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Sample records for radio-induced death modulation

  1. The Celebration of Death: Two Folk Tales about DEath. Mini-Module.

    ERIC Educational Resources Information Center

    African-American Inst., New York, NY. School Services Div.

    This module contains two African folk tales about death, two descriptions of African funerals, a lesson plan with 11 questions exploring the finality of and customs surrounding death, and a bibliography of five books which deal with African religious beliefs. The folk tales present concepts of death and immortality of the soul. The descriptions of…

  2. [Prevention of radio-induced cancers].

    PubMed

    Cosset, J-M; Chargari, C; Demoor, C; Giraud, P; Helfre, S; Mornex, F; Mazal, A

    2016-09-01

    The article deals with the prevention of cancers only directly related to therapeutic radiation which are distinguished from "secondary cancer". The consideration of the risk of radiation-induced cancers after radiation therapy, although it is fortunately rare events, has become indispensable today. With a review of the literature, are detailed the various involved parameters. The age of the irradiated patient is one of the main parameters. The impact of the dose is also discussed based on the model used, and based on clinical data. Other parameters defining a radiation treatment are discussed one after the other: field with the example of Hodgkin's disease, the type of radiation and the participation of secondary neutrons, spreading and splitting. All these parameters are discussed according to each organ whose sensitivity is different. The article concludes with a list of recommendations to reduce the risk of radio-induced cancers. Even with the advent of conformal radiotherapy, intensity modulation, the modulated volume arctherapy, and the development of specific machinery for the extra-cranial stereotactic, the radiation therapist must consider this risk and use of reasonable and justified control imaging. Although they constitute a small percentage of cancers that occur secondarily after a first malignant tumor, radiation-induced cancers, can not and must not be concealed or ignored and justify regular monitoring over the long term, precisely adapted on the described parameters. PMID:27523416

  3. Arabidopsis ACCELERATED CELL DEATH2 Modulates Programmed Cell DeathW⃞

    PubMed Central

    Yao, Nan; Greenberg, Jean T.

    2006-01-01

    The Arabidopsis thaliana chloroplast protein ACCELERATED CELL DEATH2 (ACD2) modulates the amount of programmed cell death (PCD) triggered by Pseudomonas syringae and protoporphyrin IX (PPIX) treatment. In vitro, ACD2 can reduce red chlorophyll catabolite, a chlorophyll derivative. We find that ACD2 shields root protoplasts that lack chlorophyll from light- and PPIX-induced PCD. Thus, chlorophyll catabolism is not obligatory for ACD2 anti-PCD function. Upon P. syringae infection, ACD2 levels and localization change in cells undergoing PCD and in their close neighbors. Thus, ACD2 shifts from being largely in chloroplasts to partitioning to chloroplasts, mitochondria, and, to a small extent, cytosol. ACD2 protects cells from PCD that requires the early mitochondrial oxidative burst. Later, the chloroplasts of dying cells generate NO, which only slightly affects cell viability. Finally, the mitochondria in dying cells have dramatically altered movements and cellular distribution. Overproduction of both ACD2 (localized to mitochondria and chloroplasts) and ascorbate peroxidase (localized to chloroplasts) greatly reduces P. syringae–induced PCD, suggesting a pro-PCD role for mitochondrial and chloroplast events. During infection, ACD2 may bind to and/or reduce PCD-inducing porphyrin-related molecules in mitochondria and possibly chloroplasts that generate reactive oxygen species, cause altered organelle behavior, and activate a cascade of PCD-inducing events. PMID:16387834

  4. Using Radio-Induced Aurora to Observe Ionospheric Irregularities

    NASA Astrophysics Data System (ADS)

    Bernhardt, P.; Gondarenko, N.; Guzdar, P.; Huba, J.; Ossakow, S.; Djuth, F.; Tepley, C.; Sulzer, M.; Kagan, L.; Kelley, M.

    Two-dimensional images of F- and E- layers have been obtained using the technique called radio-induced aurora (RIA). This technique makes the plasma layers glow in the ionosphere glow when being stimulated by high power radio waves. Normally the irregularities in the ionosphere do not radiate strong enough visible emissions to be observed from the ground. Experiments at Arecibo Observatory in Puerto Rico and the SURA facility in Russia have shown that the plasma structures can be made to glow at 630.0 nm, 557.7 nm and other wavelengths by illuminating them by HF radio waves with effective radiated powers of 80 megawatts. The regions of the sporadic-E layers that have electron densities greater than the critical density for reflection of the radio waves emit electrons that collide with and excite atmospheric atomic oxygen and molecular nitrogen. A charge-coupled-device (CCD) imager located on the ground is used to capture images of the glowing E and F-region structures. The camera exposure- times were in the range of 15 to 45 seconds. The images obtained using this technique show a wide variety of both field-aligned and wind-aligned irregularities. Some layers cover the antenna pattern cone illuminated by the radio wave beam. Other layers show strong modulations by both plasma and neutral instabilities. Two-dimensional computer simulations of the coupling between neutral winds, electric fields and the ion layers simulate the structure in the images.

  5. Modulation of cell death in age-related diseases.

    PubMed

    Tezil, Tugsan; Basaga, Huveyda

    2014-01-01

    Aging is a stage of life of all living organisms. According to the free-radical theory, aging cells gradually become unable to maintain cellular homeostasis due to the adverse effects of reactive oxygen species (ROS). ROS can cause irreversible DNA mutations, protein and lipid damage which are increasingly accumulated in the course of time if cells could not overcome these effects by the antioxidant defence system. Accrued damaged molecules in cells may either induce cellular death or contribute to develop various pathologies. Hence, programmed cell death mechanisms, apoptosis and autophagy, play a vital role in the aging process. Although they are strictly controlled by various interconnected signalling pathways, alterations in their regulations may contribute to severe pathologies including cancer, Alzheimer's and Parkinson's diseases. In this review, we summarized our current understanding and hypotheses regarding oxidative stress and age-related dysregulation of cell death signalling pathways. PMID:24079770

  6. ACCELERATED CELL DEATH2 suppresses mitochondrial oxidative bursts and modulates cell death in Arabidopsis

    PubMed Central

    Pattanayak, Gopal K.; Venkataramani, Sujatha; Hortensteiner, Stefan; Kunz, Lukas; Christ, Bastien; Moulin, Michael; Smith, Alison G.; Okamoto, Yukihiro; Tamiaki, Hitoshi; Sugishima, Masakazu; Greenberg, Jean T.

    2012-01-01

    SUMMARY The Arabidopsis ACCELERATED CELL DEATH 2 (ACD2) protein protects cells from programmed cell death (PCD) caused by endogenous porphyrin-related molecules like red chlorophyll catabolite or exogenous protoporphyrin IX. We previously found that during bacterial infection, ACD2, a chlorophyll breakdown enzyme, localizes to both chloroplasts and mitochondria in leaves. Additionally, acd2 cells show mitochondrial dysfunctions. In plants with acd2 and ACD2+ sectors, ACD2 functions cell autonomously, implicating a pro-death ACD2 substrate as cell non-autonomous in promoting spreading PCD. ACD2 targeted solely to mitochondria can reduce the accumulation of an ACD2 substrate that originates in chloroplasts, indicating that ACD2 substrate molecules are likely mobile within cells. Two different light-dependent reactive oxygen bursts in mitochondria play prominent and causal roles in the acd2 PCD phenotype. Finally, ACD2 can complement acd2 when targeted to mitochondria or chloroplasts, respectively, as long as it is catalytically active; the ability to bind substrate is not sufficient for ACD2 to function in vitro or in vivo. Together the data suggest that ACD2 localizes dynamically during infection to protect cells from pro-death mobile substrate molecules, some of which may originate in chloroplasts, but have major effects on mitochondria. PMID:21988537

  7. A Module on Death and Dying to Develop Empathy in Student Pharmacists

    PubMed Central

    Olin, Jacqueline L.; Thornton, Phillip L.; Dolder, Christian R.; Hanrahan, Conor

    2011-01-01

    Objective To implement an integrated module on death and dying into a 15-week bioethics course and determine whether it increased student pharmacists’ empathy. Design Students participated in a 5-week death and dying module that included presentation of the film Wit, an interactive lecture on hospice, and a lecture on the ethics of pain management. Assessment Fifty-six students completed the 30-item Balanced Emotional Empathy Scale (BEES) before and after completing the module and wrote a reflective essay. Students demonstrated an appreciation of patient-specific values in their essay. Quantitative data collected via BEES scores demonstrated significant improvement in measured empathy. Conclusion A 5-week instructional model on death and dying significantly increased student empathy. PMID:21769147

  8. Proteinase 3–dependent caspase-3 cleavage modulates neutrophil death and inflammation

    PubMed Central

    Loison, Fabien; Zhu, Haiyan; Karatepe, Kutay; Kasorn, Anongnard; Liu, Peng; Ye, Keqiang; Zhou, Jiaxi; Cao, Shannan; Gong, Haiyan; Jenne, Dieter E.; Remold-O’Donnell, Eileen; Xu, Yuanfu; Luo, Hongbo R.

    2014-01-01

    Caspase-3–mediated spontaneous death in neutrophils is a prototype of programmed cell death and is critical for modulating physiopathological inflammatory responses; however, the underlying regulatory pathways remain ill defined. Here we determined that in aging neutrophils, the cleavage and activation of caspase-3 is independent of the canonical caspase-8– or caspase-9–mediated pathway. Instead, caspase-3 activation was mediated by serine protease proteinase 3 (PR3), which is present in the cytosol of aging neutrophils. Specifically, PR3 cleaved procaspase-3 at a site upstream of the canonical caspase-9 cleavage site. In mature neutrophils, PR3 was sequestered in granules and released during aging via lysosomal membrane permeabilization (LMP), leading to procaspase-3 cleavage and apoptosis. Pharmacological inhibition or knockdown of PR3 delayed neutrophil death in vitro and consistently delayed neutrophil death and augmented neutrophil accumulation at sites of inflammation in a murine model of peritonitis. Adoptive transfer of both WT and PR3-deficient neutrophils revealed that the delayed death of neutrophils lacking PR3 is due to an altered intrinsic apoptosis/survival pathway, rather than the inflammatory microenvironment. The presence of the suicide protease inhibitor SERPINB1 counterbalanced the protease activity of PR3 in aging neutrophils, and deletion of Serpinb1 accelerated neutrophil death. Taken together, our results reveal that PR3-mediated caspase-3 activation controls neutrophil spontaneous death. PMID:25180606

  9. Mitochondrial fusion is regulated by Reaper to modulate Drosophila programmed cell death.

    PubMed

    Thomenius, M; Freel, C D; Horn, S; Krieser, R; Abdelwahid, E; Cannon, R; Balasundaram, S; White, K; Kornbluth, S

    2011-10-01

    In most multicellular organisms, the decision to undergo programmed cell death in response to cellular damage or developmental cues is typically transmitted through mitochondria. It has been suggested that an exception is the apoptotic pathway of Drosophila melanogaster, in which the role of mitochondria remains unclear. Although IAP antagonists in Drosophila such as Reaper, Hid and Grim may induce cell death without mitochondrial membrane permeabilization, it is surprising that all three localize to mitochondria. Moreover, induction of Reaper and Hid appears to result in mitochondrial fragmentation during Drosophila cell death. Most importantly, disruption of mitochondrial fission can inhibit Reaper and Hid-induced cell death, suggesting that alterations in mitochondrial dynamics can modulate cell death in fly cells. We report here that Drosophila Reaper can induce mitochondrial fragmentation by binding to and inhibiting the pro-fusion protein MFN2 and its Drosophila counterpart dMFN/Marf. Our in vitro and in vivo analyses reveal that dMFN overexpression can inhibit cell death induced by Reaper or γ-irradiation. In addition, knockdown of dMFN causes a striking loss of adult wing tissue and significant apoptosis in the developing wing discs. Our findings are consistent with a growing body of work describing a role for mitochondrial fission and fusion machinery in the decision of cells to die. PMID:21475305

  10. Mitochondrial fusion is regulated by Reaper to modulate Drosophila programmed cell death

    PubMed Central

    Thomenius, M; Freel, C D; Horn, S; Krieser, R; Abdelwahid, E; Cannon, R; Balasundaram, S; White, K; Kornbluth, S

    2011-01-01

    In most multicellular organisms, the decision to undergo programmed cell death in response to cellular damage or developmental cues is typically transmitted through mitochondria. It has been suggested that an exception is the apoptotic pathway of Drosophila melanogaster, in which the role of mitochondria remains unclear. Although IAP antagonists in Drosophila such as Reaper, Hid and Grim may induce cell death without mitochondrial membrane permeabilization, it is surprising that all three localize to mitochondria. Moreover, induction of Reaper and Hid appears to result in mitochondrial fragmentation during Drosophila cell death. Most importantly, disruption of mitochondrial fission can inhibit Reaper and Hid-induced cell death, suggesting that alterations in mitochondrial dynamics can modulate cell death in fly cells. We report here that Drosophila Reaper can induce mitochondrial fragmentation by binding to and inhibiting the pro-fusion protein MFN2 and its Drosophila counterpart dMFN/Marf. Our in vitro and in vivo analyses reveal that dMFN overexpression can inhibit cell death induced by Reaper or γ-irradiation. In addition, knockdown of dMFN causes a striking loss of adult wing tissue and significant apoptosis in the developing wing discs. Our findings are consistent with a growing body of work describing a role for mitochondrial fission and fusion machinery in the decision of cells to die. PMID:21475305

  11. Pelle Modulates dFoxO-Mediated Cell Death in Drosophila.

    PubMed

    Wu, Chenxi; Chen, Yujun; Wang, Feng; Chen, Changyan; Zhang, Shiping; Li, Chaojie; Li, Wenzhe; Wu, Shian; Xue, Lei

    2015-10-01

    Interleukin-1 receptor-associated kinases (IRAKs) are crucial mediators of the IL-1R/TLR signaling pathways that regulate the immune and inflammation response in mammals. Recent studies also suggest a critical role of IRAKs in tumor development, though the underlying mechanism remains elusive. Pelle is the sole Drosophila IRAK homolog implicated in the conserved Toll pathway that regulates Dorsal/Ventral patterning, innate immune response, muscle development and axon guidance. Here we report a novel function of pll in modulating apoptotic cell death, which is independent of the Toll pathway. We found that loss of pll results in reduced size in wing tissue, which is caused by a reduction in cell number but not cell size. Depletion of pll up-regulates the transcription of pro-apoptotic genes, and triggers caspase activation and cell death. The transcription factor dFoxO is required for loss-of-pll induced cell death. Furthermore, loss of pll activates dFoxO, promotes its translocation from cytoplasm to nucleus, and up-regulates the transcription of its target gene Thor/4E-BP. Finally, Pll physically interacts with dFoxO and phosphorylates dFoxO directly. This study not only identifies a previously unknown physiological function of pll in cell death, but also shed light on the mechanism of IRAKs in cell survival/death during tumorigenesis. PMID:26474173

  12. Pelle Modulates dFoxO-Mediated Cell Death in Drosophila

    PubMed Central

    Chen, Changyan; Zhang, Shiping; Li, Chaojie; Li, Wenzhe; Wu, Shian; Xue, Lei

    2015-01-01

    Interleukin-1 receptor-associated kinases (IRAKs) are crucial mediators of the IL-1R/TLR signaling pathways that regulate the immune and inflammation response in mammals. Recent studies also suggest a critical role of IRAKs in tumor development, though the underlying mechanism remains elusive. Pelle is the sole Drosophila IRAK homolog implicated in the conserved Toll pathway that regulates Dorsal/Ventral patterning, innate immune response, muscle development and axon guidance. Here we report a novel function of pll in modulating apoptotic cell death, which is independent of the Toll pathway. We found that loss of pll results in reduced size in wing tissue, which is caused by a reduction in cell number but not cell size. Depletion of pll up-regulates the transcription of pro-apoptotic genes, and triggers caspase activation and cell death. The transcription factor dFoxO is required for loss-of-pll induced cell death. Furthermore, loss of pll activates dFoxO, promotes its translocation from cytoplasm to nucleus, and up-regulates the transcription of its target gene Thor/4E-BP. Finally, Pll physically interacts with dFoxO and phosphorylates dFoxO directly. This study not only identifies a previously unknown physiological function of pll in cell death, but also shed light on the mechanism of IRAKs in cell survival/death during tumorigenesis. PMID:26474173

  13. Fusaric acid induction of programmed cell death modulated through nitric oxide signalling in tobacco suspension cells.

    PubMed

    Jiao, Jiao; Zhou, Benguo; Zhu, Xiaoping; Gao, Zhengliang; Liang, Yuancun

    2013-10-01

    Fusaric acid (FA) is a nonhost-selective toxin mainly produced by Fusarium oxysporum, the causal agent of plant wilt diseases. We demonstrate that FA can induce programmed cell death (PCD) in tobacco suspension cells and the FA-induced PCD is modulated by nitric oxide (NO) signalling. Cells undergoing cell death induced by FA treatment exhibited typical characteristics of PCD including cytoplasmic shrinkage, chromatin condensation, DNA fragmentation, membrane plasmolysis, and formation of small cytoplasmic vacuoles. In addition, caspase-3-like activity was activated upon the FA treatment. The process of FA-induced PCD was accompanied by a rapid accumulation of NO in a FA dose-dependent manner. Pre-treatment of cells with NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) or NO synthase inhibitor N(G)-monomethyl-arginine monoacetate (L-NMMA) significantly reduced the rate of FA-induced cell death. Furthermore, the caspase-3-like activity and the expression of PAL and Hsr203J genes were alleviated by application of cPTIO or L-NMMA to FA-treated tobacco cells. This indicates that NO is an important factor involved in the FA-induced PCD. Our results also show that pre-treatment of tobacco cells with a caspase-3-specific inhibitor, Ac-DEVD-CHO, can reduce the rate of FA-induced cell death. These results demonstrate that the FA-induced cell death is a PCD and is modulated by NO signalling through caspase-3-like activation. PMID:23838885

  14. Thoughts of Death Modulate Psychophysical and Cortical Responses to Threatening Stimuli

    PubMed Central

    Valentini, Elia; Koch, Katharina; Aglioti, Salvatore Maria

    2014-01-01

    Existential social psychology studies show that awareness of one's eventual death profoundly influences human cognition and behaviour by inducing defensive reactions against end-of-life related anxiety. Much less is known about the impact of reminders of mortality on brain activity. Therefore we explored whether reminders of mortality influence subjective ratings of intensity and threat of auditory and painful thermal stimuli and the associated electroencephalographic activity. Moreover, we explored whether personality and demographics modulate psychophysical and neural changes related to mortality salience (MS). Following MS induction, a specific increase in ratings of intensity and threat was found for both nociceptive and auditory stimuli. While MS did not have any specific effect on nociceptive and auditory evoked potentials, larger amplitude of theta oscillatory activity related to thermal nociceptive activity was found after thoughts of death were induced. MS thus exerted a top-down modulation on theta electroencephalographic oscillatory amplitude, specifically for brain activity triggered by painful thermal stimuli. This effect was higher in participants reporting higher threat perception, suggesting that inducing a death-related mind-set may have an influence on body-defence related somatosensory representations. PMID:25386905

  15. PARP-1-modulated AIF translocation is involved in streptomycin-induced cochlear hair cell death.

    PubMed

    Song, Yongdong; Fan, Zhaomin; Bai, Xiaohui; Liu, Wenwen; Han, Yuechen; Xu, Lei; Wang, Mingming; Li, Jianfeng; Zheng, Qingyin; Zhang, Daogong; Wang, Haibo

    2016-06-01

    Conclusion SM-induced dose- and location-dependent cochlear hair cell death in vitro. AIF might be translocated from mitochondria to nucleus and cytoplasm within SM-treated hair cells. The translocation of AIF might be modulated by PARP-1. Objective Streptomycin (SM), one of the widely used aminoglycoside nowadays, is still causing significant permanent sensorineural hearing loss owing to sensory hair cell death. This study was designed to investigate the role of apoptosis-inducing factor (AIF), an important mitochondrial cell death regulator, in SM ototoxicity within neonatal rat cochleae and HEI-OC1 cells. Methods The viability of HEI-OC1 cells was quantified by MTT assay. AIF, PARP-1, and myosin VIIa distributions were achieved by immunofluorescence. mRNA and protein expression of AIF and PARP-1 were examined by q-PCR and Western-blot. Results The hair cell loss was concomitant with the SM concentration variation, and aggravated from apical to basal turn. AIF was detected in nuclear region and AIF mRNA was up-regulated after SM incubation. Besides, AIF protein expression in mitochondria was decreased, whereas in cytosol it was increased. PARP-1 mRNA and protein were also up-regulated. 3-AB could attenuate the cell death and reverse the changes of AIF distribution by blocking PARP-1. PMID:26963167

  16. Modulating cell-to-cell variability and sensitivity to death ligands by co-drugging

    NASA Astrophysics Data System (ADS)

    Flusberg, Deborah A.; Sorger, Peter K.

    2013-06-01

    TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) holds promise as an anti-cancer therapeutic but efficiently induces apoptosis in only a subset of tumor cell lines. Moreover, even in clonal populations of responsive lines, only a fraction of cells dies in response to TRAIL and individual cells exhibit cell-to-cell variability in the timing of cell death. Fractional killing in these cell populations appears to arise not from genetic differences among cells but rather from differences in gene expression states, fluctuations in protein levels and the extent to which TRAIL-induced death or survival pathways become activated. In this study, we ask how cell-to-cell variability manifests in cell types with different sensitivities to TRAIL, as well as how it changes when cells are exposed to combinations of drugs. We show that individual cells that survive treatment with TRAIL can regenerate the sensitivity and death-time distribution of the parental population, demonstrating that fractional killing is a stable property of cell populations. We also show that cell-to-cell variability in the timing and probability of apoptosis in response to treatment can be tuned using combinations of drugs that together increase apoptotic sensitivity compared to treatment with one drug alone. In the case of TRAIL, modulation of cell-to-cell variability by co-drugging appears to involve a reduction in the threshold for mitochondrial outer membrane permeabilization.

  17. Identification of a Small Molecule that induces ATG5-and-Cathepsin-L-Dependent Cell Death and modulates Polyglutamine Toxicity

    PubMed Central

    Varma, Hemant; Gangadhar, Nidhi M.; Letso, Reka R.; Wolpaw, Adam J.; Sriramaratnam, Rohitha; Stockwell, Brent R.

    2013-01-01

    Non-apoptotic cell death mechanisms are largely uncharacterized despite their importance in physiology and disease (P. Kreuzaler and C.J. Watson, Nature Reviews Cancer). Here we sought to systematically identify non-apoptotic cell death pathways in mammalian cells. We screened 69,612 compounds for those that induce non-canonical cell death by counter screening in the presence of inhibitors of apoptosis and necrosis. We further selected compounds that require active protein synthesis for inducing cell death. Using this tiered approach, we identified NID-1 (Novel Inducer of Death-1), a small molecule that induces an active, energy-dependent cell death in diverse mammalian cell lines. NID-1-induced death required components of the autophagic machinery, including ATG5, and the lysosomal hydrolase cathepsin L, but was distinct from classical macroautophagy. Since macroautophagy can prevent cell death in several contexts, we tested and found that NID-1 suppressed cell death in a cell-based model of Huntington’s disease, suggesting that NID-1 activates a specific pathway. Thus the discovery of NID-1 identifies a previously unexplored cell death pathway, and modulating this pathway may have therapeutic applications. Furthermore, these findings provide a proof-of-principle for using chemical screening to identify novel cell death paradigms. PMID:23588206

  18. Discover the Molecular Biomarker Associated with Cell Death and Extracellular Matrix Module in Ovarian Cancer

    PubMed Central

    Liu, Qiang; Guo, Jianxin; Cui, Jinghong; Wang, Jing; Yi, Ping

    2015-01-01

    High throughput technologies have provided many new research methods for ovarian cancer investigation. In tradition, in order to find the underlying functional mechanisms of the survival-associated genes, gene sets enrichment analysis (GSEA) is always regarded as the important choice. However, GSEA produces too many candidate genes and cannot discover the signaling transduction cascades. In this work, we have used a network-based strategy to optimize the discovery of biomarkers using multifactorial data, including patient expression, clinical survival, and protein-protein interaction (PPI) data. The biomarkers discovered by this strategy belong to the network-based biomarker, which is apt to reveal the underlying functional mechanisms of the biomarker. In this work, over 400 expression arrays in ovarian cancer have been analyzed: the results showed that cell death and extracellular module are the main themes related to ovarian cancer progression. PMID:25861644

  19. Hop/STI1 modulates retinal proliferation and cell death independent of PrP{sup C}

    SciTech Connect

    Arruda-Carvalho, Maithe; Njaine, Brian; Silveira, Mariana S.; Linden, Rafael; Chiarini, Luciana B. . E-mail: chiarini@biof.ufrj.br

    2007-09-21

    Hop/STI1 is a co-chaperone adaptor protein for Hsp70/Hsp90 complexes. Hop/STI1 is found extracellularly and modulates cell death and differentiation through interaction with the prion protein (PrP{sup C}). Here, we investigated the expression of hop/STI1 and its role upon cell proliferation and cell death in the developing retina. Hop/STI1 is more expressed in developing rat retina than in the mature tissue. Hop/STI1 blocks retinal cell death in the neuroblastic layer (NBL) in a PrP{sup C} dependent manner, but failed to protect ganglion cells against axotomy-induced cell death. An antibody raised against hop/STI1 ({alpha}-STI1) blocked both ganglion cell and NBL cell death independent of PrP{sup C}. cAMP/PKA, ERK, PI3K and PKC signaling pathways were not involved in these effects. Hop/STI1 treatment reduced proliferation, while {alpha}-STI1 increased proliferation in the developing retina, both independent of PrP{sup C}. We conclude that hop/STI1 can modulate both proliferation and cell death in the developing retina independent of PrP{sup C}.

  20. [Radiosurgery and brain radio-induced carcinogenesis: update].

    PubMed

    Muracciole, X; Cowen, D; Régis, J

    2004-06-01

    The use of radiosurgery Gamma-knife for many benign tumors and diseases has increased significantly over the last two decades. The long-term potential carcinogenic risk has not been evaluated until recently. The definition of radio-induced tumors was based on Cahan's criteria: it must occur in the previously irradiated field, with a sufficiently long interval from irradiation, it must be pathologically different from the primary tumor, not be present at time of irradiation and no genetic predisposition for second tumor. The brain is one of most sensitive tIssues and no minimal dose has been established. Even doses as low as 1 Gy have been associated with second tumor formation and relative risk between 1.57 and 8.75. This relative risk increases to 18.4 for an interval time between 20 and 25 Years. Many publications emphaze the risks after larger-field, fractionated radiotherapy with low non-cell-killing dose delivered to central nervous system. Furthermore, therapeutic radiation doses for benign tumors associated with a long life (parasellar tumors, meningioma) were implicated in carcinogenesis. Incidence of radiation-associated tumors is linked to different factors such as age and individual genetic susceptibility. At this time and to our knowledge, 3 radiation-associated gliomas and 5 malignant acoustic neurinomas have been reported in the literature. Moreover, these second tumors met some but not all Cahan criteria. We also report 2 cases from our radiosurgical experience and discuss these points. Long time follow-up is needed to observe the crude incidence of radiation-induced tumors at 5 to 30 Years. The relative risk is estimated less than 1 and must be announced to each patient before the radiosurgical procedure and counterbalanced wit the 1% annual risk of mortality from bleeding of untreated MAV or the 1% mortality rate of benign tumors after surgery alone. PMID:15179297

  1. Oleuropein Prevents Neuronal Death, Mitigates Mitochondrial Superoxide Production and Modulates Autophagy in a Dopaminergic Cellular Model

    PubMed Central

    Achour, Imène; Arel-Dubeau, Anne-Marie; Renaud, Justine; Legrand, Manon; Attard, Everaldo; Germain, Marc; Martinoli, Maria-Grazia

    2016-01-01

    Parkinson’s disease (PD) is a progressive neurodegenerative disorder, primarily affecting dopaminergic neurons in the substantia nigra. There is currently no cure for PD and present medications aim to alleviate clinical symptoms, thus prevention remains the ideal strategy to reduce the prevalence of this disease. The goal of this study was to investigate whether oleuropein (OLE), the major phenolic compound in olive derivatives, may prevent neuronal degeneration in a cellular dopaminergic model of PD, differentiated PC12 cells exposed to the potent parkinsonian toxin 6-hydroxydopamine (6-OHDA). We also investigated OLE’s ability to mitigate mitochondrial oxidative stress and modulate the autophagic flux. Our results obtained by measuring cytotoxicity and apoptotic events demonstrate that OLE significantly decreases neuronal death. OLE could also reduce mitochondrial production of reactive oxygen species resulting from blocking superoxide dismutase activity. Moreover, quantification of autophagic and acidic vesicles in the cytoplasm alongside expression of specific autophagic markers uncovered a regulatory role for OLE against autophagic flux impairment induced by bafilomycin A1. Altogether, our results define OLE as a neuroprotective, anti-oxidative and autophagy-regulating molecule, in a neuronal dopaminergic cellular model. PMID:27517912

  2. Oleuropein Prevents Neuronal Death, Mitigates Mitochondrial Superoxide Production and Modulates Autophagy in a Dopaminergic Cellular Model.

    PubMed

    Achour, Imène; Arel-Dubeau, Anne-Marie; Renaud, Justine; Legrand, Manon; Attard, Everaldo; Germain, Marc; Martinoli, Maria-Grazia

    2016-01-01

    Parkinson's disease (PD) is a progressive neurodegenerative disorder, primarily affecting dopaminergic neurons in the substantia nigra. There is currently no cure for PD and present medications aim to alleviate clinical symptoms, thus prevention remains the ideal strategy to reduce the prevalence of this disease. The goal of this study was to investigate whether oleuropein (OLE), the major phenolic compound in olive derivatives, may prevent neuronal degeneration in a cellular dopaminergic model of PD, differentiated PC12 cells exposed to the potent parkinsonian toxin 6-hydroxydopamine (6-OHDA). We also investigated OLE's ability to mitigate mitochondrial oxidative stress and modulate the autophagic flux. Our results obtained by measuring cytotoxicity and apoptotic events demonstrate that OLE significantly decreases neuronal death. OLE could also reduce mitochondrial production of reactive oxygen species resulting from blocking superoxide dismutase activity. Moreover, quantification of autophagic and acidic vesicles in the cytoplasm alongside expression of specific autophagic markers uncovered a regulatory role for OLE against autophagic flux impairment induced by bafilomycin A1. Altogether, our results define OLE as a neuroprotective, anti-oxidative and autophagy-regulating molecule, in a neuronal dopaminergic cellular model. PMID:27517912

  3. Neisseria gonorrhoeae Modulates Cell Death in Human Endocervical Epithelial Cells through Export of Exosome-Associated cIAP2

    PubMed Central

    Nudel, Kathleen; Massari, Paola

    2015-01-01

    Several bacterial pathogens persist and survive in the host by modulating host cell death pathways. We previously demonstrated that Neisseria gonorrhoeae, a Gram-negative pathogen responsible for the sexually transmitted infection gonorrhea, protects against exogenous induction of apoptosis in human cervical epithelial cells. However, induction of cell death by N. gonorrhoeae has also been reported in other cell types. The mechanisms by which N. gonorrhoeae modulates cell death are not clear, although a role for the inhibitor of apoptosis-2 (cIAP2) has been proposed. In this study, we confirmed that N. gonorrhoeae induces production of cIAP2 in human cervical epithelial cells. High levels of intracellular cIAP2 were detected early after N. gonorrhoeae stimulation, which was followed by a marked decrease at 24 h. At this time point, we observed increased levels of extracellular cIAP2 associated with exosomes and an overall increase in production of exosomes. Inhibition of cIAP2 in N. gonorrhoeae-stimulated epithelial cells resulted in increased cell death and interleukin-1β (IL-1β) production. Collectively these results indicate that N. gonorrhoeae stimulation of human endocervical epithelial cells induces the release of cIAP2, an essential regulator of cell death and immune signaling. PMID:26077759

  4. Neisseria gonorrhoeae Modulates Cell Death in Human Endocervical Epithelial Cells through Export of Exosome-Associated cIAP2.

    PubMed

    Nudel, Kathleen; Massari, Paola; Genco, Caroline A

    2015-09-01

    Several bacterial pathogens persist and survive in the host by modulating host cell death pathways. We previously demonstrated that Neisseria gonorrhoeae, a Gram-negative pathogen responsible for the sexually transmitted infection gonorrhea, protects against exogenous induction of apoptosis in human cervical epithelial cells. However, induction of cell death by N. gonorrhoeae has also been reported in other cell types. The mechanisms by which N. gonorrhoeae modulates cell death are not clear, although a role for the inhibitor of apoptosis-2 (cIAP2) has been proposed. In this study, we confirmed that N. gonorrhoeae induces production of cIAP2 in human cervical epithelial cells. High levels of intracellular cIAP2 were detected early after N. gonorrhoeae stimulation, which was followed by a marked decrease at 24 h. At this time point, we observed increased levels of extracellular cIAP2 associated with exosomes and an overall increase in production of exosomes. Inhibition of cIAP2 in N. gonorrhoeae-stimulated epithelial cells resulted in increased cell death and interleukin-1β (IL-1β) production. Collectively these results indicate that N. gonorrhoeae stimulation of human endocervical epithelial cells induces the release of cIAP2, an essential regulator of cell death and immune signaling. PMID:26077759

  5. Nucleotide Excision Repair, Mismatch Repair, and R-Loops Modulate Convergent Transcription-Induced Cell Death and Repeat Instability

    PubMed Central

    Lin, Yunfu; Wilson, John H.

    2012-01-01

    Expansion of CAG•CTG tracts located in specific genes is responsible for 13 human neurodegenerative disorders, the pathogenic mechanisms of which are not yet well defined. These disease genes are ubiquitously expressed in human tissues, and transcription has been identified as one of the major pathways destabilizing the repeats. Transcription-induced repeat instability depends on transcription-coupled nucleotide excision repair (TC-NER), the mismatch repair (MMR) recognition component MSH2/MSH3, and RNA/DNA hybrids (R-loops). Recently, we reported that simultaneous sense and antisense transcription–convergent transcription–through a CAG repeat not only promotes repeat instability, but also induces a cell stress response, which arrests the cell cycle and eventually leads to massive cell death via apoptosis. Here, we use siRNA knockdowns to investigate whether NER, MMR, and R-loops also modulate convergent-transcription-induced cell death and repeat instability. We find that siRNA-mediated depletion of TC-NER components increases convergent transcription-induced cell death, as does the simultaneous depletion of RNase H1 and RNase H2A. In contrast, depletion of MSH2 decreases cell death. These results identify TC-NER, MMR recognition, and R-loops as modulators of convergent transcription-induced cell death and shed light on the molecular mechanism involved. We also find that the TC-NER pathway, MSH2, and R-loops modulate convergent transcription-induced repeat instability. These observations link the mechanisms of convergent transcription-induced repeat instability and convergent transcription-induced cell death, suggesting that a common structure may trigger both outcomes. PMID:23056461

  6. The Endoplasmic Reticulum Binding Protein BiP Displays Dual Function in Modulating Cell Death Events1[W][OPEN

    PubMed Central

    Carvalho, Humberto H.; Silva, Priscila A.; Mendes, Giselle C.; Brustolini, Otávio J.B.; Pimenta, Maiana R.; Gouveia, Bianca C.; Valente, Maria Anete S.; Ramos, Humberto J.O.; Soares-Ramos, Juliana R.L.; Fontes, Elizabeth P.B.

    2014-01-01

    The binding protein (BiP) has been demonstrated to participate in innate immunity and attenuate endoplasmic reticulum- and osmotic stress-induced cell death. Here, we employed transgenic plants with manipulated levels of BiP to assess whether BiP also controlled developmental and hypersensitive programmed cell death (PCD). Under normal conditions, the BiP-induced transcriptome revealed a robust down-regulation of developmental PCD genes and an up-regulation of the genes involved in hypersensitive PCD triggered by nonhost-pathogen interactions. Accordingly, the BiP-overexpressing line displayed delayed leaf senescence under normal conditions and accelerated hypersensitive response triggered by Pseudomonas syringae pv tomato in soybean (Glycine max) and tobacco (Nicotiana tabacum), as monitored by measuring hallmarks of PCD in plants. The BiP-mediated delay of leaf senescence correlated with the attenuation of N-rich protein (NRP)-mediated cell death signaling and the inhibition of the senescence-associated activation of the unfolded protein response (UPR). By contrast, under biological activation of salicylic acid (SA) signaling and hypersensitive PCD, BiP overexpression further induced NRP-mediated cell death signaling and antagonistically inhibited the UPR. Thus, the SA-mediated induction of NRP cell death signaling occurs via a pathway distinct from UPR. Our data indicate that during the hypersensitive PCD, BiP positively regulates the NRP cell death signaling through a yet undefined mechanism that is activated by SA signaling and related to ER functioning. By contrast, BiP’s negative regulation of leaf senescence may be linked to its capacity to attenuate the UPR activation and NRP cell death signaling. Therefore, BiP can function either as a negative or positive modulator of PCD events. PMID:24319082

  7. Network-based survival-associated module biomarker and its crosstalk with cell death genes in ovarian cancer

    PubMed Central

    Jin, Nana; Wu, Hao; Miao, Zhengqiang; Huang, Yan; Hu, Yongfei; Bi, Xiaoman; Wu, Deng; Qian, Kun; Wang, Liqiang; Wang, Changliang; Wang, Hongwei; Li, Kongning; Li, Xia; Wang, Dong

    2015-01-01

    Ovarian cancer remains a dismal disease with diagnosing in the late, metastatic stages, therefore, there is a growing realization of the critical need to develop effective biomarkers for understanding underlying mechanisms. Although existing evidences demonstrate the important role of the single genetic abnormality in pathogenesis, the perturbations of interactors in the complex network are often ignored. Moreover, ovarian cancer diagnosis and treatment still exist a large gap that need to be bridged. In this work, we adopted a network-based survival-associated approach to capture a 12-gene network module based on differential co-expression PPI network in the advanced-stage, high-grade ovarian serous cystadenocarcinoma. Then, regulatory genes (protein-coding genes and non-coding genes) direct interacting with the module were found to be significantly overlapped with cell death genes. More importantly, these overlapping genes tightly clustered together pointing to the module, deciphering the crosstalk between network-based survival-associated module and cell death in ovarian cancer. PMID:26099452

  8. The canonical Wg signaling modulates Bsk-mediated cell death in Drosophila

    PubMed Central

    Zhang, S; Chen, C; Wu, C; Yang, Y; Li, W; Xue, L

    2015-01-01

    Cell death is an essential regulatory mechanism for removing unneeded cells in animal development and tissue homeostasis. The c-Jun N-terminal kinase (JNK) pathway has pivotal roles in the regulation of cell death in response to various intrinsic and extrinsic stress signals. The canonical Wingless (Wg) signaling has been implicated in cell proliferation and cell fate decisions, whereas its role in cell death remains largely elusive. Here, we report that activated Bsk (the Drosophila JNK homolog) induced cell death is mediated by the canonical Wg signaling. First, loss of Wg signaling abrogates Bsk-mediated caspase-independent cell death. Second, activation of Wg signaling promotes cell death in a caspase-independent manner. Third, activation of Bsk signaling results in upregulated transcription of wingless (wg) gene. Finally, Wg pathway participates in the physiological function of Bsk signaling in development. These findings not only reveal a previously undiscovered role of Wg signaling in Bsk-mediated cell death, but also provide a novel mechanism for the interplay between the two important signaling pathways in development. PMID:25855961

  9. Substance P reduces apoptotic cell death possibly by modulating the immune response at the early stage after spinal cord injury.

    PubMed

    Jiang, Mei Hua; Lim, Ji Eun; Chi, Guang Fan; Ahn, Woosung; Zhang, Mingzi; Chung, Eunkyung; Son, Youngsook

    2013-10-23

    Previously, we have reported that substance P (SP) enhanced functional recovery from spinal cord injury (SCI) possibly by the anti-inflammatory modulation associated with the induction of M2-type macrophages at the injured lesion. In this study, we explored the cytokine expression profiles and apoptotic cell death in the lesion site of the SCI after an immediate intravenous injection of SP. SP injection increased the levels of interleukin-4 (IL-4), IL-6, and IL-10 at day 1 after the SCI approximately by 2-, 9-, and 10-folds when compared with the control SCI, respectively. On the basis of double immunofluorescence staining with IL-10 and CD11b, activated macrophages or microglia expressing IL-10 appeared in the margin of the lesion site at day 1 only after the SP injection. This SP-mediated alteration in the lesion microenvironment was shown to be associated with the lower cell death of neuronal cells at day 1 and oligodendrocytes at day 5 by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, which was also accompanied by a decrease in caspase-3 activation. These findings suggest that SP may reduce the inflammation-induced secondary cell death, possibly through immune modulation at an early stage after the SCI. PMID:23995292

  10. Inhibition of RNA interference and modulation of transposable element expression by cell death in Drosophila.

    PubMed

    Xie, Weiwu; Liang, Chengzhi; Birchler, James A

    2011-08-01

    RNA interference (RNAi) regulates gene expression by sequence-specific destruction of RNA. It acts as a defense mechanism against viruses and represses the expression of transposable elements (TEs) and some endogenous genes. We report that mutations and transgene constructs that condition cell death suppress RNA interference in adjacent cells in Drosophila melanogaster. The reversal of RNAi is effective for both the white (w) eye color gene and green fluorescent protein (GFP), indicating the generality of the inhibition. Antiapoptotic transgenes that reverse cell death will also reverse the inhibition of RNAi. Using GFP and a low level of cell death produced by a heat shock-head involution defective (hs-hid) transgene, the inhibition appears to occur by blocking the conversion of double-stranded RNA (dsRNA) to short interfering RNA (siRNA). We also demonstrate that the mus308 gene and endogenous transposable elements, which are both regularly silenced by RNAi, are increased in expression and accompanied by a reduced level of siRNA, when cell death occurs. The finding that chronic ectopic cell death affects RNAi is critical for an understanding of the application of the technique in basic and applied studies. These results also suggest that developmental perturbations, disease states, or environmental insults that cause ectopic cell death would alter transposon and gene expression patterns in the organism by the inhibition of small RNA silencing processes. PMID:21596898

  11. Prediction of clinical toxicity in localized cervical carcinoma by radio-induced apoptosis study in peripheral blood lymphocytes (PBLs)

    PubMed Central

    2009-01-01

    Background Cervical cancer is treated mainly by surgery and radiotherapy. Toxicity due to radiation is a limiting factor for treatment success. Determination of lymphocyte radiosensitivity by radio-induced apoptosis arises as a possible method for predictive test development. The aim of this study was to analyze radio-induced apoptosis of peripheral blood lymphocytes. Methods Ninety four consecutive patients suffering from cervical carcinoma, diagnosed and treated in our institution, and four healthy controls were included in the study. Toxicity was evaluated using the Lent-Soma scale. Peripheral blood lymphocytes were isolated and irradiated at 0, 1, 2 and 8 Gy during 24, 48 and 72 hours. Apoptosis was measured by flow cytometry using annexin V/propidium iodide to determine early and late apoptosis. Lymphocytes were marked with CD45 APC-conjugated monoclonal antibody. Results Radiation-induced apoptosis (RIA) increased with radiation dose and time of incubation. Data strongly fitted to a semi logarithmic model as follows: RIA = βln(Gy) + α. This mathematical model was defined by two constants: α, is the origin of the curve in the Y axis and determines the percentage of spontaneous cell death and β, is the slope of the curve and determines the percentage of cell death induced at a determined radiation dose (β = ΔRIA/Δln(Gy)). Higher β values (increased rate of RIA at given radiation doses) were observed in patients with low sexual toxicity (Exp(B) = 0.83, C.I. 95% (0.73-0.95), p = 0.007; Exp(B) = 0.88, C.I. 95% (0.82-0.94), p = 0.001; Exp(B) = 0.93, C.I. 95% (0.88-0.99), p = 0.026 for 24, 48 and 72 hours respectively). This relation was also found with rectal (Exp(B) = 0.89, C.I. 95% (0.81-0.98), p = 0.026; Exp(B) = 0.95, C.I. 95% (0.91-0.98), p = 0.013 for 48 and 72 hours respectively) and urinary (Exp(B) = 0.83, C.I. 95% (0.71-0.97), p = 0.021 for 24 hours) toxicity. Conclusion Radiation induced apoptosis at different time points and radiation doses

  12. Group A Streptococcus Modulates Host Inflammation by Manipulating Polymorphonuclear Leukocyte Cell Death Responses.

    PubMed

    Tsatsaronis, James A; Ly, Diane; Pupovac, Aleta; Goldmann, Oliver; Rohde, Manfred; Taylor, Jude M; Walker, Mark J; Medina, Eva; Sanderson-Smith, Martina L

    2015-01-01

    Polymorphonuclear leukocyte (PMN) cell death strongly influences the resolution of inflammatory episodes, and may exacerbate adverse pathologies in response to infection. We investigated PMN cell death mechanisms following infection by virulent group A Streptococcus (GAS). Human PMNs were infected in vitro with a clinical, virulent GAS isolate and an avirulent derivative strain, and compared for phagocytosis, the production of reactive oxygen species (ROS), mitochondrial membrane depolarization and apoptotic markers. C57BL/6J mice were then infected, in order to observe the effects on murine PMNs in vivo. Human PMNs phagocytosed virulent GAS less efficiently, produced less ROS and underwent reduced mitochondrial membrane depolarization compared with phagocytosis of avirulent GAS. Morphological and biochemical analyses revealed that PMNs infected with avirulent GAS exhibited nuclear fragmentation and caspase-3 activation consistent with an anti-inflammatory apoptotic phenotype. Conversely, virulent GAS induced PMN vacuolization and plasma membrane permeabilization, leading to a necrotic form of cell death. Infection of the mice with virulent GAS engendered significantly higher systemic pro-inflammatory cytokine release and localized infiltration of murine PMNs, with cells associated with virulent GAS infection exhibiting reduced apoptotic potential. Avirulent GAS infection was associated with lower levels of proinflammatory cytokines and tissue PMN apoptosis. We propose that the differences in PMN cell death mechanisms influence the inflammatory responses to infection by GAS. PMID:25997401

  13. Identification of new modulators and protein alterations in non-apoptotic programmed cell death.

    PubMed

    Sperandio, Sabina; Poksay, Karen S; Schilling, Birgit; Crippen, Danielle; Gibson, Bradford W; Bredesen, Dale E

    2010-12-15

    This study describes the first proteomic analysis of paraptosis--a non-apoptotic form of programmed cell death. As with apoptosis, the first description of paraptosis was based on morphological criteria. Since there are no known markers for paraptosis, the purpose of this study was to dissect changes in the proteome profile occurring during paraptosis. Using one- and two-dimensional SDS-PAGE, Western analysis, and mass spectrometry, we show that during paraptosis, alterations occur mainly in cytoskeletal proteins, signal transduction proteins, mitochondrial proteins, and some metabolic proteins. We also report the identification of: (1) a paraptosis inhibitor, phosphatidylethanolamine binding protein (PEBP-1), and (2) a candidate mediator of paraptosis, prohibitin. Identification of specific paraptotic changes will ultimately lead to tools to detect this type of programmed cell death in in vivo systems and allow for its further characterization. PMID:20830744

  14. Cyclic dinucleotides modulate human T-cell response through monocyte cell death.

    PubMed

    Tosolini, Marie; Pont, Frédéric; Verhoeyen, Els; Fournié, Jean-Jacques

    2015-12-01

    Cyclic dinucleotides, a class of microbial messengers, have been recently identified in bacteria, but their activity in humans remains largely unknown. Here, we have studied the function of cyclic dinucleotides in humans. We found that c-di-AMP and cGAMP, two adenosine-based cyclic dinucleotides, activated T lymphocytes in an unusual manner through monocyte cell death. c-di-AMP and cGAMP induced the selective apoptosis of human monocytes, and T lymphocytes were activated by the direct contact with these dying monocytes. The ensuing T-cell response comprised cell-cycle exit, phenotypic maturation into effector memory cells and proliferation arrest, but not cell death. This quiescence was transient since T cells remained fully responsive to further restimulation. Together, our results depict a novel activation pattern for human T lymphocytes: a transient quiescence induced by c-di-AMP- or cGAMP-primed apoptotic monocytes. PMID:26460927

  15. Microglia and macrophages differentially modulate cell death after brain injury caused by oxygen-glucose deprivation in organotypic brain slices.

    PubMed

    Girard, Sylvie; Brough, David; Lopez-Castejon, Gloria; Giles, James; Rothwell, Nancy J; Allan, Stuart M

    2013-05-01

    Macrophage can adopt several phenotypes, process call polarization, which is crucial for shaping inflammatory responses to injury. It is not known if microglia, a resident brain macrophage population, polarizes in a similar way, and whether specific microglial phenotypes modulate cell death in response to brain injury. In this study, we show that both BV2-microglia and mouse bone marrow derived macrophages (BMDMs) were able to adopt different phenotypes after LPS (M1) or IL-4 (M2) treatment in vitro, but regulated cell death differently when added to mouse organotypic hippocampal brain slices. BMDMs induced cell death when added to control slices and exacerbated damage when combined with oxygen-glucose deprivation (OGD), independently of their phenotype. In contrast, vehicle- and M2-BV2-microglia were protective against OGD-induced death. Direct treatment of brain slices with IL-4 (without cell addition) was protective against OGD and induced an M2 phenotype in the slice. In vivo, intracerebral injection of LPS or IL-4 in mice induced microglial phenotypes similar to the phenotypes observed in brain slices and in cultured cells. After injury induced by middle cerebral artery occlusion, microglial cells did not adopt classical M1/M2 phenotypes, suggesting that another subtype of regulatory phenotype was induced. This study highlights functional differences between macrophages and microglia, in response to brain injury with fundamentally different outcomes, even if both populations were able to adopt M1 or M2 phenotypes. These data suggest that macrophages infiltrating the brain from the periphery after an injury may be cytotoxic, independently of their phenotype, while microglia may be protective. PMID:23404620

  16. Quercetin Sensitizes Fluconazole-Resistant Candida albicans To Induce Apoptotic Cell Death by Modulating Quorum Sensing

    PubMed Central

    Singh, B. R.; Pandey, G.; Verma, S.; Roy, S.; Naqvi, A. H.

    2015-01-01

    Quorum sensing (QS) regulates group behaviors of Candida albicans such as biofilm, hyphal growth, and virulence factors. The sesquiterpene alcohol farnesol, a QS molecule produced by C. albicans, is known to regulate the expression of virulence weapons of this fungus. Fluconazole (FCZ) is a broad-spectrum antifungal drug that is used for the treatment of C. albicans infections. While FCZ can be cytotoxic at high concentrations, our results show that at much lower concentrations, quercetin (QC), a dietary flavonoid isolated from an edible lichen (Usnea longissima), can be implemented as a sensitizing agent for FCZ-resistant C. albicans NBC099, enhancing the efficacy of FCZ. QC enhanced FCZ-mediated cell killing of NBC099 and also induced cell death. These experiments indicated that the combined application of both drugs was FCZ dose dependent rather than QC dose dependent. In addition, we found that QC strongly suppressed the production of virulence weapons—biofilm formation, hyphal development, phospholipase, proteinase, esterase, and hemolytic activity. Treatment with QC also increased FCZ-mediated cell death in NBC099 biofilms. Interestingly, we also found that QC enhances the anticandidal activity of FCZ by inducing apoptotic cell death. We have also established that this sensitization is reliant on the farnesol response generated by QC. Molecular docking studies also support this conclusion and suggest that QC can form hydrogen bonds with Gln969, Thr1105, Ser1108, Arg1109, Asn1110, and Gly1061 in the ATP binding pocket of adenylate cyclase. Thus, this QS-mediated combined sensitizer (QC)-anticandidal agent (FCZ) strategy may be a novel way to enhance the efficacy of FCZ-based therapy of C. albicans infections. PMID:25645848

  17. Quercetin sensitizes fluconazole-resistant candida albicans to induce apoptotic cell death by modulating quorum sensing.

    PubMed

    Singh, B N; Upreti, D K; Singh, B R; Pandey, G; Verma, S; Roy, S; Naqvi, A H; Rawat, A K S

    2015-04-01

    Quorum sensing (QS) regulates group behaviors of Candida albicans such as biofilm, hyphal growth, and virulence factors. The sesquiterpene alcohol farnesol, a QS molecule produced by C. albicans, is known to regulate the expression of virulence weapons of this fungus. Fluconazole (FCZ) is a broad-spectrum antifungal drug that is used for the treatment of C. albicans infections. While FCZ can be cytotoxic at high concentrations, our results show that at much lower concentrations, quercetin (QC), a dietary flavonoid isolated from an edible lichen (Usnea longissima), can be implemented as a sensitizing agent for FCZ-resistant C. albicans NBC099, enhancing the efficacy of FCZ. QC enhanced FCZ-mediated cell killing of NBC099 and also induced cell death. These experiments indicated that the combined application of both drugs was FCZ dose dependent rather than QC dose dependent. In addition, we found that QC strongly suppressed the production of virulence weapons-biofilm formation, hyphal development, phospholipase, proteinase, esterase, and hemolytic activity. Treatment with QC also increased FCZ-mediated cell death in NBC099 biofilms. Interestingly, we also found that QC enhances the anticandidal activity of FCZ by inducing apoptotic cell death. We have also established that this sensitization is reliant on the farnesol response generated by QC. Molecular docking studies also support this conclusion and suggest that QC can form hydrogen bonds with Gln969, Thr1105, Ser1108, Arg1109, Asn1110, and Gly1061 in the ATP binding pocket of adenylate cyclase. Thus, this QS-mediated combined sensitizer (QC)-anticandidal agent (FCZ) strategy may be a novel way to enhance the efficacy of FCZ-based therapy of C. albicans infections. PMID:25645848

  18. Porphyromonas gingivalis Differentially Modulates Cell Death Profile in Ox-LDL and TNF-α Pre-Treated Endothelial Cells

    PubMed Central

    Bugueno, Isaac Maximiliano; Khelif, Yacine; Seelam, Narendra; Morand, David-Nicolas; Tenenbaum, Henri; Davideau, Jean-Luc; Huck, Olivier

    2016-01-01

    Objective Clinical studies demonstrated a potential link between atherosclerosis and periodontitis. Porphyromonas gingivalis (Pg), one of the main periodontal pathogen, has been associated to atheromatous plaque worsening. However, synergism between infection and other endothelial stressors such as oxidized-LDL or TNF-α especially on endothelial cell (EC) death has not been investigated. This study aims to assess the role of Pg on EC death in an inflammatory context and to determine potential molecular pathways involved. Methods Human umbilical vein ECs (HUVECs) were infected with Pg (MOI 100) or stimulated by its lipopolysaccharide (Pg-LPS) (1μg/ml) for 24 to 48 hours. Cell viability was measured with AlamarBlue test, type of cell death induced was assessed using Annexin V/propidium iodide staining. mRNA expression regarding caspase-1, -3, -9, Bcl-2, Bax-1 and Apaf-1 has been evaluated with RT-qPCR. Caspases enzymatic activity and concentration of APAF-1 protein were evaluated to confirm mRNA results. Results Pg infection and Pg-LPS stimulation induced EC death. A cumulative effect has been observed in Ox-LDL pre-treated ECs infected or stimulated. This effect was not observed in TNF-α pre-treated cells. Pg infection promotes EC necrosis, however, in infected Ox-LDL pre-treated ECs, apoptosis was promoted. This effect was not observed in TNF-α pre-treated cells highlighting specificity of molecular pathways activated. Regarding mRNA expression, Pg increased expression of pro-apoptotic genes including caspases-1,-3,-9, Bax-1 and decreased expression of anti-apoptotic Bcl-2. In Ox-LDL pre-treated ECs, Pg increased significantly the expression of Apaf-1. These results were confirmed at the protein level. Conclusion This study contributes to demonstrate that Pg and its Pg-LPS could exacerbate Ox-LDL and TNF-α induced endothelial injury through increase of EC death. Interestingly, molecular pathways are differentially modulated by the infection in function of the

  19. Using radio-induced fluorescence to determine the horizontal structure of ion layers in the mesosphere and lower thermosphere

    NASA Astrophysics Data System (ADS)

    Bernhardt, Paul A.; Gondarenko, Natalia A.; Guzdar, Parvez N.; Huba, Joseph D.; Ossakow, S. L.; Djuth, Frank T.; Tepley, C. A.; Sulzer, Michael P.; Kagan, Ludmila; Kelley, M. C.

    2002-01-01

    Two-dimensional images of Sporadic-E layers have been produced using a new technique called radio induced fluorescence (RIF). This technique makes the ion layers glow when being stimulated by high power radio waves. Normally the ion-layers do not radiate visible emissions. Experiments on January 1998 at Arecibo Observatory in Puerto Rico have shown that the layers can be made to glow at 557.7 nm and other wavelengths by illuminating them with radio waves at 3.175 MHz with effective radiated powers of 80 megawatts. The regions of the sporadic-E layers that have electron densities greater than the critical density for reflection of the radio waves emit electrons that collide with and excite atmospheric atomic oxygen and molecular nitrogen. A charge-coupled-device (CCD) imager located on the ground is used to capture images of the glowing E-region structures. The camera exposure times were in the range of 15 to 45 seconds. The images obtained using this technique show a wide variety of structures in the sporadic-E layers. Some layers cover the 15 x 30 km region illuminated by the radio wave beam. Other layers show strong modulation of the E-region by neutral wind instabilities. Two-dimensional computer simulations of the coupling between neutral wind turbulence and the ion layers simulate the structure in the images.

  20. Mitochondrial membrane lipids in life and death and their molecular modulation by diet: tuning the furnace.

    PubMed

    Monteiro, João P; Morais, Catarina M; Oliveira, Paulo J; Jurado, Amália S

    2014-01-01

    The traditional view of mitochondria as cell powerhouses is a matter of common knowledge, but the overall view of these extraordinary organelles has been revolutionized in the last years. In fact, a large number of important and diverse processes take place at the mitochondrial level, which clearly surpass the energy production scope, intruding the critical fragile balance between cell life and death. The entangled biochemistry of mitochondrial membranes has been found to be dependent on specific lipid requirements, with cardiolipin holding a great part of the raised functional interest. Mitochondria contain a complex membrane system, based on a variety of lipids and exquisite asymmetries. Mitochondria lipid membrane composition depends on a tight interplay with the endoplasmic reticulum, from which some of the lipids present in the mitochondrial membranes have to be imported, at least in the form of precursors. Here, we review some external interventions resulting in alterations of mitochondrial lipid content, namely dietary interventions and genetic manipulation. Such manipulations of mitochondrial membrane lipid composition should result in physiological impact, given the importance of lipid-protein interactions within the mitochondrial membrane boundaries. We provide arguments for future experiments using the most modern chemical and biophysical approaches as well as computer simulation studies applied to appropriate biological membrane model systems, in order to identify the effects exerted by diet-induced lipid changes on membrane physical properties. PMID:24953065

  1. Curcumin modulates cell death and is protective in Huntington's disease model.

    PubMed

    Chongtham, Anjalika; Agrawal, Namita

    2016-01-01

    Huntington's disease (HD) is a progressive, dominantly inherited neurological disorder caused by an abnormal expansion of polyglutamine (polyQ) repeat within the Huntingtin (Htt) protein with no disease modifying treatments. In a Drosophila model of HD, expression of mutant Huntingtin (Htt) protein with expanded polyQ leads to formation of inclusion bodies (IBs), increase in cellular toxicity, progression of motor disabilities and reduced viability. Multiple cellular events such as oxidative stress, mitochondrial dysfunction, inflammation and transcriptional dysregulation are reported to contribute to pathology, however, till date there are no disease-modifying treatments with least side effects. Therefore, we investigated effect of the phytochemical curcumin on HD pathogenesis. Curcumin, a phytochemical and commonly used ingredient in Asian food has a wide spectrum of anti-oxidant, anti-inflammatory and anti-fibrilogenic properties. In this study, we provide evidence that curcumin significantly ameliorates disease symptoms in a Drosophila model of HD by suppressing cell death and can be a key to halting the progression of Huntington's disease with least side effects. PMID:26728250

  2. Curcumin modulates cell death and is protective in Huntington’s disease model

    PubMed Central

    Chongtham, Anjalika; Agrawal, Namita

    2016-01-01

    Huntington’s disease (HD) is a progressive, dominantly inherited neurological disorder caused by an abnormal expansion of polyglutamine (polyQ) repeat within the Huntingtin (Htt) protein with no disease modifying treatments. In a Drosophila model of HD, expression of mutant Huntingtin (Htt) protein with expanded polyQ leads to formation of inclusion bodies (IBs), increase in cellular toxicity, progression of motor disabilities and reduced viability. Multiple cellular events such as oxidative stress, mitochondrial dysfunction, inflammation and transcriptional dysregulation are reported to contribute to pathology, however, till date there are no disease-modifying treatments with least side effects. Therefore, we investigated effect of the phytochemical curcumin on HD pathogenesis. Curcumin, a phytochemical and commonly used ingredient in Asian food has a wide spectrum of anti-oxidant, anti-inflammatory and anti-fibrilogenic properties. In this study, we provide evidence that curcumin significantly ameliorates disease symptoms in a Drosophila model of HD by suppressing cell death and can be a key to halting the progression of Huntington’s disease with least side effects. PMID:26728250

  3. Apoptotic cell death during Drosophila oogenesis is differentially increased by electromagnetic radiation depending on modulation, intensity and duration of exposure.

    PubMed

    Sagioglou, Niki E; Manta, Areti K; Giannarakis, Ioannis K; Skouroliakou, Aikaterini S; Margaritis, Lukas H

    2016-01-01

    Present generations are being repeatedly exposed to different types and doses of non-ionizing radiation (NIR) from wireless technologies (FM radio, TETRA and TV stations, GSM and UMTS phones/base stations, Wi-Fi networks, DECT phones). Although there is controversy on the published data regarding the non-thermal effects of NIR, studies have convincingly demonstrated bioeffects. Their results indicate that modulation, intensity, exposure duration and model system are important factors determining the biological response to irradiation. Attempting to address the dependence of NIR bioeffectiveness on these factors, apoptosis in the model biological system Drosophila melanogaster was studied under different exposure protocols. A signal generator was used operating alternatively under Continuous Wave (CW) or Frequency Modulation (FM) emission modes, at three power output values (10 dB, 0, -10 dB), under four carrier frequencies (100, 395, 682, 900 MHz). Newly emerged flies were exposed either acutely (6 min or 60 min on the 6th day), or repeatedly (6 min or 60 min daily for the first 6 days of their life). All exposure protocols resulted in an increase of apoptotic cell death (ACD) observed in egg chambers, even at very low electric field strengths. FM waves seem to have a stronger effect in ACD than continuous waves. Regarding intensity and temporal exposure pattern, EMF-biological tissue interaction is not linear in response. Intensity threshold for the induction of biological effects depends on frequency, modulation and temporal exposure pattern with unknown so far mechanisms. Given this complexity, translating such experimental data into possible human exposure guidelines is yet arbitrary. PMID:25333897

  4. S-Nitrosylation—Mediated Redox Transcriptional Switch Modulates Neurogenesis and Neuronal Cell Death

    PubMed Central

    Okamoto, Shu-ichi; Nakamura, Tomohiro; Cieplak, Piotr; Chan, Shing Fai; Kalashnikova, Evgenia; Liao, Lujian; Saleem, Sofiyan; Han, Xuemei; Clemente, Arjay; Nutter, Anthony; Sances, Sam; Brechtel, Christopher; Haus, Daniel; Haun, Florian; Sanz-Blasco, Sara; Huang, Xiayu; Li, Hao; Zaremba, Jeffrey D.; Cui, Jiankun; Gu, Zezong; Nikzad, Rana; Harrop, Anne; McKercher, Scott R.; Godzik, Adam; Yates, John R.; Lipton, Stuart A.

    2014-01-01

    SUMMARY Redox-mediated posttranslational modifications represent a molecular switch that controls major mechanisms of cell function. Nitric oxide (NO) can mediate redox reactions via S-nitrosylation, representing transfer of an NO group to a critical protein thiol. NO is known to modulate neurogenesis and neuronal survival in various brain regions in disparate neurodegenerative conditions. However, a unifying molecular mechanism linking these phenomena remains unknown. Here we report that S-nitrosylation of myocyte enhancer factor 2 (MEF2) transcription factors acts as a redox switch to inhibit both neurogenesis and neuronal survival. Structure-based analysis reveals that MEF2 dimerization creates a pocket, facilitating S-nitrosylation at an evolutionally conserved cysteine residue in the DNA binding domain. S-Nitrosylation disrupts MEF2-DNA binding and transcriptional activity, leading to impaired neurogenesis and survival in vitro and in vivo. Our data define a novel molecular switch whereby redox-mediated posttranslational modification controls both neurogenesis and neurodegeneration via a single transcriptional signaling cascade. PMID:25001280

  5. S-nitrosylation-mediated redox transcriptional switch modulates neurogenesis and neuronal cell death.

    PubMed

    Okamoto, Shu-Ichi; Nakamura, Tomohiro; Cieplak, Piotr; Chan, Shing Fai; Kalashnikova, Evgenia; Liao, Lujian; Saleem, Sofiyan; Han, Xuemei; Clemente, Arjay; Nutter, Anthony; Sances, Sam; Brechtel, Christopher; Haus, Daniel; Haun, Florian; Sanz-Blasco, Sara; Huang, Xiayu; Li, Hao; Zaremba, Jeffrey D; Cui, Jiankun; Gu, Zezong; Nikzad, Rana; Harrop, Anne; McKercher, Scott R; Godzik, Adam; Yates, John R; Lipton, Stuart A

    2014-07-10

    Redox-mediated posttranslational modifications represent a molecular switch that controls major mechanisms of cell function. Nitric oxide (NO) can mediate redox reactions via S-nitrosylation, representing transfer of an NO group to a critical protein thiol. NO is known to modulate neurogenesis and neuronal survival in various brain regions in disparate neurodegenerative conditions. However, a unifying molecular mechanism linking these phenomena remains unknown. Here, we report that S-nitrosylation of myocyte enhancer factor 2 (MEF2) transcription factors acts as a redox switch to inhibit both neurogenesis and neuronal survival. Structure-based analysis reveals that MEF2 dimerization creates a pocket, facilitating S-nitrosylation at an evolutionally conserved cysteine residue in the DNA binding domain. S-Nitrosylation disrupts MEF2-DNA binding and transcriptional activity, leading to impaired neurogenesis and survival in vitro and in vivo. Our data define a molecular switch whereby redox-mediated posttranslational modification controls both neurogenesis and neurodegeneration via a single transcriptional signaling cascade. PMID:25001280

  6. Nicotine-mediated signals modulate cell death and survival of T lymphocytes

    SciTech Connect

    Oloris, Silvia C.S.; Frazer-Abel, Ashley A.; Jubala, Cristan M.; Fosmire, Susan P.; Helm, Karen M.; Robinson, Sally R.; Korpela, Derek M.; Duckett, Megan M.; Baksh, Shairaz; Modiano, Jaime F.

    2010-02-01

    The capacity of nicotine to affect the behavior of non-neuronal cells through neuronal nicotinic acetylcholine receptors (nAChRs) has been the subject of considerable recent attention. Previously, we showed that exposure to nicotine activates the nuclear factor of activated T cells (NFAT) transcription factor in lymphocytes and endothelial cells, leading to alterations in cellular growth and vascular endothelial growth factor production. Here, we extend these studies to document effects of nicotine on lymphocyte survival. The data show that nicotine induces paradoxical effects that might alternatively enforce survival or trigger apoptosis, suggesting that depending on timing and context, nicotine might act both as a survival factor or as an inducer of apoptosis in normal or transformed lymphocytes, and possibly other non-neuronal cells. In addition, our results show that, while having overlapping functions, low and high affinity nAChRs also transmit signals that promote distinct outcomes in lymphocytes. The sum of our data suggests that selective modulation of nAChRs might be useful to regulate lymphocyte activation and survival in health and disease.

  7. Positive allosteric modulation of alpha-7 nicotinic receptors promotes cell death by inducing Ca(2+) release from the endoplasmic reticulum.

    PubMed

    Guerra-Álvarez, María; Moreno-Ortega, Ana J; Navarro, Elisa; Fernández-Morales, José Carlos; Egea, Javier; López, Manuela G; Cano-Abad, María F

    2015-05-01

    Positive allosteric modulation of α7 isoform of nicotinic acetylcholine receptors (α7-nAChRs) is emerging as a promising therapeutic approach for central nervous system disorders such as schizophrenia or Alzheimer's disease. However, its effect on Ca(2+) signaling and cell viability remains controversial. This study focuses on how the type II positive allosteric modulator (PAM II) PNU120596 affects intracellular Ca(2+) signaling and cell viability. We used human SH-SY5Y neuroblastoma cells overexpressing α7-nAChRs (α7-SH) and their control (C-SH). We monitored cytoplasmic and endoplasmic reticulum (ER) Ca(2+) with Fura-2 and the genetically encoded cameleon targeting the ER, respectively. Nicotinic inward currents were measured using patch-clamp techniques. Viability was assessed using methylthiazolyl blue tetrazolium bromide or propidium iodide staining. We observed that in the presence of a nicotinic agonist, PNU120596 (i) reduced viability of α7-SH but not of C-SH cells; (ii) significantly increased inward nicotinic currents and cytosolic Ca(2+) concentration; (iii) released Ca(2+) from the ER by a Ca(2+) -induced Ca(2+) release mechanism only in α7-SH cells; (iv) was cytotoxic in rat organotypic hippocampal slice cultures; and, lastly, all these effects were prevented by selective blockade of α7-nAChRs, ryanodine receptors, or IP3 receptors. In conclusion, positive allosteric modulation of α7-nAChRs with the PAM II PNU120596 can lead to dysregulation of ER Ca(2+) , overloading of intracellular Ca(2+) , and neuronal cell death. This study focuses on how the type II positive allosteric modulator PNU120596 (PAM II PNU12) affects intracellular Ca(2+) signaling and cell viability. Using SH-SY5Y neuroblastoma cells overexpressing α7-nAChRs (α7-SH) and their control (C-SH), we find that PAM of α7-nAChRs with PNU120596: (i) increases inward calcium current (ICa ) and cytosolic Ca(2+) concentration ([Ca(2+) ]cyt ); (ii) releases Ca(2+) from the ER ([Ca(2

  8. TAK1 Is Essential for Osteoclast Differentiation and Is an Important Modulator of Cell Death by Apoptosis and Necroptosis

    PubMed Central

    Lai, YunJu; Xie, Min; Schneider, Michael D.

    2013-01-01

    Transforming growth factor β (TGF-β)-activated kinase 1 (TAK1), a mitogen-activated protein 3 (MAP3) kinase, plays an essential role in inflammation by activating the IκB kinase (IKK)/nuclear factor κB (NF-κB) and stress kinase (p38 and c-Jun N-terminal kinase [JNK]) pathways in response to many stimuli. The tumor necrosis factor (TNF) superfamily member receptor activator of NF-κB ligand (RANKL) regulates osteoclastogenesis through its receptor, RANK, and the signaling adaptor TRAF6. Because TAK1 activation is mediated through TRAF6 in the interleukin 1 receptor (IL-1R) and toll-like receptor (TLR) pathways, we sought to investigate the consequence of TAK1 deletion in RANKL-mediated osteoclastogenesis. We generated macrophage colony-stimulating factor (M-CSF)-derived monocytes from the bone marrow of mice with TAK1 deletion in the myeloid lineage. Unexpectedly, TAK1-deficient monocytes in culture died rapidly but could be rescued by retroviral expression of TAK1, inhibition of receptor-interacting protein 1 (RIP1) kinase activity with necrostatin-1, or simultaneous genetic deletion of TNF receptor 1 (TNFR1). Further investigation using TAK1-deficient mouse embryonic fibroblasts revealed that TNF-α-induced cell death was abrogated by the simultaneous inhibition of caspases and knockdown of RIP3, suggesting that TAK1 is an important modulator of both apoptosis and necroptosis. Moreover, TAK1-deficient monocytes rescued from programmed cell death did not form mature osteoclasts in response to RANKL, indicating that TAK1 is indispensable to RANKL-induced osteoclastogenesis. To our knowledge, we are the first to report that mice in which TAK1 has been conditionally deleted in osteoclasts develop osteopetrosis. PMID:23166301

  9. Studying p53 family proteins in yeast: Induction of autophagic cell death and modulation by interactors and small molecules

    SciTech Connect

    Leão, Mariana; Gomes, Sara; Bessa, Cláudia; Soares, Joana; Raimundo, Liliana; Monti, Paola; Fronza, Gilberto; Pereira, Clara; Saraiva, Lucília

    2015-01-01

    In this work, the yeast Saccharomyces cerevisiae was used to individually study human p53, p63 (full length and truncated forms) and p73. Using this cell system, the effect of these proteins on cell proliferation and death, and the influence of MDM2 and MDMX on their activities were analyzed. When expressed in yeast, wild-type p53, TAp63, ΔNp63 and TAp73 induced growth inhibition associated with S-phase cell cycle arrest. This growth inhibition was accompanied by reactive oxygen species production and autophagic cell death. Furthermore, they stimulated rapamycin-induced autophagy. On the contrary, none of the tested p53 family members induced apoptosis either per se or after apoptotic stimuli. As previously reported for p53, also TAp63, ΔNp63 and TAp73 increased actin expression levels and its depolarization, suggesting that ACT1 is also a p63 and p73 putative yeast target gene. Additionally, MDM2 and MDMX inhibited the activity of all tested p53 family members in yeast, although the effect was weaker on TAp63. Moreover, Nutlin-3a and SJ-172550 were identified as potential inhibitors of the p73 interaction with MDM2 and MDMX, respectively. Altogether, the yeast-based assays herein developed can be envisaged as a simplified cell system to study the involvement of p53 family members in autophagy, the modulation of their activities by specific interactors (MDM2 and MDMX), and the potential of new small molecules to modulate these interactions. - Highlights: • p53, p63 and p73 are individually studied in the yeast S. cerevisiae. • p53 family members induce ROS production, cell cycle arrest and autophagy in yeast. • p53 family members increase actin depolarization and expression levels in yeast. • MDM2 and MDMX inhibit the activity of p53 family members in yeast. • Yeast can be a useful tool to study the biology and drugability of p53, p63 and p73.

  10. Thioredoxin-2 Modulates Neuronal Programmed Cell Death in the Embryonic Chick Spinal Cord in Basal and Target-Deprived Conditions

    PubMed Central

    Pirson, Marc; Debrulle, Stéphanie; Clippe, André; Clotman, Frédéric; Knoops, Bernard

    2015-01-01

    Thioredoxin-2 (Trx2) is a mitochondrial protein using a dithiol active site to reduce protein disulfides. In addition to the cytoprotective function of this enzyme, several studies have highlighted the implication of Trx2 in cellular signaling events. In particular, growing evidence points to such roles of redox enzymes in developmental processes taking place in the central nervous system. Here, we investigate the potential implication of Trx2 in embryonic development of chick spinal cord. To this end, we first studied the distribution of the enzyme in this tissue and report strong expression of Trx2 in chick embryo post-mitotic neurons at E4.5 and in motor neurons at E6.5. Using in ovo electroporation, we go on to highlight a cytoprotective effect of Trx2 on the programmed cell death (PCD) of neurons during spinal cord development and in a novel cultured spinal cord explant model. These findings suggest an implication of Trx2 in the modulation of developmental PCD of neurons during embryonic development of the spinal cord, possibly through redox regulation mechanisms. PMID:26540198

  11. Identification of an anabolic selective androgen receptor modulator that actively induces death of androgen-independent prostate cancer cells.

    PubMed

    Schmidt, Azriel; Meissner, Robert S; Gentile, Michael A; Chisamore, Michael J; Opas, Evan E; Scafonas, Angela; Cusick, Tara E; Gambone, Carlo; Pennypacker, Brenda; Hodor, Paul; Perkins, James J; Bai, Chang; Ferraro, Damien; Bettoun, David J; Wilkinson, Hilary A; Alves, Stephen E; Flores, Osvaldo; Ray, William J

    2014-09-01

    Prostate cancer (PCa) initially responds to inhibition of androgen receptor (AR) signaling, but inevitably progresses to hormone ablation-resistant disease. Much effort is focused on optimizing this androgen deprivation strategy by improving hormone depletion and AR antagonism. However we found that bicalutamide, a clinically used antiandrogen, actually resembles a selective AR modulator (SARM), as it partially regulates 24% of endogenously 5α-dihydrotestosterone (DHT)-responsive genes in AR(+) MDA-MB-453 breast cancer cells. These data suggested that passive blocking of all AR functions is not required for PCa therapy. Hence, we adopted an active strategy that calls for the development of novel SARMs, which induce a unique gene expression profile that is intolerable to PCa cells. Therefore, we screened 3000 SARMs for the ability to arrest the androgen-independent growth of AR(+) 22Rv1 and LNCaP PCa cells but not AR(-) PC3 or DU145 cells. We identified only one such compound; the 4-aza-steroid, MK-4541, a potent and selective SARM. MK-4541 induces caspase-3 activity and cell death in both androgen-independent, AR(+) PCa cell lines but spares AR(-) cells or AR(+) non-PCa cells. This activity correlates with its promoter context- and cell-type dependent transcriptional effects. In rats, MK-4541 inhibits the trophic effects of DHT on the prostate, but not the levator ani muscle, and triggers an anabolic response in the periosteal compartment of bone. Therefore, MK-4541 has the potential to effectively manage prostatic hypertrophic diseases owing to its antitumor SARM-like mechanism, while simultaneously maintaining the anabolic benefits of natural androgens. PMID:24565564

  12. Activation and modulation of cardiac poly-adenosine diphosphate ribose polymerase activity in a rat model of brain death.

    PubMed

    Brain, John G; Rostron, Anthony J; Dark, John H; Kirby, John A

    2008-05-15

    DNA damage during transplantation can activate poly-adenosine diphosphate ribose polymerase (PARP) resulting in the generation of polymers of adenosine diphosphate-ribose (PAR). Excessive linkage of PAR to nuclear proteins can induce cell death, thereby limiting the function of transplanted organs. This study uses a rat model of brain death to determine the profile of PARP activation and whether mechanisms that lead to cell death can be ameliorated by appropriate donor resuscitation. The expression of PAR-linked nuclear proteins within cardiac myocytes was greatly increased after the induction of donor brain death. Importantly, infusion of noradrenaline or vasopressin to normalize the chronic hypotension produced by brain death reduced the expression of PAR to a level below baseline. These data suggest that chronic hypotension after donor brain death has the potential to limit cardiac function through the activation of PARP; however, this early cause of graft damage can be mitigated by appropriate donor resuscitation. PMID:18475194

  13. Prediction of clinical toxicity in locally advanced head and neck cancer patients by radio-induced apoptosis in peripheral blood lymphocytes (PBLs)

    PubMed Central

    2010-01-01

    Head and neck cancer is treated mainly by surgery and radiotherapy. Normal tissue toxicity due to x-ray exposure is a limiting factor for treatment success. Many efforts have been employed to develop predictive tests applied to clinical practice. Determination of lymphocyte radio-sensitivity by radio-induced apoptosis arises as a possible method to predict tissue toxicity due to radiotherapy. The aim of the present study was to analyze radio-induced apoptosis of peripheral blood lymphocytes in head and neck cancer patients and to explore their role in predicting radiation induced toxicity. Seventy nine consecutive patients suffering from head and neck cancer, diagnosed and treated in our institution, were included in the study. Toxicity was evaluated using the Radiation Therapy Oncology Group scale. Peripheral blood lymphocytes were isolated and irradiated at 0, 1, 2 and 8 Gy during 24 hours. Apoptosis was measured by flow cytometry using annexin V/propidium iodide. Lymphocytes were marked with CD45 APC-conjugated monoclonal antibody. Radiation-induced apoptosis increased in order to radiation dose and fitted to a semi logarithmic model defined by two constants: α and β. α, as the origin of the curve in the Y axis determining the percentage of spontaneous cell death, and β, as the slope of the curve determining the percentage of cell death induced at a determined radiation dose, were obtained. β value was statistically associated to normal tissue toxicity in terms of severe xerostomia, as higher levels of apoptosis were observed in patients with low toxicity (p = 0.035; Exp(B) 0.224, I.C.95% (0.060-0.904)). These data agree with our previous results and suggest that it is possible to estimate the radiosensitivity of peripheral blood lymphocytes from patients determining the radiation induced apoptosis with annexin V/propidium iodide staining. β values observed define an individual radiosensitivity profile that could predict late toxicity due to radiotherapy

  14. Apoptin-induced cell death is modulated by Bcl-2 family members and is Apaf-1 dependent

    PubMed Central

    Burek, M; Maddika, S; Burek, CJ; Daniel, PT; Schulze-Osthoff, K; Los, M

    2010-01-01

    Apoptin, a chicken anemia virus-derived protein, selectively induces apoptosis in transformed but not in normal cells, thus making it a promising candidate as a novel anticancer therapeutic. The mechanism of apoptin-induced apoptosis is largely unknown. Here, we report that contrary to previous assumptions, Bcl-2 and Bcl-xL inhibit apoptin-induced cell death in several tumor cell lines. In contrast, deficiency of Bax conferred resistance, whereas Bax expression sensitized cells to apoptin-induced death. Cell death induction by apoptin was associated with cytochrome c release from mitochondria as well as with caspase-3 and -7 activation. Benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone, a broad spectrum caspase inhibitor, was highly protective against apoptin-induced cell death. Apoptosis induced by apoptin required Apaf-1, as immortalized Apaf-1-deficient fibroblasts as well as tumor cells devoid of Apaf-1were strongly protected. Thus, our data indicate that apoptin-induced apoptosis is not only Bcl-2- and caspase dependent, but also engages an Apaf-1apoptosome-mediated mitochondrial death pathway. PMID:16288204

  15. [Importance of local skin treatments during radiotherapy for prevention and treatment of radio-induced epithelitis].

    PubMed

    Chargari, C; Fromantin, I; Kirova, Y M

    2009-07-01

    Radio-epithelitis represents a common problem, for which treatments are characterized by a great heterogeneity. The present review of literature focuses on data referenced in Pubmed((c))/Medline((c)) and published in French/English. Despite a real preclinical rationale, aloe vera and trolamine failed to demonstrate any benefit in the prophylactic settings. In a prospective assessment phase III assessment, Calendula Officinalis was shown to be superior to trolamine for the prevention of radio-epithelitis. In the curative settings, sucrafalte failed to demonstrate any benefit. The benefit of dermocorticoids was suggested in terms of erythema and itching. Promising clinical results are available with hyaluronic acid (MA S065D and Ialugen) and silver leaf may reduce the intensity of cutaneous radio-induced side effects. Data from the literature are conflicting, making real the difficulty to adopt from clinical trials any proof-of-principle strategy. Considering these uncertainties, several strategies are allowed. New topics are under investigation. Present data from the literature highlight the need for further trials, in order to propose evidence-based treatments and to harmonize clinical practice. PMID:19524470

  16. METACASPASE9 modulates autophagy to confine cell death to the target cells during Arabidopsis vascular xylem differentiation

    PubMed Central

    Escamez, Sacha; André, Domenique; Zhang, Bo; Bollhöner, Benjamin; Pesquet, Edouard; Tuominen, Hannele

    2016-01-01

    ABSTRACT We uncovered that the level of autophagy in plant cells undergoing programmed cell death determines the fate of the surrounding cells. Our approach consisted of using Arabidopsis thaliana cell cultures capable of differentiating into two different cell types: vascular tracheary elements (TEs) that undergo programmed cell death (PCD) and protoplast autolysis, and parenchymatic non-TEs that remain alive. The TE cell type displayed higher levels of autophagy when expression of the TE-specific METACASPASE9 (MC9) was reduced using RNAi (MC9-RNAi). Misregulation of autophagy in the MC9-RNAi TEs coincided with ectopic death of the non-TEs, implying the existence of an autophagy-dependent intercellular signalling from within the TEs towards the non-TEs. Viability of the non-TEs was restored when AUTOPHAGY2 (ATG2) was downregulated specifically in MC9-RNAi TEs, demonstrating the importance of autophagy in the spatial confinement of cell death. Our results suggest that other eukaryotic cells undergoing PCD might also need to tightly regulate their level of autophagy to avoid detrimental consequences for the surrounding cells. PMID:26740571

  17. Anti-cancer fatty-acid derivative induces autophagic cell death through modulation of PKM isoform expression profile mediated by bcr-abl in chronic myeloid leukemia.

    PubMed

    Shinohara, Haruka; Taniguchi, Kohei; Kumazaki, Minami; Yamada, Nami; Ito, Yuko; Otsuki, Yoshinori; Uno, Bunji; Hayakawa, Fumihiko; Minami, Yosuke; Naoe, Tomoki; Akao, Yukihiro

    2015-04-28

    The fusion gene bcr-abl develops chronic myeloid leukemia (CML), and stimulates PI3K/Akt/mTOR signaling, leading to impaired autophagy. PI3K/Akt/mTOR signaling also plays an important role in cell metabolism. The Warburg effect is a well-recognized hallmark of cancer energy metabolism, and is regulated by the mTOR/c-Myc/hnRNP/PKM signaling cascade. To develop a new strategy for the treatment of CML, we investigated the associations among bcr-abl, the cascade related to cancer energy metabolism, and autophagy induced by a fatty-acid derivative that we had previously reported as being an autophagy inducer. Here we report that a fatty-acid derivative, AIC-47, induced transcriptional repression of the bcr-abl gene and modulated the expression profile of PKM isoforms, resulting in autophagic cell death. We show that c-Myc functioned as a transcriptional activator of bcr-abl, and regulated the hnRNP/PKM cascade. AIC-47, acting through the PPARγ/β-catenin pathway, induced down-regulation of c-Myc, leading to the disruption of the bcr-abl/mTOR/hnRNP signaling pathway, and switching of the expression of PKM2 to PKM1. This switching caused autophagic cell death through an increase in the ROS level. Our findings suggest that AIC-47 induced autophagic cell death through the PPARγ/β-catenin/bcr-abl/mTOR/hnRNP/PKM cascade. PMID:25644089

  18. The Caspase 8 Inhibitor c-FLIPL Modulates T-Cell Receptor-Induced Proliferation but Not Activation-Induced Cell Death of Lymphocytes

    PubMed Central

    Lens, Susanne M. A.; Kataoka, Takao; Fortner, Karen A.; Tinel, Antoine; Ferrero, Isabel; MacDonald, Robson H.; Hahne, Michel; Beermann, Friedrich; Attinger, Antoine; Orbea, Hans-Acha; Budd, Ralph C.; Tschopp, Jürg

    2002-01-01

    The caspase 8 inhibitor c-FLIPL can act in vitro as a molecular switch between cell death and growth signals transmitted by the death receptor Fas (CD95). To elucidate its function in vivo, transgenic mice were generated that overexpress c-FLIPL in the T-cell compartment (c-FLIPL Tg mice). As anticipated, FasL-induced apoptosis was inhibited in T cells from the c-FLIPL Tg mice. In contrast, activation-induced cell death of T cells in c-FLIPL Tg mice was unaffected, suggesting that this deletion process can proceed in the absence of active caspase 8. Accordingly, c-FLIPL Tg mice differed from Fas-deficient mice by showing no accumulation of B220+ CD4− CD8− T cells. However, stimulation of T lymphocytes with suboptimal doses of anti-CD3 or antigen revealed increased proliferative responses in T cells from c-FLIPL Tg mice. Thus, a major role of c-FLIPL in vivo is the modulation of T-cell proliferation by decreasing the T-cell receptor signaling threshold. PMID:12101236

  19. Functional characterization of NAC55 transcription factor from oilseed rape (Brassica napus L.) as a novel transcriptional activator modulating reactive oxygen species accumulation and cell death.

    PubMed

    Niu, Fangfang; Wang, Chen; Yan, Jingli; Guo, Xiaohua; Wu, Feifei; Yang, Bo; Deyholos, Michael K; Jiang, Yuan-Qing

    2016-09-01

    NAC transcription factors (TFs) are plant-specific and play important roles in development, responses to biotic and abiotic cues and hormone signaling. So far, only a few NAC genes have been reported to regulate cell death. In this study, we identified and characterized a NAC55 gene isolated from oilseed rape (Brassica napus L.). BnaNAC55 responds to multiple stresses, including cold, heat, abscisic acid (ABA), jasmonic acid (JA) and a necrotrophic fungal pathogen Sclerotinia sclerotiorum. BnaNAC55 has transactivation activity and is located in the nucleus. BnaNAC55 is able to form homodimers in planta. Unlike ANAC055, full-length BnaNAC55, but not either the N-terminal NAC domain or C-terminal regulatory domain, induces ROS accumulation and hypersensitive response (HR)-like cell death when expressed both in oilseed rape protoplasts and Nicotiana benthamiana. Furthermore, BnaNAC55 expression causes obvious nuclear DNA fragmentation. Moreover, quantitative reverse transcription PCR (qRT-PCR) analysis identified that the expression levels of multiple genes regulating ROS production and scavenging, defense response as well as senescence are significantly induced. Using a dual luciferase reporter assay, we further confirm that BnaNAC55 could activate the expression of a few ROS and defense-related gene expression. Taken together, our work has identified a novel NAC TF from oilseed rape that modulates ROS accumulation and cell death. PMID:27312204

  20. Importance of PdpC, IglC, IglI, and IglG for modulation of a host cell death pathway induced by Francisella tularensis.

    PubMed

    Lindgren, Marie; Eneslätt, Kjell; Bröms, Jeanette E; Sjöstedt, Anders

    2013-06-01

    Modulation of host cell death pathways appears to be a prerequisite for the successful lifestyles of many intracellular pathogens. The facultative intracellular bacterium Francisella tularensis is highly pathogenic, and effective proliferation in the macrophage cytosol leading to host cell death is a requirement for its virulence. To better understand the prerequisites of this cell death, macrophages were infected with the F. tularensis live vaccine strain (LVS), and the effects were compared to those resulting from infections with deletion mutants lacking expression of either of the pdpC, iglC, iglG, or iglI genes, which encode components of the Francisella pathogenicity island (FPI), a type VI secretion system. Within 12 h, a majority of the J774 cells infected with the LVS strain showed production of mitochondrial superoxide and, after 24 h, marked signs of mitochondrial damage, caspase-9 and caspase-3 activation, phosphatidylserine expression, nucleosome formation, and membrane leakage. In contrast, neither of these events occurred after infection with the ΔiglI or ΔiglC mutants, although the former strain replicated. The ΔiglG mutant replicated effectively but induced only marginal cytopathogenic effects after 24 h and intermediate effects after 48 h. In contrast, the ΔpdpC mutant showed no replication but induced marked mitochondrial superoxide production and mitochondrial damage, caspase-3 activation, nucleosome formation, and phosphatidylserine expression, although the effects were delayed compared to those obtained with LVS. The unique phenotypes of the mutants provide insights regarding the roles of individual FPI components for the modulation of the cytopathogenic effects resulting from the F. tularensis infection. PMID:23529623

  1. Quercetin modulates NF-kappa B and AP-1/JNK pathways to induce cell death in human hepatoma cells.

    PubMed

    Granado-Serrano, Ana Belén; Martín, María Angeles; Bravo, Laura; Goya, Luis; Ramos, Sonia

    2010-01-01

    Quercetin, a dietary flavonoid, has been shown to possess anticarcinogenic properties, but the precise molecular mechanisms of action are not thoroughly elucidated. The aim of this study was to investigate the regulatory effect of quercetin (50 microM) on two main transcription factors (NF-kappa B and AP-1) related to survival/proliferation pathways in a human hepatoma cell line (HepG2) over time. Quercetin induced a significant time-dependent inactivation of the NF-kappa B pathway consistent with a downregulation of the NF-kappa B binding activity (from 15 min onward). These features were in concert with a time-dependent activation (starting at 15 min and maintained up to 18 h) of the AP-1/JNK pathway, which played an important role in the control of the cell death induced by the flavonoid and contributed to the regulation of survival/proliferation (AKT, ERK) and death (caspase-3, p38, unbalance of Bcl-2 proapoptotic and antiapoptotic proteins) signals. These data suggest that NF-kappa B and AP-1 play a main role in the tight regulation of survival/proliferation pathways exerted by quercetin and that the sustained JNK/AP-1 activation and inhibition of NF-kappa B provoked by the flavonoid induced HepG2 death. PMID:20358477

  2. Radio Induced Fluorescence (RIF) Imaging Of E-region Quasi-periodic Structures

    NASA Astrophysics Data System (ADS)

    Bernhardt, P. A.

    The horizontal structure of sporadic-E layers has been imaged using artificial airglow excited by high power radio waves. In January 1998, the HF facility at Arecibo, Puerto Rico beamed a 80 MW signal upward at 3.175 MHz. The beam reflected in the E- region near 120 km altitude to excite green-line emissions at 557.7 nm. Ground based images showed quasi-periodic structures with periods near 2 and 10 km. These struc- tures been interpreted as being produced by Kelvin-Helmholtz (K-H) instabilities in the neutral atmosphere. The excitation of radio induced fluorescence (RIF) emissions has been studied with both one-dimensional and two-dimensional computer simulations of the conversion of electromagnetic waves into electron plasma waves. The steep gradients on the bottomside of the E-layer provide conditions for efficient mode conversion. The re- sulting Langmuir waves accelerate electrons to energies between 2 and 10 eV. These suprathermal electrons collide with oxygen atoms to produce green-line emissions. The optical glow only occurs in the parts of the E-region where the plamsa is dense enough to reflect the 3.175 MHz radio waves. Results of the E-layer observations using the RIF technique have shown horizontal stuctures that are most likely produced by the K-H instability. A numerical model has been generated to demonstrate the effects of neutral wind shears on the E-region structures. The model includes the effects of both speed-shear and turning shear dy- namics. The results of the numerical model are used to suggest future research using high-power radio wave to study the ion dynamics of the lower thermosphere.

  3. Polyamines modulate the roscovitine-induced cell death switch decision autophagy vs. apoptosis in MCF-7 and MDA-MB-231 breast cancer cells.

    PubMed

    Arisan, Elif Damla; Akkoç, Yunus; Akyüz, Kaan Gencer; Kerman, Ezgi Melek; Obakan, Pinar; Çoker-Gürkan, Ajda; Palavan Ünsal, Narçin

    2015-06-01

    Current clinical strategies against breast cancer mainly involve the use of anti‑hormonal agents to decrease estrogen production; however, development of resistance is a major problem. The resistance phenotype depends on the modulation of cell‑cycle regulatory proteins, cyclins and cyclin‑dependent kinases. Roscovitine, a selective inhibitor of cyclin‑dependent kinases, shows high therapeutic potential by causing cell‑cycle arrest in various cancer types. Autophagy is a type of cell death characterized by the enzymatic degradation of macromolecules and organelles in double‑ or multi‑membrane autophagic vesicles. This process has important physiological functions, including the degradation of misfolded proteins and organelle turnover. Recently, the switch between autophagy and apoptosis has been proposed to constitute an important regulator of cell death in response to chemotherapeutic drugs. The process is regulated by several proteins, such as the proteins of the Atg family, essential for the initial formation of the autophagosome, and PI3K, important at the early stages of autophagic vesicle formation. Polyamines (PAs) are small aliphatic amines that play major roles in a number of eukaryotic processes, including cell proliferation. The PA levels are regulated by ornithine decarboxylase (ODC), the rate‑limiting enzyme in PA biosynthesis. In this study, we aimed to investigate the role of PAs in roscovitine‑induced autophagic/apoptotic cell death in estrogen receptor‑positive MCF‑7 and estrogen receptor‑negative MDA‑MB‑231 breast cancer cells. We show that MDA‑MB‑231 cells are more resistant to roscovitine than MCF‑7 cells. This difference was related to the regulation of autophagic key molecules in MDA‑MB‑231 cells. In addition, we found that exogenous PAs have a role in the cell death decision between roscovitine‑induced apoptosis or autophagy in MCF‑7 and MDA‑MB‑231 breast cancer cells. PMID:25650699

  4. Overexpression of alpha-synuclein at non-toxic levels increases dopaminergic cell death induced by copper exposure via modulation of protein degradation pathways.

    PubMed

    Anandhan, Annadurai; Rodriguez-Rocha, Humberto; Bohovych, Iryna; Griggs, Amy M; Zavala-Flores, Laura; Reyes-Reyes, Elsa M; Seravalli, Javier; Stanciu, Lia A; Lee, Jaekwon; Rochet, Jean-Christophe; Khalimonchuk, Oleh; Franco, Rodrigo

    2015-09-01

    Gene multiplications or point mutations in alpha (α)-synuclein are associated with familial and sporadic Parkinson's disease (PD). An increase in copper (Cu) levels has been reported in the cerebrospinal fluid and blood of PD patients, while occupational exposure to Cu has been suggested to augment the risk to develop PD. We aimed to elucidate the mechanisms by which α-synuclein and Cu regulate dopaminergic cell death. Short-term overexpression of wild type (WT) or mutant A53T α-synuclein had no toxic effect in human dopaminergic cells and primary midbrain cultures, but it exerted a synergistic effect on Cu-induced cell death. Cell death induced by Cu was potentiated by overexpression of the Cu transporter protein 1 (Ctr1) and depletion of intracellular glutathione (GSH) indicating that the toxic effects of Cu are linked to alterations in its intracellular homeostasis. Using the redox sensor roGFP, we demonstrated that Cu-induced oxidative stress was primarily localized in the cytosol and not in the mitochondria. However, α-synuclein overexpression had no effect on Cu-induced oxidative stress. WT or A53T α-synuclein overexpression exacerbated Cu toxicity in dopaminergic and yeast cells in the absence of α-synuclein aggregation. Cu increased autophagic flux and protein ubiquitination. Impairment of autophagy by overexpression of a dominant negative Atg5 form or inhibition of the ubiquitin/proteasome system (UPS) with MG132 enhanced Cu-induced cell death. However, only inhibition of the UPS stimulated the synergistic toxic effects of Cu and α-synuclein overexpression. Our results demonstrate that α-synuclein stimulates Cu toxicity in dopaminergic cells independent from its aggregation via modulation of protein degradation pathways. PMID:25497688

  5. Silymarin modulates doxorubicin-induced oxidative stress, Bcl-xL and p53 expression while preventing apoptotic and necrotic cell death in the liver

    SciTech Connect

    Patel, Nirav; Joseph, Cecil; Corcoran, George B.; Ray, Sidhartha D.

    2010-06-01

    The emergence of silymarin (SMN) as a natural remedy for liver diseases, coupled with its entry into NIH clinical trial, signifies its hepatoprotective potential. SMN is noted for its ability to interfere with apoptotic signaling while acting as an antioxidant. This in vivo study was designed to explore the hepatotoxic potential of Doxorubicin (Dox), the well-known cardiotoxin, and in particular whether pre-exposures to SMN can prevent hepatotoxicity by reducing Dox-induced free radical mediated oxidative stress, by modulating expression of apoptotic signaling proteins like Bcl-xL, and by minimizing liver cell death occurring by apoptosis or necrosis. Groups of male ICR mice included Control, Dox alone, SMN alone, and Dox with SMN pre/co-treatment. Control and Dox groups received saline i.p. for 14 days. SMN was administered p.o. for 14 days at 16 mg/kg/day. An approximate LD{sub 50} dose of Dox, 60 mg/kg, was administered i.p. on day 12 to animals receiving saline or SMN. Animals were euthanized 48 h later. Dox alone induced frank liver injury (> 50-fold increase in serum ALT) and oxidative stress (> 20-fold increase in malondialdehyde [MDA]), as well as direct damage to DNA (> 15-fold increase in DNA fragmentation). Coincident genomic damage and oxidative stress influenced genomic stability, reflected in increased PARP activity and p53 expression. Decreases in Bcl-xL protein coupled with enhanced accumulation of cytochrome c in the cytosol accompanied elevated indexes of apoptotic and necrotic cell death. Significantly, SMN exposure reduced Dox hepatotoxicity and associated apoptotic and necrotic cell death. The effects of SMN on Dox were broad, including the ability to modulate changes in both Bcl-xL and p53 expression. In animals treated with SMN, tissue Bcl-xL expression exceeded control values after Dox treatment. Taken together, these results demonstrated that SMN (i) reduced, delayed onset, or prevented toxic effects of Dox which are typically associated

  6. The biphosphinic paladacycle complex induces melanoma cell death through lysosomal-mitochondrial axis modulation and impaired autophagy.

    PubMed

    Gigli, Rafael; Pereira, Gustavo J S; Antunes, Fernanda; Bechara, Alexandre; Garcia, Daniel M; Spindola, Daniel G; Jasiulionis, Mirian G; Caires, Antonio C F; Smaili, Soraya S; Bincoletto, Claudia

    2016-01-01

    Recently, palladium complexes have been extensively studied as cyclization of these complexes by cyclometallation reactions increased their stability making them promising antitumor compounds. In this study, we have investigated apoptosis induced by the Biphosphinic Paladacycle Complex (BPC11) and possible cross talk between apoptosis and autophagy in cell line models of metastatic (Tm5) and non-metastatic (4C11-) melanoma. The BPC11-induced cell death in melanoma involved the lysosomal-mitochondrial axis, which is characterized by LMP, CatB activation and increased Bax protein levels following its translocation to mitochondria. Mitochondrial hyperpolarization, followed by membrane potential dissipation and cleavage of caspase-3, also resulted in cell death after 24 h of incubation. We also found that BPC11-mediated LC3II formation and increased p62 protein levels, suggesting blocked autophagy, probably due to LMP. Interestingly, the treatment of Tm5 and 4C11(-) cells with 3-methyladenine (3-MA), an inhibitor of the initial stage of autophagy, potentiated the effects of BPC11. We conclude that BPC11 is an anti-melanoma agent and that autophagy may be acting as a mechanism of melanoma cells resistance. Also, these data highlight the importance of studies involving autophagy and apoptosis during pre-clinical studies of new drugs with anticancer properties. PMID:26599531

  7. Vitamin B₂ Sensitizes Cancer Cells to Vitamin-C-Induced Cell Death via Modulation of Akt and Bad Phosphorylation.

    PubMed

    Chen, Ni; Yin, Shutao; Song, Xinhua; Fan, Lihong; Hu, Hongbo

    2015-08-01

    Vitamin C is an essential dietary nutrient that has a variety of biological functions. Recent studies have provided promising evidence for its additional health benefits, including anticancer activity. Vitamin B2, another essential dietary nutrient, often coexists with vitamin C in some fruits, vegetables, or dietary supplements. The objective of the present study is to determine whether the combination of vitamin C and B2 can achieve a synergistic anticancer activity. MDA-MB-231, MCF-7, and A549 cells were employed to evaluate the combinatory effects of vitamin C and B2. We found that the combination of vitamin C and B2 resulted in a synergistic cell death induction in all cell lines tested. Further mechanistic investigations revealed that vitamin B2 sensitized cancer cells to vitamin C through inhibition of Akt and Bad phosphorylation. Our findings identified vitamin B2 as a promising sensitizer for improving the efficacy of vitamin-C-based cancer chemoprevention and chemotherapy. PMID:26165392

  8. Amelioration of neuronal cell death in a spontaneous obese rat model by dietary restriction through modulation of ubiquitin proteasome system.

    PubMed

    Shruthi, Karnam; Reddy, S Sreenivasa; Reddy, P Yadagiri; Shivalingam, Potula; Harishankar, Nemani; Reddy, G Bhanuprakash

    2016-07-01

    Dietary restriction (DR) has been shown to increase longevity, delay onset of aging, reduce DNA damage and oxidative stress and prevent age-related decline of neuronal activity. We previously reported the role of altered ubiquitin proteasome system (UPS) in the neuronal cell death in a spontaneous obese rat model (WNIN/Ob rat). In this study, we investigated the effect of DR on obesity-induced neuronal cell death in a rat model. Two groups of 40-day-old WNIN/Ob rats were either fed ad libitum (Ob) or pair-fed with lean. The lean phenotype of WNIN/Ob rats served as ad libitum control. These animals were maintained for 6.5months on their respective diet regime. At the end of the study, cerebral cortex was collected and markers of UPS, endoplasmic reticulum (ER) stress and autophagy were analyzed by quantitative real-time polymerase chain reaction, immunoblotting and immunohistochemistry. Chymotrypsin-like activity of proteasome was assayed by the fluorimetric method. Apoptotic cells were analyzed by TUNEL assay. DR improved metabolic abnormalities in obese rats. Alterations in UPS (up-regulation of UCHL1, down-regulation of UCHL5, declined proteasomal activity), increased ER stress, declined autophagy and increased expression of α-synuclein, p53 and BAX were observed in obese rats and DR alleviated these changes in obese rats. Further, DR decreased TUNEL-positive cells. In conclusion, DR in obese rats could not only restore the metabolic abnormalities but also preserved neuronal health in the cerebral cortex by preventing alterations in the UPS. PMID:27260470

  9. Radio-induced alteration in cordierite - Implications for petrology, gemmology and materials science

    NASA Astrophysics Data System (ADS)

    Krickl, R.; Nasdala, L.; Grambole, D.; Kaindl, R.

    2009-04-01

    Cordierite is a common metamorphic and magmatic mineral, which is used as petrologic tool for reconstructing the history of its host rock. Further applications include cordierite gemstones and the use of synthetic analogs in ceramics. Cordierite is stable over a wide temperature and pressure range and relatively resistant to chemical alteration; however, its properties can be significantly changed upon the impact of external irradiation. In the course of a comprehensive study, natural radiohaloes in cordierite (a widespread feature caused by the impact of alpha-particles originating from radioactive inclusions) as well as artificial analogs produced by implantation of 8.8 MeV He2+ ions were investigated using modern micro-techniques. Additional irradiation experiments were performed using O6+ ions, electrons and gamma-rays. Ion irradiation causes yellow colouration that is strongly pleochroic, and fades at higher doses. The possibility of radiation-treatment for enhancing the quality of gem-cordierite is discussed. While samples remain crystalline up to doses of 1016 He2+/cm2, the same material is fully amorphised when irradiated with the same dose of 30 MeV O6+ ions. These different observations may help to estimate the performance assessment of cordierite-ceramics in radiated environments. A very important result concerning the petrological use of cordierite is the radio-induced transformation of channel constituents: Inside the irradiated areas the vibrational bands of CO2 decrease in intensity, whereas two new bands appear at 2135 cm-1 (both IR- and Raman-active; cf. Nasdala et al., 2006) and 1550 cm-1 (only Raman-activ). They are assigned to stretching vibrations of carbon monoxide and molecular oxygen, respectively, thus indicating a radio-chemical transformation 2CO2 → 2CO + O2 in alpha-irradiated cordierite. This study yields the first spectroscopic evidence for the irradiation-induced formation of molecular oxygen in cordierite. Polarised vibrational

  10. Quercetin derivative induces cell death in glioma cells by modulating NF-κB nuclear translocation and caspase-3 activation.

    PubMed

    Kiekow, Cíntia J; Figueiró, Fabrício; Dietrich, Fabrícia; Vechia, Luciana Dalla; Pires, Elisa N S; Jandrey, Elisa H F; Gnoatto, Simone C B; Salbego, Christianne G; Battastini, Ana Maria O; Gosmann, Grace

    2016-03-10

    Treated glioblastoma multiforme (GBM) patients only survive 6 to 14months after diagnosis; therefore, the development of novel therapeutic strategies to treat gliomas remains critically necessary. Considering that phenolic compounds, like quercetin, have the potential to be used in the chemotreatment of gliomas and that some flavonoids exhibit the ability to cross the BBB, in the present study, we investigated the antitumor effect of flavonoids (including chalcones, flavones, flavanones and flavonols). Initially their activities were tested in C6 glioma cells screened using the MTT method, resulting in the selection of chalcone 2 whose feasibility was confirmed by a Trypan Blue exclusion assay in the low μM range on C6 glioma cells. Cell cycle and apoptotic death analyses on C6 glioma cells were also performed, and chalcone 2 increased the apoptosis of the cells but did not alter the cell cycle progression. In addition, treatments with these two compounds were not cytotoxic to hippocampal organotypic cultures, a model of healthy neural cells. Furthermore, the results indicated that 2 induced apoptosis by inhibition of NF-κB and activation of active caspase-3 in glioma cells, suggesting that it is a potential prototype to develop new treatments for GBM in the future. PMID:26802551

  11. Docosahexaenoic acid enhances iron uptake by modulating iron transporters and accelerates apoptotic death in PC12 cells.

    PubMed

    Schonfeld, Eldi; Yasharel, Ilanit; Yavin, Ephraim; Brand, Annette

    2007-10-01

    The effect of docosahexaenoic acid (DHA; 22:6 n-3) on Fe(2+)-mediated and/or H(2)O(2)-mediated oxidative stress (OS) was investigated in a PC12 pheochromocytoma cell line in the presence or absence of 50 ng/ml nerve growth factor (NGF). DHA-supplemented cells showed enhanced Fe(2+)-induced cell damage as evident by increased lipid peroxides formation (10-fold) and reduced neutral red (NR) dye uptake in a NGF-independent fashion. DHA caused a nearly 10-fold increase in free iron uptake in NGF-treated cells and doubled iron uptake in nondifferentiated cells. DHA-enrichment induced an elevation in the transferrin receptor protein in the nondifferentiated cells whereas NGF-treatment led to a substantial increase in the ubiquitous divalent metal ion transporter 1 (DMT-1) as detected by mRNA levels using qRT-PCR. The mechanism of action of DHA to accelerate cell death may be associated with the externalization of amino-phosphoglycerides (PG) species of which, increased ethanolamine plasmalogen levels, may be essential for cell rescue as noted in NGF-treated PC12 cells. PMID:17551831

  12. Bifurcation analysis and potential landscapes of the p53-Mdm2 module regulated by the co-activator programmed cell death 5.

    PubMed

    Bi, Yuanhong; Yang, Zhuoqin; Zhuge, Changjing; Lei, Jinzhi

    2015-11-01

    The dynamics of p53 play important roles in the regulation of cell fate decisions in response to various stresses, and programmed cell death 5 (PDCD5) functions as a co-activator of p53 that modulates p53 dynamics. In the present paper, we investigated how p53 dynamics are modulated by PDCD5 during the deoxyribose nucleic acid damage response using methods of bifurcation analysis and potential landscape. Our results revealed that p53 activities display rich dynamics under different PDCD5 levels, including monostability, bistability with two stable steady states, oscillations, and the coexistence of a stable steady state (or two states) and an oscillatory state. The physical properties of the p53 oscillations were further demonstrated by the potential landscape in which the potential force attracts the system state to the limit cycle attractor, and the curl flux force drives coherent oscillation along the cyclic trajectory. We also investigated the efficiency with which PDCD5 induced p53 oscillations. We show that Hopf bifurcation can be induced by increasing the PDCD5 efficiency and that the system dynamics exhibited clear transition features in both barrier height and energy dissipation when the efficiency was close to the bifurcation point. PMID:26627563

  13. Bifurcation analysis and potential landscapes of the p53-Mdm2 module regulated by the co-activator programmed cell death 5

    NASA Astrophysics Data System (ADS)

    Bi, Yuanhong; Yang, Zhuoqin; Zhuge, Changjing; Lei, Jinzhi

    2015-11-01

    The dynamics of p53 play important roles in the regulation of cell fate decisions in response to various stresses, and programmed cell death 5 (PDCD5) functions as a co-activator of p53 that modulates p53 dynamics. In the present paper, we investigated how p53 dynamics are modulated by PDCD5 during the deoxyribose nucleic acid damage response using methods of bifurcation analysis and potential landscape. Our results revealed that p53 activities display rich dynamics under different PDCD5 levels, including monostability, bistability with two stable steady states, oscillations, and the coexistence of a stable steady state (or two states) and an oscillatory state. The physical properties of the p53 oscillations were further demonstrated by the potential landscape in which the potential force attracts the system state to the limit cycle attractor, and the curl flux force drives coherent oscillation along the cyclic trajectory. We also investigated the efficiency with which PDCD5 induced p53 oscillations. We show that Hopf bifurcation can be induced by increasing the PDCD5 efficiency and that the system dynamics exhibited clear transition features in both barrier height and energy dissipation when the efficiency was close to the bifurcation point.

  14. α-Tocopherol at Nanomolar Concentration Protects PC12 Cells from Hydrogen Peroxide-Induced Death and Modulates Protein Kinase Activities

    PubMed Central

    Zakharova, Irina O.; Sokolova, Tatyana V.; Bayunova, Liubov V.; Vlasova, Yulia A.; Rychkova, Maria P.; Avrova, Natalia F.

    2012-01-01

    The aim of this work was to compare protective and anti-apoptotic effects of α-tocopherol at nanomolar and micromolar concentrations against 0.2 mM H2O2-induced toxicity in the PC12 neuronal cell line and to reveal protein kinases that contribute to α-tocopherol protective action. The protection by 100 nM α-tocopherol against H2O2-induced PC12 cell death was pronounced if the time of pre-incubation with α-tocopherol was 3–18 h. For the first time, the protective effect of α-tocopherol was shown to depend on its concentration in the nanomolar range (1 nM < 10 nM < 100 nM), if the pre-incubation time was 18 h. Nanomolar and micromolar α-tocopherol decreased the number of PC12 cells in late apoptosis induced by H2O2 to the same extent if pre-incubation time was 18 h. Immunoblotting data showed that α-tocopherol markedly diminished the time of maximal activation of extracellular signal-regulated kinase 1/2 (ERK 1/2) and protein kinase B (Akt)-induced in PC12 cells by H2O2. Inhibitors of MEK 1/2, PI 3-kinase and protein kinase C (PKC) diminished the protective effect of α-tocopherol against H2O2-initiated toxicity if the pre-incubation time was long. The modulation of ERK 1/2, Akt and PKC activities appears to participate in the protection by α-tocopherol against H2O2-induced death of PC12 cells. The data obtained suggest that inhibition by α-tocopherol in late stage ERK 1/2 and Akt activation induced by H2O2 in PC12 cells makes contribution to its protective effect, while total inhibition of these enzymes is not protective. PMID:23109870

  15. Newly synthesized quinazolinone HMJ-38 suppresses angiogenetic responses and triggers human umbilical vein endothelial cell apoptosis through p53-modulated Fas/death receptor signaling

    SciTech Connect

    Chiang, Jo-Hua; Yang, Jai-Sing; Lu, Chi-Cheng; Hour, Mann-Jen; Chang, Shu-Jen; Lee, Tsung-Han; Chung, Jing-Gung

    2013-06-01

    The current study aims to investigate the antiangiogenic responses and apoptotic death of human umbilical vein endothelial cells (HUVECs) by a newly synthesized compound named 2-(3′-methoxyphenyl)-6-pyrrolidinyl-4-quinazolinone (HMJ-38). This work attempted to not only explore the effects of angiogenesis on in vivo and ex vivo studies but also hypothesize the implications for HUVECs (an ideal cell model for angiogenesis in vitro) and further undermined apoptotic experiments to verify the underlying molecular signaling by HMJ-38. Our results demonstrated that HMJ-38 significantly inhibited blood vessel growth and microvessel formation by the mouse Matrigel plug assay of angiogenesis, and the suppression of microsprouting from the rat aortic ring assay was observed after HMJ-38 exposure. In addition, HMJ-38 disrupted the tube formation and blocked the ability of HUVECs to migrate in response to VEGF. We also found that HMJ-38 triggered cell apoptosis of HUVECs in vitro. HMJ-38 concentration-dependently suppressed viability and induced apoptotic damage in HUVECs. HMJ-38-influenced HUVECs were performed by determining the oxidative stress (ROS production) and ATM/p53-modulated Fas and DR4/DR5 signals that were examined by flow cytometry, Western blotting, siRNA and real-time RT-PCR analyses, respectively. Our findings demonstrate that p53-regulated extrinsic pathway might fully contribute to HMJ-38-provoked apoptotic death in HUVECs. In view of these observations, we conclude that HMJ-38 reduces angiogenesis in vivo and ex vivo as well as induces apoptosis of HUVECs in vitro. Overall, HMJ-38 has a potent anti-neovascularization effect and could warrant being a vascular targeting agent in the future. - Highlights: • HMJ-38 suppresses angiogenic actions in vivo and ex vivo. • Inhibitions of blood vessel and microvessel formation by HMJ-38 are acted. • Cytotoxic effects of HUVECs occur by HMJ-38 challenge. • p53-modulated extrinsic pathway contributes to HMJ-38

  16. Genistein inhibition of OGD-induced brain neuron death correlates with its modulation of apoptosis, voltage-gated potassium and sodium currents and glutamate signal pathway.

    PubMed

    Ma, Xue-Ling; Zhang, Feng; Wang, Yu-Xiang; He, Cong-Cong; Tian, Kun; Wang, Hong-Gang; An, Di; Heng, Bin; Liu, Yan-Qiang

    2016-07-25

    In the present study, we established an in vitro model of hypoxic-ischemia via exposing primary neurons of newborn rats to oxygen-glucose deprivation (OGD) and observing the effects of genistein, a soybean isoflavone, on hypoxic-ischemic neuron viability, apoptosis, voltage-activated potassium (Kv) and sodium (Nav) currents, and glutamate receptor subunits. The results indicated that OGD exposure reduced the viability and increased the apoptosis of brain neurons. Meanwhile, OGD exposure caused changes in the current-voltage curves and current amplitude values of voltage-activated potassium and sodium currents; OGD exposure also decreased GluR2 expression and increased NR2 expression. However, genistein at least partially reversed the effects caused by OGD. The results suggest that hypoxic-ischemia-caused neuronal apoptosis/death is related to an increase in K(+) efflux, a decrease in Na(+) influx, a down-regulation of GluR2, and an up-regulation of NR2. Genistein may exert some neuroprotective effects via the modulation of Kv and Nav currents and the glutamate signal pathway, mediated by GluR2 and NR2. PMID:27238724

  17. Modulation of P2X4/P2X7/Pannexin-1 sensitivity to extracellular ATP via Ivermectin induces a non-apoptotic and inflammatory form of cancer cell death

    PubMed Central

    Draganov, Dobrin; Gopalakrishna-Pillai, Sailesh; Chen, Yun-Ru; Zuckerman, Neta; Moeller, Sara; Wang, Carrie; Ann, David; Lee, Peter P.

    2015-01-01

    Overexpression of P2X7 receptors correlates with tumor growth and metastasis. Yet, release of ATP is associated with immunogenic cancer cell death as well as inflammatory responses caused by necrotic cell death at sites of trauma or ischemia-reperfusion injury. Using an FDA-approved anti-parasitic agent Ivermectin as a prototype agent to allosterically modulate P2X4 receptors, we can switch the balance between the dual pro-survival and cytotoxic functions of purinergic signaling in breast cancer cells. This is mediated through augmented opening of the P2X4/P2X7-gated Pannexin-1 channels that drives a mixed apoptotic and necrotic mode of cell death associated with activation of caspase-1 and is consistent with pyroptosis. We show that cancer cell death is dependent on ATP release and death signals downstream of P2X7 receptors that can be reversed by inhibition of NADPH oxidases-generated ROS, Ca2+/Calmodulin-dependent protein kinase II (CaMKII) or mitochondrial permeability transition pore (MPTP). Ivermectin induces autophagy and release of ATP and HMGB1, key mediators of inflammation. Potentiated P2X4/P2X7 signaling can be further linked to the ATP rich tumor microenvironment providing a mechanistic explanation for the tumor selectivity of purinergic receptors modulation and its potential to be used as a platform for integrated cancer immunotherapy. PMID:26552848

  18. Hydrogen sulfide delays GA-triggered programmed cell death in wheat aleurone layers by the modulation of glutathione homeostasis and heme oxygenase-1 expression.

    PubMed

    Xie, Yanjie; Zhang, Chen; Lai, Diwen; Sun, Ya; Samma, Muhammad Kaleem; Zhang, Jing; Shen, Wenbiao

    2014-01-15

    Hydrogen sulfide (H2S) is considered as a cellular signaling intermediate in higher plants, but corresponding molecular mechanisms and signal transduction pathways in plant biology are still limited. In the present study, a combination of pharmacological and biochemical approaches was used to study the effect of H2S on the alleviation of GA-induced programmed cell death (PCD) in wheat aleurone cells. The results showed that in contrast with the responses of ABA, GA brought about a gradual decrease of l-cysteine desulfhydrase (LCD) activity and H2S production, and thereafter PCD occurred. Exogenous H2S donor sodium hydrosulfide (NaHS) not only effectively blocked the decrease of endogenous H2S release, but also alleviated GA-triggered PCD in wheat aleurone cells. These responses were sensitive to hypotaurine (HT), a H2S scavenger, suggesting that this effect of NaHS was in an H2S-dependent fashion. Further experiment confirmed that H2S, rather than other sodium- or sulphur-containing compounds derived from the decomposing of NaHS, was attributed to the rescuing response. Importantly, the reversing effect was associated with glutathione (GSH) because the NaHS triggered increases of endogenous GSH content and the ratio of GSH/oxidized GSH (GSSG) in GA-treated layers, and the NaHS-mediated alleviation of PCD was markedly eliminated by l-buthionine-sulfoximine (BSO, a selective inhibitor of GSH biosynthesis). The inducible effect of NaHS was also ascribed to the modulation of heme oxygenase-1 (HO-1), because the specific inhibitor of HO-1 zinc protoporphyrin IX (ZnPP) significantly suppressed the NaHS-related responses. By contrast, the above inhibitory effects were reversed partially when carbon monoxide (CO) aqueous solution or bilirubin (BR), two of the by-products of HO-1, was added, respectively. NaHS-triggered HO-1 gene expression in GA-treated layers was also confirmed. Together, the above results clearly suggested that the H2S-delayed PCD in GA-treated wheat

  19. Cot Deaths.

    ERIC Educational Resources Information Center

    Tyrrell, Shelagh

    1985-01-01

    Addresses the tragedy of crib deaths, giving particular attention to causes, prevention, and medical research on Sudden Infant Death Syndrome (SIDS). Gives anecdotal accounts of coping strategies used by parents and families of SIDS infants. (DT)

  20. Understanding Death.

    ERIC Educational Resources Information Center

    Heath, Charles P.

    1986-01-01

    Bibliotherapy can help children prepare for and understand the death of a loved one. An annotated bibliography lists references with age level information on attitudes toward death and deaths of a father, friend, grandparent, mother, pet, and sibling. (Author/CL)

  1. An autologous in situ tumor vaccination approach for hepatocellular carcinoma. 1. Flt3 ligand gene transfer increases antitumor effects of a radio-inducible suicide gene therapy in an ectopic tumor model.

    PubMed

    Kawashita, Yujo; Deb, Niloy J; Garg, Madhur; Kabarriti, Rafi; Alfieri, Alan; Takahashi, Masahiko; Roy-Chowdhury, Jayanta; Guha, Chandan

    2014-08-01

    Hepatocellular carcinoma (HCC) often presents as a diffuse or multifocal tumor making it difficult to control by surgery or radiation. Radio-inducible herpes simplex virus thymidine kinase (HSV-TK) gene therapy has been shown to enhance local tumor control after radiation therapy (RT), while limiting the expression of the transgene in the irradiated tumor tissues. To prevent liver tumor recurrence and control systemic disease while limiting the potential bystander toxicity of HSV-TK therapy, we proposed to stimulate endogenous dendritic cell (DC) proliferation with systemic adenovirus Flt3 ligand (Adeno-Flt3L) gene therapy, followed by primary tumor radiation therapy combined with a radio-inducible HSV-TK gene therapy. We hypothesized that adenovirus-expressing Flt3L gene therapy will stimulate DC proliferation, allowing the upregulated DCs to locally harness tumor antigens released from HSV-TK/RT-treated HCC cells, thereby converting irradiated tumors to an autologous in situ tumor vaccine in mice with primary liver tumors. To test this hypothesis, an expression vector of HSV-TK was constructed under the control of a radio-inducible promoter early-growth response (Egr-TK) and a recombinant adenovirus-expressing human Flt3L was constructed. The Adeno-Flt3L [10(9) plaque forming units (pfu)] was administered intravenously on days 1 and 8 after radiation therapy. The murine hepatoma cell line (BNL1ME) was stably transfected by Egr-TK or Egr-Null (encoding no therapeutic gene). Palpable tumors in BALB/c mice were treated with a localized dose of 25 Gy of radiation followed by ganciclovir (GCV, 100 mg/kg, 14 days). Four treatment cohorts were compared: Egr-Null/GCV + RT + Adeno-LacZ; Egr-Null/GCV + RT + Adeno-Flt3L; Egr-TK/GCV + RT + Adeno-LacZ; and Egr-TK/GCV + RT + Adeno-Flt3L. There was no primary tumor regression in the Egr-Null tumors after radiation therapy alone. In contrast, Egr-TK tumors had nearly complete tumor regression for 3 weeks after radiation therapy

  2. Practicing death.

    PubMed

    Avny, Ohad; Alon, Aya

    2016-07-01

    This narrative describes the struggle of a primary care physician contending with the challenge of remaining committed to his patient's care despite a sense of burnout in relation to an intense period of patient deaths. The story presents two patient deaths and the physician's reflections on how he handled both cases. PMID:26899633

  3. Death duties

    PubMed Central

    Myers, Kathryn A.; Eden, David

    2007-01-01

    PROBLEM BEING ADDRESSED Family physicians are often called upon to pronounce and certify the deaths of patients. Inadequate knowledge of the Coroners Act (in the province of Ontario) and of the correct process of certifying death can make physicians uncomfortable when confronted with these tasks. OBJECTIVE OF PROGRAM To educate family physicians about how to perform the administrative tasks required of them when patients die. PROGRAM DESCRIPTION The program included an educational video, a tutorial outlining the process of death certification, and discussion with a regional coroner about key features of the Coroners Act. In small groups, participants worked through cases of patient deaths in which they were asked to determine whether a coroner needed to be involved, to determine the manner of death, and to complete a mock death certificate for each case. CONCLUSION All participants reported a high level of satisfaction with the workshop and thought the main objective of the program had been achieved. Results of a test given 3 months after the workshop showed substantial improvement in participants’ knowledge of the coroner’s role and of the process of death certification. PMID:17872782

  4. Ectopic expression of H2AX protein promotes TrkA-induced cell death via modulation of TrkA tyrosine-490 phosphorylation and JNK activity upon DNA damage

    SciTech Connect

    Jung, Eun Joo; Kim, Deok Ryong

    2011-01-21

    Research highlights: {yields} We established TrkA-inducible U2OS cells stably expressing GFP-H2AX proteins. {yields} GFP-H2AX was colocalized with TrkA in the cytoplasm. {yields} {gamma}H2AX production was significantly increased upon activation of TrkA and suppressed by TrkA inhibitor or JNK inhibitor. {yields} Ectopic expression of H2AX promoted TrkA-mediated cell death through the modulation of TrkA tyrosine-490 phosphorylation and JNK activity upon DNA damage. -- Abstract: We previously reported that TrkA overexpression causes accumulation of {gamma}H2AX proteins in the cytoplasm, subsequently leading to massive cell death in U2OS cells. To further investigate how cytoplasmic H2AX is associated with TrkA-induced cell death, we established TrkA-inducible cells stably expressing GFP-tagged H2AX. We found that TrkA co-localizes with ectopically expressed GFP-H2AX proteins in the cytoplasm, especially at the juxta-nuclear membranes, which supports our previous results about a functional connection between TrkA and {gamma}H2AX in TrkA-induced cell death. {gamma}H2AX production from GFP-H2AX proteins was significantly increased when TrkA was overexpressed. Moreover, ectopic expression of H2AX activated TrkA-mediated signal pathways via up-regulation of TrkA tyrosine-490 phosphorylation. In addition, suppression of TrkA tyrosine-490 phosphorylation under a certain condition was removed by ectopic expression of H2AX, indicating a functional role of H2AX in the maintenance of TrkA activity. Indeed, TrkA-induced cell death was highly elevated by ectopic H2AX expression, and it was further accelerated by DNA damage via JNK activation. These all results suggest that cytoplasmic H2AX could play an important role in TrkA-mediated cell death by modulating TrkA upon DNA damage.

  5. Neonatal Death

    MedlinePlus

    ... story First Candle Centering Corporation The Compassionate Friends Star Legacy Foundation Last reviewed: November, 2015 Neonatal death ... story First Candle Centering Corporation The Compassionate Friends Star Legacy Foundation Last reviewed: November, 2015 Complications & Loss ...

  6. Steroidal Saponin Diosgenin from Dioscorea bulbifera Protects Cardiac Cells from Hypoxia-reoxygenation Injury Through Modulation of Pro-survival and Pro-death Molecules

    PubMed Central

    Jayachandran, Karuppiah Shanmugasundarapandian; Vasanthi, A. Hannah Rachel; Gurusamy, Narasimman

    2016-01-01

    Background: Diosgenin, a steroidal saponin from plants, exhibits many biological potentials. Herein, the cardioprotective role of diosgenin is studied. Materials and Methods: The effect of diosgenin, isolated from Dioscorea bulbifera, was studied on hypoxia-reoxygenation (HR) in H9c2 cardiomyoblast cells. The amount of diosgenin in the plant extract was analyzed by high-performance thin layer chromatography using a solvent system comprising of chloroform:methanol:acetic acid:formic acid (13:4.5:1.5:1). Cardioprotection was checked by (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Further, the release of lactate dehydrogenase, an enzyme released during cell death was checked. The proteins responsible for cell death (Bax) and cell survival (Bcl-2, hemeoxygenase-1 and Akt) were analyzed using Western blot to check the cardioprotective role of diosgenin. Conclusion: Supplementation of diosgenin mitigates HR injury, thereby exhibiting cardioprotective potential. SUMMARY The cardioprotective effect of Diosgenin was evidenced from the improved cell survival after hypoxia-reoxygenation injury demonstrated through MTT cell survival assay.The release of lactate dehydrogenase, an enzyme released during cell death was decreased by Diosgenin.Diosgenin upregulated the pro-survival molecules like B-cell lymphoma 2 (Bcl-2), heme oxygenase-1 and the phosphorylation of ATK (at serine 473); and at the same time pro-.death molecules like Bax was downregulated.Thus, Diosgenin as a plant based steroidal saponin is confirmed to mitigate ischemic reperfusion injury. Figure PMID:27041852

  7. GOLPH3 Mediated Golgi Stress Response in Modulating N2A Cell Death upon Oxygen-Glucose Deprivation and Reoxygenation Injury.

    PubMed

    Li, Ting; You, Hong; Mo, Xiaoye; He, Wenfang; Tang, Xiangqi; Jiang, Zheng; Chen, Shiyu; Chen, Yang; Zhang, Jie; Hu, Zhiping

    2016-03-01

    Increasing evidence implicating that the organelle-dependent initiation of cell death merits further research. The evidence also implicates Golgi as a sensor and common downstream-effector of stress signals in cell death pathways, and it undergoes disassembly and fragmentation during apoptosis in several neurological disorders. It has also been reported that during apoptotic cell death, there is a cross talk between ER, mitochondria, and Golgi. Thus, we hypothesized that Golgi might trigger death signals during oxidative stress through its own machinery. The current study found that GOLPH3, an outer membrane protein of the Golgi complex, was significantly upregulated in N2A cells upon oxygen-glucose deprivation and reoxygenation (OGD/R), positioning from the compact perinuclear ribbon to dispersed vesicle-like structures throughout the cytoplasm. Additionally, elevated GOLPH3 promoted a stress-induced conversion of the LC3 subunit I to II and reactive oxygen species (ROS) production in long-term OGD/R groups. The collective data indicated that GOLPH3 not only acted as a sensor of Golgi stress for its prompt upregulation during oxidative stress but also as an initiator that triggered and propagated specific Golgi stress signals to downstream effectors. This affected ROS production and stress-related autophagy and finally controlled the entry into apoptosis. The data also supported the hypothesis that the Golgi apparatus could be an ideal target for stroke, neurodegenerative diseases, or cancer therapy through its own functional proteins. PMID:25633094

  8. Small molecule-mediated up-regulation of microRNA targeting a key cell death modulator BNIP3 improves cardiac function following ischemic injury

    PubMed Central

    Lee, Se-Yeon; Lee, Seahyoung; Choi, Eunhyun; Ham, Onju; Lee, Chang Youn; Lee, Jiyun; Seo, Hyang-Hee; Cha, Min-Ji; Mun, Bohyun; Lee, Yunmi; Yoon, Cheesoon; Hwang, Ki-Chul

    2016-01-01

    Genetic ablation of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), an essential regulator of cardiac cell death, is an effective way to prevent cardiac cell death triggered by pathologic conditions. However, currently there exists no known means, such as inhibitors, to down-regulate BNIP3 in mature heart. Here, we report that a small molecule inducer of microRNA-182 (miR-182) suppressed ischemia/reperfusion (I/R)-induced cardiac cell death by down-regulating BNIP3. We first selected miR-182 as a potent BNIP3-targeting miRNA based on miRNA-target prediction databases and empirical data. The subsequent screening of small molecules for inducing miR-182 expression identified Kenpaullone as a hit compound. Both exogenous miR-182 and Kenpaullone significantly suppressed hypoxia-induced cardiomyocyte death in vitro. To investigate the effect of changing substituents of Kenpaullone on miR-182 expression, we synthesized 9 derivatives of Kenpaullone. Among these derivatives, compound 5 showed significantly improved ability to induce miR-182 expression. The results of the in vivo study showed that compound 5 significantly improved heart function following I/R-injury in rats. Our study provides strong evidence that the small molecule-mediated up-regulation of miRNAs is a viable strategy to down-regulate target proteins with no known chemical inhibitor and that compound 5 may have potential to prevent I/R-inflicted cardiac cell death. PMID:27008992

  9. Small molecule-mediated up-regulation of microRNA targeting a key cell death modulator BNIP3 improves cardiac function following ischemic injury.

    PubMed

    Lee, Se-Yeon; Lee, Seahyoung; Choi, Eunhyun; Ham, Onju; Lee, Chang Youn; Lee, Jiyun; Seo, Hyang-Hee; Cha, Min-Ji; Mun, Bohyun; Lee, Yunmi; Yoon, Cheesoon; Hwang, Ki-Chul

    2016-01-01

    Genetic ablation of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), an essential regulator of cardiac cell death, is an effective way to prevent cardiac cell death triggered by pathologic conditions. However, currently there exists no known means, such as inhibitors, to down-regulate BNIP3 in mature heart. Here, we report that a small molecule inducer of microRNA-182 (miR-182) suppressed ischemia/reperfusion (I/R)-induced cardiac cell death by down-regulating BNIP3. We first selected miR-182 as a potent BNIP3-targeting miRNA based on miRNA-target prediction databases and empirical data. The subsequent screening of small molecules for inducing miR-182 expression identified Kenpaullone as a hit compound. Both exogenous miR-182 and Kenpaullone significantly suppressed hypoxia-induced cardiomyocyte death in vitro. To investigate the effect of changing substituents of Kenpaullone on miR-182 expression, we synthesized 9 derivatives of Kenpaullone. Among these derivatives, compound 5 showed significantly improved ability to induce miR-182 expression. The results of the in vivo study showed that compound 5 significantly improved heart function following I/R-injury in rats. Our study provides strong evidence that the small molecule-mediated up-regulation of miRNAs is a viable strategy to down-regulate target proteins with no known chemical inhibitor and that compound 5 may have potential to prevent I/R-inflicted cardiac cell death. PMID:27008992

  10. 6-Shogaol Inhibits Breast Cancer Cells and Stem Cell-Like Spheroids by Modulation of Notch Signaling Pathway and Induction of Autophagic Cell Death.

    PubMed

    Ray, Anasuya; Vasudevan, Smreti; Sengupta, Suparna

    2015-01-01

    Cancer stem cells (CSCs) pose a serious obstacle to cancer therapy as they can be responsible for poor prognosis and tumour relapse. In this study, we have investigated inhibitory activity of the ginger-derived compound 6-shogaol against breast cancer cells both in monolayer and in cancer-stem cell-like spheroid culture. The spheroids were generated from adherent breast cancer cells. 6-shogaol was effective in killing both breast cancer monolayer cells and spheroids at doses that were not toxic to noncancerous cells. The percentages of CD44+CD24-/low cells and the secondary sphere content were reduced drastically upon treatment with 6-shogaol confirming its action on CSCs. Treatment with 6-shogaol caused cytoplasmic vacuole formation and cleavage of microtubule associated protein Light Chain3 (LC3) in both monolayer and spheroid culture indicating that it induced autophagy. Kinetic analysis of the LC3 expression and a combination treatment with chloroquine revealed that the autophagic flux instigated cell death in 6-shogaol treated breast cancer cells in contrast to the autophagy inhibitor chloroquine. Furthermore, 6-shogaol-induced cell death got suppressed in the presence of chloroquine and a very low level of apoptosis was exhibited even after prolonged treatment of the compound, suggesting that autophagy is the major mode of cell death induced by 6-shogaol in breast cancer cells. 6-shogaol reduced the expression levels of Cleaved Notch1 and its target proteins Hes1 and Cyclin D1 in spheroids, and the reduction was further pronounced in the presence of a γ-secretase inhibitor. Secondary sphere formation in the presence of the inhibitor was also further reduced by 6-shogaol. Together, these results indicate that the inhibitory action of 6-shogaol on spheroid growth and sustainability is conferred through γ-secretase mediated down-regulation of Notch signaling. The efficacy of 6-shogaol in monolayer and cancer stem cell-like spheroids raise hope for its

  11. 6-Shogaol Inhibits Breast Cancer Cells and Stem Cell-Like Spheroids by Modulation of Notch Signaling Pathway and Induction of Autophagic Cell Death

    PubMed Central

    Ray, Anasuya; Vasudevan, Smreti; Sengupta, Suparna

    2015-01-01

    Cancer stem cells (CSCs) pose a serious obstacle to cancer therapy as they can be responsible for poor prognosis and tumour relapse. In this study, we have investigated inhibitory activity of the ginger-derived compound 6-shogaol against breast cancer cells both in monolayer and in cancer-stem cell-like spheroid culture. The spheroids were generated from adherent breast cancer cells. 6-shogaol was effective in killing both breast cancer monolayer cells and spheroids at doses that were not toxic to noncancerous cells. The percentages of CD44+CD24-/low cells and the secondary sphere content were reduced drastically upon treatment with 6-shogaol confirming its action on CSCs. Treatment with 6-shogaol caused cytoplasmic vacuole formation and cleavage of microtubule associated protein Light Chain3 (LC3) in both monolayer and spheroid culture indicating that it induced autophagy. Kinetic analysis of the LC3 expression and a combination treatment with chloroquine revealed that the autophagic flux instigated cell death in 6-shogaol treated breast cancer cells in contrast to the autophagy inhibitor chloroquine. Furthermore, 6-shogaol-induced cell death got suppressed in the presence of chloroquine and a very low level of apoptosis was exhibited even after prolonged treatment of the compound, suggesting that autophagy is the major mode of cell death induced by 6-shogaol in breast cancer cells. 6-shogaol reduced the expression levels of Cleaved Notch1 and its target proteins Hes1 and Cyclin D1 in spheroids, and the reduction was further pronounced in the presence of a γ-secretase inhibitor. Secondary sphere formation in the presence of the inhibitor was also further reduced by 6-shogaol. Together, these results indicate that the inhibitory action of 6-shogaol on spheroid growth and sustainability is conferred through γ-secretase mediated down-regulation of Notch signaling. The efficacy of 6-shogaol in monolayer and cancer stem cell-like spheroids raise hope for its

  12. Brain death.

    PubMed

    Wijdicks, Eelco F M

    2013-01-01

    The diagnosis of brain death should be based on a simple premise. If every possible confounder has been excluded and all possible treatments have been tried or considered, irreversible loss of brain function is clinically recognized as the absence of brainstem reflexes, verified apnea, loss of vascular tone, invariant heart rate, and, eventually, cardiac standstill. This condition cannot be reversed - not even partly - by medical or surgical intervention, and thus is final. Many countries in the world have introduced laws that acknowledge that a patient can be declared brain-dead by neurologic standards. The U.S. law differs substantially from all other brain death legislation in the world because the U.S. law does not spell out details of the neurologic examination. Evidence-based practice guidelines serve as a standard. In this chapter, I discuss the history of development of the criteria, the current clinical examination, and some of the ethical and legal issues that have emerged. Generally, the concept of brain death has been accepted by all major religions. But patients' families may have different ideas and are mostly influenced by cultural attitudes, traditional customs, and personal beliefs. Suggestions are offered to support these families. PMID:24182378

  13. Reciprocal modulation of C/EBP-α and C/EBP-β by IL-13 in activated microglia prevents neuronal death.

    PubMed

    Pan, Hung Chuan; Yang, Cheng Ning; Hung, Yi Wen; Lee, Wen Jane; Tien, Hsing Ru; Shen, Chin Chang; Sheehan, Jason; Chou, Chiang Ting; Sheu, Meei Ling

    2013-11-01

    In response to aggravation by activated microglia, IL-13 can significantly enhance ER stress induction, apoptosis, and death via reciprocal signaling through CCAAT/enhancer-binding protein alpha (C/EBP-α) and C/EBP-beta (C/EBP-β). This reciprocal signaling promotes neuronal survival. Since the induction of cyclooxygenase-2 (COX-2) and peroxisome proliferator-activated receptor gamma/heme oxygenase 1 (PPAR-γ/HO-1) by IL-13 plays a crucial role in the promotion of and protection from activated microglia, respectively; here, we investigated the role of IL-13 in regulating C/EBPs in activated microglia and determined its correlation with neuronal function. The results revealed that IL-13 significantly enhanced C/EBP-α/COX-2 expression and PGE2 production in LPS-treated microglial cells. Paradoxically, IL-13 abolished C/EBP-β/PPAR-γ/HO-1 expression. IL-13 also enhanced ER stress-evoked calpain activation by promoting the association of C/EBP-β and PPAR-γ. SiRNA-C/EBP-α effectively reversed the combined LPS-activated caspase-12 activation and IL-13-induced apoptosis. In contrast, siRNA-C/EBP-β partially increased microglial cell apoptosis. By NeuN immunochemistry and CD11b staining, there was improvement in the loss of CA3 neuronal cells after intrahippocampal injection of IL-13. This suggests that IL-13-enhanced PLA2 activity regulates COX-2/PGE2 expression through C/EBP-α activation. In parallel, ER stress-related calpain downregulates the PPAR-γ/HO-1 pathway via C/EBP-β and leads to aggravated death of activated microglia via IL-13, thereby preventing cerebral inflammation and neuronal injury. PMID:23881867

  14. Regulation of death induction and chemosensitizing action of 3-bromopyruvate in myeloid leukemia cells: energy depletion, oxidative stress, and protein kinase activity modulation.

    PubMed

    Calviño, Eva; Estañ, María Cristina; Sánchez-Martín, Carlos; Brea, Rocío; de Blas, Elena; Boyano-Adánez, María del Carmen; Rial, Eduardo; Aller, Patricio

    2014-02-01

    3-Bromopyruvate (3-BrP) is an alkylating, energy-depleting drug that is of interest in antitumor therapies, although the mechanisms underlying its cytotoxicity are ill-defined. We show here that 3-BrP causes concentration-dependent cell death of HL60 and other human myeloid leukemia cells, inducing both apoptosis and necrosis at 20-30 μM and a pure necrotic response at 60 μM. Low concentrations of 3-BrP (10-20 μM) brought about a rapid inhibition of glycolysis, which at higher concentrations was followed by the inhibition of mitochondrial respiration. The combination of these effects causes concentration-dependent ATP depletion, although this cannot explain the lethality at intermediate 3-BrP concentrations (20-30 μM). The oxidative stress caused by exposure to 3-BrP was evident as a moderate overproduction of reactive oxygen species and a concentration-dependent depletion of glutathione, which was an important determinant of 3-BrP toxicity. In addition, 3-BrP caused glutathione-dependent stimulation of p38 mitogen-activated protein kinase (MAPK), mitogen-induced extracellular kinase (MEK)/extracellular signal-regulated kinase (ERK), and protein kinase B (Akt)/mammalian target of rapamycin/p70S6K phosphorylation or activation, as well as rapid LKB-1/AMP kinase (AMPK) activation, which was later followed by Akt-mediated inactivation. Experiments with pharmacological inhibitors revealed that p38 MAPK activation enhances 3-BrP toxicity, which is conversely restrained by ERK and Akt activity. Finally, 3-BrP was seen to cooperate with antitumor agents like arsenic trioxide and curcumin in causing cell death, a response apparently mediated by both the generation of oxidative stress induced by 3-BrP and the attenuation of Akt and ERK activation by curcumin. In summary, 3-BrP cytotoxicity is the result of several combined regulatory mechanisms that might represent important targets to improve therapeutic efficacy. PMID:24307199

  15. Eriodictyol Protects Endothelial Cells against Oxidative Stress-Induced Cell Death through Modulating ERK/Nrf2/ARE-Dependent Heme Oxygenase-1 Expression.

    PubMed

    Lee, Seung Eun; Yang, Hana; Son, Gun Woo; Park, Hye Rim; Park, Cheung-Seog; Jin, Young-Ho; Park, Yong Seek

    2015-01-01

    The pathophysiology of cardiovascular diseases is complex and may involve oxidative stress-related pathways. Eriodictyol is a flavonoid present in citrus fruits that demonstrates anti-inflammatory, anti-cancer, neurotrophic, and antioxidant effects in a range of pathophysiological conditions including vascular diseases. Because oxidative stress plays a key role in the pathogenesis of cardiovascular disease, the present study was designed to verify whether eriodictyol has therapeutic potential. Upregulation of heme oxygenase-1 (HO-1), a phase II detoxifying enzyme, in endothelial cells is considered to be helpful in cardiovascular disease. In this study, human umbilical vein endothelial cells (HUVECs) treated with eriodictyol showed the upregulation of HO-1 through extracellular-regulated kinase (ERK)/nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathways. Further, eriodictyol treatment provided protection against hydrogen peroxide-provoked cell death. This protective effect was eliminated by treatment with a specific inhibitor of HO-1 and RNA interference-mediated knockdown of HO-1 expression. These data demonstrate that eriodictyol induces ERK/Nrf2/ARE-mediated HO-1 upregulation in human endothelial cells, which is directly associated with its vascular protection against oxidative stress-related endothelial injury, and propose that targeting the upregulation of HO-1 is a promising approach for therapeutic intervention in cardiovascular disease. PMID:26132561

  16. Eriodictyol Protects Endothelial Cells against Oxidative Stress-Induced Cell Death through Modulating ERK/Nrf2/ARE-Dependent Heme Oxygenase-1 Expression

    PubMed Central

    Lee, Seung Eun; Yang, Hana; Son, Gun Woo; Park, Hye Rim; Park, Cheung-Seog; Jin, Young-Ho; Park, Yong Seek

    2015-01-01

    The pathophysiology of cardiovascular diseases is complex and may involve oxidative stress-related pathways. Eriodictyol is a flavonoid present in citrus fruits that demonstrates anti-inflammatory, anti-cancer, neurotrophic, and antioxidant effects in a range of pathophysiological conditions including vascular diseases. Because oxidative stress plays a key role in the pathogenesis of cardiovascular disease, the present study was designed to verify whether eriodictyol has therapeutic potential. Upregulation of heme oxygenase-1 (HO-1), a phase II detoxifying enzyme, in endothelial cells is considered to be helpful in cardiovascular disease. In this study, human umbilical vein endothelial cells (HUVECs) treated with eriodictyol showed the upregulation of HO-1 through extracellular-regulated kinase (ERK)/nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathways. Further, eriodictyol treatment provided protection against hydrogen peroxide-provoked cell death. This protective effect was eliminated by treatment with a specific inhibitor of HO-1 and RNA interference-mediated knockdown of HO-1 expression. These data demonstrate that eriodictyol induces ERK/Nrf2/ARE-mediated HO-1 upregulation in human endothelial cells, which is directly associated with its vascular protection against oxidative stress-related endothelial injury, and propose that targeting the upregulation of HO-1 is a promising approach for therapeutic intervention in cardiovascular disease. PMID:26132561

  17. Design and Synthesis of Antitumor Heck-Coupled Sclareol Analogues: Modulation of BH3 Family Members by SS-12 in Autophagy and Apoptotic Cell Death.

    PubMed

    Shakeel-u-Rehman; Rah, Bilal; Lone, Shabir H; Rasool, Reyaz Ur; Farooq, Saleem; Nayak, Debasis; Chikan, Naveed Anjum; Chakraborty, Souneek; Behl, Akanksha; Mondhe, Dilip Manikaro; Goswami, Anindya; Bhat, Khursheed Ahmad

    2015-04-23

    Sclareol, a promising anticancer labdane diterpene, was isolated from Salvia sclarea. Keeping the basic stereochemistry-rich framework of the molecule intact, a method for the synthesis of novel sclareol analogues was designed using palladium(II)-catalyzed oxidative Heck coupling reaction in order to study their structure-activity relationship. Both sclareol and its derivatives showed an interesting cytotoxicity profile, with 15-(4-fluorophenyl)sclareol (SS-12) as the most potent analogue, having IC50 = 0.082 μM against PC-3 cells. It was found that SS-12 commonly interacts with Bcl-2 and Beclin 1 BH3 domain proteins and enhances autophagic flux by modulating autophagy-related proteins. Moreover, inhibition of autophagy by autophagy inhibitors protected against SS-12-induced apoptosis. Finally, SS-12 effectively suppressed tumor growth in vivo in Ehrlich's ascitic and solid Sarcoma-180 mouse models. PMID:25825934

  18. Tetrandrine and caffeine modulated cell cycle and increased glioma cell death via caspase-dependent and caspase-independent apoptosis pathways.

    PubMed

    Chen, Jin-Cherng; Hwang, Juen-Haur; Chiu, Wen-Hsuan; Chan, Yin-Ching

    2014-01-01

    Viability, cell cycle distribution, and expressions of eukaryotic translation initiation factor-2α (eIF-2α), cyclin D1, poly(ADP-ribose) polymerase 1 (PARP-1), and apoptosis-inducing factor (AIF) of RT-2 glioma cells were assayed under treatment of tetrandrine and caffeine for 48 h. The results showed that cell viability decreased significantly under treatment with tetrandrine (5 μM) alone or under combined treatment with tetrandrine (5 μM) and caffeine (0.5 or 1 mM). The ratio of RT-2 cells at sub G1 and G0/G1 stages increased significantly during combined treatment of tetrandrine (5 μM) and caffeine (0.5, 1 mM). The ratio of phospharylated eIF-2α to dephospharylated eIF-2α increased, whereas cyclin D1 decreased significantly under combined treatment of tetrandrine (5 μM) and caffeine (1 mM). The cleaved PARP-1 to PARP-1 ratio was elevated significantly under treatment of 5 μM tetrandrine alone, and combined treatment of 5 μM tetrandrine and caffeine (0.5, 1 mM). The expression levels of AIF increased significantly under treatment of 5 μM tetrandrine alone or 1 mM caffeine alone, and combined treatment of 5 μM tetrandrine and caffeine (0.5, 1 mM). In conclusion, tetrandrine and caffeine could induce glioma cell death possibly via increasing eIF-2α phospharylation, decreasing cyclin-D1 expression, and increasing caspase-dependent and -independent apoptosis pathways. PMID:24738643

  19. Pathogen-mediated proteolysis of the cell death regulator RIPK1 and the host defense modulator RIPK2 in human aortic endothelial cells.

    PubMed

    Madrigal, Andrés G; Barth, Kenneth; Papadopoulos, George; Genco, Caroline Attardo

    2012-01-01

    Porphyromonas gingivalis is the primary etiologic agent of periodontal disease that is associated with other human chronic inflammatory diseases, including atherosclerosis. The ability of P. gingivalis to invade and persist within human aortic endothelial cells (HAEC) has been postulated to contribute to a low to moderate chronic state of inflammation, although how this is specifically achieved has not been well defined. In this study, we demonstrate that P. gingivalis infection of HAEC resulted in the rapid cleavage of receptor interacting protein 1 (RIPK1), a mediator of tumor necrosis factor (TNF) receptor-1 (TNF-R1)-induced cell activation or death, and RIPK2, a key mediator of both innate immune signaling and adaptive immunity. The cleavage of RIPK1 or RIPK2 was not observed in cells treated with apoptotic stimuli, or cells stimulated with agonists to TNF-R1, nucleotide oligomerization domain receptor 1(NOD1), NOD2, Toll-like receptor 2 (TLR2) or TLR4. P. gingivalis-induced cleavage of RIPK1 and RIPK2 was inhibited in the presence of a lysine-specific gingipain (Kgp) inhibitor. RIPK1 and RIPK2 cleavage was not observed in HAEC treated with an isogenic mutant deficient in the lysine-specific gingipain, confirming a role for Kgp in the cleavage of RIPK1 and RIPK2. Similar proteolysis of poly (ADP-ribose) polymerase (PARP) was observed. We also demonstrated direct proteolysis of RIPK2 by P. gingivalis in a cell-free system which was abrogated in the presence of a Kgp-specific protease inhibitor. Our studies thus reveal an important role for pathogen-mediated modification of cellular kinases as a potential strategy for bacterial persistence within target host cells, which is associated with low-grade chronic inflammation, a hallmark of pathogen-mediated chronic inflammatory disorders. PMID:22685397

  20. Programmed death 1 regulates memory phenotype CD4 T cell accumulation, inhibits expansion of the effector memory phenotype subset and modulates production of effector cytokines.

    PubMed

    Charlton, Joanna J; Tsoukatou, Debbie; Mamalaki, Clio; Chatzidakis, Ioannis

    2015-01-01

    Memory phenotype CD4 T cells are found in normal mice and arise through response to environmental antigens or homeostatic mechanisms. The factors that regulate the homeostasis of memory phenotype CD4 cells are not clear. In the present study we demonstrate that there is a marked accumulation of memory phenotype CD4 cells, specifically of the effector memory (T(EM)) phenotype, in lymphoid organs and tissues of mice deficient for the negative co-stimulatory receptor programmed death 1 (PD-1). This can be correlated with decreased apoptosis but not with enhanced homeostatic turnover potential of these cells. PD-1 ablation increased the frequency of memory phenotype CD4 IFN-γ producers but decreased the respective frequency of IL-17A-producing cells. In particular, IFN-γ producers were more abundant but IL-17A producing cells were more scarce among PD-1 KO T(EM)-phenotype cells relative to WT. Transfer of peripheral naïve CD4 T cells suggested that accumulated PD-1 KO T(EM)-phenotype cells are of peripheral and not of thymic origin. This accumulation effect was mediated by CD4 cell-intrinsic mechanisms as shown by mixed bone marrow chimera experiments. Naïve PD-1 KO CD4 T cells gave rise to higher numbers of TEM-phenotype lymphopenia-induced proliferation memory cells. In conclusion, we provide evidence that PD-1 has an important role in determining the composition and functional aspects of memory phenotype CD4 T cell pool. PMID:25803808

  1. Encountering Death: Structured Activities for Death Awareness.

    ERIC Educational Resources Information Center

    Welch, Ira David; And Others

    This book is intended to be used as a supplement to standard textbooks on death and dying for college students. Chapter 1 "Encountering Death in the Self" builds the foundation for increased self-awareness for the study of death and dying. Chapter 2 "Encountering Death in the Family" provides activities which are appropriate for a wide variety of…

  2. Gemfibrozil pretreatment resulted in a sexually dimorphic outcome in the rat models of global cerebral ischemia-reperfusion via modulation of mitochondrial pro-survival and apoptotic cell death factors as well as MAPKs.

    PubMed

    Mohagheghi, Fatemeh; Ahmadiani, Abolhassan; Rahmani, Behrouz; Moradi, Fatemeh; Romond, Nathalie; Khalaj, Leila

    2013-07-01

    Inducers of mitochondrial biogenesis are widely under investigation for use in a novel therapeutic approach in neurodegenerative disorders. The ability of Gemfibrozil, a fibrate, is investigated for the first time to modulate mitochondrial pro-survival factors involved in the mitochondrial biogenesis signaling pathway, including peroxisome proliferator-activated receptor coactivator-1α (PGC-1α), nuclear respiratory factor (NRF-1), and mitochondrial transcription factor A (TFAM) in the brain. Gemfibozil is clinically administered to control hyperlipidemia. It secondarily prevents cardiovascular events such as cardiac arrest in susceptible patients. In this study, pretreatment of animals with gemfibrozil prior to ischemia-reperfusion (I/R) resulted in a sexually dimorphic outcome. While the expression of NRF-1 and TFAM were induced in gemfibrozil-pretreated met-estrous females, they were suppressed in males. Gemfibrozil also proved to be neuroprotective in met-estrous females, as it inhibited caspase-dependent apoptosis while in males it led to hippocampal neurodegeneration via activation of both the caspase-dependent and caspase-independent apoptosis. In the mitogen-activated protein kinase (MAPKs) pathway, gemfibrozil pretreatment induced the expression of extracellular signal-regulated kinases (ERK1/2) in met-estrous females and reduced it in males. These findings correlatively point to the sexual-dimorphic effects of gemfibrozil in global cerebral I/R context by affecting important factors involved in the mitochondrial biogenesis, MAPKs, and apoptotic cell death pathways. PMID:23288702

  3. Identification, cloning and characterization of R2R3-MYB gene family in canola (Brassica napus L.) identify a novel member modulating ROS accumulation and hypersensitive-like cell death.

    PubMed

    Chen, Bisi; Niu, Fangfang; Liu, Wu-Zhen; Yang, Bo; Zhang, Jingxiao; Ma, Jieyu; Cheng, Hao; Han, Feng; Jiang, Yuan-Qing

    2016-04-01

    The R2R3-MYB proteins comprise one of the largest families of transcription factors in plants. Although genome-wide analysis of this family has been carried out in some plant species, little is known about R2R3-MYB genes in canola (Brassica napus L.). In this study, we have identified 76 R2R3-MYB genes in the canola genome through mining of expressed sequence tags (ESTs). The cDNA sequences of 44 MYB genes were successfully cloned. The transcriptional activities of BnaMYB proteins encoded by these genes were assayed in yeast. The subcellular localizations of representative R2R3-MYB proteins were investigated through GFP fusion. Besides, the transcript abundance level analysis during abiotic conditions and ABA treatment identified a group of R2R3-MYB genes that responded to one or more treatments. Furthermore, we identified a previously functionally unknown MYB gene-BnaMYB78, which modulates reactive oxygen species (ROS)-dependent cell death in Nicotiana benthamiana, through regulating the transcription of a few ROS- and defence-related genes. Taken together, this study has provided a solid foundation for understanding the roles and regulatory mechanism of canola R2R3-MYB genes. PMID:26800702

  4. Identification, cloning and characterization of R2R3-MYB gene family in canola (Brassica napus L.) identify a novel member modulating ROS accumulation and hypersensitive-like cell death

    PubMed Central

    Chen, Bisi; Niu, Fangfang; Liu, Wu-Zhen; Yang, Bo; Zhang, Jingxiao; Ma, Jieyu; Cheng, Hao; Han, Feng; Jiang, Yuan-Qing

    2016-01-01

    The R2R3-MYB proteins comprise one of the largest families of transcription factors in plants. Although genome-wide analysis of this family has been carried out in some plant species, little is known about R2R3-MYB genes in canola (Brassica napus L.). In this study, we have identified 76 R2R3-MYB genes in the canola genome through mining of expressed sequence tags (ESTs). The cDNA sequences of 44 MYB genes were successfully cloned. The transcriptional activities of BnaMYB proteins encoded by these genes were assayed in yeast. The subcellular localizations of representative R2R3-MYB proteins were investigated through GFP fusion. Besides, the transcript abundance level analysis during abiotic conditions and ABA treatment identified a group of R2R3-MYB genes that responded to one or more treatments. Furthermore, we identified a previously functionally unknown MYB gene-BnaMYB78, which modulates reactive oxygen species (ROS)-dependent cell death in Nicotiana benthamiana, through regulating the transcription of a few ROS- and defence-related genes. Taken together, this study has provided a solid foundation for understanding the roles and regulatory mechanism of canola R2R3-MYB genes. PMID:26800702

  5. Sudden infant death syndrome

    MedlinePlus

    Crib death; SIDS ... However, SIDS is still a major cause of death in infants under 1 year old. Thousands of ... affects boys more often than girls. Most SIDS deaths occur in the winter. The following may increase ...

  6. Death: 'nothing' gives insight.

    PubMed

    Ettema, Eric J

    2013-08-01

    According to a widely accepted belief, we cannot know our own death--death means 'nothing' to us. At first sight, the meaning of 'nothing' just implies the negation or absence of 'something'. Death then simply refers to the negation or absence of life. As a consequence, however, death has no meaning of itself. This leads to an ontological paradox in which death is both acknowledged and denied: death is … nothing. In this article, I investigate whether insight into the ontological paradox of the nothingness of death can contribute to a good end-of-life. By analysing Aquinas', Heidegger's and Derrida's understanding of death as nothingness, I explore how giving meaning to death on different ontological levels connects to, and at the same time provides resistance against, the harsh reality of death. By doing so, I intend to demonstrate that insight into the nothingness of death can count as a framework for a meaningful dealing with death. PMID:23054426

  7. Sudden Infant Death Syndrome

    MedlinePlus

    Sudden infant death syndrome (SIDS) is the sudden, unexplained death of an infant younger than one year old. Some people call SIDS "crib death" because many babies who die of SIDS are found in their ...

  8. Is It Time to Tailor the Prediction of Radio-Induced Toxicity in Prostate Cancer Patients? Building the First Set of Nomograms for Late Rectal Syndrome

    SciTech Connect

    Valdagni, Riccardo; Kattan, Michael W.; Rancati, Tiziana; Yu Changhong; Vavassori, Vittorio; Fellin, Giovanni; Cagna, Elena; Gabriele, Pietro; Mauro, Flora Anna; Baccolini, Micaela; Bianchi, Carla; Menegotti, Loris; Monti, Angelo F.; Stasi, Michele; Giganti, Maria Olga; and others

    2012-04-01

    Purpose: Development of user-friendly tools for the prediction of single-patient probability of late rectal toxicity after conformal radiotherapy for prostate cancer. Methods and Materials: This multicenter protocol was characterized by the prospective evaluation of rectal toxicity through self-assessed questionnaires (minimum follow-up, 36 months) by 718 adult men in the AIROPROS 0102 trial. Doses were between 70 and 80 Gy. Nomograms were created based on multivariable logistic regression analysis. Three endpoints were considered: G2 to G3 late rectal bleeding (52/718 events), G3 late rectal bleeding (24/718 events), and G2 to G3 late fecal incontinence (LINC, 19/718 events). Results: Inputs for the nomogram for G2 to G3 late rectal bleeding estimation were as follows: presence of abdominal surgery before RT, percentage volume of rectum receiving >75 Gy (V75Gy), and nomogram-based estimation of the probability of G2 to G3 acute gastrointestinal toxicity (continuous variable, which was estimated using a previously published nomogram). G3 late rectal bleeding estimation was based on abdominal surgery before RT, V75Gy, and NOMACU. Prediction of G2 to G3 late fecal incontinence was based on abdominal surgery before RT, presence of hemorrhoids, use of antihypertensive medications (protective factor), and percentage volume of rectum receiving >40 Gy. Conclusions: We developed and internally validated the first set of nomograms available in the literature for the prediction of radio-induced toxicity in prostate cancer patients. Calculations included dosimetric as well as clinical variables to help radiation oncologists predict late rectal morbidity, thus introducing the possibility of RT plan corrections to better tailor treatment to the patient's characteristics, to avoid unnecessary worsening of quality of life, and to provide support to the patient in selecting the best therapeutic approach.

  9. Death by fraternity hazing.

    PubMed

    Boglioli, L R; Taff, M L

    1995-03-01

    Fraternity hazing can cause a variety of injuries and deaths. We recently had the opportunity to investigate a heat-related death that occurred during a college fraternity event. The original death investigation did not consider the circumstances of death, environmental conditions, or the subtle autopsy findings related to heat stroke. This case is intended to alert health care professionals that deaths on college campuses may be related to fraternity hazing and may require in-depth investigations. An analysis of the death and a discussion of heat-related injuries are presented. PMID:7771381

  10. Sudden Infant Death Syndrome

    MedlinePlus

    Sudden infant death syndrome (SIDS) is the sudden, unexplained death of an infant younger than one year old. Some people call ... boys, African Americans, and American Indian/Alaska Native infants have a higher risk of SIDS. Although health ...

  11. Children's Experience with Death.

    ERIC Educational Resources Information Center

    Zeligs, Rose

    Children's concepts of death grow with their age and development The three-year-old begins to notice that living things move and make sounds. The five-year-old thinks that life and death are reversable, but the six-year-old knows that death is final and brings sorrow. Children from eight through ten are interested in the causes of death and what…

  12. Sudden Cardiac Death

    PubMed Central

    Weinberg, Marc

    1978-01-01

    Over the past decade, there has been a significant decrease in the hospital mortality of patients with coronary artery disease. However, sudden cardiac death, which accounts for the majority of deaths from coronary artery disease, hasbeen little affected. This report reviews the pathology, electrophysiology, demographics and clinical presentation of sudden cardiac death. Emergency care and possible preventative measures are examined. PMID:356435

  13. Dreams of Death.

    ERIC Educational Resources Information Center

    Barrett, Deirdre

    1989-01-01

    Examined frequency and characteristics of overt dreams of dying among healthy young adults. Dreams of dying were found to be rare but distinctive content category, representing overwhelmingly pleasant dreams. Over one-half of death dreams involved lengthy afterlife sequence, remainder focused on process of death. Death dreams of these healthy…

  14. Separation, Part I: Death.

    ERIC Educational Resources Information Center

    Jordan, Anne Devereaux

    1997-01-01

    Contends literature is the one place where death still abides, where grief is felt and consolation can be sought. States that young readers can gain a recognition in books that death is natural. Discusses death in folk and fairy tales, in 17th-century didactic children's books and in modern and contemporary literature. Outlines characteristics of…

  15. Infant death scene investigation.

    PubMed

    Tabor, Pamela D; Ragan, Krista

    2015-01-01

    The sudden unexpected death of an infant is a tragedy to the family, a concern to the community, and an indicator of national health. To accurately determine the cause and manner of the infant's death, a thorough and accurate death scene investigation by properly trained personnel is key. Funding and resources are directed based on autopsy reports, which are only as accurate as the scene investigation. The investigation should include a standardized format, body diagrams, and a photographed or videotaped scene recreation utilizing doll reenactment. Forensic nurses, with their basic nursing knowledge and additional forensic skills and abilities, are optimally suited to conduct infant death scene investigations as well as train others to properly conduct death scene investigations. Currently, 49 states have child death review teams, which is an idea avenue for a forensic nurse to become involved in death scene investigations. PMID:25642921

  16. The Effects of Death Education.

    ERIC Educational Resources Information Center

    Freitag, Carl B.; Hassler, Shawn David

    Although fear of death is recorded in the writings of the oldest major religions, the study of death and the fear of death have only occurred for the last few decades. Death education courses have grown in number since the early 1970's. College students participated in an investigation of the effects of death education on death anxiety by…

  17. Brain Death and Islam

    PubMed Central

    Ziad-Miller, Amna; Elamin, Elamin M.

    2014-01-01

    How one defines death may vary. It is important for clinicians to recognize those aspects of a patient’s religious beliefs that may directly influence medical care and how such practices may interface with local laws governing the determination of death. Debate continues about the validity and certainty of brain death criteria within Islamic traditions. A search of PubMed, Scopus, EMBASE, Web of Science, PsycNet, Sociological Abstracts, DIALOGUE ProQuest, Lexus Nexus, Google, and applicable religious texts was conducted to address the question of whether brain death is accepted as true death among Islamic scholars and clinicians and to discuss how divergent opinions may affect clinical care. The results of the literature review inform this discussion. Brain death has been acknowledged as representing true death by many Muslim scholars and medical organizations, including the Islamic Fiqh Academies of the Organization of the Islamic Conference and the Muslim World League, the Islamic Medical Association of North America, and other faith-based medical organizations as well as legal rulings by multiple Islamic nations. However, consensus in the Muslim world is not unanimous, and a sizable minority accepts death by cardiopulmonary criteria only. PMID:25287999

  18. The Sociology of Death

    ERIC Educational Resources Information Center

    Fulton, Robert

    1977-01-01

    When we start to look at the issues associated with dying and death, we must do so in terms of the broadest parameters imaginable. Presented at the Conference on Death and Dying: Education, Counseling, and Care, December 1-3, 1976, Orlando, Florida. (Author)

  19. Death Acceptance through Ritual

    ERIC Educational Resources Information Center

    Reeves, Nancy C.

    2011-01-01

    This article summarizes the author's original research, which sought to discover the elements necessary for using death-related ritual as a psychotherapeutic technique for grieving people who experience their grief as "stuck," "unending," "maladaptive," and so on. A "death-related ritual" is defined as a ceremony, directly involving at least 1…

  20. Conflicting Thoughts about Death

    ERIC Educational Resources Information Center

    Harris, Paul L.

    2011-01-01

    Most research on children's conception of death has probed their understanding of its biological aspects: its inevitability, irreversibility and terminal impact. Yet many adults subscribe to a religious conception implying that death marks the beginning of a new life. Two recent empirical studies confirm that in the course of development, children…

  1. Reflections on Death Education

    ERIC Educational Resources Information Center

    Riskey, Raymond J.

    1977-01-01

    The author comments on the need to discuss death openly in the classroom, noting that engaging students with the idea of coming to grips with the fact of their own death can prepare them for living, working, and loving more fully. (SH)

  2. Education for Death

    ERIC Educational Resources Information Center

    Puolimatka, Tapio; Solasaari, Ulla

    2006-01-01

    Death is an unavoidable fact of human life, which cannot be totally ignored in education. Children reflect on death and raise questions that deserve serious answers. If an educator completely evades the issue, children will seek other conversation partners. It is possible to find arguments both from secular and religious sources, which alleviate…

  3. Mozart's illnesses and death.

    PubMed Central

    Davies, P J

    1983-01-01

    Throughout his life Mozart suffered frequent attacks of tonsillitis. In 1784 he developed post-streptococcal Schönlein-Henoch syndrome which caused chronic glomerular nephritis and chronic renal failure. His fatal illness was due to Schönlein-Henoch purpura, with death from cerebral haemorrhage and bronchopneumonia. Venesection(s) may have contributed to his death. PMID:6352940

  4. Programmed cell death

    SciTech Connect

    1995-12-31

    The purpose of this conference to provide a multidisciplinary forum for exchange of state-of-the-art information on the role programmed cell death plays in normal development and homeostasis of many organisms. This volume contains abstracts of papers in the following areas: invertebrate development; immunology/neurology; bcl-2 family; biochemistry; programmed cell death in viruses; oncogenesis; vertebrate development; and diseases.

  5. Death Obsession in Palestinians

    ERIC Educational Resources Information Center

    Abdel-Khalek, Ahmed M.; Al-Arja, Nahida S.; Abdalla, Taysir

    2006-01-01

    The authors explored death obsession level and correlates among a sample (N=601) of Palestinians living in the city of Beit Jala, the village of Al-Khader, and the Aida refugee camp in the Bethlehem area. They live in war conditions; the houses of half of them have been demolished. The Death Obsession Scale (DOS) was administered. Its alpha…

  6. SUICIDE ON DEATH ROW.

    PubMed

    Tartaro, Christine; Lester, David

    2015-12-01

    For the period 1976-2011, the suicide rate on death rows in the United States was only weakly (and non-significantly) associated with the marriage, birth, divorce, and unemployment rates in the general population. Possible explanations for why social indicators in the larger society might be associated with the behavior of prisoners on death row were discussed. PMID:26595302

  7. Death Writ Large

    ERIC Educational Resources Information Center

    Kastenbaum, Robert

    2004-01-01

    Mainstream thanatology has devoted its efforts to improving the understanding, care, and social integration of people who are confronted with life-threatening illness or bereavement. This article suggests that it might now be time to expand the scope and mission to include large-scale death and death that occurs through complex and multi-domain…

  8. Near-death experiences.

    PubMed Central

    Blackmore, S J

    1996-01-01

    Reactions to claims of near-death experiences (NDE) range from the popular view that this must be evidence for life after death, to outright rejection of the experiences as, at best, drug induced hallucinations or, at worse, pure invention. Twenty years, and much research, later, it is clear that neither extreme is correct. PMID:8683504

  9. Death in Denmark.

    PubMed Central

    Evans, M

    1990-01-01

    Does it matter that the hearts of 'brainstem dead' patients may persist in beating spontaneously? Hostile reactions, to the Danish inclusion of cardiac criteria in the determination of death, betray reductionist views of human life at the core of 'brainstem' conceptions of death. Such views (whether centred on neurological function or on abstractions concerning 'personhood') supplant the richness of human life and death with the poverty of essentialism: and mask the lethal nature of beating-heart organ retrieval. The affirmation of cardiac criteria for death is not an alternative form of essentialism as some critics suppose, but part of an understanding of human life and death which rejects essentialism altogether. The spontaneously persistent heartbeat does not constitute human life, but most certainly counts for it. PMID:2287015

  10. Unusual sudden death.

    PubMed Central

    Warren, J. V.

    1985-01-01

    In contrast to usual sudden death seen in the course of coronary artery disease, individuals dying suddenly from other causes form a complex array of situations. In some the causes are readily identifiable. No simple pattern is available to identify the potential candidate, but on review of the many causes some moves by the physician may be helpful. For example, a more complete physical evaluation of young individuals participating in competitive athletics is in order. This is particularly true if the athlete reports an episode of unexplained syncope. This may well be the warning of a propensity towards sudden death under physical and emotional stress. Knowledge of the specific problems in underwater swimming and diving, in high altitude exposure and in various circumstances such as certain weight reduction diets and industrial exposures may lead to control of some types of unusual sudden death. Clearly, more studies are needed to give answers in so called crib death. As the incidence of usual sudden death falls, these unusual forms of sudden death will represent a more important fraction of sudden death in general. PMID:6537674

  11. Unnatural sudden infant death

    PubMed Central

    Meadow, R.

    1999-01-01

    AIM—To identify features to help paediatricians differentiate between natural and unnatural infant deaths.
METHOD—Clinical features of 81 children judged by criminal and family courts to have been killed by their parents were studied. Health and social service records, court documents, and records from meetings with parents, relatives, and social workers were studied.
RESULTS—Initially, 42 children had been certified as dying from sudden infant death syndrome (SIDS), and 29 were given another cause of natural death. In 24 families, more than one child died; 58died before the age of 6 months and most died in the afternoon or evening. Seventy per cent had experienced unexplained illnesses; over half were admitted to hospital within the previous month, and 15 had been discharged within 24 hours of death. The mother, father, or both were responsible for death in 43, five, and two families, respectively. Most homes were disadvantaged—no regular income, receiving income support—and mothers smoked. Half the perpetrators had a history of somatising or factitious disorder. Death was usually by smothering and 43% of children had bruises, petechiae, or blood on the face.
CONCLUSIONS—Although certain features are indicative of unnatural infant death, some are also associated with SIDS. Despite the recent reduction in numbers of infants dying suddenly, inadequacies in the assessment of their deaths exist. Until a thorough postmortem examination is combined with evaluation of the history and circumstances of death by an experienced paediatrician, most cases of covert fatal abuse will go undetected. The term SIDS requires revision or abandonment.

 PMID:10325752

  12. Eaten to death

    PubMed Central

    Nelson, Charles; Baehrecke, Eric H.

    2014-01-01

    Macro-autophagy (hereafter referred to as autophagy) delivers cytoplasmic material to the lysosome for degradation, and has been implicated in many cellular processes, including stress, infection, survival, and death. While the regulation and role that autophagy plays in stress, infection, and survival is apparent, the regulation of and role that autophagy has during cell death remains relatively unclear. In this review, we highlight what is known about the role that autophagy can play during physiological cell death, and discuss the implications of better understanding cellular destruction that involves autophagy. PMID:25323556

  13. Children's Death Concepts and Ethnicity.

    ERIC Educational Resources Information Center

    Wass, Hannelore; Towry, Betty J.

    1980-01-01

    Relationships between death concepts of Black and White children and their racial status were examined. Lower-middle-class elementary children completed a four-item questionnaire on death. Most children defined death as the end of living and listed physical causes as the explanation of death. In general, children's death concepts were similar.…

  14. Death and Grief

    MedlinePlus

    ... for Parents for Kids for Teens Teens Home Body Mind Sexual Health Food & Fitness Diseases & Conditions Infections Q& ... a death or loss. Grief can affect our body, mind, emotions, and spirit. People might notice or show ...

  15. Eighth Amendment & Death Penalty.

    ERIC Educational Resources Information Center

    Shortall, Joseph M.; Merrill, Denise W.

    1987-01-01

    Presents a lesson on capital punishment for juveniles based on three hypothetical cases. The goal of the lesson is to have students understand the complexities of decisions regarding the death penalty for juveniles. (JDH)

  16. Hitler's Death Camps.

    ERIC Educational Resources Information Center

    Wieser, Paul

    1995-01-01

    Presents a high school lesson on Hitler's death camps and the widespread policy of brutality and oppression against European Jews. Includes student objectives, instructional procedures, and a chart listing the value of used clothing taken from the Jews. (CFR)

  17. Funerals against death

    PubMed Central

    Bailey, Tara; Walter, Tony

    2016-01-01

    While anthropological studies in non-Western societies show how funerals protect the community from the threat of death, sociological studies of British funerals have so far focused on meanings for the private family. The article reports on results from a Mass Observation directive – the first British study to focus specifically on the entire funeral congregation – and shows how attendees experience the contemporary life-centred funeral as a symbolic conquest of death. While the eulogy’s accuracy is important, even more so – at least for some – is its authenticity, namely that the speaker has personal knowledge of the deceased. Whereas Davies analyses the power of professionally delivered ritual words against death, our data reveals how admired is the courage exercised by non-professionals in speaking against death, however faltering their words. Further, the very presence of a congregation whose members have known the deceased in diverse ways embodies a configurational eulogy, which we term relationships against death. We thus argue that funerals symbolically conquer death not only through words delivered by ritual specialists, but also through those who knew the deceased congregating and speaking. PMID:27019605

  18. Classification of cell death

    PubMed Central

    Kroemer, G; Galluzzi, L; Vandenabeele, P; Abrams, J; Alnemri, ES; Baehrecke, EH; Blagosklonny, MV; El-Deiry, WS; Golstein, P; Green, DR; Hengartner, M; Knight, RA; Kumar, S; Lipton, SA; Malorni, W; Nuñez, G; Peter, ME; Tschopp, J; Yuan, J; Piacentini, M; Zhivotovsky, B; Melino, G

    2009-01-01

    Different types of cell death are often defined by morphological criteria, without a clear reference to precise biochemical mechanisms. The Nomenclature Committee on Cell Death (NCCD) proposes unified criteria for the definition of cell death and of its different morphologies, while formulating several caveats against the misuse of words and concepts that slow down progress in the area of cell death research. Authors, reviewers and editors of scientific periodicals are invited to abandon expressions like ‘percentage apoptosis’ and to replace them with more accurate descriptions of the biochemical and cellular parameters that are actually measured. Moreover, at the present stage, it should be accepted that caspase-independent mechanisms can cooperate with (or substitute for) caspases in the execution of lethal signaling pathways and that ‘autophagic cell death’ is a type of cell death occurring together with (but not necessarily by) autophagic vacuolization. This study details the 2009 recommendations of the NCCD on the use of cell death-related terminology including ‘entosis’, ‘mitotic catastrophe’, ‘necrosis’, ‘necroptosis’ and ‘pyroptosis’. PMID:18846107

  19. Deaths: Final Data for 2014.

    PubMed

    Kochanek, Kenneth D; Murphy, Sherry L; Xu, Jiaquan; Tejada-Vera, Betzaida

    2016-06-01

    Objectives-This report presents final 2014 data on U.S. deaths, death rates, life expectancy, infant mortality, and trends, by selected characteristics such as age, sex, Hispanic origin, race, state of residence, and cause of death. PMID:27378572

  20. Brain death declaration

    PubMed Central

    Wahlster, Sarah; Wijdicks, Eelco F.M.; Patel, Pratik V.; Greer, David M.; Hemphill, J. Claude; Carone, Marco

    2015-01-01

    Objective: To assess the practices and perceptions of brain death determination worldwide and analyze the extent and nature of variations among countries. Methods: An electronic survey was distributed globally to physicians with expertise in neurocritical care, neurology, or related disciplines who would encounter patients at risk of brain death. Results: Most countries (n = 91, response rate 76%) reported a legal provision (n = 63, 70%) and an institutional protocol (n = 70, 77%) for brain death. Institutional protocols were less common in lower-income countries (2/9 of low [22%], 9/18 lower-middle [50%], 22/26 upper-middle [85%], and 37/38 high-income countries [97%], p < 0.001). Countries with an organized transplant network were more likely to have a brain death provision compared with countries without one (53/64 [83%] vs 6/25 [24%], p < 0.001). Among institutions with a formalized brain death protocol, marked variability occurred in requisite examination findings (n = 37, 53% of respondents deviated from the American Academy of Neurology criteria), apnea testing, necessity and type of ancillary testing (most commonly required test: EEG [n = 37, 53%]), time to declaration, number and qualifications of physicians present, and criteria in children (distinct pediatric criteria: n = 38, 56%). Conclusions: Substantial differences in perceptions and practices of brain death exist worldwide. The identification of discrepancies, improvement of gaps in medical education, and formalization of protocols in lower-income countries provide first pragmatic steps to reconciling these variations. Whether a harmonized, uniform standard for brain death worldwide can be achieved remains questionable. PMID:25854866

  1. Perspectives on Death: An Experiential Course on Death Education.

    ERIC Educational Resources Information Center

    Stefan, Edwin S.

    1978-01-01

    Describes and evaluates a college psychology course on death education (thanatology). Course objectives were to help students become aware of the feelings involved in facing death, encourage discussion on the subject of death, motivate students to change their attitudes about death, and encourage practical planning for funeral arrangements.…

  2. Death Threat and Death Concerns in the College Student.

    ERIC Educational Resources Information Center

    Tobacyk, Jerome; Eckstein, Daniel

    1980-01-01

    Thanatology students reported significantly lesser death threat and significantly greater death concerns. Trait anxiety was found to be a significant predictor of change in death threat in the Thanatology Group, with lesser anxiety associated with greater decline in death threat. (Author)

  3. Pathophysiological mechanisms of death resistance in colorectal carcinoma

    PubMed Central

    Huang, Ching-Ying; Yu, Linda Chia-Hui

    2015-01-01

    Colon cancers develop adaptive mechanisms to survive under extreme conditions and display hallmarks of unlimited proliferation and resistance to cell death. The deregulation of cell death is a key factor that contributes to chemoresistance in tumors. In a physiological context, balance between cell proliferation and death, and protection against cell damage are fundamental processes for maintaining gut epithelial homeostasis. The mechanisms underlying anti-death cytoprotection and tumor resistance often bear common pathways, and although distinguishing them would be a challenge, it would also provide an opportunity to develop advanced anti-cancer therapeutics. This review will outline cell death pathways (i.e., apoptosis, necrosis, and necroptosis), and discuss cytoprotective strategies in normal intestinal epithelium and death resistance mechanisms of colon tumor. In colorectal cancers, the intracellular mechanisms of death resistance include the direct alteration of apoptotic and necroptotic machinery and the upstream events modulating death effectors such as tumor suppressor gene inactivation and pro-survival signaling pathways. The autocrine, paracrine and exogenous factors within a tumor microenvironment can also instigate resistance against apoptotic and necroptotic cell death in colon cancers through changes in receptor signaling or transporter uptake. The roles of cyclooxygenase-2/prostaglandin E2, growth factors, glucose, and bacterial lipopolysaccharides in colorectal cancer will be highlighted. Targeting anti-death pathways in the colon cancer tissue might be a promising approach outside of anti-proliferation and anti-angiogenesis strategies for developing novel drugs to treat refractory tumors. PMID:26557002

  4. Infant deaths in slings.

    PubMed

    Madre, Chrystèle; Rambaud, Caroline; Avran, David; Michot, Charlotte; Sachs, Philippe; Dauger, Stéphane

    2014-12-01

    Although the incidence of sudden unexpected death in infancy (SUDI) decreased markedly after campaigns to promote supine positioning during sleeping, it has remained unchanged over the last decade. Epidemiological data suggest a role for new causes such as suffocation, asphyxia, and entrapment. Health authorities in several countries have issued warnings about slings used to carry infants. However, few reports of infant deaths in slings have been published in medical journals. Our paediatric intensive care unit has admitted two infants who experienced cardiorespiratory arrest while carried in a sling. Diagnostic investigations including a post-mortem examination established asphyxia as the mechanism of death. In conclusion, baby slings may carry a risk of SUDI, either by compression of the baby into a forward-flexed position or by direct suffocation. European recommendations for the cautious use of baby slings should be disseminated to families and professionals involved in caring for infants, as done recently in Australia, Canada, and the USA. PMID:24343674

  5. The "moment of death".

    PubMed

    Valentine, Christine

    2007-01-01

    The "moment of death," once a dominant concept in preparing for a "good death", has been eclipsed by a focus on the wider concept of the "dying trajectory". However, findings from interviews with 25 bereaved individuals suggest that dying loved ones' final moments may still be experienced as highly significant in their own right. In some accounts the dying individual's final moments did not feature or made little impression, either because the survivor was not present, or there was no obviously definable moment, or because other, usually medical factors, such as whether to resuscitate the person, took precedence. However, in six cases such moments were constructed as profound, special, and memorable occasions. These constructions are explored in relation to achieving a good death, the dying trajectory as a whole, and making sense of the bereavement experience. Their implications for sociological theories of identity and embodiment are also considered. PMID:18214069

  6. [Sexuality and death].

    PubMed

    Sapetti, Adrián

    2006-01-01

    It is intented to show two apparently antithetic poles: Sexuality and Death, in fact interpenetrate themselves, disguising the fear of death, or the desire to die, Eros' world. Different expressions of culture are analyzed, especially the one known as The Profane Time, the time for work, which is characterized by the submission to interdicts (prohibitions) and, on the other hand, the Time for Joy or The Sacred Time, characterized by the transgression of such prohibitions. Its relationship with the interdicts'violations in the sexual as well as in the death arena is analyzed in order to connect the human being's fear in the presence of the unrestraint, the overflow and the abandonment of the time established for work that would imply free sexuality. The latter is connected with some conclusions that could be considered useful in the field of Sexual Therapies, with a certain critical look at the mechanist settlement applied to those treatments. PMID:16645674

  7. [The death of Cleopatra].

    PubMed

    Guillemain, Bernard

    2009-01-01

    The image of a queen bitten by a snake is controversial and the facts, such as the swiftness of her death and her servants, and scientific experiments are in favour of a deadly poisoning. The author reminds that in the ancient texts the snake had sacred virtues and it was a symbolic image to embellish the suicide of the one who was sentenced to death by the Romans. Octaves set up the myth of a fatal bite which became an iconographic image for the cinema. PMID:20503640

  8. [Near death experiences].

    PubMed

    Rubia Vila, Francisco José

    2012-01-01

    Near Death Experiences are those accounted by people who after being clinically dead return to life spontaneously or after reanimation. These experiences have been used traditionally to support the belief in the existence of the soul and of life after death. However, today neuroscience tries to explain these experiences from the scientific point of view, i.e. explaining them based on their brain substrates. Their resemblance to mystic experiences and to altered states of consciousness seems to indicate that they may be produced by hyperactivity of limbic structures caused by anoxia or hypercapnia. PMID:24294729

  9. Sudden Death Syndrome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sudden death syndrome (SDS) is an important disease of soybean in North and South America. SDS first occurred in South America in the early 1990s. In the U.S.A., SDS was first detected in AK in 1971. Now SDS occurs in most soybean production areas of the U.S. The SDS pathogen is a soil-borne fungu...

  10. The Death Penalty.

    ERIC Educational Resources Information Center

    Crockett, Mark

    1990-01-01

    Provides a lesson plan on the Eighth Amendment to the U.S. Constitution and the imposition of the death penalty. Focuses on the controversy concerning capital punishment and stimulates critical thinking in an analysis and discussion of eight hypothetical situations. Includes suggestions for readings, videotapes, and writing assignments. (NL)

  11. Death of a Leader.

    ERIC Educational Resources Information Center

    McLaughlin, Thomas E.

    1994-01-01

    When Issaquah (Washington) superintendent, after battling a brain tumor, entered the hospital for the last time, school district had to develop a crisis plan to deal with the possible death of the superintendent. A contingency planning team developed a telephone tree for school officials to keep in close contact with teachers and administrators.…

  12. Digital Language Death

    PubMed Central

    Kornai, András

    2013-01-01

    Of the approximately 7,000 languages spoken today, some 2,500 are generally considered endangered. Here we argue that this consensus figure vastly underestimates the danger of digital language death, in that less than 5% of all languages can still ascend to the digital realm. We present evidence of a massive die-off caused by the digital divide. PMID:24167559

  13. Diagnosis of brain death

    PubMed Central

    Machado, Calixto

    2010-01-01

    Brain death (BD) should be understood as the ultimate clinical expression of a brain catastrophe characterized by a complete and irreversible neurological stoppage, recognized by irreversible coma, absent brainstem reflexes, and apnea. The most common pattern is manifested by an elevation of intracranial pressure to a point beyond the mean arterial pressure, and hence cerebral perfusion pressure falls and, as a result, no net cerebral blood flow is present, in due course leading to permanent cytotoxic injury of the intracranial neuronal tissue. A second mechanism is an intrinsic injury affecting the nervous tissue at a cellular level which, if extensive and unremitting, can also lead to BD. We review here the methodology of diagnosing death, based on finding any of the signs of death. The irreversible loss of cardio-circulatory and respiratory functions can cause death only when ischemia and anoxia are prolonged enough to produce an irreversible destruction of the brain. The sign of such loss of brain functions, that is to say BD diagnosis, is fully reviewed. PMID:21577338

  14. Sudden Infant Death Syndrome.

    ERIC Educational Resources Information Center

    Barnett, Henry L.; And Others

    There is a growing body of evidence that Sudden Infant Death Syndrome (SIDS) victims are not completely normal and healthy, as was once believed. A variety of new information from several disciplines strongly suggests that the infant who dies suddenly and unexpectedly may do so because of subtle developmental, neurologic, cardiorespiratory, and…

  15. Digital language death.

    PubMed

    Kornai, András

    2013-01-01

    Of the approximately 7,000 languages spoken today, some 2,500 are generally considered endangered. Here we argue that this consensus figure vastly underestimates the danger of digital language death, in that less than 5% of all languages can still ascend to the digital realm. We present evidence of a massive die-off caused by the digital divide. PMID:24167559

  16. The Excess Winter Deaths Measure

    PubMed Central

    Gasparrini, Antonio

    2016-01-01

    Background: Excess winter deaths, the ratio between average daily deaths in December–March versus other months, is a measure commonly used by public health practitioners and analysts to assess health burdens associated with wintertime weather. We seek to demonstrate that this measure is fundamentally biased and can lead to misleading conclusions about health impacts associated with current and future winter climate. Methods: Time series regression analysis of 779,372 deaths from natural causes in London over 15 years (1 August 1997–31 July 2012),collapsed by day of death and linked to daily temperature values. The outcome measures were the excess winter deaths index, and daily and annual deaths attributable specifically to cold. Results: Most of the excess winter deaths are driven by cold: The excess winter deaths index decreased from 1.19 to 1.07 after excluding deaths attributable to low temperatures. Over 40% of cold-attributable deaths occurred outside of the December–March period, leading to bias in the excess winter deaths measure. Although there was no relationship between winter severity and annual excess winter deaths, there was a clear correlation with annual cold-attributable deaths. Conclusions: Excess winter deaths is not an appropriate indicator of cold-related health impacts, and its use should be discontinued. We advocate alternative measures. The findings we present bring into doubt previous claims that cold-related deaths in the UK will not reduce in future as a result of climate change. PMID:26986872

  17. Adolescent Russian roulette deaths.

    PubMed

    Collins, Kim A

    2010-03-01

    Adolescence, between the ages of 10 and 19 years, is a unique period both physically and emotionally. During this time of life, individuals are known to experiment and engage in risky behavior, sometimes with unforeseen morbidity and mortality. We also see suicide emerge as a manner of death in this age group. The most common method is gunshot wound and sometimes in the form of Russian roulette. Few studies have looked at deaths by Russian roulette, the victims, and scenarios. In particular, no study examines the adolescent victim of Russian roulette. To better understand and classify this entity, adolescent Russian roulette autopsy cases over a 20-year period were examined looking at the victims, scenarios, autopsy findings, cause and manner of death, and the weapons. All victims were males, ages 13 to 19 years, with a Black-to-White ratio of 1:1. No victim had a previous psychiatric history. Toxicology was positive for alcohol and/or marijuana in 50% of the victims. Friends were present when the victim shot himself which occurred in the home the majority of the time. In all but 1 case, premeditation of the game was involved as the victim provided the weapon for the roulette. The cause of death was gunshot wound to the head (6 to the right side, 1 to the mouth, 1 to the forehead), and the manner of death was suicide in 6 cases and accident in 2 cases. A review of the literature discusses the adolescent victim, suicide, and Russian roulette. PMID:20010290

  18. Near-death experiences and the psychology of death.

    PubMed

    Tassell-Matamua, Natasha A

    Little is known about the psychological phenomenology of death. Reported across known history and in all cultures by those who have died or been close to death, NDEs challenge objective-mechanistic models by suggesting the phenomenology of death may involve a variety of complex psychological processes. This article discusses three notable characteristics of the NDE--loss of the fear of death, psychological sequelae, and complex conscious abilities--supporting this claim. The implications these have for advancing societal understandings of death are discussed, and their pragmatic application for professions where death is frequently encountered, such as palliative care, is addressed. PMID:24834668

  19. Actin as Deathly Switch? How Auxin Can Suppress Cell-Death Related Defence

    PubMed Central

    Chang, Xiaoli; Riemann, Michael; Liu, Qiong; Nick, Peter

    2015-01-01

    Plant innate immunity is composed of two layers – a basal immunity, and a specific effector-triggered immunity, which is often accompanied by hypersensitive cell death. Initiation of cell death depends on a complex network of signalling pathways. The phytohormone auxin as central regulator of plant growth and development represents an important component for the modulation of plant defence. In our previous work, we showed that cell death is heralded by detachment of actin from the membrane. Both, actin response and cell death, are triggered by the bacterial elicitor harpin in grapevine cells. In this study we investigated, whether harpin-triggered actin bundling is necessary for harpin-triggered cell death. Since actin organisation is dependent upon auxin, we used different auxins to suppress actin bundling. Extracellular alkalinisation and transcription of defence genes as the basal immunity were examined as well as cell death. Furthermore, organisation of actin was observed in response to pharmacological manipulation of reactive oxygen species and phospholipase D. We find that induction of defence genes is independent of auxin. However, auxin can suppress harpin-induced cell death and also counteract actin bundling. We integrate our findings into a model, where harpin interferes with an auxin dependent pathway that sustains dynamic cortical actin through the activity of phospholipase D. The antagonism between growth and defence is explained by mutual competition for signal molecules such as superoxide and phosphatidic acid. Perturbations of the auxin-actin pathway might be used to detect disturbed integrity of the plasma membrane and channel defence signalling towards programmed cell death. PMID:25933033

  20. The Influenza Virus H5N1 Infection Can Induce ROS Production for Viral Replication and Host Cell Death in A549 Cells Modulated by Human Cu/Zn Superoxide Dismutase (SOD1) Overexpression.

    PubMed

    Lin, Xian; Wang, Ruifang; Zou, Wei; Sun, Xin; Liu, Xiaokun; Zhao, Lianzhong; Wang, Shengyu; Jin, Meilin

    2016-01-01

    Highly pathogenic H5N1 infections are often accompanied by excessive pro-inflammatory response, high viral titer, and apoptosis; as such, the efficient control of these infections poses a great challenge. The pathogenesis of influenza virus infection is also related to oxidative stress. However, the role of endogenic genes with antioxidant effect in the control of influenza viruses, especially H5N1 viruses, should be further investigated. In this study, the H5N1 infection in lung epithelial cells decreased Cu/Zn superoxide dismutase (SOD1) expression at mRNA and protein levels. Forced SOD1 expression significantly inhibited the H5N1-induced increase in reactive oxygen species, decreased pro-inflammatory response, prevented p65 and p38 phosphorylation, and impeded viral ribonucleoprotein nuclear export and viral replication. The SOD1 overexpression also rescued H5N1-induced cellular apoptosis and alleviated H5N1-caused mitochondrial dysfunction. Therefore, this study described the role of SOD1 in the replication of H5N1 influenza virus and emphasized the relevance of this enzyme in the control of H5N1 replication in epithelial cells. Pharmacological modulation or targeting SOD1 may open a new way to fight H5N1 influenza virus. PMID:26761025

  1. Metabolism and epigenetics in the nervous system: Creating cellular fitness and resistance to neuronal death in neurological conditions via modulation of oxygen-, iron-, and 2-oxoglutarate-dependent dioxygenases.

    PubMed

    Karuppagounder, Saravanan S; Kumar, Amit; Shao, Diana S; Zille, Marietta; Bourassa, Megan W; Caulfield, Joseph T; Alim, Ishraq; Ratan, Rajiv R

    2015-12-01

    Modern definitions of epigenetics incorporate models for transient but biologically important changes in gene expression that are unrelated to DNA code but responsive to environmental changes such as injury-induced stress. In this scheme, changes in oxygen levels (hypoxia) and/or metabolic co-factors (iron deficiency or diminished 2-oxoglutarate levels) are transduced into broad genetic programs that return the cell and the organism to a homeostatic set point. Over the past two decades, exciting studies have identified a superfamily of iron-, oxygen-, and 2-oxoglutarate-dependent dioxygenases that sit in the nucleus as modulators of transcription factor stability, co-activator function, histone demethylases, and DNA demethylases. These studies have provided a concrete molecular scheme for how changes in metabolism observed in a host of neurological conditions, including stroke, traumatic brain injury, and Alzheimer's disease, could be transduced into adaptive gene expression to protect the nervous system. We will discuss these enzymes in this short review, focusing primarily on the ten eleven translocation (TET) DNA demethylases, the jumonji (JmJc) histone demethylases, and the oxygen-sensing prolyl hydroxylase domain enzymes (HIF PHDs). This article is part of a Special Issue entitled SI: Neuroprotection. PMID:26232572

  2. Sudden death of feedlot cattle.

    PubMed

    Glock, R D; DeGroot, B D

    1998-01-01

    Sudden deaths or the sudden death syndrome are perceived as major concerns in cattle feedlots because most of these deaths occur in cattle near market weight. Etiology and preventive measures are poorly defined. The current literature indicates that sudden deaths are associated most commonly with digestive upsets. Death is thought to be the result of interactions between factors including acidosis, bloat, and endotoxemia. Trauma, peracute interstitial pneumonia, and other identifiable events are specifically defined but relatively uncommon. Enterotoxemia is of questionable significance as a cause of sudden deaths. PMID:9464913

  3. Emergency department deaths.

    PubMed

    Webb, G L; McSwain, N E; Webb, W R; Rodriguez, C

    1990-04-01

    This study reviews 186 deaths resulting from trauma in a 2-year period in the Charity Hospital of Louisiana at New Orleans Accident Room in order to evaluate problems in prehospital and hospital resuscitative care. All subjects underwent autopsy, and only six were found to have injuries compatible with survival. Three of these were late arrivals (by transfer or self-imposed delay) and died of protracted hemorrhage. Only three deaths occurring in the Emergency Department itself were found to have been potentially preventable. The important factors in maximizing survival of trauma patients remain rapid transport; immediate, appropriate, rapid evaluation; and quick diagnosis, resuscitation, and definitive therapy. These require a well-trained emergency medical ambulance service delivering patients quickly to a hospital designed to handle trauma patients. One person, preferably a general surgeon with trauma experience, should supervise and monitor the patient continually until the resuscitation phase and all diagnostic tests are completed and definitive therapy is initiated. PMID:2316801

  4. [Death after anal "fisting"].

    PubMed

    Preuss, Johanna; Strehler, Marco; Dettmeyer, Reinhard; Madea, Burkhard

    2008-01-01

    A 45-year-old homeless woman was found dead at her usual sleeping place. Apart from traces of blood on the lower abdomen of the body, the police investigations did not produce any clues pointing to an unnatural death. At autopsy, it was found, however, that death had been caused by extensive disruptions of the intestine. After being confronted with the results, the sexual partner of the victim admitted manual anal penetration, but claimed that this had been done by mutual agreement. The court did not accept that statement and sentenced him to life imprisonment for murder. The frequency of such fatal outcomes of anal penetration, the relationship between the perpetrator and the victim and the special features at the scene are discussed. PMID:18389861

  5. [Karoshi, death by overwork].

    PubMed

    Uehata, Tetsunojo

    2005-07-01

    Karoshi (death by overwork) is one of social medical terms, which used by survivors of victims who attacked with cardiovascular diseases such as stroke, myocardial infarction and sudden cardiac death. In Dec. 2000, Compensation Standard of cardiovascular diseases in Workers' Insurance was changed and admitted the relationship between chronic fatigue and cardiovascular attacks. As a result, compensation numbers of Karoshi attributed to three hundred and more from about 80 cases. The Ministry of Health, Labour and Welfare thinks that most of Karoshi caused by long working hours continuing for several months, especially without payment, so that the Labour Standard Inspector Office requests to decrease overtime work more than 45 hours per month to firm administrators. PMID:16001791

  6. Atypical autoerotic deaths

    SciTech Connect

    Gowitt, G.T.; Hanzlick, R.L. )

    1992-06-01

    So-called typical' autoerotic fatalities are the result of asphyxia due to mechanical compression of the neck, chest, or abdomen, whereas atypical' autoeroticism involves sexual self-stimulation by other means. The authors present five atypical autoerotic fatalities that involved the use of dichlorodifluoromethane, nitrous oxide, isobutyl nitrite, cocaine, or compounds containing 1-1-1-trichloroethane. Mechanisms of death are discussed in each case and the pertinent literature is reviewed.

  7. Peroxiredoxins and the Regulation of Cell Death

    PubMed Central

    Hampton, Mark B.; O’Connor, Karina M.

    2016-01-01

    Cell death pathways such as apoptosis can be activated in response to oxidative stress, enabling the disposal of damaged cells. In contrast, controlled intracellular redox events are proposed to be a significant event during apoptosis signaling, regardless of the initiating stimulus. In this scenario oxidants act as second messengers, mediating the post-translational modification of specific regulatory proteins. The exact mechanism of this signaling is unclear, but increased understanding offers the potential to promote or inhibit apoptosis through modulating the redox environment of cells. Peroxiredoxins are thiol peroxidases that remove hydroperoxides, and are also emerging as important players in cellular redox signaling. This review discusses the potential role of peroxiredoxins in the regulation of apoptosis, and also their ability to act as biomarkers of redox changes during the initiation and progression of cell death. PMID:26810076

  8. A Death in the Family: Death as a Zen Concept

    ERIC Educational Resources Information Center

    Black, Helen K.; Rubinstein, Robert L.

    2013-01-01

    This study is based on original research that explored family reaction to the death of an elderly husband and father. We interviewed 34 families (a family included a widow and two adult biological children) approximately 6 to 10 months after the death. In one-on-one interviews, we discussed family members' initial reaction to the death, how the…

  9. Death Sentences: A Content Analysis of Children's Death Literature

    ERIC Educational Resources Information Center

    Poling, Devereaux A.; Hupp, Julie M.

    2008-01-01

    A multidimensional concept of death must include biological, sociocultural, and emotional components. Children glean information about death in many ways, one of which is through books. In this study, the authors compared the 3 dimensions of death-related information (irreversibility, inevitability, nonfunctionality) in 24 young children's picture…

  10. Life, Death, and Second Chances

    MedlinePlus

    ... Home Current Issue Past Issues Special Section Life, Death, and Second Chances Past Issues / Fall 2007 Table ... New Asthma Guidelines: What You Should Know / Life, Death, and Second Chances / Asthma Research: The NIH-NJRC ...

  11. Sudden Infant Death Syndrome (SIDS)

    MedlinePlus

    ... Information Clinical Trials Resources and Publications Sudden Infant Death Syndrome (SIDS): Condition Information Skip sharing on social ... Share this: Page Content SIDS is the sudden death of an infant younger than 1 year of ...

  12. Childhood Deaths from Physical Abuse.

    ERIC Educational Resources Information Center

    Kasim, Mohd. Sham; and Others

    1995-01-01

    This paper describes 30 cases of childhood deaths caused by physical abuse in Kuala Lumpur, Malaysia. Data presented include ethnic origins, age, causes of death, identity of perpetrators, and marital situation of parents. (DB)

  13. Death in Denmark: a reply.

    PubMed Central

    Lamb, D

    1991-01-01

    This reply to Martyn Evans's support for a cardiac-centered concept of death attempts to meet some objections to the brainstem definition of death. Evans's appeal to Wittgenstein's philosophy is also criticised. PMID:1870081

  14. On social death: ostracism and the accessibility of death thoughts.

    PubMed

    Steele, Caroline; Kidd, David C; Castano, Emanuele

    2015-01-01

    Being rejected, excluded, or simply ignored is a painful experience. Ostracism researchers have shown its powerful negative consequences (Williams, 2007), and sociologists have referred to such experiences as social death (Bauman, 1992). Is this is just a metaphor or does being ostracized make death more salient in people's minds? An experiment was conducted in which participants experienced ostracism or inclusion using the Cyberball manipulation, and the accessibility of death-related thoughts was measured via a word-stem completion puzzle. Results showed enhanced death-thought accessibility in the ostracism condition, as well as a negative effect of dispositional self-esteem on the accessibility of death-related thoughts. PMID:24592875

  15. Deaths: Leading Causes for 2014.

    PubMed

    Heron, Melonie

    2016-06-01

    Objectives-This report presents final 2014 data on the 10 leading causes of death in the United States by age, sex, race, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements "Deaths: Final Data for 2014," the National Center for Health Statistics' annual report of final mortality statistics. PMID:27376998

  16. Death of an Adult Child

    MedlinePlus

    ... iGive.com Purchase Through AmazonSmile Contact Us Donate Death of an Adult Child The death of any child, regardless of cause or age, ... the situations that may have caused their child’s death. Judgmental statements from others indicating that the child ...

  17. Death: Realism in Children's Books.

    ERIC Educational Resources Information Center

    Danielson, Kathy Everts

    In the past, books for children treated death fearfully, morbidly, and didactically, but now children's literature treats death in a more realistic manner and is sensitive to its emotional aspects. Current theories suggest that children perceive death differently at various ages. G. P. Koocher (1973) used J. Piaget's cognitive stages as the basis…

  18. Deaths: Final Data for 1998.

    ERIC Educational Resources Information Center

    Murphy, Sherry L.

    2000-01-01

    This report presents final 1998 data on U.S. deaths and death rates according to demographic and medical characteristics such as age, sex, race, Hispanic origin, marital status, educational attainment, injury at work, state of residence, and cause of death. Trends and patterns in general mortality, life expectancy, and infant and maternal…

  19. Changing Breton Responses to Death.

    ERIC Educational Resources Information Center

    Badone, Ellen

    1988-01-01

    Based on fieldwork conducted in Brittany, France, during 1983 and 1984, discusses changes in Breton responses to death which have accompanied modernization and economic development. Suggests that familiarity with death and acceptance of it are being replaced by the "denial of death" characteristic of contemporary Western culture. Notes parallel…

  20. Teaching about Death to Undergraduates.

    ERIC Educational Resources Information Center

    Pine, Vanderlyn R.; And Others

    Development, implementation, and teaching of a college-level course on dying and death are described. The authors review their own experiences in becoming involved with death education and describe teaching methods, problems, and content of their current course in dying and death at the State University of New York, College at New Paltz. Because…

  1. Magnesium and sudden death.

    PubMed

    Leary, W P; Reyes, A J

    1983-10-22

    Magnesium deficiency may result from reduced dietary intake of the ion or increased losses in sweat, urine or faeces. Stress potentiates magnesium deficiency, and an increased incidence of sudden death associated with ischaemic heart disease is found in some areas in which soil and drinking water lack magnesium. Furthermore, it has been demonstrated experimentally that reduction of the plasma magnesium level is associated with arterial spasm. Careful studies are required to assess the clinical importance of magnesium and the benefits of magnesium supplementation in man. PMID:6353622

  2. Death after Taking Medicaments

    PubMed Central

    Girdwood, R. H.

    1974-01-01

    A register of reported adverse reactions, recently made available to major hospitals and medical schools gives an indication of prescribing habits under the N.H.S. in England and Wales. An analysis is made here of the chief medicaments allegedly leading to death. Such data are incomplete because of lack of knowledge of the total use of each drug in the United Kingdom and because reporting of adverse reactions is very incomplete. Nevertheless, data about various groups of drugs do draw attention to some hazards and should encourage more widespread reporting of reactions to drugs and other medicaments. PMID:4817164

  3. Anesthetic Complications and Deaths

    PubMed Central

    Pender, John W.

    1968-01-01

    Anesthesiologists should fully inform patients of the possible complications from anesthesia. For rapport with the patient, with whom they usually have no acquaintance until a day or so before an operative procedure, the anesthesiologist should enlist the help of the internist or surgeon who already has established an atmosphere of trust. The extent of morbidity and minor complications from anesthesia has not been adequately recorded. One out of every 1,000 to 2,000 anesthetized patients dies of complications primarily due to or contributed to by anesthesia. Leading causes of death vary from study to study and from year to year. PMID:5652756

  4. Happiness and Death Distress: Two Separate Factors

    ERIC Educational Resources Information Center

    Abdel-Khalek, Ahmed M.

    2005-01-01

    The aim of the present study was to explore the relationship between happiness and death distress (death anxiety, death depression, and death obsession) in 275 volunteer Kuwaiti undergraduates. They responded to the Oxford Happiness Inventory, the Death Anxiety Scale, the Arabic Scale of Death Anxiety, the Death Depression Scale-Revised, and the…

  5. Sudden infant death syndrome.

    PubMed

    Adams, Stephen M; Ward, Chad E; Garcia, Karla L

    2015-06-01

    Sudden infant death syndrome (SIDS) is the sudden unexpected death of a child younger than one year during sleep that cannot be explained after a postmortem evaluation including autopsy, a thorough history, and scene evaluation. The incidence of SIDS has decreased more than 50% in the past 20 years, largely as a result of the Back to Sleep campaign. The most important risk factors relate to the sleep environment. Prone and side sleeping positions are significantly more dangerous than the supine position. Bed sharing with a parent is strongly correlated with an increased risk of SIDS, especially in infants younger than 12 weeks. Apparent life-threatening events are not a risk factor for SIDS. Parents should place infants on their backs to sleep, should not share a bed, and should avoid exposing the infant to tobacco smoke. Other risk-reducing measures include using a firm crib mattress, breastfeeding, keeping vaccinations up to date, avoiding overheating due to overbundling, avoiding soft bedding, and considering the use of a pacifier during sleep once breastfeeding is established. One consequence of the Back to Sleep campaign is a significant increase in the incidence of occipital flattening. Infants who develop a flat spot should be placed with the head facing alternating directions each time he or she is put to bed. Supervised prone positioning while the infant is awake, avoiding excessive use of carriers, and upright positioning while awake are also recommended. PMID:26034855

  6. PDT: death pathways

    NASA Astrophysics Data System (ADS)

    Kessel, David

    2007-02-01

    Cellular targets of photodynamic therapy include mitochondria, lysosomes, the endoplasmic reticulum (ER) and the plasma membrane. PDT can evoke necrosis, autophagy and apoptosis, or combinations of these, depending on the PDT dose, the site(s) of photodamage and the cellular phenotype. It has been established that loss of viability occurs even when the apoptotic program is inhibited. Studies assessing effects of ER or mitochondrial photodamage, involving loss of Bcl-2 function, indicate that low-dose PDT elicited a rapid autophagic response in L1210 cells. This was attributed to the ability of autophagy to recycle photodamaged organelles, and there was partial protection from loss of viability. This effect was not observed in L1210/Atg7, where autophagy was silenced. At higher PDT doses, apoptotic cells were observed within 60 min in both cell lines, but more so in L1210. The ability of L1210 cells to undergo autophagy did not offer protection from cell death at the higher PDT dose. Previous studies had indicated that autophagy can contribute to cell death, since L1210 cells that do not undergo an initial apoptotic response often contain multiple autophagic vacuoles 24 hr later. With L1210/Atg7, apoptosis alone may account for the loss of viability at an LD 90 PDT dose.

  7. Sudden infant death syndrome

    PubMed Central

    Hunt, Carl E.; Hauck, Fern R.

    2006-01-01

    Sudden infant death syndrome (SIDS) continues to be the most common cause of postneonatal infant death. SIDS is a complex, multifactorial disorder, the cause of which is still not fully understood. However, much is known now about environmental risk factors, some of which are modifiable. These include maternal and antenatal risk factors such as smoking during pregnancy, as well as infant-related risk factors such as non-supine sleeping position and soft bedding. Emerging evidence also substantiates an expanding number of genetic risk factors. Interactions between environmental and genetic risk factors may be of critical importance in determining an infant's actual risk of SIDS. Although no practical way exists to identify which infants will die of SIDS, nor is there a safe and proven prevention strategy even if identification were feasible, reducing exposure to modifiable risk factors has helped to lower the incidence of SIDS. Current challenges include wider dissemination of guidelines to all people who care for infants, dissemination of guidelines in culturally appropriate ways, and surveillance of SIDS trends and other outcomes associated with implementation of these guidelines. PMID:16785462

  8. Stressing mitosis to death.

    PubMed

    Burgess, Andrew; Rasouli, Mina; Rogers, Samuel

    2014-01-01

    The final stage of cell division (mitosis), involves the compaction of the duplicated genome into chromatid pairs. Each pair is captured by microtubules emanating from opposite spindle poles, aligned at the metaphase plate, and then faithfully segregated to form two identical daughter cells. Chromatids that are not correctly attached to the spindle are detected by the constitutively active spindle assembly checkpoint (SAC). Any stress that prevents correct bipolar spindle attachment, blocks the satisfaction of the SAC, and induces a prolonged mitotic arrest, providing the cell time to obtain attachment and complete segregation correctly. Unfortunately, during mitosis repairing damage is not generally possible due to the compaction of DNA into chromosomes, and subsequent suppression of gene transcription and translation. Therefore, in the presence of significant damage cell death is instigated to ensure that genomic stability is maintained. While most stresses lead to an arrest in mitosis, some promote premature mitotic exit, allowing cells to bypass mitotic cell death. This mini-review will focus on the effects and outcomes that common stresses have on mitosis, and how this impacts on the efficacy of mitotic chemotherapies. PMID:24926440

  9. Definitions and implications of death.

    PubMed

    Schlotzhauer, Anna V; Liang, Bryan A

    2002-12-01

    Understanding the legal definition of whole-brain death is imperative for hematologists and oncologists who deal with end-of-life patients on a regular basis. At present, only whole-brain death in which there is no function of the upper brain or brain stem is legally recognized as legal death. Those advocating expansion of the current definition of death to encompass patients with higher brain death and brain-absent anencephalic infants cite increasing the organ pool and decreasing unnecessary treatment and costs as benefits. Those advocating a more narrow definition of death typically fear being misdiagnosed or prefer the traditional cardiopulmonary definition for personal and religious reasons. As medical technology advances, offering new hope to both the critically injured patients who might be potential donors and to those patients in need of donated organs, the definition of death will continue to be a topic of passionate debate. PMID:12512174

  10. Behavior of chickens prior to death from sudden death syndrome.

    PubMed

    Newberry, R C; Gardiner, E E; Hunt, J R

    1987-09-01

    A study was made to determine if chickens dying from sudden death syndrome (SDS) showed any unusual behavioral characteristics during the final 12 h preceding death. Continuous video recordings were made of floor pens of 50 to 120 individually marked male broiler chickens between 3 and 10 wk of age. Behavioral data were obtained from video tapes played back following death of chickens from SDS. Analysis of the video tapes revealed no significant differences between 10 SDS chickens and their matched controls in the frequencies or proportions of time spent in each of 19 different behavioral activities. All SDS chickens exhibited a sudden attack prior to death lasting an average of 53 s and characterized by loss of balance, violent flapping, and strong muscular contractions. There was no evidence that death was preceded by a particular environmental or behavioral event. It was concluded that there were no consistent behavioral symptoms which could be used to identify SDS chickens prior to death. PMID:3684869

  11. [Periodic Repolarization Dynamics--innovative strategies for preventing sudden death].

    PubMed

    Rizas, Konstantinos; Bauer, Axel

    2016-04-01

    Sudden cardiac death (SCD) is the most common single cause of death in the industrialized world. Survivors of acute myocardial infarction (MI) are at increased risk of death. The vast majority of deaths occur in post-MI patients with preserved left ventricular ejection fraction (LVEF) for whom no prophylactic strategies exist. Periodic repolarization dynamics (PRD) is a novel electrocardiographic phenomenon that refers to low frequency (< 0.1 Hz) modulations of cardiac repolarization, most likely linked to sympathetic activity. Increased PRD is a strong and independent predictor of mortality after acute MI. PRD assessment allows to identify a new high risk group of post-MI patients with preserved LVEF (35-50 %) who have the same mortality risk as patients with LVEF ≤ 35 %. Future studies are needed to test the efficacy of preventive strategies in this new high risk group. PMID:27031208

  12. Host-Cell Survival and Death During Chlamydia Infection

    PubMed Central

    Ying, Songmin; Pettengill, Matthew; Ojcius, David M.; Häcker, Georg

    2008-01-01

    Different Chlamydia trachomatis strains are responsible for prevalent bacterial sexually-transmitted disease and represent the leading cause of preventable blindness worldwide. Factors that predispose individuals to disease and mechanisms by which chlamydiae cause inflammation and tissue damage remain unclear. Results from recent studies indicate that prolonged survival and subsequent death of infected cells and their effect on immune effector cells during chlamydial infection may be important in determining the outcome. Survival of infected cells is favored at early times of infection through inhibition of the mitochondrial pathway of apoptosis. Death at later times displays features of both apoptosis and necrosis, but pro-apoptotic caspases are not involved. Most studies on chlamydial modulation of host-cell death until now have been performed in cell lines. The consequences for pathogenesis and the immune response will require animal models of chlamydial infection, preferably mice with targeted deletions of genes that play a role in cell survival and death. PMID:18843378

  13. Death Valley, California

    NASA Technical Reports Server (NTRS)

    1994-01-01

    This is an image of Death Valley, California, centered at 36.629 degrees north latitude, 117.069 degrees west longitude. The image shows Furnace Creek alluvial fan and Furnace Creek Ranch at the far right, and the sand dunes near Stove Pipe Wells at the center. The dark fork-shaped feature between Furnace Creek fan and the dunes is a smooth flood-plain which encloses Cottonball Basin. The bright dots near the center of the image are corner refectors that have been set-up to calibrate the radar as the Shuttle passes overhead with the SIR-C/X-SAR system. The Jet Propulsion Laboratory alternative photo number is P-43883.

  14. Deaths from electricity.

    PubMed

    Brokenshire, B; Cairns, F J; Koelmeyer, T D; Smeeton, W M; Tie, A B

    1984-03-14

    This paper reviews the circumstances of 95 fatalities from electrical injuries. Eighty-nine were accidental, four were suicides and two occurred during autoerotic electrical stimulation. Forty-nine of the accidental fatalities occurred at work, Twenty-eight in the home and twelve in the course of outside recreational activities. In many accidents the circumstances were distressingly similar and included: (1) Contact with overhead distribution lines by a length of conductor such as a yacht mast or crane. (2) Faulty wiring or electrical repairs performed by unqualified people. (3) Badly deteriorated cords, plugs and occasionally appliances. (4) Failure to use isolating transformers when indicated. Deaths involving children are a particular cause of concern. Nine fatalites involved children under the age of five years who contacted inadequately protected wires. PMID:6584755

  15. Role of polyphenols in cell death control.

    PubMed

    Giovannini, Claudio; Masella, Roberta

    2012-05-01

    Dietary consumption of fruit, vegetables, fish, and olive oil has been demonstrated to exert beneficial effects on human health. This finding may be due to the high content of antioxidant compounds including polyphenols. Current evidence strongly supports a contribution of polyphenols to the prevention of several chronic degenerative diseases such as cancer, atherosclerosis and cardiovascular diseases, central nervous system disorders, as well as aging. Apoptosis is a genetically controlled and evolutionarily conserved form of cell death of critical importance for the maintenance of tissue homeostasis in the adult organism. The malfunction of the death machinery may play a primary role in various pathologic processes, leading to proliferative or degenerative diseases. Polyphenols can interact with specific steps and/or proteins regulating the apoptotic process in different ways depending on their concentration, the cell system, the type or stage of the pathological process. Because of their ability to modulate cell death, polyphenols have been proposed as chemopreventive and therapeutic agents. This paper reviews and discusses the last 3-year findings related to the principal molecular mechanisms involved in the control of the balance between apoptosis and cell proliferation exerted by polyphenols. PMID:22584012

  16. Dynamic Neural Processing of Linguistic Cues Related to Death

    PubMed Central

    Ma, Yina; Qin, Jungang; Han, Shihui

    2013-01-01

    Behavioral studies suggest that humans evolve the capacity to cope with anxiety induced by the awareness of death’s inevitability. However, the neurocognitive processes that underlie online death-related thoughts remain unclear. Our recent functional MRI study found that the processing of linguistic cues related to death was characterized by decreased neural activity in human insular cortex. The current study further investigated the time course of neural processing of death-related linguistic cues. We recorded event-related potentials (ERP) to death-related, life-related, negative-valence, and neutral-valence words in a modified Stroop task that required color naming of words. We found that the amplitude of an early frontal/central negativity at 84–120 ms (N1) decreased to death-related words but increased to life-related words relative to neutral-valence words. The N1 effect associated with death-related and life-related words was correlated respectively with individuals’ pessimistic and optimistic attitudes toward life. Death-related words also increased the amplitude of a frontal/central positivity at 124–300 ms (P2) and of a frontal/central positivity at 300–500 ms (P3). However, the P2 and P3 modulations were observed for both death-related and negative-valence words but not for life-related words. The ERP results suggest an early inverse coding of linguistic cues related to life and death, which is followed by negative emotional responses to death-related information. PMID:23840787

  17. A primatological perspective on death.

    PubMed

    Anderson, James R

    2011-05-01

    Some questions that arise from observations of responses to dead and dying individuals by nonhuman primates are discussed, focusing on psychological issues. The phenomenon of transport and care of dead infants is reviewed, along with the consequences of the mother dying for orphaned offspring. It is argued that particular attention should be paid to how the context of a death affects individuals, for example, traumatic accidental or predation-induced death versus peaceful death following illness. Some primates kill others of their own or other species, which raises additional questions about death awareness and empathy. Observations from both the field and captivity can contribute toward a better understanding of the psychological meaning of death for primates. Some aspects of death awareness recognized by developmental psychologists might help guide research efforts in this area. PMID:21432870

  18. An autologous in situ tumor vaccination approach for hepatocellular carcinoma. 2. Tumor-specific immunity and cure after radio-inducible suicide gene therapy and systemic CD40-ligand and Flt3-ligand gene therapy in an orthotopic tumor model.

    PubMed

    Kawashita, Yujo; Deb, Niloy J; Garg, Madhur K; Kabarriti, Rafi; Fan, Zuoheng; Alfieri, Alan A; Roy-Chowdhury, Jayanta; Guha, Chandan

    2014-08-01

    Diffuse hepatocellular carcinoma (HCC) is a lethal disease that radiation therapy (RT) currently has a limited role in treating because of the potential for developing fatal radiation-induced liver disease. However, recently diffuse HCC, "radio-inducible suicide gene therapy" has been shown to enhance local tumor control and residual microscopic disease within the liver for diffuse HCC, by using a combination of chemoactivation and molecular radiosensitization. We have demonstrated that the addition of recombinant adenovirus-expressing human Flt3 ligand (Adeno-Flt3L) after radio-inducible suicide gene therapy induced a Th1-biased, immune response and enhanced tumor control in an ectopic model of HCC. We hypothesized that sequential administration of recombinant adenovirus-expressing CD40L (Adeno-CD40L) could further potentiate the efficacy of our trimodal therapy with RT + HSV-TK + Adeno-Flt3L. We examined our hypothesis in an orthotopic model of diffuse HCC using BNL1ME A.7R.1 (BNL) cells in Balb/c mice. BNL murine hepatoma cells (5 × 10(4)) transfected with an expression vector of HSV-TK under the control of a radiation-inducible promoter were injected intraportally into BALB/cJ mice. Fourteen days after the HCC injection, mice were treated with a 25 Gy dose of radiation to the whole liver, followed by ganciclovir (GCV) treatment and systemic adenoviral cytokine gene therapy (Flt3L or CD40L or both). Untreated mice died in 27 ± 4 days. Radiation therapy alone had a marginal effect on survival (median = 35 ± 7 days) and the addition of HSV-TK/GCV gene therapy improved the median survival to 47 ± 6 days. However, the addition of Adeno-Flt3L to radiation therapy and HSV-TK/GCV therapy significantly (P = 0.0005) increased survival to a median of 63 ± 20 days with 44% (7/16) of the animals still alive 116 days after tumor implantation. The curative effect of Flt3L was completely abolished when using immunodeficient nude mice or mice depleted for CD4, CD8 and

  19. An approach to iatrogenic deaths.

    PubMed

    McGuire, Angela R; DeJoseph, Maura E; Gill, James R

    2016-03-01

    Iatrogenic deaths are a concern for patients, physicians, and public health specialists. Most medicolegal investigation jurisdictions in the United States have the legal authority and mandate to investigate deaths associated with diagnostic/therapeutic procedures. Given the decreasing trends of autopsies performed in U.S. hospitals, forensic pathologists are likely to take on an even greater role in investigating these deaths. This is an overview and forensic pathological approach to fatal complications due to diagnostic and therapeutic medical events. PMID:26820284

  20. Birthday and date of death.

    PubMed Central

    Angermeyer, M C; Kühn, L; Osterwald, P

    1987-01-01

    The relation between birthday and date of death has so far been studied from two different perspectives: birthdays were either conceived of as emotionally invested deadlines motivating people to ward off their death which causes a 'dip' in death rates before their birthday, or they were considered as stressful events leading to an increase of mortality on or after their birthday. Using a collection of biographies of famous people from the whole world and another of well-known Swiss citizens we tested hypotheses derived from these assumptions. Neither the 'death-dip' hypotheses nor the 'birthday stress' hypothesis was supported by our results. PMID:3655631

  1. [Genetics of sudden unexplained death].

    PubMed

    Campuzano, Oscar; Allegue, Catarina; Brugada, Ramon

    2014-03-20

    Sudden unexplained death is defined by death without a conclusive diagnosis after autopsy and it is responsible for a large percentage of sudden deaths. The progressive interaction between genetics and forensics in post-mortem studies has identified inheritable alterations responsible for pathologies associated with arrhythmic sudden death. The genetic diagnosis of the deceased enables the undertaking of preventive measures in family members, many of them asymptomatic but at risk. The implications of this multidisciplinary translational medical approach are complex, requiring the dedication of a specialized team. PMID:24018251

  2. Deaths of amateur scuba divers.

    PubMed

    Obafunwa, J O; Busuttil, A; Purdue, B

    1994-04-01

    Four scuba diving deaths investigated by the Forensic Medicine Unit, University of Edinburgh Medical School, are reported. The pathological investigation of such deaths requires that a detailed history of the events prior to death is obtained and that the site of the accident is fully examined with underwater photographic recording where possible. The diving suits, breathing apparatus and other diving accessories also have to be examined carefully by experts and a complete autopsy with toxicological and histological examination is essential. The causes and mechanisms of death are discussed, as are the importance of special autopsy techniques and investigations. Possible interpretative problems are highlighted. PMID:8028487

  3. "Death-telling" research project.

    PubMed

    McQuay, J E; Schwartz, R; Goldblatt, P C; Giangrasso, V M

    1995-09-01

    An unexpected death is a traumatic event for everyone affected by it, especially family members. The manner in which a family is told that a death has occurred has a profound effect on their grief and bereavement process. The task of the health care professional working with these patients and their families is to assist their healing by being skilled in the "death-telling" process. This article focuses on the project that developed a teaching tool and videotape used to educate individuals about the proper way to inform families of the death of a loved one. PMID:7546520

  4. Death Attitudes among Mid-Life Women.

    ERIC Educational Resources Information Center

    Richardson, Virginia; Sands, Roberta

    1987-01-01

    Examined death attitudes among 74 female college reentry students aged 30 through 49. Found relationships between: (1) developmental factors and death concern, death as interpersonal loss, and death as dimension of time; (2) age and death anticipation; and (3) income and death denial. Results suggest importance of considering both developmental…

  5. History of brain death as death: 1968 to the present.

    PubMed

    De Georgia, Michael A

    2014-08-01

    The concept of brain death was formulated in 1968 in the landmark report A Definition of Irreversible Coma. While brain death has been widely accepted as a determination of death throughout the world, many of the controversies that surround it have not been settled. Some may be rooted in a misconstruction about the history of brain death. The concept evolved as a result of the convergence of several parallel developments in the second half of the 20th century including advances in resuscitation and critical care, research into the underlying physiology of consciousness, and growing concerns about technology, medical futility, and the ethics of end of life care. Organ transplantation also developed in parallel, and though it clearly benefited from a new definition of death, it was not a principal driving force in its creation. Since 1968, the concept of brain death has been extensively analyzed, debated, and reworked. Still there remains much misunderstanding and confusion, especially in the general public. In this comprehensive review, I will trace the evolution of the definition of brain death as death from 1968 to the present, providing background, history and context. PMID:24930367

  6. Expressing death risk as condensed life experience and death intensity.

    PubMed

    Ioannidis, John P A

    2013-08-01

    Some risk exposures, including many medical and surgical procedures, typically carry hazards of death that are difficult to convey and appreciate in absolute terms. I propose presenting the death risk as a condensed life experience (i.e., the equivalent amount of life T that would carry the same cumulative mortality hazard for a person of the same age and sex based on life tables). For example, if the risk of death during an elective 1-hour procedure is 0.01%, and same-age and same-sex people have a 0.01% death risk over 1 month, one can inform the patient that "this procedure carries the same death risk as living 1 month of normal life." Comparative standards from other risky activities or from a person with the same disease at the same stage and same predictive profile could also be used. A complementary metric that may be useful to consider is the death intensity. The death intensity λ is the hazard function that shows the fold-risk estimate of dying compared with the reference person. The death intensity can vary substantially for different phases of the event, operation, or procedure (e.g., intraoperative, early postoperative, late postoperative), and this variability may also be useful to convey. T will vary depending on the time window for which it is computed. I present examples for calculating T and λ using literature data on accidents, ascent to Mount Everest, and medical and surgical procedures. PMID:23579043

  7. Education for Death, or Death Becomes Less a Stranger.

    ERIC Educational Resources Information Center

    Leviton, Dan

    The purpose of this paper is to describe 1.) the Death Education and Suicide Behavior course offered at the University of Maryland; 2.) the comments of the students both before and after the course as a means of determining any effect of the course; and 3.) some insights gained from teaching taboo topics such as human death and sexuality. The…

  8. [Near-death experiences].

    PubMed

    Bonilla, Ernesto

    2011-03-01

    Near-death experiences (NDE) are lucid events that take place when a person is so physically compromised that he would die if its condition does not improve. He is unconscious, without heartbeats and breath, and with a flat-line electroencephalogram. NDE may include some of the following elements: Out of the body experiences or separation of consciousness from the physical body, increase in sensory perception and intense emotions, travel into or through a tunnel, encounter with a brilliant light and mystical beings, deceased relatives or friends, a sense of alteration in time and space, visualization of unworldly realms and a special knowledge, encounter with a barrier or boundary, and a return to the body, either voluntary or involuntary. The fact that children NDE are similar to adult NDE is an evidence that these experiences are real and not due to pre-existing beliefs, cultural influences or previous experiences in the present life. The characteristics of NDE are similar worldwide. No evidence supports the physiological, psychological, neurochemical, and neuroanatomical hypothesis proposed to explain the NDE. Multifactorial models, based on the combination of all of them (brain anoxia or hypoxia, release of serotonin, endorphins and ketamine-like compounds) have also been proposed. Although physiological, psychological, and socio-cultural factors could interact in the NDE, the hypothesis proposed consist essentially in unsupported speculations about what might be happening during the NDE. PMID:21614815

  9. Death: A Part of Life.

    ERIC Educational Resources Information Center

    Otero, George G.; Harris, Zoanne

    This two-part curriculum unit includes 20 slides depicting Days of the Dead in Mexico and the United States. The unit is designed to help middle school students compare customs and practices associated with death throughout the world in a way that promotes understanding of the values and needs that produce and are reinforced by death rituals and…

  10. Child Abuse and Cot Deaths.

    ERIC Educational Resources Information Center

    Newlands, Mary; Emery, John S.

    1991-01-01

    A search was made of confidential health department records in Great Britain for abused children, or children at risk for abuse, with siblings who had died of Sudden Infant Death Syndrome (SIDS). An association was found between child abuse and about 10 percent of deaths of children diagnosed as SIDS. (BRM)

  11. Death Competence: An Ethical Imperative

    ERIC Educational Resources Information Center

    Gamino, Louis A.; Ritter, R. Hal, Jr.

    2012-01-01

    The authors argued that death competence, defined as specialized skill in tolerating and managing clients' problems related to dying, death, and bereavement, is a necessary prerequisite for ethical practice in grief counseling. A selected review of the literature tracing the underpinnings of this concept reveals how a robust construct of death…

  12. Parthanatos, a messenger of death.

    PubMed

    David, Karen Kate; Andrabi, Shaida Ahmad; Dawson, Ted Murray; Dawson, Valina Lynn

    2009-01-01

    Poly-ADP-ribose polymerase-1 (PARP-1)'s roles in the cell span from maintaining life to inducing death. The processes PARP-1 is involved in include DNA repair, DNA transcription, mitosis, and cell death. Of PARP-1's different cellular functions, its role in cell death is of particular interest to designing therapies for diseases. Genetic deletion of PARP-1 revealed that PARP-1 overactivation underlies cell death in models of stroke, diabetes, inflammation and neurodegeneration. Since interfering with PARP-1 mediated cell death will be clinically beneficial, great effort has been invested into understanding mechanisms downstream of PARP-1 overactivation. Recent evidence shows that poly-ADP ribose (PAR) polymer itself can act as a cell death effector downstream of PARP-1. We coined the term parthanatos after Thanatos, the personification of death in Greek mythology, to refer to PAR-mediated cell death. In this review, we will present evidence and questions raised by these recent findings, and summarize the proposed mechanisms by which PARP-1 overactivation kills. It is evident that further understanding of parthanatos opens up new avenues for therapy in ameliorating diseases related to PARP-1 overactivation. PMID:19273119

  13. Death Anxiety and Mental Ability.

    ERIC Educational Resources Information Center

    Templer, Donald I.; Salter, Charles A.

    1979-01-01

    Measures of death anxiety, the Thrustone Interest Inventory, the A-B Scale, and the SAT and ACT aptitude tests, were taken among college students. The implications are discussed in terms of a theoretical five-component biosocial model and its relationship to death anxiety. (Author)

  14. Cell death in mammalian development.

    PubMed

    Penaloza, C; Orlanski, S; Ye, Y; Entezari-Zaher, T; Javdan, M; Zakeri, Z

    2008-01-01

    During embryogenesis there is an exquisite orchestration of cellular division, movement, differentiation, and death. Cell death is one of the most important aspects of organization of the developing embryo, as alteration in timing, level, or pattern of cell death can lead to developmental anomalies. Cell death shapes the embryo and defines the eventual functions of the organs. Cells die using different paths; understanding which path a dying cell takes helps us define the signals that regulate the fate of the cell. Our understanding of cell death in development stems from a number of observations indicating genetic regulation of the death process. With today's increased knowledge of the pathways of cell death and the identification of the genes whose products regulate the pathways we know that, although elimination of some of these gene products has no developmental phenotype, alteration of several others has profound effects. In this review we discuss the types and distributions of cell death seen in developing mammalian embryos as well as the gene products that may regulate the process. PMID:18220829

  15. Death Outlook and Social Issues.

    ERIC Educational Resources Information Center

    Feifel, Herman; Schag, Daniel

    1980-01-01

    Examined the hypothesis that there is a relationship between outlook on death and orientation toward mercy killing, abortion, suicide, and euthanasia. Some relationships between death attitudes and perspectives on the social issues emphasized the need to consider specific circumstances as well as abstract concepts. (Author)

  16. Sudden cardiac death.

    PubMed

    Sra, J; Dhala, A; Blanck, Z; Deshpande, S; Cooley, R; Akhtar, M

    1999-08-01

    SCD continues to be an important cause of death and morbidity. Despite expanding insight into the mechanisms causing SCD, the population at high risk is not being effectively identified. Although there is still much to do in the management phase of SCD (predicting the efficacy of various therapies), recent clinical trials have helped define the relative risks and benefits of therapies in preventing SCD. Trials are underway to determine whether treating other patient populations, including asymptomatic patients after MI, will improve survival rate. The approach to reducing mortality rate will always be multifaceted; primary prevention of coronary artery disease and prompt salvage of jeopardized myocardium are 2 important aspects of this approach. In addition to interventions for MI, such as myocardial revascularization when indicated, simple and easily administered therapies that are likely to remain the most effective prophylactic interventions are aspirin, ACE inhibitors, beta-blockers, and cholesterol-lowering agents. However, the MADIT and AVID data clearly demonstrate a role for ICD therapy in a subgroup of patients who have VT/VF and are at risk of cardiac arrest. Even though the absolute magnitude of benefit associated with ICDs is still to be determined, the AVID study and other recent reports provide convincing evidence that patients who have VT/VF fare better with ICDs than with antiarrhythmic drug therapy. For the high-risk population described in this article, in addition to aggressive anti-ischemic and heart failure therapy, ICDs are now a mainstay of life-saving treatment. Still to be surmounted is the challenge of identifying patients who have nonischemic substrates and of providing them with the appropriate therapy. Guided by genetic studies and new insight into the mechanisms of such problems as congenital long QT syndrome, life-saving and life-enhancing therapies may soon be available for the management of SCD. PMID:10459474

  17. Parthanatos, a messenger of death

    PubMed Central

    David, Karen Kate; Andrabi, Shaida Ahmad; Dawson, Ted Murray; Dawson, Valina Lynn

    2015-01-01

    Poly-ADP-ribose polymerase-1 (PARP-1)'s multiple roles in the cell span from maintaining life to inducing death. The processes PARP-1 is involved in include, but are not limited to DNA repair, DNA transcription, mitosis, and cell death. Of PARP-1's different cellular functions, its active role in cell death is of particular interest to designing therapies for diseases. Genetic deletion of PARP-1 revealed that PARP-1 over activation underlies cell death in experimental models of stroke, diabetes, inflammation and neurodegeneration. Since interfering with PARP-1 mediated cell death will be clinically beneficial, great effort has been invested into designing PARP-1 inhibitors and understanding mechanisms downstream of PARP-1 over activation. PARP-1 overactivation may kill by depleting cellular energy through nicotinamide adenine dinucleotide (NAD+) consumption, and by releasing the cell death effector apoptosis-inducing factor (AIF). Unexpectedly, recent evidence shows that poly-ADP ribose (PAR) polymer itself, and not the consumption of NAD+ is the source of cytotoxicity. Thus, PAR polymer acts as a cell death effector downstream of PARP-1-mediated cell death signaling. We coined the term parthanatos after Thanatos, the personification of death in Greek mythology, to refer to PAR-mediated cell death. In this review, we will summarize the proposed mechanisms by which PARP-1 overactivation kills. We will present evidence for parthanatos, and the questions raised by these recent findings. It is evident that further understanding of parthanatos opens up new avenues for therapy in ameliorating diseases related to PARP-1 over activation. PMID:19273119

  18. Facility Death Review of Maternal and Neonatal Deaths in Bangladesh

    PubMed Central

    Biswas, Animesh; Rahman, Fazlur; Eriksson, Charli; Halim, Abdul; Dalal, Koustuv

    2015-01-01

    Objectives To explore the experiences, acceptance, and effects of conducting facility death review (FDR) of maternal and neonatal deaths and stillbirths at or below the district level in Bangladesh. Methods This was a qualitative study with healthcare providers involved in FDRs. Two districts were studied: Thakurgaon district (a pilot district) and Jamalpur district (randomly selected from three follow-on study districts). Data were collected between January and November 2011. Data were collected from focus group discussions, in-depth interviews, and document review. Hospital administrators, obstetrics and gynecology consultants, and pediatric consultants and nurses employed in the same departments of the respective facilities participated in the study. Content and thematic analyses were performed. Results FDR for maternal and neonatal deaths and stillbirths can be performed in upazila health complexes at sub-district and district hospital levels. Senior staff nurses took responsibility for notifying each death and conducting death reviews with the support of doctors. Doctors reviewed the FDRs to assign causes of death. Review meetings with doctors, nurses, and health managers at the upazila and district levels supported the preparation of remedial action plans based on FDR findings, and interventions were planned accordingly. There were excellent examples of improved quality of care at facilities as a result of FDR. FDR also identified gaps and challenges to overcome in the near future to improve maternal and newborn health. Discussion FDR of maternal and neonatal deaths is feasible in district and upazila health facilities. FDR not only identifies the medical causes of a maternal or neonatal death but also explores remediable gaps and challenges in the facility. FDR creates an enabled environment in the facility to explore medical causes of deaths, including the gaps and challenges that influence mortality. FDRs mobilize health managers at upazila and district

  19. Module Configuration

    DOEpatents

    Oweis, Salah; D'Ussel, Louis; Chagnon, Guy; Zuhowski, Michael; Sack, Tim; Laucournet, Gaullume; Jackson, Edward J.

    2002-06-04

    A stand alone battery module including: (a) a mechanical configuration; (b) a thermal management configuration; (c) an electrical connection configuration; and (d) an electronics configuration. Such a module is fully interchangeable in a battery pack assembly, mechanically, from the thermal management point of view, and electrically. With the same hardware, the module can accommodate different cell sizes and, therefore, can easily have different capacities. The module structure is designed to accommodate the electronics monitoring, protection, and printed wiring assembly boards (PWAs), as well as to allow airflow through the module. A plurality of modules may easily be connected together to form a battery pack. The parts of the module are designed to facilitate their manufacture and assembly.

  20. The intersection of cell death and inflammasome activation.

    PubMed

    Vince, James E; Silke, John

    2016-06-01

    Inflammasomes sense cellular danger to activate the cysteine-aspartic protease caspase-1, which processes precursor interleukin-1β (IL-1β) and IL-18 into their mature bioactive fragments. In addition, activated caspase-1 or the related inflammatory caspase, caspase-11, can cleave gasdermin D to induce a lytic cell death, termed pyroptosis. The intertwining of IL-1β activation and cell death is further highlighted by research showing that the extrinsic apoptotic caspase, caspase-8, may, like caspase-1, directly process IL-1β, activate the NLRP3 inflammasome itself, or bind to inflammasome complexes to induce apoptotic cell death. Similarly, RIPK3- and MLKL-dependent necroptotic signaling can activate the NLRP3 inflammasome to drive IL-1β inflammatory responses in vivo. Here, we review the mechanisms by which cell death signaling activates inflammasomes to initiate IL-1β-driven inflammation, and highlight the clinical relevance of these findings to heritable autoinflammatory diseases. We also discuss whether the act of cell death can be separated from IL-1β secretion and evaluate studies suggesting that several cell death regulatory proteins can directly interact with, and modulate the function of, inflammasome and IL-1β containing protein complexes. PMID:27066895

  1. Sudden death in eating disorders

    PubMed Central

    Jáuregui-Garrido, Beatriz; Jáuregui-Lobera, Ignacio

    2012-01-01

    Eating disorders are usually associated with an increased risk of premature death with a wide range of rates and causes of mortality. “Sudden death” has been defined as the abrupt and unexpected occurrence of fatality for which no satisfactory explanation of the cause can be ascertained. In many cases of sudden death, autopsies do not clarify the main cause. Cardiovascular complications are usually involved in these deaths. The purpose of this review was to report an update of the existing literature data on the main findings with respect to sudden death in eating disorders by means of a search conducted in PubMed. The most relevant conclusion of this review seems to be that the main causes of sudden death in eating disorders are those related to cardiovascular complications. The predictive value of the increased QT interval dispersion as a marker of sudden acute ventricular arrhythmia and death has been demonstrated. Eating disorder patients with severe cardiovascular symptoms should be hospitalized. In general, with respect to sudden death in eating disorders, some findings (eg, long-term eating disorders, chronic hypokalemia, chronically low plasma albumin, and QT intervals >600 milliseconds) must be taken into account, and it must be highlighted that during refeeding, the adverse effects of hypophosphatemia include cardiac failure. Monitoring vital signs and performing electrocardiograms and serial measurements of plasma potassium are relevant during the treatment of eating disorder patients. PMID:22393299

  2. Psychosocial Aspects of the Sudden Infant Death Syndrome ("Cot Death").

    ERIC Educational Resources Information Center

    Bluglass, Kerry

    1981-01-01

    Reviews literature on reactions of parents and siblings to Sudden Infant Death Syndrome (SIDS). The prospects for prolonged, adverse reactions are considered, and professional concerns regarding abnormal adaptation are noted. (Author/DB)

  3. [The death of Ignatius Loyola].

    PubMed

    Huguier, Michel; Lacaine, Francois

    2011-12-01

    A recent examination of a bilioportal fistula led us to suspect a link between this case and the death of Ignatius of Loyola. Realdo Colombo, professor of anatomy, eviscerated Ignatius prior to his embalming In his book De re anatomica, published in 1559, he wrote that he extracted stones from the portal vein of the venerable Ignatius. Before his death, Ignatius suffered from epigastric pain and fever (Monumenta historica societatis Jesu). Colombo latin text is difficult to interpret and the data are meager. Other possible causes of Ignatius' death include gastroduodenal ulcer, tuberculosis and hyperparathyroidism, but despite of rarity bilioportal fistula is the best guess. PMID:22930868

  4. Cell death proteomics database: consolidating proteomics data on cell death.

    PubMed

    Arntzen, Magnus Ø; Bull, Vibeke H; Thiede, Bernd

    2013-05-01

    Programmed cell death is a ubiquitous process of utmost importance for the development and maintenance of multicellular organisms. More than 10 different types of programmed cell death forms have been discovered. Several proteomics analyses have been performed to gain insight in proteins involved in the different forms of programmed cell death. To consolidate these studies, we have developed the cell death proteomics (CDP) database, which comprehends data from apoptosis, autophagy, cytotoxic granule-mediated cell death, excitotoxicity, mitotic catastrophe, paraptosis, pyroptosis, and Wallerian degeneration. The CDP database is available as a web-based database to compare protein identifications and quantitative information across different experimental setups. The proteomics data of 73 publications were integrated and unified with protein annotations from UniProt-KB and gene ontology (GO). Currently, more than 6,500 records of more than 3,700 proteins are included in the CDP. Comparing apoptosis and autophagy using overrepresentation analysis of GO terms, the majority of enriched processes were found in both, but also some clear differences were perceived. Furthermore, the analysis revealed differences and similarities of the proteome between autophagosomal and overall autophagy. The CDP database represents a useful tool to consolidate data from proteome analyses of programmed cell death and is available at http://celldeathproteomics.uio.no. PMID:23537399

  5. KEAP the balance between life and death

    PubMed Central

    Cazanave, Sophie C; Sanyal, Arun J

    2015-01-01

    Hepatocyte apoptosis in association with oxidative stress represent key pathogenic factors involved in tumor development in patients with non-alcoholic fatty liver disease (NAFLD). In our recent study, we established that cellular degradation of Kelch-like ECH-associated protein 1 (KEAP1) through sequestrosome (SQSTM)1/p62-dependent autophagy activates c-Jun NH2 terminal kinase (JNK), upregulates expression of Bcl-2–interacting mediator (BIM) and p53 upregulated modulator of apoptosis (PUMA), and contributes to hepatocyte apoptosis induced by saturated free fatty acids. These findings raise the possibility that dysregulation of KEAP1 may contribute to liver cell death and tumorigenesis during chronic inflammatory liver disease. PMID:27308418

  6. Child Deaths in New Jersey: Social Characteristics.

    ERIC Educational Resources Information Center

    Crowley, Charles J.

    This report discusses trends in the causes of child deaths in New Jersey in recent years and closely examines child deaths in the state in 1974. Demographic data on child deaths are reported with an emphasis on types of deaths in which neglect or nonaccidental injury are likely to have been a factor. Death certificate data were obtained from the…

  7. 32 CFR 700.815 - Deaths.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 5 2010-07-01 2010-07-01 false Deaths. 700.815 Section 700.815 National Defense... § 700.815 Deaths. The commanding officer, in the event of the death of any person within his or her command, shall ensure that the cause of death and the circumstances under which death occurred...

  8. 38 CFR 3.211 - Death.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Death. 3.211 Section 3..., Compensation, and Dependency and Indemnity Compensation Evidence Requirements § 3.211 Death. Death should be... community where death occurred. (2) A copy of a coroner's report of death or a verdict of a coroner's...

  9. 38 CFR 3.211 - Death.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Death. 3.211 Section 3..., Compensation, and Dependency and Indemnity Compensation Evidence Requirements § 3.211 Death. Death should be... community where death occurred. (2) A copy of a coroner's report of death or a verdict of a coroner's...

  10. 32 CFR 700.815 - Deaths.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 5 2014-07-01 2014-07-01 false Deaths. 700.815 Section 700.815 National Defense... § 700.815 Deaths. The commanding officer, in the event of the death of any person within his or her command, shall ensure that the cause of death and the circumstances under which death occurred...

  11. 32 CFR 700.815 - Deaths.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 5 2011-07-01 2011-07-01 false Deaths. 700.815 Section 700.815 National Defense... § 700.815 Deaths. The commanding officer, in the event of the death of any person within his or her command, shall ensure that the cause of death and the circumstances under which death occurred...

  12. 32 CFR 700.815 - Deaths.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 5 2012-07-01 2012-07-01 false Deaths. 700.815 Section 700.815 National Defense... § 700.815 Deaths. The commanding officer, in the event of the death of any person within his or her command, shall ensure that the cause of death and the circumstances under which death occurred...

  13. 32 CFR 700.815 - Deaths.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 5 2013-07-01 2013-07-01 false Deaths. 700.815 Section 700.815 National Defense... § 700.815 Deaths. The commanding officer, in the event of the death of any person within his or her command, shall ensure that the cause of death and the circumstances under which death occurred...

  14. 38 CFR 3.211 - Death.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Death. 3.211 Section 3..., Compensation, and Dependency and Indemnity Compensation Evidence Requirements § 3.211 Death. Death should be... community where death occurred. (2) A copy of a coroner's report of death or a verdict of a coroner's...

  15. 38 CFR 3.211 - Death.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Death. 3.211 Section 3..., Compensation, and Dependency and Indemnity Compensation Evidence Requirements § 3.211 Death. Death should be... community where death occurred. (2) A copy of a coroner's report of death or a verdict of a coroner's...

  16. 38 CFR 3.211 - Death.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Death. 3.211 Section 3..., Compensation, and Dependency and Indemnity Compensation Evidence Requirements § 3.211 Death. Death should be... community where death occurred. (2) A copy of a coroner's report of death or a verdict of a coroner's...

  17. Brain death: the Asian perspective.

    PubMed

    Chua, Hoe Chin; Kwek, Tong Kiat; Morihara, Hirofumi; Gao, Daiquan

    2015-04-01

    Asia is the largest and most populous continent in the world with people from many diverse ethnic groups, religions and government systems. The authors surveyed 14 countries accounting for the majority of Asia's population and found that, although the concept of brain death is widely accepted, there is wide variability in the criteria for certification. Although most Asian countries have adopted the "whole-brain" concept of brain death, most countries with past colonial links to the United Kingdom follow the UK "brainstem" concept of brain death. Despite this difference, most countries require only neurologic testing of irreversible coma and absent brainstem reflexes as criteria for certification of brain death. Variability exists in the number of personnel required, qualifications of certifying doctors, need for repeat examination, minimum time interval between examinations, and requirement for and choice of confirmatory tests. PMID:25839724

  18. Death among children and adolescents

    MedlinePlus

    ... and genetic conditions that were present at birth Homicide 5 to 9 years: Accidents (unintentional injuries) Cancer ... 15 to 24 years Accidents (unintentional injuries) Suicide Homicide There are almost twice as many deaths in ...

  19. Life, Death, and Second Chances

    MedlinePlus

    ... Bar Home Current Issue Past Issues Special Section Life, Death, and Second Chances Past Issues / Fall 2007 ... that she was beginning to fear for her life. Was there any hope at all? Dr. Richard ...

  20. Faith healers, myths and deaths.

    PubMed

    Wasti, Harihar; Kanchan, Tanuj; Acharya, Jenash

    2015-09-01

    Science and myth have been closely linked and argued upon by philosophers, educationalists, scientists, enthusiasts and the general public. Faith healing, when added as an adjuvant or alternative aid to medical science, will not necessarily be confined to mere arguments and debates but may also give rise to series of complications, medical emergencies and even result in death. We present an unusual case where reliance on faith healing led to the death of a young man. PMID:25872779

  1. Brain death and organ donation.

    PubMed

    Lovasik, D

    2000-12-01

    Critical care nurses are essential team members during the process of determining brain death and preparing for organ donation. Using their knowledge of the criteria for brain death, they care for the dying patient, support the grieving family, and participate in the consent process for organ donation. Nurses make a critical difference in saving the lives of others through the gift of life. PMID:11855256

  2. Treating the condemned to death.

    PubMed

    Sargent, D A

    1986-12-01

    Psychiatrists should refrain from treating mentally ill prisoners on death row in order to restore their "competency to be executed." Such "treatment" renders them double agents, in the service of the state as well as the prisoner. Participation in an act that will bring about a prisoner's death is expressly forbidden by the AMA Code of Ethics. It recalls the behavior of Nazi physicians, who used their professional skills not to heal but to kill. PMID:3804727

  3. Poisoning deaths in married women.

    PubMed

    Kumar, Virendra

    2004-02-01

    Unnatural deaths of married women amongst the total female deaths have been an increasing trend in Indian society during the recent past years. These unnatural deaths may be suicide, homicide or even accidents. But these suicides and homicides are currently more commonly associated with the dowry disputes. In India, dowries are a continuing series of gifts endowed before and after the marriage. When dowry expectations are not met, the young bride may be killed or compelled to commit suicide, either by burning, poisoning or by some other means. Here, in the study, the main objective is to present the different epidemiological and medicolegal aspects of poisoning deaths in the married women. In a cohort of 200 married female deaths, 35 (18%) were poisoning deaths and these were analyzed from both epidemiological and medicolegal aspects. In this series, most of the women consumed organophosphorus compound and died within 10 days. The majority of the affected wives due to dowry problems were below 35 years of age. Most incidents occurred either during morning hour or during daytime. PMID:15261005

  4. Assessment of death attitudes: an empirical approach.

    PubMed

    Patterson, K S; Gates, L J; Faulkender, P J

    1987-09-01

    The Threat Index and the Death Anxiety Scale were administered to 228 subjects. Based on the high/low criterion scores, 105 subjects were assigned to the following four groups: (a) high death threat/high death anxiety, (b) high death threat/low death anxiety, (c) low death threat/high death anxiety, and (d) low death threat/low death anxiety. During the experimental phase of the study, subjects viewed a filmstrip on death rituals in various cultures. A recall test was then administered. Results indicated no significant group differences on recall performance. Initial no-show rates for the second part of the experiment were observed in the four groups reflecting a significant negative relationship between death anxiety and initial no-show rates. The possibility of defensive responding on the Death Anxiety Scale was suggested. PMID:3681768

  5. The Concept of Death and Loss Education.

    ERIC Educational Resources Information Center

    Wrenn, Robert L.

    1982-01-01

    Presents an overview of topics and concepts appropriate for a secondary course on death and dying including stress, environments within which death occurs, those models explaining the emotional impact of death, treatment of dying patients, and concepts for students. (DC)

  6. Happiness and death distress: two separate factors.

    PubMed

    Abdel-Khalek, Ahmed M

    2005-12-01

    The aim of the present study was to explore the relationship between happiness and death distress (death anxiety, death depression, and death obsession) in 275 volunteer Kuwaiti undergraduates. They responded to the Oxford Happiness Inventory, the Death Anxiety Scale, the Arabic Scale of Death Anxiety, the Death Depression Scale-Revised, and the Death Obsession Scale. Gender differences were significant on all 5 scales, with women showing a lower mean score of happiness and a higher mean score for the death distress. All the correlations between happiness and the death distress scales were non-significant except one pertaining to happiness and death depression (negative) in women. Two oblique factors were extracted: death distress and happiness. Therefore, these constructs represent 2 distinct and independent factors. PMID:16265799

  7. An accessible method for teaching doctors about death certification.

    PubMed

    Walker, Sue; Rampatige, Rasika; Wainiqolo, Iris; Aumua, Audrey

    2012-01-01

    The World Health Organization (WHO) recommends that data on mortality in its member countries are collected utilising the Medical Certificate of Cause of Death published in the instruction volume of the ICD-10. However, investment in health information processes necessary to promote the use of this certificate and improve mortality information is lacking in many countries. An appeal for support to make improvements has been launched through the Health Metrics Network's MOVE-IT strategy (Monitoring of Vital Events Information Technology) (WHO 2011). Despite this international spotlight on the need for capture of mortality data and in the use of the ICD-10 to code the data reported on such certificates, there is little cohesion in the way that certifiers of deaths receive instruction in how to complete the death certificate, which is the main source document for mortality statistics. Complete and accurate documentation of the immediate, underlying and contributory causes of death of the decedent on the death certificate is a requirement to produce standardised statistical information and to the ability to produce cause-specific mortality statistics that can be compared between populations and across time. This paper reports on a research project conducted to determine the efficacy and accessibility of the certification module of the WHO's newly-developed web based training tool for coders and certifiers of deaths. Involving a population of medical students from the Fiji School of Medicine and a pre- and post-research design, the study entailed completion of death certificates based on vignettes before and after access to the training tool. The ability of the participants to complete the death certificates and analysis of the completeness and specificity of the ICD-10 coding of the reported causes of death were used to measure the effect of the students' learning from the training tool. The quality of death certificate completion was assessed using a Quality Index

  8. Exploring Children's Understanding of Death: Through Drawings and the Death Concept Questionnaire

    ERIC Educational Resources Information Center

    Bonoti, Fotini; Leondari, Angeliki; Mastora, Adelais

    2013-01-01

    To investigate whether children's understanding of the concept of death varies as a function of death experience and age, 52 children aged 7, 9, and 11 years (26 had a personal death experience), drew a picture reflecting the meaning of the word death and completed the Death Concept Questionnaire for examination of Human and Animal Death. The…

  9. Therapeutic approaches to preventing cell death in Huntington disease

    PubMed Central

    Kaplan, Anna; Stockwell, Brent R.

    2012-01-01

    Neurodegenerative diseases affect the lives of millions of patients and their families. Due to the complexity of these diseases and our limited understanding of their pathogenesis, the design of therapeutic agents that can effectively treat these diseases has been challenging. Huntington disease (HD) is one of several neurological disorders with few therapeutic options. HD, like numerous other neurodegenerative diseases, involves extensive neuronal cell loss. One potential strategy to combat HD and other neurodegenerative disorders is to intervene in the execution of neuronal cell death. Inhibiting neuronal cell death pathways may slow the development of neurodegeneration. However, discovering small molecule inhibitors of neuronal cell death remains a significant challenge. Here, we review candidate therapeutic targets controlling cell death mechanisms that have been the focus of research in HD, as well as an emerging strategy that has been applied to developing small molecule inhibitors—fragment-based drug discovery (FBDD). FBDD has been successfully used in both industry and academia to identify selective and potent small molecule inhibitors, with a focus on challenging proteins that are not amenable to traditional high-throughput screening approaches. FBDD has been used to generate potent leads, pre-clinical candidates, and has led to the development of an FDA approved drug. This approach can be valuable for identifying modulators of cell-death-regulating proteins; such compounds may prove to be the key to halting the progression of HD and other neurodegenerative disorders. PMID:22967354

  10. Therapeutic approaches to preventing cell death in Huntington disease.

    PubMed

    Kaplan, Anna; Stockwell, Brent R

    2012-12-01

    Neurodegenerative diseases affect the lives of millions of patients and their families. Due to the complexity of these diseases and our limited understanding of their pathogenesis, the design of therapeutic agents that can effectively treat these diseases has been challenging. Huntington disease (HD) is one of several neurological disorders with few therapeutic options. HD, like numerous other neurodegenerative diseases, involves extensive neuronal cell loss. One potential strategy to combat HD and other neurodegenerative disorders is to intervene in the execution of neuronal cell death. Inhibiting neuronal cell death pathways may slow the development of neurodegeneration. However, discovering small molecule inhibitors of neuronal cell death remains a significant challenge. Here, we review candidate therapeutic targets controlling cell death mechanisms that have been the focus of research in HD, as well as an emerging strategy that has been applied to developing small molecule inhibitors-fragment-based drug discovery (FBDD). FBDD has been successfully used in both industry and academia to identify selective and potent small molecule inhibitors, with a focus on challenging proteins that are not amenable to traditional high-throughput screening approaches. FBDD has been used to generate potent leads, pre-clinical candidates, and has led to the development of an FDA approved drug. This approach can be valuable for identifying modulators of cell-death-regulating proteins; such compounds may prove to be the key to halting the progression of HD and other neurodegenerative disorders. PMID:22967354

  11. Life Experience with Death: Relation to Death Attitudes and to the Use of Death-Related Memories

    ERIC Educational Resources Information Center

    Bluck, Susan; Dirk, Judith; Mackay, Michael M.; Hux, Ashley

    2008-01-01

    The study examines the relation of death experience to death attitudes and to autobiographical memory use. Participants (N = 52) completed standard death attitude measures and wrote narratives about a death-related autobiographical memory and (for comparison) a memory of a low point. Self-ratings of the memory narratives were used to assess their…

  12. Completing Death Certificates from an EMR: Analysis of a Novel Public-Private Partnership.

    PubMed

    Tripp, Jacob S; Duncan, Jeffrey D; Finch, Leisa; Huff, Stanley M

    2015-01-01

    With the objective of increasing electronic death registration, Intermountain Healthcare and the Utah Office of Vital Records and Statistics have developed a system enabling death certification from within Intermountain's electronic medical record (EMR), consisting of an EMR module and an HL7 interface. Comparison of post-intervention death certification at Intermountain Healthcare against a baseline study found a slight increase in the percentage of deaths certified electronically (73% pre vs. 77% post). Analysis of deaths certified using the EMR-module found that they were completed significantly sooner than those certified on paper or using the state's web-based electronic death registration system (EDRS) (Mean time: Paper = 114.72 hours, EDRS = 81.84 hours, EMR = 43.92 hours; p < 0.0001). EMR-certified deaths also contained significantly more causes of deaths than either alternative method (Mean number of causes: Paper = 3.9 causes, EDRS = 4.0 causes, EMR = 5.5 causes; p < 0.0001). PMID:26958261

  13. Completing Death Certificates from an EMR: Analysis of a Novel Public-Private Partnership

    PubMed Central

    Tripp, Jacob S.; Duncan, Jeffrey D.; Finch, Leisa; Huff, Stanley M.

    2015-01-01

    With the objective of increasing electronic death registration, Intermountain Healthcare and the Utah Office of Vital Records and Statistics have developed a system enabling death certification from within Intermountain’s electronic medical record (EMR), consisting of an EMR module and an HL7 interface. Comparison of post-intervention death certification at Intermountain Healthcare against a baseline study found a slight increase in the percentage of deaths certified electronically (73% pre vs. 77% post). Analysis of deaths certified using the EMR-module found that they were completed significantly sooner than those certified on paper or using the state’s web-based electronic death registration system (EDRS) (Mean time: Paper = 114.72 hours, EDRS = 81.84 hours, EMR = 43.92 hours; p < 0.0001). EMR-certified deaths also contained significantly more causes of deaths than either alternative method (Mean number of causes: Paper = 3.9 causes, EDRS = 4.0 causes, EMR = 5.5 causes; p < 0.0001). PMID:26958261

  14. Allosteric modulation of caspases.

    PubMed

    Häcker, Hans-Georg; Sisay, Mihiret Tekeste; Gütschow, Michael

    2011-11-01

    Caspases are proteolytic enzymes mainly involved in the induction and execution phases of apoptosis. This type of programmed cell death is an essential regulatory process required to maintain the integrity and homeostasis of multicellular organisms. Inappropriate apoptosis is attributed a key role in many human diseases, including neurodegenerative disorders, ischemic damage, autoimmune diseases and cancer. Allosteric modulation of the function of a protein occurs when the regulatory trigger, such as the binding of a small effector or inhibitor molecule, takes place some distance from the protein's active site. In recent years, several caspases have been identified that possess allosteric sites and binding of small molecule to these sites resulted in the modulation of enzyme activities. Regulation of caspase activity by small molecule allosteric modulators is believed to be of great therapeutic importance. In this review we give brief highlights on recent developments in identifying and characterizing natural and synthetic allosteric inhibitors as well as activators of caspases and discuss their potential in drug discovery and protein engineering. PMID:21807025

  15. Cell Death in Genome Evolution

    PubMed Central

    Teng, Xinchen; Hardwick, J. Marie

    2015-01-01

    Inappropriate survival of abnormal cells underlies tumorigenesis. Most discoveries about programmed cell death have come from studying model organisms. Revisiting the experimental contexts that inspired these discoveries helps explain confounding biases that inevitably accompany such discoveries. Amending early biases has added a newcomer to the collection of cell death models. Analysis of gene-dependent death in yeast revealed the surprising influence of single gene mutations on subsequent eukaryotic genome evolution. Similar events may influence the selection for mutations during early tumorigenesis. The possibility that an early random mutation might drive the selection for a cancer driver mutation is conceivable but difficult to demonstrate. This was tested in yeast, revealing that mutation of almost any gene appears to specify the selection for a new second mutation. Some human tumors contain pairs of mutant genes homologous to co-occurring mutant genes in yeast. Here we consider how yeast again provide novel insights into tumorigenesis. PMID:25725369

  16. Experiencing death: an insider's perspective.

    PubMed

    Paulson, Steve; Fenwick, Peter; Neal, Mary; Nelson, Kevin; Parnia, Sam

    2014-11-01

    For millennia, human beings have wondered what happens after death. What is the first-person experience of dying and being brought back to life? Technological advances in resuscitation science have now added an intriguing new chapter to the literature of out-of-body or near-death experiences by eliciting detailed and vivid accounts of those who have approached the threshold of death. Steve Paulson, executive producer and host of To the Best of Our Knowledge, moderated a discussion that included neurologist Kevin Nelson, neuropsychiatrist Peter Fenwick, emergency medicine expert Sam Parnia, and orthopedic surgeon and drowning survivor Mary Neal; they share some remarkable stories and discuss how they analyze such experiences in light of their own backgrounds and training. The following is an edited transcript of the discussion from December 11, 2013, 7:00-8:30 PM, at the New York Academy of Sciences in New York City. PMID:25059901

  17. Autophagy, cell death, and cancer

    PubMed Central

    Lin, Lin; Baehrecke, Eric H

    2015-01-01

    Autophagy is an evolutionarily conserved intracellular catabolic process that is used by all cells to degrade dysfunctional or unnecessary cytoplasmic components through delivery to the lysosome. Increasing evidence reveals that autophagic dysfunction is associated with human diseases, such as cancer. Paradoxically, although autophagy is well recognized as a cell survival process that promotes tumor development, it can also participate in a caspase-independent form of programmed cell death. Induction of autophagic cell death by some anticancer agents highlights the potential of this process as a cancer treatment modality. Here, we review our current understanding of the molecular mechanism of autophagy and the potential roles of autophagy in cell death, cancer development, and cancer treatment. PMID:27308466

  18. Sudden death of effective entanglement

    SciTech Connect

    Roszak, K.; Horodecki, P.; Horodecki, R.

    2010-04-15

    Sudden death of entanglement is a well-known effect resulting from the finite volume of separable states. We study the case when the observer has a limited measurement capability and analyze the effective entanglement (i.e., entanglement minimized over the output data). We show that in the well-defined system of two quantum dots monitored by single-electron transistors, one may observe a sudden death of effective entanglement when real, physical entanglement is still alive. For certain measurement setups, this occurs even for initial states for which sudden death of physical entanglement is not possible at all. The principles of the analysis may be applied to other analogous scenarios, such as estimation of the parameters arising from quantum process tomography.

  19. Deaths of teenagers in car crashes: a child death review.

    PubMed

    Jones, Sarah J; Heatman, Beverley

    2016-08-01

    MVCs are a leading cause of death and disability for teenagers. In Wales, a child death review process has been established to carry out thematic reviews of deaths; this approach is believed to highlight opportunities for prevention that individual case review could not. Cases were 13-year-old to 17-year-old Welsh residents who died as car drivers or passengers between 1 January 2006 and 31 December 2010. An expert panel was convened to review these cases. 28 MVCs occurred and 34 13-17 year olds died; 24 males, 10 females. 51 vehicles were involved; 23 driven by 17-year-old to 19-year-old males. 19 of the 28 MVCs occurred between 21:00 and 05:00. The risk factors identified were consistent with global research on MVC deaths and injuries to teenagers. However, there is a lack of effective interventions to tackle these in the UK. It is recommended that the implementation of Graduated Driver Licensing is considered. PMID:26251467

  20. Psychiatry and the death penalty.

    PubMed Central

    Kastrup, M

    1988-01-01

    Mentally ill people are not to be judged by the same rules as the mentally fit. Prisoners evaluated medically unfit for execution must undergo psychiatric treatment until their mental health is restored. Psychiatrists are placed in an ethical dilemma when asked to judge the mental health of prisoners on death row. A high prevalence of psychiatric and neurological disorders are reported on death row. Health professionals have an important role in implementing codes of ethics prohibiting any involvement in the execution process. Resolutions have already been passed by several associations including the World Medical Association, the American Psychiatric Association and Nordic medical associations. PMID:3236345

  1. Early Childhood Injury Deaths in Washington State.

    ERIC Educational Resources Information Center

    Starzyk, Patricia M.

    This paper discusses data on the deaths of children aged 1-4 years in Washington State. A two-fold approach was used in the analysis. First, Washington State death certificate data for 1979-85 were used to characterize the deaths and identify hazardous situations. Second, death certificates were linked to birth certificates of children born in…

  2. Can Suicide Be a Good Death?

    ERIC Educational Resources Information Center

    Lester, David

    2006-01-01

    The issue of whether suicide can be a good death was separated into two different questions: (1) can suicide be an appropriate death, and (2) can suicide be a rational death? Several definitions of an "appropriate" death were proposed, and suicide was seen as potentially appropriate. Similarly, several criteria for rationality were proposed and…

  3. 22 CFR 192.51 - Death benefit.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Death benefit. 192.51 Section 192.51 Foreign... or Death § 192.51 Death benefit. (a) The Secretary of State or Agency Head may provide for payment, by the employing agency, of a death benefit to the surviving dependents of any eligible...

  4. 38 CFR 21.7280 - Death benefit.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Death benefit. 21.7280... Bill-Active Duty) Approval of Courses § 21.7280 Death benefit. (a) Overview. VA will pay a death benefit under 38 U.S.C. ch. 30 when an individual's death meets the criteria of this section;...

  5. 38 CFR 3.460 - Death pension.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Death pension. 3.460..., Compensation, and Dependency and Indemnity Compensation Apportionments § 3.460 Death pension. Death pension... individual case in accordance with § 3.451. (b) Section 306 and old-law death pension. Appointment...

  6. Death Perception in People with Suicidal Tendencies.

    ERIC Educational Resources Information Center

    George, Veronique; Dussaucy, Edith

    The perception of death gradually develops in a child's mind, reaching maturity at about 8 or 9 years of age. A mature death concept usually means a definition which includes the perception of death as a natural process, its finality, its irreversibility, and its universality. A study was undertaken to improve knowledge about the death concept.…

  7. Multidimensional Treatment of Fear of Death.

    ERIC Educational Resources Information Center

    Hoelter, Jon W.

    1979-01-01

    Presents a multidimensional conception of fear of death and provides subscales for measuring suggested dimensions (fear of the dying process, of the dead, of being destroyed, for significant others, of the unknown, of conscious death, for body after death, and of premature death). Evidence for construct validity is provided. (Author/BEF)

  8. 38 CFR 21.7280 - Death benefit.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2013-07-01 2013-07-01 false Death benefit. 21.7280... Bill-Active Duty) Approval of Courses § 21.7280 Death benefit. (a) Overview. VA will pay a death benefit under 38 U.S.C. ch. 30 when an individual's death meets the criteria of this section;...

  9. 38 CFR 3.460 - Death pension.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Death pension. 3.460..., Compensation, and Dependency and Indemnity Compensation Apportionments § 3.460 Death pension. Death pension... individual case in accordance with § 3.451. (b) Section 306 and old-law death pension. Appointment...

  10. 22 CFR 192.51 - Death benefit.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Death benefit. 192.51 Section 192.51 Foreign... or Death § 192.51 Death benefit. (a) The Secretary of State or Agency Head may provide for payment, by the employing agency, of a death benefit to the surviving dependents of any eligible...

  11. 22 CFR 192.51 - Death benefit.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Death benefit. 192.51 Section 192.51 Foreign... or Death § 192.51 Death benefit. (a) The Secretary of State or Agency Head may provide for payment, by the employing agency, of a death benefit to the surviving dependents of any eligible...

  12. 38 CFR 3.460 - Death pension.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Death pension. 3.460..., Compensation, and Dependency and Indemnity Compensation Apportionments § 3.460 Death pension. Death pension... individual case in accordance with § 3.451. (b) Section 306 and old-law death pension. Appointment...

  13. 38 CFR 21.7280 - Death benefit.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2011-07-01 2011-07-01 false Death benefit. 21.7280... Bill-Active Duty) Approval of Courses § 21.7280 Death benefit. (a) Overview. VA will pay a death benefit under 38 U.S.C. ch. 30 when an individual's death meets the criteria of this section;...

  14. 38 CFR 21.7280 - Death benefit.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2014-07-01 2014-07-01 false Death benefit. 21.7280... Bill-Active Duty) Approval of Courses § 21.7280 Death benefit. (a) Overview. VA will pay a death benefit under 38 U.S.C. ch. 30 when an individual's death meets the criteria of this section;...

  15. 38 CFR 21.7280 - Death benefit.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2012-07-01 2012-07-01 false Death benefit. 21.7280... Bill-Active Duty) Approval of Courses § 21.7280 Death benefit. (a) Overview. VA will pay a death benefit under 38 U.S.C. ch. 30 when an individual's death meets the criteria of this section;...

  16. 38 CFR 3.460 - Death pension.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Death pension. 3.460..., Compensation, and Dependency and Indemnity Compensation Apportionments § 3.460 Death pension. Death pension... individual case in accordance with § 3.451. (b) Section 306 and old-law death pension. Appointment...

  17. 22 CFR 192.51 - Death benefit.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Death benefit. 192.51 Section 192.51 Foreign... or Death § 192.51 Death benefit. (a) The Secretary of State or Agency Head may provide for payment, by the employing agency, of a death benefit to the surviving dependents of any eligible...

  18. 22 CFR 192.51 - Death benefit.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Death benefit. 192.51 Section 192.51 Foreign... or Death § 192.51 Death benefit. (a) The Secretary of State or Agency Head may provide for payment, by the employing agency, of a death benefit to the surviving dependents of any eligible...

  19. 38 CFR 3.460 - Death pension.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Death pension. 3.460..., Compensation, and Dependency and Indemnity Compensation Apportionments § 3.460 Death pension. Death pension... individual case in accordance with § 3.451. (b) Section 306 and old-law death pension. Appointment...

  20. [The Sudden Infant Death Syndrome.

    ERIC Educational Resources Information Center

    Florida's Health, 1976

    1976-01-01

    This collection of articles on the Sudden Infant Death Syndrome (SIDS), drawn from a southeastern regional symposium on the subject, summarizes much of what is known about the occurrence of SIDS, including current information about its causes. The background of state action in Florida is reviewed, with emphasis on the need for increased public and…

  1. Ordinal Position and Death Concerns.

    ERIC Educational Resources Information Center

    Eckstein, Daniel; Tobacyk, Jerome

    The relationship between birth order and how a person deals with death is investigated. Both theoretical and empirical evidence indicates that birth order influences how a person deals with life tasks. First-borns appear more achievement-oriented than their younger siblings, as exemplified by the fact that disproportionately greater numbers of…

  2. The Experience of Near Death

    ERIC Educational Resources Information Center

    Sabom, M. B.; Kreutziger, S.

    1977-01-01

    Reported phenomena occurring in people encountering near-death situations have recently stimulated considerable public interest. In an informal survey, few professionals who care for critically ill patients were aware of these occurrences. Approximately 50 patients with documented near-fatal encounters were interviewed to confirm the existence and…

  3. Reading Guidance: Death and Grief.

    ERIC Educational Resources Information Center

    Smith, Alice Gullen

    1989-01-01

    Gives guidelines for the librarian using reading guidance (similar to bibliotherapy). Provides a nine-item annotated bibliography of novels for children and adolescents on the subject of death and grief. Appends an embryo list of categories suitable for content analysis of any file librarians might wish to keep on books suitable for use in this…

  4. Navigating the valley of death

    NASA Astrophysics Data System (ADS)

    Dacey, James

    2014-11-01

    Taking an innovation from the lab to the market is hard in any discipline, but physics start-ups face some unique challenges crossing the so-called "valley of death". James Dacey speaks to scientists and business professionals in the Boston area of the US who have dared to take on this journey.

  5. Attitudes on Death and Dying.

    ERIC Educational Resources Information Center

    Andrus, Charles E.

    This paper explored attitudes toward death and dying revealed through interviews with members of the clergy, the medical profession, funeral directors, nursing home residents, and selected others. The sampling was small and results are not intended to be representative of the groups to which these people belong. Rather, the study may be used as a…

  6. Reconstructing Death in Postmodern Society.

    ERIC Educational Resources Information Center

    Kastenbaum, Robert

    1993-01-01

    Examines interaction between emerging thanatological movement and its sociohistorical context. Notes that thanatology will take on new shape as individuals and society attempt to cope with postmodernistic forces and deconstructive mentality. Considers prospect for authentic solidarity against distress in reconstructed death system. (Author/NB)

  7. Death Penalty Issues Following Atkins

    ERIC Educational Resources Information Center

    Patton, James R.; Keyes, Denis W.

    2006-01-01

    In light of the U.S. Supreme Court's 2002 landmark decision in "Atkins v. Virginia," a diagnosis of mild mental retardation has taken on a life and death significance for people who are the most deeply involved in criminal justice. As such, each aspect of the mental retardation definition (American Association on Mental Retardation, 2002) is a…

  8. Confidential inquiry into malaria deaths.

    PubMed Central

    Dürrheim, D. N.; Frieremans, S.; Kruger, P.; Mabuza, A.; de Bruyn, J. C.

    1999-01-01

    The results of a confidential inquiry into mortality attributed to malaria in South Africa's Mpumalanga Province are being used to guide the design of strategies for improving the management of cases and reducing the probability of deaths from the disease. PMID:10212518

  9. Religiosity and the Construction of Death in Turkish Death Announcements, 1970-2009

    ERIC Educational Resources Information Center

    Ergin, Murat

    2012-01-01

    Death and rituals performed after death reflect and reproduce social distinctions despite death's popular reputation as a great leveler. This study examines expressions of religiosity and constructions of death in Turkish death announcements, paying particular attention to gendered, ethnic, and temporal variations as well as markers of status and…

  10. Biomedical Potential of mTOR Modulation by Nanoparticles.

    PubMed

    Hulea, Laura; Markovic, Zoran; Topisirovic, Ivan; Simmet, Thomas; Trajkovic, Vladimir

    2016-05-01

    Modulation of the mammalian target of rapamycin (mTOR), the principal regulator of cellular homeostasis, underlies the biological effects of engineered nanoparticles, including regulation of cell death/survival and metabolic responses. Understanding the mechanisms and biological actions of nanoparticle-mediated mTOR modulation may help in developing safe and efficient nanotherapeutics to fight human disease. PMID:26900005

  11. Cell death, damage-associated molecular patterns, and sterile inflammation in cardiovascular disease.

    PubMed

    Zheng, Yue; Gardner, Sarah E; Clarke, Murray C H

    2011-12-01

    Cell death and inflammation are ancient processes of fundamental biological importance in both normal physiology and pathology. This is evidenced by the profound conservation of mediators, with ancestral homologues identified from plants to humans, and the number of diseases driven by aberrant control of either process. Apoptosis is the most well-studied cell death, but many forms exist, including autophagy, necrosis, pyroptosis, paraptosis, and the obscure dark cell death. Cell death occurs throughout the cardiovascular system, from initial shaping of the heart and vasculature during development to involvement in pathologies, including atherosclerosis, aneurysm, cardiomyopathy, restenosis, and vascular graft rejection. However, determining whether cell death primarily drives pathology or is a secondary bystander effect is difficult. Inflammation, the primary response of innate immunity, is considered essential in initiating and driving vascular diseases. Cell death and inflammation are inextricably linked with their effectors modulating the other process. Indeed, an evolutionary link between cell death and inflammation occurs at caspase-1 (which activates interleukin-1β), which can induce death by pyroptosis, and is a member of the caspase family vital for apoptosis. This review examines cell death in vascular disease, how it can induce inflammation, and finally the emergence of inflammasomes in vascular pathology. PMID:22096097

  12. p53 regulates a non-apoptotic death induced by ROS

    PubMed Central

    Montero, J; Dutta, C; van Bodegom, D; Weinstock, D; Letai, A

    2013-01-01

    DNA damage induced by reactive oxygen species and several chemotherapeutic agents promotes both p53 and poly (ADP-ribose) polymerase (PARP) activation. p53 activation is well known to regulate apoptotic cell death, whereas robust activation of PARP-1 has been shown to promote a necrotic cell death associated with energetic collapse. Here we identify a novel role for p53 in modulating PARP enzymatic activity to regulate necrotic cell death. In mouse embryonic fibroblasts, human colorectal and human breast cancer cell lines, loss of p53 function promotes resistance to necrotic, PARP-mediated cell death. We therefore demonstrate that p53 can regulate both necrotic and apoptotic cell death, mutations or deletions in this tumor-suppressor protein may be selected by cancer cells to provide not only their resistance to apoptosis but also to necrosis, and explain resistance to chemotherapy and radiation even when it kills via non-apoptotic mechanisms. PMID:23703322

  13. Violent death in Connecticut, 2001 to 2004.

    PubMed

    Borrup, Kevin; Gelven, Erica S; Carver, H Wayne; Banco, Leonard; Lapidus, Garry

    2008-04-01

    We reviewed medical examiner, law enforcement, crime laboratory data, and death certificates on all 1,530 violent deaths (homicide, suicide, undetermined firearm) in Connecticut occurring from 2001-2004. There was an average of 383 deaths (rate = 11.2 deaths per 100,000 persons annually). Overall, males aged 20 to 29 were at the greatest risk of violent death (rate = 30.5/100,000). Of all violent deaths 72% were suicides and 28% were homicides. Firearms were used in 33% of suicides and 58% of homicides. The rate of violent death is lower than most other states in the country. In Connecticut suicide is the leading cause of violent death overall; however, in areas characterized by the highest levels of poverty and lowest levels of education, homicide is the leading cause of violent death. PMID:18478984

  14. Firefighting Module

    NASA Technical Reports Server (NTRS)

    1981-01-01

    Aviation Power Supply's mobile firefighting module called Firefly II is mounted on a trailer pulled by a pickup truck. Trailer unit has two three- inch water cannons, and the pickup carries a six inch cannon. Completely self contained, module pumps 3,000 gallons of water a minute from hydrants or open bodies of water. Stream can go as far as 400 feet or can be employed in a high-loft mode to reach the tops of tall refinery towers. Compact Firefly II weighs only 2,500 pounds when fully fueled. Key component is a specially designed two stage pump. Power for the pump is generated by a gas turbine engine. Module also includes an electronic/pump controller, multiple hose connections, up to 1,500 feet of hose and fuel for four hours operation. Firefly trailer can be backed onto specially-built large fireboat.

  15. Firefighting Module

    NASA Astrophysics Data System (ADS)

    1980-01-01

    Aviation Power Supply's mobile firefighting module called Firefly II is mounted on a trailer pulled by a pickup truck. Trailer unit has two three- inch water cannons, and the pickup carries a six inch cannon. Completely self contained, module pumps 3,000 gallons of water a minute from hydrants or open bodies of water. Stream can go as far as 400 feet or can be employed in a high-loft mode to reach the tops of tall refinery towers. Compact Firefly II weighs only 2,500 pounds when fully fueled. Key component is a specially designed two stage pump. Power for the pump is generated by a gas turbine engine. Module also includes an electronic/pump controller, multiple hose connections, up to 1,500 feet of hose and fuel for four hours operation. Firefly trailer can be backed onto specially-built large fireboat.

  16. Thermionic modules

    DOEpatents

    King, Donald B.; Sadwick, Laurence P.; Wernsman, Bernard R.

    2002-06-18

    Modules of assembled microminiature thermionic converters (MTCs) having high energy-conversion efficiencies and variable operating temperatures manufactured using MEMS manufacturing techniques including chemical vapor deposition. The MTCs incorporate cathode to anode spacing of about 1 micron or less and use cathode and anode materials having work functions ranging from about 1 eV to about 3 eV. The MTCs also exhibit maximum efficiencies of just under 30%, and thousands of the devices and modules can be fabricated at modest costs.

  17. Longitudinal Neuropsychiatric Predictors of Death in Alzheimer's Disease.

    PubMed

    Spalletta, Gianfranco; Long, Jeffrey D; Robinson, Robert G; Trequattrini, Alberto; Pizzoli, Sonia; Caltagirone, Carlo; Orfei, Maria D

    2015-01-01

    Characteristics associated with life expectancy in Alzheimer's disease (AD) are still far from known. Here we aimed at examining the ability of baseline/longitudinal clinical variables to predict time to death. One-hundred fifty AD outpatients underwent diagnostic, neuropsychiatric, and functional assessment at baseline (when ApoE ɛ4 was also investigated) and at each subsequent annual visit. A random effects joint modeling approach was used to simultaneously model the baseline and longitudinal trajectory of each factor and predict the time to death, adjusting for demographic covariates. An ancillary analysis of ApoE ɛ4 status as a predictor was also conducted. Kaplan-Meier survival curves were constructed to elucidate the relationship between each factor and the estimated probability of death over time. Shorter survival was associated with male gender, higher education, older age, lower cognition, and worse functioning in daily life, but not ApoE ɛ4 status. Longitudinal trajectories increased predictive power over using just baseline levels highlighting apathy, and secondarily aberrant motor behaviors and sleep disorders, as a highly reliable predictor for mortality. Apathy was the strongest neuropsychiatric predictor of time to death, which supports its role in the pathogenesis of the disorder. An increased knowledge of factors modulating survival in AD is a strategic prerequisite to plan therapeutic interventions. PMID:26402103

  18. Timing determines dexamethasone and rituximab induced synergistic cell death.

    PubMed

    Adem, Jemal; Eray, Mine; Eeva, Jonna; Nuutinen, Ulla; Pelkonen, Jukka

    2016-07-01

    Dysregulation of cell death signaling pathways in many cell types such as B lymphocytes (B-cells) can lead to cancer, for example to B-cell lymphomas. Rituximab (RTX) and glucocorticoids such as dexamethasone (Dex) are widely used to treat hematological malignancies including B-cell lymphomas. Although the combination of Dex and RTX improves the treatment outcome of lymphoma patients, most lymphomas remain incurable diseases. Therefore, a detailed investigation of Dex- and RTX-induced signaling might provide new insights into the therapeutic benefits of these drugs. In this paper, we describe Dex- and RTX-induced signaling pathways and their downstream target proteins/cells. In addition, we also overview how the signaling initiated by Dex and RTX modulate the outcome of Dex- and RTX-mediated cell death in lymphoma cells. The combination of Dex and RTX results in massive cell death in lymphoma cells. However, pretreatment of lymphoma cells or mononuclear cytotoxic cells with Dex followed by RTX leads to a decrease in apoptosis or it impairs antibody-dependent cellular cytotoxicity (ADCC). RTX-mediated ADCC is impaired by Dex-induced depletion of cytotoxic cells, whereas RTX-mediated short-term ERK1/2 activation decreases Dex-induced apoptosis. Therefore, the timing of the combination of Dex and RTX is a determining factor for the synergistic effect of these cell death inducing agents. PMID:27290654

  19. Vaginal "fisting" as a cause of death.

    PubMed

    Fain, D B; McCormick, G M

    1989-03-01

    We describe the death of a young girl that resulted from the insertion of a clenched hand and forearm into her vagina during heterosexual activity. (The male homosexual practice of rectal fist insertion has been described previously.) We believe this death to be the first reported case of a "fisting" death due to vaginal fist insertion during heterosexual activity. This death is reported to alert forensic pathologists, medicolegal death investigators, and coroners aware of the role of aberrant sexual activity and its potential to cause death. PMID:2929548

  20. Bioethics for clinicians: 24. Brain death

    PubMed Central

    Lazar, Neil M.; Shemie, Sam; Webster, George C.; Dickens, Bernard M.

    2001-01-01

    BRAIN DEATH IS DEFINED AS THE COMPLETE AND IRREVERSIBLE absence of all brain function. It is diagnosed by means of rigorous testing at the bedside. The advent of neurologic or brain death criteria to establish the death of a person was a significant departure from the traditional way of defining death and remains ethically challenging to some. We review the ethical, cultural, religious and legal issues surrounding brain death and outline an approach to establishing a diagnosis of brain death in clinical practice. PMID:11276553

  1. [Sudden death in young athletes].

    PubMed

    Gojanovic, B; Feihl, F; Gremion, G; Waeber, B

    2007-02-01

    Sudden cardiac death in a young athlete is a tragic and marking event, even though the media attention it gets is more important than its incidence (1-2/100000 per year). The main etiology is hypertrophic cardiomyopathy, followed by coronary artery anomalies. Sometimes signs of myocarditis are found at autopsy. The pre-participation examination recommandations ask for oriented history and physical examination, routine EKG being controversial. A systematic screening program in Italy has reduced the occurrence of such deaths, which statistics are non-existant in Switzerland. It would be appropriate to implement a standardized pre-participation examination, as well as to make sure that the trainers, teachers and athletes themselves are able to recognize the frequent warning symptoms. PMID:17330410

  2. Sleep, death, and the heart.

    PubMed

    Mansukhani, Meghna P; Wang, Shihan; Somers, Virend K

    2015-09-01

    Obstructive and central sleep apnea have been associated with increased risk of adverse cardiovascular events and mortality. Sympathetic dysregulation occurring as a result of the respiratory disturbance is thought to play a role in this increased risk. Sleep apnea increases the risk of arrhythmias, myocardial ischemia/infarction, stroke, and heart failure, all of which may increase mortality risk. A higher incidence of nocturnal arrhythmias, cardiac ischemia, and sudden death has been noted in subjects with sleep-disordered breathing (SDB). In this review, the association between SDB and each of these conditions is discussed, as well as the potential mechanisms underlying these risks and the effects of treatment of SDB. Particular emphasis is placed on the relationship between SDB and nocturnal atrial and ventricular arrhythmias, myocardial ischemia/infarction and sudden death. PMID:26188022

  3. Sudden Cardiac Death in Athletes.

    PubMed

    Wasfy, Meagan M; Hutter, Adolph M; Weiner, Rory B

    2016-01-01

    There are clear health benefits to exercise; even so, patients with cardiac conditions who engage in exercise and athletic competition may on rare occasion experience sudden cardiac death (SCD). This article reviews the epidemiology and common causes of SCD in specific athlete populations. There is ongoing debate about the optimal mechanism for SCD prevention, specifically regarding the inclusion of the ECG and/or cardiac imaging in routine preparticipation sports evaluation. This controversy and contemporary screening recommendations are also reviewed. PMID:27486488

  4. Sudden Cardiac Death in Athletes

    PubMed Central

    Wasfy, Meagan M.; Hutter, Adolph M.; Weiner, Rory B.

    2016-01-01

    There are clear health benefits to exercise; even so, patients with cardiac conditions who engage in exercise and athletic competition may on rare occasion experience sudden cardiac death (SCD). This article reviews the epidemiology and common causes of SCD in specific athlete populations. There is ongoing debate about the optimal mechanism for SCD prevention, specifically regarding the inclusion of the ECG and/or cardiac imaging in routine preparticipation sports evaluation. This controversy and contemporary screening recommendations are also reviewed. PMID:27486488

  5. Pediatric fire deaths in Ontario

    PubMed Central

    Chen, Yingming Amy; Bridgman-Acker, Karen; Edwards, Jim; Lauwers, Albert Edward

    2011-01-01

    Abstract Objective To identify the predictors of residential fire deaths in the Ontario pediatric population using systematically collected data from the Office of the Chief Coroner. Design Retrospective cohort study. Setting Ontario. Participants Children younger than 16 years of age who died in accidental residential fires in Ontario between January 1, 2001, and December 31, 2006. Main outcome measures The study retrospectively reviewed the coroner’s case files for 60 subjects who qualified according to the selection criteria. Reviewed documents included the coroner’s investigation statements, autopsy reports, toxicology reports, fire marshal’s reports, police reports, and Children’s Aid Society (CAS) reports. Information on a range of demographic, behavioural, social, and environmental factors was collected. Statistical tests, including relative risk, relative risk confidence intervals, and χ2 tests were performed to determine the correlation between factors of interest and to establish their significance. Results Thirty-nine fire events resulting in 60 deaths occurred between 2001 and 2006. Fire play and electrical failures were the top 2 causes of residential fires. More fires occurred during the night (midnight to 9 am) than during the day (9 am to midnight). Nighttime fires were most commonly due to electrical failures or unattended candles, whereas daytime fires were primarily caused by unsupervised fire play and stove fires. Smoke alarms were present at 32 of 39 fire events (82%), but overall alarm functionality was only 54%. Children from families with a history of CAS involvement were approximately 32 times more likely to die in fires. Conclusion Risk factors for pediatric fire death in Ontario include smoke alarm functionality, fire play, fire escape behaviour, and CAS involvement. Efforts to prevent residential fire deaths should target these populations and risk factors, and primary care physicians should consider education around these

  6. Regulation of Ferroptotic Cancer Cell Death by GPX4

    PubMed Central

    Welsch, Matthew E.; Shimada, Kenichi; Skouta, Rachid; Viswanathan, Vasanthi S.; Cheah, Jaime H.; Clemons, Paul A.; Shamji, Alykhan F.; Clish, Clary B.; Brown, Lewis M.; Girotti, Albert W.; Cornish, Virginia W.; Schreiber, Stuart L.; Stockwell, Brent R.

    2014-01-01

    SUMMARY Ferroptosis is a form of nonapoptotic cell death for which key regulators remain unknown. We sought a common mediator for the lethality of 12 ferroptosisinducing small molecules. We used targeted metabolomic profiling to discover that depletion of glutathione causes inactivation of glutathione peroxidases (GPXs) in response to one class of compounds and a chemoproteomics strategy to discover that GPX4 is directly inhibited by a second class of compounds. GPX4 overexpression and knockdown modulated the lethality of 12 ferroptosis inducers, but not of 11 compounds with other lethal mechanisms. In addition, two representative ferroptosis inducers prevented tumor growth in xenograft mouse tumor models. Sensitivity profiling in 177 cancer cell lines revealed that diffuse large B cell lymphomas and renal cell carcinomas are particularly susceptible to GPX4-regulated ferroptosis. Thus, GPX4 is an essential regulator of ferroptotic cancer cell death. PMID:24439385

  7. The death system according to Robert Kastenbaum.

    PubMed

    Corr, Charles A

    This article focuses on Robert Kastenbaum's seminal concept of the societal death system. Beginning with conflicting claims that America is a death-denying society versus a death-accepting society, the article reports Kastenbaum's definition and description of the death system in American society and sets forth the seven functions and five elements or components of that death system. Next, the article notes Kastenbaum's further claim that "All cultures, past and present, have had death systems." Finally, two basic lessons are drawn from the foregoing: (1) Kastenbaum's concept of the death system provides a robust framework to explain the networks societies interpose between their members and death, focusing in particular on a more or less integrated and dynamic network within American society whose functions and components are not difficult to recognize in the ways in which they organize many aspects of the lives of individuals who live within that society; and (2) It is preposterous to assert without qualification that America is a death-denying society when there are so many activities and components within that society that are in whole or in part related to death, i.e., although it may be true that many aspects of the contemporary American death system appear to seek to remove death from the mainstream of life, there is ample evidence to indicate that American society as a whole and individuals within that society both accept and deny death simultaneously. PMID:25351587

  8. Deaths in Custody: A 25-Year Review of Jail Deaths in Bexar County, Texas.

    PubMed

    Lozano, Jason G; Molina, D Kimberley

    2015-12-01

    Although deaths in custody are an expected occurrence, they are often subjected to increased scrutiny and raise many questions as to circumstances surrounding the death as well as the cause and manner of death. It is usually the responsibility of the medical examiner to answer these questions. Relatively few studies have reviewed the causes and manners of death that occur while in custody and even fewer specific to jail populations. This study reviews the cause and manner of death of persons in custody in an urban county from 1985 to 2010. A retrospective review of death investigations, including death certificates and autopsy reports, was conducted on all deaths that occurred in custody during the period. The age and sex of the decedent as well as the place of death were also recorded. Most deaths were attributed to natural disease followed by suicide, and most deaths occurred either in the emergency department or in the hospital. Regarding the cause of death, cardiovascular disease followed by suicide by hanging accounted for the most number of deaths (25% and 20% of all deaths, respectively). It is recommended that all deaths in custody be reported to the medical examiner and that a thorough death investigation be conducted to properly define and document the cause and manner of death. This is particularly important given the increased scrutiny to which deaths in custody are often subjected. PMID:26196271

  9. Cardiac Innervation and Sudden Cardiac Death

    PubMed Central

    Fukuda, Keiichi; Kanazawa, Hideaki; Aizawa, Yoshiyasu; Ardell, Jeffrey L.; Shivkumar, Kalyanam

    2015-01-01

    Afferent and efferent cardiac neurotransmission via the cardiac nerves intricately modulates nearly all physiological functions of the heart (chronotropy, dromotropy, lusitropy and inotropy). Afferent information from the heart is transmitted to higher levels of the nervous system for processing (intrinsic cardiac nervous system, extracardiac-intrathoracic ganglia, spinal cord, brain stem and higher centers) which ultimately results in efferent cardiomotor neural impulses (via the sympathetic and parasympathetic nerves). This system forms interacting feedback loops that provide physiological stability for maintaining normal rhythm and life-sustaining circulation. This system also ensures that there is fine-tuned regulation of sympathetic-parasympathetic balance in the heart under normal and stressed states in the short (beat to beat), intermediate (minutes-hours) and long term (days-years). This important neurovisceral /autonomic nervous system also plays a major role in the pathophysiology and progression of heart disease, including heart failure and arrhythmias leading to sudden cardiac death (SCD). Transdifferentiation of neurons in heart failure, functional denervation, cardiac and extra-cardiac neural remodeling have also been identified and characterized during the progression of disease. Recent advances in understanding the cellular and molecular processes governing innervation and the functional control of the myocardium in health and disease provides a rational mechanistic basis for development of neuraxial therapies for preventing SCD and other arrhythmias. Advances in cellular, molecular, and bioengineering realms have underscored the emergence of this area as an important avenue of scientific inquiry and therapeutic intervention. PMID:26044253

  10. CDC Vital Signs: Motor Vehicle Crash Deaths

    MedlinePlus

    ... Press Kit Read the MMWR Science Clips Motor Vehicle Crash Deaths How is the US doing? Language: ... Sweden, Switzerland, and the United Kingdom. Problem Motor vehicle crash deaths in the US are still too ...

  11. CDC Vital Signs: Alcohol Poisoning Deaths

    MedlinePlus

    ... Digital Press Kit Read the MMWR Science Clips Alcohol Poisoning Deaths A deadly consequence of binge drinking ... less binge drinking. Problem There are 2,200 alcohol poisoning deaths in the US each year. Alcohol ...

  12. Fast Action Can Prevent Sepsis Death: CDC

    MedlinePlus

    ... fullstory_160574.html Fast Action Can Prevent Sepsis Death: CDC Know the signs of extreme response to ... treated long before it causes severe illness or death, U.S. health officials report. Sepsis, or septicemia, occurs ...

  13. Death of a Special Needs Child

    MedlinePlus

    ... iGive.com Purchase Through AmazonSmile Contact Us Donate Death of a Special Needs Child When a child ... Needs Child Dies The grief that follows the death of a special-needs child comes not only ...

  14. Surviving the Sudden Death of a Baby

    MedlinePlus

    ... Funds Request Information Get Involved Surviving the Sudden Death of a Baby Home Grieving Families Surviving the ... Candle on For Families Who Have Experienced the Death of a Baby The numbers are staggering. Every ...

  15. Sudden Arrhythmia Death Syndromes (SADS) Foundation

    MedlinePlus

    ... all proceeds benefiting the SADS Foundation (Sudden Arrhythmia Death Syndrome). Each year 4,000 young Americans die ... Investigator Awardees 5/19/2016 The Sudden Arrhythmia Death Syndromes (SADS) Foundation announces the winners for the ...

  16. Diabetes Ups Risk of Heart Attack Death

    MedlinePlus

    ... 159557.html Diabetes Ups Risk of Heart Attack Death Study points to need for better coordinated care, ... people with diabetes have a higher risk of death after a heart attack. "We knew that following ...

  17. Progress Against Heart Deaths Starting to Wane

    MedlinePlus

    ... medlineplus/news/fullstory_159623.html Progress Against Heart Deaths Starting to Wane, Report Warns Obesity, diabetes epidemics ... study warns that the rate of decline in deaths from heart disease and stroke has stalled. "It ...

  18. Sudden Infant Death Syndrome: Facts for Caregivers.

    ERIC Educational Resources Information Center

    Texas Child Care, 2000

    2000-01-01

    Presents risk factors and prevention measures related to Sudden Infant Death Syndrome. Offers infant sleep recommendations and five discussion questions to test knowledge of Sudden Infant Death Syndrome. (DLH)

  19. Cell death in the cardiovascular system

    PubMed Central

    Clarke, Murray; Bennett, Martin; Littlewood, Trevor

    2007-01-01

    Cell death is important for both development and tissue homeostasis in the adult. As such, it is tightly controlled and deregulation is associated with diverse pathologies; for example, regulated cell death is involved in vessel remodelling during development or following injury, but deregulated death is implicated in pathologies such as atherosclerosis, aneurysm formation, ischaemic and dilated cardiomyopathies and infarction. We describe the mechanisms of cell death and its role in the normal physiology and various pathologies of the cardiovascular system. PMID:16547202

  20. Mechanisms of Sudden Cardiac Death: Oxidants and Metabolism

    PubMed Central

    Yang, Kai-Chien; Kyle, John W.; Makielski, Jonathan C.; Dudley, Samuel C.

    2015-01-01

    Ventricular arrhythmia is the leading cause of sudden cardiac death (SCD). Deranged cardiac metabolism and abnormal redox state during cardiac diseases foment arrhythmogenic substrates through direct or indirect modulation of cardiac ion channel/transporter function. This review presents current evidence on the mechanisms linking metabolic derangement and excessive oxidative stress to ion channel/transporter dysfunction that predisposes to ventricular arrhythmias and SCD. As conventional anti-arrhythmic agents aiming at ion channels have proven challenging to use, targeting arrhythmogenic metabolic changes and redox imbalance may provide novel therapeutics to treat or prevent life-threatening arrhythmias and SCD. PMID:26044249

  1. Physician's Death Anxiety and Patient Outcomes.

    ERIC Educational Resources Information Center

    Schulz, Richard; Aderman, David

    1978-01-01

    It was shown that terminal patients of physicians with high death anxiety survive longer during their final hospital stay than terminal patients of physicians with low death anxiety. Physicians high in death anxiety seem to be less willing to accept patients' terminality and use heroic measures to keep them alive. (Author)

  2. Attitudes and Experiences of Death Workshop Attendees

    ERIC Educational Resources Information Center

    Kubler-Ross, Elisabeth; Worden, J. William

    1977-01-01

    Attendees at workshops and lectures were asked to complete a questionnaire which assessed the following: 1) First death experience, 2) Present conceptualization of death, 3) Anticipated reactions to a personal terminal illness, 4) Resources in managing one's own death, and 5) Difficulties experienced in working with dying persons. (Author)

  3. Cell death in the nervous system

    PubMed Central

    Bredesen, Dale E.; Rao, Rammohan V.; Mehlen, Patrick

    2014-01-01

    Neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease trigger neuronal cell death through endogenous suicide pathways. Surprisingly, although the cell death itself may occur relatively late in the course of the degenerative process, the mediators of the underlying cell-death pathways have shown promise as potential therapeutic targets. PMID:17051206

  4. Directions in Near-Death Research.

    ERIC Educational Resources Information Center

    Lundahl, C.R.

    1981-01-01

    Explains that near-death research is moving in three directions: (1) the ongoing accumulation of knowledge on the near-death experience through scientifically derived studies; (2) the examination of post-mortem survival; and (3) the clinical application of the findings of near- death research. (Author/RC)

  5. Exploring Children's Understanding of Death Concepts

    ERIC Educational Resources Information Center

    Lee, Joo Ok; Lee, Joohi; Moon, Sung Seek

    2009-01-01

    This study is an investigation of the effects of death education on children and their understanding of death. The participants of this study were eighty 5- and 6-year-olds who were enrolled in a suburban kindergarten in Korea. To examine the level of children's understanding of death, researchers interviewed each child in both the control and…

  6. 5 CFR 1651.11 - Simultaneous death.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Simultaneous death. 1651.11 Section 1651.11 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD DEATH BENEFITS § 1651.11 Simultaneous death. If a beneficiary dies at the same time as the participant, the beneficiary will be...

  7. 20 CFR 638.513 - Death.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Death. 638.513 Section 638.513 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.513 Death. In each case of student death,...

  8. Children's Reactions to the Word Death.

    ERIC Educational Resources Information Center

    Wenestam, Claes-Goran

    Although some research has been conducted in the past, few studies have investigated children's conceptions of life, death and dying. To study children's ideas about death, 112 children, age 4-18, were asked to draw what they thought of when they heard the word "death" and also to make verbal comments about their drawings. Three qualitatively…

  9. 5 CFR 1651.11 - Simultaneous death.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 3 2014-01-01 2014-01-01 false Simultaneous death. 1651.11 Section 1651.11 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD DEATH BENEFITS § 1651.11 Simultaneous death. If a beneficiary dies at the same time as the participant, the beneficiary will be...

  10. 7 CFR 707.3 - Death.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 7 2014-01-01 2014-01-01 false Death. 707.3 Section 707.3 Agriculture Regulations of... Death. (a) Where any person who would otherwise be eligible to receive a payment dies before the payment... timely program application has been filed by the deceased before the death or filed in a timely...

  11. 7 CFR 707.3 - Death.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 7 2013-01-01 2013-01-01 false Death. 707.3 Section 707.3 Agriculture Regulations of... Death. (a) Where any person who would otherwise be eligible to receive a payment dies before the payment... timely program application has been filed by the deceased before the death or filed in a timely...

  12. 5 CFR 1651.11 - Simultaneous death.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 3 2011-01-01 2011-01-01 false Simultaneous death. 1651.11 Section 1651.11 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD DEATH BENEFITS § 1651.11 Simultaneous death. If a beneficiary dies at the same time as the participant, the beneficiary will be...

  13. 20 CFR 638.513 - Death.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Death. 638.513 Section 638.513 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.513 Death. In each case of student death,...

  14. 5 CFR 1651.11 - Simultaneous death.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 3 2013-01-01 2013-01-01 false Simultaneous death. 1651.11 Section 1651.11 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD DEATH BENEFITS § 1651.11 Simultaneous death. If a beneficiary dies at the same time as the participant, the beneficiary will be...

  15. 5 CFR 1651.11 - Simultaneous death.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 3 2012-01-01 2012-01-01 false Simultaneous death. 1651.11 Section 1651.11 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD DEATH BENEFITS § 1651.11 Simultaneous death. If a beneficiary dies at the same time as the participant, the beneficiary will be...

  16. 20 CFR 638.513 - Death.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false Death. 638.513 Section 638.513 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.513 Death. In each case of student death,...

  17. 7 CFR 707.3 - Death.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 7 2011-01-01 2011-01-01 false Death. 707.3 Section 707.3 Agriculture Regulations of... Death. (a) Where any person who would otherwise be eligible to receive a payment dies before the payment... timely program application has been filed by the deceased before the death or filed in a timely...

  18. 7 CFR 707.3 - Death.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 7 2012-01-01 2012-01-01 false Death. 707.3 Section 707.3 Agriculture Regulations of... Death. (a) Where any person who would otherwise be eligible to receive a payment dies before the payment... timely program application has been filed by the deceased before the death or filed in a timely...

  19. Dealing with Human Death: The Floating Perspective.

    ERIC Educational Resources Information Center

    Kenyon, Gary M.

    1991-01-01

    Explores approach to dealing with human death. Describes floating perspective, based on insights from Choron and Jaspers, as suggesting it is possible to deal with human death by refraining from taking ultimate position on the problem. Position encourages openness to death. Examines role of anxiety and describes possible meaningful outcomes of…

  20. Death Education for the Health Professional.

    ERIC Educational Resources Information Center

    Benoliel, Jeanne Quint, Ed.

    The perspectives of a number of health professionals based on their experiences in providing death education courses are presented in essays. In "Interdisciplinary Death Education in a Nursing School" (Helen L. Swain and Kathleen V. Cowles), the development of an undergraduate elective course in death, dying, and bereavement at the University of…

  1. Firefighting Module

    NASA Technical Reports Server (NTRS)

    1984-01-01

    Firefly II pump module is NASA's Marshall Space Flight Center's commercial offshoot of a NASA/US Coast Guard program involving development of a lightweight, helicopter-transportable firefighting module for a quick response in combating shipboard or harbor fires. Operable on land or water, the Amphib One is equipped with 3 water cannons. When all 3 are operating, unit pumps more than 3,000 gallons a minute. Newly developed model used by U.S. Coast Guard can pump 5,000 gallons per minute. It was designed for applications such as firefighting onboard ship fires, emergency dockside water pumping, dewatering ships in danger of sinking, flood control, and emergency water supply at remote locations.

  2. Pancreatic β Cell Mass Death.

    PubMed

    Marrif, Husnia I; Al-Sunousi, Salma I

    2016-01-01

    Type two diabetes (T2D) is a challenging metabolic disorder for which a cure has not yet been found. Its etiology is associated with several phenomena, including significant loss of insulin-producing, beta cell (β cell) mass via progressive programmed cell death and disrupted cellular autophagy. In diabetes, the etiology of β cell death and the role of mitochondria are complex and involve several layers of mechanisms. Understanding the dynamics of those mechanisms could permit researchers to develop an intervention for the progressive loss of β cells. Currently, diabetes research has shifted toward rejuvenation and plasticity technology and away from the simplified approach of hormonal compensation. Diabetes research is currently challenged by questions such as how to enhance cell survival, decrease apoptosis and replenish β cell mass in diabetic patients. In this review, we discuss evidence that β cell development and mass formation are guided by specific signaling systems, particularly hormones, transcription factors, and growth factors, all of which could be manipulated to enhance mass growth. There is also strong evidence that β cells are dynamically active cells, which, under specific conditions such as obesity, can increase in size and subsequently increase insulin secretion. In certain cases of aggressive or advanced forms of T2D, β cells become markedly impaired, and the only alternatives for maintaining glucose homeostasis are through partial or complete cell grafting (the Edmonton protocol). In these cases, the harvesting of an enriched population of viable β cells is required for transplantation. This task necessitates a deep understanding of the pharmacological agents that affect β cell survival, mass, and function. The aim of this review is to initiate discussion about the important signals in pancreatic β cell development and mass formation and to highlight the process by which cell death occurs in diabetes. This review also examines the

  3. Pancreatic β Cell Mass Death

    PubMed Central

    Marrif, Husnia I.; Al-Sunousi, Salma I.

    2016-01-01

    Type two diabetes (T2D) is a challenging metabolic disorder for which a cure has not yet been found. Its etiology is associated with several phenomena, including significant loss of insulin-producing, beta cell (β cell) mass via progressive programmed cell death and disrupted cellular autophagy. In diabetes, the etiology of β cell death and the role of mitochondria are complex and involve several layers of mechanisms. Understanding the dynamics of those mechanisms could permit researchers to develop an intervention for the progressive loss of β cells. Currently, diabetes research has shifted toward rejuvenation and plasticity technology and away from the simplified approach of hormonal compensation. Diabetes research is currently challenged by questions such as how to enhance cell survival, decrease apoptosis and replenish β cell mass in diabetic patients. In this review, we discuss evidence that β cell development and mass formation are guided by specific signaling systems, particularly hormones, transcription factors, and growth factors, all of which could be manipulated to enhance mass growth. There is also strong evidence that β cells are dynamically active cells, which, under specific conditions such as obesity, can increase in size and subsequently increase insulin secretion. In certain cases of aggressive or advanced forms of T2D, β cells become markedly impaired, and the only alternatives for maintaining glucose homeostasis are through partial or complete cell grafting (the Edmonton protocol). In these cases, the harvesting of an enriched population of viable β cells is required for transplantation. This task necessitates a deep understanding of the pharmacological agents that affect β cell survival, mass, and function. The aim of this review is to initiate discussion about the important signals in pancreatic β cell development and mass formation and to highlight the process by which cell death occurs in diabetes. This review also examines the

  4. Thermoelectric module

    DOEpatents

    Kortier, William E.; Mueller, John J.; Eggers, Philip E.

    1980-07-08

    A thermoelectric module containing lead telluride as the thermoelectric mrial is encapsulated as tightly as possible in a stainless steel canister to provide minimum void volume in the canister. The lead telluride thermoelectric elements are pressure-contacted to a tungsten hot strap and metallurgically bonded at the cold junction to iron shoes with a barrier layer of tin telluride between the iron shoe and the p-type lead telluride element.

  5. Tracking animals to their death.

    PubMed

    Hays, Graeme C

    2014-01-01

    Migration may be a high-risk period. In a study involving three species of raptor migrating from Europe to Sub-Saharan Africa, Klaassen et al. (2014) satellite-tracked 51 out of 69 birds to their deaths and showed that rate of mortality during migration was 6x that during stationary phases when birds were on their winter and summer grounds. Travel across the Sahara was particularly risky. Satellite tracking has also been used to infer mortality in other taxa (e.g. sea turtles) and may allow high-risk hotspots to be identified for wide-ranging species. PMID:24192383

  6. [Death on a sauna stove].

    PubMed

    Guddat, Saskia Sabrina; Tsokos, Michael

    2007-01-01

    A 67-year-old woman noticed a strange smell from the cellar of her house. When she followed the smell, she found her 64-year-old husband with the face and upper part of his body lying on the stove of the private sauna. He was dead when the emergency doctor arrived. The autopsy revealed upper gastrointestinal bleeding from mucosal lesions in the esophagus with an agonal fall on the sauna stove as the cause of death. In addition, there were signs of chronic alcohol and drug abuse. PMID:18020143

  7. Photothermally induced delayed tissue death.

    PubMed

    Gordon, Jeffrey M; Shaco-Levy, Ruthy; Feuermann, Daniel; Huleihil, Mahmoud; Mizrahi, Solly

    2006-01-01

    We report pronounced delayed tissue death in photothermal surgery performed on the livers of live healthy rats with highly concentrated sunlight (ultrabright noncoherent light). Exposure times and power levels were selected to produce immediate necroses of the order of hundreds of cubic millimeters. Pathology reveals that lesion volumes increase by up to a factor of 5 within approximately 24 h after surgery, and then stabilize. Islands of viable cells can persist within damaged tissue, in the immediate vicinity of blood vessels, but also necrose within about 48 h. PMID:16822049

  8. Radiofrequency Ablation to Prevent Sudden Cardiac Death

    PubMed Central

    Atoui, Moustapha; Gunda, Sampath; Lakkireddy, Dhanunjaya; Mahapatra, Srijoy

    2015-01-01

    Radiofrequency ablation may prevent or treat atrial and ventricular arrhythmias. Since some of these arrhythmias are associated with sudden cardiac death, it has been hypothesized that ablation may prevent sudden death in certain cases. We performed a literature search to better understand under which circumstances ablation may prevent sudden death and found little randomized data demonstrating the long-term effects of ablation. Current literature shows that ablation clearly prevents symptoms of arrhythmia and may reduce the incidence of sudden cardiac death in select patients, although data does not indicate improved mortality. Ongoing clinical trials are needed to better define the role of ablation in preventing sudden cardiac death. PMID:26306130

  9. [Morphological and biochemical criteria for cell death].

    PubMed

    Chernikov, V P; Belousova, T A; Kakturskiĭ, L V

    2010-01-01

    The state-of-the-art of classifications of and criteria for cell death in the light of the 2009 recommendations of the Nomenclature Committee on Cell Death is presented as a lecture. Motivation is given for the necessity of using the unified criteria in the description of cell death and more than one study in its verification. The major structural and biochemical signs of four typical types of cell death--apoptosis, autophagia, keratinization, and necrosis are compared. Data are given on the major atypical forms of cell death--mitotic catastrophe, anoikis, exitotoxicity, Wallerian degeneration, paraptosis, pyroptosis, pyronecrosis, and entosis. PMID:20734836

  10. Death anxiety among emergency care workers.

    PubMed

    Brady, Mike

    2015-07-01

    Death anxiety, or 'thanatophobia', is a state in which people experience negative emotional reactions in recognition of their own mortality. Emergency and unscheduled healthcare workers, such as emergency nurses and paramedics, are constantly reminded of death and therefore of their own mortality, and this makes them susceptible to death anxiety. This article introduces the concept of death anxiety, and highlights the need for staff, employers and universities to recognise its signs and symptoms. It also suggests some interventions that could prevent the debilitating effects of death anxiety, to improve staff's mental health and the care they provide to patients. PMID:26159347

  11. The Study of Personal Constructs of Death and Fear of Death among Taiwanese Adolescents

    ERIC Educational Resources Information Center

    Yang, Shu Ching; Chen, Shih-Fen

    2009-01-01

    This study administered an open-ended questionnaire about death and the Multidimensional Fear of Death Scale (MODS) to explore the relationships between personal constructs about death and fears of death among Taiwanese adolescents. The sample included 329 adolescents in junior and senior high school grades 7 to 12. A coding manual was used to…

  12. Relationship of Death Education to the Anxiety, Fear, and Meaning Associated with Death.

    ERIC Educational Resources Information Center

    Knight, Kim H.; Elfenbein, Morton H.

    1993-01-01

    Compared death anxiety and fear of death levels expressed by 29 college students who had completed death and dying course with comparison group of 74 students. Found that those enrolled in thanatology class reported significantly higher death anxiety at end of semester. Results suggest different effect that thanatology course can have on…

  13. p53 directly regulates the glycosidase FUCA1 to promote chemotherapy-induced cell death

    PubMed Central

    Baudot, Alice D.; Crighton, Diane; O'Prey, Jim; Somers, Joanna; Sierra Gonzalez, Pablo; Ryan, Kevin M.

    2016-01-01

    ABSTRACT p53 is a central factor in tumor suppression as exemplified by its frequent loss in human cancer. p53 exerts its tumor suppressive effects in multiple ways, but the ability to invoke the eradication of damaged cells by programmed cell death is considered a key factor. The ways in which p53 promotes cell death can involve direct activation or engagement of the cell death machinery, or can be via indirect mechanisms, for example though regulation of ER stress and autophagy. We present here another level of control in p53-mediated tumor suppression by showing that p53 activates the glycosidase, FUCA1, a modulator of N-linked glycosylation. We show that p53 transcriptionally activates FUCA1 and that p53 modulates fucosidase activity via FUCA1 up-regulation. Importantly, we also report that chemotherapeutic drugs induce FUCA1 and fucosidase activity in a p53-dependent manner. In this context, while we found that over-expression of FUCA1 does not induce cell death, RNAi-mediated knockdown of endogenous FUCA1 significantly attenuates p53-dependent, chemotherapy-induced apoptotic death. In summary, these findings add an additional component to p53s tumor suppressive response and highlight another mechanism by which the tumor suppressor controls programmed cell death that could potentially be exploited for cancer therapy. PMID:27315169

  14. A long-awaited merger of the pathways mediating host defence and programmed cell death.

    PubMed

    Blander, J Magarian

    2014-09-01

    Historically, cell death and inflammation have been closely linked, but the necessary divergence of the fields in the past few decades has enriched our molecular understanding of the signalling pathways that mediate various programmes of cell death and multiple types of inflammatory responses. The fields have now come together again demonstrating a surprising level of integration. Intimate interconnections at multiple levels are revealed between the cell death and inflammatory signal transduction pathways that are mobilized in response to the engagement of pattern recognition receptors during microbial infection. Molecules such as receptor-interacting protein kinase 1 (RIPK1), RIPK3, FAS-associated death domain protein (FADD), FLICE-like inhibitory protein (FLIP) and caspase 8 - which are associated with different forms of cell death - are incorporated into compatible and exceedingly dynamic Toll-like receptor, NOD-like receptor and RIG-I-like receptor signalling modules. These signalling modules have a high capacity to switch from inflammation to cell death, or a programmed execution of both, all in an orchestrated battle for host defence and survival. PMID:25145756

  15. p53 directly regulates the glycosidase FUCA1 to promote chemotherapy-induced cell death.

    PubMed

    Baudot, Alice D; Crighton, Diane; O'Prey, Jim; Somers, Joanna; Sierra Gonzalez, Pablo; Ryan, Kevin M

    2016-09-01

    p53 is a central factor in tumor suppression as exemplified by its frequent loss in human cancer. p53 exerts its tumor suppressive effects in multiple ways, but the ability to invoke the eradication of damaged cells by programmed cell death is considered a key factor. The ways in which p53 promotes cell death can involve direct activation or engagement of the cell death machinery, or can be via indirect mechanisms, for example though regulation of ER stress and autophagy. We present here another level of control in p53-mediated tumor suppression by showing that p53 activates the glycosidase, FUCA1, a modulator of N-linked glycosylation. We show that p53 transcriptionally activates FUCA1 and that p53 modulates fucosidase activity via FUCA1 up-regulation. Importantly, we also report that chemotherapeutic drugs induce FUCA1 and fucosidase activity in a p53-dependent manner. In this context, while we found that over-expression of FUCA1 does not induce cell death, RNAi-mediated knockdown of endogenous FUCA1 significantly attenuates p53-dependent, chemotherapy-induced apoptotic death. In summary, these findings add an additional component to p53s tumor suppressive response and highlight another mechanism by which the tumor suppressor controls programmed cell death that could potentially be exploited for cancer therapy. PMID:27315169

  16. Death following ingestion of methylone.

    PubMed

    Barrios, L; Grison-Hernando, H; Boels, D; Bouquie, R; Monteil-Ganiere, C; Clement, R

    2016-03-01

    Methylone is a synthetic derivative of cathinone. It is sold principally on the Internet in powder form under the name «bath salts». Deaths following consumption are very rare. This report details the first case of a death in France (a 21-year-old man), following ingestion of methylone during an evening with friends. Anoxia was observed at the time of autopsy. Toxicological analyses highlighted a consumption of methylone and cannabis. However, biological analyses showed an absence of ethanol, cocaine, amphetamines, and opiate derivatives. Likewise, no medications were found. High concentrations of methylone were found in the peripheral blood (3.13 mg/L) and in the central blood (6.64 mg/L). Its presence in the gastric contents provides evidence that the substance was taken orally. The dosage of δ9-tetrahydrocannabinol (THC) suggests a recent cannabis consumption (THC 12.9 μg/L, THC-COOH 29.3 μg/L, 11-OH-THC 4.9 μg/L). This case illustrates that the consumption of methylone, which has a reputation of being less «powerful» than ecstasy, is not without its dangers. PMID:26071183

  17. Childhood deaths from physical abuse.

    PubMed

    Kasim, M S; Cheah, I; Shafie, H M

    1995-07-01

    This paper gives a detailed account of 30 cases of childhood deaths caused by physical abuse, detected by the Suspected Child Abuse and Neglect (SCAN) team, General Hospital, Kuala Lumpur. They consisted of 12 Malays, 6 Chinese, 9 Indian, and 1 Indonesian child. Three cases could not be ascertained as to their ethnic origin. There were 13 male and 17 female children. The average age of the abused children was 2 years 5 months. The most frequent causes of death were intracranial hemorrhage and intraabdominal trauma. Of the 17 cases of intracranial hemorrhage, only four had X-ray evidence of skull fracture. This suggests the possibility of whiplash injuries with/without the abuser suspecting that he/she had injured the child. Of the 22 abusers who could be identified, there was no sex differentiation. Fathers formed the largest group of perpetrators, followed by mothers and childminders. Fifteen of the natural parents of the abused children were married, four were divorced and four were never married. Five of the abusers had aggressive personalities and three were drug addicts. Only one abuser was found to be an alcoholic even though a few were also under suspicion. For most cases, trigger factors could not be identified. PMID:7583742

  18. Metabolic control of cell death

    PubMed Central

    Green, Douglas R.; Galluzzi, Lorenzo; Kroemer, Guido

    2014-01-01

    Summary Beyond their contribution to basic metabolism, the major cellular organelles, in particular mitochondria, can determine whether cells respond to stress in an adaptive or suicidal manner. Thus, mitochondria can continuously adapt their shape to changing bioenergetic demands as they are subjected to quality control by autophagy, or they can undergo a lethal permeabilization process that initiates apoptosis. Along similar lines, multiple proteins involved in metabolic circuitries including oxidative phosphorylation and transport of metabolites across membranes may participate in the regulated or catastrophic dismantling of organelles. Many factors that were initially characterized as cell death regulators are now known to physically or functionally interact with metabolic enzymes. Thus, several metabolic cues regulate the propensity of cells to activate self-destructive programs, in part by acting on nutrient sensors. This suggests the existence of “metabolic checkpoints” that dictate cell fate in response to metabolic fluctuations. Here, we discuss recent insights into the intersection between metabolism and cell death regulation that have major implications for the comprehension and manipulation of unwarranted cell loss. PMID:25237106

  19. [Organ donation after circulatory death].

    PubMed

    de Jonge, J; Kalisvaart, M; van der Hoeven, M; Epker, J; de Haan, J; IJzermans, J N M; Grüne, F

    2016-02-01

    Approximately 17 million inhabitants live in the Netherlands. The number of potential organ donors in 1999 was the lowest in Europe with only 10 donors per million inhabitants. Medical associations, public health services, health insurance companies and the government had to find common solutions in order to improve organ allocation, logistics of donations and to increase the number of transplantations. After a prolonged debate on medical ethical issues of organ transplantation, all participants were able to agree on socio-medico-legal regulations for organ donation and transplantation. In addition to improving the procedure for organ donation after brain death (DBD) the most important step was the introduction of organ donation after circulatory death (DCD). Measures such as the introduction of a national organ donor database, improved information to the public, further education on intensive care units (ICU), guidelines for end of life care on the ICU, establishment of transplantation coordinators on site, introduction of autonomous explantation teams and strict procedures on the course of organ donations, answered many practical issues about logistics and responsibilities for DBD and DCD. In 2014 the number of postmortem organ donations rose to 16.4 per million inhabitants. Meanwhile, up to 60 % of organ donations in the Netherlands originate from a DCD procedure compared to approximately 10 % in the USA. This overview article discusses the developments and processes of deceased donation in the Netherlands after 15 years of experience with DCD. PMID:26810404

  20. Genetics of sudden cardiac death.

    PubMed

    Refaat, Marwan M; Hotait, Mostafa; London, Barry

    2015-07-01

    Sudden cardiac death (SCD) is defined by the World Health Organization (WHO) as death within 1 h of symptom onset (witnessed) or within 24 h of being observed alive and symptom free (unwitnessed). It affects more than 3 million people annually worldwide and affects approximately 1/1000 people each year in the USA. Familial studies of syndromes with Mendelian inheritance, candidate genes analyses, and genome-wide association studies (GWAS) have helped our understanding of the genetics of SCD. We will review the genetics of arrhythmogenic hereditary syndromes with Mendelian inheritance from familial studies with structural heart disease (hypertrophic cardiomyopathy, dilated cardiomyopathy, and arrhythmogenic cardiomyopathy) as well as primary electrical causes (long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, and short QT syndrome). In addition, we will review the genetics of intermediate phenotypes for SCD such as coronary artery disease and electrocardiographic variables (QT interval, QRS duration, and RR interval). Finally, we will review rare and common variants that are associated with SCD in the general population and were identified from candidate gene analyses and GWAS. Our understanding of the genetics of SCD will improve by the use of next-generation sequencing/whole-exome sequencing as well as whole-genome sequencing which have the potential to discover unsuspected common and rare genetic variants that might be associated with SCD. PMID:26026997

  1. Cryoethics: seeking life after death.

    PubMed

    Shaw, David

    2009-11-01

    Cryonic suspension is a relatively new technology that offers those who can afford it the chance to be 'frozen' for future revival when they reach the ends of their lives. This paper will examine the ethical status of this technology and whether its use can be justified. Among the arguments against using this technology are: it is 'against nature', and would change the very concept of death; no friends or family of the 'freezee' will be left alive when he is revived; the considerable expense involved for the freezee and the future society that will revive him; the environmental cost of maintaining suspension; those who wish to use cryonics might not live life to the full because they would economize in order to afford suspension; and cryonics could lead to premature euthanasia in order to maximize chances of success. Furthermore, science might not advance enough to ever permit revival, and reanimation might not take place due to socio-political or catastrophic reasons. Arguments advanced by proponents of cryonics include: the potential benefit to society; the ability to cheat death for at least a few more years; the prospect of immortality if revival is successful; and all the associated benefits that delaying or avoiding dying would bring. It emerges that it might be imprudent not to use the technology, given the relatively minor expense involved and the potential payoff. An adapted and more persuasive version of Pascal's Wager is presented and offered as a conclusive argument in favour of utilizing cryonic suspension. PMID:19788649

  2. Attitudes to death: some historical notes.

    PubMed Central

    Boyd, K

    1977-01-01

    Men have been talking of death from time immemorial - sometimes sublimely in prose and poetry, in painting and sculpture and in music - till silence seemed to fall in the recent past. Now men are again talking about death - interminably but colloquially. They talk on television, on the radio, in books and in pamphlets. Dr Kenneth Boyd therefore finds it entirely timely to offer this historical sketch of attitudes to death. The earlier part of his paper covers fairly familiar ground but his final and longest section on the work of a social historian, Philippe Ariès, may be new to many. Ariès is reinterpreting the long history of attitudes to death in a form which may well interest those who today are concerned with helping modern man to accept his own death - death which still, for most people, is the death of another, not of oneself. PMID:336891

  3. Correlates of death anxiety in Pakistan.

    PubMed

    Suhail, Kausar; Akram, Saima

    2002-01-01

    To ascertain the effect of gender, age, and religiosity on death anxiety, 132 participants were interviewed using Templer Death Anxiety Scale and Collett-Lester Fear of Death Scale (CLS). Women, older participants, and less religious participants were found to be more scared of their impending death. Gender effect was more pronounced, however, on the CLS. Women and less religious people reported to experience greater anxiety than their respective counterparts about different dimensions of death, for example, the shortness of life, total isolation of death, fear of not being, and disintegration of body after dying. The findings of the current work indicate that the general predictors of death anxiety, gender, age, and religiosity reported in Western, predominantly Christian samples also hold in an Eastern, Muslim sample. PMID:11865882

  4. The study of personal constructs of death and fear of death among Taiwanese adolescents.

    PubMed

    Yang, Shu Ching; Chen, Shih-Fen

    2009-11-01

    This study administered an open-ended questionnaire about death and the Multidimensional Fear of Death Scale (MFODS) to explore the relationships between personal constructs about death and fears of death among Taiwanese adolescents. The sample included 329 adolescents in junior and senior high school grades 7 to 12. A coding manual was used to conduct content analysis of death constructs in paragraphs about death written by respondents, and the MFODS was used to measure fear of death. The results revealed that concepts and fears about death differed significantly according to grade, gender, religion, death-related experiences, and death-related discussions in the family. Constructs regarding negative emotional states, as well as low levels of attachment, emerged as significant predictors of the seven MFODS subscales. Generalization of these results to other populations merits further investigation. PMID:19877367

  5. Quality insights of university teachers on dying, death, and death education.

    PubMed

    Mak, Mui-Hing June

    One of the main responsibilities of teachers is to help individual students cope with life difficulties such as grief following a death. However, very little research explores teachers' views on death, dying, and how they handle grief and loss in schools. This study aims to explore university teachers' knowledge and attitudes on dying, death, and death education. Fifteen university teachers were recruited using a qualitative method. This study reveals that most teachers' views on death and related issues are largely affected by their death experiences, religious beliefs, professional background, and the mass media. Although they have a general negative response toward death and dying, some teachers begin to affirm their meanings of life and death. Most teachers agree that they do not feel adequate about managing and teaching on life and death issues, so they strongly support including death education in the formal programs in Hong Kong. PMID:23472324

  6. Photovoltaic module and module arrays

    DOEpatents

    Botkin, Jonathan; Graves, Simon; Lenox, Carl J. S.; Culligan, Matthew; Danning, Matt

    2012-07-17

    A photovoltaic (PV) module including a PV device and a frame. The PV device has a PV laminate defining a perimeter and a major plane. The frame is assembled to and encases the laminate perimeter, and includes leading, trailing, and side frame members, and an arm that forms a support face opposite the laminate. The support face is adapted for placement against a horizontal installation surface, to support and orient the laminate in a non-parallel or tilted arrangement. Upon final assembly, the laminate and the frame combine to define a unitary structure. The frame can orient the laminate at an angle in the range of 3.degree.-7.degree. from horizontal, and can be entirely formed of a polymeric material. Optionally, the arm incorporates integral feature(s) that facilitate interconnection with corresponding features of a second, identically formed PV module.

  7. Photovoltaic module and module arrays

    DOEpatents

    Botkin, Jonathan; Graves, Simon; Lenox, Carl J. S.; Culligan, Matthew; Danning, Matt

    2013-08-27

    A photovoltaic (PV) module including a PV device and a frame, The PV device has a PV laminate defining a perimeter and a major plane. The frame is assembled to and encases the laminate perimeter, and includes leading, trailing, and side frame members, and an arm that forms a support face opposite the laminate. The support face is adapted for placement against a horizontal installation surface, to support and orient the laminate in a non-parallel or tilted arrangement. Upon final assembly, the laminate and the frame combine to define a unitary structure. The frame can orient the laminate at an angle in the range of 3.degree.-7.degree. from horizontal, and can be entirely formed of a polymeric material. Optionally, the arm incorporates integral feature(s) that facilitate interconnection with corresponding features of a second, identically formed PV module.

  8. Macromitophagy, neutral lipids synthesis, and peroxisomal fatty acid oxidation protect yeast from "liponecrosis", a previously unknown form of programmed cell death.

    PubMed

    Sheibani, Sara; Richard, Vincent R; Beach, Adam; Leonov, Anna; Feldman, Rachel; Mattie, Sevan; Khelghatybana, Leila; Piano, Amanda; Greenwood, Michael; Vali, Hojatollah; Titorenko, Vladimir I

    2014-01-01

    We identified a form of cell death called "liponecrosis." It can be elicited by an exposure of the yeast Saccharomyces cerevisiae to exogenous palmitoleic acid (POA). Our data imply that liponecrosis is: (1) a programmed, regulated form of cell death rather than an accidental, unregulated cellular process and (2) an age-related form of cell death. Cells committed to liponecrotic death: (1) do not exhibit features characteristic of apoptotic cell death; (2) do not display plasma membrane rupture, a hallmark of programmed necrotic cell death; (3) akin to cells committed to necrotic cell death, exhibit an increased permeability of the plasma membrane for propidium iodide; (4) do not display excessive cytoplasmic vacuolization, a hallmark of autophagic cell death; (5) akin to cells committed to autophagic death, exhibit a non-selective en masse degradation of cellular organelles and require the cytosolic serine/threonine protein kinase Atg1p for executing the death program; and (6) display a hallmark feature that has not been reported for any of the currently known cell death modalities-namely, an excessive accumulation of lipid droplets where non-esterified fatty acids (including POA) are deposited in the form of neutral lipids. We therefore concluded that liponecrotic cell death subroutine differs from the currently known subroutines of programmed cell death. Our data suggest a hypothesis that liponecrosis is a cell death module dynamically integrated into a so-called programmed cell death network, which also includes the apoptotic, necrotic, and autophagic modules of programmed cell death. Based on our findings, we propose a mechanism underlying liponecrosis. PMID:24196447

  9. Secretory phospholipase A2-mediated neuronal cell death involves glutamate ionotropic receptors.

    PubMed

    Kolko, Miriam; de Turco, Elena B; Diemer, Nils Henrik; Bazan, Nicolas G

    2002-10-28

    To define the significance of glutamate ionotropic receptors in sPLA -mediated neuronal cell death we used the NMDA receptor antagonist MK-801 and the AMPA receptor antagonist PNQX. In primary neuronal cell cultures both MK-801 and PNQX inhibited sPLA - and glutamate-induced neuronal death. [ H]Arachidonic acid release induced by both sPLA and glutamate was partially blocked by MK-801, indicating that the glutamate-NMDA-cPLA pathway contributes to sPLA -induced arachidonic acid release. Systemic administration of MK-801 to rats that had sPLA injected into the right striatum significantly decreased neuronal cell death. We conclude that glutamatergic synaptic activity modulates sPLA -induced neuronal cell death. PMID:12395100

  10. Fetal deaths in Brazil: a systematic review

    PubMed Central

    Barbeiro, Fernanda Morena dos Santos; Fonseca, Sandra Costa; Tauffer, Mariana Girão; Ferreira, Mariana de Souza Santos; da Silva, Fagner Paulo; Ventura, Patrícia Mendonça; Quadros, Jesirée Iglesias

    2015-01-01

    OBJECTIVE To review the frequency of and factors associated with fetal death in the Brazilian scientific literature. METHODS A systematic review of Brazilian studies on fetal deaths published between 2003 and 2013 was conducted. In total, 27 studies were analyzed; of these, 4 studies addressed the quality of data, 12 were descriptive studies, and 11 studies evaluated the factors associated with fetal death. The databases searched were PubMed and Lilacs, and data extraction and synthesis were independently performed by two or more examiners. RESULTS The level of completeness of fetal death certificates was deficient, both in the completion of variables, particularly sociodemographic variables, and in defining the underlying causes of death. Fetal deaths have decreased in Brazil; however, inequalities persist. Analysis of the causes of death indicated maternal morbidities that could be prevented and treated. The main factors associated with fetal deaths were absent or inadequate prenatal care, low education level, maternal morbidity, and adverse reproductive history. CONCLUSIONS Prenatal care should prioritize women that are most vulnerable (considering their social environment or their reproductive history and morbidities) with the aim of decreasing the fetal mortality rate in Brazil. Adequate completion of death certificates and investment in the committees that investigate fetal and infant deaths are necessary. PMID:25902565

  11. The definition and criterion of death.

    PubMed

    Bernat, James L

    2013-01-01

    The definition and criterion of death have been rendered ambiguous by developments in organ support technology, particularly the positive-pressure ventilator and vasopressor medications, that uncouple the unitary loss of vital functions in death and create cases in which the brain has been destroyed while circulation and ventilation can be supported. Developing a biophilosophic analysis of the meaning of death before physicians can declare it requires four sequential steps: (1) agreement on the paradigm conditions that frame the analysis and clarify the task; (2) identifying the definition of death, which makes explicit the meaning of death that is accepted in our consensual usage of the term but that has become obscured by technology; (3) identifying the criterion of death that shows that the definition has been fulfilled, and that can be incorporated into a death statute; and (4) devising bedside tests of death for physicians to perform to satisfy the criterion. Although there is a strong consensus on death determination medical standards in countries around the world that has been enshrined into laws, and accepted by most societies and religions, there remains an active dispute among scholars on the precise definition and criterion of death. PMID:24182395

  12. Apoptotic Cell Death in Neuroblastoma

    PubMed Central

    Li, Yuanyuan; Nakagawara, Akira

    2013-01-01

    Neuroblastoma (NB) is one of the most common malignant solid tumors in childhood, which derives from the sympathoadrenal lineage of the neural crest and exhibits extremely heterogeneous biological and clinical behaviors. The infant patients frequently undergo spontaneous regression even with metastatic disease, whereas the patients of more than one year of age who suffer from disseminated disease have a poor outcome despite intensive multimodal treatment. Spontaneous regression in favorable NBs has been proposed to be triggered by nerve growth factor (NGF) deficiency in the tumor with NGF dependency for survival, while aggressive NBs have defective apoptotic machinery which enables the tumor cells to evade apoptosis and confers the resistance to treatment. This paper reviews the molecules and pathways that have been recently identified to be involved in apoptotic cell death in NB and discusses their potential prospects for developing more effective therapeutic strategies against aggressive NB. PMID:24709709

  13. Moral individualism and elective death.

    PubMed

    Prado, C G

    2013-01-01

    Moral individualism (Brooks, 2011; Smith, 2011) is a contemporary interpretation of morality as entirely a matter of personal choice. It is a popular rather than theory-based interpretation and has a number of social generative sources related to present-day preoccupation with individuality and personal distinctiveness. A key generative source is popularization of postmodernism, which prioritizes self-reinvention and provides moral individualism with the appearance of intellectual legitimacy. Moral individualism is a deeply flawed misconception of morality because it abolishes moral communality. My concern in this paper is that in doing so, it seriously jeopardizes productive discussion of the moral permissibility of elective death or choosing to die in despairingly and dire circumstances. PMID:23845164

  14. How cell death shapes cancer

    PubMed Central

    Labi, V; Erlacher, M

    2015-01-01

    Apoptosis has been established as a mechanism of anti-cancer defense. Members of the BCL-2 family are critical mediators of apoptotic cell death in health and disease, often found to be deregulated in cancer and believed to lead to the survival of malignant clones. However, over the years, a number of studies pointed out that a model in which cell death resistance unambiguously acts as a barrier against malignant disease might be too simple. This is based on paradoxical observations made in tumor patients as well as mouse models indicating that apoptosis can indeed drive tumor formation, at least under certain circumstances. One possible explanation for this phenomenon is that apoptosis can promote proliferation critically needed to compensate for cell loss, for example, upon therapy, and to restore tissue homeostasis. However, this, at the same time, can promote tumor development by allowing expansion of selected clones. Usually, tissue resident stem/progenitor cells are a major source for repopulation, some of them potentially carrying (age-, injury- or therapy-induced) genetic aberrations deleterious for the host. Thereby, apoptosis might drive genomic instability by facilitating the emergence of pathologic clones during phases of proliferation and subsequent replication stress-associated DNA damage. Tumorigenesis initiated by repeated cell attrition and repopulation, as confirmed in different genetic models, has parallels in human cancers, exemplified in therapy-induced secondary malignancies and myelodysplastic syndromes in patients with congenital bone marrow failure syndromes. Here, we aim to review evidence in support of the oncogenic role of stress-induced apoptosis. PMID:25741600

  15. Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012

    PubMed Central

    Galluzzi, L; Vitale, I; Abrams, J M; Alnemri, E S; Baehrecke, E H; Blagosklonny, M V; Dawson, T M; Dawson, V L; El-Deiry, W S; Fulda, S; Gottlieb, E; Green, D R; Hengartner, M O; Kepp, O; Knight, R A; Kumar, S; Lipton, S A; Lu, X; Madeo, F; Malorni, W; Mehlen, P; Nuñez, G; Peter, M E; Piacentini, M; Rubinsztein, D C; Shi, Y; Simon, H-U; Vandenabeele, P; White, E; Yuan, J; Zhivotovsky, B; Melino, G; Kroemer, G

    2012-01-01

    In 2009, the Nomenclature Committee on Cell Death (NCCD) proposed a set of recommendations for the definition of distinct cell death morphologies and for the appropriate use of cell death-related terminology, including ‘apoptosis', ‘necrosis' and ‘mitotic catastrophe'. In view of the substantial progress in the biochemical and genetic exploration of cell death, time has come to switch from morphological to molecular definitions of cell death modalities. Here we propose a functional classification of cell death subroutines that applies to both in vitro and in vivo settings and includes extrinsic apoptosis, caspase-dependent or -independent intrinsic apoptosis, regulated necrosis, autophagic cell death and mitotic catastrophe. Moreover, we discuss the utility of expressions indicating additional cell death modalities. On the basis of the new, revised NCCD classification, cell death subroutines are defined by a series of precise, measurable biochemical features. PMID:21760595

  16. Donation after cardio-circulatory death liver transplantation

    PubMed Central

    Le Dinh, Hieu; de Roover, Arnaud; Kaba, Abdour; Lauwick, Séverine; Joris, Jean; Delwaide, Jean; Honoré, Pierre; Meurisse, Michel; Detry, Olivier

    2012-01-01

    The renewed interest in donation after cardio-circulatory death (DCD) started in the 1990s following the limited success of the transplant community to expand the donation after brain-death (DBD) organ supply and following the request of potential DCD families. Since then, DCD organ procurement and transplantation activities have rapidly expanded, particularly for non-vital organs, like kidneys. In liver transplantation (LT), DCD donors are a valuable organ source that helps to decrease the mortality rate on the waiting lists and to increase the availability of organs for transplantation despite a higher risk of early graft dysfunction, more frequent vascular and ischemia-type biliary lesions, higher rates of re-listing and re-transplantation and lower graft survival, which are obviously due to the inevitable warm ischemia occurring during the declaration of death and organ retrieval process. Experimental strategies intervening in both donors and recipients at different phases of the transplantation process have focused on the attenuation of ischemia-reperfusion injury and already gained encouraging results, and some of them have found their way from pre-clinical success into clinical reality. The future of DCD-LT is promising. Concerted efforts should concentrate on the identification of suitable donors (probably Maastricht category III DCD donors), better donor and recipient matching (high risk donors to low risk recipients), use of advanced organ preservation techniques (oxygenated hypothermic machine perfusion, normothermic machine perfusion, venous systemic oxygen persufflation), and pharmacological modulation (probably a multi-factorial biologic modulation strategy) so that DCD liver allografts could be safely utilized and attain equivalent results as DBD-LT. PMID:22969222

  17. Mcl-1 dynamics influence mitotic slippage and death in mitosis

    PubMed Central

    Sloss, Olivia; Topham, Caroline; Diez, Maria; Taylor, Stephen

    2016-01-01

    Microtubule-binding drugs such as taxol are frontline treatments for a variety of cancers but exactly how they yield patient benefit is unclear. In cell culture, inhibiting microtubule dynamics prevents spindle assembly, leading to mitotic arrest followed by either apoptosis in mitosis or slippage, whereby a cell returns to interphase without dividing. Myeloid cell leukaemia-1 (Mcl-1), a pro-survival member of the Bcl-2 family central to the intrinsic apoptosis pathway, is degraded during a prolonged mitotic arrest and may therefore act as a mitotic death timer. Consistently, we show that blocking proteasome-mediated degradation inhibits taxol-induced mitotic apoptosis in a Mcl-1-dependent manner. However, this degradation does not require the activity of either APC/C-Cdc20, FBW7 or MULE, three separate E3 ubiquitin ligases implicated in targeting Mcl-1 for degradation. This therefore challenges the notion that Mcl-1 undergoes regulated degradation during mitosis. We also show that Mcl-1 is continuously synthesized during mitosis and that blocking protein synthesis accelerates taxol induced death-in-mitosis. Modulating Mcl-1 levels also influences slippage; overexpressing Mcl-1 extends the time from mitotic entry to mitotic exit in the presence of taxol, while inhibiting Mcl-1 accelerates it. We suggest that Mcl-1 competes with Cyclin B1 for binding to components of the proteolysis machinery, thereby slowing down the slow degradation of Cyclin B1 responsible for slippage. Thus, modulating Mcl-1 dynamics influences both death-in-mitosis and slippage. However, because mitotic degradation of Mcl-1 appears not to be under the control of an E3 ligase, we suggest that the notion of network crosstalk is used with caution. PMID:26769847

  18. Clarifying the discussion on brain death.

    PubMed

    Dagi, F T; Kaufman, R

    2001-10-01

    Definitions of death are based on subjective standards, priorities, and social conventions rather than on objective facts about the state of human physiology. It is the meaning assigned to the facts that determines when someone may be deemed to have died, not the facts themselves. Even though subjective standards for the diagnosis of death show remarkable consistency across communities, they are extrinsic. They are driven, implicitly or explicitly, by ideas about what benefits the community rather than what benefits the individual. The differences that do exist across communities generally reduce to questions about legitimacy and not fact. The questions at the core of the debate about brain death are better framed by asking: "Whom ought we deem to be dead?" rather than: "Who is dead." The rationale for equating brain death with death, therefore, extends well beyond somatic and biological concepts of death. PMID:11588657

  19. Death in Unverricht-Lundborg disease.

    PubMed

    Khiari, Hela Mrabet; Franceschetti, Silvana; Jovic, Nebojsa; Mrabet, Amel; Genton, Pierre

    2009-08-01

    The objective of this study is to report cases of unexpected deaths in Unverricht-Lundborg disease (ULD) patients, a comparatively benign form of progressive myoclonus epilepsy. We performed a multicentric study of the circumstances of death in ULD patients seen in the last 16 years. We assessed age, sex, severity and duration of disease, antiepileptic drugs, circumstances and presumed cause of death. Nineteen observations (12 females, 7 males) were collected from four centers (Tunis, Marseille, Milan, Belgrade). The most common causes of death are (1) SUDEP (six cases, all female), with 4/6 on phenobarbital alone, and (2) complications of severe ULD (six cases). Two patients committed suicide. Only one death was clearly unrelated to ULD (car accident), while four patients died of stroke, drowning, complications of chronic alcoholism and Wernicke encephalopathy, respectively. In conclusion, although the prognosis of ULD has progressed, there are still spontaneously severe forms and high risk of early death, including SUDEP. PMID:19499178

  20. Pathogen Tactics to Manipulate Plant Cell Death.

    PubMed

    Mukhtar, M Shahid; McCormack, Maggie E; Argueso, Cristiana T; Pajerowska-Mukhtar, Karolina M

    2016-07-11

    Cell death is a vital process for multicellular organisms. Programmed cell death (PCD) functions in a variety of processes including growth, development, and immune responses for homeostasis maintenance. In particular, plants and animals utilize PCD to control pathogen invasion and infected cell populations. Despite some similarity, there are a number of key differences between how these organisms initiate and regulate cell death. In contrast to animals, plants are sessile, lack a circulatory system, and have additional cellular structures, including cell walls and chloroplasts. Plant cells have the autonomous ability to induce localized cell death using conserved eukaryotic pathways as well as unique plant-specific pathways. Thus, in order to successfully infect host cells, pathogens must subvert immune responses and avoid detection to prevent PCD and allow infection. Here we discuss the roles of cell death in plant immune responses and the tactics pathogens utilize to avert cell death. PMID:27404256

  1. Detection of Cell Death in Drosophila Tissues

    PubMed Central

    Vasudevan, Deepika; Ryoo, Hyung Don

    2016-01-01

    Drosophila has served as a particularly attractive model to study cell death due to the vast array of tools for genetic manipulation under defined spatial and temporal conditions in vivo as well as in cultured cells. These genetic methods have been well supplemented by enzymatic assays and a panel of antibodies recognizing cell death markers. This chapter discusses reporters, mutants and assays used by various laboratories to study cell death in the context of development and in response to external insults. PMID:27108437

  2. [Fear of death: fear of life?].

    PubMed

    Erthal, T C

    1986-09-01

    This paper analyzes death as it is perceived and experienced in psychotherapeutic contexts: as a future possibility, as a loss of loved persons and as the near end as it happens with terminal patients. After a distinction between biological and psychological death, the hermeneutics of Heidegger, Sartre, Feifel and Krishnamurti are discussed. It is then suggested that death becomes more actual as a threat the less the individual profits from his existential possibilities. PMID:3591397

  3. What cell death does in development.

    PubMed

    Zakeri, Zahra; Penaloza, Carlos G; Smith, Kyle; Ye, Yixia; Lockshin, Richard A

    2015-01-01

    Cell death is prominent in gametogenesis and shapes and sculpts embryos. In non-mammalian embryos one sees little or no cell death prior to the maternal-zygotic transition, but, in mammalian embryos, characteristic deaths of one or two cells occur at the end of compaction and are apparently necessary for the separation of the trophoblast from the inner cell mass. Considerable sculpting of the embryo occurs by cell deaths during organogenesis, and appropriate cell numbers, especially in the CNS and in the immune system, are generated by massive overproduction of cells and selection of a few, with death of the rest. The timing, identity, and genetic control of specific cells that die have been well documented in Caenorhabditis, but in other embryos the stochastic nature of the deaths limit our ability to do more than identify the regions in which cells will die. Complete disruption of the cell death machinery can be lethal, but many mutations of the regulatory machinery yield only modest or no phenotypes, indicating substantial redundancy and compensation of regulatory mechanisms. Most of the deaths are apoptotic and are identified by techniques used to recognize apoptosis, but techniques identifying lysosomes (whether in dying or involuting cells or in the phagocytes that invade the tissue) also reveal patterns of cell death. Aberrant cell deaths that produce known phenotypes are typically localized, indicating that the mechanism of activating a programmed death in a specific region, rather than the mechanism of death, is aberrant. These results lead us to conclude that we need to know much more about the conversations among cells that lead cells to commit suicide. PMID:26374521

  4. Setting up a Death Row Psychiatry Program

    PubMed Central

    2011-01-01

    Death row psychiatry contains a complex set of clinical, ethical, and legal questions. This Forensic Files column makes a case for correctional institutions starting death row programs to address these issues through uniform policies. A list of the relevant issues is provided. Specific issues discussed include death row psychiatric assessment, considering “justifiable” depression, treating for competency to be executed, and balancing boundaries between clinical and forensic work. PMID:21468293

  5. Death-Defining Immune Responses After Apoptosis

    PubMed Central

    Campisi, L.; Cummings, R. J.; Blander, J. Magarian

    2014-01-01

    Apoptosis is a programmed form of cell death whereby characteristic internal cellular dismantling is accompanied by the preservation of plasma membrane integrity. Maintaining this order during apoptosis prevents the release of cellular contents and ensures a noninflammatory death. Here, we consider examples of apoptosis in different contexts and discuss how the same form of cell death could have different immunological consequences. Multiple parameters such as cell death as a result of microbial infection, the nature of the inflammatory microenvironment, the type of responding phagocytic cells and the genetic background of the host organism all differentially influence the immunological consequences of apoptosis. PMID:24903539

  6. 5 CFR 880.205 - Determinations of death.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Determinations of death. 880.205 Section... Determinations of death. OPM does not make findings of presumed death. A claimant for CSRS, FERS, or FEGLI death... § 880.207 must submit a death certificate or other legal certification of death issued by an...

  7. Death Education in the Nigerian Home: The Mother's Role.

    ERIC Educational Resources Information Center

    Okafor, Tr. Reuben Uche

    1993-01-01

    Notes that, in Nigeria, the death-awareness movement is new and the subject of death is still taboo. Sees women as occupying middle place between life and death. Offers rationale for death education in home and delineates role of mother with regard to death. Identifies likely problems mother may encounter in course of discharging her death duties.…

  8. 5 CFR 880.205 - Determinations of death.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 2 2012-01-01 2012-01-01 false Determinations of death. 880.205 Section... Determinations of death. OPM does not make findings of presumed death. A claimant for CSRS, FERS, or FEGLI death... § 880.207 must submit a death certificate or other legal certification of death issued by an...

  9. 5 CFR 880.205 - Determinations of death.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 2 2013-01-01 2013-01-01 false Determinations of death. 880.205 Section... Determinations of death. OPM does not make findings of presumed death. A claimant for CSRS, FERS, or FEGLI death... § 880.207 must submit a death certificate or other legal certification of death issued by an...

  10. 5 CFR 880.205 - Determinations of death.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false Determinations of death. 880.205 Section... Determinations of death. OPM does not make findings of presumed death. A claimant for CSRS, FERS, or FEGLI death... § 880.207 must submit a death certificate or other legal certification of death issued by an...

  11. 5 CFR 880.205 - Determinations of death.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 2 2014-01-01 2014-01-01 false Determinations of death. 880.205 Section... Determinations of death. OPM does not make findings of presumed death. A claimant for CSRS, FERS, or FEGLI death... § 880.207 must submit a death certificate or other legal certification of death issued by an...

  12. [Death certificates of women in childbearing age: search for maternal deaths].

    PubMed

    Gil, Mariana Marcos; Gomes-Sponholz, Flavia Azevedo

    2013-01-01

    In Brazil, there is a lack of complete records on death certificates, and its reliability is questioned, especially for causes attributed to pregnancy and childbirth. We investigated, based on death certificates of women in reproductive age, any fields for identifying maternal deaths. Documentary research, conducted in hospital records. We analyzed in death certificates, maternal and no maternal deaths, inconclusive deaths and hidden deaths. To analyze the underlying causes of death we used ICD 10th Revision. Of the 301 death certificates reviewed, 60% had the fields 43/44 completed, and 40% had these fields blank and/or ignored. We found 58.5% of no maternal deaths, 2% of maternal deaths and 39.5% inconclusive. The analysis of inconclusive deaths allowed us to classify 4.3% as hidden deaths. To overcome the incompletitudes of civil registries, it is necessary that all health professionals be committed to the reliability of the information, so the priority target could be reached. PMID:23887780

  13. Death Anxiety and Voluntary Passive Euthanasia: Influences of Proximity to Death and Experiences with Death in Important Other Persons.

    ERIC Educational Resources Information Center

    Devins, Gerald M.

    1979-01-01

    Identified five sources of death anxiety. Significant relationships were observed between each source and experimental factors. The relationship between death anxiety and attitude toward voluntary passive euthanasia was explored, and a significant correlation was noted among elderly persons. Results were consistent with an idiographic orientation…

  14. How should we measure maternal mortality in the developing world? A comparison of household deaths and sibling history approaches.

    PubMed Central

    Hill, Kenneth; El Arifeen, Shams; Koenig, Michael; Al-Sabir, Ahmed; Jamil, Kanta; Raggers, Han

    2006-01-01

    OBJECTIVE: A reduction in the maternal mortality ratio (MMR) is one of six health-related Millennium Development Goals (MDGs). However, there is no consensus about how to measure MMR in the many countries that do not have complete registration of deaths and accurate ascertainment of cause of death. In this study, we compared estimates of pregnancy-related deaths and maternal mortality in a developing country from three different household survey measurement approaches: a module collecting information on deaths of respondents' sisters; collection of information about recent household deaths with a time-of-death definition of maternal deaths; and a verbal autopsy instrument to identify maternal deaths. METHODS: We used data from a very large nationally-representative household sample survey conducted in Bangladesh in 2001. A total of 104 323 households were selected for participation, and 99 202 households (95.1% of selected households, 98.8% of contacted households) were successfully interviewed. FINDINGS: The sisterhood and household death approaches gave very similar estimates of all-cause and pregnancy-related mortality; verbal autopsy gave an estimate of maternal deaths that was about 15% lower than the pregnancy-related deaths. Even with a very large sample size, however, confidence intervals around mortality estimates were similar for all approaches and exceeded +/- 15%. CONCLUSION: Our findings suggest that with improved training for survey data collectors, both the sisterhood and household deaths methods are viable approaches for measuring pregnancy-related mortality. However, wide confidence intervals around the estimates indicate that routine sample surveys cannot provide the information needed to monitor progress towards the MDG target. Other approaches, such as inclusion of questions about household deaths in population censuses, should be considered. PMID:16583075

  15. Supported PV module assembly

    SciTech Connect

    Mascolo, Gianluigi; Taggart, David F.; Botkin, Jonathan D.; Edgett, Christopher S.

    2013-10-15

    A supported PV assembly may include a PV module comprising a PV panel and PV module supports including module supports having a support surface supporting the module, a module registration member engaging the PV module to properly position the PV module on the module support, and a mounting element. In some embodiments the PV module registration members engage only the external surfaces of the PV modules at the corners. In some embodiments the assembly includes a wind deflector with ballast secured to a least one of the PV module supports and the wind deflector. An array of the assemblies can be secured to one another at their corners to prevent horizontal separation of the adjacent corners while permitting the PV modules to flex relative to one another so to permit the array of PV modules to follow a contour of the support surface.

  16. Sudden Death Following Exercise; a Case Series

    PubMed Central

    Najari, Fares; Alimohammadi, Alimohammad; Ghodrati, Parisa

    2016-01-01

    Introduction: Natural and unexpected death that happens within less than one hour of first symptom occurrence is called sudden death. Cardiovascular diseases are the main known reason of sudden death and more than 75% of sudden deaths in athletes are assigned to it. Here we reported the autopsy results of all cases with sudden death following exercise that were referred to forensic center of Tehran, Iran, from 2009 to 2014. Methods: In this cross sectional study all subjects who were registered to forensic medicine center of Tehran, Iran, from 2009 to 2014, as a case of sudden death following exercise were evaluated. Demographic data and medical history as well as autopsy and toxicology findings were retrospectively gathered using profiles of the deceased. Results were reported using descriptive analysis. Results: 14 cases were registered as sudden death following exercise in forensic medicine profiles during the study period. Exploring the files of the mentioned deceased, revealed five non-compatible cases in this regard. Finally, 9 eligible cases were enrolled (88.9% male). The mean age of the deceased was 28.66 ± 10.86 years (range: 7 – 40). Toxicological tests were available for 7 cases, one of which was positive for tramadol. Sudden death following football was reported most frequently (44.4%). Only 3 (33.3%) cases had herald signs such as chest pain, syncope, or loss of consciousness. 1 case (11.11%) had a positive history of sudden death in relatives. Conclusion: Although most sudden death victims are asymptomatic until the event, all those who suffer from symptoms such as chest pain, shortness of breath, dizziness, fatigue and irregular heart rate during physical activities, should be screened regarding common probable causes of sudden death. PMID:27274521

  17. Sudden Cardiac Death Risk Stratification

    PubMed Central

    Deyell, Marc W.; Krahn, Andrew D.; Goldberger, Jeffrey J.

    2015-01-01

    Arrhythmic sudden cardiac death (SCD) may be due to ventricular tachycardia/fibrillation (SCD-VT/VF) or pulseless electrical activity/asystole. Effective risk stratification to identify patients at risk of arrhythmic SCD is essential for targeting our health care and research resources to tackle this important public health issue. Although our understanding of SCD due to pulseless electrical activity/asystole is growing, the overwhelming majority of research in risk stratification has focused on SCD-VT/VF. This review focuses on existing and novel risk stratification tools for SCD-VT/VF. For patients with left ventricular dysfunction and/or myocardial infarction, advances in imaging, measures of cardiac autonomic function, and measures of repolarization have shown considerable promise in refining risk. Yet the majority of SCD-VT/VF occurs in patients without known cardiac disease. Biomarkers and novel imaging techniques may provide further risk stratification in the general population beyond traditional risk stratification for coronary artery disease alone. Despite these advances, significant challenges in risk stratification remain that must be overcome before a meaningful impact on SCD can be realized. PMID:26044247

  18. Thymineless death, at the origin

    PubMed Central

    Guzmán, Elena C.; Martín, Carmen M.

    2015-01-01

    Thymineless death (TLD) in bacteria has been a focus of research for decades. Nevertheless, the advances in the last 5 years, with Escherichia coli as the model organism, have been outstanding. Independent research groups have presented compelling results that establish that the initiation of chromosome replication under thymine starvation is a key element in the scenario of TLD. Here we review the experimental results linking the initiation of replication to the lethality under thymine starvation and the proposed mechanisms by which TLD occurs. The concept of this relationship was ‘in the air,’ but approaches were not sufficiently developed to demonstrate the crucial role of DNA initiation in TLD. Genome-wide marker frequency analysis and Two Dimensional agarose gel electrophoresis have been critical methods employed to reveal that initiation events and the degradation of the oriC region occur during thymine starvation. The relationships between these events and TLD have established them to be the main underlying causes of the lethality under thymine starvation. Furthermore, we summarize additional important findings from the study of different mutant strains, which support the idea that the initiation of chromosomal replication and TLD are connected. PMID:26042116

  19. Death in the South Pacific.

    PubMed

    Beaglehole, R; Prior, I A; Foulkes, M A; Eyles, E F

    1980-05-28

    The pattern of mortality and the influence of blood pressure, serum cholesterol, and body mass on mortality is examined in 1980 adults in four contrasting South Pacific populations. Three of the populations are Polynesian: Pakapuka, an isolated coral atoll, Rarotonga, a less isolated volcanic island, and the New Zealand Maoris, and they are compared with a New Zealand caucasian sample. The baseline examinations were performed in 1963-64 and the cardiovascular risk factors and associated disease were found to be more prevalent in Polynesians with increasing westernisation. The dead or alive status was ascertained in 1974 for 99 percent of the subjects. The age standardised 10-11 year death rates also increased with increasing westernisation from 11.7 percent in Pukapukan men to 26.7 percent in Maori men. The Mantel-Haenszel method of analysis of survivorship data demonstrated a significant inverse relationship between baseline serum cholesterol and mortality in the New Zealand Maoris. Cox's proportional hazards regression model was used to examine the population differences in mortality and it was found that the variables studied do not explain these differences. This study demonstrates the adverse effect of esternisation on the health of Polynesians and suggests that the relationsip between risk factors and mortality differs between populations. PMID:6931320

  20. Accidental death involving professional fireworks.

    PubMed

    Romolo, Francesco Saverio; Aromatario, Mariarosaria; Bottoni, Edoardo; Cappelletti, Simone; Fiore, Paola Antonella; Ciallella, Costantino

    2014-01-01

    An interesting case of accidental death involving the explosion of professional fireworks in an apartment is described. The examination of the scene permitted to study several effects of the explosion on walls, ceiling, furniture and especially on a balcony where the victim was found. The external examination of the victim showed extensive thermal injuries, degloving injuries and extensive shrapnel wounds. The autopsy examination showed subarachnoid haemorrhage localized to the cerebellum, haemorrhage in the soft tissues of the neck and chest and fracture of one clavicle. Almost the entire surface of lungs showed blunt injuries and the liver showed tearing of parenchyma and multiple cavities. Histological analysis were carried out showing thickening of alveolar septae, enlargement of alveolar spaces and alveolar ruptures in lung sections while numerous, round, empty spaces were detected in the parenchyma of the liver. The examination of the scene and of the fragments found showed that at least eight pyrotechnical charges exploded on the balcony, in close proximity of the threshold with the living room of the apartment. According to the chemical findings, the charges were typical for professional use and were filled with a mixture of potassium perchlorate and aluminium. A conservative calculation results in more than 1.5 kg total mass of pyrotechnic composition exploding very close to the victim. PMID:24279979

  1. Natural Death and the Noble Savage.

    ERIC Educational Resources Information Center

    Walter, Tony

    1995-01-01

    The belief that dying and grieving are natural processes is widely held in modern bereavement care. Examines four assumption often made in this connection: (1) most primitive cultures deal with death in an accepting way; (2) this way is different than our own; (3) it is a good and noble way; and (4) traditional societies see death as natural. (JBJ)

  2. Programmed Cell Death During Caenorhabditis elegans Development.

    PubMed

    Conradt, Barbara; Wu, Yi-Chun; Xue, Ding

    2016-08-01

    Programmed cell death is an integral component of Caenorhabditis elegans development. Genetic and reverse genetic studies in C. elegans have led to the identification of many genes and conserved cell death pathways that are important for the specification of which cells should live or die, the activation of the suicide program, and the dismantling and removal of dying cells. Molecular, cell biological, and biochemical studies have revealed the underlying mechanisms that control these three phases of programmed cell death. In particular, the interplay of transcriptional regulatory cascades and networks involving multiple transcriptional regulators is crucial in activating the expression of the key death-inducing gene egl-1 and, in some cases, the ced-3 gene in cells destined to die. A protein interaction cascade involving EGL-1, CED-9, CED-4, and CED-3 results in the activation of the key cell death protease CED-3, which is tightly controlled by multiple positive and negative regulators. The activation of the CED-3 caspase then initiates the cell disassembly process by cleaving and activating or inactivating crucial CED-3 substrates; leading to activation of multiple cell death execution events, including nuclear DNA fragmentation, mitochondrial elimination, phosphatidylserine externalization, inactivation of survival signals, and clearance of apoptotic cells. Further studies of programmed cell death in C. elegans will continue to advance our understanding of how programmed cell death is regulated, activated, and executed in general. PMID:27516615

  3. Circadian variation in unexpected postoperative death.

    PubMed

    Rosenberg, J; Pedersen, M H; Ramsing, T; Kehlet, H

    1992-12-01

    Unexpected deaths still occur following major surgical procedures. The cause is often unknown but may be cardiac or thromboembolic in nature. Postoperative ischaemia, infarction and sudden cardiac death may be triggered by episodic or constant arterial hypoxaemia, which increases during the night. This study examined the circadian variation of sudden unexpected death following abdominal surgery between 1985 and 1989 inclusive. Deaths were divided into those occurring during the day (08.00-16.00 hours), evening (16.00-24.00 hours) and night (24.00-08.00 hours). Twenty-three deaths were considered to have been totally unexpected. Of 16 such patients undergoing autopsy, pulmonary embolism was the cause of death in five. In the remaining 11 patients, death occurred at night in eight (P < 0.005). Five of the seven patients without an autopsy died at night (P < 0.04); overall, 13 of 18 unexpected deaths occurred at night-time. These results suggest a need for further studies of sleep- and respiration-related effects on postoperative nocturnal cardiac function. The efficacy of monitoring during this apparent high-risk period should be evaluated. PMID:1486424

  4. Athletes at Risk for Sudden Cardiac Death

    ERIC Educational Resources Information Center

    Subasic, Kim

    2010-01-01

    High school athletes represent the largest group of individuals affected by sudden cardiac death, with an estimated incidence of once or twice per week. Structural cardiovascular abnormalities are the most frequent cause of sudden cardiac death. Athletes participating in basketball, football, track, soccer, baseball, and swimming were found to…

  5. Near-Death Experiences and Antisuicidal Attitudes.

    ERIC Educational Resources Information Center

    Greyson, Bruce

    1993-01-01

    One hundred-fifty near death experiencers (NDErs) and 43 individuals who had come close to death without having NDEs (nonNDErs) rated 12 antisuicidal attitudes. NDErs endorsed significantly more statements than did nonNDErs, and, among NDErs, number of statements endorsed was positively associated with depth of experience. Findings support…

  6. 5 CFR 1604.8 - Death benefits.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Death benefits. 1604.8 Section 1604.8 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD UNIFORMED SERVICES ACCOUNTS § 1604.8 Death benefits. The account balance of a deceased service member will be paid as described at 5 CFR part...

  7. 7 CFR 707.3 - Death.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false Death. 707.3 Section 707.3 Agriculture Regulations of the Department of Agriculture (Continued) FARM SERVICE AGENCY, DEPARTMENT OF AGRICULTURE AGRICULTURAL... Death. (a) Where any person who is otherwise eligible to receive a payment dies before the payment...

  8. 77 FR 64405 - Death of Arlen Specter

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-19

    ... thirty-seventh. (Presidential Sig.) [FR Doc. 2012-26011 Filed 10-18-12; 11:15 am] Billing code 3295-F3 ... October 19, 2012 Part III The President Proclamation 8890--Death of Arlen Specter #0; #0; #0; Presidential... Documents#0;#0; #0; #0;Title 3-- #0;The President ] Proclamation 8890 of October 15, 2012 Death of...

  9. 77 FR 53137 - Death of Neil Armstrong

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-30

    ... America the two hundred and thirty- seventh. (Presidential Sig.) [FR Doc. 2012-21638 Filed 8-29-12; 11:15... August 30, 2012 Part VII The President Proclamation 8849--Death of Neil Armstrong #0; #0; #0... / Presidential Documents#0;#0; #0; #0;Title 3-- #0;The President ] Proclamation 8849 of August 27, 2012 Death...

  10. 38 CFR 3.459 - Death compensation.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Death compensation. 3.459 Section 3.459 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency and Indemnity Compensation Apportionments § 3.459 Death compensation. (a)...

  11. Intergenerational Family Support Following Infant Death

    ERIC Educational Resources Information Center

    White, Diana L.; Walker, Alexis J.; Richards, Leslie N.

    2008-01-01

    The death of a child is a traumatic, nonnormative family life event. Although parental bereavement has received substantial attention, little research has focused on extended family members affected by a child's death, and still less on how multiple family members perceive and respond to one another following the loss. Guided by a life course…

  12. 42 CFR 110.33 - Death benefits.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Death benefits. 110.33 Section 110.33 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES COUNTERMEASURES INJURY COMPENSATION PROGRAM Available Benefits § 110.33 Death benefits. (a) Eligible survivors may be able to...

  13. 42 CFR 110.33 - Death benefits.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Death benefits. 110.33 Section 110.33 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES COUNTERMEASURES INJURY COMPENSATION PROGRAM Available Benefits § 110.33 Death benefits. (a) Eligible survivors may be able to...

  14. 42 CFR 110.33 - Death benefits.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Death benefits. 110.33 Section 110.33 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES COUNTERMEASURES INJURY COMPENSATION PROGRAM Available Benefits § 110.33 Death benefits. (a) Eligible survivors may be able to...

  15. 42 CFR 110.33 - Death benefits.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Death benefits. 110.33 Section 110.33 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES COUNTERMEASURES INJURY COMPENSATION PROGRAM Available Benefits § 110.33 Death benefits. (a) Eligible survivors may be able to...

  16. [Brain death, bioethics and organ transplantation].

    PubMed

    Flores, Juan Carlos; Pérez, Manuel; Thambo, Sergio; Valdivieso, Andrés

    2004-01-01

    The concept of death has evolved medically, legally and culturally since the introduction of life support technologies in the middle of the 20th century. The traditional cardiopulmonary and the new neurologically based brain death criterions of death are examined. We conclude that brain death, defined as total and irreversible loss of function of the whole brain, fulfills better "the permanent cessation of functioning of the organism as a whole" definition of death. Brain death diagnosis, based on standard neurologic clinical examination performed accurately, is unequivocal. Transplantation medicine, mostly based on organ donation of brain dead people, has become a routine and universally accepted therapeutic intervention nowadays, which benefits many people. Ethics foundations of organ transplantation are reviewed. Even though brain death and organ donation are widely accepted in medical, legal, religious and public opinion today, the whole society and medical community need to be further educated about these matters, so that unavoidable changes of traditional concepts might be better understood. Permanent education should be the best way to dissipate social fears and distrust towards organ donation and brain death. PMID:15379061

  17. Towards a definition of death anxiety.

    PubMed

    Nyatunga, Brian

    2006-09-01

    There is currently no consensus about what the notion of death anxiety means. This commentary explores the complexity of death anxiety, asserts the distinction between anxiety and fear, and attempts a definition that encompasses the many facets associated with the term. PMID:17077799

  18. 5 CFR 1604.8 - Death benefits.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 3 2012-01-01 2012-01-01 false Death benefits. 1604.8 Section 1604.8 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD UNIFORMED SERVICES ACCOUNTS § 1604.8 Death benefits. The account balance of a deceased service member will be paid as described at 5 CFR part 1651....

  19. 5 CFR 1604.8 - Death benefits.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 3 2011-01-01 2011-01-01 false Death benefits. 1604.8 Section 1604.8 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD UNIFORMED SERVICES ACCOUNTS § 1604.8 Death benefits. The account balance of a deceased service member will be paid as described at 5 CFR part 1651....

  20. 38 CFR 3.459 - Death compensation.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Death compensation. 3.459 Section 3.459 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency and Indemnity Compensation Apportionments § 3.459 Death compensation. (a)...

  1. 38 CFR 3.459 - Death compensation.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Death compensation. 3.459 Section 3.459 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency and Indemnity Compensation Apportionments § 3.459 Death compensation. (a)...

  2. 38 CFR 3.459 - Death compensation.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Death compensation. 3.459 Section 3.459 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency and Indemnity Compensation Apportionments § 3.459 Death compensation. (a)...

  3. 38 CFR 3.459 - Death compensation.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Death compensation. 3.459 Section 3.459 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency and Indemnity Compensation Apportionments § 3.459 Death compensation. (a)...

  4. Cell death independent of caspases: a review.

    PubMed

    Bröker, Linda E; Kruyt, Frank A E; Giaccone, Giuseppe

    2005-05-01

    Patterns of cell death have been divided into apoptosis, which is actively executed by specific proteases, the caspases, and accidental necrosis. However, there is now accumulating evidence indicating that cell death can occur in a programmed fashion but in complete absence and independent of caspase activation. Alternative models of programmed cell death (PCD) have therefore been proposed, including autophagy, paraptosis, mitotic catastrophe, and the descriptive model of apoptosis-like and necrosis-like PCD. Caspase-independent cell death pathways are important safeguard mechanisms to protect the organism against unwanted and potential harmful cells when caspase-mediated routes fail but can also be triggered in response to cytotoxic agents or other death stimuli. As in apoptosis, the mitochondrion can play a key role but also other organelles such as lysosomes and the endoplasmic reticulum have an important function in the release and activation of death factors such as cathepsins, calpains, and other proteases. Here we review the various models of PCD and their death pathways at molecular and organelle level and discuss the relevance of the growing knowledge of caspase-independent cell death pathways for cancer. PMID:15867207

  5. The Making of a Death Educator.

    ERIC Educational Resources Information Center

    Crase, Darrell

    1982-01-01

    Suggests that although death education has become part of the curriculum within many colleges, few attempts have been made toward providing formal preparation for the beginning teacher. Provides some answers to questions that may confront the neophyte death educator relative to self-development, resources, goals, and student reactions. (Author)

  6. The Declaration of Sydney on human death.

    PubMed

    Machado, C; Korein, J; Ferrer, Y; Portela, L; García, M de la C; Chinchilla, M; Machado, Y; Machado, Y; Manero, J M

    2007-12-01

    On 5 August 1968, publication of the Harvard Committee's report on the subject of "irreversible coma" established a standard for diagnosing death on neurological grounds. On the same day, the 22nd World Medical Assembly met in Sydney, Australia, and announced the Declaration of Sydney, a pronouncement on death, which is less often quoted because it was overshadowed by the impact of the Harvard Report. To put those events into present-day perspective, the authors reviewed all papers published on this subject and the World Medical Association web page and documents, and corresponded with Dr A G Romualdez, the son of Dr A Z Romualdez. There was vast neurological expertise among some of the Harvard Committee members, leading to a comprehensible and practical clinical description of the brain death syndrome and the way to diagnose it. This landmark account had a global medical and social impact on the issue of human death, which simultaneously lessened reception of the Declaration of Sydney. Nonetheless, the Declaration of Sydney faced the main conceptual and philosophical issues on human death in a bold and forthright manner. This statement differentiated the meaning of death at the cellular and tissue levels from the death of the person. This was a pioneering view on the discussion of human death, published as early as in 1968, that should be recognised by current and future generations. PMID:18055899

  7. Death and Society in Twentieth Century America.

    ERIC Educational Resources Information Center

    Fulton, Robert; Owen, Greg

    1988-01-01

    Discusses how American experiences with death have changed since 1900 and shows how changes have served to transform attitudes and responses toward death. Compares individuals born prior to advent of atomic bomb to those born in nuclear age, and considers pervasive influence of television and other media in changing attitudes. (Author/NB)

  8. Cell death regulates muscle fiber number.

    PubMed

    Sarkissian, Tatevik; Arya, Richa; Gyonjyan, Seda; Taylor, Barbara; White, Kristin

    2016-07-01

    Cell death can have both cell autonomous and non-autonomous roles in normal development. Previous studies have shown that the central cell death regulators grim and reaper are required for the developmentally important elimination of stem cells and neurons in the developing central nervous system (CNS). Here we show that cell death in the nervous system is also required for normal muscle development. In the absence of grim and reaper, there is an increase in the number of fibers in the ventral abdominal muscles in the Drosophila adult. This phenotype can be partially recapitulated by inhibition of cell death specifically in the CNS, indicating a non-autonomous role for neuronal death in limiting muscle fiber number. We also show that FGFs produced in the cell death defective nervous system are required for the increase in muscle fiber number. Cell death in the muscle lineage during pupal stages also plays a role in specifying fiber number. Our work suggests that FGFs from the CNS act as a survival signal for muscle founder cells. Thus, proper muscle fiber specification requires cell death in both the nervous system and in the developing muscle itself. PMID:27131625

  9. The Declaration of Sydney on human death

    PubMed Central

    Machado, C; Korein, J; Ferrer, Y; Portela, L; de la C García, M; Chinchilla, M; Machado, Y; Machado, Y; Manero, J M

    2007-01-01

    On 5 August 1968, publication of the Harvard Committee's report on the subject of “irreversible coma” established a standard for diagnosing death on neurological grounds. On the same day, the 22nd World Medical Assembly met in Sydney, Australia, and announced the Declaration of Sydney, a pronouncement on death, which is less often quoted because it was overshadowed by the impact of the Harvard Report. To put those events into present-day perspective, the authors reviewed all papers published on this subject and the World Medical Association web page and documents, and corresponded with Dr A G Romualdez, the son of Dr A Z Romualdez. There was vast neurological expertise among some of the Harvard Committee members, leading to a comprehensible and practical clinical description of the brain death syndrome and the way to diagnose it. This landmark account had a global medical and social impact on the issue of human death, which simultaneously lessened reception of the Declaration of Sydney. Nonetheless, the Declaration of Sydney faced the main conceptual and philosophical issues on human death in a bold and forthright manner. This statement differentiated the meaning of death at the cellular and tissue levels from the death of the person. This was a pioneering view on the discussion of human death, published as early as in 1968, that should be recognised by current and future generations. PMID:18055899

  10. "Death with dignity" in the Japanese context.

    PubMed

    Shimoda, Motomu

    2005-01-01

    In Japan, "death with dignity" is a widely known term that is distinguished from "euthanasia." It is generally defined as "the act of letting a terminally ill or a patient in a persistent vegetative state die by withdrawing life-sustaining treatment on request in the form of a living will." Most Japanese people consider death with dignity a desirable way of terminating one's life and it is therefore acceptable as a "natural death" or "humane death." Originally, death with dignity was regarded as a passive intervention, but since the 1990s, its connotations have changed in western countries; people claim that voluntary active euthanasia and physician-assisted suicide should be legalized as death with dignity or the "right to die." In this paper, I examine the points and problems of this new type of death with dignity and propose an alternative version of death with dignity especially for the Japanese context, i.e. the end-of-life care process in support of terminal living with dignity. PMID:16637137

  11. Making War on Death and on Persons.

    ERIC Educational Resources Information Center

    Balk, David E.

    1994-01-01

    Reviews "On Death without Dignity: The Human Impact of Technological Dying" by David W. Moller. Describes author as well grounded in concepts and theories chosen for analysis. States that the author supports contention that modern society fosters dehumanized dying which obscures death through technological control with little communal support for…

  12. Student Death Protocols: A Practitioner's Perspective

    ERIC Educational Resources Information Center

    Callahan, Cheryl M.; Fox, Erin K.

    2008-01-01

    Student death on college campuses is a reality that occurs all too often, and dealing with the aftermath of a student's death is something that all higher education administrators must be prepared to address. Given the proliferation of media outlets, breaking news reports, and instant technologies used by students today, news about these deaths…

  13. The Academic Study of Death and Dying.

    ERIC Educational Resources Information Center

    Amend, Edward W.

    The current study of death and dying is an example of constant change and development in academic disciplines. While the discussion of death in time of crisis is hard, if not impossible, youthful undergraduates find this topic to be of considerable interest. For them, a course can be organized effectively as a small and intimate seminar, which…

  14. Teachers' Attitudes Toward Death-Related Issues

    ERIC Educational Resources Information Center

    Perkes, A. Cordell

    1978-01-01

    Reports a study to assess teachers attitudes toward death-related issues. A questionnaire was given to 61 teachers in a graduate education course. It was found that the teachers tended to favor liberal abortion laws (67 percent), euthanasia (83 percent), and the majority (65 percent) believed in life after death. (SLH)

  15. JNK Inhibition Reduced Retinal Ganglion Cell Death after Ischemia/Reperfusion In Vivo and after Hypoxia In Vitro.

    PubMed

    Produit-Zengaffinen, Nathalie; Favez, Tatiana; Pournaras, Constantin J; Schorderet, Daniel F

    2016-01-01

    Mitogen-activated protein kinases (MAPKs) are key regulators that have been linked to cell survival and death. Among the main classes of MAPKs, c-jun N-terminal kinase (JNK) has been shown to mediate cell stress responses associated with apoptosis. In Vitro, hypoxia induced a significant increase in 661W cell death that paralleled increased activity of JNK and c-jun. 661W cells cultured in presence of the inhibitor of JNK (D-JNKi) were less sensitive to hypoxia-induced cell death. In vivo, elevation in intraocular pressure (IOP) in the rat promoted cell death that correlated with modulation of JNK activation. In vivo inhibition of JNK activation with D-JNKi resulted in a significant and sustained decrease in apoptosis in the ganglion cell layer, the inner nuclear layer and the photoreceptor layer. These results highlight the protective effect of D-JNKi in ischemia/reperfusion induced cell death of the retina. PMID:26427475

  16. Death Education and Attitudes of Counselors-in-Training toward Death: An Exploratory Study

    ERIC Educational Resources Information Center

    Harrawood, Laura K.; Doughty, Elizabeth A.; Wilde, Brandon

    2011-01-01

    This study reviewed how attitudes of counselors-in-training toward death develop after completing a course on death education. Participants included 11 graduate counseling students enrolled in a 2-credit-hour course addressing death and dying, and grief and loss. Qualitative results from a content analysis of free-response narratives suggest the…

  17. Attitude Toward Death, Fear of Being Declared Dead Too Soon, and Donation of Organs After Death.

    ERIC Educational Resources Information Center

    Hessing, Dick J.; Elffers, Henk

    1987-01-01

    Describes a study of willingness to donate organs for transplantation after death based on Weyant's cost-benefit model for altruistic behavior. Two death anxieties (the attitude toward death and the fear of being declared dead too soon) were introduced to help explain the discrepancy between attitudes and behavior in the matter of organ donation.…

  18. Death in dental clinic: Indian scenario.

    PubMed

    Seshappa, Kedarnath Nakkalahalli; Rangaswamy, Shruthi

    2016-01-01

    Deaths during dental treatment or as a result of dental treatment are rare, but the unfortunate fact is that such deaths do occur. Unexpected death of a patient can be emotionally draining and even harrowing to his or her relatives. The death of a patient may bring an enormous feeling of anxiety both at the personal and professional level, stress, profound grief, damage to self-esteem, loss of self-confidence, reputation, and specter of litigation on a dental surgeon. No dentist can be guaranteed to be free of such an incident during the course of his or her practice. The dentist should respond in a compassionate and respectful manner in case of such unfortunate tragic events, and also ensure self-protection. This article emphasizes on prevention of such incidents and throws some light on how to respond in case of an unfortunate death in a dental clinic, including the medico-legal aspects. PMID:27555720

  19. Sudden death in hemodialysis: an update.

    PubMed

    Kanbay, Mehmet; Afsar, Baris; Goldsmith, David; Covic, Adrian

    2010-01-01

    Cardiovascular disease including sudden death, myocardial infarction, cardiac arrest, malignant arrhythmias and other cardiac causes is the major cause of death accounting for 43% of all-cause mortality among hemodialysis patients. In addition to increased traditional risk factors, hemodialysis patients also have a number of nontraditional cardiovascular risk factors, which may play a prominent role in the development of sudden death such as left ventricular hypertrophy, coronary artery disease, rapid electrolyte shifts, QT dispersion, sympathetic overactivity, calcium-phosphate deposition. The purpose of the present review was to critically review the current literature to summarize the following aspects: (1) the pathophysiological mechanism responsible for sudden death in hemodialysis patients, and (2) the prevention and management of sudden death in hemodialysis patients. PMID:20798493

  20. Death in dental clinic: Indian scenario

    PubMed Central

    Seshappa, Kedarnath Nakkalahalli; Rangaswamy, Shruthi

    2016-01-01

    Deaths during dental treatment or as a result of dental treatment are rare, but the unfortunate fact is that such deaths do occur. Unexpected death of a patient can be emotionally draining and even harrowing to his or her relatives. The death of a patient may bring an enormous feeling of anxiety both at the personal and professional level, stress, profound grief, damage to self-esteem, loss of self-confidence, reputation, and specter of litigation on a dental surgeon. No dentist can be guaranteed to be free of such an incident during the course of his or her practice. The dentist should respond in a compassionate and respectful manner in case of such unfortunate tragic events, and also ensure self-protection. This article emphasizes on prevention of such incidents and throws some light on how to respond in case of an unfortunate death in a dental clinic, including the medico-legal aspects. PMID:27555720

  1. [Death as a process: an anthropological perspective].

    PubMed

    Martínez, Bárbara

    2013-09-01

    This article combines recent approximations that question the homology between death and biological demise from an anthropological perspective with the tradition of studies that review the death rituals in the Andean geographical area. In particular, it examines how in El Cajón, Catamarca, Northeast Argentina the dead are incorporated in the cosmologic scheme, and how death, being the initial step for this to occur, is not merely a biological event but also a highly dynamic social process. Based on ethnographical field work and using multiple-session open interviews and participant observation as methodological tools, it presents an analytical proposal that seeks to transcend the homology between death and biological demise, suggesting a notion that includes not only the organic dimension but also the social dimension: the process of death. PMID:23989575

  2. Brain death and organ donation of children.

    PubMed

    Gündüz, Ramiz Coşkun; Şahin, Şanlıay; Uysal-Yazıcı, Mutlu; Ayar, Ganime; Yakut, Halil İbrahim; Akman, Alkım Öden; Hirfanoğlu, İbrahim Murat; Kalkan, Gökhan

    2014-01-01

    We aimed to define the demographic characteristics, clinical features and outcome of patients with brain death, and to emphasize the importance of organ donation from children. Data for the period from September 2009 to October 2012 were collected retrospectively. Twenty children who were diagnosed as brain death were included. Data including demographics, major cause leading to brain death, duration of brain death evaluation, ancillary tests used to confirm brain death, complications and outcome, duration of hospitalization and organ donation were collected for statistical evaluation. The mean age was 6.2 years, and the male/female ratio 1.85. The major cause leading to brain death was most often traumatic brain injury, seen in 11 patients (55%). The mean duration of brain death evaluation was 6.7 and 1.7 days in Centers I and II respectively. The mean duration of hospitalization was 12.5 days. Electroencephalography (EEG) was used in 18 patients (90%). Complications included hyperglycemia in 13 cases and diabetes incipitus in 7 cases (65% and 35%, respectively). Mean duration of survival was 9.8 days. In Center I, one of the patients' parents gave consent to organ donation, while four parents in Center II agreed to organ donation. The study demonstrated that the duration of brain death evaluation was longer in Center I than in Center II (p<0.05). When both centers were compared, there was no significant difference in regard to obtaining consent for organ donation, survival after diagnosis of brain death and length of stay in the PICU (p>0.05). Early diagnosis of brain death and prompt evaluation of patients by ICU physicians once the diagnosis is taken into consideration will probably yield better organs and reduce costs. Training PICU physicians, nurses and organ donation coordinators, and increasing children's awareness of the need for organ donation via means of public communication may increase families' rate of agreement to organ donation in the future. PMID

  3. Death in the eyes of the beholder.

    PubMed

    Fry-Revere, S; Bastani, B

    2010-01-01

    The US Uniform Determination of Death Act provides two alternatives for determining death-the circulatory criteria and the neurological criteria-yet history and the public's current understanding of death in the US may mean that only brain death criteria can be relied upon without raising public suspicion that the medical profession is sacrificing the well-being of one group of patients (i.e., those dying after traumatic injury) to save another group (i.e., those in need of organs). The problem is exacerbated by existing debate on the appropriate waiting time after which death is inevitable and when the brain should be actually considered dead through prolonged absence of autoresuscitation. Given the difficulty of definitive determination of the time when brain function has ceased, two solutions are proposed: abandon the Dead Donor Rule or redefine death. Implementing the former would mean convincing the public to accept organ harvesting before the dying patient is completely brain dead through the writing of advance directives to permit organ harvest when death is inevitable though not confirmed. For the latter, reeducation would be necessary to persuade the public to accept the circulatory criteria for death as an independent determinant for death or the medical community would need to reconsider if the cessation of higher brain function is enough to be the basis for determining death. In conclusion, organ retrieval policies, no matter how medically sound, should seek to avoid the possibility of a public backlash that could result in fewer organs available for transplant. PMID:25013572

  4. The child and the fear of death.

    PubMed

    Mitchell, N L; Schulman, K R

    1981-10-01

    The central hypothesis of this paper is that the innate fear of death in the human being is universal and that the child, least of all, is immune to death fear and its symbolic representation. This cuts across all ages and developmental levels. This paper is not concerned with the empirical knowledge of death, an area that has been extensively explored by others such as Nagy (1948), Piaget (1929), and Anthony (1940).Examination of the child and his relationship to death is important in order to reach the truth and understand the human meaning of the fear of death.The child's conception of himself and his relationship to the world is an ironic paradox. On one hand, he feels endowed with magical feelings of omnipotence. This feeling is the main defense against the fear of death. On the other hand, his wishes, both benevolent and malevolent, have power independent of him to influence events. The concept of chance is alien, and the differentiation between objective and wishful causation is obscured. Thus, the way in which the child perceives his world makes the terror of death more formidable.SEVERAL CONCLUSIONS ARE REACHED IN THIS PAPER: (1) that even in childhood, loss, endings, separations, and death are core concerns of the individual; (2) that fear of death in children is intensified by the absence of the intellectual equipment and the absence of the necessary defense mechanisms essential for comprehending the experience of loss; and (3) that repression of the fear of death is an evolutionary process which has its origin in childhood. PMID:7310912

  5. Lunar Module Ascent Stage

    NASA Technical Reports Server (NTRS)

    1969-01-01

    The Lunar Module 'Spider' ascent stage is photographed from the Command/Service Module on the fifth day of the Apollo 9 earth-orbital mission. The Lunar Module's descent stage had already been jettisoned.

  6. Predictors of death anxiety among midwives who have experienced maternal death situations at work.

    PubMed

    Muliira, Rhoda Suubi; Sendikadiwa, Vito Bosco; Lwasampijja, Fred

    2015-05-01

    One of the hardships faced by midwives in developing countries is dealing with maternal death. Taking care of pregnant women who end up dying makes midwives mindful of their own mortality and this experience provokes discomfort and anxiety. To determine the predictors of death anxiety among midwives who have experienced maternal death at work in order to recommend interventions to facilitate effective coping with the distress. An exploratory, descriptive design was used to collect data about death anxiety from 224 midwives working in two rural districts of Uganda. Death anxiety was measured using a subscale of the Death Distress Scale. The majority of participants were female (80 %) and with associate degree level professional education (92 %). Participant's mean age and years of professional experience were 34 (±6.3) and 4 (±2.1) years, respectively. Most participants (74.6 %) had moderate or high death anxiety. The predictors of death anxiety were: having witnessed two and more maternal death in the past 2 years [odds ratio (OR) = 3.175; p ≤ .01]; being in charge of four or more maternal deaths (OR = 5.13; p ≤ .01); lack of professional training in handling death situations (OR = 3.32; p ≤ .01); and coping with maternal death situations using methods such as: planning (OR = 4.90; p ≤ .01), active coping (OR = 3.43; p ≤ .05) and acceptance (OR = 2.99; p ≤ .05). Multiple exposure to maternal death situations is associated with an increase in death anxiety among midwives working in rural settings. Employers need to provide deliberate support to enable midwives to cope effectively with death anxiety at work. PMID:25098369

  7. Children's Deaths in Maine, 1976-1980 Final Report.

    ERIC Educational Resources Information Center

    Shaper, Ruth; And Others

    The final report of a statistical study of 1,737 childhood deaths in Maine from 1976-80 by cause and age also looks at distribution of deaths by cause and age in Maine's low-income population. The findings showed disease was the major cause of death (1,068 deaths) followed by accidents (578 deaths), suicide (50 deaths), and homicide (29 deaths).…

  8. Hepatic leukemia factor promotes resistance to cell death: Implications for therapeutics and chronotherapy

    SciTech Connect

    Waters, Katrina M.; Sontag, Ryan L.; Weber, Thomas J.

    2013-04-15

    Physiological variation related to circadian rhythms and aberrant gene expression patterns are believed to modulate therapeutic efficacy, but the precise molecular determinants remain unclear. Here we examine the regulation of cell death by hepatic leukemia factor (HLF), which is an output regulator of circadian rhythms and is aberrantly expressed in human cancers, using an ectopic expression strategy in JB6 mouse epidermal cells and human keratinocytes. Ectopic HLF expression inhibited cell death in both JB6 cells and human keratinocytes, as induced by serum-starvation, tumor necrosis factor alpha and ionizing radiation. Microarray analysis indicates that HLF regulates a complex multi-gene transcriptional program encompassing upregulation of anti-apoptotic genes, downregulation of pro-apoptotic genes, and many additional changes that are consistent with an anti-death program. Collectively, our results demonstrate that ectopic expression of HLF, an established transcription factor that cycles with circadian rhythms, can recapitulate many features associated with circadian-dependent physiological variation. - Highlights: ► Circadian-dependent physiological variation impacts therapeutic efficacy. ► Hepatic leukemia factor inhibits cell death and is a candidate circadian factor. ► Hepatic leukemia factor anti-death program is conserved in murine and human cells. ► Transcriptomics indicates the anti-death program results from a systems response.

  9. The Effect of Geography and Citizen Behavior on Motor Vehicle Deaths in the United States

    PubMed Central

    Abaid, Nicole; Macinko, James; Silver, Diana; Porfiri, Maurizio

    2015-01-01

    Death due to motor vehicle collisions (MVCs) remains a leading cause of death in the US and alcohol plays a prominent role in a large proportion of these fatalities nationwide. Rates for these incidents vary widely among states and over time. Here, we explore the extent to which driving volume, alcohol consumption, legislation, political ideology, and geographical factors influence MVC deaths across states and time. We specify structural equation models for extracting associations between the factors and outcomes for MVC deaths and compute correlation functions of states’ relative geographic and political positions to elucidate the relative contribution of these factors. We find evidence that state-level variation in MVC deaths is associated with time-varying driving volume, alcohol consumption, and legislation. These relationships are modulated by state spatial proximity, whereby neighboring states are found to share similar MVC death rates over the thirty-year observation period. These results support the hypothesis that neighboring states exhibit similar risk and protective characteristics, despite differences in political ideology. PMID:25850105

  10. Sudden cardiac death in athletes.

    PubMed

    Schmied, C; Borjesson, M

    2014-02-01

    A 'paradox of sport' is that in addition to the undisputed health benefits of physical activity, vigorous exertion may transiently increase the risk of acute cardiac events. In general, the risk of sudden cardiac death (SCD) approximately doubles during physical activity and is 2- to 3-fold higher in athletes compared to nonathletes. The incidence of SCD in young athletes is in fact very low, at around 1-3 per 100,000, but attracts much public attention. Variations in incidence figures may be explained by the methodology used for data collection and more importantly by differences between subpopulations of athletes. The incidence of SCD in older (≥ 35 years) athletes is higher and may be expected to rise, as more and older individuals take part in organized sports. SCD is often the first clinical manifestation of a potentially fatal underlying cardiovascular disorder and usually occurs in previously asymptomatic athletes. In the young (<35 years), SCD is mainly due to congenital/inherited cardiac abnormalities, whilst coronary artery disease (CAD) is the most common cause in older athletes. Cardiac screening including family/personal history, physical examination and resting electrocardiogram (ECG) may identify individuals at risk and has the potential to decrease the risk of SCD in young athletes. Screening including the ECG has a high sensitivity for underlying disease in young athletes, but the specificity needs to be improved, whereas the sensitivity of screening without the use of ECG is very low. The screening modality recommended for young athletes is of limited value in older athletes, who should receive individualized screening with cardiac stress testing for patients with high risk of underlying CAD. As cardiovascular screening will never be able to identify all athletes at risk, adequate preparedness is vital in case of a potentially fatal event at the sporting arena/facility. Firstly, we will review the magnitude of the problem of SCD in athletes of

  11. [Sudden death. Role of the electrophysiologic study].

    PubMed

    Colín Lizalde, Luis

    2002-01-01

    At present, sudden death is considered a major health problem, DeBoer in 1935, recognized the clinical importance of ventricular fibrillation as the cause of sudden cardiac death. Sudden death due to cardiovascular problems has been established as one of the main causes of death in the developed countries and in developing countries as ours, where the deaths caused by cardiovascular diseases represent 15% of the total, exceeding other causes of death. The frequency of sudden death in our country is unknown, but more frequently we hear about cases of patients that have been reanimated for cardiac arrest; in the United States of America the frequency has been estimated between 400,000 at 500,000 per year although, recently, 250,000 at 300,000 events are being mentioned. It is convenient to comment that the causal arrhythmias are diverse and may vary depending on the underlying disease, although, generally, it can be pointed out that 80% of them are due to tachyarrhythmias. It's important to point out that there is a strong relationship between left ventricular dysfunction, the frequency of ventricular arrhythmias, and fatal cardiac events due to cardiac rhythm disturbances. The recommendations for electrophysiological studies are: 1) patients surviving cardiac arrest, occurring without evidence of an acute Q-wave myocardial infarction and 2) patients surviving cardiac arrest occurring more than 48 hours after the acute phase of myocardial infarction in the absence of a recurrent ischemic event. PMID:12001869

  12. Defining death for persons and human organisms.

    PubMed

    Lizza, J P

    1999-09-01

    This paper discusses how alternative concepts of personhood affect the definition of death. I argue that parties in the debate over the definition of death have employed different concepts of personhood, and thus have been talking past each other by proposing definitions of death for different kinds of things. In particular, I show how critics of the consciousness-related, neurological formation of death have relied on concepts of personhood that would be rejected by proponents of that formulation. These critics rest on treating persons as qualitative specifications of human organisms (Bernat, Culver, and Gert) or as identical to human organisms (Capron, Seifert, and Shewmon). Since advocates of the consciousness-related, neurological formulation of death are not committed to either of these views of personhood, these critics commit the fallacy of attacking a straw man. I then clarify the "substantive" concept of personhood (Boethius, Strawson, and Wiggins) that may be invoked in the consciousness-related, neurological formulation of death, and argue that, on this view and contra Bernat, Culver, and Gert, persons have always been the kind of thing that can literally die. I conclude by suggesting that the discussion of defining death needs to focus on which approach to personhood makes the most sense metaphysically and morally. PMID:10616321

  13. Nonthermal-plasma-mediated animal cell death

    NASA Astrophysics Data System (ADS)

    Kim, Wanil; Woo, Kyung-Chul; Kim, Gyoo-Cheon; Kim, Kyong-Tai

    2011-01-01

    Animal cell death comprising necrosis and apoptosis occurred in a well-regulated manner upon specific stimuli. The physiological meanings and detailed molecular mechanisms of cell death have been continuously investigated over several decades. Necrotic cell death has typical morphological changes, such as cell swelling and cell lysis followed by DNA degradation, whereas apoptosis shows blebbing formation and regular DNA fragmentation. Cell death is usually adopted to terminate cancer cells in vivo. The current strategies against tumour are based on the induction of cell death by adopting various methods, including radiotherapy and chemotherapeutics. Among these, radiotherapy is the most frequently used treatment method, but it still has obvious limitations. Recent studies have suggested that the use of nonthermal air plasma can be a prominent method for inducing cancer cell death. Plasma-irradiated cells showed the loss of genomic integrity, mitochondrial dysfunction, plasma membrane damage, etc. Tumour elimination with plasma irradiation is an emerging concept in cancer therapy and can be accelerated by targeting certain tumour-specific proteins with gold nanoparticles. Here, some recent developments are described so that the mechanisms related to plasma-mediated cell death and its perspectives in cancer treatment can be understood.

  14. The compression of deaths above the mode

    PubMed Central

    Thatcher, A. Roger; Cheung, Siu Lan K.; Horiuchi, Shiro; Robine, Jean-Marie

    2013-01-01

    Kannisto (2001) has shown that as the frequency distribution of ages at death has shifted to the right, the age distribution of deaths above the modal age has become more compressed. In order to further investigate this old-age mortality compression, we adopt the simple logistic model with two parameters, which is known to fit data on old-age mortality well (Thatcher 1999). Based on the model, we show that three key measures of old-age mortality (the modal age of adult deaths, the life expectancy at the modal age, and the standard deviation of ages at death above the mode) can be estimated fairly accurately from death rates at only two suitably chosen high ages (70 and 90 in this study). The distribution of deaths above the modal age becomes compressed when the logits of death rates fall more at the lower age than at the higher age. Our analysis of mortality time series in six countries, using the logistic model, endorsed Kannisto’s conclusion. Some possible reasons for the compression are discussed. PMID:24058281

  15. Death in the Eyes of the Beholder

    PubMed Central

    Fry-Revere, S.; Bastani, B.

    2010-01-01

    The US Uniform Determination of Death Act provides two alternatives for determining death—the circulatory criteria and the neurological criteria—yet history and the public’s current understanding of death in the US may mean that only brain death criteria can be relied upon without raising public suspicion that the medical profession is sacrificing the well-being of one group of patients (i.e., those dying after traumatic injury) to save another group (i.e., those in need of organs). The problem is exacerbated by existing debate on the appropriate waiting time after which death is inevitable and when the brain should be actually considered dead through prolonged absence of autoresuscitation. Given the difficulty of definitive determination of the time when brain function has ceased, two solutions are proposed: abandon the Dead Donor Rule or redefine death. Implementing the former would mean convincing the public to accept organ harvesting before the dying patient is completely brain dead through the writing of advance directives to permit organ harvest when death is inevitable though not confirmed. For the latter, reeducation would be necessary to persuade the public to accept the circulatory criteria for death as an independent determinant for death or the medical community would need to reconsider if the cessation of higher brain function is enough to be the basis for determining death. In conclusion, organ retrieval policies, no matter how medically sound, should seek to avoid the possibility of a public backlash that could result in fewer organs available for transplant. PMID:25013572

  16. Ballasted photovoltaic module and module arrays

    DOEpatents

    Botkin, Jonathan; Graves, Simon; Danning, Matt

    2011-11-29

    A photovoltaic (PV) module assembly including a PV module and a ballast tray. The PV module includes a PV device and a frame. A PV laminate is assembled to the frame, and the frame includes an arm. The ballast tray is adapted for containing ballast and is removably associated with the PV module in a ballasting state where the tray is vertically under the PV laminate and vertically over the arm to impede overt displacement of the PV module. The PV module assembly can be installed to a flat commercial rooftop, with the PV module and the ballast tray both resting upon the rooftop. In some embodiments, the ballasting state includes corresponding surfaces of the arm and the tray being spaced from one another under normal (low or no wind) conditions, such that the frame is not continuously subjected to a weight of the tray.

  17. Death representation of caregivers in hospice.

    PubMed

    Andruccioli, Jessica; Russo, Maria Maffia; Bruschi, Angela; Pedrabissi, Luigi; Sarti, Donatella; Monterubbianesi, Maria Cristina; Rossi, Sabina; Rocconi, Sabina; Raffaeli, William

    2012-11-01

    In this study, we investigated caregiver's death representation in hospice. The results presented here are a further analysis of the data collected in our previous study, concerning the evaluation of the caregiver in hospice. The data analysis of 24 caregivers of patients hospitalized in Rimini Hospice (Italy) underlined that caregivers avoiding death representation of the patient admitted to hospice had fewer protective factors (52.3%) and more risk factors (47.7%) than caregivers nonavoiding (66.5% and 33.5%, respectively). Caregivers avoiding death representation, moreover, experienced a greater distress (58%) than those nonavoiding (42%). PMID:22241459

  18. Plant Proteases Involved in Regulated Cell Death.

    PubMed

    Zamyatnin, A A

    2015-12-01

    Each plant genome encodes hundreds of proteolytic enzymes. These enzymes can be divided into five distinct classes: cysteine-, serine-, aspartic-, threonine-, and metalloproteinases. Despite the differences in their structural properties and activities, members of all of these classes in plants are involved in the processes of regulated cell death - a basic feature of eukaryotic organisms. Regulated cell death in plants is an indispensable mechanism supporting plant development, survival, stress responses, and defense against pathogens. This review summarizes recent advances in studies of plant proteolytic enzymes functioning in the initiation and execution of distinct types of regulated cell death. PMID:26878575

  19. [Criminalistic and penal problems with "dyadic deaths"].

    PubMed

    Kaliszczak, Paweł; Kunz, Jerzy; Bolechała, Filip

    2002-01-01

    This paper is a supplement to the article "Medico legal problems of dyadic death" elaborated by the same authors. Recalling the cases presented there. It is also an attempt to present the basic criminalistic, penal and definitional problems of dyadic death called also postagressional suicide. Criminalistic problems of dyadic death were presented in view of widely known "rule of seven golden questions"--what?, where?, when?, how?, why?, what method? and who? Criminalistic analysis of cases makes some differences in conclusions but it seemed interesting to match both--criminalistc and forensic points of views to the presented material. PMID:14669688

  20. Sudden cardiac death – Historical perspectives

    PubMed Central

    Abhilash, S.P.; Namboodiri, Narayanan

    2014-01-01

    Sudden cardiac death (SCD) is an unexpected death due to cardiac causes that occurs in a short time period (generally within 1 h of symptom onset) in a person with known or unknown cardiac disease. It is believed to be involved in nearly a quarter of human deaths, with ventricular fibrillation being the most common mechanism. It is estimated that more than 7 million lives per year are lost to SCD worldwide. Historical perspectives of SCD are analyzed with a brief description on how the developments in the management of sudden cardiac arrest evolved over time. PMID:24568828

  1. Joint aging and chondrocyte cell death

    PubMed Central

    Grogan, Shawn P; D’Lima, Darryl D

    2010-01-01

    Articular cartilage extracellular matrix and cell function change with age and are considered to be the most important factors in the development and progression of osteoarthritis. The multifaceted nature of joint disease indicates that the contribution of cell death can be an important factor at early and late stages of osteoarthritis. Therefore, the pharmacologic inhibition of cell death is likely to be clinically valuable at any stage of the disease. In this article, we will discuss the close association between diverse changes in cartilage aging, how altered conditions influence chondrocyte death, and the implications of preventing cell loss to retard osteoarthritis progression and preserve tissue homeostasis. PMID:20671988

  2. Tantalizing Thanatos: unexpected links in death pathways.

    PubMed

    Cohen, Isabelle; Castedo, Maria; Kroemer, Guido

    2002-07-01

    Cell death is most frequently the result of apoptosis, an event that is often controlled by mitochondrial membrane permeabilization (MMP). Recent data reveal unexpected functional links between apoptosis and autophagic cell death, in the sense that MMP can trigger autophagy of damaged mitochondria. Conversely, one of the major signal-transducing molecules involved in the activation of autophagy during apoptosis--the so-called DAP kinase--can induce cell death through MMP. Connections are also emerging between apoptosis, autophagy, replicative senescence and cancer-specific metabolic changes. PMID:12185842

  3. The Historical Perspective of Athletic Sudden Death.

    PubMed

    Hoyt, Walter J; Dean, Peter N; Battle, Robert W

    2015-07-01

    Since antiquity, the athlete has been elevated to a heroic status both within small communities and at the international level. Although numerous population studies have estimated athletic sudden death to be a rare event, the consequences resonate far beyond those directly affected. Sports cardiology has evolved as a result of these tragedies, which highlighted a need for safer play and more programmatic protection of the athlete in play. In this article, athletic sudden death is analyzed from a historical and literary perspective and the development of modern initiatives to protect athletes from sudden death is reviewed. PMID:26100429

  4. Getting comfortable with death & near-death experiences. Near-death experiences: an essay in medicine & philosophy.

    PubMed

    Moody, Raymond A

    2013-01-01

    Near-death experiences are an ancient and very common phenomenon that spans from ancient philosophy, religion and healing to the most modern clinical practice of medicine. Probably we are not much closer to an ultimate explanation of NDEs than were early thinkers like Plato and Democritus. Puzzling cases of near-death experiences continue to come to light and the ancient debate about what they mean continues unabated. PMID:24279183

  5. Programmed death-1 & its ligands: promising targets for cancer immunotherapy.

    PubMed

    Shrimali, Rajeev K; Janik, John E; Abu-Eid, Rasha; Mkrtichyan, Mikayel; Khleif, Samir N

    2015-01-01

    Novel strategies for cancer treatment involving blockade of immune inhibitors have shown significant progress toward understanding the molecular mechanism of tumor immune evasion. The preclinical findings and clinical responses associated with programmed death-1 (PD-1) and PD-ligand pathway blockade seem promising, making these targets highly sought for cancer immunotherapy. In fact, the anti-PD-1 antibodies, pembrolizumab and nivolumab, were recently approved by the US FDA for the treatment of unresectable and metastatic melanoma resistant to anticytotoxic T-lymphocyte antigen-4 antibody (ipilimumab) and BRAF inhibitor. Here, we discuss strategies of combining PD-1/PD-ligand interaction inhibitors with other immune checkpoint modulators and standard-of-care therapy to break immune tolerance and induce a potent antitumor activity, which is currently a research area of key scientific pursuit. PMID:26250412

  6. Death Education as a Learning Experience. SCIP No. 3.

    ERIC Educational Resources Information Center

    Bensley, Loren B., Jr.

    This monograph on death education defines death education, discusses the need for it, and suggests ways of teaching it. Death education is defined as the process by which one explores man's relationship with life. The basic philosophy underlying death education is that through the study of death students will gain an appreciation for life which…

  7. Religiosity and Death Distress in Arabic College Students

    ERIC Educational Resources Information Center

    Al-Sabwah, Mohammed N.; Abdel-Khalek, Ahmed M.

    2006-01-01

    The purpose of the present study was to explore the relationship between religiosity and death distress (death anxiety, death depression, and death obsession) among a sample (N = 570) of Egyptian women nursing undergraduates, mainly Muslims. Their ages ranged from 17 to 25. The correlations between religiosity and both death anxiety and death…

  8. 22 CFR 72.6 - Report of presumptive death.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Report of presumptive death. 72.6 Section 72.6... DEATHS AND ESTATES Reporting Deaths of United States Nationals § 72.6 Report of presumptive death. (a) Local finding. When there is a local finding of presumptive death by a competent local authority,...

  9. 20 CFR 219.23 - Evidence to prove death.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Evidence to prove death. 219.23 Section 219... EVIDENCE REQUIRED FOR PAYMENT Evidence of Age and Death § 219.23 Evidence to prove death. (a) Preferred evidence of death. The best evidence of a person's death is— (1) A certified copy of or extract from...

  10. 22 CFR 72.4 - Notifications of death.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Notifications of death. 72.4 Section 72.4... DEATHS AND ESTATES Reporting Deaths of United States Nationals § 72.4 Notifications of death. The... legal representative (if any, and if different from the next of kin), of the death of a United...

  11. 20 CFR 718.303 - Death from a respirable disease.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Death from a respirable disease. 718.303... OR DEATH DUE TO PNEUMOCONIOSIS Presumptions Applicable to Eligibility Determinations § 718.303 Death... death was due to pneumoconiosis. (2) Under this presumption, death shall be found due to a...

  12. 20 CFR 219.23 - Evidence to prove death.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 1 2012-04-01 2012-04-01 false Evidence to prove death. 219.23 Section 219... EVIDENCE REQUIRED FOR PAYMENT Evidence of Age and Death § 219.23 Evidence to prove death. (a) Preferred evidence of death. The best evidence of a person's death is— (1) A certified copy of or extract from...

  13. 22 CFR 72.6 - Report of presumptive death.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Report of presumptive death. 72.6 Section 72.6... DEATHS AND ESTATES Reporting Deaths of United States Nationals § 72.6 Report of presumptive death. (a) Local finding. When there is a local finding of presumptive death by a competent local authority,...

  14. 20 CFR 219.23 - Evidence to prove death.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 1 2011-04-01 2011-04-01 false Evidence to prove death. 219.23 Section 219... EVIDENCE REQUIRED FOR PAYMENT Evidence of Age and Death § 219.23 Evidence to prove death. (a) Preferred evidence of death. The best evidence of a person's death is— (1) A certified copy of or extract from...

  15. 20 CFR 219.23 - Evidence to prove death.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 1 2013-04-01 2012-04-01 true Evidence to prove death. 219.23 Section 219.23... REQUIRED FOR PAYMENT Evidence of Age and Death § 219.23 Evidence to prove death. (a) Preferred evidence of death. The best evidence of a person's death is— (1) A certified copy of or extract from the...

  16. 22 CFR 72.4 - Notifications of death.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Notifications of death. 72.4 Section 72.4... DEATHS AND ESTATES Reporting Deaths of United States Nationals § 72.4 Notifications of death. The... legal representative (if any, and if different from the next of kin), of the death of a United...

  17. 22 CFR 72.4 - Notifications of death.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Notifications of death. 72.4 Section 72.4... DEATHS AND ESTATES Reporting Deaths of United States Nationals § 72.4 Notifications of death. The... legal representative (if any, and if different from the next of kin), of the death of a United...

  18. 22 CFR 72.6 - Report of presumptive death.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Report of presumptive death. 72.6 Section 72.6... DEATHS AND ESTATES Reporting Deaths of United States Nationals § 72.6 Report of presumptive death. (a) Local finding. When there is a local finding of presumptive death by a competent local authority,...

  19. 22 CFR 72.6 - Report of presumptive death.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Report of presumptive death. 72.6 Section 72.6... DEATHS AND ESTATES Reporting Deaths of United States Nationals § 72.6 Report of presumptive death. (a) Local finding. When there is a local finding of presumptive death by a competent local authority,...

  20. 22 CFR 72.6 - Report of presumptive death.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Report of presumptive death. 72.6 Section 72.6... DEATHS AND ESTATES Reporting Deaths of United States Nationals § 72.6 Report of presumptive death. (a) Local finding. When there is a local finding of presumptive death by a competent local authority,...

  1. 22 CFR 72.4 - Notifications of death.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Notifications of death. 72.4 Section 72.4... DEATHS AND ESTATES Reporting Deaths of United States Nationals § 72.4 Notifications of death. The... legal representative (if any, and if different from the next of kin), of the death of a United...

  2. 22 CFR 72.4 - Notifications of death.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Notifications of death. 72.4 Section 72.4... DEATHS AND ESTATES Reporting Deaths of United States Nationals § 72.4 Notifications of death. The... legal representative (if any, and if different from the next of kin), of the death of a United...

  3. 20 CFR 219.23 - Evidence to prove death.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 1 2014-04-01 2012-04-01 true Evidence to prove death. 219.23 Section 219.23... REQUIRED FOR PAYMENT Evidence of Age and Death § 219.23 Evidence to prove death. (a) Preferred evidence of death. The best evidence of a person's death is— (1) A certified copy of or extract from the...

  4. Mitochondrial dynamics and cell death in heart failure.

    PubMed

    Marín-García, José; Akhmedov, Alexander T

    2016-03-01

    The highly regulated processes of mitochondrial fusion (joining), fission (division) and trafficking, collectively called mitochondrial dynamics, determine cell-type specific morphology, intracellular distribution and activity of these critical organelles. Mitochondria are critical for cardiac function, while their structural and functional abnormalities contribute to several common cardiovascular diseases, including heart failure (HF). The tightly balanced mitochondrial fusion and fission determine number, morphology and activity of these multifunctional organelles. Although the intracellular architecture of mature cardiomyocytes greatly restricts mitochondrial dynamics, this process occurs in the adult human heart. Fusion and fission modulate multiple mitochondrial functions, ranging from energy and reactive oxygen species production to Ca(2+) homeostasis and cell death, allowing the heart to respond properly to body demands. Tightly controlled balance between fusion and fission is of utmost importance in the high energy-demanding cardiomyocytes. A shift toward fission leads to mitochondrial fragmentation, while a shift toward fusion results in the formation of enlarged mitochondria and in the fusion of damaged mitochondria with healthy organelles. Mfn1, Mfn2 and OPA1 constitute the core machinery promoting mitochondrial fusion, whereas Drp1, Fis1, Mff and MiD49/51 are the core components of fission machinery. Growing evidence suggests that fusion/fission factors in adult cardiomyocytes play essential noncanonical roles in cardiac development, Ca(2+) signaling, mitochondrial quality control and cell death. Impairment of this complex circuit causes cardiomyocyte dysfunction and death contributing to heart injury culminating in HF. Pharmacological targeting of components of this intricate network may be a novel therapeutic modality for HF treatment. PMID:26872674

  5. Cell death sensitization of leukemia cells by opioid receptor activation

    PubMed Central

    Friesen, Claudia; Roscher, Mareike; Hormann, Inis; Fichtner, Iduna; Alt, Andreas; Hilger, Ralf A.; Debatin, Klaus-Michael; Miltner, Erich

    2013-01-01

    Cyclic AMP (cAMP) regulates a number of cellular processes and modulates cell death induction. cAMP levels are altered upon stimulation of specific G-protein-coupled receptors inhibiting or activating adenylyl cyclases. Opioid receptor stimulation can activate inhibitory Gi-proteins which in turn block adenylyl cyclase activity reducing cAMP. Opioids such as D,L-methadone induce cell death in leukemia cells. However, the mechanism how opioids trigger apoptosis and activate caspases in leukemia cells is not understood. In this study, we demonstrate that downregulation of cAMP induced by opioid receptor activation using the opioid D,L-methadone kills and sensitizes leukemia cells for doxorubicin treatment. Enhancing cAMP levels by blocking opioid-receptor signaling strongly reduced D,L-methadone-induced apoptosis, caspase activation and doxorubicin-sensitivity. Induction of cell death in leukemia cells by activation of opioid receptors using the opioid D,L-methadone depends on critical levels of opioid receptor expression on the cell surface. Doxorubicin increased opioid receptor expression in leukemia cells. In addition, the opioid D,L-methadone increased doxorubicin uptake and decreased doxorubicin efflux in leukemia cells, suggesting that the opioid D,L-methadone as well as doxorubicin mutually increase their cytotoxic potential. Furthermore, we found that opioid receptor activation using D,L-methadone alone or in addition to doxorubicin inhibits tumor growth significantly in vivo. These results demonstrate that opioid receptor activation via triggering the downregulation of cAMP induces apoptosis, activates caspases and sensitizes leukemia cells for doxorubicin treatment. Hence, opioid receptor activation seems to be a promising strategy to improve anticancer therapies. PMID:23633472

  6. Molecular mechanisms of Ebola virus pathogenesis: focus on cell death.

    PubMed

    Falasca, L; Agrati, C; Petrosillo, N; Di Caro, A; Capobianchi, M R; Ippolito, G; Piacentini, M

    2015-08-01

    Ebola virus (EBOV) belongs to the Filoviridae family and is responsible for a severe disease characterized by the sudden onset of fever and malaise accompanied by other non-specific signs and symptoms; in 30-50% of cases hemorrhagic symptoms are present. Multiorgan dysfunction occurs in severe forms with a mortality up to 90%. The EBOV first attacks macrophages and dendritic immune cells. The innate immune reaction is characterized by a cytokine storm, with secretion of numerous pro-inflammatory cytokines, which induces a huge number of contradictory signals and hurts the immune cells, as well as other tissues. Other highly pathogenic viruses also trigger cytokine storms, but Filoviruses are thought to be particularly lethal because they affect a wide array of tissues. In addition to the immune system, EBOV attacks the spleen and kidneys, where it kills cells that help the body to regulate its fluid and chemical balance and that make proteins that help the blood to clot. In addition, EBOV causes liver, lungs and kidneys to shut down their functions and the blood vessels to leak fluid into surrounding tissues. In this review, we analyze the molecular mechanisms at the basis of Ebola pathogenesis with a particular focus on the cell death pathways induced by the virus. We also discuss how the treatment of the infection can benefit from the recent experience of blocking/modulating cell death in human degenerative diseases. PMID:26024394

  7. Molecular mechanisms of Ebola virus pathogenesis: focus on cell death

    PubMed Central

    Falasca, L; Agrati, C; Petrosillo, N; Di Caro, A; Capobianchi, M R; Ippolito, G; Piacentini, M

    2015-01-01

    Ebola virus (EBOV) belongs to the Filoviridae family and is responsible for a severe disease characterized by the sudden onset of fever and malaise accompanied by other non-specific signs and symptoms; in 30–50% of cases hemorrhagic symptoms are present. Multiorgan dysfunction occurs in severe forms with a mortality up to 90%. The EBOV first attacks macrophages and dendritic immune cells. The innate immune reaction is characterized by a cytokine storm, with secretion of numerous pro-inflammatory cytokines, which induces a huge number of contradictory signals and hurts the immune cells, as well as other tissues. Other highly pathogenic viruses also trigger cytokine storms, but Filoviruses are thought to be particularly lethal because they affect a wide array of tissues. In addition to the immune system, EBOV attacks the spleen and kidneys, where it kills cells that help the body to regulate its fluid and chemical balance and that make proteins that help the blood to clot. In addition, EBOV causes liver, lungs and kidneys to shut down their functions and the blood vessels to leak fluid into surrounding tissues. In this review, we analyze the molecular mechanisms at the basis of Ebola pathogenesis with a particular focus on the cell death pathways induced by the virus. We also discuss how the treatment of the infection can benefit from the recent experience of blocking/modulating cell death in human degenerative diseases. PMID:26024394

  8. Making death 'good': instructional tales for dying in newspaper accounts of Jade Goody's death.

    PubMed

    Frith, Hannah; Raisborough, Jayne; Klein, Orly

    2013-03-01

    Facilitating a 'good' death is a central goal for hospices and palliative care organisations. The key features of such a death include an acceptance of death, an open awareness of and communication about death, the settling of practical and interpersonal business, the reduction of suffering and pain, and the enhancement of autonomy, choice and control. Yet deaths are inherently neither good nor bad; they require cultural labour to be 'made over' as good. Drawing on media accounts of the controversial death of UK reality television star Jade Goody, and building on existing analyses of her death, we examine how cultural discourses actively work to construct deaths as good or bad and to position the dying and those witnessing their death as morally accountable. By constructing Goody as bravely breaking social taboos by openly acknowledging death, by contextualising her dying as occurring at the end of a life well lived and by emphasising biographical continuity and agency, newspaper accounts serve to position themselves as educative rather than exploitative, and readers as information-seekers rather than ghoulishly voyeuristic. We argue that popular culture offers moral instruction in dying well which resonates with the messages from palliative care. PMID:22882726

  9. Taboo and the different death? Perceptions of those bereaved by suicide or other traumatic death.

    PubMed

    Chapple, Alison; Ziebland, Sue; Hawton, Keith

    2015-05-01

    Views differ on how far the subject of death has ever been taboo in Western Society. Walter (1991) criticised the way the 'taboo thesis' has been presented, arguing that it has often been 'grossly overdrawn and lacking in subtlety'. Research suggests that suicide and other traumatic death may be particularly difficult for people to talk about or even acknowledge. We interviewed 80 people bereaved due to suicide, or other traumatic death and used interpretative thematic analysis to consider whether the 'death taboo' is evident in these bereavement narratives. People referred to suicide as a different, even stigmatised, death but we also found that those bereaved through other traumatic death felt that their reactions had to be contained and relatively silent. The exception was those bereaved through terrorism or train crash, who were encouraged to grieve openly and angrily: reactions to deaths which are seen as 'private troubles' differ from reactions to deaths which are seen as 'public issues'. Using a symbolic interactionist approach we conclude that the shock and suddenness of the death is tied up both with the circumstances of the death (suicide, murder, accident, terrorism) and the attendant consequences for the social acceptance of public displays of mourning. PMID:25683372

  10. Hepatic Leukemia Factor Promotes Resistance To Cell Death: Implications For Therapeutics and Chronotherapy

    SciTech Connect

    Waters, Katrina M.; Sontag, Ryan L.; Weber, Thomas J.

    2013-04-15

    Physiological variation related to circadian rhythms and aberrant gene expression patterns are believed to modulate therapeutic efficacy, but the precise molecular determinants remain unclear. Here we examine the regulation of cell death by hepatic leukemia factor (HLF), which is an output regulator of circadian rhythms and is aberrantly expressed in human cancers, using an ectopic expression strategy in JB6 mouse epidermal cells and human keratinocytes. Ectopic HLF expression inhibited cell death in both JB6 cells and human keratinocytes, as induced by serum-starvation, tumor necrosis factor alpha and ionizing radiation. Microarray analysis indicates that HLF regulates a complex multi-gene transcriptional program encompassing upregulation of anti-apoptotic genes, downregulation of pro-apoptotic genes, and many additional changes that are consistent with an anti-death program. Collectively, our results demonstrate that ectopic expression of HLF, an established transcription factor that cycles with circadian rhythms, can recapitulate many features associated with circadian-dependent physiological variation.

  11. Module utilization committee

    NASA Technical Reports Server (NTRS)

    Volkmer, K.; Praver, G.

    1984-01-01

    Photovoltaic collector modules were declared surplus to the needs of the U.S. Dept. of Energy. The Module Utilization Committee was formed to make appropriate disposition of the surplus modules on a national basis and to act as a broker for requests for these modules originating outside of the National Photovoltaics Program.

  12. Are suicide deaths under-reported? Nationwide re-evaluations of 1800 deaths in Scandinavia

    PubMed Central

    Tøllefsen, Ingvild Maria; Helweg-Larsen, Karin; Thiblin, Ingemar; Hem, Erlend; Kastrup, Marianne C; Nyberg, Ullakarin; Rogde, Sidsel; Zahl, Per-Henrik; Østevold, Gunvor; Ekeberg, Øivind

    2015-01-01

    Objective Valid mortality statistics are important for healthcare planning and research. Suicides and accidents often present a challenge in the classification of the manner of death. The aim of this study was to analyse the reliability of the national suicide statistics by comparing the classification of suicide in the Scandinavian cause of death registers with a reclassification by 8 persons with different medical expertise (psychiatry, forensic pathology and public health) from each of the 3 Scandinavian countries. Methods The cause of death registers in Norway, Sweden and Denmark retrieved available information on a sample of 600 deaths in 2008 from each country. 200 were classified in the registers as suicides, 200 as accidents or undetermined and 200 as natural deaths. The reclassification comprised an assessment of the manner and cause of death as well as the level of certainty. Results In total, 81%, 88% and 90% of deaths registered as suicide in the official mortality statistics were confirmed by experts using the Swedish, Norwegian and Danish data sets, respectively. About 3% of deaths classified as accidents or natural deaths in the cause of death registers were reclassified as suicides. However, after a second reclassification based on additional information, 9% of the natural deaths and accidents were reclassified as suicides in the Norwegian data set, and 21% of the undetermined deaths were reclassified as suicides in the Swedish data set. In total, the levels of certainty of the experts were 87% of suicides in the Norwegian data set, 77% in the Swedish data set and 92% in Danish data set; the uncertainty was highest in poisoning suicides. Conclusions A high percentage of reported suicides were confirmed as being suicides. Few accidents and natural deaths were reclassified as suicides. Hence, reclassification did not increase the overall official suicide statistics of the 3 Scandinavian countries. PMID:26608638

  13. The Moldovan experience of maternal death reviews.

    PubMed

    Hodorogea, S; Friptu, V

    2014-09-01

    A Confidential Enquiry into Maternal Deaths is an anonymous, multidisciplinary and systematic review of all cases of maternal mortality. This paper describes one such process implemented at national level in Moldova. Its aim was to conduct an in-depth review of the underlying causes and circumstances surrounding each mother's death to learn lessons to improve care in future. Its findings showed that deaths were predominantly due to direct obstetric causes, especially haemorrhage and sepsis, and adverse social determinants, particularly poverty and migration also played a decisive role in more than half of the cases. The final report identified potentially remediable actions and the key areas requiring interventions by the health sector, administrators and the community. Its recommendations have enabled the implementation of some solutions to help prevent future maternal deaths, including the development of evidence-based clinical guidelines. PMID:25236639

  14. Sarcoidosis and mechanisms of unexpected death.

    PubMed

    Byard, Roger W; Manton, Nicholas; Tsokos, Michael

    2008-03-01

    Sarcoidosis is a multisystem disease of uncertain etiology characterized by multifocal areas of discrete and confluent granulomatous inflammation that may rarely be responsible for sudden and unexpected death. Two cases are reported to demonstrate disparate pathological features in fatal cases, one involving cardiac sarcoidosis, and the other neurosarcoidosis with hypothalamic infiltration. Sarcoidosis in individuals dying suddenly may be completely unrelated to the death, contributory or causal. Cardiovascular causes of sudden death in sarcoidosis include arrhythmias associated with cardiomyopathy and ischemia, ventricular rupture, and cor pulmonale due to pulmonary hypertension; respiratory causes include hemorrhage and upper airway obstruction; central nervous system causes include arrhythmias from infiltration of autonomic centers, epilepsy, and obstructive hydrocephalus from brainstem involvement; and gastrointestinal deaths may be due to hemorrhage from esophageal varices associated with portal hypertension. The diagnosis relies on the demonstration of typical noncaseating granulomas and the exclusion of other infective and environmental diseases with similar histopathological findings. PMID:18366580

  15. [The theme of death: an educational proposal].

    PubMed

    Boemer, M R; Veiga, E V; Mendes, M M; do Valle, E R

    1991-01-01

    The necessity of educating the Health Professionals to the theme Death is concerned has become so evident during our educational activities that we have striven for the construction of a knowledge body about death and dying. Therefore, the knowledge we have generating refers to the pedagogical aspect of the theme. The aim of this study was to focus such dimension as far as it describes and analyses our experience in educating nursing undergraduates to deal with situations involving death and dying. In particular, we try to developing our students in order to be able to provide care to the dead body in a proposal to transcend the technical aspect of this care. Bearing this educational purpose, we strive for a space that makes possible a formation in the perspective of leading the students to another existencial dimension when facing and understanding death. PMID:1961946

  16. Staying alive: cell death in antiviral immunity.

    PubMed

    Upton, Jason W; Chan, Francis Ka-Ming

    2014-04-24

    Programmed cell death is an integral part of host defense against invading intracellular pathogens. Apoptosis, programmed necrosis, and pyroptosis each serve to limit pathogen replication in infected cells, while simultaneously promoting the inflammatory and innate responses that shape effective long-term host immunity. The importance of carefully regulated cell death is evident in the spectrum of inflammatory and autoimmune disorders caused by defects in these pathways. Moreover, many viruses encode inhibitors of programmed cell death to subvert these host responses during infection, thereby facilitating their own replication and persistence. Thus, as both virus and cell vie for control of these pathways, the battle for survival has shaped a complex host-pathogen interaction. This review will discuss the multifaceted role that programmed cell death plays in maintaining the immune system and its critical function in host defense, with a special emphasis on viral infections. PMID:24766891

  17. Anemia Boosts Stroke Death Risk, Study Finds

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_160476.html Anemia Boosts Stroke Death Risk, Study Finds Blood condition ... 2016 (HealthDay News) -- Older stroke victims suffering from anemia -- a lack of red blood cells -- may have ...

  18. Diabetes Ups Risk of Heart Attack Death

    MedlinePlus

    ... news/fullstory_159557.html Diabetes Ups Risk of Heart Attack Death Study points to need for better coordinated ... are much more likely to die after a heart attack than people without the blood sugar condition, a ...

  19. [Revision of the diagnostic label death anxiety].

    PubMed

    Tomás-Sábado, Joaquín; Fernández-Narváez, Pilar; Fernández-Donaire, Lidia; Aradilla-Herrero, Amor

    2007-01-01

    The inclusion of the diagnostic label of "death anxiety" by the North Americvan Nursing Diagnosis Association (NANDA) in the 2001-2002 taxonomy is justified by the interest in establishing the specific care required in terminal patients. Nevertheless, the definition of "death anxiety" does not delimit the concept precisely, since it does not clearly establish the difference between the terms "death anxiety" and "fear of death". Consequently, the need arose to design a project whose goal was to modify the nursing diagnostic label and defining characteristics proposed by the NANDA, as well as to formulate the related factors, which had not yet been developed. At the meeting of the Diagnostic Review Committee in February 2005, the NANDA considered the proposal, accepting both the modification of the definition of the diagnostic label and the inclusion of the related factors. The revision will be included in the 2007 NANDA taxonomy. PMID:17686418

  20. Life and Death Drawings in Adolescence.

    ERIC Educational Resources Information Center

    Berg, Constance DeMuth

    1979-01-01

    Believing that adolescents need to explore their feelings about life and their fantasies about death, an art teacher was prompted to use a human skeleton as a still life subject. The success of this art project is described. (KC)