reasoning, so this paper aims to examine the issue from a liberal perspective. More specifically, focus is on how ENDS policy can help to promote freedom in a broader sense, with 'freedom' considered as originating from having options and the necessary information and ability to autonomously choose between these options. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  13. Study supporting the phasing out of environmentally harmful subsidies

    Withana, S.; Ten Brink, P.; Franckx, L.; Hirschnitz-Garbers, M.; Mayeres, I.; Oosterhuis, F.; Porsch, L.

    2012-10-15

    The need to reform ineffective or harmful public subsidies has long been recognised and has been a contentious point of discussion for several years. The EU has a long-standing commitment to removing or phasing out environmentally harmful subsidies (EHS). Most recently, the need to phase out EHS is reiterated in the 'Roadmap for a resource efficient Europe' which includes a milestone that 'by 2020 EHS will be phased out, with due regard to the impact on people in need'. Despite several commitments, progress has been slow and subsidies remain an issue in most EU countries. This study focuses specifically on EHS at the level of EU Member States; it identifies key types of EHS and examines cases of existing EHS across a range of environmental sectors and issues, including subsidies from non-action. The study also analyses examples of good practices in the reform of EHS in EU Member States and the lessons that can be learnt from these cases. Finally, based on this analysis, it develops practical recommendations on phasing out and reforming EHS to support the objectives of the Europe 2020 Strategy and the resource efficiency agenda. The study was carried out between January and October 2012 and is based on an analysis of literature and consultation with experts and policy makers. The sectoral cases studied are listed and discussed in the annexes report: agriculture, climate and energy, fisheries, food, forestry, materials, transport, waste, and water.

  14. Science under pressure: problematic behaviours and social harms

    Rita Faria

    2014-09-01

    Full Text Available This paper will suggest the use of the Social Harm Approach (Hillyard, Pantazis, Tobs & Gordon, 2004 to problematic behaviours occurring in scientific research and higher education teaching. By analyzing data collected through interviews to scholars, it is possible to state that fabrication, falsification and plagiarism are the most criticized deviant behaviours in science. It is less common for actors to consider other problematic behaviours arising from the pressure (to publish, to get grants felt by them and originated at the heart of the organizations devoted to science. Or problematic behaviours created on the intersection of universities, corporations and/or the state (ex. commissioned research. Also, those interviewed did not have a coherent view on the rules governing science and higher education. Thus, considering the scattering of (individual and organizational problematic behaviours and rules governing them, a new approach will be put forward, one by which processes of scientific production and dissemination must be considered according to the social harms (financial, economic, physical they may cause.

  15. Algae as test organisms of harmful effects of various radiations

    Necas, J.

    1989-01-01

    The report describes a complex biotest in which algae serve as the test organisms and where a variety of algal characteristics are employed as indicators of the effects of harmful radiations on the cultures and single organisms. Rules for a successful choice of a suitable algal organism are discussed and the preparation of the latter for the test as well as the growth and morphogenic tests and some physiological responses of algae to harmful radiation are described. The survival and lethality are related to the interpretation of the test results particularly from the physiological and genetic points of view. The complex biotest concerns not only toxic but also mutagenic effects of the factors tested. Some easily detectable mutations in algae are mentioned and their spectra are recommended. The stability of the mutations and the possibility of their delayed manifestation are considered. The possibility of occurrence of teratogenic effects is also dealt with and the negative role of phenocopies in the correct evaluation of the mutation effects is mentioned. Advice for the breeding and laboratory maintenance of suitable algal strains for the biotest is given. Practical use of the biotest is demonstrated on the results of a test using modified samples of waste water from uranium industries. It is recommended that biotests confined to the evaluation of single characteristics of the test organism be replaced by this complex biotest whose results can be interpreted more extensively and exhibit a higher reliability. (author). 268 refs., 1 tab., 9 figs

  16. Suicidal ideation and self-harm following K2 use.

    Thomas, Shannon; Bliss, Sarah; Malik, Mohammed

    2012-11-01

    There is emerging evidence of adverse effects associated with K2 and similar synthetic cannabinoid compounds marketed as herbal alternatives to marijuana. Few studies were identified regarding the psychiatric effects of K2, including suicidal ideation, and to our knowledge none have been written related to self-harm following use of K2. A healthy 20-year-old single Caucasian male with no previous psychiatric diagnoses or treatment was brought by police to the ED with acute agitation, confusion, suicidal ideation, and self-inflicted trauma after smoking K2. Evaluation in the ED was notable for agitation, significant abrasions, respiratory rate of 30, negative UDS, and sinus tachycardia on EKG. Once medically stabilized, he was transferred to the inpatient psychiatric unit for continued monitoring. Upon evaluation on the psychiatric unit the following day, his symptoms had completely resolved, he continued to deny any previous psychiatric history, and was discharged home. K2 and other synthetic cannabinoids have been shown to have significant medical and psychiatric adverse effects and they are still readily available for purchase. Evidence is limited regarding the psychiatric effects; however, synthetic cannabinoid products may potentially lead to suicidal ideation and self-harm behaviors amongst many other psychiatric symptoms.The long-term risks are still unclear, but some studies suggest the possibility of inducing chronic psychotic symptoms and worsening underlying psychiatric illness. Continued research is needed regarding the effects of these substances as well as an increase in public awareness of the risks.

  17. Niche of harmful alga Aureococcus anophagefferens revealed through ecogenomics

    Gobler, C J; Grigoriev, I V; Berry, D L; Dyhrman, S T; Wilhelm, S W; Salamov, A; Lobanov, A V; Zhang, Y; Collier, J L; Wurch, L L; Kustka, A B; Dill, B D; Shah, M; VerBerkomes, N C; Kuo, A; Terry, A; Pangilinan, J; Lindquist, E A; Lucas, S; Paulsen, I; Hattenrath-Lehmann, T K; Talmage, S; Walker, E A; Koch, F; Burson, A M; Marcoval, M A; Tang, Y; LeCleir, G R; Coyne, K J; Berg, G M; Bertrand, E M; Saito, M A; Gladyshev, V N

    2011-03-02

    Harmful algal blooms (HABs) cause significant economic and ecological damage worldwide. Despite considerable efforts, a comprehensive understanding of the factors that promote these blooms has been lacking because the biochemical pathways that facilitate their dominance relative to other phytoplankton within specific environments have not been identified. Here, biogeochemical measurements demonstrated that the harmful alga Aureococcus anophagefferens outcompeted co-occurring phytoplankton in estuaries with elevated levels of dissolved organic matter and turbidity and low levels of dissolved inorganic nitrogen. We subsequently sequenced the first HAB genome (A. anophagefferens) and compared its gene complement to those of six competing phytoplankton species identified via metaproteomics. Using an ecogenomic approach, we specifically focused on the gene sets that may facilitate dominance within the environmental conditions present during blooms. A. anophagefferens possesses a larger genome (56 mbp) and more genes involved in light harvesting, organic carbon and nitrogen utilization, and encoding selenium- and metal-requiring enzymes than competing phytoplankton. Genes for the synthesis of microbial deterrents likely permit the proliferation of this species with reduced mortality losses during blooms. Collectively, these findings suggest that anthropogenic activities resulting in elevated levels of turbidity, organic matter, and metals have opened a niche within coastal ecosystems that ideally suits the unique genetic capacity of A. anophagefferens and thus has facilitated the proliferation of this and potentially other HABs.

  18. Niche of harmful alga Aureococcus anophagefferens revealed through ecogenomics

    Grigoriev, Igor; Gobler, Christopher; Salamov, Asaf; Kuo, Alan; Terry, Astrid; Pangillian, Jasmyn; Lindquist, Erika; Lucas, Susan; Berry, Dianna; Dyhrman, Sonya; Wilhelm, Steven; Lobanov, Alexei; Zhang, Yan; Collier, Jackie; Wurch, Louie; Kusta, Adam; Dill, Brian; Shsh, Manesh; VerBerkmoes, Nathan; Paulsen, Ian; Hattenrath-Lehmann, Theresa; Talmage, Stephanie; Walker, Elyse; Koch, Florian; Burson, Amanda; Marcoval, Maria; Tang, Yin-Zhong; LeCleir, Gary; Coyne, Kathyrn; Berg, Gry; Bertrand, Erin; Saito, Mak; Gladyshev, Vadim

    2011-02-18

    Harmful algal blooms (HABs) cause significant economic and ecological damage worldwide. Despite considerable efforts, a comprehensive understanding of the factors that promote these blooms has been lacking, because the biochemical pathways that facilitate their dominance relative to other phytoplankton within specific environments have not been identified. Here, biogeochemical measurements showed that the harmful alga Aureococcus anophagefferens outcompeted co-occurring phytoplankton in estuaries with elevated levels of dissolved organic matter and turbidity and low levels of dissolved inorganic nitrogen. We subsequently sequenced the genome of A. anophagefferens and compared its gene complement with those of six competing phytoplankton species identified through metaproteomics. Using an ecogenomic approach, we specifically focused on gene sets that may facilitate dominance within the environmental conditions present during blooms. A. anophagefferens possesses a larger genome (56 Mbp) and has more genes involved in light harvesting, organic carbon and nitrogen use, and encoding selenium- and metal-requiring enzymes than competing phytoplankton. Genes for the synthesis of microbial deterrents likely permit the proliferation of this species, with reduced mortality losses during blooms. Collectively, these findings suggest that anthropogenic activities resulting in elevated levels of turbidity, organic matter, and metals have opened a niche within coastal ecosystems that ideally suits the unique genetic capacity of A. anophagefferens and thus, has facilitated the proliferation of this and potentially other HABs.

  19. A media information analysis for implementing effective countermeasure against harmful rumor

    Nagao, Mitsuyoshi; Suto, Kazuhiro; Ohuchi, Azuma

    2010-04-01

    When large scale earthquake occurred, the word of "harmful rumor" came to be frequently heard. The harmful rumor means an economic damage which is caused by the action that people regard actually safe foods or areas as dangerous and then abort consumption or sightseeing. In the case of harmful rumor caused by earthquake, especially, tourism industry receives massive economic damage. Currently, harmful rumor which gives substantial economic damage have become serious social issue which must be solved. In this paper, we propose a countermeasure method for harmful rumor on the basis of media trend in order to implement speedy recovery from harmful rumor. Here, we investigate the amount and content of information which is transmitted to the general public by the media when an earthquake occurred. In addition, the media information in three earthquakes is treated as instance. Finally, we discuss an effective countermeasure method for dispeling harmful rumor through these analysis results.

  20. The Theory of Dyadic Morality: Reinventing Moral Judgment by Redefining Harm.

    Schein, Chelsea; Gray, Kurt

    2018-02-01

    The nature of harm-and therefore moral judgment-may be misunderstood. Rather than an objective matter of reason, we argue that harm should be redefined as an intuitively perceived continuum. This redefinition provides a new understanding of moral content and mechanism-the constructionist Theory of Dyadic Morality (TDM). TDM suggests that acts are condemned proportional to three elements: norm violations, negative affect, and-importantly-perceived harm. This harm is dyadic, involving an intentional agent causing damage to a vulnerable patient (A→P). TDM predicts causal links both from harm to immorality (dyadic comparison) and from immorality to harm (dyadic completion). Together, these two processes make the "dyadic loop," explaining moral acquisition and polarization. TDM argues against intuitive harmless wrongs and modular "foundations," but embraces moral pluralism through varieties of values and the flexibility of perceived harm. Dyadic morality impacts understandings of moral character, moral emotion, and political/cultural differences, and provides research guidelines for moral psychology.

  1. Getting out of (self-) harm's way: A study of factors associated with self-harm among asylum seekers in Australian immigration detention.

    Hedrick, Kyli

    2017-07-01

    The monitoring of self-harm among asylum seekers in Australian immigration detention has not occurred routinely or transparently. Thus whilst concerns regarding rates of self-harm among asylum seekers have been frequently raised, a paucity of systematic information regarding key factors associated with self-harm among asylum seekers exists. The present study was designed therefore to fill a number of gaps in government monitoring by examining the government's own archived self-harm data. Via a descriptive analysis of self-harm incident reports from all operational Australian immigration detention facilities over a 20-month period to May 2011, obtained under Freedom of Information, the present study identified that 959 incidents of self-harm occurred during this period. A gender bias towards men was also found. In addition to this, 10 different methods of self-harm were identified, the four most common being: cutting (47%), attempted hanging (19%), head hitting (12%) and self-poisoning by medication (6%). Seven different precipitating factors for self-harm were also identified, the four most common were: detention conditions (39%), processing arrangements (27%), negative decisions (24%) and family separation (3%). These findings point strongly to the health benefits of considering alternatives to held immigration detention, such as community based processing. Copyright © 2017 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  2. Deliberate Self-Harm within an International Community Sample of Young People: Comparative Findings from the Child & Adolescent Self-Harm in Europe (CASE) Study

    Madge, Nicola; Hewitt, Anthea; Hawton, Keith; de Wilde, Erik Jan; Corcoran, Paul; Fekete, Sandor; van Heeringen, Kees; De Leo, Diego; Ystgaard, Mette

    2008-01-01

    Background: Deliberate self-harm among young people is an important focus of policy and practice internationally. Nonetheless, there is little reliable comparative international information on its extent or characteristics. We have conducted a seven-country comparative community study of deliberate self-harm among young people. Method: Over 30,000…

  3. How people who self-harm negotiate the inpatient environment: the mental healthcare workers perspective.

    Thomas, J B; Haslam, C O

    2017-09-01

    WHAT IS KNOWN ABOUT THE SUBJECT?: Self-harm plays a function, commonly in the form of distress management. There has been little focussed exploration of how individuals who use self-harm to manage distress cope when prevented from self-harm in an inpatient environment and how staff respond to this issue. This paper uses the experiences of mental health staff to add to the existing knowledge that self-harm has a functional role and supports the notion that interventions for self-harm should focus on the origins of distress. It describes the potential consequences that focussing on prevention of self-harm as opposed to actually managing distress may have on service-users, how staff attempt to manage these consequences and factors that may impact on staff interventions to prevent further distress/harm. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: The findings suggest that mental healthcare staff should aim to understand the function of self-harm, use this understanding to develop an individualized care plan with the aim of managing distress and identify barriers to the effectiveness of the interventions so they can be worked around. Introduction Literature describes self-harm as functional and meaningful. This creates difficulties for service-users detained in an inpatient environment where self-harm is prevented. Aim Mental healthcare staff were interviewed to build on existing evidence of issues with the prevention approach and explore, from a staff perspective, how self-harm prevention impacts on service-users, how they manage distress and how this impacts on staff and their approach to care. Methods Qualitative methods were used to allow unexpected themes to arise. Ten semi-structured interviews were carried out with mental healthcare staff and thematically analysed. Findings and discussion The findings provide new evidence on the benefits and limitations of the inpatient environment for individuals who self-harm. Findings indicate that being unable to self-harm can

  4. Exposure of ventilation system cleaning workers to harmful microbiological agents.

    Gołofit-Szymczak, Małgorzata; Ławniczek-Wałczyk, Anna; Górny, Rafał L

    2013-01-01

    Regular inspection of the cleanliness of the ventilation systems, as well as their periodic cleaning and disinfection, if necessary, are the main factors of the proper maintenance of each system. Performing maintenance operations on the ventilation system, workers are exposed to risk associated with the exposure to harmful biological agents. The aim of this study was to assess the employees' exposure to bioaerosols during maintenance work on ventilation systems. Bioaerosol measurements were carried out using a button sampler. The microbial particles were collected on gelatin filters. Settled-dust samples from the inner surface of the air ducts and filter-mat samples were selected for the microbiological analysis. In the collected air, dust and filter samples the concentration of bacteria and fungi were determined. Bacteria and fungi concentrations ranged between 3.6 x 10(2)-2.2 x 10(4) CFU/m3 and 4.7 x 10(2)-4.5 x 10(3) CFU/m3 at workplaces where the operations connected with mechanical ventilation cleaning were performed and 2.2 x 10(4)-1.2 x 10(5) CFU/m2 and 9.8 x 10(1)-2.5 x 10(2) CFU/m3 at workplaces where filter exchange was performed, respectively. The qualitative analysis of microorganisms isolated from the air in all studied workplaces revealed that the most prevalent bacteria belonged to Bacillus genus. The average concentrations of bacteria and fungi in filter-mat samples were 3.3 x 10(3) CFU/cm2 and 1.4 x 10(4) CFU/cm2, respectively. In settled-dust samples, average concentrations were 591 CFU/100 cm2 and 52 CFU/100 cm2, for bacteria and fungi respectively. Workers cleaning ventilation systems are exposed to harmful biological agents classified into risk groups, 1 and 2, according to their level of the risk of infection. The research conducted in the workplace can be the basis of risk assessment related to exposure to harmful biological agents during maintenance work in ventilation.

  5. Harmful Freshwater Algal Blooms, With an Emphasis on Cyanobacteria

    Hans W. Paerl

    2001-01-01

    Full Text Available Suspended algae, or phytoplankton, are the prime source of organic matter supporting food webs in freshwater ecosystems. Phytoplankton productivity is reliant on adequate nutrient supplies; however, increasing rates of nutrient supply, much of it manmade, fuels accelerating primary production or eutrophication. An obvious and problematic symptom of eutrophication is rapid growth and accumulations of phytoplankton, leading to discoloration of affected waters. These events are termed blooms. Blooms are a prime agent of water quality deterioration, including foul odors and tastes, deoxygenation of bottom waters (hypoxia and anoxia, toxicity, fish kills, and food web alterations. Toxins produced by blooms can adversely affect animal (including human health in waters used for recreational and drinking purposes. Numerous freshwater genera within the diverse phyla comprising the phytoplankton are capable of forming blooms; however, the blue-green algae (or cyanobacteria are the most notorious bloom formers. This is especially true for harmful toxic, surface-dwelling, scum-forming genera (e.g., Anabaena, Aphanizomenon, Nodularia, Microcystis and some subsurface bloom-formers (Cylindrospermopsis, Oscillatoria that are adept at exploiting nutrient-enriched conditions. They thrive in highly productive waters by being able to rapidly migrate between radiance-rich surface waters and nutrient-rich bottom waters. Furthermore, many harmful species are tolerant of extreme environmental conditions, including very high light levels, high temperatures, various degrees of desiccation, and periodic nutrient deprivation. Some of the most noxious cyanobacterial bloom genera (e.g., Anabaena, Aphanizomenon, Cylindrospermopsis, Nodularia are capable of fixing atmospheric nitrogen (N2, enabling them to periodically dominate under nitrogen-limited conditions. Cyanobacteria produce a range of organic compounds, including those that are toxic to higher-ranked consumers, from

  6. Climate change, irrigation, and Israeli agriculture. Will warming be harmful?

    Fleischer, Aliza; Lichtman, Ivgenia [Hebrew University of Jerusalem, Jerusalem (Israel); Mendelsohn, Robert [Yale University, New Haven, Connecticut (United States)

    2008-04-15

    This paper utilizes a Ricardian model to test the relationship between annual net revenues and climate across Israeli farms. The study finds that it is important to include the amount of irrigation water available to each farm in order to measure the response of farms to climate. With irrigation water omitted, the model predicts climate change is strictly beneficial. However, with water included, the model predicts that only modest climate changes are beneficial while drastic climate change in the long run will be harmful. Using the AOGCM Scenarios we show that farm net revenue is expected to increase. Although Israel has a relatively warm climate a mild increase in temperature is beneficial due to the ability to supply international markets with farm product early in the season. (author)

  7. Climate change, irrigation, and Israeli agriculture. Will warming be harmful?

    Fleischer, Aliza; Lichtman, Ivgenia; Mendelsohn, Robert

    2008-01-01

    This paper utilizes a Ricardian model to test the relationship between annual net revenues and climate across Israeli farms. The study finds that it is important to include the amount of irrigation water available to each farm in order to measure the response of farms to climate. With irrigation water omitted, the model predicts climate change is strictly beneficial. However, with water included, the model predicts that only modest climate changes are beneficial while drastic climate change in the long run will be harmful. Using the AOGCM Scenarios we show that farm net revenue is expected to increase. Although Israel has a relatively warm climate a mild increase in temperature is beneficial due to the ability to supply international markets with farm product early in the season. (author)

  8. On strategic ignorance of environmental harm and social norms

    Thunström, Linda; van’t Veld, Klaas; Shogren, Jason. F.

    2014-01-01

    decreases (to 29 percent) when the information additionally reveals the share of air travelers who buy carbon offsets. We find evidence that some people use ignorance as an excuse to reduce pro-environmental behavior—ignorance significantly decreases the probability of buying carbon offsets.......Are people strategically ignorant of the negative externalities their activities cause the environment? Herein we examine if people avoid costless information on those externalities and use ignorance as an excuse to reduce pro-environmental behavior. We develop a theoretical framework in which...... people feel internal pressure (“guilt”) from causing harm to the environment (e.g., emitting carbon dioxide) as well as external pressure to conform to the social norm for pro-environmental behavior (e.g., offsetting carbon emissions). Our model predicts that people may benefit from avoiding information...

  9. [Harmful alcohol consumption: prevalence, trends, health burden, reduction strategy].

    Грузева, Татьяна С; Дуфинец, Василий А; Замкевич, Виктория Б

    2016-01-01

    Harmful alcohol consumption constitutes a significant cause of the global burden of disease, causing more than 200 different diseases, 5.9% of all deaths worldwide, causing substantial medical and social costs, major economic loss, slowing progress towards the strategic goals of human development. to substantiate approaches to the formation of a national strategy to combat the harmful use of alcohol in Ukraine based on the analysis of the prevalence of alcohol consumption and related health and social problems and international experience and recommendations of WHO. The study was based on analysis of the extent and patterns of alcohol consumption in Ukraine, levels, structure and dynamics of morbidity and mortality from diseases associated with alcohol abuse; investigation of preventive activities in primary healthcare, the existing problems and doctors' needs for prevention alcohol abuse, national and international experience on this problem.This work usesbibliosemantic, medical, statistical, sociological, epidemiological methods. The information base are: European Health for All Database (HFA-DB)for 2000-2012,Center of Medical Statistics, Ministry of Health of Ukraine for 2000-2015, questionnaire survey of physicians in primary care, strategic and policy documents of WHO, WHO Regional Office for Europe. In Ukraine, as in most countries in the WHO European Region prevalence of alcohol is high. In the ranking of the WHO European Region Ukraine ranks fifth in alcohol consumption per capita. The structure of consumption of alcoholic drinks is dominated by strong spirits (48%). There has been a negative trend for this indicator from 5.4 liters in 2002 to 15.6 liters in 2012.The dominant pattern of alcohol consumption is characterized by early onset of alcohol consumption, significant frequency, large doses, mostly strong alcohol beverages, with significant share of low-quality alcohol. This factor contributes to high levels of morbidity. A total of546.3 thousandpeople

  10. The Body of Hurt in Margaret Atwood's Novel Bodily Harm

    Avital Gad Cykman

    2015-01-01

    This article analyses Margaret Atwood’s novel BODILY HARM (1981 in regard to its exploration of the link between corporeality and contextuality, focusing on the relation between the historical and socio-cultural context in which identity is constructed and the female character’s perception of body and self. The character’s retrospective journey serves as a ground for a deconstruction of the character’s values, behavior, relationships, and discomfort with the body in order to reveal the power relations and social causes behind her present situation. The study focuses on the literary articulation of the problems of being female, the exploration of the relation between the biological body and the cultural concept of the body, and the criticism of social representations of women.

  11. Fish Kill Incidents and Harmful Algal Blooms in Omani Waters

    Hamed Mohammed Al Gheilani

    2011-01-01

    Full Text Available Red tide, one of the harmful algal blooms (HABs is a natural ecological phenomenon and often this event is accompanied by severe impacts on coastal resources, local economies, and public health. The occurrence of red tides has become more frequent in Omani waters in recent years. Some of them caused fish kill, damaged fishery resources and mariculture, threatened the marine environment and the osmosis membranes of desalination plants. However, a number of them have been harmless. The most common dinoflagellate Noctiluca scintillans is associated with the red tide events in Omani waters. Toxic species like Karenia selliformis, Prorocentrum arabianum, and Trichodesmium erythraeum have also been reported recently. Although red tides in Oman have been considered a consequence of upwelling in the summer season (May to September, recent phytoplankton outbreaks in Oman are not restricted to summer. Frequent algal blooms have been reported during winter (December to March. HABs may have contributed to hypoxia and/or other negative ecological impacts.

  12. The globalization of ayahuasca: harm reduction or benefit maximization?

    Tupper, Kenneth W

    2008-08-01

    Ayahuasca is a tea made from two plants native to the Amazon, Banisteriopsis caapi and Psychotria viridis, which, respectively, contain the psychoactive chemicals harmala alkaloids and dimethyltryptamine. The tea has been used by indigenous peoples in countries such as Brazil, Ecuador and Peru for medicinal, spiritual and cultural purposes since pre-Columbian times. In the 20th century, ayahuasca spread beyond its native habitat and has been incorporated into syncretistic practices that are being adopted by non-indigenous peoples in modern Western contexts. Ayahuasca's globalization in the past few decades has led to a number of legal cases which pit religious freedom against national drug control laws. This paper explores some of the philosophical and policy implications of contemporary ayahuasca use. It addresses the issue of the social construction of ayahuasca as a medicine, a sacrament and a "plant teacher." Issues of harm reduction with respect to ayahuasca use are explored, but so too is the corollary notion of "benefit maximization."

  13. Ordinary physical punishment: is it harmful? Comment on Gershoff (2002).

    Baumrind, Diana; Larzelere, Robert E; Cowan, Philip A

    2002-07-01

    E. T. Gershoff (2002) reviewed processes that might mediate and contexts that might moderate the associations between corporal punishment (CP) and child behaviors and provided an account of the methodological weaknesses of the research reviewed in her meta-analyses. In this examination of Gershoff, the authors argue that the biases and confounds in the meta-analyses further limit any causal inferences that can be drawn concerning the detrimental "effects" of CP on associated child behaviors. The authors suggest that undesirable child outcomes are associated with CP because the construct marks inept harsh parenting and conclude that although the harmful effects of physical abuse and other extreme punishments are clear, a blanket injunction against spanking is not justified by the evidence presented by Gershoff.

  14. Pollutants in drinking water - sources, harmful effects and removal procedures

    Qadeer, R.

    2005-01-01

    The underground water resources available for human consumption are being continuously contaminated by the natural sources and anthropogenic activities. The pollutants include toxic microorganism, inorganic and organic chemicals and radionuclide etc. This is an acute problem in our country, where free style way of disposal of industrial effluents into the natural water bodies contaminates the surface and ground water. These contaminants make their way into human body through contaminated drinking water, which leads to the malfunctioning of the body organs. Details of some pollutants present in drinking water, their source and harmful effects on human beings are reviewed in this communication Merits and demerits of methods used to remove the pollutants from drinking water are also discussed. (author)

  15. Love as harm reduction: fighting AIDS and stigma in Vietnam

    Small Dan

    2009-12-01

    Full Text Available Abstract In the summer of 2009, I visited a humble orphanage for children with HIV/AIDS in Vietnam. Here, like many parts in the world, the very existence of marginalized people with stigmatized illness is hidden away. Relegated to the shadows of society, these children lacked something more fundamental than housing, shelter, nutrition and medications. They lacked families to love and care for them unconditionally. One might think it self-evident that a visit to an orphanage for children with HIV would be profound, but the profundity wasn't where I expected to find it. It was in how the children had created their own family, loving each other like brothers and sisters, and the way the priest who operated the shelters was more than a Father, he was a dad to dozens of children. This is an account of love as harm reduction in the Mai Tam orphanage in Ho Chi Minh City.

  16. Strategies for an effective tobacco harm reduction policy in Indonesia

    Fariz Nurwidya

    2014-12-01

    Full Text Available Tobacco consumption is a major causative agent for various deadly diseases such as coronary artery disease and cancer. It is the largest avoidable health risk in the world, causing more problems than alcohol, drug use, high blood pressure, excess body weight or high cholesterol. As countries like Indonesia prepare to develop national policy guidelines for tobacco harm reduction, the scientific community can help by providing continuous ideas and a forum for sharing and distributing information, drafting guidelines, reviewing best practices, raising funds, and establishing partnerships. We propose several strategies for reducing tobacco consumption, including advertisement interference, cigarette pricing policy, adolescent smoking prevention policy, support for smoking cessation therapy, special informed consent for smokers, smoking prohibition in public spaces, career incentives, economic incentives, and advertisement incentives. We hope that these strategies would assist people to avoid starting smoking or in smoking cessation.

  17. Protection of atmosphere from harmful emissions of stationary fuelburn installations

    Lebedeva Еvgeniya А.

    2013-01-01

    Full Text Available The article analyzes domestic and foreign researches in the field of combustion gas cleaning from harmful matters. The drawbacks of the existing methods of cleaning emissions of small-capacity boilers are revealed. The results of the researches conducted by the authors are presented. Complex schemes of cleaning emissions of the industrial boilers of the DKVR series are considered. The results of the tests of afterburning devices installed in the industrial boilers are presented. The simplest design of an afterburning device by the example of an industrial boiler of the DKVR series is considered. It is shown that the application of the afterburning devices prevents emissions of the incomplete burning products (CO, carbon black, benzpyrene and reduces the nitric oxide content by (50-80%, depending on the scheme of cleaning. The usage of the afterburning devices improves boiler performance owing to the increase of the radiant component in a furnace chamber, reduction of heat losses, increase of efficiency.

  18. [Plants as a source of natural harmful substances].

    Czerwiecki, Ludwik

    2005-01-01

    In this review the several data concerning phytotoxins as natural harmful substances of plants and phycotoxins--toxicants of algae were described. For example plants are source of pyrrolizidine alkaloids, glycoalkaloids, glucosinolates as well as glycosides, saponine and psolarens. Possible adverse effects of phytoestrogens as endocrine disruptors versus beneficial influence these substances on human organism were mentioned. About lectins as possible factors of some diseases was reported, as well as some proteins as allergens of soy and peanuts was mentioned. Accumulated by shellfish and fish the most important phycotoxins such as saxitoxin, okadaic acid, brevetoxins and ciguatoxins were described. Phycotoxins produced several poisoning symptoms. Microcystins and nodularin--cyanobacterial phycotoxins of freshwater, was mentioned. In conclusion, the need of limitation of permissible levels of some plant toxicants, development of analytical methods as well as knowledge of influence of some technological processes on toxic plant substances was highlighted. The importance of balanced diet as a tool of defense against plant toxicants was concluded.

  19. Effects of Harmful Algae on the Physiology of Fishes

    Svendsen, Morten Bo Søndergaard

    Blooms of harmful planktonic algae causing adverse effects in aquatic environments are a global problem, causing both human morbidity and killing aquatic lifeforms worldwide. Focusing on fish kills, it is largely unknown what mechanisms of the fish’s physiology are affected during exposure...... is deemed unlikely on basis of rainbow trout (Onchorhyncus mykiss) not recovering. The specific toxicity of Pseudochattonella spp. is unknown, but by studying the effects of Pseudochattonella spp. on fish during a natural bloom occurring at a trout farm an adverse outcome could be created. The adverse...... Alexandrium monilatum has been studied intensively the effects of Alexandrium monilatum on fish is largely unknown. In the Chesapeake Bay, Eastern U.S.A., fishes are further challenged in late summer by an oxygen squeeze from deep part of the water column, limiting their utilizable habitat to mid...

  20. Self-harming in depressed patients: pattern analysis.

    Parker, G; Malhi, Gin; Mitchell, Philip; Kotze, Beth; Wilhelm, Kay; Parker, Kay

    2005-10-01

    As deliberate self-harm (DSH) is a common concomitant of depressive disorders, we undertook a study examining the relevance of possible determinants and correlates of DSH. Three separate samples of depressed outpatients were studied to determine consistency of identified factors across samples, with principal analyses involving gender, age and diagnosis-matched DSH and non-DSH subjects. Across the samples, some 20% of subjects admitted to episodes of DSH. Women reported higher rates and there was a consistent trend for higher rates in bipolar patients. Univariate analyses examined the relevance of several sociodemographic variables, illicit drug and alcohol use, past deprivational and abusive experiences, past suicidal attempts and disordered personality functioning. Multivariate analyses consistently identified previous suicide attempts and high 'acting out' behaviours across the three samples, suggesting the relevance of an externalizing response to stress and poor impulse control. Results assist the identification and management of depressed patients who are at greater risk of DSH behaviours.

  1. Benefit and harm of pregabalin in acute pain treatment

    Fabritius, M L; Strøm, C; Koyuncu, S

    2017-01-01

    Pregabalin has demonstrated anti-hyperalgesic properties and was introduced into acute pain treatment in 2001. Our aim was to evaluate the beneficial and harmful effects of pregabalin in postoperative pain management. We included randomized clinical trials investigating perioperative pregabalin......, Peto's odds ratio was 2.9 (1.2, 6.8; TSA adjusted confidence interval: 0.1, 97.1). Based on trials with low risk of bias, pregabalin may have a minimal opioid-sparing effect, but the risk of SAEs seems increased. However, the GRADE-rated evaluations showed only moderate to very low quality of evidence....... Consequently, a routine use of pregabalin for postoperative pain treatment cannot be recommended....

  2. Non-suicidal reasons for self-harm: A systematic review of self-reported accounts.

    Edmondson, Amanda J; Brennan, Cathy A; House, Allan O

    2016-02-01

    Self-harm is a major public health problem yet current healthcare provision is widely regarded as inadequate. One of the barriers to effective healthcare is the lack of a clear understanding of the functions self-harm may serve for the individual. The aim of this review is to identify first-hand accounts of the reasons for self-harm from the individual's perspective. A systematic review of the literature reporting first-hand accounts of the reasons for self-harm other than intent to die. A thematic analysis and 'best fit' framework synthesis was undertaken to classify the responses. The most widely researched non-suicidal reasons for self-harm were dealing with distress and exerting interpersonal influence. However, many first-hand accounts included reasons such as self-validation, and self-harm to achieve a personal sense of mastery, which suggests individuals thought there were positive or adaptive functions of the act not based only on its social effects. Associations with different sub-population characteristics or with the method of harm were not available from most studies included in the analysis. Our review identified a number of themes that are relatively neglected in discussions about self-harm, which we summarised as self-harm as a positiveexperience and defining the self. These self-reported "positive" reasons may be important in understanding and responding especially to repeated acts of self-harm. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Selective algicidal action of peptides against harmful algal bloom species.

    Seong-Cheol Park

    Full Text Available Recently, harmful algal bloom (HAB, also termed "red tide", has been recognized as a serious problem in marine environments according to climate changes worldwide. Many novel materials or methods to prevent HAB have not yet been employed except for clay dispersion, in which can the resulting sedimentation on the seafloor can also cause alteration in marine ecology or secondary environmental pollution. In the current study, we investigated that antimicrobial peptide have a potential in controlling HAB without cytotoxicity to harmless marine organisms. Here, antimicrobial peptides are proposed as new algicidal compounds in combating HAB cells. HPA3 and HPA3NT3 peptides which exert potent antimicrobial activity via pore forming action in plasma membrane showed that HPA3NT3 reduced the motility of algal cells, disrupted their plasma membrane, and induced the efflux of intracellular components. Against raphidoflagellate such as Heterosigma akashiwo, Chattonella sp., and C. marina, it displayed a rapid lysing action in cell membranes at 1~4 µM within 2 min. Comparatively, its lysing effects occurred at 8 µM within 1 h in dinoflagellate such as Cochlodium polykrikoides, Prorocentrum micans, and P. minimum. Moreover, its lysing action induced the lysis of chloroplasts and loss of chlorophyll a. In the contrary, this peptide was not effective against Skeletonema costatum, harmless algal cell, even at 256 µM, moreover, it killed only H. akashiwo or C. marina in co-cultivation with S. costatum, indicating to its selective algicidal activity between harmful and harmless algal cells. The peptide was non-hemolytic against red blood cells of Sebastes schlegeli, the black rockfish, at 120 µM. HAB cells were quickly and selectively lysed following treatment of antimicrobial peptides without cytotoxicity to harmless marine organisms. Thus, the antibiotic peptides examined in our study appear to have much potential in effectively controlling HAB with minimal

  4. Castor oil for induction of labour: not harmful, not helpful.

    Boel, Machteld Elisabeth; Lee, Sue Jean; Rijken, Marcus Johannes; Paw, Moo Koo; Pimanpanarak, Mupawjay; Tan, Saw Oo; Singhasivanon, Pratap; Nosten, François; McGready, Rose

    2009-10-01

    Castor oil is one of the most popular drugs for induction of labour in a non-medical setting; however, published data on safety and effectiveness of this compound to induce labour remain sparse. To assess the safety and effectiveness of castor oil for induction of labour in pregnancies with an ultrasound estimated gestational at birth of more than 40 weeks. Data were extracted from hospital-based records of all pregnant women who attended antenatal clinics on the Thai-Burmese border and who were more than 40 weeks pregnant. The effectiveness of castor oil to induce labour was expressed as time to birth and analysed with a Cox proportional hazards regression model. Measures associated with safety were fetal distress, meconium-stained amniotic fluid, tachysystole of the uterus, uterine rupture, abnormal maternal blood pressure during labour, Apgar scores, neonatal resuscitation, stillbirth, post-partum haemorrhage, severe diarrhoea and maternal death. Proportions were compared using Fisher's exact test. Of 612 women with a gestation of more than 40 weeks, 205 received castor oil for induction and 407 did not. The time to birth was not significantly different between the two groups (hazard ratio 0.99 (95% confidence interval: 0.81 to 1.20; n = 509)). Castor oil use was not associated with any harmful effects on the mother or fetus. Castor oil for induction of labour had no effect on time to birth nor were there any harmful effects observed in this large series. Our findings leave no justification for recommending castor oil for this purpose.

  5. Perceptions of Harm to Children Exposed to Secondhand Aerosol From Electronic Vapor Products, Styles Survey, 2015.

    Nguyen, Kimberly H; Tong, Van T; Marynak, Kristy; King, Brian A

    2017-05-25

    The US Surgeon General has concluded that e-cigarette aerosol is not harmless and can contain harmful and potentially harmful chemicals, including nicotine. We assessed factors associated with adults' perceptions of harm related to children's exposure to secondhand aerosol from electronic vapor products (EVPs). Data came from the 2015 Styles, an Internet panel survey of US adults aged 18 years or older (n = 4,127). Respondents were asked whether they believe aerosol from other people's EVPs causes children harm. Harm perceptions were assessed overall and by cigarette smoking, EVP use, and sociodemographic characteristics. Multinomial logistic regression was used to assess odds of perceived harm. Overall, 5.3% of adults responded that secondhand EVP exposure caused "no harm" to children, 39.9% responded "little harm" or "some harm," 21.5% responded "a lot of harm," and 33.3% responded "don't know." Odds of "no harm" response were greater among men than among women, current and former cigarette smokers than among never smokers, and current and former EVP users than among never users; odds were lower among non-Hispanic blacks, Hispanics, and non-Hispanic other races than among non-Hispanic whites. Odds of responding "don't know" were greater among men, current cigarette smokers, and current and former EVP users; odds were lower among those aged 45 to 64 years than those aged 18 to 24 years and lower among non-Hispanic other races and Hispanics than non-Hispanic whites. Two-fifths of US adults believe that children's exposure to secondhand EVP aerosol causes some or little harm, while one-third do not know whether it causes harm. Efforts are warranted to educate the public about the health risks of secondhand EVP aerosol, particularly for children.

  6. Out of the blue: Untangling the association between impulsivity and planning in self-harm.

    Rawlings, Jodie; Shevlin, Mark; Corcoran, Rhiannon; Morriss, Richard; Taylor, Peter James

    2015-09-15

    Planned and unplanned acts of self-harm may have distinct clinical and psychological correlates. Trait impulsivity is one factor that might be expected to determine whether self-harm is planned. Research so far has focussed on suicide attempts and little is known about how individuals engaging in planned and unplanned acts of self-harm differ. The aim of the current study was to examine how individuals who report planned self-harm, unplanned self-harm, and no self-harm differ in terms of impulsivity and affective symptoms (depression, anxiety, and activated mood). An online survey of University students (n = 1350) was undertaken including measures of impulsivity, affective symptoms and self-harm. Analyses made use of a multinomial logistic regression model with affective and cognitive forms of impulsivity estimated as latent variables. Trait affective impulsivity, but not cognitive, was a general risk factor for whether self-harm occurred. There was no evidence of differences between planned and unplanned self-harm. Affective symptoms of depression and anxiety mediated the relationship between affective impulsivity and self-harm. The study was cross-sectional, relied on a student sample which may not generalise to other populations. Trait affective impulsivity is associated with self-harm but it appears to be mediated by depression and anxiety symptoms. The exact relationships between trait affective impulsivity, depression, anxiety and self-harm require further longitudinal research in clinical populations but might lead to improved risk assessment and new therapeutic approaches to self-harm. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Self-Harm among Young People Detained in the Youth Justice System in Sri Lanka

    Lushan V. Hettiarachchi

    2018-01-01

    Full Text Available Self-harm is prevalent in incarcerated adults, yet comparatively few studies of self-harm in detained youth (and even fewer in low- and middle-income countries have been published. We examined the prevalence and correlates of self-harm in a sample of 181 young people (mean age 15.0 years, SD = 2.3 detained in the youth justice system in Sri Lanka. Structured face-to-face questionnaires assessed demographic characteristics, family and social background, substance use, self-harm history (including frequency, method, and intention, bullying victimization, physical and sexual abuse (victimization and perpetration, and exposure to self-harm/suicide by others. Seventy-seven participants (43% reported a lifetime history of self-harm, 19 of whom (25% who reported doing so with suicidal intent. Fifty participants (65% of those with a history of self-harm reported engaging in self-harm impulsively, with no prior planning. A history of self-harm was associated with being female, prior sexual abuse victimization, prior exposure to self-harm by friends, and a lifetime history of self-harm ideation. High rates of substance use, bullying victimization, parental incarceration, and exposure to suicide were reported across the sample. Young people detained in the youth justice system in Sri Lanka are a vulnerable group with high rates of self-harm, substance use, and psychosocial risk factors. Strategies for identifying and preventing self-harm, and targeted psychological interventions designed specifically to address impulsivity, may contribute to more positive outcomes in this marginalised population.

  8. Oxidative and proteolysis-related parameters of skeletal muscle from hamsters with experimental pulmonary emphysema: a comparison between papain and elastase induction.

    Brunnquell, Cláudia R; Vieira, Nichelle A; Sábio, Laís R; Sczepanski, Felipe; Cecchini, Alessandra L; Cecchini, Rubens; Guarnier, Flávia A

    2015-06-01

    The objective of this study was to investigate whether emphysema induced by elastase or papain triggers the same effects on skeletal muscle, related to oxidative stress and proteolysis, in hamsters. For this purpose, we evaluated pulmonary lesions, body weight, muscle loss, oxidative stress (thiobarbituric acid-reactive substances, total and oxidized glutathiones, chemiluminescence stimulated by tert-butyl hydroperoxide and carbonyl proteins), chymotrypsin-like and calpain-like proteolytic activities and muscle fibre cross-sectional area in the gastrocnemius muscles of emphysemic hamsters. Two groups of animals received different intratracheal inductions of experimental emphysema: by 40 mg/ml papain (EP) or 5.2 IU/100 g animal (EE) elastase (n = 10 animals/group). The control group received intratracheal instillation of 300 μl sterile NaCl 0.9%. Compared with the control group, the EP group had reduced muscle weight (18.34%) and the EE group had increased muscle weight (8.37%). Additionally, tert-butyl hydroperoxide-initiated chemiluminescence, carbonylated proteins and chymotrypsin-like proteolytic activity were all elevated in the EP group compared to the CS group, while total glutathione was decreased compared to the EE group. The EE group showed more fibres with increased cross-sectional areas and increased calpain-like activity. Together, these data show that elastase and papain, when used to induce experimental models of emphysema, lead to different speeds and types of adaptation. These findings provide more information on choosing a suitable experimental model for studying skeletal muscle adaptations in emphysema. © 2015 The Authors. International Journal of Experimental Pathology © 2015 International Journal of Experimental Pathology.

  9. Effects of FlAsH/Tetracysteine (TC) tag on PrP proteolysis and PrPres formation by TC-scanning

    Taguchi, Yuzuru; Hohsfield, Lindsay A.; Hollister, Jason R.

    2014-01-01

    The FlAsH/tetracysteine (FlAsH/TC) tag is a powerful tool for fluorescent labeling of proteins. However, even small tags such as FlAsH/TC could alter the behavior of the tagged proteins, especially if the insertion occurs at internal sites. Defining the influence of FlAsH/TC on nearby protein-protein interactions might aid in selecting appropriate positions for internal TC insertions and allow the exploitation of serial FlAsH/TC insertions (TC-scanning) as a probe to characterize sites of protein-protein interaction. To explore this application in the context of substrate-protease interactions, we analyzed the effect of FlAsH/TC insertions on proteolysis of cellular prion protein (PrPsen) in in vitro reactions and generation of the C1 metabolic fragment of PrPsen in live neuroblastoma cells. The influence of FlAsH/TC insertion was evaluated by TC-scanning across the cleavage sites of each protease. The results showed that FlAsH/TC inhibited protease cleavage only within limited ranges of the cleavage sites that varied from about 1 to 6 residues-wide depending on the protease, providing an estimate of the PrP residues interacting with each protease. TC-scanning was also used to probe a different type of protein-protein interaction, the conformational conversion of FlAsH-PrPsen to the prion disease-associated isoform, PrPres. PrP constructs with FlAsH/TC insertions at residues 90–96 but not 97–101 were converted to FlAsH-PrPres, identifying a boundary separating loosely versus compactly folded regions of PrPres. Our observations demonstrate that TC-scanning with the FlAsH/TC tag can be a versatile method for probing protein-protein interactions and folding processes. PMID:23943295

  10. Novel BET protein proteolysis-targeting chimera exerts superior lethal activity than bromodomain inhibitor (BETi) against post-myeloproliferative neoplasm secondary (s) AML cells.

    Saenz, D T; Fiskus, W; Qian, Y; Manshouri, T; Rajapakshe, K; Raina, K; Coleman, K G; Crew, A P; Shen, A; Mill, C P; Sun, B; Qiu, P; Kadia, T M; Pemmaraju, N; DiNardo, C; Kim, M-S; Nowak, A J; Coarfa, C; Crews, C M; Verstovsek, S; Bhalla, K N

    2017-09-01

    The PROTAC (proteolysis-targeting chimera) ARV-825 recruits bromodomain and extraterminal (BET) proteins to the E3 ubiquitin ligase cereblon, leading to degradation of BET proteins, including BRD4. Although the BET-protein inhibitor (BETi) OTX015 caused accumulation of BRD4, treatment with equimolar concentrations of ARV-825 caused sustained and profound depletion (>90%) of BRD4 and induced significantly more apoptosis in cultured and patient-derived (PD) CD34+ post-MPN sAML cells, while relatively sparing the CD34+ normal hematopoietic progenitor cells. RNA-Seq, Reverse Phase Protein Array and mass cytometry 'CyTOF' analyses demonstrated that ARV-825 caused greater perturbations in messenger RNA (mRNA) and protein expressions than OTX015 in sAML cells. Specifically, compared with OTX015, ARV-825 treatment caused more robust and sustained depletion of c-Myc, CDK4/6, JAK2, p-STAT3/5, PIM1 and Bcl-xL, while increasing the levels of p21 and p27. Compared with OTX015, PROTAC ARV-771 treatment caused greater reduction in leukemia burden and further improved survival of NSG mice engrafted with luciferase-expressing HEL92.1.7 cells. Co-treatment with ARV-825 and JAK inhibitor ruxolitinib was synergistically lethal against established and PD CD34+ sAML cells. Notably, ARV-825 induced high levels of apoptosis in the in vitro generated ruxolitinib-persister or ruxolitinib-resistant sAML cells. These findings strongly support the in vivo testing of the BRD4-PROTAC based combinations against post-MPN sAML.

  11. An evaluation of electronic cigarette formulations and aerosols for harmful and potentially harmful constituents (HPHCs) typically derived from combustion.

    Wagner, Karl A; Flora, Jason W; Melvin, Matt S; Avery, Karen C; Ballentine, Regina M; Brown, Anthony P; McKinney, Willie J

    2018-06-01

    U.S. FDA draft guidance recommends reporting quantities of designated harmful and potentially harmful constituents (HPHCs) in e-cigarette e-liquids and aerosols. The HPHC list comprises potential matrix-related compounds, flavors, nicotine, tobacco-related impurities, leachables, thermal degradation products, and combustion-related compounds. E-cigarettes contain trace levels of many of these constituents due to tobacco-derived nicotine and thermal degradation. However, combustion-related HPHCs are not likely to be found due to the relatively low operating temperatures of most e-cigarettes. The purpose of this work was to use highly sensitive, selective, and validated analytical methods to determine if these combustion-related HPHCs (three aromatic amines, five volatile organic compounds, and the polycyclic aromatic hydrocarbon benzo[a]pyrene) are detectable in commercial refill e-liquids, reference e-cigarette e-liquids, and aerosols generated from rechargeable e-cigarettes with disposable cartridges (often referred to as "cig-a-likes"). In addition, the transfer efficiency of these constituents from e-liquid to aerosol was evaluated when these HPHCs were added to the e-liquids prior to aerosol formation. This work demonstrates that combustion-related HPHCs are not present at measurable levels in the commercial and reference e-liquids or e-cigarette aerosols tested. Additionally, when combustion-related HPHCs are added to the e-liquids, they transfer to the aerosol with transfer efficiencies ranging from 49% to 99%. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  12. An Empirical Analysis of Internet Message Boards for Self-Harming Behavior.

    Eichenberg, Christiane; Schott, Markus

    2017-01-01

    Much debate surrounds the potential effects of self-harm forum use. Arguments in favor highlight factors such as providing access to a supportive community. However critical voice highlighting potential dangers such as forums serving as a platform to promote self-harm, clearly dominate the debate. Using an online questionnaire, the goal of the current study was to examine sociodemographic characteristics, the psychopathology of forum users, motives for participating, and subjective effects of self-harm forum use. A total of 309 self-harm forum users participated in this study. 3 heterogeneous user types with differing motives for visiting the forum and different usage effects were identified. The results question the assumptions that self-harm forums are a source of harm and point to their predominantly constructive and preventive functions.

  13. Positive attitudes and self-harming behavior of adolescents in a juvenile detention house in Taiwan.

    Tsai, Mei-Hua; Fang, Kai-Chi; Lu, Chia-Hui; Chen, Chih-Dao; Hsieh, Chi-Pan; Chen, Tsung-Tai

    2011-08-01

    This study aimed to evaluate the less stigmatizing positivity construct screening measurement and its association with recent self-harming behaviors among adolescents. Participants were 193 detained Taiwanese adolescents. Questionnaires consisted of a deliberate self-harm inventory, a positivity construct measurement, a depression scale, data concerning risky health behaviors and demographics. The prevalence rate of recent self-harming behavior among adolescents in the detention house was 43.5%. The logistic model showed that age, gender and level of positivity demonstrated significant odds ratios for self-harm behavior. Results showed that younger age and female gender increased self-harming behavior. In addition, low score on positivity construct screening measurement increased the probability of self-harming behavior. Furthermore, these adolescents also engaged in risky health behaviors and were more depressed. Parental and school awareness for these risky behaviors should be enhanced and appropriate early interventions implemented to prevent negative health outcomes.

  14. Characteristics and trends of self-harming behaviour in young people.

    Cleaver, Karen

    Deliberate self-harm is recognized as a serious public health issue in young people. There is evidence that young people who self-harm are more likely to repeat self-harm, and this in turn increases their risk of completed suicide. Prevalence studies have identified that the rate of self-harm among young people is on the increase, information largely based on data arising from review and analysis of hospital attendances. However, community-based studies indicate that the prevalence is much higher, with those seen in emergency departments representing the 'tip of the iceberg' (Hawton and Rodham, 2006). Young people's motives for self-harm are discussed, as are research findings which indicate that nurses can have negative attitudes towards patients who self-harm. The article considers the implications of this for young people and identifies areas for future research.

  15. Dealing with difficult days: Functional coping dynamics in self-harm ideation and enactment.

    Nielsen, Emma; Sayal, Kapil; Townsend, Ellen

    2017-01-15

    Self-harm affords people a means of coping. However, little is known about how functional coping dynamics differ between stressful situations in which people self-harm (enactment), think about harming (ideation), or experience no self-harmful thoughts or behaviours. Participants (N = 1,157) aged 16-49 years (M = 18.21, SD = 3.24) with a recent history of self-harm (past 3 months) reported how they coped in response to their most significant recent stressor (3 months). Almost 40% of participants, all of whom had self-harmed in the last 3 months, had no self-harm experience (thoughts or behaviours) in response to their most significant stressor in that time frame. In multivariate analysis, adjusting for symptoms of depression and anxiety, reappraisal coping was predictive of self-harm thoughts. Approach, emotion regulation and reappraisal coping were predictive of self-harm behaviour. Emotion regulation coping differentiated self-harm ideation and enactment groups. The cross-sectional design of the study precludes the ability to make inferences regarding causality. Further, there is no agreed definition of 'recent' self-harm. Taken together, the findings suggest that functional coping dynamics may be differentially associated with self-harm ideation and enactment. This is important, given that understanding the transitions between ideation and enactment has been identified as a critical frontier in suicide prevention. Further, results indicate that seemingly innocuous events may have a profound impact as tipping points for enaction; this has implications for clinical practice, including the co-production of safety plans. Copyright © 2016. Published by Elsevier B.V.

  16. Development of an Electronic Pediatric All-Cause Harm Measurement Tool Using a Modified Delphi Method.

    Stockwell, David Christopher; Bisarya, Hema; Classen, David C; Kirkendall, Eric S; Lachman, Peter I; Matlow, Anne G; Tham, Eric; Hyman, Dan; Lehman, Samuel M; Searles, Elizabeth; Muething, Stephen E; Sharek, Paul J

    2016-12-01

    To have impact on reducing harm in pediatric inpatients, an efficient and reliable process for harm detection is needed. This work describes the first step toward the development of a pediatric all-cause harm measurement tool by recognized experts in the field. An international group of leaders in pediatric patient safety and informatics were charged with developing a comprehensive pediatric inpatient all-cause harm measurement tool using a modified Delphi technique. The process was conducted in 5 distinct steps: (1) literature review of triggers (elements from a medical record that assist in identifying patient harm) for inclusion; (2) translation of triggers to likely associated harm, improving the ability for expert prioritization; (3) 2 applications of a modified Delphi selection approach with consensus criteria using severity and frequency of harm as well as detectability of the associated trigger as criteria to rate each trigger and associated harm; (4) developing specific trigger logic and relevant values when applicable; and (5) final vetting of the entire trigger list for pilot testing. Literature and expert panel review identified 108 triggers and associated harms suitable for consideration (steps 1 and 2). This list was pared to 64 triggers and their associated harms after the first of the 2 independent expert reviews. The second independent expert review led to further refinement of the trigger package, resulting in 46 items for inclusion (step 3). Adding in specific trigger logic expanded the list. Final review and voting resulted in a list of 51 triggers (steps 4 and 5). Application of a modified Delphi method on an expert-constructed list of 108 triggers, focusing on severity and frequency of harms as well as detectability of triggers in an electronic medical record, resulted in a final list of 51 pediatric triggers. Pilot testing this list of pediatric triggers to identify all-cause harm for pediatric inpatients is the next step to establish the

  17. Emergency Department Staff Beliefs About Self-Harm: A Thematic Framework Analysis.

    Koning, Kate Louise; McNaught, Angela; Tuffin, Keith

    2017-11-03

    To explore the beliefs and attitudes of emergency department staff about self-harm behaviour. Existing studies looking at views regarding self-harm rely solely on the information provided by medical and nursing staff using a questionnaire format. No studies currently consider ancillary staff members' beliefs about self-harm, even though they also work with these patients. A thematic framework analysis of interview transcripts was carried out. Individual semi-structured interviews were conducted from December 2015 to February 2016. Fifteen medical, nursing, and ancillary staff members from a large, tertiary emergency department participated. There were 5 major themes identified-causes of self-harm are multifactorial; beliefs about self-harm can change over time; emergency departments should only focus on the physical; self-harm occurs on a spectrum; and the system has failed. The results suggest participants felt ill-prepared and lacking in appropriate training to help patients that self-harm, and furthermore they have little faith in the mental health system. Staff beliefs and attitudes may change over time with exposure to patients who self-harm, possibly becoming more positive in response to a greater understanding of why the self-harm behaviour is occurring.

  18. Stock Market Fluctuations and Self-Harm among Children and Adolescents in Hong Kong.

    Wong, Wilfred Hing-Sang; Lee, James Chun-Yin; Ho, Frederick Ka-Wing; Li, Tim Man-Ho; Ip, Patrick; Chow, Chun-Bong

    2017-06-09

    Although a few studies investigated the impact of stock market fluctuations on population health, the question of whether stock market fluctuations have an impact on self-harm in children and adolescents remain unanswered. This study therefore investigated the association between stock market fluctuations and self-harm among children and adolescents in Hong Kong. Daily self-harm attendance records were retrieved from all 18 local Accident and Emergency Departments (AED) from 2001 to 2012. 4931 children and adolescents who committed self-harm were included. The results indicated positive correlation between daily change in stock market index, Hang Seng Index (∇HSI, per 300 points), and daily self-harm incident risk of children and adolescents, without time lag between the two. The incident risk ratio for ∇HSI was 1.09 ( p = 0.0339) in children and 1.06 ( p = 0.0246) in adolescents. Importantly, non-trading days were found to impose significant protective effect in both groups against self-harm risk. Our results showed that stock market fluctuations were related to self-harm behaviors in children and adolescents. Parents and professionals should be educated about the potential harm of stock market fluctuations and the importance of effective parenting in reducing self-harm among children and adolescents.

  19. E-cigarette Regulation and Harm Reduction: The Case of Hong Kong.

    Churk, Shue Sing

    Harm reduction is an internationally recognized tobacco control strategy. E-cigarettes, being a less harmful alternative to smoking, have the potential to achieve harm reduction. Within this context, this article critiques Hong Kong’s legal regime governing e-cigarettes and the proposed prohibition of the product. It is argued that the current law is uncertain and inadequate. Although a reform of laws relating to e-cigarettes is needed, it is argued that banning the product altogether as a means to reducing the harm of tobacco use is unsupported by evidence.

  20. Virtue ethics as an alternative to deontological and consequential reasoning in the harm reduction debate.

    Christie, Timothy; Groarke, Louis; Sweet, William

    2008-02-01

    There is strong evidence that harm reduction interventions such as Supervised Injection Sites and Needle Exchange Programs prevent many of the negative consequences of problematic substance use. Yet many governments, including the United States and Canada, still do not endorse these interventions, claiming that they do not get people off of drugs and send a mixed message. This paper will analyze objections to harm reduction in light of the ethical theories of John Stuart Mill, Immanuel Kant and Aristotle. The most important ethical issue in the abstinence vs. harm reduction debate is whether harm reduction - because it does not require individuals to either reduce their consumption of illicit substances or to abstain from illicit substance use - can be ethically justified. Harm reduction interventions are clearly justified on Utilitarian grounds because, based on the evidence, such policies would produce the greatest good for the greatest number. However, Kant would not think that the values guiding harm reduction are ethical because the justification of harm reduction interventions focuses exclusively on examining consequences. Virtue Ethics seeks to find the proper balance between harm reduction and abstinence. We claim that the virtue of compassion would provide a defense of harm reduction.

  1. Public health officials and MECs should be held liable for harm ...

    Public health officials and MECs should be held liable for harm caused to patients through incompetence, indifference, maladministration or negligence regarding the availability of hospital equipment.

  2. Self-harm and attempted suicide within inpatient psychiatric services: a review of the literature.

    James, Karen; Stewart, Duncan; Bowers, Len

    2012-08-01

    Self harm is a major public health concern, yet there are considerable challenges in providing support for those who self harm within psychiatric inpatient services. This paper presents the first review of research into self harm within inpatient settings. Searches of the main electronic databases were conducted using key words for self harm and inpatient care. There was substantial variation in the rates of self-harm and attempted suicide between studies, but rates were highest on forensic wards. There was no evidence of differences in prevalence of self-harm between men and women; women, however, were at increased risk of attempting suicide. People were more likely to self-harm in private areas of the ward and in the evening hours, and often self-harmed in response to psychological distress, or elements of nursing care that restricted their freedom. Wards used a variety of strategies to prevent self-harm; however, there is little research into their effectiveness. © 2012 The Authors. International Journal of Mental Health Nursing © 2012 Australian College of Mental Health Nurses Inc.

  3. Experienced Harm from Other People's Drinking: A Comparison of Northern European Countries

    Inger Synnøve Moan

    2015-01-01

    Full Text Available Objective This study addresses how experienced harm from other people's drinking varies between six Northern European countries by comparing 1 the prevalence of experienced harm and 2 the correlates of harm. Method The data comprise 18ȓ69-year olds who participated in general population surveys in Denmark, Finland, Iceland, Norway, Sweden, and Scotland during the period 2008–2013. Comparative data were available on five types of harm: physical abuse, damage of clothes/belongings, verbal abuse, being afraid, and being kept awake at night. Results This study shows that harms from other's drinking are commonly experienced in all six countries. Being kept awake at night is the most common harm, while being physically harmed is the least common. The proportions that reported at least one of the five problems were highest in Finland and Iceland and lowest in Norway, but also relatively low in Sweden. Across countries, the level of harm was highest among young, single, urban residents, and for some countries among women and those who frequently drank to intoxication themselves. Conclusions The study revealed large differences in the prevalence of harm in countries with fairly similar drinking cultures. However, the correlates of such experiences were similar across countries. Possible explanations of the findings are discussed, including differences in study design.

  4. The relationship between alcohol consumption and related harm among young university students.

    Hart, Ellen; Burns, Sharyn

    2016-04-01

    Issue addressed Research has shown that Australian university students consume alcohol at a higher level than their peers from the general population and are therefore more likely to witness and experience alcohol-related harm. This study measured the prevalence of alcohol consumption among 18-24-year-old university students and the association between alcohol consumption and witnessed and experienced harms. Methods A random cross-sectional sample of university students aged 18-24 years (n=2466) was recruited via the University Survey Office and through random intercept at campus market day. All participants completed an online survey that included the Alcohol Use Disorders Identification Test, Alcohol Problems Scale and an additional scale measuring witnessed harm. Results Principal Components Analysis revealed three factors within the Alcohol Problems Scale; i.e. Criminal and Aggressive Behaviour, Health and Emotional Harms and Sexual Harms. Students who consume alcohol at high-risk levels were significantly more likely to score highly on each factor, 1.6 times more likely to experience harm and 1.1 times more likely to witness harm than students who consume alcohol at low-risk levels. Conclusions The positive association between alcohol consumption and alcohol-related harm supports previous findings. This study adds previous research through the categorisation of harm into factors. So what? Integrated and comprehensive interventions addressing alcohol consumption among young university students that are informed by evidence-based research can be tailored to ensure that they meet the needs of the target group.

  5. Harmful algal bloom smart device application: using image analysis and machine learning techniques for early classification of harmful algal blooms (SETAC presentation)

    Reports of toxic cyanobacterial blooms, also known as Harmful Algal Blooms (HABS) have increased drastically in recent years. HABS impact human health from causing mild allergies to liver damage and death. The Ecological Stewardship Institute (ESI) at Northern Kentucky Universi...

  6. Environments, risk and health harms: a qualitative investigation into the illicit use of anabolic steroids among people using harm reduction services in the UK.

    Kimergård, Andreas; McVeigh, Jim

    2014-06-04

    The illicit use of anabolic steroids among the gym population continues to rise, along with the number of steroid using clients attending harm reduction services in the UK. This presents serious challenges to public health. Study objectives were to account for the experiences of anabolic steroid users and investigate how 'risk environments' produce harm. Qualitative face-to-face interviews with 24 users of anabolic steroids engaged with harm reduction services in the UK. Body satisfaction was an important factor when deciding to start the use of anabolic steroids. Many users were unaware of the potential dangers of using drugs from the illicit market, whereas some had adopted a range of strategies to negotiate the hazards relating to the use of adulterated products, including self-experimentation to gauge the perceived efficacy and unwanted effects of these drugs. Viewpoints, first-hand anecdotes, norms and practices among groups of steroid users created boundaries of 'sensible' drug use, but also promoted practices that may increase the chance of harms occurring. Established users encouraged young users to go to harm reduction services but, at the same time, promoted risky injecting practices in the belief that this would enhance the efficacy of anabolic steroids. Current steroid-related viewpoints and practices contribute to the risk environment surrounding the use of these drugs and may undermine the goal of current public health strategies including harm reduction interventions. The level of harms among anabolic steroid users are determined by multiple and intertwining factors, in addition to the harms caused by the pharmacological action or injury and illness associated with incorrect injecting techniques. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  7. ICHTHYOLOGICAL ASPECTS OF THE MATERIALITITY HARM TO FISHERIES DETERMINING

    І. Нrytsyniak

    2013-09-01

    Full Text Available Purpose. Definition and analysis of biological criteria for qualified materiality harm caused by the fishing industry as a result of illegal extraction of water biological resources. Methodology. The calculations were carried out for the top of the Kanev reservoir and were based on data from the Water of Life reserves the Kanev reservoir identified Institute of Fisheries NAAS within acceptable elaboration of industrial catches for 2013 year. Index of an average natural mortality were determined by the method of P.V. Tyurin. In the calculations indicators used listed in the acting regulatory and technical literature. Findings. As a criterion for determining the materiality of damage used daily natural mortality rate, which is accepted at 0,1 % of the balance. It is established that for certain types of top of the Kanev reservoir extraction already 1 ind., can lead to consequences that are assessed as significant. However, the simultaneous extraction of several species in an amount which is less than the limit also requires evaluation from the standpoint of materiality. To this end, proposed criterion is expensive - in calculating losses greater than 266 tax-free minimum incomes of citizens, damage fisheries can be considered significant. Originality. First proposed procedure for assessing the impact on the ichthyopopulation of illegal fishing from the standpoint of materiality damage. Practical value. The results are used in the preparation of expert reports for regulatory environmental agencies.

  8. Binational collaboration to study Gulf of Mexico's harmful algae

    Soto, Inia; Hu, Chuanmin; Steidinger, Karen; Muller-Karger, Frank; Cannizzaro, Jennifer; Wolny, Jennifer; Cerdeira-Estrada, Sergio; Santamaria-del-Angel, Eduardo; Tafoya-del-Angel, Fausto; Alvarez-Torres, Porfirio; Herrera Silveira, Jorge; Allen, Jeanne

    2012-01-01

    Blooms of the toxic marine dinoflagellate Karenia brevis cause massive fish kills and other public health and economic problems in coastal waters throughout the Gulf of Mexico [Steidinger, 2009]. These harmful algal blooms (HABs) are a gulf-wide problem that require a synoptic observing system for better serving decision-making needs. The major nutrient sources that initiate and maintain these HABs and the possible connectivity of blooms in different locations are important questions being addressed through new collaborations between Mexican and U.S. researchers and government institutions. These efforts were originally organized under the U.S./Mexico binational partnership for the HABs Observing System (HABSOS), led by the U.S. Environmental Protection Agency's Gulf of Mexico Program (EPAGMP) and several agencies in Veracruz, Mexico, since 2006. In 2010 these efforts were expanded to include other Mexican states and institutions with the integrated assessment and management of the Gulf of Mexico Large Marine Ecosystem (GoMLME) program sponsored by the Global Environment Facility (GEF), the United Nations Industrial Development Organization (UNIDO), the Secretaría de Medio Ambiente y Recursos Naturales (SEMARNAT), and the National Oceanic and Atmospheric Administration (NOAA).

  9. Early marriage in Africa--trends, harmful effects and interventions.

    Walker, Judith-Ann

    2012-06-01

    This article explores the pattern of early marriage in Africa. It focuses on the sub-Saharan region as an area with the highest rates of early marriage in the world. The harmful effects of early marriage are explored in terms of impact on the health, education and economic well-being of young girls. The paper outlines a framework for analyzing global, regional and local initiatives to curb early marriage and examines the application of these interventions in sub-Saharan countries. Regional patterns are then examined and countries which have made progress in reducing age of marriage are compared to countries in which age of marriage amongst girls has reminded low. The paper concludes on the note that countries with the highest rates of early marriage are also the countries with the highest rates of poverty and highest population growth rates. The paper argues for a sub-regional strategy to address the problem of early marriage in the zone with the highest incidence.

  10. Disclosing harmful medical errors to patients: tackling three tough cases.

    Gallagher, Thomas H; Bell, Sigall K; Smith, Kelly M; Mello, Michelle M; McDonald, Timothy B

    2009-09-01

    A gap exists between recommendations to disclose errors to patients and current practice. This gap may reflect important, yet unanswered questions about implementing disclosure principles. We explore some of these unanswered questions by presenting three real cases that pose challenging disclosure dilemmas. The first case involves a pancreas transplant that failed due to the pancreas graft being discarded, an error that was not disclosed partly because the family did not ask clarifying questions. Relying on patient or family questions to determine the content of disclosure is problematic. We propose a standard of materiality that can help clinicians to decide what information to disclose. The second case involves a fatal diagnostic error that the patient's widower was unaware had happened. The error was not disclosed out of concern that disclosure would cause the widower more harm than good. This case highlights how institutions can overlook patients' and families' needs following errors and emphasizes that benevolent deception has little role in disclosure. Institutions should consider whether involving neutral third parties could make disclosures more patient centered. The third case presents an intraoperative cardiac arrest due to a large air embolism where uncertainty around the clinical event was high and complicated the disclosure. Uncertainty is common to many medical errors but should not deter open conversations with patients and families about what is and is not known about the event. Continued discussion within the medical profession about applying disclosure principles to real-world cases can help to better meet patients' and families' needs following medical errors.

  11. Epidemiologic perspectives on smokeless tobacco marketing and population harm.

    Tomar, Scott L

    2007-12-01

    Moist snuff is the most popular form of orally-used smokeless tobacco in North America and parts of Europe. Because moist snuff use conveys lower risks for morbidity or mortality than does cigarette smoking, its use has been proposed as a tobacco harm-reduction strategy. This article critically reviews new and published epidemiologic evidence on health effects of moist snuff and its patterns of use relative to smoking in the United States, Sweden, and Norway. The available evidence suggests that: (1) moist snuff is a human carcinogen and toxin, (2) increased promotion of moist snuff has led to increased sales in those countries, (3) the uptake of moist snuff in these three countries during the past several decades has occurred primarily among adolescent and young adult men, (4) increased prevalence of snuff use has not been associated consistently with a reduction in smoking initiation or prevalence, (5) moist snuff use apparently plays a very minor role in smoking cessation in the U.S. and an inconsistent role in Sweden, (6) U.S. states with the lowest smoking prevalence also tend to have the lowest prevalence of snuff use, (7) there are no data on the efficacy of snuff as a smoking-cessation method, (8) the prevalence of cigarette smoking is relatively high among people who use snuff, and (9) snuff use is more consistently associated with partial substitution for smoking than with complete substitution. The evidence base for promotion of snuff use as a public health strategy is weak and inconsistent.

  12. First do no harm: iatrogenic maintaining factors in anorexia nervosa.

    Treasure, Janet; Crane, Anna; McKnight, Rebecca; Buchanan, Emmakate; Wolfe, Melissa

    2011-01-01

    The aim of this paper is to reflect on the way that we as clinicians may play an inadvertent role in perpetuating eating disordered behaviour. This is considered within the theoretical framework of Schmidt and Treasures' maintenance model of anorexia nervosa (AN). The model includes four main domains; interpersonal factors, pro-AN beliefs, emotional style and thinking style. Interpersonal reactions are of particular relevance as clinicians (as with family members) may react with high expressed emotion and unknowingly encourage eating disorder behaviours to continue. Hostility in the form of coercive refeeding in either a hospital or outpatient setting may strengthen conditioned food avoidance and pessimism may hamper motivation to change. Negative schema common to eating disorders, for example low self-esteem, perfectionism and striving for social value may augment existing or initiate new eating disorder behaviour. Services can become a reinforcing influence by providing an overly protective, palliating environment which ensures safety, security and acceptance whilst reducing loneliness and isolation. This stifles the need for an individual to develop their own sense of responsibility, autonomy and independence allowing avoidance to dominate. Furthermore, the highly structured environment of inpatient care supports the rigid attention to detail and inflexibility that is characteristic of people with eating disorders, and allows these negative behaviours to thrive. Careful planning of service provision, reflective practice, supervision and regular team feedback is essential to prevent iatrogenic harm. Copyright © 2011 John Wiley & Sons, Ltd and Eating Disorders Association.

  13. Impulse noise: can hitting a softball harm your hearing?

    Cook, Korrine; Atcherson, Samuel R

    2014-01-01

    The purpose of this study is to identify whether or not different materials of softball bats (wooden, aluminum, and composite) are a potential risk harm to hearing when batting players strike a 12'' core .40 softball during slow, underhand pitch typical of recreational games. Peak sound pressure level measurements and spectral analyses were conducted for three controlled softball pitches to a batting participant using each of the different bat materials in an unused outdoor playing field with regulation distances between the pitcher's mound and batter's box. The results revealed that highest recorded peak sound pressure level was recorded from the aluminum (124.6 dBC) bat followed by the composite (121.2 dBC) and wooden (120.0 dBC) bats. Spectral analysis revealed composite and wooden bats with similar broadly distributed amplitude-frequency response. The aluminum bat also produced a broadly distributed amplitude-frequency response, but there were also two very distinct peaks at around 1700 Hz and 2260 Hz above the noise floor that produced its ringing (or ping) sound after being struck. Impulse (transient) sounds less than 140 dBC may permit multiple exposures, and softball bats used in a recreational slow pitch may pose little to no risk to hearing.

  14. Impulse Noise: Can Hitting a Softball Harm Your Hearing?

    Korrine Cook

    2014-01-01

    Full Text Available The purpose of this study is to identify whether or not different materials of softball bats (wooden, aluminum, and composite are a potential risk harm to hearing when batting players strike a 12′′ core .40 softball during slow, underhand pitch typical of recreational games. Peak sound pressure level measurements and spectral analyses were conducted for three controlled softball pitches to a batting participant using each of the different bat materials in an unused outdoor playing field with regulation distances between the pitcher’s mound and batter’s box. The results revealed that highest recorded peak sound pressure level was recorded from the aluminum (124.6 dBC bat followed by the composite (121.2 dBC and wooden (120.0 dBC bats. Spectral analysis revealed composite and wooden bats with similar broadly distributed amplitude-frequency response. The aluminum bat also produced a broadly distributed amplitude-frequency response, but there were also two very distinct peaks at around 1700 Hz and 2260 Hz above the noise floor that produced its ringing (or ping sound after being struck. Impulse (transient sounds less than 140 dBC may permit multiple exposures, and softball bats used in a recreational slow pitch may pose little to no risk to hearing.

  15. Benefit and harms of new anti-cancer drugs.

    Vera-Badillo, Francisco E; Al-Mubarak, Mustafa; Templeton, Arnoud J; Amir, Eitan

    2013-06-01

    Phase III randomized controlled trials (RCTs) assess clinically important differences in endpoints that reflect benefit to and harm of patients. Defining benefit of cancer drugs can be difficult. Overall survival and quality of life are the most relevant primary endpoints, but difficulty in measuring these mean that other endpoints are often used, although their surrogacy or clinical relevance has not always been established. In general, advances in drug development have led to numerous new drugs to enter the market. Pivotal RCT of several new drugs have shown that benefit appeared greater for targeted anticancer agents than for chemotherapeutic agents. This effect seems particularly evident with targeted agents evaluated in biomarker-driven studies. Unfortunately, new therapies have also shown an increase in toxicity. Such toxicity is not always evident in the initial reports of RCTs. This may be a result of a statistical inability to detect differences between arms of RCTs, or occasionally due to biased reporting. There are several examples where reports of new toxicities could only be found in drug labels. In some cases, the small improvement in survival has come at a cost of substantial excess toxicity, leading some to consider such therapy as having equipoise.

  16. Harmful cleats of football boots: a biomechanical evaluation.

    Bentley, J A; Ramanathan, A K; Arnold, G P; Wang, W; Abboud, R J

    2011-09-01

    Football players wear boots of varying cleat designs with some preferring the bladed cleats while others opting for the conventional studded cleats. The current study compares biomechanically the boots with differing cleat designs and their effect on feet, if any. Twenty-nine healthy male volunteers were recruited from amateur football teams. They were asked to perform three trials each of two activities: a straight run and a run cutting at a 60° angle wearing bladed and studded Adidas®-F series boots on artificial turf. Plantar pressure values were recorded using the Pedar®-X in-shoe pressure measuring device. Peak pressure and pressure-time integral were analysed over 11 clinically relevant areas under the foot. While the in-shoe pressure and pressure-time integral were higher under the medial half of the foot with studded boots, they were higher under the lateral half of the foot with the bladed design. The studded boots can be considered safer as the pressure distribution across the foot and the pattern of centre of pressure progression mimicked the normal motif, whereas the bladed boots could potentially be deemed relatively more harmful due to the unnatural increased loading under the lateral half of the foot, predisposing the foot to injuries. Copyright © 2010 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

  17. Deliberate self-harm behavior among young violent offenders.

    Laporte, Natalie; Ozolins, Andrejs; Westling, Sofie; Westrin, Åsa; Billstedt, Eva; Hofvander, Björn; Wallinius, Märta

    2017-01-01

    Deliberate self-harm behavior (DSH) can have profound effects on a person's quality of life, and challenges the health care system. Even though DSH has been associated with aggressive interpersonal behaviors, the knowledge on DSH in persons exhibiting such behaviors is scarce. This study aims to (1) specify the prevalence and character of DSH, (2) identify clinical, neurocognitive, psychosocial, and criminological characteristics associated with DSH, and (3) determine predictors of DSH among young violent offenders. Data were collected from a nationally representative cohort of 270 male violent offenders, 18-25 years old, imprisoned in Sweden. Participants were interviewed and investigated neuropsychologically, and their files were reviewed for psychosocial background, criminal history, mental disorders, lifetime aggressive antisocial behaviors, and DSH. A total of 62 offenders (23%) had engaged in DSH at some point during their lifetime, many on repeated occasions, yet without suicidal intent. DSH was significantly associated with attention deficit hyperactivity disorder, mood disorders, anxiety disorders, various substance use disorders, being bullied at school, and repeated exposure to violence at home during childhood. Mood disorders, anxiety disorders, and being bullied at school remained significant predictors of DSH in a total regression model. Violent offenders direct aggressive behaviors not only toward other people, but also toward themselves. Thus, DSH must be assessed and prevented in correctional institutions as early as possible, and more knowledge is needed of the function of DSH among offenders.

  18. Aerosol Emissions from Great Lakes Harmful Algal Blooms

    May, Nathaniel W. [Department; Olson, Nicole E. [Department; Panas, Mark [Department; Axson, Jessica L. [Department; Tirella, Peter S. [Department; Kirpes, Rachel M. [Department; Craig, Rebecca L. [Department; Gunsch, Matthew J. [Department; China, Swarup [William; Laskin, Alexander [William; Ault, Andrew P. [Department; Department; Pratt, Kerri A. [Department; Department

    2017-12-20

    In freshwater lakes, harmful algal blooms (HABs) of Cyanobacteria (blue-green algae) produce toxins that impact human health. However, little is known about the chemical species present in lake spray aerosol (LSA) produced from wave-breaking in freshwater HABs. In this study, a laboratory LSA generator produced aerosols from freshwater samples collected from Lake Michigan and Lake Erie during HAB and non-bloom conditions. Particles were analyzed for size and chemical composition by single particle mass spectrometry, electron microscopy, and fluorescence microscopy, with three distinct types of LSA identified with varying levels of organic carbon and biological material associated with calcium salts. LSA autofluorescence increases with blue-green algae concentration, showing that organic molecules of biological origin are incorporated in LSA from HABs. The number fraction of LSA with biological mass spectral markers also increases with particle diameter (greater than 0.5 μm), showing that HABs have size-dependent impacts on aerosol composition. The highest number fraction of LSA enriched in organic carbon were observed in particles less than 0.5 μm in diameter. Understanding the transfer of organic and biogenic material from freshwater to the atmosphere via LSA particles is crucial for determining health and climate effects due to HABs.

  19. Adrenaline in anaphylaxis treatment. Balancing benefits and harms.

    Cervellin, Gianfranco; Sanchis-Gomar, Fabian; Lippi, Giuseppe

    2016-06-01

    Although anaphylaxis is a relatively common disorder, clinicians and scientists have debated on how to best define and manage this condition. The current recommendations are focused on the central role of adrenaline, but evidence in support of this therapeutic approach is modest, mainly for the lack of well-designed trials. Conversely, serious adverse effects are commonly reported following adrenaline use, especially when given intravenously. These include hypertension, ventricular arrhythmias, myocardial infarction, pulmonary edema. Anaphylaxis treatment, with special focus on adrenaline utilization, both in pre-hospital and in-hospital settings. Aim is to examine in depth the balance between benefits and harms of this important drug. Due to the lack of solid evidence supporting the use of adrenaline in patients with anaphylaxis, except in severe cases, the strength of recommendations should be readdressed, limiting administration to selected categories of patients. Caregivers should promptly act in pre-hospital setting, given the shortness of time and lack of technology. In the hospital setting, and more specifically in the ED, clinicians should consider the prompt use of adrenaline in severe anaphylaxis cases, but they should also be able to judiciously wait in the vast majority of milder anaphylactic reactions, which may resolve spontaneously.

  20. L-lysine escinat, thiotriazolin, gordox and mydocalm influence on oxygen tension in the intestinal wall and acid-base balance and limited proteolysis in intestinal venous blood in terms of intraabdominal hypertension modeling

    Sapegin V.I.

    2014-11-01

    Full Text Available In acute experiments on rabbits there were studied changes in oxygen tension in the intestinal wall tissues, acid-base balance and limited proteolysis and its inhibitors in intestinal venous blood, protective action of L-lysine escinat (0,15 mg/kg / single dose, thiotriazolin (25 mg/kg / single dose, aprotinin (gordox (10,000 units/kg / single dose in sequential modeling of standard levels increasing of intra-abdominal hypertension (IAH — 50, 100, 150, 200, 250, 300, 350 m H2O, and also of tolperison (mydocalm (5 mg/kg / single dose on modeling of stable 3-hour IAH 200 m H2O. The IAH modeling was performed by means of stand of our construction. Under the influence of IAH the compensated metabolic acidosis in intestinal venous blood with a compensative hyperpnoe develops, decline of oxygen tension in tissues and activating of a limited proteolysis as well as decline of its inhibitors activity in intestinal venous blood occur. By the degree of metabolic acidosis prevention investigational preparations were distributed as follows gordox > thiotriazolin = L-lysine escinat = mydocalm, and by prevention of decline of oxygen tension in tissues — thiotriazolin > L-lysine escinat > mydocalm > gordox, it is is connected with different rate of methabolic products excretion into the blood, due to the influence on blood circulation and transcapilary exchange. By the degree of prevention of proteolytic activity and inhibitory potential changes, investigational preparations were distributed as follows: gordox > mydocalm > thiotriazolin > L-lysine escinat, this is connected with inhibition of proteolysis in gordox, and in other ones – with reduction of ischemic damage of tissues. Owing to different mechanism of action thiotriazolin, L-lysine escinat and mydocalm may be simultaneously recommended for a conservative treatment of patients with intraabdominal hypertension syndrome.

  1. Harm reduction with pharmacotherapy for homeless people with alcohol dependence: protocol for a randomized controlled trial.

    Collins, Susan E; Saxon, Andrew J; Duncan, Mark H; Smart, Brian F; Merrill, Joseph O; Malone, Daniel K; Jackson, T Ron; Clifasefi, Seema L; Joesch, Jutta; Ries, Richard K

    2014-07-01

    Interventions requiring abstinence from alcohol are neither preferred by nor shown to be highly effective with many homeless individuals with alcohol dependence. It is therefore important to develop lower-threshold, patient-centered interventions for this multimorbid and high-utilizing population. Harm-reduction counseling requires neither abstinence nor use reduction and pairs a compassionate style with patient-driven goal-setting. Extended-release naltrexone (XR-NTX), a monthly injectable formulation of an opioid receptor antagonist, reduces craving and may support achievement of harm-reduction goals. Together, harm-reduction counseling and XR-NTX may support alcohol harm reduction and quality-of-life improvement. Study aims include testing: a) the relative efficacy of XR-NTX and harm-reduction counseling compared to a community-based, supportive-services-as-usual control, b) theory-based mediators of treatment effects, and c) treatment effects on publicly funded service costs. This RCT involves four arms: a) XR-NTX+harm-reduction counseling, b) placebo+harm-reduction counseling, c) harm-reduction counseling only, and d) community-based, supportive-services-as-usual control conditions. Participants are currently/formerly homeless, alcohol dependent individuals (N=300). Outcomes include alcohol variables (i.e., craving, quantity/frequency, problems and biomarkers), health-related quality of life, and publicly funded service utilization and associated costs. Mediators include 10-point motivation rulers and the Penn Alcohol Craving Scale. XR-NTX and harm-reduction counseling are administered every 4weeks over the 12-week treatment course. Follow-up assessments are conducted at weeks 24 and 36. If found efficacious, XR-NTX and harm-reduction counseling will be well-positioned to support reductions in alcohol-related harm, decreases in costs associated with publicly funded service utilization, and increases in quality of life among homeless, alcohol

  2. Differences in heavy-ion-induced DNA double-strand breaks in a mouse DNA repair-deficient mutant cell line (SL3-147) before and after chromatin proteolysis

    Murakami, Masahiro; Eguchi-Kasai, Kiyomi; Sato, Koki; Minohara, Shinichi; Kanai, Tatsuaki; Yatagai, Fumio.

    1995-01-01

    DNA double-strand breaks induced by X- or neon beam-irradiation in a DNA double-strand break-repair-deficient mutant cell line (SL3-147) were examined. The increase in the number of DNA double-strand breaks was dose-depend after irradiation with X-rays and neon beams and was enhanced by chromatin-proteolysis treatment before irradiation. These results suggest that the induction of DNA double-strand breaks by ionizing radiation, including heavy-ions, is influenced by the chromatin structure. (author)

  3. Genderedness of Bar Drinking Culture and Alcohol-Related Harms: A Multi-Country Study

    Roberts, Sarah C. M.; Bond, Jason; Korcha, Rachael; Greenfield, Thomas K.

    2013-01-01

    This study explores whether associations between consuming alcohol in bars and alcohol-related harms are consistent across countries and whether country-level characteristics modify associations. We hypothesized that genderedness of bar drinking modifies associations, such that odds of harms associated with bar drinking increase more rapidly in…

  4. Do Coping Strategies Mediate the Relationship Between Parental Attachment and Self-Harm in Young People?

    Glazebrook, Katie; Townsend, Ellen; Sayal, Kapil

    2016-01-01

    Insecure attachment is associated with self-harm in young people, but little research has explored the pathways through which this relationship develops. We investigated whether attachment impacts on self-harm via its effect on coping strategies and appraisal of problem-solving abilities. A total of 314 students aged 18-20 years completed an online survey with measures of parental attachment, emotion-focused and problem-focused coping strategies, and psychological distress and self-harm. A mediational model was not supported as there were no direct effects between parental attachment and self-harm. However, analysis of specific indirect pathways revealed that perceived parental attachment impacts on self-harm through problem-focused coping. Higher quality of attachment was associated with greater reliance on problem-focused (adaptive) coping, which in turn was associated with a decreased risk of having self-harmed. Furthermore, poorer paternal attachment was associated with lower appraisal of problem-solving skills, which in turn was associated with an increased risk of having self-harmed. Individuals with insecure attachment may be more vulnerable to self-harm because they lack other more constructive coping strategies for relieving stress.

  5. 17 CFR 1.67 - Notification of final disciplinary action involving financial harm to a customer.

    2010-04-01

    ... disciplinary action involving financial harm to a customer. 1.67 Section 1.67 Commodity and Securities... Miscellaneous § 1.67 Notification of final disciplinary action involving financial harm to a customer. (a) Definitions. For purposes of this section: (1) Final disciplinary action means any decision by or settlement...

  6. Lung cancer screening in the NELSON trial: balancing harms and benefits

    N. Horeweg (Nanda)

    2014-01-01

    markdownabstract__Abstract__ In this thesis, the harms and benefits of lung cancer screening using low-dose computed tomography were investigated. Data of the Dutch-Belgian NELSON trial were used to quantify its harms and benefits and develop strategies to improve the balance between them. If the

  7. Recent self-harm and psychological measures in the emergency department

    Jason R. Randall

    2014-11-01

    Full Text Available The assessment of self-harm risk is a common, difficult, and perplexing task for many physicians, especially those working in emergency departments (ED. Attempts have been made to determine objective methods for assessing patients with suicidal ideation or self-harm though there is still a lack of knowledge about objective assessments of these patients. A study was conducted where 181 suicidal patients were enrolled in two EDs within the city of Edmonton, Canada. Initial interviews were conducted in the ED which collected basic demographics and medical history as well as psychometric measures including the Beck Hopelessness Scale, Barratt Impulsiveness Scale, Brief Symptom Inventory, Drug Abuse Screening Test 10, and CAGE questionnaire. The results of these measures were compared between those who presented to the ED with self-harm and those who presented only with ideation. Those with recent self-harm scored lower on many of the scales and subscales of distress and impulsivity measured compared to those with no recent self-harm. Possible explanations for this difference include differences in psychological traits between the two groups and possible cathartic effects of self-harm. The lower scores obtained by those that present with self-harm may complicate attempts to use psychometric tools to determine future self-harm risk.

  8. Contamination vs. harm-relevant outcome expectancies and covariation bias in spider phobia

    de Jong, Peter J.; Peters, Madelon L.

    There is increasing evidence that spiders are not feared because of harmful outcome expectancies but because of disgust and contamination-relevant outcome expectancies. This study investigated the relative strength of contamination- and harm-relevant UCS expectancies and covariation bias in spider

  9. An agent harms a victim: A functional magnetic resonance imaging study on specific moral emotions

    Kedia, G.; Kedia, G.; Martinot, J.L.; Kedia, G.; Martinot, J.L.; Kedia, G.; Hilton, D.; Berthoz, S.; Wessa, M.

    2008-01-01

    The statement 'An agent harms a victim' depicts a situation that triggers moral emotions. Depending on whether the agent and the victim are the self or someone else, it can lead to four different moral emotions: self-anger ('I harm myself'), guilt ('I harm someone'), other-anger ('someone harms me'), and compassion ('someone harms someone'). In order to investigate the neural correlates of these emotions, we examined brain activation patterns elicited by variations in the agent (self vs. other) and the victim (self vs. other) of a harmful action. Twenty-nine healthy participants underwent functional magnetic resonance imaging while imagining being in situations in which they or someone else harmed themselves or someone else. Results indicated that the three emotional conditions associated with the involvement of other, either as agent or victim (guilt, other-anger, and compassion conditions), all activated structures that have been previously associated with the Theory of Mind (ToM, the attribution of mental states to others), namely, the dorsal medial prefrontal cortex, the precuneus, and the bilateral temporo-parietal junction. Moreover, the two conditions in which both the self and other were concerned by the harmful action (guilt and other-anger conditions) recruited emotional structures (i. e., the bilateral amygdala, anterior cingulate, and basal ganglia). These results suggest that specific moral emotions induce different neural activity depending on the extent to which they involve the self and other. (authors)

  10. Initial Development and Validation of the BullyHARM: The Bullying, Harassment, and Aggression Receipt Measure

    Hall, William J.

    2016-01-01

    This article describes the development and preliminary validation of the Bullying, Harassment, and Aggression Receipt Measure (BullyHARM). The development of the BullyHARM involved a number of steps and methods, including a literature review, expert review, cognitive testing, readability testing, data collection from a large sample, reliability…

  11. Secondary harm mitigation: A more humanitarian framework for international drug law enforcement.

    Blaustein, Jarrett; McLay, Miki; McCulloch, Jude

    2017-08-01

    This article introduces the concept of 'secondary harm mitigation' as a framework for improving the humanitarian credentials of international drug law enforcement agencies. The concept is rooted in a critical analysis of the compatibility of the harm reduction philosophy with Australia's international drug law enforcement practices. On a utilitarian level, the net benefits of international drug law enforcement are determined to be, at best inconclusive, arguably counterproductive and in most cases, incalculable. On a humanitarian level, international drug law enforcement is also determined to be problematic from a criminological standpoint because it generates secondary harms and it is indifferent to the vulnerability of individuals who participate in illicit drug trafficking. Accordingly, the article concludes that a philosophy of harm reduction grounded in the public health perspective is inadequate for mitigating secondary harms arising from Australia's efforts to combat international illicit drug trafficking. A tentative list of secondary harm mitigation principles is presented and the article argues that secondary harm mitigation should replace supply reduction as a core tenet of Australia's National Drug Strategy. The article also concludes that secondary harm mitigation may provide a viable framework for stimulating a productive dialogue between those who advocate prohibition and those who call for decriminalisation at the global level. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Relating faults in diagnostic reasoning with diagnostic errors and patient harm.

    Zwaan, L.; Thijs, A.; Wagner, C.; Wal, G. van der; Timmermans, D.R.M.

    2012-01-01

    Purpose: The relationship between faults in diagnostic reasoning, diagnostic errors, and patient harm has hardly been studied. This study examined suboptimal cognitive acts (SCAs; i.e., faults in diagnostic reasoning), related them to the occurrence of diagnostic errors and patient harm, and studied

  13. Serotonin selectively influences moral judgment and behavior through effects on harm aversion.

    Crockett, Molly J; Clark, Luke; Hauser, Marc D; Robbins, Trevor W

    2010-10-05

    Aversive emotional reactions to real or imagined social harms infuse moral judgment and motivate prosocial behavior. Here, we show that the neurotransmitter serotonin directly alters both moral judgment and behavior through increasing subjects' aversion to personally harming others. We enhanced serotonin in healthy volunteers with citalopram (a selective serotonin reuptake inhibitor) and contrasted its effects with both a pharmacological control treatment and a placebo on tests of moral judgment and behavior. We measured the drugs' effects on moral judgment in a set of moral 'dilemmas' pitting utilitarian outcomes (e.g., saving five lives) against highly aversive harmful actions (e.g., killing an innocent person). Enhancing serotonin made subjects more likely to judge harmful actions as forbidden, but only in cases where harms were emotionally salient. This harm-avoidant bias after citalopram was also evident in behavior during the ultimatum game, in which subjects decide to accept or reject fair or unfair monetary offers from another player. Rejecting unfair offers enforces a fairness norm but also harms the other player financially. Enhancing serotonin made subjects less likely to reject unfair offers. Furthermore, the prosocial effects of citalopram varied as a function of trait empathy. Individuals high in trait empathy showed stronger effects of citalopram on moral judgment and behavior than individuals low in trait empathy. Together, these findings provide unique evidence that serotonin could promote prosocial behavior by enhancing harm aversion, a prosocial sentiment that directly affects both moral judgment and moral behavior.

  14. Self-Harm Behaviour in Adolescents: Body Image and Self-Esteem

    Oktan, Vesile

    2017-01-01

    This research aimed to reveal the relationship between self-harm behaviour, body image, and self-esteem, and examined whether there was a difference between the body image and self-esteem of the adolescents who exhibited self-harm behaviour and those who did not. The study was conducted with the participation of 263 high school students--143…

  15. Genetic and Environmental Contributions to Self-Reported Thoughts of Self-Harm and Suicide

    Althoff, R.R.; Hudziak, J.J.; Willemsen, G.; Hudziak, V.; Bartels, M.; Boomsma, D.I.

    2012-01-01

    Thoughts of self-harm and suicidal behavior are thought to be influenced by both genetics and environment. Molecular genetic studies are beginning to address the question of which genes may be involved and whether different genes may be expressed in men and women. We examined thoughts of self-harm

  16. Responding to Self-Harm: A Documentary Analysis of Agency Policy and Procedure

    Paul, Sally; Hill, Malcolm

    2013-01-01

    This paper reports on the findings of a documentary analysis of policies and procedures relating to self-harm from a range of organisations working with young people in the UK. It identifies the extent to which policies and/or procedures relating to self-harm are available for service providers and offers a wider understanding of the concepts of…

  17. Psychometric properties of the Dutch version of the Attitude Towards Deliberate Self-Harm Questionnaire

    Kool, N.; van Meijel, B.; van der Bijl, J.; Koekkoek, B.; Kerkhof, A.

    2015-01-01

    The attitude of nurses and treatment staff is crucial in the treatment of patients who self-harm. However, many patients experience that attitude as negative. The aim of this study was to investigate the psychometric properties of the Dutch version of the Attitude Towards Deliberate Self-Harm

  18. Evaluation of a novel risk assessment method for self-harm associated with Borderline Personality Disorder.

    Rao, Sathya; Broadbear, Jillian H; Thompson, Katherine; Correia, Anna; Preston, Martin; Katz, Paul; Trett, Robert

    2017-10-01

    Borderline personality disorder (BPD) is associated with frequent self-harm and suicidal behaviours. This study compared physician-assessed self-harm risk and intervention choice according to a (i) standard risk assessment and (ii) BPD-specific risk assessment methods. Forty-five junior and senior mental health physicians were assigned to standard or BPD-specific risk training groups. The assessment utilized a BPD case vignette containing four scenarios describing high/low lethality self-harm and chronic/new patterns of self-harm behaviour. Participants chose from among four interventions, each corresponding to a risk category. Standard and BPD-specific groups were alike in their assessment of self-harm risk. Divergence occurred on intervention choice for assessments of low lethality, chronic risk ( pself harm-associated risk, BPD-specific training raised awareness of BPD-appropriate interventions, particularly in the context of chronic patterns of self-harm behaviour. Wider dissemination of BPD-specific risk training may enhance the confidence of mental health clinicians in identifying the nature of self-harm risk as well as the most clinically appropriate interventions for clients with BPD.

  19. On balance: weighing harms and benefits in fundamental neurological research using nonhuman primates.

    Arnason, Gardar; Clausen, Jens

    2016-06-01

    One of the most controversial areas of animal research is the use of nonhuman primates for fundamental research. At the centre of the controversy is the question of whether the benefits of research outweigh the harms. We argue that the evaluation of harms and benefits is highly problematic. We describe some common procedures in neurological research using nonhuman primates and the difficulties in evaluating the harm involved. Even if the harm could be quantified, it is unlikely that it could be meaningfully aggregated over different procedures, let alone different animals. A similar problem arises for evaluating benefits. It is not clear how benefits could be quantified, and even if they could be, values for different aspects of expected benefits cannot be simply added up. Sorting harms and benefits in three or four categories cannot avoid the charge of arbitrariness and runs the risk of imposing its structure on the moral decision. The metaphor of weighing or balancing harms and benefits is inappropriate for the moral decision about whether to use nonhuman primates for research. Arguing that the harms and benefits in this context are incommensurable, we suggest describing the moral consideration of harms and benefits as a coherent trade-off. Such a decision does not require commensurability. It must be well-informed about the suffering involved and the potential benefits, it must be consistent with the legal, regulatory and institutional framework within which it is made, and it must cohere with other judgments in relevant areas.

  20. A Duty of Care: Non-Drinkers and Alcohol Related Harm among an Australian University Sample

    Mikhailovich, Katja; George, Amanda; Rickwood, Debra; Parker, Rhian

    2011-01-01

    Studies documenting the harm associated with excessive drinking amongst university students are numerous. Fewer studies have explored the experience of non-drinkers in the university setting. In 2008, 826 students aged 18-29 years responded to an online survey aiming to investigate alcohol use and alcohol related harm at an Australian university.…