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Sample records for survival causing increased

  1. Rutin increases neural crest stem cell survival against damage caused by aflatoxin B1

    Directory of Open Access Journals (Sweden)

    Jader Nones

    2015-09-01

    Full Text Available http://dx.doi.org/10.5007/2175-7925.2015v28n4p1 The neural crest (NC corresponds to a collection of multipotent and oligopotent progenitors endowed with both neural and mesenchymal potential. The derivatives of the NC at the trunk level include neurons and glial cells of the peripheral nervous system, melanocytes, smooth muscle cells and some endocrine cells. The present work investigated, for the first time, the influence of aflatoxin B1 (AFB1 and the flavonoid rutin on the survival and proliferation of NC and NC-derived melanocytes. Quail NC cell cultures were treated with AFB1 (30 μM and/or rutin (20 μM for 6 days. Cell viability was assessed by MTT and trypan blue analyses and cell proliferation by BrdU staining. Melanocytes were identified by immunocytochemistry against the melanocyte-specific cellular marker MelEM. The AFB1 treatment decreased both NC cell viability and proliferation. The total number of MelEM-positive cells was also reduced after this treatment, an effect partially prevented by the addition of rutin. On the other hand, rutin added alone did not influence the NC cell population. Our results demonstrated that rutin increases the survival of the NC after damage caused by AFB1. However, additional studies are needed to better understand the mechanisms involved in AFB1 and rutin interactions.

  2. Causes and consequences of increase in child survival rates: ethnoepidemiology among the Hmong of Thailand.

    Science.gov (United States)

    Kunstadter, P; Kunstadter, S L; Leepreecha, P; Podhisita, C; Laoyang, M; Thao, C S; Thao, R S; Yang, W S

    1992-12-01

    The Hmong "hill tribe" minority in Thailand has much higher exposure to factors usually associated with risk of child mortality (high fertility, low status of women, low education, less use of modern medical care for births, exposure to warfare, economic and physical disruption, and poor hygienic conditions) than the rural ethnic Thai population. Nonetheless, infant mortality has declined from over 120 per 1000 to under 50 per 1000 live births among both these populations in the past 30 years. The reason for the rapid increase in child survival among the Hmong appears to be better access to and more use of modern curative and preventive medical care associated with road construction rather than major changes in social or hygienic conditions. Conventional wisdom suggests that high fertility is both a cause and a consequence of high infant and child mortality and that parents will not reduce fertility until they see that mortality has declined. Most Hmong parents recognize the decline in child mortality and attribute it to better access to modern medical care. Most Hmong parents also say that, if they were starting to have children now, they would want to have fewer children. Fear of child death is infrequently mentioned as a motive for having more children, and the perceived decline in child mortality is rarely mentioned as a reason for reduced fertility. Most Hmong parents explain their desired family size in terms of economic conditions rather than perceived risk of child mortality. Results of this study suggest that fertility and child mortality can vary independently of one another and that major reductions in child mortality can be accomplished without waiting for major social changes (e.g., improved education or status of women) or major reductions in fertility.

  3. Bee bread increases honeybee haemolymph protein and promote better survival despite of causing higher Nosema ceranae abundance in honeybees.

    Science.gov (United States)

    Basualdo, Marina; Barragán, Sergio; Antúnez, Karina

    2014-08-01

    Adequate protein nutrition supports healthy honeybees and reduces the susceptibility to disease. However little is known concerning the effect of the diet on Nosema ceranae development, an obligate intracellular parasite that disturbs the protein metabolism of honeybees (Apis mellifera). Here we tested the effect of natural (bee bread) and non-natural protein diets (substitute) on haemolymph proteins titers of honeybee and N. ceranae spore production. The natural diet induced higher levels of protein and parasite development, but the survival of bees was also higher than with non-natural diets. The data showed that the administration of an artificially high nutritious diet in terms of crude protein content is not sufficient to promote healthy bees; rather the protein ingested should be efficiently assimilated. The overall results support the idea that the physiological condition of the bees is linked to protein levels in the haemolymph, which affects the tolerance to parasite; consequently the negative impact of the parasite on host fitness is not associated only with the level of infection. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

  4. Lack of potassium channel induces proliferation and survival causing increased neurogenesis and two-fold hippocampus enlargement

    DEFF Research Database (Denmark)

    Almgren, Malin; Persson, Ann-Sophie; Fenghua, Chen

    2007-01-01

    -fold within dentate gyrus (DG), CA2/3, and hilus of 12-week-old mceph/mceph versus wild type mice. In CA1, there was a tendency toward an increase in volume and in number of astrocytes. The volume estimates in newborn and p14 mice suggest that the overgrowth in mceph/mceph hippocampus starts between birth...

  5. Attributing death to cancer: cause-specific survival estimation.

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    Mathew A

    2002-10-01

    Full Text Available Cancer survival estimation is an important part of assessing the overall strength of cancer care in a region. Generally, the death of a patient is taken as the end point in estimation of overall survival. When calculating the overall survival, the cause of death is not taken into account. With increasing demand for better survival of cancer patients it is important for clinicians and researchers to know about survival statistics due to disease of interest, i.e. net survival. It is also important to choose the best method for estimating net survival. Increase in the use of computer programmes has made it possible to carry out statistical analysis without guidance from a bio-statistician. This is of prime importance in third- world countries as there are a few trained bio-statisticians to guide clinicians and researchers. The present communication describes current methods used to estimate net survival such as cause-specific survival and relative survival. The limitation of estimation of cause-specific survival particularly in India and the usefulness of relative survival are discussed. The various sources for estimating cancer survival are also discussed. As survival-estimates are to be projected on to the population at large, it becomes important to measure the variation of the estimates, and thus confidence intervals are used. Rothman′s confidence interval gives the most satisfactory result for survival estimate.

  6. Prostate cancer: net survival and cause-specific survival rates after multiple imputation.

    Science.gov (United States)

    Morisot, Adeline; Bessaoud, Faïza; Landais, Paul; Rébillard, Xavier; Trétarre, Brigitte; Daurès, Jean-Pierre

    2015-07-28

    Estimations of survival rates are diverse and the choice of the appropriate method depends on the context. Given the increasing interest in multiple imputation methods, we explored the interest of a multiple imputation approach in the estimation of cause-specific survival, when a subset of causes of death was observed. By using European Randomized Study of Screening for Prostate Cancer (ERSPC), 20 multiply imputed datasets were created and analyzed with a Multivariate Imputation by Chained Equation (MICE) algorithm. Then, cause-specific survival was estimated on each dataset with two methods: Kaplan-Meier and competing risks. The two pooled cause-specific survival and confidence intervals were obtained using Rubin's rules after complementary log-log transformation. Net survival was estimated using Pohar-Perme's estimator and was compared to pooled cause-specific survival. Finally, a sensitivity analysis was performed to test the robustness of our constructed multiple imputation model. Cause-specific survival performed better than net survival, since this latter exceeded 100 % for almost the first 2 years of follow-up and after 9 years whereas the cause-specific survival decreased slowly and than stabilized at around 94 % at 9 years. Sensibility study results were satisfactory. On our basis of prostate cancer data, the results obtained by cause-specific survival after multiple imputation appeared to be better and more realistic than those obtained using net survival.

  7. Prostate cancer: net survival and cause-specific survival rates after multiple imputation

    OpenAIRE

    Morisot, Adeline; Bessaoud, Fa?za; Landais, Paul; R?billard, Xavier; Tr?tarre, Brigitte; Daur?s, Jean-Pierre

    2015-01-01

    Background Estimations of survival rates are diverse and the choice of the appropriate method depends on the context. Given the increasing interest in multiple imputation methods, we explored the interest of a multiple imputation approach in the estimation of cause-specific survival, when a subset of causes of death was observed. Methods By using European Randomized Study of Screening for Prostate Cancer (ERSPC), 20 multiply imputed datasets were created and analyzed with a Multivariate Imput...

  8. Fledgling survival increases with development time and adult survival across north and south temperate zones

    Science.gov (United States)

    Lloyd, Penn; Martin, Thomas E.

    2016-01-01

    Slow life histories are characterized by high adult survival and few offspring, which are thought to allow increased investment per offspring to increase juvenile survival. Consistent with this pattern, south temperate zone birds are commonly longer-lived and have fewer young than north temperate zone species. However, comparative analyses of juvenile survival, including during the first few weeks of the post-fledging period when most juvenile mortality occurs, are largely lacking. We combined our measurements of fledgling survival for eight passerines in South Africa with estimates from published studies of 57 north and south temperate zone songbird species to test three predictions: (1) fledgling survival increases with length of development time in the nest; (2) fledgling survival increases with adult survival and reduced brood size controlled for development time; and (3) south temperate zone species, with their higher adult survival and smaller brood sizes, exhibit higher fledgling survival than north temperate zone species controlled for development time. We found that fledgling survival was higher among south temperate zone species and generally increased with development time and adult survival within and between latitudinal regions. Clutch size did not explain additional variation, but was confounded with adult survival. Given the importance of age-specific mortality to life history evolution, understanding the causes of these geographical patterns of mortality is important.

  9. Increasing incidence and survival in oral cancer

    DEFF Research Database (Denmark)

    Karnov, Kirstine Kim Schmidt; Grønhøj, Christian; Jensen, David Hebbelstrup

    2017-01-01

    Background: Oral carcinomas (OCs) make up a significant proportion of head and neck carcinomas (HNCs) and are an important cause of morbidity and mortality globally. The purpose of this population-based study was to determine trends in incidence and survival in OC in the Danish population from 1980...... regression analysis in relation to location, gender, age, and calendar year at diagnosis. Results: Altogether, 8299 patients with oral cancer were identified, 5062 (61%) of whom were males and 3237 (39%) were females. The median age at diagnosis was 63 years. The AAIR of patients with OC increased from 1.......9 per 100,000 in 1980 to 3.5 per 100,000 in 2014, and we observed a significant increase in 5-year OS of 12% points (a relative increase of 38%) from the period 1980–1984 to 2005–2009. Women were found to have a better prognosis than men. Conclusions: We found an unexpected increase in the age...

  10. Seasonal survival rates and causes of mortality of Little Owls in Denmark

    DEFF Research Database (Denmark)

    Thorup, Kasper; Pedersen, Dorthe; Sunde, Peter

    2013-01-01

    the causes of current survival rates, we estimated age- and season-specific survival rates and causes of mortality in Danish Little Owls on the basis of ringed birds 1920–2002, radio tagged adult and juveniles 2005–2008 and nest surveys 2006–2008. We estimate that 32 % of all eggs fledge and survive to 2...... weeks post hatching (age of ringing) and 47 %of the nestlings from ringing to fledging. Fifty-five percentage of the radio-tracked fledged young survived to dispersal, i.e. a total survival rate from egg to dispersal of 8 %. Analyses of combined ringing and radio tracking data showed a lower survival......Survival rate is an essential component of population dynamics; therefore, identification of variation in mortality rates and the factors that influence them might be of key importance in understanding why populations increase or decrease. In Denmark, the Little Owl Athene noctua, a species...

  11. Long-term survival and causes of death after stroke

    DEFF Research Database (Denmark)

    Brønnum-Hansen, Henrik; Davidsen, M; Thorvaldsen, P

    2001-01-01

    As part of the Danish contribution to the World Health Organization (WHO) MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Project, a register of patients with stroke was established in 1982. The purpose of the present study was to analyze long-term survival and causes of death...... after a first stroke and to compare them with those of the background population....

  12. Attenuation caused by infrequently updated covariates in survival analysis

    DEFF Research Database (Denmark)

    Andersen, Per Kragh; Liestøl, Knut

    2003-01-01

    Attenuation; Cox regression model; Measurement errors; Survival analysis; Time-dependent covariates......Attenuation; Cox regression model; Measurement errors; Survival analysis; Time-dependent covariates...

  13. Melatonin prevents experimental preterm labor and increases offspring survival.

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    Domínguez Rubio, Ana P; Sordelli, Micaela S; Salazar, Ana I; Aisemberg, Julieta; Bariani, María V; Cella, Maximiliano; Rosenstein, Ruth E; Franchi, Ana M

    2014-03-01

    Preterm delivery is the leading cause of neonatal mortality and contributes to delayed physical and cognitive development in children. At present, there is no efficient therapy to prevent preterm labor. A large body of evidence suggests that intra-amniotic infections may be a significant and potentially preventable cause of preterm birth. This work assessed the effect of melatonin in a murine model of inflammation-associated preterm delivery which mimics central features of preterm infection in humans. For this purpose, preterm labor was induced in BALB/c mice by intraperitoneal injections of bacterial lipopolysaccharide (LPS) at 10.00 hr (10 μg LPS) and 13.00 hr (20 μg LPS) on day 15 of pregnancy. On day 14 of pregnancy, a pellet of melatonin (25 mg) had been subcutaneously implanted into a group of animals. In the absence of melatonin, a 100% incidence of preterm birth was observed in LPS-treated animals, and the fetuses showed widespread damage. By comparison, treatment with melatonin prevented preterm birth in 50% of the cases, and all pups from melatonin-treated females were born alive and their body weight did not differ from control animals. Melatonin significantly prevented the LPS-induced rises in uterine prostaglandin (PG) E2 , PGF2α, and cyclooxygenase-2 protein levels. In addition, melatonin prevented the LPS-induced increase in uterine nitric oxide (NO) production, inducible NO synthase protein, and tumor necrosis factor-alpha (TNFα) levels. Collectively, our results suggest that melatonin could be a new therapeutic tool to prevent preterm labor and to increase offspring survival. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Increased Sleep Promotes Survival during a Bacterial Infection in Drosophila

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    Kuo, Tzu-Hsing; Williams, Julie A.

    2014-01-01

    Study Objectives: The relationship between sleep and immune function is not well understood at a functional or molecular level. We therefore used a genetic approach in Drosophila to manipulate sleep and evaluated effects on the ability of flies to fight bacterial infection. Setting: Laboratory. Participants: Drosophila melanogaster. Methods and Results: We used a genetic approach to transiently alter neuronal excitability in the mushroom body, a region in the central brain that is known to regulate sleep. Flies with increased sleep for up to two days prior to a bacterial infection showed increased resistance to the infection and improved survival. These flies also had increased expression levels of a subset of anti-microbial peptide mRNA prior to infection, as well as increased NFκB activity during infection as indicated by in vivo luciferase reporter activity. In contrast, flies that experienced reduced sleep for up to two days prior to infection had no effect on survival or on NFκB activity during infection. However, flies with reduced sleep showed an altered defense mechanism, such that resistance to infection was increased, but at the expense of reduced tolerance. This effect was dependent on environmental condition. Conclusions: Increasing sleep enhanced activity of an NFκB transcription factor, increased resistance to infection, and strongly promoted survival. Together, these findings support the hypothesis that sleep is beneficial to the host by maintaining a robust immune system. Citation: Kuo TH, Williams JA. Increased sleep promotes survival during a bacterial infection in Drosophila. SLEEP 2014;37(6):1077-1086. PMID:24882902

  15. Pharmacovigilance: Tiens Slimming Tea Causes Increased Blood ...

    African Journals Online (AJOL)

    ... possible link between the constituents of the slimming tea and increased blood pressure and also provide evidence of other possible harmful effects that may occur with the use of the slimming tea. Keywords: Pharmacovigilance, hypertension, slimming tea. West African Journal of Pharmacology and Drug Research Vol.

  16. Increased survival of antibiotic-resistant Escherichia coli inside macrophages.

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    Miskinyte, Migla; Gordo, Isabel

    2013-01-01

    Mutations causing antibiotic resistance usually incur a fitness cost in the absence of antibiotics. The magnitude of such costs is known to vary with the environment. Little is known about the fitness effects of antibiotic resistance mutations when bacteria confront the host's immune system. Here, we study the fitness effects of mutations in the rpoB, rpsL, and gyrA genes, which confer resistance to rifampin, streptomycin, and nalidixic acid, respectively. These antibiotics are frequently used in the treatment of bacterial infections. We measured two important fitness traits-growth rate and survival ability-of 12 Escherichia coli K-12 strains, each carrying a single resistance mutation, in the presence of macrophages. Strikingly, we found that 67% of the mutants survived better than the susceptible bacteria in the intracellular niche of the phagocytic cells. In particular, all E. coli streptomycin-resistant mutants exhibited an intracellular advantage. On the other hand, 42% of the mutants incurred a high fitness cost when the bacteria were allowed to divide outside of macrophages. This study shows that single nonsynonymous changes affecting fundamental processes in the cell can contribute to prolonged survival of E. coli in the context of an infection.

  17. Veratridine increases the survival of retinal ganglion cells in vitro

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    S.P.F. Pereira

    1997-12-01

    Full Text Available Neuronal cell death is an important phenomenon involving many biochemical pathways. This degenerative event has been studied to understand how the cells activate the mechanisms that lead to self-destruction. Target cells and afferent cells play a relevant role in the regulation of natural cell death. We studied the effect of veratridine (1.5, 3.0, 4.5 and 6.0 µM on the survival of neonatal rat retinal ganglion cells in vitro. Veratridine (3.0 µM, a well-known depolarizing agent that opens the Na+ channel, promoted a two-fold increase in the survival of retinal ganglion cells kept in culture for 48 h. This effect was dose-dependent and was blocked by 1.0 µM tetrodotoxin (a classical voltage-dependent Na+ channel blocker and 30.0 µM flunarizine (a Na+ and Ca2+ channel blocker. These results indicate that electrical activity is also important for the maintenance of retinal ganglion cell survival in vitro

  18. Novel Resuscitation from Lethal Hemorrhage. Increasing Survival of Combat Casualties

    National Research Council Canada - National Science Library

    Safar, Peter

    2001-01-01

    Using our novel animal models of severe hemorrhage, focusing on evaluation of outcome to 3-10 days, the following strategies were found superior in terms of intact survival compared to standard resuscitation...

  19. Hydrostatic pressure does not cause detectable changes in survival of human retinal ganglion cells.

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    Andrew Osborne

    Full Text Available PURPOSE: Elevated intraocular pressure (IOP is a major risk factor for glaucoma. One consequence of raised IOP is that ocular tissues are subjected to increased hydrostatic pressure (HP. The effect of raised HP on stress pathway signaling and retinal ganglion cell (RGC survival in the human retina was investigated. METHODS: A chamber was designed to expose cells to increased HP (constant and fluctuating. Accurate pressure control (10-100 mmHg was achieved using mass flow controllers. Human organotypic retinal cultures (HORCs from donor eyes (<24 h post mortem were cultured in serum-free DMEM/HamF12. Increased HP was compared to simulated ischemia (oxygen glucose deprivation, OGD. Cell death and apoptosis were measured by LDH and TUNEL assays, RGC marker expression by qRT-PCR (THY-1 and RGC number by immunohistochemistry (NeuN. Activated p38 and JNK were detected by Western blot. RESULTS: Exposure of HORCs to constant (60 mmHg or fluctuating (10-100 mmHg; 1 cycle/min pressure for 24 or 48 h caused no loss of structural integrity, LDH release, decrease in RGC marker expression (THY-1 or loss of RGCs compared with controls. In addition, there was no increase in TUNEL-positive NeuN-labelled cells at either time-point indicating no increase in apoptosis of RGCs. OGD increased apoptosis, reduced RGC marker expression and RGC number and caused elevated LDH release at 24 h. p38 and JNK phosphorylation remained unchanged in HORCs exposed to fluctuating pressure (10-100 mmHg; 1 cycle/min for 15, 30, 60 and 90 min durations, whereas OGD (3 h increased activation of p38 and JNK, remaining elevated for 90 min post-OGD. CONCLUSIONS: Directly applied HP had no detectable impact on RGC survival and stress-signalling in HORCs. Simulated ischemia, however, activated stress pathways and caused RGC death. These results show that direct HP does not cause degeneration of RGCs in the ex vivo human retina.

  20. Physical activity increases survival after heart valve surgery

    DEFF Research Database (Denmark)

    Lund, K.; Sibilitz, Kirstine Lærum; Kikkenborg Berg, Selina

    2016-01-01

    physical activity levels 6-12 months after heart valve surgery and (1) survival, (2) hospital readmission 18-24 months after surgery and (3) participation in exercise-based cardiac rehabilitation. METHODS: Prospective cohort study with registry data from The CopenHeart survey, The Danish National Patient...... readmission. Patients who participated in exercise-based cardiac rehabilitation (n=297) were more likely than the non-participants (n=200) to have a moderate or high physical activity level than a low physical activity level (fully adjusted OR: 1.52, 95% CI 1.03 to 2.24). CONCLUSIONS: Moderate to high levels...... of physical activity after heart valve surgery are positively associated with higher survival rates and participation in cardiac rehabilitation....

  1. Plant circadian clocks increase photosynthesis, growth, survival, and competitive advantage.

    Science.gov (United States)

    Dodd, Antony N; Salathia, Neeraj; Hall, Anthony; Kévei, Eva; Tóth, Réka; Nagy, Ferenc; Hibberd, Julian M; Millar, Andrew J; Webb, Alex A R

    2005-07-22

    Circadian clocks are believed to confer an advantage to plants, but the nature of that advantage has been unknown. We show that a substantial photosynthetic advantage is conferred by correct matching of the circadian clock period with that of the external light-dark cycle. In wild type and in long- and short-circadian period mutants of Arabidopsis thaliana, plants with a clock period matched to the environment contain more chlorophyll, fix more carbon, grow faster, and survive better than plants with circadian periods differing from their environment. This explains why plants gain advantage from circadian control.

  2. Survival and Cause of Death among a Cohort of Confirmed Amyotrophic Lateral Sclerosis Cases

    Science.gov (United States)

    Paulukonis, Susan T.; Roberts, Eric M.; Valle, Jhaqueline P.; Collins, Natalie N.; English, Paul B.; Kaye, Wendy E.

    2015-01-01

    Introduction Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder. Estimates of survival from disease onset range from 20 to 48 months and have been generated using clinical populations or death records alone. Methods Data on a cohort of ALS cases diagnosed between 2009–2011 were collected as part of the Los Angeles and San Francisco Bay Area Metropolitan ALS Surveillance projects; death records 2009–2013 were linked to these confirmed cases to determine survival post diagnosis and factors associated with survival time. Results There were 618 cases identified and 283 of these died during the follow up time period. Median age at death was 64.3 years, and median survival time post-diagnosis was 2.6 years. Age at diagnosis and year of diagnosis were predictors of survival time in adjusted models; those diagnosed at age 80 or older had shorter survival than those diagnosed at age 50 or younger. Most (92%) had ALS noted as a cause of death. Discussion Survival post-diagnosis may be improved compared with previous reports. Age at diagnosis continues to be the strongest predictor of prognosis; recall case reporting bias may play a role in estimates of survival time. PMID:26172548

  3. Survival in a population-based cohort of dementia patients: predictors and causes of mortality

    NARCIS (Netherlands)

    Boersma, F.; van den Brink, W.; Deeg, D. J.; Eefsting, J. A.; van Tilburg, W.

    1999-01-01

    To examine predictors of survival time and causes of mortality in a population-based cohort of demented subjects. Longitudinal naturalistic follow-up study. A rural area in The Netherlands. The study population consisted of 102 demented subjects derived from a population-based, two-stage prevalence

  4. Trends in survival and cause of death in Danish patients with multiple sclerosis

    DEFF Research Database (Denmark)

    Brønnum-Hansen, Henrik; Koch-Henriksen, Nils; Stenager, Egon

    2004-01-01

    The Danish Multiple Sclerosis Registry contains information about all Danish patients in whom multiple sclerosis has been diagnosed since 1948. The purpose of this study was to analyse trends in survival and causes of death of these patients and to compare them with those of the general population....... The study comprised all patients with onset in the period 1949-1996. All case records were validated and classified according to standardized diagnostic criteria. Data on emigration and death were obtained by record linkage to official registers. The end of follow-up was 1 January 2000 for emigration...... and death, and 1 January 1999 for cause-specific deaths. Standardized mortality ratios and excess death rates were calculated for various causes of death and periods after multiple sclerosis onset, and time trends in survival probability were analysed by Cox regression. The study comprised 9881 patients...

  5. Patient survival and causes of death on hemodialysis and peritoneal dialysis--single-center study.

    Science.gov (United States)

    Litwin, M; Grenda, R; Prokurat, S; Abuauba, M; Latoszyñska, J; Jobs, K; Boguszewska-Baczkowska, A; Wawer, Z T

    2001-12-01

    Survival and causes of death in children dialyzed in a single center were analyzed. During the last 12 years a chronic dialysis program was introduced in 146 children in our center and 125 of them, eligible for observation, were included in this analysis; 58 patients were on hemodialysis (HD) and 67 on peritoneal dialysis [continuous ambulatory peritoneal dialysis/automated peritoneal dialysis (CAPD/APD)]. Mean age at the start of dialysis was 13.1 years in HD and 9.8 years in CAPD/APD patients. Overall, 16 patients died (12.5%); 6 (10.3%) on HD and 10 (14.9%) on CAPD/APD; 4 HD patients died of hemorrhagic stroke and 2 were killed in road traffic accidents. Of 10 CAPD/APD patients, 7 died of heart failure, ischemic stroke, and/or disseminated thromboembolic disease. Another was killed in a road traffic accident and 2 died during the course of severe infections. The 1-year patient survival rate was 96.6% in HD patients and 95% in CAPD/APD patients, 2-year survival 94% and 93% and 5-year survival 91% and 78%, respectively (P=0.2, NS). In conclusion, the survival rate for HD and CAPD patients is similar, although after 2 years of therapy, it is lower in CAPD patients. The main causes of death are cardiovascular. However, in CAPD/APD patients, heart failure with low cardiac output and thromboembolic complications are major causes of death, and in HD patients the main cause is hemorrhagic stroke.

  6. Maternal allergic contact dermatitis causes increased asthma risk in offspring.

    Science.gov (United States)

    Lim, Robert H; Arredouani, Mohamed S; Fedulov, Alexey; Kobzik, Lester; Hubeau, Cedric

    2007-07-27

    Offspring of asthmatic mothers have increased risk of developing asthma, based on human epidemiologic data and experimental animal models. The objective of this study was to determine whether maternal allergy at non-pulmonary sites can increase asthma risk in offspring. BALB/c female mice received 2 topical applications of vehicle, dinitrochlorobenzene, or toluene diisocyanate before mating with untreated males. Dinitrochlorobenzene is a skin-sensitizer only and known to induce a Th1 response, while toluene diisocyanate is both a skin and respiratory sensitizer that causes a Th2 response. Both cause allergic contact dermatitis. Offspring underwent an intentionally suboptimal protocol of allergen sensitization and aerosol challenge, followed by evaluation of airway hyperresponsiveness, allergic airway inflammation, and cytokine production. Mothers were tested for allergic airway disease, evidence of dermatitis, cellularity of the draining lymph nodes, and systemic cytokine levels. The role of interleukin-4 was also explored using interleukin-4 deficient mice. Offspring of toluene diisocyanate but not dinitrochlorobenzene-treated mothers developed an asthmatic phenotype following allergen sensitization and challenge, seen as increased Penh values, airway inflammation, bronchoalveolar lavage total cell counts and eosinophilia, and Th2 cytokine imbalance in the lung. Toluene diisocyanate treated interleukin-4 deficient mothers were able to transfer asthma risk to offspring. Mothers in both experimental groups developed allergic contact dermatitis, but not allergic airway disease. Maternal non-respiratory allergy (Th2-skewed dermatitis caused by toluene diisocyanate) can result in the maternal transmission of asthma risk in mice.

  7. Maternal allergic contact dermatitis causes increased asthma risk in offspring

    Directory of Open Access Journals (Sweden)

    Kobzik Lester

    2007-07-01

    Full Text Available Abstract Background Offspring of asthmatic mothers have increased risk of developing asthma, based on human epidemiologic data and experimental animal models. The objective of this study was to determine whether maternal allergy at non-pulmonary sites can increase asthma risk in offspring. Methods BALB/c female mice received 2 topical applications of vehicle, dinitrochlorobenzene, or toluene diisocyanate before mating with untreated males. Dinitrochlorobenzene is a skin-sensitizer only and known to induce a Th1 response, while toluene diisocyanate is both a skin and respiratory sensitizer that causes a Th2 response. Both cause allergic contact dermatitis. Offspring underwent an intentionally suboptimal protocol of allergen sensitization and aerosol challenge, followed by evaluation of airway hyperresponsiveness, allergic airway inflammation, and cytokine production. Mothers were tested for allergic airway disease, evidence of dermatitis, cellularity of the draining lymph nodes, and systemic cytokine levels. The role of interleukin-4 was also explored using interleukin-4 deficient mice. Results Offspring of toluene diisocyanate but not dinitrochlorobenzene-treated mothers developed an asthmatic phenotype following allergen sensitization and challenge, seen as increased Penh values, airway inflammation, bronchoalveolar lavage total cell counts and eosinophilia, and Th2 cytokine imbalance in the lung. Toluene diisocyanate treated interleukin-4 deficient mothers were able to transfer asthma risk to offspring. Mothers in both experimental groups developed allergic contact dermatitis, but not allergic airway disease. Conclusion Maternal non-respiratory allergy (Th2-skewed dermatitis caused by toluene diisocyanate can result in the maternal transmission of asthma risk in mice.

  8. Survival rates and worker compensation expenses in a national cohort of Mexican workers with permanent occupational disability caused by diabetes

    Directory of Open Access Journals (Sweden)

    Iván de Jesús Ascencio-Montiel

    2016-09-01

    Full Text Available Abstract Background Permanent occupational disability is one of the most severe consequences of diabetes that impedes the performance of usual working activities among economically active individuals. Survival rates and worker compensation expenses have not previously been examined among Mexican workers. We aimed to describe the worker compensation expenses derived from pension payments and also to examine the survival rates and characteristics associated with all-cause mortality, in a cohort of 34,014 Mexican workers with permanent occupational disability caused by diabetes during the years 2000–2013 at the Mexican Institute of Social Security. Methods A cross-sectional analysis study was conducted using national administrative records data from the entire country, regarding permanent occupational disability medical certification, pension payment and vital status. Survival rates were estimated using the Kaplan–Meier method. Multivariate Cox proportional hazard model was used to estimate adjusted hazard ratios (HR and 95 % confidence intervals (95 % CI in order to assess the cohort characteristics and all-cause mortality risk. Total expenses derived from pension payments for the period were accounted for in U.S. dollars (USD, 2013. Results There were 12,917 deaths in 142,725.1 person-years. Median survival time was 7.26 years. After multivariate adjusted analysis, males (HR, 1.39; 95 % CI, 1.29–1.50, agricultural, forestry, and fishery workers (HR, 1.41; 95 % CI, 1.15–1.73 and renal complications (HR, 3.49; 95 % CI, 3.18–3.83 had the highest association with all-cause mortality. The all-period expenses derived from pension payments amounted to $777.78 million USD (2013, and showed a sustained increment: from $58.28 million USD in 2000 to $111.62 million USD in 2013 (percentage increase of 91.5 %. Conclusions Mexican workers with permanent occupational disability caused by diabetes had a median survival of 7.26 years, and those

  9. Ciprofloxacin Derivatives Affect Parasite Cell Division and Increase the Survival of Mice Infected with Toxoplasma gondii.

    Directory of Open Access Journals (Sweden)

    Erica S Martins-Duarte

    Full Text Available Toxoplasmosis, caused by the protozoan Toxoplasma gondii, is a worldwide disease whose clinical manifestations include encephalitis and congenital malformations in newborns. Previously, we described the synthesis of new ethyl-ester derivatives of the antibiotic ciprofloxacin with ~40-fold increased activity against T. gondii in vitro, compared with the original compound. Cipro derivatives are expected to target the parasite's DNA gyrase complex in the apicoplast. The activity of these compounds in vivo, as well as their mode of action, remained thus far uncharacterized. Here, we examined the activity of the Cipro derivatives in vivo, in a model of acute murine toxoplasmosis. In addition, we investigated the cellular effects T. gondii tachyzoites in vitro, by immunofluorescence and transmission electron microscopy (TEM. When compared with Cipro treatment, 7-day treatments with Cipro derivatives increased mouse survival significantly, with 13-25% of mice surviving for up to 60 days post-infection (vs. complete lethality 10 days post-infection, with Cipro treatment. Light microscopy examination early (6 and 24h post-infection revealed that 6-h treatments with Cipro derivatives inhibited the initial event of parasite cell division inside host cells, in an irreversible manner. By TEM and immunofluorescence, the main cellular effects observed after treatment with Cipro derivatives and Cipro were cell scission inhibition--with the appearance of 'tethered' parasites--malformation of the inner membrane complex, and apicoplast enlargement and missegregation. Interestingly, tethered daughter cells resulting from Cipro derivatives, and also Cipro, treatment did not show MORN1 cap or centrocone localization. The biological activity of Cipro derivatives against C. parvum, an apicomplexan species that lacks the apicoplast, is, approximately, 50 fold lower than that in T. gondii tachyzoites, supporting that these compounds targets the apicoplast. Our results

  10. Carbon monoxide inhalation increases microparticles causing vascular and CNS dysfunction

    International Nuclear Information System (INIS)

    Xu, Jiajun; Yang, Ming; Kosterin, Paul; Salzberg, Brian M.; Milovanova, Tatyana N.; Bhopale, Veena M.; Thom, Stephen R.

    2013-01-01

    We hypothesized that circulating microparticles (MPs) play a role in pro-inflammatory effects associated with carbon monoxide (CO) inhalation. Mice exposed for 1 h to 100 ppm CO or more exhibit increases in circulating MPs derived from a variety of vascular cells as well as neutrophil activation. Tissue injury was quantified as 2000 kDa dextran leakage from vessels and as neutrophil sequestration in the brain and skeletal muscle; and central nervous system nerve dysfunction was documented as broadening of the neurohypophysial action potential (AP). Indices of injury occurred following exposures to 1000 ppm for 1 h or to 1000 ppm for 40 min followed by 3000 ppm for 20 min. MPs were implicated in causing injuries because infusing the surfactant MP lytic agent, polyethylene glycol telomere B (PEGtB) abrogated elevations in MPs, vascular leak, neutrophil sequestration and AP prolongation. These manifestations of tissue injury also did not occur in mice lacking myeloperoxidase. Vascular leakage and AP prolongation were produced in naïve mice infused with MPs that had been obtained from CO poisoned mice, but this did not occur with MPs obtained from control mice. We conclude that CO poisoning triggers elevations of MPs that activate neutrophils which subsequently cause tissue injuries. - Highlights: • Circulating microparticles (MPs) increase in mice exposed to 100 ppm CO or more. • MPs are lysed by infusing the surfactant polyethylene glycol telomere B. • CO-induced MPs cause neutrophil activation, vascular leak and CNS dysfunction. • Similar tissue injuries do not arise with MPs obtained from air-exposed, control mice

  11. Carbon monoxide inhalation increases microparticles causing vascular and CNS dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Jiajun; Yang, Ming [Department of Emergency Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Kosterin, Paul [Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Salzberg, Brian M. [Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Milovanova, Tatyana N.; Bhopale, Veena M. [Department of Emergency Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Thom, Stephen R., E-mail: sthom@smail.umaryland.edu [Department of Emergency Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States)

    2013-12-01

    We hypothesized that circulating microparticles (MPs) play a role in pro-inflammatory effects associated with carbon monoxide (CO) inhalation. Mice exposed for 1 h to 100 ppm CO or more exhibit increases in circulating MPs derived from a variety of vascular cells as well as neutrophil activation. Tissue injury was quantified as 2000 kDa dextran leakage from vessels and as neutrophil sequestration in the brain and skeletal muscle; and central nervous system nerve dysfunction was documented as broadening of the neurohypophysial action potential (AP). Indices of injury occurred following exposures to 1000 ppm for 1 h or to 1000 ppm for 40 min followed by 3000 ppm for 20 min. MPs were implicated in causing injuries because infusing the surfactant MP lytic agent, polyethylene glycol telomere B (PEGtB) abrogated elevations in MPs, vascular leak, neutrophil sequestration and AP prolongation. These manifestations of tissue injury also did not occur in mice lacking myeloperoxidase. Vascular leakage and AP prolongation were produced in naïve mice infused with MPs that had been obtained from CO poisoned mice, but this did not occur with MPs obtained from control mice. We conclude that CO poisoning triggers elevations of MPs that activate neutrophils which subsequently cause tissue injuries. - Highlights: • Circulating microparticles (MPs) increase in mice exposed to 100 ppm CO or more. • MPs are lysed by infusing the surfactant polyethylene glycol telomere B. • CO-induced MPs cause neutrophil activation, vascular leak and CNS dysfunction. • Similar tissue injuries do not arise with MPs obtained from air-exposed, control mice.

  12. A natural form of learning can increase and decrease the survival of new neurons in the dentate gyrus.

    Science.gov (United States)

    Olariu, Ana; Cleaver, Kathryn M; Shore, Lauren E; Brewer, Michelle D; Cameron, Heather A

    2005-01-01

    Granule cells born in the adult dentate gyrus undergo a 4-week developmental period characterized by high susceptibility to cell death. Two forms of hippocampus-dependent learning have been shown to rescue many of the new neurons during this critical period. Here, we show that a natural form of associative learning, social transmission of food preference (STFP), can either increase or decrease the survival of young granule cells in adult rats. Increased numbers of pyknotic as well as phospho-Akt-expressing BrdU-labeled cells were seen 1 day after STFP training, indicating that training rapidly induces both cell death and active suppression of cell death in different subsets. A single day of training for STFP increased the survival of 8-day-old BrdU-labeled cells when examined 1 week later. In contrast, 2 days of training decreased the survival of BrdU-labeled cells and the density of immature neurons, identified with crmp-4. This change from increased to decreased survival could not be accounted for by the ages of the cells. Instead, we propose that training may initially increase young granule cell survival, then, if continued, cause them to die. This complex regulation of cell death could potentially serve to maintain granule cells that are actively involved in memory consolidation, while rapidly using and discarding young granule cells whose training is complete to make space for new naïve neurons. Published 2005 Wiley-Liss, Inc.

  13. 20-year follow-up study of Danish HHT patients-survival and causes of death

    DEFF Research Database (Denmark)

    Kjeldsen, Anette; Aagaard, Katrine Saldern; Tørring, Pernille Mathiesen

    2016-01-01

    similar survival rates in the two groups. Cancer diagnoses had been registered in the follow-up period in 4 (5%) HHT patients and in 38 (17%) controls. CONCLUSION: The mortality was not increased among Danish HHT patients compared to controls. This study is based on a clinical unselected series of HHT...

  14. Survival in 76 cats with epilepsy of unknown cause: a retrospective study

    Science.gov (United States)

    Szelecsenyi, A.; Giger, U.; Golini, L.; Mothersill, I.; Torgerson, P. R.; Steffen, F.

    2017-01-01

    Survival of cats with epilepsy of unknown cause (EUC) has not been reported. Seizure semiology and its relationship to treatment outcome and survival was studied in a population of 76 cats. A questionnaire for seizure semiology was developed based upon experimental data. Seizure semiology was characterized by owner interviews at least one year after discharge. Seizures were classified as: (1) primary generalized and (2) focal without and (3) with secondary generalization. Median age at seizure onset was four (range 0.3 to 18) years. One third of cats with EUC presented with primary generalized seizures and 78% of those with initially focal seizures progressed to secondary generalized seizures. Clinical signs of generalized seizures included sudden onset of loss of consciousness and tonic-clonic seizures, while cats with focal seizures had unilateral signs. Antiepileptic drug (AED) therapy was initiated in 62 cats. Complete remission rate was 42% and median survival time was 3.2 (range 1 to 11) years with or without AED, and 91% were still alive at the time of interview. Neither semiology nor seizure type predicted survival, response to treatment, and outcome in cats with EUC. A seizure-free status of >12 months was observed in 79% of cats without AED. PMID:29097567

  15. Survival in 76 cats with epilepsy of unknown cause: a retrospective study.

    Science.gov (United States)

    Szelecsenyi, Arlette Cornelia; Giger, Urs; Golini, Lorenzo; Mothersill, Ian; Torgerson, Paul R; Steffen, Frank

    2017-11-01

    Survival of cats with epilepsy of unknown cause (EUC) has not been reported. Seizure semiology and its relationship to treatment outcome and survival was studied in a population of 76 cats. A questionnaire for seizure semiology was developed based on experimental data. Seizure semiology was characterised by owner interviews at least one year after discharge. Seizures were classified as (1) primary generalised and (2) focal without and (3) with secondary generalisation. Median age at seizure onset was four (range 0.3-18) years. One-third of cats with EUC presented with primary generalised seizures and 78 per cent of those with initially focal seizures progressed to secondary generalised seizures. Clinical signs of generalised seizures included sudden onset of loss of consciousness and tonic-clonic seizures, while cats with focal seizures had unilateral signs. Antiepileptic drug (AED) therapy was initiated in 62 cats. Complete remission rate was 42 per cent and the median survival time was 3.2 (range 1-11) years with or without AED, and 91 per cent were still alive at the time of interview. Neither semiology nor seizure type predicted survival, response to treatment and outcome in cats with EUC. A seizure-free status of more than 12 months was observed in 79 per cent of cats without AED. © British Veterinary Association (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  16. Survival and cause of death in multiple sclerosis: a 60-year longitudinal population study.

    Science.gov (United States)

    Lunde, Hanne Marie Bøe; Assmus, Jörg; Myhr, Kjell-Morten; Bø, Lars; Grytten, Nina

    2017-08-01

    Survival and causes of death (COD) in multiple sclerosis (MS) provide ultimate endpoints. We aimed to investigate survival and COD in a 60-year population-based MS cohort compared with the general population. All patients with incident multiple sclerosis (MS) (N=1388) with onset during 1953-2012 in Hordaland County, Western Norway, were included. Data were obtained from patient records at Haukeland University Hospital and linked to the Norwegian COD registry. Survival adjusted for sex, age and disease course were estimated by Kaplan-Meier analyses from birth and from disease onset. Mortality and COD in MS relative to the general population were examined by standardised mortality ratio (SMR). Of 1388 patients, 291 had deceased, mainly of MS (56.4%). Median life expectancy was 74.7 years for MS and 81.8 years for the general population (p0.0001); 2.9 in women and 2.5 in men (p=0.0009). SMR was 2.4 in RRMS and 3.9 in PPMS (ppopulation. A rise in survival in MS was observed during the entire observation period. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  17. Goat Meat Does Not Cause Increased Blood Pressure

    Directory of Open Access Journals (Sweden)

    Katsunori Sunagawa

    2014-01-01

    Full Text Available While there are persistent rumors that the consumption of goat meat dishes increases blood pressure, there is no scientific evidence to support this. Two experiments were conducted to clarify whether or not blood pressure increases in conjunction with the consumption of goat meat dishes. In experiment 1, 24 Dahl/Iwai rats (15 weeks old, body weight 309.3±11.1 g were evenly separated into 4 groups. The control group (CP was fed a diet containing 20% chicken and 0.3% salt on a dry matter basis. The goat meat group (GM was fed a diet containing 20% goat meat and 0.3% salt. The goat meat/salt group (GS was fed a diet containing 20% goat meant and 3% to 4% salt. The Okinawan mugwort (Artemisia Princeps Pampan/salt group (GY was fed a diet containing 20% goat meat, 3% to 4% salt and 5% of freeze-dried mugwort powder. The experiment 1 ran for a period of 14 weeks during which time the blood pressure of the animals was recorded. The GS, and GY groups consumed significantly more water (p<0.01 than the CP and GM groups despite the fact that their diet consumption levels were similar. The body weight of animals in the CP, GM, and GS groups was similar while the animals in the GY group were significantly smaller (p<0.01. The blood pressure in the GM group was virtually the same as the CP group throughout the course of the experiment. In contrast, while the blood pressure of the animals in the GS and GY group from 15 to 19 weeks old was the same as the CP group, their blood pressures were significantly higher (p<0.01 after 20 weeks of age. The GY group tended to have lower blood pressure than the GS group. In experiment 2, in order to clarify whether or not the increase in blood pressure in the GS group and the GY group in experiment 1 was caused by an excessive intake of salt, the effects on blood pressure of a reduction of salt in diet were investigated. When amount of salt in the diet of the GS and GY group was reduced from 4% to 0.3%, the animal

  18. Free Base Lysine Increases Survival and Reduces Metastasis in Prostate Cancer Model.

    Science.gov (United States)

    Ibrahim-Hashim, Arig; Wojtkowiak, Jonathan W; de Lourdes Coelho Ribeiro, Maria; Estrella, Veronica; Bailey, Kate M; Cornnell, Heather H; Gatenby, Robert A; Gillies, Robert J

    2011-11-19

    Malignant tumor cells typically metabolize glucose anaerobically to lactic acid even under normal oxygen tension, a phenomenon called aerobic glycolysis or the Warburg effect. This results in increased acid production and the acidification of the extracellular microenvironment in solid tumors. H + ions tend to flow along concentration gradients into peritumoral normal tissue causing extracellular matrix degradation and increased tumor cell motility thus promoting invasion and metastasis. We have shown that reducing this acidity with sodium bicarbonate buffer decreases the metastatic fitness of circulating tumor cells in prostate cancer and other cancer models. Mathematical models of the tumor-host dynamics predicted that buffers with a pka around 7 will be more effective in reducing intra- and peri-tumoral acidosis and, thus, and possibly more effective in inhibiting tumor metastasis than sodium bicarbonate which has a pKa around 6. Here we test this prediction the efficacy of free base lysine; a non-bicarbonate/non-volatile buffer with a higher pKa (~10), on prostate tumor metastases model. Oxygen consumption and acid production rate of PC3M prostate cancer cells and normal prostate cells were determined using the Seahorse Extracellular Flux (XF-96) analyzer. In vivo effect of 200 mM lysine started four days prior to inoculation on inhibition of metastasis was examined in PC3M-LUC-C6 prostate cancer model using SCID mice. Metastases were followed by bioluminescence imaging. PC3M prostate cancer cells are highly acidic in comparison to a normal prostate cell line indicating that reduction of intra- and perit-tumoral acidosis should inhibit metastases formation. In vivo administration of 200 mM free base lysine increased survival and reduced metastasis. PC3M prostate cancer cells are highly glycolytic and produce large amounts of acid when compared to normal prostate cells. Administration of non-volatile buffer decreased growth of metastases and improved survival

  19. Prolonged hypoxia increases survival even in Zebrafish (Danio rerio showing cardiac arrhythmia.

    Directory of Open Access Journals (Sweden)

    Renate Kopp

    Full Text Available Tolerance towards hypoxia is highly pronounced in zebrafish. In this study even beneficial effects of hypoxia, specifically enhanced survival of zebrafish larvae, could be demonstrated. This effect was actually more pronounced in breakdance mutants, which phenotypically show cardiac arrhythmia. Breakdance mutants (bre are characterized by chronically reduced cardiac output. Despite an about 50% heart rate reduction, they become adults, but survival rate significantly drops to 40%. Normoxic bre animals demonstrate increased hypoxia inducible factor 1 a (Hif-1α expression, which indicates an activated hypoxic signaling pathway. Consequently, cardiovascular acclimation, like cardiac hypertrophy and increased erythrocyte concentration, occurs. Thus, it was hypothesized, that under hypoxic conditions survival might be even more reduced. When bre mutants were exposed to hypoxic conditions, they surprisingly showed higher survival rates than under normoxic conditions and even reached wildtype values. In hypoxic wildtype zebrafish, survival yet exceeded normoxic control values. To specify physiological acclimation, cardiovascular and metabolic parameters were measured before hypoxia started (3 dpf, when the first differences in survival rate occurred (7 dpf and when survival rate plateaued (15 dpf. Hypoxic animals expectedly demonstrated Hif-1α accumulation and consequently enhanced convective oxygen carrying capacity. Moreover, bre animals showed a significantly enhanced heart rate under hypoxic conditions, which reached normoxic wildtype values. This improvement in convective oxygen transport ensured a sufficient oxygen and nutrient supply and was also reflected in the significantly higher mitochondrial activity. The highly optimized energy metabolism observed in hypoxic zebrafish larvae might be decisive for periods of higher energy demand due to organ development, growth and increased activity. However, hypoxia increased survival only during a

  20. Increasing Winter Maximal Metabolic Rate Improves Intrawinter Survival in Small Birds.

    Science.gov (United States)

    Petit, Magali; Clavijo-Baquet, Sabrina; Vézina, François

    Small resident bird species living at northern latitudes increase their metabolism in winter, and this is widely assumed to improve their chances of survival. However, the relationship between winter metabolic performance and survival has yet to be demonstrated. Using capture-mark-recapture, we followed a population of free-living black-capped chickadees (Poecile atricapillus) over 3 yr and evaluated their survival probability within and among winters. We also measured the size-independent body mass (M s ), hematocrit (Hct), basal metabolic rate (BMR), and maximal thermogenic capacity (Msum) and investigated how these parameters influenced survival within and among winters. Results showed that survival probability was high and constant both within (0.92) and among (0.96) winters. They also showed that while M s , Hct, and BMR had no significant influence, survival was positively related to Msum-following a sigmoid relationship-within but not among winter. Birds expressing an Msum below 1.26 W (i.e., similar to summer levels) had a winter. Our data therefore suggest that black-capped chickadees that are either too slow or unable to adjust their phenotype from summer to winter have little chances of survival and thus that seasonal upregulation of metabolic performance is highly beneficial. This study is the first to document in an avian system the relationship between thermogenic capacity and winter survival, a proxy of fitness.

  1. Volunteering is associated with increased survival in able-bodied participants of the English Longitudinal Study of Ageing.

    Science.gov (United States)

    Rogers, Nina Trivedy; Demakakos, Panayotes; Taylor, Mark Steven; Steptoe, Andrew; Hamer, Mark; Shankar, Aparna

    2016-06-01

    Volunteering has been linked to reduced mortality in older adults, but the mechanisms explaining this effect remain unclear. This study investigated whether volunteering is associated with increased survival in participants of the English Longitudinal Study of Ageing and whether differences in survival are modified by functional disabilities. A multivariate Cox Proportional Hazards model was used to estimate the association of volunteering with survival over a period of 10.9 years in 10 324 participants, while controlling for selected confounders. To investigate effect modification by disability, the analyses were repeated in participants with and without self-reported functional disabilities. Volunteering was associated with a reduced probability of death from all causes in univariate analyses (HR=0.65, CI 0.58 to 0.73, pvolunteers had significantly increased survival compared with able-bodied non-volunteers (HR=0.81, 95% CI 0.69 to 0.95, p=0.009). There was no significant survival advantage among disabled volunteers, compared with disabled non-volunteers (HR=1.06, CI 0.88 to 1.29, p=0.53). Volunteering is associated with reduced mortality in older adults in England, but this effect appears to be limited to volunteers who report no disabilities. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  2. L-proline increases survival of tilapias infected by Streptococcus agalactiae in higher water temperature.

    Science.gov (United States)

    Zhao, Xian-Liang; Han, Yi; Ren, Shi-Tong; Ma, Yan-Mei; Li, Hui; Peng, Xuan-Xian

    2015-05-01

    Streptococcosis causes massive tilapia kills, which results in heavy economic losses of tilapia farming industry. Out of the Streptococcosis, Streptococcus agalactiae is the major pathogen. The bacterium causes higher mortality of tilapias in higher than lower temperatures. However, effect of temperature on metabolic regulation which is related to the mortality is largely unknown. The present study showed 50% and 70% mortality of tilapias cultured in 25 °C and 30 °C, respectively, in comparison with no death in 20 °C following infection caused by S. agalactiae. Then, GC/MS based metabolomics was used to investigate a global metabolic response of tilapia liver to the two higher water temperatures compared to 20 °C. Thirty-six and forty-five varied abundance of metabolites were identified in livers of tilapias cultured at 25 °C and 30 °C, respectively. More decreasing abundance of amino acids and increasing abundance of carbohydrates were detected in 30 °C than 25 °C groups. On the other hand, out of the pathways enriched, the first five biggest impact pathways belong to amino acid metabolism. Decreasing abundance of l-proline was identified as a crucial biomarker for indexing higher water temperature and a potential modulator to reduce the high death. This was validated by engineering injection or oral addition of l-proline. Exogenous l-proline led to elevated amino acid metabolism, which contributes to the elevated survivals. Our findings provide a potential metabolic modulator for controlling the disease, and shed some light on host metabolic prevention to infectious diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Causes and consequences of increased sympathetic activity in renal disease

    NARCIS (Netherlands)

    Joles, JA; Koomans, HA

    Much evidence indicates increased sympathetic nervous activity (SNA) in renal disease. Renal ischemia is probably a primary event leading to increased SNA. Increased SNA often occurs in association with hypertension. However, the deleterious effect of increased SNA on the diseased kidney is not only

  4. Causes of Artificial Urinary Sphincter Failure and Strategies for Surgical Revision: Implications of Device Component Survival.

    Science.gov (United States)

    Srivastava, Arnav; Joice, Gregory A; Patel, Hiten D; Manka, Madeleine G; Sopko, Nikolai A; Wright, E James

    2018-03-12

    Up to 50% of patients receiving an artificial urinary sphincter (AUS) require surgical revision after initial placement. However, the literature is heterogeneous regarding the leading causes of AUS failure and appropriate surgical management. To inform a revision approach by tabulating the causes of AUS failure, assessing AUS component survival, and examining the single-component revision efficacy. We retrospectively reviewed 168 patients receiving AUS placements carried out by a single surgeon from 2008 to 2016 at a high-volume academic institution. The median follow-up from initial placement was 2.7 yr, with 37.5% experiencing recurrent incontinence. The cuff size ranged from 4.0 to 5.5cm, with median size of 4.5cm. Patients without infection or erosion underwent systematic device interrogation and revision, starting with the pressure-regulating balloon (PRB) and then, if necessary, the urethral cuff. Device revision involved either PRB-only correction or cuff and PRB revision. We used bootstrapped intervals to estimate the mean time to failure for individual AUS components. Kaplan-Meier estimates were used to compare survival for individual components and for revised devices by revision technique. PRB malfunction most commonly caused device failure, while cuff or pump malfunction was rare. Among patients undergoing surgical revision, those with PRB-only correction had similar outcomes to those with more extensive device correction (cuff and PRB exchange; p=0.46). This study, while systematic and detailed, is limited by sample size, follow-up length, and its retrospective nature. PRB malfunction most commonly caused AUS failure in our cohort. PRB-only correction may satisfactorily restore AUS function in select patients. Consequently, initial interrogation of the PRB may avoid a second incision and urethral exposure for many patients requiring AUS revision. Artificial urinary sphincters remain prone to failure over time. In many instances, correcting only the

  5. Chronic ethanol consumption causes increased glucuronidation of morphine in rabbits.

    Science.gov (United States)

    Narayan, S S; Hayton, W L; Yost, G S

    1991-04-01

    1. Male rabbits were given an i.p. injection of 15 mg/kg morphine and plasma concentrations of morphine and morphine-3-glucuronide (M3G) were simultaneously quantified by h.p.l.c. After 14 days of 10% ethanol in the rabbits' drinking water, a second injection of morphine was administered and plasma concentrations were determined again. 2. Morphine plasma clearance increased significantly by 42% after ethanol treatment. The area under the plasma concentration time curve (AUC) for morphine decreased by 23% while the AUC for the glucuronide increased by 22%. 3. The ratio of the AUCs (glucruonide/morphine) increased by 72%. These results demonstrate that chronic ethanol treatment of rabbits results in increased clearance of morphine after an i.p. dose. The increase in clearance is most likely due to induction of UDP-glucuronosyltransferase isozymes by ethanol.

  6. Schinus terebinthifolius Leaf Extract Causes Midgut Damage, Interfering with Survival and Development of Aedes aegypti Larvae.

    Science.gov (United States)

    Procópio, Thamara Figueiredo; Fernandes, Kenner Morais; Pontual, Emmanuel Viana; Ximenes, Rafael Matos; de Oliveira, Aline Rafaella Cardoso; Souza, Carolina de Santana; Melo, Ana Maria Mendonça de Albuquerque; Navarro, Daniela Maria do Amaral Ferraz; Paiva, Patrícia Maria Guedes; Martins, Gustavo Ferreira; Napoleão, Thiago Henrique

    2015-01-01

    In this study, a leaf extract from Schinus terebinthifolius was evaluated for effects on survival, development, and midgut of A. aegypti fourth instar larvae (L4), as well as for toxic effect on Artemia salina. Leaf extract was obtained using 0.15 M NaCl and evaluated for phytochemical composition and lectin activity. Early L4 larvae were incubated with the extract (0.3-1.35%, w/v) for 8 days, in presence or absence of food. Polymeric proanthocyanidins, hydrolysable tannins, heterosid and aglycone flavonoids, cinnamic acid derivatives, traces of steroids, and lectin activity were detected in the extract, which killed the larvae at an LC50 of 0.62% (unfed larvae) and 1.03% (fed larvae). Further, the larvae incubated with the extract reacted by eliminating the gut content. No larvae reached the pupal stage in treatments at concentrations between 0.5% and 1.35%, while in the control (fed larvae), 61.7% of individuals emerged as adults. The extract (1.0%) promoted intense disorganization of larval midgut epithelium, including deformation and hypertrophy of cells, disruption of microvilli, and vacuolization of cytoplasms, affecting digestive, enteroendocrine, regenerative, and proliferating cells. In addition, cells with fragmented DNA were observed. Separation of extract components by solid phase extraction revealed that cinnamic acid derivatives and flavonoids are involved in larvicidal effect of the extract, being the first most efficient in a short time after larvae treatment. The lectin present in the extract was isolated, but did not show deleterious effects on larvae. The extract and cinnamic acid derivatives were toxic to A. salina nauplii, while the flavonoids showed low toxicity. S. terebinthifolius leaf extract caused damage to the midgut of A. aegypti larvae, interfering with survival and development. The larvicidal effect of the extract can be attributed to cinnamic acid derivatives and flavonoids. The data obtained using A. salina indicates that caution

  7. Schinus terebinthifolius Leaf Extract Causes Midgut Damage, Interfering with Survival and Development of Aedes aegypti Larvae.

    Directory of Open Access Journals (Sweden)

    Thamara Figueiredo Procópio

    Full Text Available In this study, a leaf extract from Schinus terebinthifolius was evaluated for effects on survival, development, and midgut of A. aegypti fourth instar larvae (L4, as well as for toxic effect on Artemia salina. Leaf extract was obtained using 0.15 M NaCl and evaluated for phytochemical composition and lectin activity. Early L4 larvae were incubated with the extract (0.3-1.35%, w/v for 8 days, in presence or absence of food. Polymeric proanthocyanidins, hydrolysable tannins, heterosid and aglycone flavonoids, cinnamic acid derivatives, traces of steroids, and lectin activity were detected in the extract, which killed the larvae at an LC50 of 0.62% (unfed larvae and 1.03% (fed larvae. Further, the larvae incubated with the extract reacted by eliminating the gut content. No larvae reached the pupal stage in treatments at concentrations between 0.5% and 1.35%, while in the control (fed larvae, 61.7% of individuals emerged as adults. The extract (1.0% promoted intense disorganization of larval midgut epithelium, including deformation and hypertrophy of cells, disruption of microvilli, and vacuolization of cytoplasms, affecting digestive, enteroendocrine, regenerative, and proliferating cells. In addition, cells with fragmented DNA were observed. Separation of extract components by solid phase extraction revealed that cinnamic acid derivatives and flavonoids are involved in larvicidal effect of the extract, being the first most efficient in a short time after larvae treatment. The lectin present in the extract was isolated, but did not show deleterious effects on larvae. The extract and cinnamic acid derivatives were toxic to A. salina nauplii, while the flavonoids showed low toxicity. S. terebinthifolius leaf extract caused damage to the midgut of A. aegypti larvae, interfering with survival and development. The larvicidal effect of the extract can be attributed to cinnamic acid derivatives and flavonoids. The data obtained using A. salina indicates

  8. Increased Lymph Node Yield Is Associated with Improved Survival in Rectal Cancer Irrespective of Neoadjuvant Treatment

    DEFF Research Database (Denmark)

    Lykke, Jakob; Jess, Per; Roikjaer, Ole

    2015-01-01

    BACKGROUND: It has been proposed that the lymph node yield achieved during rectal cancer resection is associated with survival. It is debated whether a high lymph node yield improves survival, per se, or whether it does so by diminishing the International Union Against Cancer stage drifting effect....... OBJECTIVE: The purpose of this study was to evaluate the prognostic implications of the lymph node yield in curative resected rectal cancer. DESIGN: This study was based on data from a prospectively maintained colorectal cancer database. SETTINGS: This was a national cohort study. PATIENTS: All 6793...... are associations rather than causal relationships. CONCLUSIONS: Increased lymph node yield was associated with better overall survival in rectal cancer, irrespective of neoadjuvant treatment. Stage migration was observed....

  9. Extracorporeal Life Support Increases Survival After Prolonged Ventricular Fibrillation Cardiac Arrest in the Rat.

    Science.gov (United States)

    Magnet, Ingrid Anna Maria; Ettl, Florian; Schober, Andreas; Warenits, Alexandra-Maria; Grassmann, Daniel; Wagner, Michael; Schriefl, Christoph; Clodi, Christian; Teubenbacher, Ursula; Högler, Sandra; Weihs, Wolfgang; Sterz, Fritz; Janata, Andreas

    2017-12-01

    Extracorporeal life support (ECLS) for cardiopulmonary resuscitation (CPR) may increase end organ perfusion and thus survival when conventional CPR fails. The aim was to investigate, if after ventricular fibrillation cardiac arrest in rodents ECLS improves outcome compared with conventional CPR. In 24 adult male Sprague-Dawley rats (460-510 g) resuscitation was started after 10 min of no-flow with ECLS (consisting of an open reservoir, roller pump, and membrane oxygenator, connected to cannulas in the jugular vein and femoral artery, n = 8) or CPR (mechanical chest compressions plus ventilations, n = 8) and compared with a sham group (n = 8). After return of spontaneous circulation (ROSC), all rats were maintained at 33°C for 12 h. Survival to 14 days, neurologic deficit scores and overall performance categories were assessed. ECLS leads to sustained ROSC in 8 of 8 (100%) and neurological intact survival to 14 days in 7 of 8 rats (88%), compared with 5 of 8 (63%) and 1 of 8 CPR rats. The median survival time was 14 days (IQR: 14-14) in the ECLS and 1 day (IQR: 0 to 5) for the CPR group (P = 0.004). In a rat model of prolonged ventricular fibrillation cardiac arrest, ECLS with mild hypothermia produces 100% resuscitability and 88% long-term survival, significantly better than conventional CPR.

  10. Combined cisplatin and aurora inhibitor treatment increase neuroblastoma cell death but surviving cells overproduce BDNF

    Directory of Open Access Journals (Sweden)

    Alessio Polacchini

    2016-07-01

    Full Text Available Drug-resistance to chemotherapics in aggressive neuroblastoma (NB is characterized by enhanced cell survival mediated by TrkB and its ligand, brain-derived neurotrophic factor (BDNF; thus reduction in BDNF levels represent a promising strategy to overcome drug-resistance, but how chemotherapics regulate BDNF is unknown. Here, cisplatin treatment in SK-N-BE neuroblastoma upregulated multiple BDNF transcripts, except exons 5 and 8 variants. Cisplatin increased BDNF mRNA and protein, and enhanced translation of a firefly reporter gene flanked by BDNF 5′UTR exons 1, 2c, 4 or 6 and 3′UTR-long. To block BDNF translation we focused on aurora kinases inhibitors which are proposed as new chemotherapeutics. NB cell survival after 24 h treatment was 43% with cisplatin, and 22% by cisplatin+aurora kinase inhibitor PHA-680632, while the aurora kinases inhibitor alone was less effective; however the combined treatment induced a paradoxical increase of BDNF in surviving cells with strong translational activation of exon6-3′UTR-long transcript, while translation of BDNF transcripts 1, 2C and 4 was suppressed. In conclusion, combined cisplatin and aurora kinase inhibitor treatment increases cell death, but induces BDNF overproduction in surviving cells through an aurora kinase-independent mechanism.

  11. What Causes Runoff and Sediment Yields to Increase After Wildfires?

    Science.gov (United States)

    Larsen, I. J.; MacDonald, L. H.; Brown, E.; Rough, D.; Welsh, M. J.; Pietraszek, J. H.; Libohova, Z.; Schaffrath, K.

    2007-12-01

    Runoff and sediment yields can increase by several orders or magnitude after high severity wildfires. These increases have been attributed to soil water repellency, loss of surface cover, and soil sealing by either mineral or ash particles, but the relative effects of these factors have rarely been isolated. The objectives of this study were hillslopes burned in high-severity wildfires, 13-34 unburned hillslopes, and 3 hillslopes where the surface cover was removed by raking; and 2) use rainfall simulations to determine whether surface sealing is more prevalent on bare soils or soils covered with varying amounts of ash. The field measurements were made over a five-year period in ponderosa pine forests in the Colorado Front Range. The burned hillslopes generally had stronger soil water repellency than the unburned hillslopes only for the first summer after burning, but the mean cumulative sediment yield from the burned hillslopes was 31 Mg ha-1 as compared to minimal sediment yields from the unburned hillslopes. The raked hillslopes had very similar sediment yields to the burned hillslopes when they had comparable surface cover, rainfall erosivity, and soil water repellency. The rainfall simulations on bare soil generated much more runoff and sediment than the simulations on ash-covered soil, and both bare soils developed a thin, structural soil seal. Runoff and sediment yields decreased as ash thickness increased, but successive simulations quickly eroded the ash cover and increased runoff rates to the levels observed for bare soil. The results indicate that: 1) post-fire sediment yields are primarily due to the loss of percent cover rather than fire-enhanced soil water repellency; 2) surface cover is important because it controls the extent of soil sealing; and 3) ash temporarily prevents soil sealing and reduces post-fire runoff and sediment yields. The results have important implications for forest management and mitigating post-fire erosion.

  12. Human and Autologous Adipose-derived Stromal Cells Increase Flap Survival in Rats Independently of Host Immune Response

    DEFF Research Database (Denmark)

    Toyserkani, Navid Mohamadpour; Jensen, Charlotte Harken; Andersen, Ditte Caroline

    2018-01-01

    evaluated after 7 days. RESULTS: The mean survival rates for SVF treatment regardless of human or autologous origin were significantly increased as compared with the control group. Adipose stem/stromal cell and SVF lysate injection did not increase flap survival. Vessel density was increased for human...... injections lead to increased vessel density, but it did not necessarily lead to increased flap survival. Further research should elaborate which molecular events make SVF treatment more efficacious than ASC....

  13. Mycobacterium tuberculosis PPE18 Protein Reduces Inflammation and Increases Survival in Animal Model of Sepsis.

    Science.gov (United States)

    Ahmed, Asma; Dolasia, Komal; Mukhopadhyay, Sangita

    2018-04-18

    Mycobacterium tuberculosis PPE18 is a member of the PPE family. Previous studies have shown that recombinant PPE18 (rPPE18) protein binds to TLR2 and triggers a signaling cascade which reduces levels of TNF-α and IL-12, and increases IL-10 in macrophages. Because TNF-α is a major mediator of the pathophysiology of sepsis and blocking inflammation is a possible line of therapy in such circumstances, we tested the efficacy of rPPE18 in reducing symptoms of sepsis in a mouse model of Escherichia coli- induced septic peritonitis. rPPE18 significantly decreased levels of serum TNF-α, IL-1β, IL-6, and IL-12 and reduced organ damage in mice injected i.p. with high doses of E. coli Peritoneal cells isolated from rPPE18-treated mice had characteristics of M2 macrophages which are protective in excessive inflammation. Additionally, rPPE18 inhibited disseminated intravascular coagulation, which can cause organ damage resulting in death. rPPE18 was able to reduce sepsis-induced mortality when given prophylactically or therapeutically. Additionally, in a mouse model of cecal ligation and puncture-induced sepsis, rPPE18 reduced TNF-α, alanine transaminase, and creatinine, attenuated organ damage, prevented depletion of monocytes and lymphocytes, and improved survival. Our studies show that rPPE18 has potent anti-inflammatory properties and can serve as a novel therapeutic to control sepsis. Copyright © 2018 by The American Association of Immunologists, Inc.

  14. Aromatase expression increases the survival and malignancy of estrogen receptor positive breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Keya De Mukhopadhyay

    Full Text Available In postmenopausal women, local estrogen produced by adipose stromal cells in the breast is believed to support estrogen receptor alpha (ERα positive breast cancer cell survival and growth. This raises the question of how the ERα positive metastatic breast cancer cells survive after they enter blood and lymph circulation, where estrogen level is very low in postmenopausal women. In this study, we show that the aromatase expression increased when ERα positive breast cancer cells were cultured in suspension. Furthermore, treatment with the aromatase substrate, testosterone, inhibited suspension culture-induced apoptosis whereas an aromatase inhibitor attenuated the effect of testosterone suggesting that suspended circulating ERα positive breast cancer cells may up-regulate intracrine estrogen activity for survival. Consistent with this notion, a moderate level of ectopic aromatase expression rendered a non-tumorigenic ERα positive breast cancer cell line not only tumorigenic but also metastatic in female nude mice without exogenous estrogen supplementation. The increased malignant phenotype was confirmed to be due to aromatase expression as the growth of orthotopic tumors regressed with systemic administration of an aromatase inhibitor. Thus, our study provides experimental evidence that aromatase plays an important role in the survival of metastatic ERα breast cancer cells by suppressing anoikis.

  15. Plasmodium Parasitemia Associated With Increased Survival in Ebola Virus-Infected Patients.

    Science.gov (United States)

    Rosenke, Kyle; Adjemian, Jennifer; Munster, Vincent J; Marzi, Andrea; Falzarano, Darryl; Onyango, Clayton O; Ochieng, Melvin; Juma, Bonventure; Fischer, Robert J; Prescott, Joseph B; Safronetz, David; Omballa, Victor; Owuor, Collins; Hoenen, Thomas; Groseth, Allison; Martellaro, Cynthia; van Doremalen, Neeltje; Zemtsova, Galina; Self, Joshua; Bushmaker, Trenton; McNally, Kristin; Rowe, Thomas; Emery, Shannon L; Feldmann, Friederike; Williamson, Brandi N; Best, Sonja M; Nyenswah, Tolbert G; Grolla, Allen; Strong, James E; Kobinger, Gary; Bolay, Fatorma K; Zoon, Kathryn C; Stassijns, Jorgen; Giuliani, Ruggero; de Smet, Martin; Nichol, Stuart T; Fields, Barry; Sprecher, Armand; Massaquoi, Moses; Feldmann, Heinz; de Wit, Emmie

    2016-10-15

    The ongoing Ebola outbreak in West Africa has resulted in 28 646 suspected, probable, and confirmed Ebola virus infections. Nevertheless, malaria remains a large public health burden in the region affected by the outbreak. A joint Centers for Disease Control and Prevention/National Institutes of Health diagnostic laboratory was established in Monrovia, Liberia, in August 2014, to provide laboratory diagnostics for Ebola virus. All blood samples from suspected Ebola virus-infected patients admitted to the Médecins Sans Frontières ELWA3 Ebola treatment unit in Monrovia were tested by quantitative real-time polymerase chain reaction for the presence of Ebola virus and Plasmodium species RNA. Clinical outcome in laboratory-confirmed Ebola virus-infected patients was analyzed as a function of age, sex, Ebola viremia, and Plasmodium species parasitemia. The case fatality rate of 1182 patients with laboratory-confirmed Ebola virus infections was 52%. The probability of surviving decreased with increasing age and decreased with increasing Ebola viral load. Ebola virus-infected patients were 20% more likely to survive when Plasmodium species parasitemia was detected, even after controlling for Ebola viral load and age; those with the highest levels of parasitemia had a survival rate of 83%. This effect was independent of treatment with antimalarials, as this was provided to all patients. Moreover, treatment with antimalarials did not affect survival in the Ebola virus mouse model. Plasmodium species parasitemia is associated with an increase in the probability of surviving Ebola virus infection. More research is needed to understand the molecular mechanism underlying this remarkable phenomenon and translate it into treatment options for Ebola virus infection. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  16. Fluoxetine reverses the memory impairment and reduction in proliferation and survival of hippocampal cells caused by methotrexate chemotherapy.

    Science.gov (United States)

    Lyons, Laura; ElBeltagy, Maha; Umka, Jariya; Markwick, Rachel; Startin, Carla; Bennett, Geoffrey; Wigmore, Peter

    2011-05-01

    Adjuvant cancer chemotherapy can cause long-lasting, cognitive deficits. It is postulated that these impairments are due to these drugs targeting neural precursors within the adult hippocampus, the loss of which has been associated with memory impairment. The present study investigates the effects of the chemotherapy, methotrexate (MTX) on spatial working memory and the proliferation and survival of the neural precursors involved in hippocampal neurogenesis, and the possible neuroprotective properties of the antidepressant fluoxetine. Male Lister hooded rats were administered MTX (75 mg/kg, two i.v. doses a week apart) followed by leucovorin rescue (i.p. 18 h after MTX at 6 mg/kg and at 26, 42 and 50 h at 3 mg/kg) and/or fluoxetine (10 mg/kg/day in drinking water for 40 days). Memory was tested using the novel location recognition (NLR) test. Using markers, cell proliferation (Ki67) and survival (bromodeoxyuridine/BrdU), in the dentate gyrus were quantified. MTX-treated rats showed a cognitive deficit in the NLR task compared with the vehicle and fluoxetine-treated groups. Cognitive ability was restored in the group receiving both MTX and fluoxetine. MTX reduced both the number of proliferating cells in the SGZ and their survival. This was prevented by the co-administration of fluoxetine, which alone increased cell numbers. These results demonstrate that MTX induces an impairment in spatial working memory and has a negative long-term effect on hippocampal neurogenesis, which is counteracted by the co-administration of fluoxetine. If translatable to patients, this finding has the potential to prevent the chemotherapy-induced cognitive deficits experienced by many cancer survivors.

  17. Association of early PSA failure time with increased distant metastasis and decreased survival in prostate brachytherapy patients

    International Nuclear Information System (INIS)

    Ko, Eric C.; Liu, Jerry T.; Stone, Nelson N.; Stock, Richard G.

    2014-01-01

    Background and purpose: We investigated whether earlier PSA failure following prostate brachytherapy is associated with increased rates of distant metastases (DM), prostate cancer-specific mortality (PCSM), and overall mortality. Materials and methods: We retrospectively analyzed 2818 patients who underwent brachytherapy ± external beam radiation therapy (EBRT) ± androgen deprivation therapy (ADT). With median follow-up of 5.52 years, 264 patients experienced PSA failure at a median time of 3.25 years. Patients were stratified to early vs. late PSA failures at cutoffs of 1.5 years, 3 years, or 5 years, and tested in univariate/multivariate analyses for freedom from DM, cause-specific survival (CSS), and overall survival (OS). Results: Among patients with PSA failures, 69 (26%) patients experienced DM, 47 (18%) PCSM, and 56 (21%) deaths from other causes. Patients with rapid PSA failures demonstrated increased rates of DM, PCSM, and overall mortality, despite higher total BED and longer ADT. In multivariate analysis with a PSA failure interval <3 years, the hazard ratio (HR) for DM was 3.92 (95% CI: 2.34–6.55; p = 0.000); HR for PCSM was 2.79 (95% CI: 1.45–5.38; p = 0.002); and HR for overall mortality was 2.28 (95% CI: 1.50–3.48; p = 0.000). Conclusion: Early PSA failure following radiation is a poor prognostic factor, as it is associated with increased DM, PCSM, and overall mortality

  18. Renal transplantation in systemic lupus erythematosus: Comparison of graft survival with other causes of end-stage renal disease.

    Science.gov (United States)

    Horta-Baas, Gabriel; Camargo-Coronel, Adolfo; Miranda-Hernández, Dafhne Guadalupe; Gónzalez-Parra, Leslie Gabriela; Romero-Figueroa, María Del Socorro; Pérez-Cristóbal, Mario

    2017-08-14

    End-stage renal disease (ESRD) due to lupus nephritis (LN) occurs in 10%-30% of patients. Initially systemic lupus erythematosus (SLE) was a contraindication for kidney transplantation (KT). Today, long-term graft survival remains controversial. Our objective was to compare the survival after KT in patients with SLE or other causes of ESRD. All SLE patients who had undergone KT in a retrospective cohort were included. Renal graft survival was compared with that of 50 controls, matched for age, sex, and year of transplantation. Survival was evaluated by the Kaplan-Meier test and the Cox proportional hazards model. Twenty-five subjects with SLE were included. The estimated 1-year, 2- and 5-year survival rates for patients with SLE were 92%, 66% and 66%. Renal graft survival did not differ between patients with SLE and other causes of ESRD (P=.39). The multivariate analysis showed no significant difference in graft survival between the two groups (hazard ratio, HR=1.95, 95% confidence interval [CI] 0.57-6.61, P=.28). The recurrence rate of LN was 8% and was not associated with graft loss. Acute rejection was the only variable associated with graft loss in patients with SLE (HR=16.5, 95% CI 1.94-140.1, P=.01). Renal graft survival in SLE patients did not differ from that reported for other causes of ESRD. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  19. Variation in dicer gene is associated with increased survival in T-cell lymphoma.

    Directory of Open Access Journals (Sweden)

    Xi Li

    Full Text Available Dicer, an endonuclease in RNase III family, is essential for the RNA interference (RNAi pathway. Aberrant expression of Dicer has been shown in various cancers including some subtypes of T cell lymphoma (TCL, which influences patient prognosis. A single-nucleotide polymorphism (SNP rs3742330A>G has been identified in the Dicer gene, located in the 3' untranslated region (3' UTR that is important for mRNA transcript stability. We investigated whether rs3742330 is associated with the survival in 163 TCL patients. Significant association between Dicer rs3742330 and TCL survival were found. Patients carrying the GG genotype (n = 12 had a significantly increased overall survival (OS compared with those carrying the GA and AA genotypes (n = 70 and n = 81, respectively; p = 0.031. Moreover, the significant association was maintained for patients with mature T type (n = 134; p = 0.026. In multivariate Cox-regression analysis, rs3742330 proved to be an independent predictor for OS, together with the commonly used International Prognostic Index (IPI and BAFF rs9514828, another SNP we have previously reported to be associated with TCL survival, with hazard ratios (HRs for patient death rate of 8.956 (95% CI, 1.210 to 66.318; p = 0.032 for the GA genotype and 10.145 (95% CI, 1.371 to 75.084; p = 0.023 for the AA genotype. Furthermore, we observed cumulative effects of Dicer rs3742330 and BAFF rs9514828 on TCL survival. Compared with patients carrying zero unfavorable genotype, those carrying one and two unfavorable genotypes had an increased risk of death with a HR of 7.104 (95% CI, 0.969-53.086; p = 0.054 and 14.932 (95% CI, 1.950-114.354; p = 0.009, respectively, with a significant dose-response trend (p(trend  = 0.004. In conclusion, Dicer rs3742330 is associated with TCL survival, suggesting that genetic variation might play a role in predicting prognosis of TCL patients.

  20. L-carnitine increases survival in a murine model of severe verapamil toxicity.

    Science.gov (United States)

    Perez, Eric; Chu, Jason; Bania, Theodore; Medlej, Kamal

    2011-11-01

    L-carnitine is an essential compound involved in cellular energy production through free fatty acid metabolism. It has been theorized that severe verapamil toxicity "shifts" heart energy production away from free fatty acids and toward other sources, contributing to profound cardiogenic shock. The primary study objective was to determine whether intravenous (IV) L-carnitine affects survival in severe verapamil toxicity. Secondary objectives were to determine the effects on hemodynamic parameters. The authors hypothesized that IV L-carnitine would increase both survival and hemodynamic parameters in severe verapamil toxicity. This was a controlled, blinded animal investigation. Sixteen male rats were anesthetized, ventilated, and instrumented to record mean arterial pressure (MAP) and heart rate. Verapamil toxicity was achieved by a constant infusion of 5 mg/kg/hr. After 5 minutes a bolus of 50 mg/kg of either L-carnitine or normal saline was given. The experiment concluded when either 10% of baseline MAP was achieved or 150 minutes had elapsed. The data were analyzed using Kaplan-Meier analysis, log rank test, and analysis of variance. The median survival for the animals in the L-carnitine group was 140.75 minutes (interquartile range [IQR] = 98.6 to 150 minutes), and for those in the normal saline group it was 49.19 minutes (IQR = 39.02 to 70.97 minutes; p = 0.0001). At 15 minutes the MAP was 20.45 mm Hg greater in the animals in the L-carnitine group than in the animals in the normal saline group (95% confidence interval [CI] = 0.25 to 40.65; p = 0.047). When compared with saline, IV L-carnitine increases survival and MAP in a murine model of severe verapamil toxicity. © 2011 by the Society for Academic Emergency Medicine.

  1. Measles Vaccination Supports Millennium Development Goal 4: Increasing Coverage and Increasing Child Survival in Northern Ghana, 1996-2012.

    Science.gov (United States)

    Welaga, Paul; Hodgson, Abraham; Debpuur, Cornelius; Aaby, Peter; Binka, Fred; Azongo, Daniel; Oduro, Abraham

    2018-01-01

    Measles vaccine (MV) administered as the last vaccine after the third dose of diphtheria-tetanus-pertussis (DTP) may be associated with better child survival unrelated to prevention of measles infection. Other studies have shown that MV administered after DTP was more beneficial and was associated with lower mortality compared with DTP administered after MV or DTP administered simultaneously with MV. We compared the difference in mortality between measles vaccinated after DTP3 and measles-unvaccinated children in Navrongo, Ghana. This was a follow-up study involving annual cohort of children aged 9-23 months from 1996 to 2012. We assessed survival in relation to the measles vaccination status within the first 12 months from interview date and until 5 years of age using Cox proportional hazards models. In all, 38,333 children were included in the study. The proportion of children vaccinated with MV-after-DTP3 increased from 45% in 1996 to 95% in 2012. The adjusted hazard ratio (HR) for measles unvaccinated compared with MV-after-DTP3 vaccinated children was 1.38 (1.15-1.66) in the first 12 months after assessment of vaccination status and 1.22 (1.05-1.41) with follow-up to 5 years of age. The national immunization days campaigns with oral polio vaccine or MV might have reduced the effect of being MV-after-DTP3 vaccinated vs MV-unvaccinated. For 12 months of follow-up, the HR before a campaign for MV-unvaccinated children was 1.63 (1.23-2.17) compared to those who received MV-after-DTP3. After the campaign, the HR reduced to 1.23 (0.97-1.54). Stratifying the analysis by sex, measles-unvaccinated boys had a HR of 1.69 (1.33-2.61) compared to measles-unvaccinated girls who had a HR 1.06 (0.79-1.40) during 1-year follow-up. In 1989, only 7% of children in the area had received MV-after-DTP3; the increase in MV-after-DTP3 coverage from 1989 to 2012 may have lowered mortality rate among children aged 9 months to 3 years by 24%. Though an observational

  2. Kearns-Sayre's syndrome developing in a boy who survived Pearson's syndrome caused by mitochondrial DNA deletion

    NARCIS (Netherlands)

    H.J. Simonsz (Huib); K.E. Bärlocher; A. Rötig

    1992-01-01

    textabstractDocumenta Ophthalmologica 1992, Volume 82, Issue 1-2, pp 73-79 Kearns-Sayre's syndrome developing in a boy who survived Pearson's syndrome caused by mitochondrial DNA deletion Dr H. J. Simonsz, K. Bärlocher, A. Rötig … show all 3 hide » Download PDF (2,322 KB) Abstract A 7-year-old

  3. Protein kinase G1 α overexpression increases stem cell survival and cardiac function after myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Linlin Wang

    Full Text Available We hypothesized that overexpression of cGMP-dependent protein kinase type 1α (PKG1α could mimic the effect of tadalafil on the survival of bone marrow derived mesenchymal stem cells (MSCs contributing to regeneration of the ischemic heart.MSCs from male rats were transduced with adenoviral vector encoding for PKG1α ((PKG1αMSCs.Controls included native MSCs ((NatMSCs and MSCs transduced with an empty vector ((NullMSCs. PKG1α activity was increased approximately 20, 5 and 16 fold respectively in (PKG1αMSCs. (PKG1αMSCs showed improved survival under oxygen and glucose deprivation (OGD which was evidenced by lower LDH release, caspase-3/7 activity and number of positive TUNEL cells. Anti-apoptotic proteins pAkt, pGSK3β, and Bcl-2 were significantly increased in (PKG1αMSCs compared to (NatMSCs and (NullMSCs. Higher release of multiple prosurvival and angiogenic factors such as HGF, bFGF, SDF-1 and Ang-1 was observed in (PKG1αMSCs before and after OGD. In a female rat model of acute myocardial infarction, (PKG1αMSCs group showed higher survival compared with (NullMSCs group at 3 and 7 days after transplantation as determined by TUNEL staining and sry-gene quantitation by real-time PCR. Increased anti-apoptotic proteins and paracrine factors in vitro were also identified. Immunostaining for cardiac troponin I combined with GFP showed increased myogenic differentiation of (PKG1αMSCs. At 4 weeks after transplantation, compared to DMEM group and (NullMSCs group, (PKG1αMSCs group showed increased blood vessel density in infarct and peri-infarct areas (62.5±7.7; 68.8±7.3 per microscopic view, p<0.05 and attenuated infarct size (27.2±2.5%, p<0.01. Heart function indices including ejection fraction (52.1±2.2%, p<0.01 and fractional shortening (24.8%±1.3%, p<0.01 were improved significantly in (PKG1αMSCs group.Overexpression of PKG1α transgene could be a powerful approach to improve MSCs survival and their angiomyogenic potential in the

  4. Inhibition of apoptosis signal-regulating kinase 1 enhances endochondral bone formation by increasing chondrocyte survival

    Science.gov (United States)

    Eaton, G J; Zhang, Q-S; Diallo, C; Matsuzawa, A; Ichijo, H; Steinbeck, M J; Freeman, T A

    2014-01-01

    Endochondral ossification is the result of chondrocyte differentiation, hypertrophy, death and replacement by bone. The careful timing and progression of this process is important for normal skeletal bone growth and development, as well as fracture repair. Apoptosis Signal-Regulating Kinase 1 (ASK1) is a mitogen-activated protein kinase (MAPK), which is activated by reactive oxygen species and other cellular stress events. Activation of ASK1 initiates a signaling cascade known to regulate diverse cellular events including cytokine and growth factor signaling, cell cycle regulation, cellular differentiation, hypertrophy, survival and apoptosis. ASK1 is highly expressed in hypertrophic chondrocytes, but the role of ASK1 in skeletal tissues has not been investigated. Herein, we report that ASK1 knockout (KO) mice display alterations in normal growth plate morphology, which include a shorter proliferative zone and a lengthened hypertrophic zone. These changes in growth plate dynamics result in accelerated long bone mineralization and an increased formation of trabecular bone, which can be attributed to an increased resistance of terminally differentiated chondrocytes to undergo cell death. Interestingly, under normal cell culture conditions, mouse embryonic fibroblasts (MEFs) derived from ASK1 KO mice show no differences in either MAPK signaling or osteogenic or chondrogenic differentiation when compared with wild-type (WT) MEFs. However, when cultured with stress activators, H2O2 or staurosporine, the KO cells show enhanced survival, an associated decrease in the activation of proteins involved in death signaling pathways and a reduction in markers of terminal differentiation. Furthermore, in both WT mice treated with the ASK1 inhibitor, NQDI-1, and ASK1 KO mice endochondral bone formation was increased in an ectopic ossification model. These findings highlight a previously unrealized role for ASK1 in regulating endochondral bone formation. Inhibition of ASK1 has

  5. Recombinant human erythropoietin increases survival and reduces neuronal apoptosis in a murine model of cerebral malaria

    DEFF Research Database (Denmark)

    Wiese, Lothar; Hempel, Casper; Penkowa, Milena

    2008-01-01

    BACKGROUND: Cerebral malaria (CM) is an acute encephalopathy with increased pro-inflammatory cytokines, sequestration of parasitized erythrocytes and localized ischaemia. In children CM induces cognitive impairment in about 10% of the survivors. Erythropoietin (Epo) has - besides of its well known...... with recombinant human Epo (rhEpo; 50-5000 U/kg/OD, i.p.) at different time points. The effect on survival was measured. Brain pathology was investigated by TUNEL (Terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-digoxigenin nick end labelling), as a marker of apoptosis. Gene...

  6. Diabetic foot reconstruction using free flaps increases 5-year-survival rate.

    Science.gov (United States)

    Oh, Tae Suk; Lee, Ho Seung; Hong, Joon Pio

    2013-02-01

    The purpose of this study was to evaluate the outcome of the diabetic foot reconstructed with free flaps and analyse the preoperative risk factors. This study reviews 121 cases of reconstructed diabetic foot in 113 patients over 9 years (average follow-up of 53.2 months). Patients' age ranged from 26 to 78 years (average, 54.6 years). Free flaps used were anterolateral thigh (ALT, 90), superficial circumflex iliac artery perforator (SCIP, 20), anteromedial thigh (AMT, 5), upper medial thigh (UMT, 3), and other perforator free flaps (3). Correlation between the surgical outcome and preoperative risk factors were analysed using logistic regression model. Total loss was seen in 10 cases and 111 free-tissue transfers were successful (flap survival rate of 91.7%). During follow-up, limb was eventually lost in 17 patients and overall limb salvage rate was 84.9% and the 5-year survival was 86.8%. Correlation between flap loss and 14 preoperative risk factors (computed tomography (CT) angiogram showing intact numbers of major vessels, history of previous angioplasty, peripheral arterial disease (PAD), heart problem, chronic renal failure (CRF), American Society of Anaesthesiologists (ASA) physical status classification system, smoking, body mass index (BMI), HBA1c, lymphocyte count, ankle-brachial index (ABI), osteomyelitis, C-reactive protein (CRP) level and whether taking immunosuppressive agents) were analysed. Significant odds ratio were seen in patients who underwent lower extremity angioplasties (odds ratio: 17.590, pDiabetic foot reconstruction using free flaps has a high chance for success and significantly increases the 5-year survival rate. Risk factors such as PAD, history of angioplasties in the extremity and using immunosuppressive agents after transplant may increase the chance for flap loss. Copyright © 2012 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  7. Increased survival and proliferation of the epidemic strain Mycobacterium abscessus subsp. massiliense CRM0019 in alveolar epithelial cells.

    Science.gov (United States)

    Ribeiro, Giovanni Monteiro; Matsumoto, Cristianne Kayoko; Real, Fernando; Teixeira, Daniela; Duarte, Rafael Silva; Mortara, Renato Arruda; Leão, Sylvia Cardoso; de Souza Carvalho-Wodarz, Cristiane

    2017-09-13

    Outbreaks of infections caused by rapidly growing mycobacteria have been reported worldwide generally associated with medical procedures. Mycobacterium abscessus subsp. massiliense CRM0019 was obtained during an epidemic of postsurgical infections and was characterized by increased persistence in vivo. To better understand the successful survival strategies of this microorganism, we evaluated its infectivity and proliferation in macrophages (RAW and BMDM) and alveolar epithelial cells (A549). For that, we assessed the following parameters, for both M. abscessus CRM0019 as well as the reference strain M. abscessus ATCC 19977: internalization, intracellular survival for up 3 days, competence to subvert lysosome fusion and the intracellular survival after cell reinfection. CRM0019 and ATCC 19977 strains showed the same internalization rate (approximately 30% after 6 h infection), in both A549 and RAW cells. However, colony forming units data showed that CRM0019 survived better in A549 cells than the ATCC 19977 strain. Phagosomal characteristics of CRM0019 showed the bacteria inside tight phagosomes in A549 cells, contrasting to the loosely phagosomal membrane in macrophages. This observation holds for the ATCC 19977 strain in both cell types. The competence to subvert lysosome fusion was assessed by acidification and acquisition of lysosomal protein. For M. abscessus strains the phagosomes were acidified in all cell lines; nevertheless, the acquisition of lysosomal protein was reduced by CRM0019 compared to the ATCC 19977 strain, in A549 cells. Conversely, in macrophages, both M. abscessus strains were located in mature phagosomes, however without bacterial death. Once recovered from macrophages M. abscessus could establish a new intracellular infection. Nevertheless, only CRM0019 showed a higher growth rate in A549, increasing nearly 10-fold after 48 and 72 h. M. abscessus CRM0019 creates a protective and replicative niche in alveolar epithelial cells mainly by

  8. Measles Vaccination Supports Millennium Development Goal 4: Increasing Coverage and Increasing Child Survival in Northern Ghana, 1996–2012

    Directory of Open Access Journals (Sweden)

    Paul Welaga

    2018-02-01

    Full Text Available BackgroundMeasles vaccine (MV administered as the last vaccine after the third dose of diphtheria-tetanus-pertussis (DTP may be associated with better child survival unrelated to prevention of measles infection. Other studies have shown that MV administered after DTP was more beneficial and was associated with lower mortality compared with DTP administered after MV or DTP administered simultaneously with MV. We compared the difference in mortality between measles vaccinated after DTP3 and measles-unvaccinated children in Navrongo, Ghana.MethodsThis was a follow-up study involving annual cohort of children aged 9–23 months from 1996 to 2012. We assessed survival in relation to the measles vaccination status within the first 12 months from interview date and until 5 years of age using Cox proportional hazards models.ResultsIn all, 38,333 children were included in the study. The proportion of children vaccinated with MV-after-DTP3 increased from 45% in 1996 to 95% in 2012. The adjusted hazard ratio (HR for measles unvaccinated compared with MV-after-DTP3 vaccinated children was 1.38 (1.15–1.66 in the first 12 months after assessment of vaccination status and 1.22 (1.05–1.41 with follow-up to 5 years of age. The national immunization days campaigns with oral polio vaccine or MV might have reduced the effect of being MV-after-DTP3 vaccinated vs MV-unvaccinated. For 12 months of follow-up, the HR before a campaign for MV-unvaccinated children was 1.63 (1.23–2.17 compared to those who received MV-after-DTP3. After the campaign, the HR reduced to 1.23 (0.97–1.54. Stratifying the analysis by sex, measles-unvaccinated boys had a HR of 1.69 (1.33–2.61 compared to measles-unvaccinated girls who had a HR 1.06 (0.79–1.40 during 1-year follow-up. In 1989, only 7% of children in the area had received MV-after-DTP3; the increase in MV-after-DTP3 coverage from 1989 to 2012 may have lowered mortality rate among children aged 9 months to

  9. Conditionally replicating adenovirus expressing TIMP2 increases survival in a mouse model of disseminated ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Sherry W Yang

    Full Text Available Ovarian cancer remains difficult to treat mainly due to presentation of the disease at an advanced stage. Conditionally-replicating adenoviruses (CRAds are promising anti-cancer agents that selectively kill the tumor cells. The present study evaluated the efficacy of a novel CRAd (Ad5/3-CXCR4-TIMP2 containing the CXCR4 promoter for selective viral replication in cancer cells together with TIMP2 as a therapeutic transgene, targeting the matrix metalloproteases (MMPs in a murine orthotopic model of disseminated ovarian cancer. An orthotopic model of ovarian cancer was established in athymic nude mice by intraperitonal injection of the human ovarian cancer cell line, SKOV3-Luc, expressing luciferase. Upon confirmation of peritoneal dissemination of the cells by non-invasive imaging, mice were randomly divided into four treatment groups: PBS, Ad-ΔE1-TIMP2, Ad5/3-CXCR4, and Ad5/3-CXCR4-TIMP2. All mice were imaged weekly to monitor tumor growth and were sacrificed upon reaching any of the predefined endpoints, including high tumor burden and significant weight loss along with clinical evidence of pain and distress. Survival analysis was performed using the Log-rank test. The median survival for the PBS cohort was 33 days; for Ad-ΔE1-TIMP2, 39 days; for Ad5/3-CXCR4, 52.5 days; and for Ad5/3-CXCR4-TIMP2, 63 days. The TIMP2-armed CRAd delayed tumor growth and significantly increased survival when compared to the unarmed CRAd. This therapeutic effect was confirmed to be mediated through inhibition of MMP9. Results of the in vivo study support the translational potential of Ad5/3-CXCR4-TIMP2 for treatment of human patients with advanced ovarian cancer.

  10. Evaluation of medical treatments to increase survival of ebullism in guinea pigs

    Science.gov (United States)

    Stegmann, Barbara J.; Pilmanis, Andrew A.; Wolf, E. G.; Derion, Toniann; Fanton, J. W.; Davis, H.; Kemper, G. B.; Scoggins, Terrell E.

    1993-01-01

    Spaceflight carriers run a constant risk of exposure to vacuum. Above 63,000 ft (47 mmHg), the ambient pressure falls below the vapor pressure of water at 37 C, and tissue vaporization (ebullism) begins. Little is know about appropriate resuscitative protocols after such an ebullism exposure. This study identified injury patterns and mortality rates associated with ebullism while verifying effectiveness of traditional pulmonary resuscitative techniques. Male Hartley guinea pigs were exposed to 87,000 ft for periods of 40 to 115 sec. After descent, those animals that did not breathe spontaneously were given artificial ventilation by bag and mask for up to 15 minutes. Those animals surviving were randomly assigned to one of three treatment groups--hyperbaric oxygen (HBO), ground-level oxygen (GLO2), and ground-level air (GLAIR). The HBO group was treated on a standard treatment table 6A while the GLO2 animals received O2 for an equivalent length of time. Those animals in the GLAIR group were observed only. All surviving animals were humanely sacrified at 48 hours. Inflation of the animal's lungs after the exposure was found to be difficult and, at times, impossible. This may be due to surfactant disruption at the alveolar lining. Electron microscopy identified a disruption of the surfactant layer in animals that did not survive initial exposure. Mortality was found to increase with exposure time: 40 sec--0 percent; 60 sec--6 percent; 70 sec--40 percent; 80 sec--13 percent; 100 sec--38 percent; 110 sec--40 percent; and 115 sec--100 percent. There was no difference in the delayed mortality among the treatment groups (HBO--15 percent, GLO2--11 percent, GLAIR--11 percent). However, since resuscitation was ineffective, the effectiveness of any post-exposure treatment was severely limited. Preliminary results indicate that reuscitation of guinea pigs following ebullism exposure is difficult, and that current techniques (such as traditional CPR) may not be appropriate.

  11. Adaptive Memory: Survival Processing Increases Both True and False Memory in Adults and Children

    Science.gov (United States)

    Otgaar, Henry; Smeets, Tom

    2010-01-01

    Research has shown that processing information in a survival context can enhance the information's memorability. The current study examined whether survival processing can also decrease the susceptibility to false memories and whether the survival advantage can be found in children. In Experiment 1, adults rated semantically related words in a…

  12. Increased beta1 integrin is associated with decreased survival in invasive breast cancer.

    Science.gov (United States)

    Yao, Evelyn S; Zhang, Hui; Chen, Yunn-Yi; Lee, Brian; Chew, Karen; Moore, Dan; Park, Catherine

    2007-01-15

    Aberrant microenvironments and loss of balance in cell-extracellular matrix signaling are associated with breast cancer invasion, metastasis, and resistance to therapy. We have recently shown that increased beta1 integrin signaling is involved in malignant progression and that inhibitory antibody to beta1 integrin leads to selective apoptosis and decreased proliferation in three-dimensional cultures and in xenograft models of breast cancer in vivo. To investigate the clinical importance of these findings, in the present study we examined the expression of beta1 integrin and extracellular beta1 integrin ligands fibronectin and laminin-1 in a cohort of 249 breast cancer patients who had a median follow-up of 8.4 years. Among the 149 scorable cases, the highest beta1 integrin intensity score (3+ versus 0-2+) was associated with significantly decreased 10-year overall survival of 48% versus 71% (Pintegrin intensity score was significantly correlated with fibronectin expression (Kendall's tau-b=0.19; P=0.03). In a multivariate Cox proportional hazards model, beta1 integrin intensity score remained a significant independent predictor of overall survival [hazard ratio (HR), 1.69; 95% confidence interval (95% CI), 1.19-2.38; Pintegrin expression has potential prognostic value in invasive breast cancer and that coexpression of fibronectin may help identify patients with more aggressive tumors who may benefit from targeted therapy.

  13. Cancer cells increase endothelial cell tube formation and survival by activating the PI3K/Akt signalling pathway.

    Science.gov (United States)

    Cheng, Hao-Wei; Chen, Yi-Fang; Wong, Jau-Min; Weng, Chia-Wei; Chen, Hsuan-Yu; Yu, Sung-Liang; Chen, Huei-Wen; Yuan, Ang; Chen, Jeremy J W

    2017-02-07

    Angiogenesis is a hallmark of cancer and plays a critical role in lung cancer progression, which involves interactions between cancer cells, endothelial cells and the surrounding microenvironment. However, the gene expression profiles and the changes in the biological phenotype of vascular endothelial cells after interactions with lung cancer cells remain unclear. An indirect transwell co-culture system was used to survey the interaction between human umbilical vein endothelial cells (HUVECs) and human lung adenocarcinoma CL1-5 cells, as well as to investigate the morphological and molecular changes of HUVECs. The differentially expressed genes (DEGs) in HUVECs after co-culture with cancer cells were identified by microarray. Moreover, a publicly available microarray dataset of 293 non-small-cell lung cancer (NSCLC) patients was employed to evaluate the prognostic power of the gene signatures derived from HUVECs. The interaction between HUVECs and lung cancer cells changes the morphology of HUVECs, causing them to have a mesenchymal-like morphology and alter their cytoskeleton organization. Furthermore, after co-culture with lung cancer cells, HUVECs showed increased cell motility and microvessel tube formation ability and a decreased apoptotic percentage. Transcriptomic profiling of HUVECs revealed that many survival-, apoptosis- and angiogenesis-related genes were differentially expressed after interactions with lung cancer cells. Further investigations showed that the PI3K/Akt signalling pathway and COX-2 are involved in endothelial tube formation under the stimulation of lung cancer cells. Moreover, Rac-1 activation might promote endothelial cell motility through the increased formation of lamellipodia and filopodia. The inhibitors of PI3K and COX-2 could reverse the increased tube formation and induce the apoptosis of HUVECs. In addition, the gene signatures derived from the DEGs in HUVECs could predict overall survival and disease-free survival in NSCLC

  14. Implications caused by SARex on the implementation of the IMO polar code on survival at sea

    Science.gov (United States)

    Solberg, K. E.

    2017-12-01

    The International Code for Ships Operating in Polar waters goes into effect on 01 January 2018 for all ships. This puts additional strain on vessel owners and operators as they will have to comply with an additional set of requirements. This includes the functional requirement of a minimum of 5 days survival time. The SARex exercise has elaborated on the issue of survival in close cooperation with the different stakeholders associated with the marine industry. Being an objective third party is important when organizing and executing these activities as all of the stakeholders has different agendas and priorities. Developing sustainable solutions is a balancing act, incorporating economic and political aspects as well as technology and requires a mutual common understanding of the mechanism involved.

  15. Splenectomy increases the survival time of heart allograft via developing immune tolerance

    Science.gov (United States)

    2013-01-01

    Background The spleen is an active lymphoid organ. The effect of splenectomy on the immune response remains unclear. This study investigated whether splenectomy can induce immune tolerance and has a beneficial role in cardiac allograft. Methods Wistar rats were used for heart donors. The Sprague–Dawley (SD) rats designated as the recipients of heart transplantation (HT) were randomly assigned into four groups: sham, splenectomy, HT, splenectomy + HT. The survival of transplanted hearts was assessed by daily checking of abdominal palpation. At various time points after transplantation, the transplanted hearts were collected and histologically examined; the level of CD4+CD25+ T regulatory lymphocytes (Tregs) and rate of lymphocyte apoptosis (annexin-v+ PI+ cells) in the blood were analyzed by using flow cytometric method. Results 1) Splenectomy significantly prolonged the mean survival time of heart allografts (7 ± 1.1 days and 27 ± 1.5 days for HT and splenectomy + HT, respectively; n = 12-14/group, HT vs. splenectomy + HT, p Splenectomy delayed pathological changes (inflammatory cell infiltration, myocardial damage) of the transplanted hearts in splenectomy + HT rats; 3) The level of CD4+CD25+ Tregs in the blood of splenectomized rats was significantly increased within 7 days (2.4 ± 0.5%, 4.9 ± 1.3% and 5.3 ± 1.0% for sham, splenectomy and splenectomy + HT, respectively; n = 15/group, sham vs. splenectomy or splenectomy + HT, p splenectomy surgery and gradually decreased to baseline level; 4) Splenectomy increased the rate of lymphocyte apoptosis (day 7: 0.3 ± 0.05%, 3.9 ± 0.9% and 4.1 ± 0.9% for sham, splenectomy and splenectomy + HT, respectively; n = 15/group, sham vs. splenectomy or splenectomy + HT, p Splenectomy inhibits the development of pathology and prolongs the survival time of cardiac allograft. The responsible mechanism is associated with induction of immune

  16. Mesenterico-portal vein resection in patients with pancreatico-duodenal cancer is safe and may increase survival.

    Science.gov (United States)

    Storkholm, Jan Henrik; Hansen, Carsten Palnæs

    2014-01-01

    Pancreatic cancer is one of the most serious gastrointestinal cancers, and in the US and Europe it is a leading cause of cancer-related mortality. Radical surgery is the only option available for long-term survival. The aim of this study was to describe the surgical technique and the results of portal vein/superior mesenteric vein resection in patients with pancreatic cancer. Between 1 April 2009 and 1 April 2013, 354 patients underwent resection for pancreatic malignancy. A total of 47 portal vein/superior mesenteric vein resections were performed in 22 men and 25 women. A total of 44 patients (93.7%) had ductal adenocarcinomas. In all, 39 patients (83%) had T3 tumours, and 38 patients (80.9%) had involvement of lymph nodes. Furthermore, 29 patients (62%) had a pancreaticoduodenectomy, 15 patients (32%) a total pancreatectomy and three patients (6%) had a distal pancreatectomy. Six patients (17%) were reconstructed with interposition grafts, and vessels (83%) were reconstructed with an end-to-end anastomosis in the remaining 39 patients. Surgical morbidity was 29.8%, and 19.1% had non-surgical complications. The perioperative mortality (30 days) was 0%. The median survival was 25.2 months (confidence interval: 19-31.4). Resection of the portal vein/superior mesenteric vein is a safe procedure. It is not associated with an increased perioperative morbidity and mortality. This latter finding is in accordance with the findings in other high-volume centres. The median survival was far better than expected, especially since our material included a considerable number of patients with lymph node metastases. not relevant. not relevant.

  17. Use of Preservative Agents and Antibiotics for Increased Poliovirus Survival on Positively Charged Filters.

    Science.gov (United States)

    Fagnant, Christine Susan; Kossik, Alexandra Lynn; Zhou, Nicolette Angela; Sánchez-Gonzalez, Liliana; Falman, Jill Christin; Keim, Erika Karen; Linden, Yarrow; Scheibe, Alana; Barnes, Kilala Sayisha; Beck, Nicola Koren; Boyle, David S; Meschke, John Scott

    2017-12-01

    Environmental surveillance of poliovirus (PV) and other non-enveloped viruses can help identify silent circulation and is necessary to certify eradication. The bag-mediated filtration system is an efficient method to filter large volumes of environmental waters at field sites for monitoring the presence of viruses. As filters may require long transit times to off-site laboratories for processing, viral inactivation or overgrowth of bacteria and fungi can interfere with virus detection and quantification (Miki and Jacquet in Aquatic Microb Ecol 51(2):195-208, 2008). To evaluate virus survival over time on ViroCap ™ filters, the filters were seeded with PV type 1 (PV1) and/or MS2 and then dosed with preservatives or antibiotics prior to storage and elution. These filters were stored at various temperatures and time periods, and then eluted for PV1 and MS2 recovery quantification. Filters dosed with the preservative combination of 2% sodium benzoate and 0.2% calcium propionate had increased virus survival over time when stored at 25 °C, compared to samples stored at 25 °C with no preservatives. While elution within 24 h of filtration is recommended, if storage or shipping is required then this preservative mixture can help preserve sample integrity. Addition of an antibiotic cocktail containing cephapirin, gentamicin, and Proclin ™ 300 increased recovery after storage at 4 and 25 °C, when compared to storage with no antibiotics. The antibiotic cocktail can aid sample preservation if access to appropriate antibiotics storage is available and sample cold chain is unreliable. This study demonstrated that the use of preservatives or antibiotics is a simple, cost-effective method to improve virus detection from ViroCap cartridge filters over time.

  18. Itraconazole treatment reduces Batrachochytrium dendrobatidis prevalence and increases overwinter field survival in juvenile Cascades frogs.

    Science.gov (United States)

    Hardy, Bennett M; Pope, Karen L; Piovia-Scott, Jonah; Brown, Richard N; Foley, Janet E

    2015-01-15

    The global spread of the fungal pathogen Batrachochytrium dendrobatidis (Bd) has led to widespread extirpation of amphibian populations. During an intervention aimed at stabilizing at-risk populations, we treated wild-caught Cascades frogs Rana cascadae with the antifungal drug itraconazole. In fall 2012, we collected 60 recently metamorphosed R. cascadae from 1 of the 11 remnant populations in the Cascades Mountains (CA, USA). Of these, 30 randomly selected frogs were treated with itraconazole and the other 30 frogs served as experimental controls; all were released at the capture site. Bd prevalence was low at the time of treatment and did not differ between treated frogs and controls immediately following treatment. Following release, Bd prevalence gradually increased in controls but not in treated frogs, with noticeable (but still non-significant) differences 3 wk after treatment (27% [4/15] vs. 0% [0/13]) and strong differences 5 wk after treatment (67% [8/12] vs. 13% [1/8]). We did not detect any differences in Bd prevalence and load between experimental controls and untreated wild frogs during this time period. In spring 2013, we recaptured 7 treated frogs but none of the experimental control frogs, suggesting that over-winter survival was higher for treated frogs. The itraconazole treatment did appear to reduce growth rates: treated frogs weighed 22% less than control frogs 3 wk after treatment (0.7 vs. 0.9 g) and were 9% shorter than control frogs 5 wk after treatment (18.4 vs. 20.2 mm). However, for critically small populations, increased survival of the most at-risk life stage could prevent or delay extinction. Our results show that itraconazole treatment can be effective against Bd infection in wild amphibians, and therefore the beneficial effects on survivorship may outweigh the detrimental effects on growth.

  19. Intermittent hypoxia selects for genotypes and phenotypes that increase survival, invasion, and therapy resistance.

    Directory of Open Access Journals (Sweden)

    Daniel Verduzco

    Full Text Available Hypoxia in tumors correlates with greater risk of metastases, increased invasiveness, and resistance to systemic and radiation therapy. The evolutionary dynamics that links specific adaptations to hypoxia with these observed tumor properties have not been well investigated. While some tumor populations may experience fixed hypoxia, cyclical and stochastic transitions from normoxia to hypoxia are commonly observed in vivo. Although some phenotypic adaptations to this cyclic hypoxia are likely reversible, we hypothesize that some adaptations may become fixed through mutations promoted by hypoxia-induced genomic instability. Here we seek to identify genetic alterations and corresponding stable phenotypes that emerge following cyclic hypoxia. Although these changes may originate as adaptations to this specific environmental stress, their fixation in the tumor genome may result in their observation in tumors from regions of normoxia, a condition known as pseudohypoxia. We exposed several epithelial cell lines to 50 cycles of hypoxia-normoxia, followed by culture in normoxia over a period of several months. Molecular analyses demonstrated permanent changes in expression of several oncogenes and tumor-suppressors, including p53, E-cadherin, and Hif-1α. These changes were associated with increased resistance to multiple cytotoxins, increased survival in hypoxia and increased anchorage-independent growth. These results suggest cycles of hypoxia encountered in early cancers can select for specific and stable genotypic and phenotypic properties that persist even in normoxic conditions, which may promote tumor progression and resistance to therapy.

  20. Increased reactive oxygen species levels cause ER stress and cytotoxicity in andrographolide treated colon cancer cells.

    Science.gov (United States)

    Banerjee, Aditi; Banerjee, Vivekjyoti; Czinn, Steven; Blanchard, Thomas

    2017-04-18

    Chemotherapy continues to play an essential role in the management of many cancers including colon cancer, the third leading cause of death due to cancer in the United States. Many naturally occurring plant compounds have been demonstrated to possess anti-cancer cell activity and have the potential to supplement existing chemotherapy strategies. The plant metabolite andrographolide induces cell death in cancer cells and apoptosis is dependent upon the induction of endoplasmic reticulum stress (ER stress) leading to the unfolded protein response (UPR). The goal of the present study was to determine the mechanism by which andrographolide induces ER stress and to further evaluate its role in promoting cell death pathways. The T84 and COLO 205 cancer cell lines were used to demonstrate that andrographolide induces increased ROS levels, corresponding anti-oxidant response molecules, and reduced mitochondrial membrane potential. No increases in ROS levels were detected in control colon fibroblast cells. Andrographolide-induced cell death, UPR signaling, and CHOP, Bax, and caspase 3 apoptosis elements were all inhibited in the presence of the ROS scavenger NAC. Additionally, andrographolide-induced suppression of cyclins B1 and D1 were also reversed in the presence of NAC. Finally, Akt phosphorylation and phospho-mTOR levels that are normally suppressed by andrographolide were also expressed at normal levels in the absence of ROS. These data demonstrate that andrographolide induces ER stress leading to apoptosis through the induction of ROS and that elevated ROS also play an important role in down-regulating cell cycle progression and cell survival pathways as well.

  1. Predicting survival causes after out of hospital cardiac arrest using data mining method.

    Science.gov (United States)

    Le Duff, Franck; Muntean, Cristian; Cuggia, Marc; Mabo, Philippe

    2004-01-01

    The prognosis of life for patients with heart failure remains poor. By using data mining methods, the purpose of this study was to evaluate the most important criteria for predicting patient survival and to profile patients to estimate their survival chances together with the most appropriate technique for health care. Five hundred and thirty three patients who had suffered from cardiac arrest were included in the analysis. We performed classical statistical analysis and data mining analysis using mainly Bayesian networks. The mean age of the 533 patients was 63 (+/- 17) and the sample was composed of 390 (73 %) men and 143 (27 %) women. Cardiac arrest was observed at home for 411 (77 %) patients, in a public place for 62 (12 %) patients and on a public highway for 60 (11 %) patients. The belief network of the variables showed that the probability of remaining alive after heart failure is directly associated to five variables: age, sex, the initial cardiac rhythm, the origin of the heart failure and specialized resuscitation techniques employed. Data mining methods could help clinicians to predict the survival of patients and then adapt their practices accordingly. This work could be carried out for each medical procedure or medical problem and it would become possible to build a decision tree rapidly with the data of a service or a physician. The comparison between classic analysis and data mining analysis showed us the contribution of the data mining method for sorting variables and quickly conclude on the importance or the impact of the data and variables on the criterion of the study. The main limit of the method is knowledge acquisition and the necessity to gather sufficient data to produce a relevant model.

  2. Human survival in volcanic eruptions: Thermal injuries in pyroclastic surges, their causes, prognosis and emergency management.

    Science.gov (United States)

    Baxter, Peter J; Jenkins, Susanna; Seswandhana, Rosadi; Komorowski, Jean-Christophe; Dunn, Ken; Purser, David; Voight, Barry; Shelley, Ian

    2017-08-01

    This study of burns patients from two eruptions of Merapi volcano, Java, in 1994 and 2010, is the first detailed analysis to be reported of thermal injuries in a large series of hospitalised victims of pyroclastic surges, one of the most devastating phenomena in explosive eruptions. Emergency planners in volcanic crises in populated areas have to integrate the health sector into disaster management and be aware of the nature of the surge impacts and the types of burns victims to be expected in a worst scenario, potentially in numbers and in severity that would overwhelm normal treatment facilities. In our series, 106 patients from the two eruptions were treated in the same major hospital in Yogyakarta and a third of these survived. Seventy-eight per cent were admitted with over 40% TBSA (total body surface area) burns and around 80% of patients were suspected of having at least some degree of inhalation injury as well. Thirty five patients suffered over 80% TBSA burns and only one of these survived. Crucially, 45% of patients were in the 40-79% TBSA range, with most suspected of suffering from inhalation injury, for whom survival was most dependent on the hospital treatment they received. After reviewing the evidence from recent major eruptions and outlining the thermal hazards of surges, we relate the type and severity of the injuries of these patients to the temperatures and dynamics of the pyroclastic surges, as derived from the environmental impacts and associated eruption processes evaluated in our field surveys and interviews conducted by our multi-disciplinary team. Effective warnings, adequate evacuation measures, and political will are all essential in volcanic crises in populated areas to prevent future catastrophes on this scale. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

  3. Developmental Ethanol Exposure Causes Reduced Feeding and Reveals a Critical Role for Neuropeptide F in Survival

    Directory of Open Access Journals (Sweden)

    Amanda Guevara

    2018-03-01

    Full Text Available Food intake is necessary for survival, and natural reward circuitry has evolved to help ensure that animals ingest sufficient food to maintain development, growth, and survival. Drugs of abuse, including alcohol, co-opt the natural reward circuitry in the brain, and this is a major factor in the reinforcement of drug behaviors leading to addiction. At the junction of these two aspects of reward are alterations in feeding behavior due to alcohol consumption. In particular, developmental alcohol exposure (DAE results in a collection of physical and neurobehavioral disorders collectively referred to as Fetal Alcohol Spectrum Disorder (FASD. The deleterious effects of DAE include intellectual disabilities and other neurobehavioral changes, including altered feeding behaviors. Here we use Drosophila melanogaster as a genetic model organism to study the effects of DAE on feeding behavior and the expression and function of Neuropeptide F. We show that addition of a defined concentration of ethanol to food leads to reduced feeding at all stages of development. Further, genetic conditions that reduce or eliminate NPF signaling combine with ethanol exposure to further reduce feeding, and the distribution of NPF is altered in the brains of ethanol-supplemented larvae. Most strikingly, we find that the vast majority of flies with a null mutation in the NPF receptor die early in larval development when reared in ethanol, and provide evidence that this lethality is due to voluntary starvation. Collectively, we find a critical role for NPF signaling in protecting against altered feeding behavior induced by developmental ethanol exposure.

  4. Biofilms Formed by Gram-Negative Bacteria Undergo Increased Lipid A Palmitoylation, Enhancing In Vivo Survival

    Science.gov (United States)

    Chalabaev, Sabina; Chauhan, Ashwini; Novikov, Alexey; Iyer, Pavithra; Szczesny, Magdalena; Beloin, Christophe; Caroff, Martine

    2014-01-01

    ABSTRACT Bacterial biofilm communities are associated with profound physiological changes that lead to novel properties compared to the properties of individual (planktonic) bacteria. The study of biofilm-associated phenotypes is an essential step toward control of deleterious effects of pathogenic biofilms. Here we investigated lipopolysaccharide (LPS) structural modifications in Escherichia coli biofilm bacteria, and we showed that all tested commensal and pathogenic E. coli biofilm bacteria display LPS modifications corresponding to an increased level of incorporation of palmitate acyl chain (palmitoylation) into lipid A compared to planktonic bacteria. Genetic analysis showed that lipid A palmitoylation in biofilms is mediated by the PagP enzyme, which is regulated by the histone-like protein repressor H-NS and the SlyA regulator. While lipid A palmitoylation does not influence bacterial adhesion, it weakens inflammatory response and enhances resistance to some antimicrobial peptides. Moreover, we showed that lipid A palmitoylation increases in vivo survival of biofilm bacteria in a clinically relevant model of catheter infection, potentially contributing to biofilm tolerance to host immune defenses. The widespread occurrence of increased lipid A palmitoylation in biofilms formed by all tested bacteria suggests that it constitutes a new biofilm-associated phenotype in Gram-negative bacteria. PMID:25139899

  5. Posterior Uterine Rupture Causing Fetal Expulsion into the Abdominal Cavity: A Rare Case of Neonatal Survival

    Directory of Open Access Journals (Sweden)

    K. Navaratnam

    2011-01-01

    Full Text Available Introduction. Uterine rupture is a potentially catastrophic complication of vaginal birth after caesarean section. We describe the sixth case of posterior uterine rupture, with intact lower segment scar, and the first neonatal survival after expulsion into the abdominal cavity with posterior rupture. Case Presentation. A multiparous woman underwent prostaglandin induction of labour for postmaturity, after one previous caesarean section. Emergency caesarean section for bradycardia revealed a complete posterior uterine rupture, with fetal and placental expulsion. Upon delivery, the baby required inflation breaths only. The patient required a subtotal hysterectomy but returned home on day 5 postnatally with her healthy baby. Discussion. Vaginal birth after caesarean section constitutes a trial of labour, and the obstetrician must be reactive to labour events. Posterior uterine rupture is extremely rare and may occur without conventional signs. Good maternal and fetal outcome is possible with a prompt, coordinated team response.

  6. Outcomes of different bearings in total hip arthroplasty - implant survival, revision causes, and patient-reported outcome.

    Science.gov (United States)

    Varnum, Claus

    2017-03-01

    Total hip arthroplasty (THA) is a common and successful treatment of patients suffering from severe osteoarthritis that significantly reduces pain and improves hip function and quality of life. Traditionally, the outcome of THA has been evaluated by orthopaedic surgeons and assessed in morbidity and mortality rates, and implant survival. As patients and surgeons may assess outcome after THA differently, patient-reported outcomes (PROMs) have gained much more interest and are today recognized as very important tools for evaluating the outcome and satisfaction after THA. One of the prognostic factors for the outcome of THA is the type of bearings. This PhD thesis focuses on the influence of different types of bearings on implant survival, revision causes, PROMs, and noises from THA. The aims of the thesis were: Study I: To examine the revision risk and to investigate the causes of revision of cementless ceramic-on-ceramic (CoC) THAs comparing them to those of "standard" metal-on-polyethylene (MoP) THAs. Study II: To compare the six-year revision risk for metal-on-metal (MoM) with that for MoP bearings in cementless stemmed THA, and further to study the revision risk for different designs of stemmed MoM THAs and the causes of revision. Study III: To examine the association between CoC, MoM, and MoP bearings and both generic and disease-specific PROMs, and furthermore to examine the incidence and types of noises from the three types of bearings and identify the effect of noises on PROM scores. In study I and III, we used data from the Danish Hip Arthroplasty Registry combined with data from the Civil Registration System and the Danish National Patient Registry. In study II, data from the Nordic Arthroplasty Register Association, containing data from hip arthroplasty registries in Denmark, Norway, Sweden, and Finland, was used. In study I, 11,096 patients operated from 2002 through 2009 with cementless THA were included. Of these, 16% had CoC THA and 84% had MoP THA. At

  7. Survival and cause of death after traumatic spinal cord injury. A long-term epidemiological survey from Denmark

    DEFF Research Database (Denmark)

    Hartkopp, A; Brønnum-Hansen, Henrik; Seidenschnur, A M

    1997-01-01

    Life expectancy among individuals with spinal cord injuries (SCI) has remained lower than in the normal population, even with optimal medical management. But significant improvement has been achieved, as will be illustrated in this retrospective study of an unselected group of traumatic survivors...... treatment and were rehabilitated at the centre for Spinal Cord Injured in Hornbaek, Denmark. At the end of the follow-up, 31st December 1992, 236 (197 men and 39 women) had died. The commonest causes of death were lung diseases, particularly pneumonia; suicide; and ischaemic heart disease. Among...... and pneumonia. A significant decrease in the overall mortality was observed from the first (1953-1973) to the second half of the observation period (1972-1992). Similarly the survival curves for both men and women demonstrate that the gap in survival probability between the normal population and the SCI has...

  8. Greater mass increases annual survival of Prothonotary Warblers wintering in northeastern Costa Rica

    Science.gov (United States)

    Jared D. Wolfe; Matthew D. Johnson; C. John Ralph

    2013-01-01

    Estimates of survival of nearctic-neotropic migrants have broadened our understanding of life-history variation across taxa and latitudes. Despite the importance of assessing migrants' survival through all phases of their life-cycle, data from their tropical winter ranges are few. In this study we used 14 years of data on captured birds to quantify the influence...

  9. Effect of BRCA Mutations on Metastatic Relapse and Cause-specific Survival After Radical Treatment for Localised Prostate Cancer.

    Science.gov (United States)

    Castro, Elena; Goh, Chee; Leongamornlert, Daniel; Saunders, Ed; Tymrakiewicz, Malgorzata; Dadaev, Tokhir; Govindasami, Koveela; Guy, Michelle; Ellis, Steve; Frost, Debra; Bancroft, Elizabeth; Cole, Trevor; Tischkowitz, Marc; Kennedy, M John; Eason, Jacqueline; Brewer, Carole; Evans, D Gareth; Davidson, Rosemarie; Eccles, Diana; Porteous, Mary E; Douglas, Fiona; Adlard, Julian; Donaldson, Alan; Antoniou, Antonis C; Kote-Jarai, Zsofia; Easton, Douglas F; Olmos, David; Eeles, Rosalind

    2015-08-01

    Germline BRCA mutations are associated with worse prostate cancer (PCa) outcomes; however, the most appropriate management for mutation carriers has not yet been investigated. To evaluate the response of BRCA carriers to conventional treatments for localised PCa by analysing metastasis-free survival (MFS) and cause-specific survival (CSS) following radical prostatectomy (RP) or external-beam radiation therapy (RT). Tumour features and outcomes of 1302 patients with local/locally advanced PCa (including 67 BRCA mutation carriers) were analysed. RP was undergone by 535 patients (35 BRCA); 767 received RT (32 BRCA). Median follow-up was 64 mo. Median survival and 3-, 5-, and 10-yr survival rates were estimated using the Kaplan-Meier method. Generated survival curves were compared using the log-rank test. Cox regression analyses were used to assess the prognostic value of BRCA mutations. A total of 67 BRCA carriers and 1235 noncarriers were included. At 3, 5, and 10 yr after treatment, 97%, 94%, and 84% of noncarriers and 90%, 72%, and 50% of carriers were free from metastasis (pBRCA mutations as an independent prognostic factor for MFS (hazard ratio [HR]: 2.36; 95% confidence interval [CI], 1.38-4.03; p=0.002) and CSS (HR: 2.17; 95% CI, 1.16-4.07; p=0.016). BRCA carriers had worse outcomes than noncarriers when conventionally treated for local/locally advanced PCa. Prostate cancer patients with germline BRCA mutations had worse outcomes than noncarriers when conventionally treated with surgery or radiation therapy. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  10. Five-year survival and causes of death in patients on home parenteral nutrition for severe chronic and benign intestinal failure

    DEFF Research Database (Denmark)

    Joly, Francisca; Baxter, Janet; Staun, Michael

    2018-01-01

    BACKGROUND & AIM: Home parenteral nutrition (HPN) is the primary treatment for chronic intestinal failure (IF). Intestinal transplantation (ITx) is indicated when there is an increased risk of death due to HPN complications or to the underlying disease. Age, pathophysiologic conditions...... and underlying disease are known predictors of HPN dependency and overall survival. Although the cause of death on HPN is mostly related to underlying disease in these patients, the relationship between mortality and duration of HPN use remains unclear. The purpose of the present study is to describe factors...... was 88%, 74% and 64% at 1, 3 and 5 years respectively. Survival was inversely related to age (p Crohn's disease or chronic idiopathic pseudo-obstruction. A total of 169 (36.5%) patients were weaned-off HPN mainly (80%) within the first year and most frequently...

  11. Empiric potassium supplementation and increased survival in users of loop diuretics.

    Directory of Open Access Journals (Sweden)

    Charles E Leonard

    Full Text Available The effectiveness of the clinical strategy of empiric potassium supplementation in reducing the frequency of adverse clinical outcomes in patients receiving loop diuretics is unknown. We sought to examine the association between empiric potassium supplementation and 1 all-cause death and 2 outpatient-originating sudden cardiac death (SD and ventricular arrhythmia (VA among new starters of loop diuretics, stratified on initial loop diuretic dose.We conducted a one-to-one propensity score-matched cohort study using 1999-2007 US Medicaid claims from five states. Empiric potassium supplementation was defined as a potassium prescription on the day of or the day after the initial loop diuretic prescription. Death, the primary outcome, was ascertained from the Social Security Administration Death Master File; SD/VA, the secondary outcome, from incident, first-listed emergency department or principal inpatient SD/VA discharge diagnoses (positive predictive value = 85%.We identified 654,060 persons who met eligibility criteria and initiated therapy with a loop diuretic, 27% of whom received empiric potassium supplementation (N = 179,436 and 73% of whom did not (N = 474,624. The matched hazard ratio for empiric potassium supplementation was 0.93 (95% confidence interval, 0.89-0.98, p = 0.003 for all-cause death. Stratifying on initial furosemide dose, hazard ratios for empiric potassium supplementation with furosemide < 40 and ≥ 40 milligrams/day were 0.93 (0.86-1.00, p = 0.050 and 0.84 (0.79-0.89, p < 0.0001. The matched hazard ratio for empiric potassium supplementation was 1.02 (0.83-1.24, p = 0.879 for SD/VA.Empiric potassium supplementation upon initiation of a loop diuretic appears to be associated with improved survival, with a greater apparent benefit seen with higher diuretic dose. If confirmed, these findings support the use of empiric potassium supplementation upon initiation of a loop diuretic.

  12. Can sorafenib increase survival for recurrent hepatocellular carcinoma after liver transplantation? A pilot study.

    Science.gov (United States)

    Alsina, Angel E; Makris, Alexia; Nenos, Vasilios; Sucre, Eduardo; Arrobas, Jade; Franco, Edson; Kemmer, Nyingi

    2014-07-01

    Recurrence of hepatocellular carcinoma (HCC) remains a main detriment to long-term survival in liver transplants (LTx) for HCC. The study aims to review the use of sorafenib in recurrent HCC LTx in the Model End Stage Liver Disease era. Two hundred forty-seven patients with HCC LTx from 2002 to 2013 were included. Survival was calculated by the Kaplan-Meier (KM) method and Cox multivariate model. Twenty-two patients recurred (11%). By KM, overall survival was 27 months (standard deviation [SD], 3.2 months; median, 28.4 months). Mean time to recurrence was 16.9 months (SD, 2.8 months; median, 12 months). Nine patients were treated with sorafenib after recurrence. Median survival for sorafenib-treated patients was 42 months compared with a median of 16.2 months without sorafenib (-2 log likelihood ratio, P = 0.0582). By Cox, only sorafenib (P = 0.0233; hazard ratio, 8.528) and pathologic stage had a significant impact on survival. The recurrence rates of HCC LTx remain acceptable considering understaging and expansion of beyond Stage A. This pilot study of sorafenib in recurrent HCC demonstrates improved survival over historic controls. Many other factors affecting improved survival are explained. However, treatment remains palliative. Quality-of-life years and cost analysis need to be performed in this population.

  13. Continues administration of Nano-PSO significantly increased survival of genetic CJD mice.

    Science.gov (United States)

    Binyamin, Orli; Keller, Guy; Frid, Kati; Larush, Liraz; Magdassi, Shlomo; Gabizon, Ruth

    2017-12-01

    We have shown previously that Nano-PSO, a nanodroplet formulation of pomegranate seed oil, delayed progression of neurodegeneration signs when administered for a designated period of time to TgMHu2ME199K mice, modeling for genetic prion disease. In the present work, we treated these mice with a self-emulsion formulation of Nano-PSO or a parallel Soybean oil formulation from their day of birth until a terminal disease stage. We found that long term Nano-PSO administration resulted in increased survival of TgMHu2ME199K lines by several months. Interestingly, initiation of treatment at day 1 had no clinical advantage over initiation at day 70, however cessation of treatment at 9months of age resulted in the rapid loss of the beneficial clinical effect. Pathological studies revealed that treatment with Nano-PSO resulted in the reduction of GAG accumulation and lipid oxidation, indicating a strong neuroprotective effect. Contrarily, the clinical effect of Nano-PSO did not correlate with reduction in the levels of disease related PrP, the main prion marker. We conclude that long term administration of Nano-PSO is safe and may be effective in the prevention/delay of onset of neurodegenerative conditions such as genetic CJD. Copyright © 2017. Published by Elsevier Inc.

  14. Kearns-Sayre's syndrome developing in a boy who survived Pearson's syndrome caused by mitochondrial DNA deletion

    OpenAIRE

    Simonsz, Huib; Bärlocher, K.E.; Rötig, A.

    1992-01-01

    textabstractDocumenta Ophthalmologica 1992, Volume 82, Issue 1-2, pp 73-79 Kearns-Sayre's syndrome developing in a boy who survived Pearson's syndrome caused by mitochondrial DNA deletion Dr H. J. Simonsz, K. Bärlocher, A. Rötig … show all 3 hide » Download PDF (2,322 KB) Abstract A 7-year-old boy presented with bilateral ptosis and atypical retinitis pigmentosa. Before age two, he had had an Fe-refractory anemia, with neutropenia and thrombopenia. Just prior to the ophthalmic examination, th...

  15. IS INCREASED INSTABILITY IN CEREAL PRODUCTION IN ETHIOPIA CAUSED BY POLICY CHANGES?

    OpenAIRE

    Alemu, Zerihun Gudeta; Oosthuizen, Klopper; van Schalkwyk, Herman D.

    2003-01-01

    In Ethiopia, growth in cereal production is accompanied by a more than proportionate increase in the standard deviation of production. This study applies descriptive and variance decomposition procedures to determine the sources of increased instability in cereal production in order to show whether they are caused by policy changes. It was found that production instability was caused more by increased yield instability. Considering the fact that use of high-powered inputs is limited to a smal...

  16. Sugar administration to newly emerged Aedes albopictus males increases their survival probability and mating performance.

    Science.gov (United States)

    Bellini, Romeo; Puggioli, Arianna; Balestrino, Fabrizio; Brunelli, Paolo; Medici, Anna; Urbanelli, Sandra; Carrieri, Marco

    2014-04-01

    Aedes albopictus male survival in laboratory cages is no more than 4-5 days when kept without any access to sugar indicating their need to feed on a sugar source soon after emergence. We therefore developed a device to administer energetic substances to newly emerged males when released as pupae as part of a sterile insect technique (SIT) programme, made with a polyurethane sponge 4 cm thick and perforated with holes 2 cm in diameter. The sponge was imbibed with the required sugar solution and due to its high retention capacity the sugar solution was available for males to feed for at least 48 h. When evaluated in lab cages, comparing adults emerged from the device with sugar solution vs the device with water only (as negative control), about half of the males tested positive for fructose using the Van Handel anthrone test, compared to none of males in the control cage. We then tested the tool in semi-field and in field conditions with different sugar concentrations (10%, 15%, and 20%) and compared results to the controls fed with water only. Males were recaptured by a battery operated manual aspirator at 24 and 48 h after pupae release. Rather high share 10-25% of captured males tested positive for fructose in recollections in the vicinity of the control stations, while in the vicinity of the sugar stations around 40-55% of males were positive, though variability between replicates was large. The sugar positive males in the control test may have been released males that had access to natural sugar sources found close to the release station and/or wild males present in the environment. Only a slight increase in the proportion of positive males was obtained by increasing the sugar concentration in the feeding device from 10% to 20%. Surprisingly, modification of the device to add a black plastic inverted funnel above the container reduced rather than increased the proportion of fructose positive males collected around the station. No evidence of difference in the

  17. Surgical techniques influence local environment of injured spinal cord and cause various grafted cell survival and integration.

    Science.gov (United States)

    Hou, Shaoping; Saltos, Tatiana M; Iredia, Idiata W; Tom, Veronica J

    2018-01-01

    Cellular transplantation to repair a complete spinal cord injury (SCI) is tremendously challenging due to the adverse local milieu for graft survival and growth. Results from cell transplantation studies yield great variability, which may possibly be due to the surgical techniques employed to induce an SCI. In order to delineate the influence of surgery on such inconsistency, we compared lesion morphology and graft survival as well as integration from different lesion methodologies of SCI. Surgical techniques, including a traditional approach cut+microaspiration, and two new approaches, cut alone as well as crush, were employed to produce a complete SCI, respectively. Approximately half of the rats in each group received injury only, whereas the other half received grafts of fetal brainstem cells into the lesion gap. Eight weeks after injury with or without graft, histological analysis showed that the cut+microaspiration surgery resulted in larger lesion cavities and severe fibrotic scars surrounding the cavity, and cellular transplants rarely formed a tissue bridge to penetrate the barrier. In contrast, the majority of cases treated with cut alone or crush exhibited smaller cavities and less scarring; the grafts expanded and blended extensively with the host tissue, which often built continuous tissue bridging the rostral and caudal cords. Scarring and cavitation were significantly reduced when microaspiration was avoided in SCI surgery, facilitating graft/host tissue fusion for signal transmission. The result suggests that microaspiration frequently causes severe scars and cavities, thus impeding graft survival and integration. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Outbreeding increases offspring survival in wild greater horseshoe bats (Rhinolophus ferrumequinum).

    OpenAIRE

    Rossiter, S. J.; Jones, G.; Ransome, R. D.; Barratt, E. M.

    2001-01-01

    The factors influencing the survival of greater horseshoe bat (Rhinolophus ferrumequinum) offspring born over seven years at a maternity colony in south-west Britain were studied. The effects of a range of phenotypic and maternal variables were analysed using a historical data set. In addition, the influence of two genetic measures on mortality, individual heterozygosity and a new measure of outbreeding, termed mean d(2), was assessed. Logistic regressions were undertaken with survival modell...

  19. Aggressive Treatment of Patients with Metastatic Colorectal Cancer Increases Survival: A Scandinavian Single-Center Experience

    Directory of Open Access Journals (Sweden)

    Kristoffer Watten Brudvik

    2013-01-01

    Full Text Available Background. We examined overall and disease-free survivals in a cohort of patients subjected to resection of liver metastasis from colorectal cancer (CRLM in a 10-year period when new treatment strategies were implemented. Methods. Data from 239 consecutive patients selected for liver resection of CRLM during the period from 2002 to 2011 at a single center were used to estimate overall and disease-free survival. The results were assessed against new treatment strategies and established risk factors. Results. The 5-year cumulative overall and disease-free survivals were 46 and 24%. The overall survival was the same after reresection, independently of the number of prior resections and irrespectively of the location of the recurrent disease. The time intervals between each recurrence were similar (11 ± 1 months. Patients with high tumor load given neoadjuvant chemotherapy had comparable survival to those with less extensive disease without neoadjuvant chemotherapy. Positive resection margin or resectable extrahepatic disease did not affect overall survival. Conclusion. Our data support that one still, and perhaps to an even greater extent, should seek an aggressive therapeutic strategy to achieve resectable status for recurrent hepatic and extrahepatic metastases. The data should be viewed in the context of recent advances in the understanding of cancer biology and the metastatic process.

  20. Pre-transplant donor HLA-specific antibodies: characteristics causing detrimental effects on survival after lung transplantation.

    Science.gov (United States)

    Smith, John D; Ibrahim, Mohamed W; Newell, Helen; Danskine, Anna J; Soresi, Simona; Burke, Margaret M; Rose, Marlene L; Carby, Martin

    2014-10-01

    The impact of Luminex-detected HLA antibodies on outcomes after lung transplantation is unclear. Herein we have undertaken a retrospective study of pre-transplant sera from 425 lung transplants performed between 1991 and 2003. Pre-transplant sera, originally screened by complement-dependent cytotoxicity (CDC) assays, were retrospectively tested for the presence of HLA-specific antibodies using HLA-coated Luminex beads and C4d deposition on Luminex beads. The results were correlated with graft survival at 1 year. Twenty-seven patients were retrospectively identified as having been transplanted against donor-specific HLA antibodies (DSA) and 36 patients against non-donor-specific HLA antibodies (NDSA). DSA-positive patients had 1-year survival of 51.9% compared with 77.8% for NDSA and 71.8% for antibody-negative patients (p = 0.029). One-year survival of patients with complement-fixing DSA was 12.5% compared with 62.5% for non-complement-fixing DSA, 75.8% for non-complement-fixing NDSA and 71.8% for antibody-negative patients (p 5,000 had 1-year survival of 33.3% compared with 71.4% for MFI 2,000 to 5000 and 62.5% for MFI 5,000 (p = 0.0001, HR = 5.512). Pre-formed DSA, particularly complement-fixing DSA, and high MFI are associated with poor survival within the first year after lung transplantation. Risk stratification according to complement fixation or MFI levels may allow for increased transplantation in sensitized patients. Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  1. Cause-Specific Mortality in HIV-Positive Patients Who Survived Ten Years after Starting Antiretroviral Therapy

    DEFF Research Database (Denmark)

    Trickey, Adam; May, Margaret T; Vehreschild, Jorg-Janne

    2016-01-01

    OBJECTIVES: To estimate mortality rates and prognostic factors in HIV-positive patients who started combination antiretroviral therapy between 1996-1999 and survived for more than ten years. METHODS: We used data from 18 European and North American HIV cohort studies contributing to the Antiretro......OBJECTIVES: To estimate mortality rates and prognostic factors in HIV-positive patients who started combination antiretroviral therapy between 1996-1999 and survived for more than ten years. METHODS: We used data from 18 European and North American HIV cohort studies contributing...... to the Antiretroviral Therapy Cohort Collaboration. We followed up patients from ten years after start of combination antiretroviral therapy. We estimated overall and cause-specific mortality rate ratios for age, sex, transmission through injection drug use, AIDS, CD4 count and HIV-1 RNA. RESULTS: During 50,593 person...... mortality in models adjusted for patient characteristics ten years after start of antiretroviral therapy. The most frequent causes of death (among 340 classified) were non-AIDS cancer, AIDS, cardiovascular, and liver-related disease. Older age was strongly associated with cardiovascular mortality, injecting...

  2. Upgrade of Coastal Defence Structures Against Increased Loadings Caused by Climate Change

    DEFF Research Database (Denmark)

    Burcharth, Hans F.; Andersen, Thomas Lykke; Lara, Javier L.

    2014-01-01

    increase in long-term wind/wave conditions as predicted for the North Sea by the Danish Coastal Authority. Both conditions of non-acceptable and acceptable increase in structure crest level are considered. Moreover, a scenario for steepening of the foreshore due to morphological changes caused by increased...

  3. Preventing fatal diseases increases healthcare costs: cause elimination life table approach

    NARCIS (Netherlands)

    L.G.A. Bonneux (Luc); J.J.M. Barendregt (Jan); W.J. Nusselder (Wilma); P.J. van der Maas (Paul)

    1998-01-01

    textabstractOBJECTIVES: To examine whether elimination of fatal diseases will increase healthcare costs. DESIGN: Mortality data from vital statistics combined with healthcare spending in a cause elimination life table. Costs were allocated to specific diseases through

  4. Liberal versus restrictive blood transfusion strategy: 3-year survival and cause of death results from the FOCUS randomised controlled trial.

    Science.gov (United States)

    Carson, Jeffrey L; Sieber, Frederick; Cook, Donald Richard; Hoover, Donald R; Noveck, Helaine; Chaitman, Bernard R; Fleisher, Lee; Beaupre, Lauren; Macaulay, William; Rhoads, George G; Paris, Barbara; Zagorin, Aleksandra; Sanders, David W; Zakriya, Khwaja J; Magaziner, Jay

    2015-03-28

    Blood transfusion might affect long-term mortality by changing immune function and thus potentially increasing the risk of subsequent infections and cancer recurrence. Compared with a restrictive transfusion strategy, a more liberal strategy could reduce cardiac complications by lowering myocardial damage, thereby reducing future deaths from cardiovascular disease. We aimed to establish the effect of a liberal transfusion strategy on long-term survival compared with a restrictive transfusion strategy. In the randomised controlled FOCUS trial, adult patients aged 50 years and older, with a history of or risk factors for cardiovascular disease, and with postoperative haemoglobin concentrations lower than 100 g/L within 3 days of surgery to repair a hip fracture, were eligible for enrolment. Patients were recruited from 47 participating hospitals in the USA and Canada, and eligible participants were randomly allocated in a 1:1 ratio by a central telephone system to either liberal transfusion in which they received blood transfusion to maintain haemoglobin level at 100 g/L or higher, or restrictive transfusion in which they received blood transfusion when haemoglobin level was lower than 80 g/L or if they had symptoms of anaemia. In this study, we analysed the long-term mortality of patients assigned to the two transfusion strategies, which was a secondary outcome of the FOCUS trial. Long-term mortality was established by linking the study participants to national death registries in the USA and Canada. Treatment assignment was not masked, but investigators who ascertained mortality and cause of death were masked to group assignment. Analyses were by intention to treat. The FOCUS trial is registered with ClinicalTrials.gov, number NCT00071032. Between July 19, 2004, and Feb 28, 2009, 2016 patients were enrolled and randomly assigned to the two treatment groups: 1007 to the liberal transfusion strategy and 1009 to the restrictive transfusion strategy. The median

  5. Increased HDAC1 deposition at hematopoietic promoters in AML and its association with patient survival

    DEFF Research Database (Denmark)

    Tickenbrock, Lara; Klein, Hans-Ulrich; Trento, Cristina

    2011-01-01

    was established, that revealed an AML specific pattern of HDAC1 distribution. Many of the HDAC1-binding altered promoters regulate genes involved in hematopoiesis, transcriptional regulation and signal transduction. HDAC1 binding patterns were associated with patients' event free survival. This is the first study...... to determine HDAC1 modification patterns in a large number of AML and ALL specimens. Our findings suggest that dyslocalization of HDAC1 is a common feature in AML. Importantly, HDAC1 modifications possess prognostic power for patient survival. Our findings suggest that altered HDAC1 localization...

  6. Different loci and mRNA copy number of the increased serum survival gene of Escherichia coli.

    Science.gov (United States)

    Xu, Wang-Ye; Li, Yi-Jing; Fan, Chen

    2018-02-01

    The increased serum survival gene (iss) has been identified as a virulence trait associated with the virulence of Escherichia coli, causing colibacillosis in poultry. However, it remains unclear as to whether iss mRNA copy number and sequence affect virulence. To examine these influences, we assessed the presence of iss, sequence analysis, iss mRNA copy number, and serum resistance. The iss gene was detected in 88 (all) E. coli isolates from different sources, and sequencing identified 16 alleles (32 different loci) and 10 amino acid sequences (10 different loci). Nested polymerase chain reaction improved iss detection. The isolates from sick chickens had >68% livability in serum resistance tests and higher iss mRNA copy number. The iss mRNA copy number highly correlated with mortality and E. coli livability. Student's t tests confirmed the relationship between the different loci to iss transcription, serum resistance, and virulence. These data suggest that iss mRNA copy number and different loci affect the virulence and serum resistance. These findings could be useful in further studies on the prevalence of iss among E. coli isolates and other virulence factors.

  7. Lundep, a sand fly salivary endonuclease increases Leishmania parasite survival in neutrophils and inhibits XIIa contact activation in human plasma.

    Directory of Open Access Journals (Sweden)

    Andrezza C Chagas

    2014-02-01

    Full Text Available Neutrophils are the host's first line of defense against infections, and their extracellular traps (NET were recently shown to kill Leishmania parasites. Here we report a NET-destroying molecule (Lundep from the salivary glands of Lutzomyia longipalpis. Previous analysis of the sialotranscriptome of Lu. longipalpis showed the potential presence of an endonuclease. Indeed, not only was the cloned cDNA (Lundep shown to encode a highly active ss- and dsDNAse, but also the same activity was demonstrated to be secreted by salivary glands of female Lu. longipalpis. Lundep hydrolyzes both ss- and dsDNA with little sequence specificity with a calculated DNase activity of 300000 Kunitz units per mg of protein. Disruption of PMA (phorbol 12 myristate 13 acetate- or parasite-induced NETs by treatment with recombinant Lundep or salivary gland homogenates increases parasite survival in neutrophils. Furthermore, co-injection of recombinant Lundep with metacyclic promastigotes significantly exacerbates Leishmania infection in mice when compared with PBS alone or inactive (mutagenized Lundep. We hypothesize that Lundep helps the parasite to establish an infection by allowing it to escape from the leishmanicidal activity of NETs early after inoculation. Lundep may also assist blood meal intake by lowering the local viscosity caused by the release of host DNA and as an anticoagulant by inhibiting the intrinsic pathway of coagulation.

  8. Low dystrophin levels increase survival and improve muscle pathology and function in dystrophin/utrophin double-knockout mice

    Science.gov (United States)

    van Putten, Maaike; Hulsker, Margriet; Young, Courtney; Nadarajah, Vishna D.; Heemskerk, Hans; van der Weerd, Louise; 't Hoen, Peter A. C.; van Ommen, Gert-Jan B.; Aartsma-Rus, Annemieke M.

    2013-01-01

    Duchenne muscular dystrophy (DMD) is a severe muscle-wasting disorder caused by the lack of functional dystrophin. There is no cure, but several clinical trials aimed to restore the synthesis of functional dystrophin are underway. The dystrophin levels needed for improvement of muscle pathology, function, and overall vitality are not known. Here, we describe the mdx/utrn−/−/XistΔhs mouse model, which expresses a range of low dystrophin levels, depending on the degree of skewing of X inactivation in a utrophin-negative background. Mdx/utrn−/− mice develop severe muscle weakness, kyphosis, respiratory and heart failure, and premature death closely resembling DMD pathology. We show that at dystrophin levels 4% dystrophin, histopathology is ameliorated, as well. These findings suggest that the dystrophin levels needed to benefit vitality and functioning of patients with DMD might be lower than those needed for full protection against muscle damage.—Van Putten, M., Hulsker, M., Young, C., Nadarajah, V. D., Heemskerk, H., van der Weerd, L., 't Hoen, P. A. C., van Ommen, G. J. B., Aartsma-Rus, A. M. Low dystrophin levels increase survival and improve muscle pathology and function in dystrophin/utrophin double-knockout mice. PMID:23460734

  9. Francisella tularensis type A Strains Cause the Rapid Encystment of Acanthamoeba castellanii and Survive in Amoebal Cysts for Three Weeks post Infection

    Energy Technology Data Exchange (ETDEWEB)

    El-Etr, S H; Margolis, J; Monack, D; Robison, R; Cohen, M; Moore, E; Rasley, A

    2009-07-28

    Francisella tularensis, the causative agent of the zoonotic disease tularemia, has recently gained increased attention due to the emergence of tularemia in geographical areas where the disease has been previously unknown, and the organism's potential as a bioterrorism agent. Although F. tularensis has an extremely broad host range, the bacterial reservoir in nature has not been conclusively identified. In this study, the ability of virulent F. tularensis strains to survive and replicate in the amoeba Acanthamoeba castellanii was explored. We observe that A. castellanii trophozoites rapidly encyst in response to F. tularensis infection and that this rapid encystment phenotype (REP) is caused by factor(s) secreted by amoebae and/or F. tularensis into the co-culture media. Further, our results indicate that in contrast to LVS, virulent strains of F. tularensis can survive in A. castellanii cysts for at least 3 weeks post infection and that induction of rapid amoeba encystment is essential for survival. In addition, our data indicate that pathogenic F. tularensis strains block lysosomal fusion in A. castellanii. Taken together, these data suggest that the interactions between F. tularensis strains and amoeba may play a role in the environmental persistence of F. tularensis.

  10. Survival of male Tengmalm’s owls increases with cover of old forest in the territory

    NARCIS (Netherlands)

    Hakkarainen, H.; Korpimäki, E.; Laaksonen, T.; Nikula, A.; Suorsa, P.

    2008-01-01

    The loss and fragmentation of forest habitats have been considered to pose a worldwide threat to the viability of forest-dwelling animals, especially to species that occupy old forests. We investigated whether the annual survival of sedentary male Tengmalm’s owls Aegolius funereus was associated

  11. Assessment of immunity against avian colibacillosis induced by an aroA mutant containing increased serum survival gene in broilers

    Directory of Open Access Journals (Sweden)

    Taghi Zahraei Salehi

    2012-03-01

    Full Text Available Colibacillosis is an important disease in the poultry industry which causes serious economic damages. As it is suggested that vaccination is one of the means to control colibacillosis, we tried to investigate the vaccine potential of a ΔaroA derivative of an O78:K80 avian pathogenic Escherichia coli containing increased serum survival gene. 490 chicks were selected as follows: For assessment of virulence of ΔaroA mutant, 30 chicks were divided into three groups and injected with 0.5ml of PBS or bacterial suspension containing either10(7colony forming units (CFU of mutant or parent strains via subcutaneous route. Macroscopic lesions and mortality rate were recorded in different groups during the week after challenge. For assessment of safety and immunogenicity of the ΔaroA mutant, three groups of 20 chicks were vaccinated by aerosol administration of 250 ml of suspension containing 10(8 CFU of mutant strain at days 1 and 14, while the two other groups received PBS or wild type strain. Macroscopic lesions and mortality rate were recorded in different groups until day 21. To determine whether the vaccination is protective against challenges or not, the chickens were vaccinated at days 1 and 14 and challenged intramuscularly with either a homologous or heterologous strains at day 21. Macroscopic lesions and mortality rate were recorded in different groups during the week after challenge. The results revealed that the ΔaroA mutant was slightly virulent, however it was safe and did not cause mortality, lesions or weight loss after vaccination. Antibody responses were similar in the control and mutant groups and vaccination did not induce a significant humoral immunity. The mutant could not protect chickens against both homologous and heterologous challenges. This could be due to several factors such as the high amount of maternal antibodies in the first two weeks of life, and the vaccination procedure.

  12. Polycythemia vera and increased hemophilic factor VIII causing acute zonal occult outer retinopathy: a case report.

    Science.gov (United States)

    Mahendradas, Padmamalini; Shetty, Rohit; Avadhani, Kavitha; Ross, Cecil; Gupta, Anchal; Shetty, Bhujang K

    2010-08-01

    To report a case of acute zonal occult outer retinopathy (AZOOR) caused by Polycythemia and increased levels of Factor VIIIC. Case Report - Interventional. We present a 23 year old male with blurring of vision and loss of lower visual fields in both eyes. Ocular examination suggested the possibility of AZOOR that was confirmed with Fluorescein Angiogram, Visual fields and Electroretinogram. Laboratory work up revealed polycythemia with increased Factor VIIIC. He was treated for the same. Ocular symptoms improved within 24 hours of treatment with venesection and asprin. Polycythemia vera and increased factor VIIIC levels, both venous thromboembolic risk factors are treatable causes of AZOOR.

  13. Increasing RpoS expression causes cell death in Borrelia burgdorferi.

    Directory of Open Access Journals (Sweden)

    Linxu Chen

    Full Text Available RpoS, one of the two alternative σ factors in Borrelia burgdorferi, is tightly controlled by multiple regulators and, in turn, determines expression of many critical virulence factors. Here we show that increasing RpoS expression causes cell death. The immediate effect of increasing RpoS expression was to promote bacterial division and as a consequence result in a rapid increase in cell number before causing bacterial death. No DNA fragmentation or degradation was observed during this induced cell death. Cryo-electron microscopy showed induced cells first formed blebs, which were eventually released from dying cells. Apparently blebbing initiated cell disintegration leading to cell death. These findings led us to hypothesize that increasing RpoS expression triggers intracellular programs and/or pathways that cause spirochete death. The potential biological significance of induced cell death may help B. burgdorferi regulate its population to maintain its life cycle in nature.

  14. Increased risk of all-cause mortality and renal graft loss in stable renal transplant recipients with hyperparathyroidism.

    Science.gov (United States)

    Pihlstrøm, Hege; Dahle, Dag Olav; Mjøen, Geir; Pilz, Stefan; März, Winfried; Abedini, Sadollah; Holme, Ingar; Fellström, Bengt; Jardine, Alan G; Holdaas, Hallvard

    2015-02-01

    Hyperparathyroidism is reported in 10% to 66% of renal transplant recipients (RTR). The influence of persisting hyperparathyroidism on long-term clinical outcomes in RTR has not been examined in a large prospective study. We investigated the association between baseline parathyroid hormone (PTH) levels and major cardiovascular events, renal graft loss, and all-cause mortality by Cox Proportional Hazard survival analyses in 1840 stable RTR derived from the Assessment of LEscol in Renal Transplantation trial. Patients were recruited in a mean of 5.1 years after transplantation, and follow-up time was 6 to 7 years. Significant associations between PTH and all 3 outcomes were found in univariate analyses. When adjusting for a range of plausible confounders, including measures of renal function and serum mineral levels, PTH remained significantly associated with all-cause mortality (4% increased risk per 10 units; P=0.004), and with graft loss (6% increased risk per 10 units; PHyperparathyroidism is an independent, potentially remediable, risk factor for renal graft loss and all-cause mortality in RTR.

  15. Fasting increases survival to cold in FOXO, DIF, autophagy mutants and in other genotypes of Drosophila melanogaster.

    Science.gov (United States)

    Le Bourg, Éric; Massou, Isabelle

    2015-08-01

    Fasting increases survival to a severe cold stress in young and middle-aged wild-type flies, this effect being lowered or absent at old age. As an attempt to determine the mechanisms of this effect, genes involved in metabolism (dFOXO), autophagy (Atg7), innate immunity (Dif (1) ), and resistance to cold (Frost) were studied. The 12 mutant, RNAi and control lines tested in this study displayed an increased survival to cold after fasting. This shows that fasting has a robust effect on survival to cold in many genotypes, but the mechanism of this effect remains unknown. This mechanism does not seem to be linked to metabolic pathways often considered to play a critical role in ageing and longevity determinations (insulin/insulin-like growth factor-1 pathway and autophagy).

  16. Increased actin polymerization and stabilization interferes with neuronal function and survival in the AMPKγ mutant Loechrig.

    Directory of Open Access Journals (Sweden)

    Mandy Cook

    Full Text Available loechrig (loe mutant flies are characterized by progressive neuronal degeneration, behavioral deficits, and early death. The mutation is due to a P-element insertion in the gene for the γ-subunit of the trimeric AMP-activated protein kinase (AMPK complex, whereby the insertion affects only one of several alternative transcripts encoding a unique neuronal isoform. AMPK is a cellular energy sensor that regulates a plethora of signaling pathways, including cholesterol and isoprenoid synthesis via its downstream target hydroxy-methylglutaryl (HMG-CoA reductase. We recently showed that loe interferes with isoprenoid synthesis and increases the prenylation and thereby activation of RhoA. During development, RhoA plays an important role in neuronal outgrowth by activating a signaling cascade that regulates actin dynamics. Here we show that the effect of loe/AMPKγ on RhoA prenylation leads to a hyperactivation of this signaling pathway, causing increased phosphorylation of the actin depolymerizating factor cofilin and accumulation of filamentous actin. Furthermore, our results show that the resulting cytoskeletal changes in loe interfere with neuronal growth and disrupt axonal integrity. Surprisingly, these phenotypes were enhanced by expressing the Slingshot (SSH phosphatase, which during development promotes actin depolymerization by dephosphorylating cofilin. However, our studies suggest that in the adult SSH promotes actin polymerization, supporting in vitro studies using human SSH1 that suggested that SSH can also stabilize and bundle filamentous actin. Together with the observed increase in SSH levels in the loe mutant, our experiments suggest that in mature neurons SSH may function as a stabilization factor for filamentous actin instead of promoting actin depolymerization.

  17. Chemotherapy increases long-term survival in patients with adult medulloblastoma--a literature-based meta-analysis.

    Science.gov (United States)

    Kocakaya, Selin; Beier, Christoph Patrick; Beier, Dagmar

    2016-03-01

    Adult medulloblastoma is a potentially curable malignant entity with an incidence of 0.5-1 per million. Valid data on prognosis, treatment, and demographics are lacking, as most current knowledge stems from retrospective studies. Surgical resection followed by radiotherapy are accepted parts of treatment regimes; however, established prognostic factors and data clarifying the role of chemotherapy are missing. We investigated 227 publications from 1969-2013, with 907 identifiable, individual patients being available for meta-analysis. Demographic data, risk stratification, and treatment of these patients were similar to previous cohorts. The median overall survival (mOS) was 65 months (95% CI: 54.6-75.3) , the 5-year overall survival was 50.9% with 16% of the patients dying more than 5 years after diagnosis. Incomplete resection, clinical and radiological signs for brainstem infiltration, and abstinence from radiotherapy were predictive of worse outcome. Metastatic disease at tumor recurrence was identified as a new prognostic factor, while neither metastasis at initial diagnosis nor desmoplastic/classic histology was correlated with survival. Patients receiving chemotherapy first-line survived significantly longer (mOS: 108 mo, 95% CI: 68.6-148.4) than patients treated with radiation alone (mOS: 57 mo, 95% CI: 39.6-74.4) or patients who received chemotherapy at tumor recurrence. This effect was not biased by tumor stage or decade of treatment. Importantly, (neo)adjuvant chemotherapy also significantly increased the chance for long-term survival (>5 y) compared with radiotherapy alone or chemotherapy at tumor recurrence. This meta-analysis clarifies relevant prognostic factors and suggests that chemotherapy as part of first-line therapy improves overall survival and increases the proportion of patients with long-term survival. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions

  18. Survival, causes of death, and estimated tissue doses in a group of human beings injected with plutonium

    International Nuclear Information System (INIS)

    Rowland, R.E.; Durbin, P.W.

    1975-01-01

    To determine the relationship between urinary excretion and plutonium body content, 18 persons of short life expectancy were injected with plutonium between 1945 and 1947. Seventeen of these 18 individuals have been identified; eight were found to have survived for at least eight years and four are still alive today (1975). The causes of death of 13 of these individuals have been determined from death certificates; none appear to be related to the administered plutonium. Doses to the liver and to the cells on the surface of bone have been calculated for these plutonium cases. The liver doses do not appear to be high enough to be carcinogenic, but comparison of the bone-surface doses with radium doses that have induced bone tumors indicates that six of these cases have received doses high enough to be considered carcinogenic. However, no bone tumors have yet appeared. (auth)

  19. Survival and cause of death after traumatic spinal cord injury. A long-term epidemiological survey from Denmark

    DEFF Research Database (Denmark)

    Hartkopp, A; Brønnum-Hansen, Henrik; Seidenschnur, A M

    1997-01-01

    Life expectancy among individuals with spinal cord injuries (SCI) has remained lower than in the normal population, even with optimal medical management. But significant improvement has been achieved, as will be illustrated in this retrospective study of an unselected group of traumatic survivors...... treatment and were rehabilitated at the centre for Spinal Cord Injured in Hornbaek, Denmark. At the end of the follow-up, 31st December 1992, 236 (197 men and 39 women) had died. The commonest causes of death were lung diseases, particularly pneumonia; suicide; and ischaemic heart disease. Among...... of SCI, dead or still living. There has been a complete follow-up over 4 decades, information being obtained from available medical records, death certificates, and post mortem records. The survey included a total of 888 individuals (713 men and 175 women) who had survived the injury and primary...

  20. Testing and diagnosis of the cause of increased vibration of the fan plant's support structure

    Directory of Open Access Journals (Sweden)

    Varju Đerđ

    2015-01-01

    Full Text Available This paper presents a procedure of determining the causes of increased vibration of a fan plant and its support structure in the PUC 'Subotička toplana'. Excessive vibrations were observed following the installation of the frequency converter, thus a methodological approach of testing-analysis-diagnosis has been applied. Based on the definition of the causes of this problem, the paper also suggests possible repair procedures.

  1. From utopia to reality: increased survival in peritoneal carcinomatosis treated with cytoreduction and hyperthermic intraperitoneal chemotherapy.

    Science.gov (United States)

    Segura-Sampedro, Juan José; Morales-Soriano, Rafael

    2017-11-01

    We have read with great interest the article by Illán et al.1 entitled "Long survival in a patient with metastatic colorectal carcinoma: reality or utopia?" This article describes the case of a 42 year old patient with mucinous-type colon adenocarcinoma who had tumor recurrence with peritoneal metastases 18 months after resection of the primary tumor and adjuvant chemotherapy. After multiple metastasectomies and several lines of chemotherapy, the patient died 27 months after the recurrence.

  2. Improvements in logistics could increase survival after out-of-hospital cardiac arrest in Sweden.

    Science.gov (United States)

    Strömsöe, A; Afzelius, S; Axelsson, C; Södersved Källestedt, M L; Enlund, M; Svensson, L; Herlitz, J

    2013-06-01

    In a review based on estimations and assumptions, to report the estimated number of survivors after out-of-hospital cardiac arrest (OHCA) in whom cardiopulmonary resuscitation (CPR) was started and to speculate about possible future improvements in Sweden. An observational study. All ambulance organisations in Sweden. Patients included in the Swedish Cardiac Arrest Registry who suffered an OHCA between January 1, 2008 and December 31, 2010. Approximately 80% of OHCA cases in Sweden in which CPR was started are included. None In 11 005 patients, the 1-month survival rate was 9.4%. There are approximately 5000 OHCA cases annually in which CPR is started and 30-day survival is achieved in up to 500 patients yearly (6 per 100 000 inhabitants). Based on findings on survival in relation to the time to calling for the Emergency Medical Service (EMS) and the start of CPR and defibrillation, it was estimated that, if the delay from collapse to (i) calling EMS, (ii) the start of CPR, and (iii) the time to defibrillation were reduced to <2 min, <2 min, and <8 min, respectively, 300-400 additional lives could be saved. Based on findings relating to the delay to calling for the EMS and the start of CPR and defibrillation, we speculate that 300-400 additional OHCA patients yearly (4 per 100 000 inhabitants) could be saved in Sweden. © 2013 The Association for the Publication of the Journal of Internal Medicine.

  3. Cause-Specific Mortality in HIV-Positive Patients Who Survived Ten Years after Starting Antiretroviral Therapy

    Science.gov (United States)

    May, Margaret T.; Vehreschild, Janne; Obel, Niels; Gill, Michael John; Crane, Heidi; Boesecke, Christoph; Samji, Hasina; Grabar, Sophie; Cazanave, Charles; Cavassini, Matthias; Shepherd, Leah; d’Arminio Monforte, Antonella; Smit, Colette; Saag, Michael; Lampe, Fiona; Hernando, Vicky; Montero, Marta; Zangerle, Robert; Justice, Amy C.; Sterling, Timothy; Miro, Jose; Ingle, Suzanne; Sterne, Jonathan A. C.

    2016-01-01

    Objectives To estimate mortality rates and prognostic factors in HIV-positive patients who started combination antiretroviral therapy between 1996–1999 and survived for more than ten years. Methods We used data from 18 European and North American HIV cohort studies contributing to the Antiretroviral Therapy Cohort Collaboration. We followed up patients from ten years after start of combination antiretroviral therapy. We estimated overall and cause-specific mortality rate ratios for age, sex, transmission through injection drug use, AIDS, CD4 count and HIV-1 RNA. Results During 50,593 person years 656/13,011 (5%) patients died. Older age, male sex, injecting drug use transmission, AIDS, and low CD4 count and detectable viral replication ten years after starting combination antiretroviral therapy were associated with higher subsequent mortality. CD4 count at ART start did not predict mortality in models adjusted for patient characteristics ten years after start of antiretroviral therapy. The most frequent causes of death (among 340 classified) were non-AIDS cancer, AIDS, cardiovascular, and liver-related disease. Older age was strongly associated with cardiovascular mortality, injecting drug use transmission with non-AIDS infection and liver-related mortality, and low CD4 and detectable viral replication ten years after starting antiretroviral therapy with AIDS mortality. Five-year mortality risk was AIDS, and transmission via injecting drug use continue to predict higher all-cause and AIDS-related mortality in patients treated with combination antiretroviral therapy for over a decade. Deaths from AIDS and non-AIDS infection are less frequent than deaths from other non-AIDS causes. PMID:27525413

  4. Increased cell survival of cells exposed to superparamagnetic iron oxide nanoparticles through biomaterial substrate-induced autophagy.

    Science.gov (United States)

    Tseng, Ting-Chen; Hsieh, Fu-Yu; Hsu, Shan-Hui

    2016-04-01

    The cellular uptake of nanoparticles (NPs) can be promoted by NP surface modification but cell viability is often sacrificed. Our previous study has shown that intracellular uptake of iron oxide NPs was significantly increased for cells cultured on chitosan. However, the mechanism for having the higher cellular uptake as well as better cell survival on the chitosan surface remains unclear. In this study, we sought to clarify if the autophagic response may contribute to cell survival under excessive NP exposure conditions on chitosan. L929 fibroblasts and neural stem cells (NSCs) were challenged with different concentrations (0-300 μg ml(-1)) of superparamagnetic iron oxide NPs. The autophagic response as well as the metabolic activity of cells was evaluated. Results showed that culturing both types of cells on chitosan substrates significantly enhanced the cellular uptake of NPs. At higher NP concentrations, cells on chitosan showed a greater survival rate than those on TCPS. The expression levels of autophagy-related genes (Atg5 and Atg7 genes) and autophagy associated protein (LC3-II) on chitosan were higher than that on TCPS. The NP exposure further increased the expressions. We suggest that cells cultured on chitosan were more tolerant to NP cytotoxicity because of the increased autophagic response. Moreover, NP exposure increased the metabolic activity of cells grown on chitosan, while it decreased the metabolism of cells cultured on TCPS. In animal studies, iron oxide-labeled NSCs were injected in zebrafish embryos. Results also showed that cells grown on chitosan had better survival after transplantation than those grown on TCPS. Taken together, chitosan as a culture substrate can induce cell autophagy to increase cell survival in particular for NP-labeled cells. This will be valuable for the biomedical application of NPs in cell therapy.

  5. Edema-induced increase in tumour cell survival for 125I and 103Pd prostate permanent seed implants - a bio-mathematical model

    International Nuclear Information System (INIS)

    Yue Ning; Chen Zhe; Nath, Ravinder

    2002-01-01

    Edema caused by the surgical procedure of prostate seed implantation expands the source-to-point distances within the prostate and hence decreases the dose coverage. The decrease of dose coverage results in an increase in tumour cell survival. To investigate the effects of edema on tumour cell survival, a bio-mathematical model of edema and the corresponding cell killing by continuous low dose rate irradiation (CLDRI) was developed so that tumour cell surviving fractions can be estimated in an edematous prostate for both 125 I and 103 Pd seed implants. The dynamic nature of edema and its resolution were modelled with an exponential function V(T)=V p (1+M exp(-0.693T/T e )) where V p is the prostate volume before implantation, M is the edema magnitude and T e is edema half-life (EHL). The dose rate of a radioactive seed was calculated according to AAPM TG43, i.e. D radical S k Δg(r) φ-bar an /r 2 , where r is the distance between a seed and a given point. The distance r is now a function of time because of edema. The g(r) was approximated as 1/r 0.4 and 1/r 0.8 for 125 I and 103 Pd, respectively. By expanding the mathematical expression of the resultant dose rate in a Taylor series of exponential functions of time, the dose rate was made equivalent to that produced from multiple fictitious radionuclides of different decay constants and strengths. The biologically effective dose (BED) for an edematous prostate implant was then calculated using a generalized Dale equation. The cell surviving fraction was computed as exp(-αBED), where α is the linear coefficient of the survival curve. The tumour cell survival was calculated for both 125 I and 103 Pd seed implants and for different tumour potential doubling time (TPDT) (from 5 days to 30 days) and for edemas of different magnitudes (from 0% to 95%) and edema half-lives (from 4 days to 30 days). Tumour cell survival increased with the increase of edema magnitude and EHL. For a typical edema of a half-life of 10 days

  6. Edema-induced increase in tumour cell survival for {sup 125}I and {sup 103}Pd prostate permanent seed implants - a bio-mathematical model

    Energy Technology Data Exchange (ETDEWEB)

    Yue Ning; Chen Zhe; Nath, Ravinder [Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT (United States)

    2002-04-01

    Edema caused by the surgical procedure of prostate seed implantation expands the source-to-point distances within the prostate and hence decreases the dose coverage. The decrease of dose coverage results in an increase in tumour cell survival. To investigate the effects of edema on tumour cell survival, a bio-mathematical model of edema and the corresponding cell killing by continuous low dose rate irradiation (CLDRI) was developed so that tumour cell surviving fractions can be estimated in an edematous prostate for both {sup 125}I and {sup 103}Pd seed implants. The dynamic nature of edema and its resolution were modelled with an exponential function V(T)=V{sub p} (1+M exp(-0.693T/T{sub e})) where V{sub p} is the prostate volume before implantation, M is the edema magnitude and T{sub e} is edema half-life (EHL). The dose rate of a radioactive seed was calculated according to AAPM TG43, i.e. D radical S{sub k}{delta}g(r) {phi}-bar{sub an}/r{sup 2}, where r is the distance between a seed and a given point. The distance r is now a function of time because of edema. The g(r) was approximated as 1/r{sup 0.4} and 1/r{sup 0.8} for {sup 125}I and {sup 103}Pd, respectively. By expanding the mathematical expression of the resultant dose rate in a Taylor series of exponential functions of time, the dose rate was made equivalent to that produced from multiple fictitious radionuclides of different decay constants and strengths. The biologically effective dose (BED) for an edematous prostate implant was then calculated using a generalized Dale equation. The cell surviving fraction was computed as exp(-{alpha}BED), where {alpha} is the linear coefficient of the survival curve. The tumour cell survival was calculated for both {sup 125}I and {sup 103}Pd seed implants and for different tumour potential doubling time (TPDT) (from 5 days to 30 days) and for edemas of different magnitudes (from 0% to 95%) and edema half-lives (from 4 days to 30 days). Tumour cell survival increased

  7. Nutritional intra-amniotic therapy increases survival in a rabbit model of fetal growth restriction

    Science.gov (United States)

    Illa, Miriam; Pla, Laura; Zamora, Monica; Crispi, Fatima; Gratacos, Eduard

    2018-01-01

    Objective To evaluate the perinatal effects of a prenatal therapy based on intra-amniotic nutritional supplementation in a rabbit model of intrauterine growth restriction (IUGR). Methods IUGR was surgically induced in pregnant rabbits at gestational day 25 by ligating 40–50% of uteroplacental vessels of each gestational sac. At the same time, modified-parenteral nutrition solution (containing glucose, amino acids and electrolytes) was injected into the amniotic sac of nearly half of the IUGR fetuses (IUGR-T group n = 106), whereas sham injections were performed in the rest of fetuses (IUGR group n = 118). A control group without IUGR induction but sham injection was also included (n = 115). Five days after the ligation procedure, a cesarean section was performed to evaluate fetal cardiac function, survival and birth weight. Results Survival was significantly improved in the IUGR fetuses that were treated with intra-amniotic nutritional supplementation as compared to non-treated IUGR animals (survival rate: controls 71% vs. IUGR 44% p = 0.003 and IUGR-T 63% vs. IUGR 44% p = 0.02), whereas, birth weight (controls mean 43g ± SD 9 vs. IUGR 36g ± SD 9 vs. IUGR-T 35g ± SD 8, p = 0.001) and fetal cardiac function were similar among the IUGR groups. Conclusion Intra-amniotic injection of a modified-parenteral nutrient solution appears to be a promising therapy for reducing mortality among IUGR. These results provide an opportunity to develop new intra-amniotic nutritional strategies to reach the fetus by bypassing the placental insufficiency. PMID:29466434

  8. Antenatal corticosteroids trial in preterm births to increase neonatal survival in developing countries: study protocol

    Directory of Open Access Journals (Sweden)

    Althabe Fernando

    2012-09-01

    Full Text Available Abstract Background Preterm birth is a major cause of neonatal mortality, responsible for 28% of neonatal deaths overall. The administration of antenatal corticosteroids to women at high risk of preterm birth is a powerful perinatal intervention to reduce neonatal mortality in resource rich environments. The effect of antenatal steroids to reduce mortality and morbidity among preterm infants in hospital settings in developed countries with high utilization is well established, yet they are not routinely used in developing countries. The impact of increasing antenatal steroid use in hospital or community settings with low utilization rates and high infant mortality among premature infants due to lack of specialized services has not been well researched. There is currently no clear evidence about the safety of antenatal corticosteroid use for community-level births. Methods We hypothesize that a multi country, two-arm, parallel cluster randomized controlled trial to evaluate whether a multifaceted intervention to increase the use of antenatal corticosteroids, including components to improve the identification of pregnancies at high risk of preterm birth and providing and facilitating the appropriate use of steroids, will reduce neonatal mortality at 28 days of life in preterm newborns, compared with the standard delivery of care in selected populations of six countries. 102 clusters in Argentina, Guatemala, Kenya, India, Pakistan, and Zambia will be randomized, and around 60,000 women and newborns will be enrolled. Kits containing vials of dexamethasone, syringes, gloves, and instructions for administration will be distributed. Improving the identification of women at high risk of preterm birth will be done by (1 diffusing recommendations for antenatal corticosteroids use to health providers, (2 training health providers on identification of women at high risk of preterm birth, (3 providing reminders to health providers on the use of the kits, and

  9. Antenatal corticosteroids trial in preterm births to increase neonatal survival in developing countries: study protocol.

    Science.gov (United States)

    Althabe, Fernando; Belizán, José M; Mazzoni, Agustina; Berrueta, Mabel; Hemingway-Foday, Jay; Koso-Thomas, Marion; McClure, Elizabeth; Chomba, Elwyn; Garces, Ana; Goudar, Shivaprasad; Kodkany, Bhalchandra; Saleem, Sarah; Pasha, Omrana; Patel, Archana; Esamai, Fabian; Carlo, Waldemar A; Krebs, Nancy F; Derman, Richard J; Goldenberg, Robert L; Hibberd, Patricia; Liechty, Edward A; Wright, Linda L; Bergel, Eduardo F; Jobe, Alan H; Buekens, Pierre

    2012-09-19

    Preterm birth is a major cause of neonatal mortality, responsible for 28% of neonatal deaths overall. The administration of antenatal corticosteroids to women at high risk of preterm birth is a powerful perinatal intervention to reduce neonatal mortality in resource rich environments. The effect of antenatal steroids to reduce mortality and morbidity among preterm infants in hospital settings in developed countries with high utilization is well established, yet they are not routinely used in developing countries. The impact of increasing antenatal steroid use in hospital or community settings with low utilization rates and high infant mortality among premature infants due to lack of specialized services has not been well researched. There is currently no clear evidence about the safety of antenatal corticosteroid use for community-level births. We hypothesize that a multi country, two-arm, parallel cluster randomized controlled trial to evaluate whether a multifaceted intervention to increase the use of antenatal corticosteroids, including components to improve the identification of pregnancies at high risk of preterm birth and providing and facilitating the appropriate use of steroids, will reduce neonatal mortality at 28 days of life in preterm newborns, compared with the standard delivery of care in selected populations of six countries. 102 clusters in Argentina, Guatemala, Kenya, India, Pakistan, and Zambia will be randomized, and around 60,000 women and newborns will be enrolled. Kits containing vials of dexamethasone, syringes, gloves, and instructions for administration will be distributed. Improving the identification of women at high risk of preterm birth will be done by (1) diffusing recommendations for antenatal corticosteroids use to health providers, (2) training health providers on identification of women at high risk of preterm birth, (3) providing reminders to health providers on the use of the kits, and (4) using a color-coded tape to measure

  10. Urban Growth Causes Significant increase in Extreme Rainfall - A modelling study

    Science.gov (United States)

    Pathirana, Assela

    2010-05-01

    World's urban centers are growing rapidly causing the impact of extreme rainfall events felt much more severely due to relatively well unerstood phenomena like decreased infiltration and flow resistance. However, an increasing set of evidence (e.g. heavy rainfall event observed at Nerima, central part of Tokyo metropolitan area, on 21 July 1999) suggest that the extreme rainfall, the driving force itself increases as a result of the microclimatic changes due to urban growth. Urban heat islands(UHI) due to heat anomalies of urban sprawl act as virtual mountains resulting in a local atmosphere more conducive for heavy rainfall. In this study, we employ a popular mesoscale atmoshperic model to numerically simulate the UHI induced rainfall enhancement. Initial idealized experiments conducted under trophical atmospheric conditions indicated that the changes in landuse due to significant urban growth will indeed cause more intense rainfall events. This is largely due to increased convective breakup, causing a favourable situation for convective cloud systems. Five historical heavy rainfall events that caused floods in five urban centres (Dhaka, Mumbai, Colombo, Lyon and Taipei) were selected from historical records. Numerical simulations were setup to assertain what would be the amount of rainfall if the same large-scale atmospheric situations (forcings) occured under a hypothetical situation of doubled urbanization level these events. Significant increases (upto 50%) of extreme rainfall was indicated for many of the events. Under major assumptions, these simulations were used to estimate the anticipated changes in the Intensity-Duration-Frequency (IDF). The magnitude of the 30min event with 25 year return period increased by about 20 percent. Without considering any changes in the external forcing the urban growth alone could cause very significant increase in local rainfall.

  11. Cervical HSV-2 infection causes cervical remodeling and increases risk for ascending infection and preterm birth

    Science.gov (United States)

    McGee, Devin; Poncil, Sharra; Patterson, Amanda

    2017-01-01

    Preterm birth (PTB), or birth before 37 weeks gestation, is the leading cause of neonatal mortality worldwide. Cervical viral infections have been established as risk factors for PTB in women, although the mechanism leading to increased risk is unknown. Using a mouse model of pregnancy, we determined that intra-vaginal HSV2 infection caused increased rates of preterm birth following an intra-vaginal bacterial infection. HSV2 infection resulted in histological changes in the cervix mimicking cervical ripening, including significant collagen remodeling and increased hyaluronic acid synthesis. Viral infection also caused aberrant expression of estrogen and progesterone receptor in the cervical epithelium. Further analysis using human ectocervical cells demonstrated a role for Src kinase in virus-mediated changes in estrogen receptor and hyaluronic acid expression. In conclusion, HSV2 affects proteins involved in tissue hormone responsiveness, causes significant changes reminiscent of premature cervical ripening, and increases risk of preterm birth. Studies such as this improve our chances of identifying clinical interventions in the future. PMID:29190738

  12. Pancreatic Digestive Enzyme Blockade in the Intestine Increases Survival After Experimental Shock

    Science.gov (United States)

    DeLano, Frank A.; Hoyt, David B.; Schmid-Schönbein, Geert W.

    2015-01-01

    Shock, sepsis, and multiorgan failure are associated with inflammation, morbidity, and high mortality. The underlying pathophysiological mechanism is unknown, but evidence suggests that pancreatic enzymes in the intestinal lumen autodigest the intestine and generate systemic inflammation. Blocking these enzymes in the intestine reduces inflammation and multiorgan dysfunction. We investigated whether enzymatic blockade also reduces mortality after shock. Three rat shock models were used here: hemorrhagic shock, peritonitis shock induced by placement of cecal material into the peritoneum, and endotoxin shock. One hour after initiation of hemorrhagic, peritonitis, or endotoxin shock, animals were administered one of three different pancreatic enzyme inhibitors—6-amidino-2-naphtyl p-guanidinobenzoate di-methanesulfate, tranexamic acid, or aprotinin—into the lumen of the small intestine. In all forms of shock, blockade of digestive proteases with protease inhibitor attenuated entry of digestive enzymes into the wall of the intestine and subsequent autodigestion and morphological damage to the intestine, lung, and heart. Animals treated with protease inhibitors also survived in larger numbers than untreated controls over a period of 12 weeks. Surviving animals recovered completely and returned to normal weight within 14 days after shock. The results suggest that the active and concentrated digestive enzymes in the lumen of the intestine play a central role in shock and multi-organ failure, which can be treated with protease inhibitors that are currently available for use in the clinic. PMID:23345609

  13. Surgical fusion of early onset severe scoliosis increases survival in Rett syndrome: a cohort study.

    Science.gov (United States)

    Downs, Jenny; Torode, Ian; Wong, Kingsley; Ellaway, Carolyn; Elliott, Elizabeth J; Izatt, Maree T; Askin, Geoffrey N; Mcphee, Bruce I; Cundy, Peter; Leonard, Helen

    2016-06-01

    Scoliosis is a common comorbidity in Rett syndrome and spinal fusion may be recommended if severe. We investigated the impact of spinal fusion on survival and risk of severe lower respiratory tract infection in Rett syndrome. Data were ascertained from hospital medical records, the Australian Rett Syndrome Database, a longitudinal and population-based registry, and from the Australian Institute of Health and Welfare National Death Index database. Cox regression and generalized estimating equation models were used to estimate the effects of spinal surgery on survival and severe respiratory infection respectively in 140 females who developed severe scoliosis (Cobb angle ≥45°) before adulthood. After adjusting for mutation type and age of scoliosis onset, the rate of death was lower in the surgery group (hazard ratio [HR] 0.30, 95% confidence interval [CI] 0.12-0.74; p=0.009) compared to those without surgery. Rate of death was particularly reduced for those with early onset scoliosis (HR 0.17, 95% CI 0.06-0.52; p=0.002). There was some evidence to suggest that spinal fusion was associated with a reduction in risk of severe respiratory infection among those with early onset scoliosis (risk ratio 0.41, 95% CI 0.16-1.03; p=0.06). With appropriate cautions, spinal fusion confers an advantage to life expectancy in Rett syndrome. © 2015 Mac Keith Press.

  14. The abundant free-living amoeba, Acanthamoeba polyphaga, increases the survival of Campylobacter jejuni in milk and orange juice

    Directory of Open Access Journals (Sweden)

    Jenny Olofsson

    2015-09-01

    Full Text Available Background: Campylobacter jejuni is a common cause of human bacterial diarrhea in most parts of the world. Most C. jejuni infections are acquired from contaminated poultry, milk, and water. Due to health care costs and human suffering, it is important to identify all possible sources of infection. Unpasteurized milk has been associated with several outbreaks of C. jejuni infection. Campylobacter has been identified on fresh fruit, and other gastrointestinal pathogens such as Salmonella, E. coli O157:H7 and Cryptosporidium have been involved in fruit juice outbreaks. C. jejuni is sensitive to the acidic environment of fruit juice, but co-cultures with the amoeba, Acanthamoeba polyphaga, have previously been shown to protect C. jejuni at low pH. Methods: To study the influence of A. polyphaga on the survival of C. jejuni in milk and juice, the bacteria were incubated in the two products at room temperature and at 4°C with the following treatments: A C. jejuni preincubated with A. polyphaga before the addition of product, B C. jejuni mixed with A. polyphaga after the addition of product, and C C. jejuni in product without A. polyphaga. Bacterial survival was assessed by colony counts on blood agar plates. Results: Co-culture with A. polyphaga prolonged the C. jejuni survival both in milk and juice. The effect of co-culture was most pronounced in juice stored at room temperature. On the other hand, A. polyphaga did not have any effect on C. jejuni survival during pasteurization of milk or orange juice, indicating that this is a good method for eliminating C. jejuni in these products. Conclusion: Amoebae-associated C. jejuni in milk and juice might cause C. jejuni infections.

  15. Increased Subventricular Zone Radiation Dose Correlates With Survival in Glioblastoma Patients After Gross Total Resection

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Linda [Department of Neurosurgery, The Johns Hopkins University, Baltimore, Maryland (United States); Duke University School of Medicine, Durham, North Carolina (United States); Guerrero-Cazares, Hugo [Department of Neurosurgery, The Johns Hopkins University, Baltimore, Maryland (United States); Ye, Xiaobu [Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University, Baltimore, Maryland (United States); Ford, Eric [Department of Radiation Oncology, University of Washington, Seattle, Washington (United States); McNutt, Todd; Kleinberg, Lawrence [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University, Baltimore, Maryland (United States); Lim, Michael; Chaichana, Kaisorn [Department of Neurosurgery, The Johns Hopkins University, Baltimore, Maryland (United States); Quinones-Hinojosa, Alfredo, E-mail: aquinon2@jhmi.edu [Department of Neurosurgery, The Johns Hopkins University, Baltimore, Maryland (United States); Redmond, Kristin, E-mail: kjanson3@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University, Baltimore, Maryland (United States)

    2013-07-15

    Purpose: Neural progenitor cells in the subventricular zone (SVZ) have a controversial role in glioblastoma multiforme (GBM) as potential tumor-initiating cells. The purpose of this study was to examine the relationship between radiation dose to the SVZ and survival in GBM patients. Methods and Materials: The study included 116 patients with primary GBM treated at the Johns Hopkins Hospital between 2006 and 2009. All patients underwent surgical resection followed by adjuvant radiation therapy with intensity modulated radiation therapy (60 Gy/30 fractions) and concomitant temozolomide. Ipsilateral, contralateral, and bilateral SVZs were contoured on treatment plans by use of coregistered magnetic resonance imaging and computed tomography. Multivariate Cox regression was used to examine the relationship between mean SVZ dose and progression-free survival (PFS), as well as overall survival (OS). Age, Karnofsky Performance Status score, and extent of resection were used as covariates. The median age was 58 years (range, 29-80 years). Results: Of the patients, 12% underwent biopsy, 53% had subtotal resection (STR), and 35% had gross total resection (GTR). The Karnofsky Performance Status score was less than 90 in 54 patients and was 90 or greater in 62 patients. The median ipsilateral, contralateral, and bilateral mean SVZ doses were 48.7 Gy, 34.4 Gy, and 41.5 Gy, respectively. Among patients who underwent GTR, a mean ipsilateral SVZ dose of 40 Gy or greater was associated with a significantly improved PFS compared with patients who received less than 40 Gy (15.1 months vs 10.3 months; P=.028; hazard ratio, 0.385 [95% confidence interval, 0.165-0.901]) but not in patients undergoing STR or biopsy. The subgroup of GTR patients who received an ipsilateral dose of 40 Gy or greater also had a significantly improved OS (17.5 months vs 15.6 months; P=.027; hazard ratio, 0.385 [95% confidence interval, 0.165-0.895]). No association was found between SVZ radiation dose and PFS

  16. Increased survival rate by local release of diclofenac in a murine model of recurrent oral carcinoma

    Directory of Open Access Journals (Sweden)

    Will OM

    2016-10-01

    Full Text Available Olga Maria Will,1,* Nicolai Purcz,2,* Athena Chalaris,3 Carola Heneweer,4,5 Susann Boretius,1 Larissa Purcz,2 Lila Nikkola,6 Nureddin Ashammakhi,6 Holger Kalthoff,7 Claus-Christian Glüer,1 Jörg Wiltfang,2 Yahya Açil,2 Sanjay Tiwari1 1Section Biomedical Imaging, Clinic for Radiology and Neuroradiology, MOIN CC, 2Department of Oral and Maxillofacial Surgery, University Hospital Schleswig-Holstein, 3Institute of Biochemistry, Christian-Albrechts-Universität zu Kiel, 4Clinic for Radiology and Neuroradiology, University Hospital Schleswig-Holstein, Kiel, 5Institute for Diagnostic and Interventional Radiology, University Hospital Cologne, Cologne, Germany; 6Department of Biomedical Engineering, Tampere University of Technology, Tampere, Finland; 7Institute for Experimental Cancer Research, University Hospital Schleswig-Holstein, Kiel, Germany *These authors contributed equally to this work Abstract: Despite aggressive treatment with radiation and combination chemotherapy following tumor resection, the 5-year survival rate for patients with head and neck cancer is at best only 50%. In this study, we examined the therapeutic potential of localized release of diclofenac from electrospun nanofibers generated from poly(d,l-lactide-co-glycolide polymer. Diclofenac was chosen since anti-inflammatory agents that inhibit cyclooxygenase have shown great potential in their ability to directly inhibit tumor growth as well as suppress inflammation-mediated tumor growth. A mouse resection model of oral carcinoma was developed by establishing tumor growth in the oral cavity by ultrasound-guided injection of 1 million SCC-9 cells in the floor of the mouth. Following resection, mice were allocated into four groups with the following treatment: 1 no treatment, 2 implanted scaffolds without diclofenac, 3 implanted scaffolds loaded with diclofenac, and 4 diclofenac given orally. Small animal ultrasound and magnetic resonance imaging were utilized for longitudinal

  17. Ilex paraguariensis Extract Increases Lifespan and Protects Against the Toxic Effects Caused by Paraquat in Caenorhabditis elegans.

    Science.gov (United States)

    Lima, Maria E; Colpo, Ana C; Salgueiro, Willian G; Sardinha, Guilherme E; Avila, Daiana S; Folmer, Vanderlei

    2014-09-26

    Recent studies have shown that phenolic compounds present in yerba mate have antioxidant defense properties. To verify whether Ilex paraguariensis extracts are capable of increasing the lifespan of an organism, we have used the free-living nematode Caenorhabditis elegans. Notably, this is the first study that analyzes the effects of the extracts of yerba mate obtained from an extraction method that mimics the manner that the plant is consumed by the population by using a live organism. Yerba mate was purchased from commercial markets from Argentina, Brazil, and Uruguay. Ilex paraguariensis extracts significantly increased the life span of C. elegans. Moreover, the extracts reduced the ROS levels per se, and protected from the reduced survival and reproduction rate induced by paraquat exposure. Considering molecular aspects, we observed that the worms pretreated with the extracts depicted higher translocation of the transcription factor DAF-16::GFP to the nucleus. However, there was no increase in the levels of the DAF-16 target genes, SOD-3 and catalase. Our results suggest that the increase of lifespan caused by the different extracts is associated to the antioxidant potential of yerba mate, however this effect is not completely mediated by daf-16.

  18. Survival from Traumatic Injury Does Not End at Hospital Discharge: Hospital-Acquired Infections Increase Post-Discharge Mortality.

    Science.gov (United States)

    Dhiman, Nitasha; Rimal, Ram C; Hamill, Mark; Love, Katie M; Lollar, Daniel; Collier, Bryan

    2017-07-01

    Hospital-acquired infections (HAI) in trauma patients increase inpatient morbidity and mortality. However, their impact on long-term mortality is not well understood. A retrospective trauma registry analysis of all patients admitted to an academic level I trauma center between July 1, 2008 and December 31, 2012 was performed. Patients included survived to discharge and were 18 years of age or older. Age, gender, Injury Severity Score (ISS), ventilator use, history of chronic obstructive pulmonary disease (COPD), and HAI were reviewed. Name, social security number, and date of birth were used to extract National Death Index data from 2008-2013 for an outcome of mortality after discharge, time to death, and cause of death. Unadjusted logistic regression was performed. Multiple logistic regression was used to adjust for patient and injury characteristics and to determine odds of mortality in the post-discharge period. A total of 8,275 patients met inclusion criteria; 65.4% were male and the median age was 47. The mean ISS was 11 ± 8.9. Nine hundred seventeen patients (11.1%) died after discharge; 4.8% of patients had hospital-acquired pneumonia (HAP) and 4.2% had a urinary tract infection (UTI). The unadjusted odds ratio (OR) of mortality after discharge in patients who had pneumonia and UTI were 1.77 (1.35, 2.31, p mortality after discharge remained significant for pneumonia (OR = 1.57 (1.09, 2.23), p = 0.013) but not for UTI (OR = 1.25 (0.93, 1.68), p = 0.147). The top causes of death after discharge in patients with HAP were COPD (11.4%) and falls (7.1%). Trauma patients with HAP have higher mortality after hospital discharge. Prevention strategies for HAP including pulmonary toilet, early mobility, pain control, and early extubation must be a priority. Unfortunately, patients who develop pneumonia may have a decreased reserve, or ability to recover from their traumatic injuries and HAI. Further characterization of HAP and its subsequent

  19. Enhanced malignant transformation is accompanied by increased survival recovery after ionizing radiation in Chinese hamster embryo fibroblasts

    International Nuclear Information System (INIS)

    Boothman, D.A.

    1994-01-01

    Transformed Chinese hamster embryo fibroblasts (CHEF), which gradually increase in tumor-forming ability in nude mice, were isolated from normal diploid CHEF/18 cells. Transformed CHEF cells (i.e., T30-4 > 21-2M3 > 21-2 > normal CHEF/18) showed gradual increases in potentially lethal damage (PLD) survival recovery. β-Lapachone and camptothecin, modulators of topoisomerase I (Topo I) activity, not only prevented survival recovery in normal as well as in tumor cells, but enhanced unscheduled DNA synthesis. These seemingly conflicting results are due to the fact that Topo I activity can be modulated by inhibitors to convert single-stranded DNA lesions into double-stranded breaks. Increases in unscheduled DNA synthesis may result from a continual supply of free ends, on which DNA repair processes may act. Altering Topo I activity with modulators appears to increase X-ray lethality via a DNA lesion modification suicide pathway. Cells down-regulate Topo I immediately after ionizing radiation to prevent Topo I-mediated lesion modification and to enhance survival recovery. 16 refs., 3 figs., 1 tab

  20. Continuous Quality Improvement Efforts Increase Survival with Favorable Neurologic Outcome after Out-of-hospital Cardiac Arrest.

    Science.gov (United States)

    Sporer, Karl; Jacobs, Michael; Derevin, Leo; Duval, Sue; Pointer, James

    2017-01-01

    To assess system-wide implementation of specific therapies focused on perfusion during cardiopulmonary resuscitation (CPR) and cerebral recovery after Return of Spontaneous Circulation (ROSC). Before and after retrospective analysis of an out-of-hospital cardiac arrest database. Implementation trial in the urban/suburban community of Alameda County, California, USA, population 1.6 million, from November 2009-December 2012. Adult patients with non-traumatic out-of-hospital cardiac arrest (OHCA) who received CPR and/or defibrillation. The impedance threshold device was used throughout this study and there was an increased use of mechanical CPR (mCPR) and in-hospital therapeutic hypothermia (HTH). Rates of ROSC, survival to hospital discharge and Cerebral Performance Category (CPC) scores were compared using univariate and multivariable analyses. A total of 2,926 adult non-traumatic patients with OHCA received CPR during the study period. From 2009-2011 to 2012, there was an increase in ROSC from 29.0% to 34.4% (p = 0.003) and a non-significant increase in hospital discharge from 10.2% to 12.0% (p = 0.16). There was a 76% relative increase in survival with favorable neurologic function between the two periods, as determined by CPC ≤ 2, from 4.5% to 7.9% (unadjusted OR = 1.80; CI = 1.31, 2.48; p improved survival by 74% with favorable neurologic function following OHCA.

  1. Mechanism and preclinical prevention of increased breast cancer risk caused by pregnancy.

    Science.gov (United States)

    Haricharan, Svasti; Dong, Jie; Hein, Sarah; Reddy, Jay P; Du, Zhijun; Toneff, Michael; Holloway, Kimberly; Hilsenbeck, Susan G; Huang, Shixia; Atkinson, Rachel; Woodward, Wendy; Jindal, Sonali; Borges, Virginia F; Gutierrez, Carolina; Zhang, Hong; Schedin, Pepper J; Osborne, C Kent; Tweardy, David J; Li, Yi

    2013-12-31

    While a first pregnancy before age 22 lowers breast cancer risk, a pregnancy after age 35 significantly increases life-long breast cancer risk. Pregnancy causes several changes to the normal breast that raise barriers to transformation, but how pregnancy can also increase cancer risk remains unclear. We show in mice that pregnancy has different effects on the few early lesions that have already developed in the otherwise normal breast-it causes apoptosis evasion and accelerated progression to cancer. The apoptosis evasion is due to the normally tightly controlled STAT5 signaling going astray-these precancerous cells activate STAT5 in response to pregnancy/lactation hormones and maintain STAT5 activation even during involution, thus preventing the apoptosis normally initiated by oncoprotein and involution. Short-term anti-STAT5 treatment of lactation-completed mice bearing early lesions eliminates the increased risk after a pregnancy. This chemoprevention strategy has important implications for preventing increased human breast cancer risk caused by pregnancy. DOI: http://dx.doi.org/10.7554/eLife.00996.001.

  2. Increasing Survivability on the Battlefield: Hemorrhage Control and the Joint Theater Trauma System

    Science.gov (United States)

    2010-04-01

    QuikCiot is a granular zeolite mineral that is composed of oxides of silicon, aluminum , sodium, magnesium and quartz.Z9 It is manufactured in a...with minimal effective pressure applied, a tourniquet may cause significant pain and should be managed with intravenous or intramuscular pain

  3. Sexual conflict and ecology: Species composition and male density interact to reduce male mating harassment and increase female survival.

    Science.gov (United States)

    Gomez-Llano, Miguel A; Bensch, Hanna M; Svensson, Erik I

    2018-02-21

    Sexual conflict is a pervasive evolutionary force that can reduce female fitness. Experimental evolution studies in the laboratory might overestimate the importance of sexual conflict because the ecological conditions in such settings typically include only a single species. Here, we experimentally manipulated conspecific male density (high or low) and species composition (sympatric or allopatric) to investigate how ecological conditions affect female survival in a sexually dimorphic insect, the banded demoiselle (Calopteryx splendens). Female survival was strongly influenced by an interaction between male density and species composition. Specifically, at low conspecific male density, female survival increased in the presence of heterospecific males (C. virgo). Behavioral mating experiments showed that interspecific interference competition reduced conspecific male mating success with large females. These findings suggest that reproductive interference competition between con- and heterospecific males might indirectly facilitate female survival by reducing mating harassment from conspecific males. Hence, interspecific competitors can show contrasting effects on the two sexes thereby influencing sexual conflict dynamics. Our results call for incorporation of more ecological realism in sexual conflict research, particularly how local community context and reproductive interference competition between heterospecific males can affect female fitness. © 2018 The Author(s). Evolution published by Wiley Periodicals, Inc. on behalf of The Society for the Study of Evolution.

  4. Severe extremity amputations in surviving Palestinian civilians caused by explosives fired from drones during the Gaza War.

    Science.gov (United States)

    Heszlein-Lossius, Hanne; Al-Borno, Yahya; Shaqoura, Samar; Skaik, Nashwa; Giil, Lasse Melvær; Gilbert, Mads

    2018-02-21

    operations (p=0·0001). Weapons fired on the Gaza Strip from Israeli drones caused severe injuries in surviving Palestinian civilians. Drone-fired missiles resulted in major amputations in almost all victims who had limb losses. Substantially more severe injuries were inflicted by the drone-launched explosives than by other weapons used during the Gaza War. Traumatic amputations caused by drones were often immediately complete. One limitation of our study is that it does not elucidate injury patterns in victims with fatal injuries. None. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Adrenocorticotrophic hormone causes an increase in cortisol, but not parathyroid hormone, in dogs.

    Science.gov (United States)

    Kilpatrick, Scott; Gow, Adam G; Evans, Helen; Mellanby, Richard J

    2015-02-01

    Dogs with spontaneous disorders of glucocorticoid production often have marked disturbances in calcium homeostasis. For example, hypercalcaemia is frequently observed in dogs with hypoadrenocorticism and secondary hyperparathyroidism is a common feature of canine hyperadrenocorticism. The mechanism(s) by which glucocorticoids modulate calcium homeostasis in dogs remains ill-defined. The hypothesis of this study is that a marked increase in serum cortisol concentrations would lead to an immediate negative calcium balance state which would drive a compensatory increase in parathyroid hormone (PTH) concentrations. This hypothesis was investigated by measuring serum cortisol and plasma PTH concentration in 19 dogs before and after administration of adrenocorticotrophic (ACTH) hormone. Post ACTH administration, there was a significant increase in serum cortisol, but not PTH, concentrations. The results of this study do not support the hypothesis that an increase in endogenous glucocorticoids influences calcium balance sufficiently to cause an immediate, compensatory increase in parathyroid hormone concentration. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Increased level of hemoglobin 1 enhances survival of hypoxic stress and promotes early growth in Arabidopsis thaliana

    OpenAIRE

    Hunt, P. W.; Klok, E. J.; Trevaskis, B.; Watts, R. A.; Ellis, M. H.; Peacock, W. J.; Dennis, E. S.

    2002-01-01

    Overexpression of a class 1 Hb (GLB1) protects Arabidopsis thaliana plants from the effects of severe hypoxia. Overexpression of the bifunctional symbiotic Hb (GLB1S) from Parasponia andersonii in A. thaliana also increases survival after hypoxia. Plants overexpressing the Hb 1 protein, mutated to have a low oxygen affinity, are as susceptible to hypoxia as WT plants, suggesting that the protection against hypoxia depends on the ability of the Hb to bind ligands, such as oxygen, with high aff...

  7. Increased Expression of the GLUT-1 Gene is Associated With Worse Overall Survival in Resected Pancreatic Adenocarcinoma

    Science.gov (United States)

    Davis-Yadley, Ashley H.; Abbott, Andrea M.; Pimiento, Jose M.; Chen, Dung-Tsa; Malafa, Mokenge P.

    2015-01-01

    Objectives There is currently no reliable method to predict the risk of relapse after curative resection of early-stage pancreatic adenocarcinoma. Increased glucose metabolism observed on 18F-fluorodeoxyglucose positron emission tomography (PET) by malignant cells, the Warburg effect, is a well-known characteristic of the malignant phenotype. We investigated the role of glucose transporter type 1 (GLUT-1) gene expression, a glucose cell plasma membrane transporter, in early-stage pancreatic cancer. Methods Associations between GLUT-1 gene expression with PET maximum standardized uptake values (SUVmax) and histologic grade were investigated in early-stage pancreatic adenocarcinoma patients. Multivariate analysis was conducted to determine predictors of prognosis. Cox proportional hazards model was used for survival analysis. Results Sixty-three patients had GLUT-1 gene analysis performed, and 50 patients had both GLUT-1 analysis and PET scan. Patients with high GLUT-1 gene expression had a decreased overall survival by univariate analysis using Cox proportional hazards model (HR=2.82, p=0.001) and remained significant on multivariate analysis (HR=2.54, p=0.03). There was no correlation of GLUT-1 gene expression with histologic grade or PET SUVmax. Conclusion Increased GLUT-1 gene expression was associated with a decreased overall survival in pancreatic adenocarcinoma. This supports increased GLUT-1 gene expression as a potential prognostic marker in resected pancreatic adenocarcinoma. PMID:26692443

  8. Honey bee (Apis mellifera) drones survive oxidative stress due to increased tolerance instead of avoidance or repair of oxidative damage.

    Science.gov (United States)

    Li-Byarlay, Hongmei; Huang, Ming Hua; Simone-Finstrom, Michael; Strand, Micheline K; Tarpy, David R; Rueppell, Olav

    2016-10-01

    Oxidative stress can lead to premature aging symptoms and cause acute mortality at higher doses in a range of organisms. Oxidative stress resistance and longevity are mechanistically and phenotypically linked; considerable variation in oxidative stress resistance exists among and within species and typically covaries with life expectancy. However, it is unclear whether stress-resistant, long-lived individuals avoid, repair, or tolerate molecular damage to survive longer than others. The honey bee (Apis mellifera L.) is an emerging model system that is well-suited to address this question. Furthermore, this species is the most economically important pollinator, whose health may be compromised by pesticide exposure, including oxidative stressors. Here, we develop a protocol for inducing oxidative stress in honey bee males (drones) via Paraquat injection. After injection, individuals from different colony sources were kept in common social conditions to monitor their survival compared to saline-injected controls. Oxidative stress was measured in susceptible and resistant individuals. Paraquat drastically reduced survival but individuals varied in their resistance to treatment within and among colony sources. Longer-lived individuals exhibited higher levels of lipid peroxidation than individuals dying early. In contrast, the level of protein carbonylation was not significantly different between the two groups. This first study of oxidative stress in male honey bees suggests that survival of an acute oxidative stressor is due to tolerance, not prevention or repair, of oxidative damage to lipids. It also demonstrates colony differences in oxidative stress resistance that might be useful for breeding stress-resistant honey bees. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Pulmonary exposure to particles during pregnancy causes increased neonatal asthma susceptibility

    DEFF Research Database (Denmark)

    Fedulov, Alexey V; Leme, Adriana; Yang, Zhiping

    2008-01-01

    Maternal immune responses can promote allergy development in offspring, as shown in a model of increased susceptibility to asthma in babies of ovalbumin (OVA)-sensitized and -challenged mother mice. We investigated whether inflammatory responses to air pollution particles (diesel exhaust particles...... exposure to both "inert" TiO(2) and DEP caused increased asthma susceptibility in offspring. We conclude that (1) pregnancy enhances lung inflammatory responses to otherwise relatively innocuous inert particles; and (2) exposures of nonallergic pregnant females to inert or toxic environmental air particles...

  10. Cancer causes increased mortality and is associated with altered apoptosis in murine sepsis.

    Science.gov (United States)

    Fox, Amy C; Robertson, Charles M; Belt, Brian; Clark, Andrew T; Chang, Katherine C; Leathersich, Ann M; Dominguez, Jessica A; Perrone, Erin E; Dunne, W Michael; Hotchkiss, Richard S; Buchman, Timothy G; Linehan, David C; Coopersmith, Craig M

    2010-03-01

    Whereas most septic patients have an underlying comorbidity, most animal models of sepsis use mice that were healthy before the onset of infection. Malignancy is the most common comorbidity associated with sepsis. The purpose of this study was to determine whether mice with cancer have a different response to sepsis than healthy animals. Prospective, randomized controlled study. Animal laboratory in a university medical center. C57Bl/6 mice. Animals received a subcutaneous injection of either 250,000 cells of the transplantable pancreatic adenocarcinoma cell line Pan02 (cancer) or phosphate-buffered saline (healthy). Three weeks later, mice given Pan02 cells had reproducible, nonmetastatic tumors. Both groups of mice then underwent intratracheal injection of either Pseudomonas aeruginosa (septic) or 0.9% NaCl (sham). Animals were killed 24 hrs postoperatively or followed-up 7 days for survival. Mice with cancer and healthy mice appeared similar when subjected to sham operation, although cancer animals had lower levels of T- and B-lymphocyte apoptosis. Septic mice with cancer had increased mortality compared to previously healthy septic mice subjected to the identical injury (52% vs. 28%; p = .04). This was associated with increased bacteremia but no difference in local pulmonary infection. Septic mice with cancer also had increased intestinal epithelial apoptosis. Although sepsis induced an increase in T- and B-lymphocyte apoptosis in all animals, septic mice with cancer had decreased T- and B-lymphocyte apoptosis compared to previously healthy septic mice. Serum and pulmonary cytokines, lung histology, complete blood counts, and intestinal proliferation were similar between septic mice with cancer and previously healthy septic mice. When subjected to the same septic insult, mice with cancer have increased mortality compared to previously healthy animals. Decreased systemic bacterial clearance and alterations in intestinal epithelial and lymphocyte apoptosis may

  11. Aging causes collateral rarefaction and increased severity of ischemic injury in multiple tissues

    Science.gov (United States)

    Faber, James E.; Zhang, Hua; Lassance-Soares, Roberta M.; Prabhakar, Pranay; Najafi, Amir H.; Burnett, Mary Susan; Epstein, Stephen E.

    2011-01-01

    Objective Aging is a major risk factor for increased ischemic tissue injury. Whether collateral rarefaction and impaired remodeling contribute to this is unknown. We quantified the number and diameter of native collaterals, and their remodeling in 3-, 16-, 24-, and 31-months-old mice. Methods and Results Aging caused an “age-dose-dependent” greater drop in perfusion immediately after femoral artery ligation, followed by a diminished recovery of flow and increase in tissue injury. These effects were associated with a decline in collateral number, diameter and remodeling. Angiogenesis was also impaired. Mechanistically, these changes were not accompanied by reduced recruitment of T-cells or macrophages to remodeling collaterals. However, eNOS signaling was dysfunctional, as indicated by increased protein nitrosylation and less phosphorylated eNOS and VASP in collateral wall cells. The cerebral circulation exhibited a similar age-dose-dependent loss of collateral number and diameter and increased tortuosity, resulting in an increase in collateral resistance and infarct volume (e.g., 6- and 3-fold, respectively, in 24-months-old mice) after artery occlusion. This was not associated with rarefaction of similarly-sized arterioles. Collateral remodeling was also reduced. Conclusions Our findings demonstrate that aging causes rarefaction and insufficiency of the collateral circulation in multiple tissues, resulting in more severe ischemic tissue injury. PMID:21617137

  12. Honokiol Increases CD4+ T Cell Activation and Decreases TNF but Fails to Improve Survival Following Sepsis.

    Science.gov (United States)

    Klingensmith, Nathan J; Chen, Ching-Wen; Liang, Zhe; Burd, Eileen M; Farris, Alton B; Arbiser, Jack L; Ford, Mandy L; Coopersmith, Craig M

    2017-10-11

    Honokiol is a biphenolic isolate extracted from the bark of the magnolia tree that has been used in traditional Chinese and Japanese medicine, and has more recently been investigated for its anti-inflammatory and anti-bacterial properties. Honokiol has previously been demonstrated to improve survival in sepsis models that have rapid 100% lethality. The purpose of this study was to determine the impact of Honokiol on the host response in a model of sepsis that more closely approximates human disease. Male and female C57BL/6 mice underwent cecal ligation and puncture (CLP) to induce polymicrobial intraabdominal sepsis. Mice were then randomized to receive an injection of either Honokiol (120 mg/kg/day) or vehicle and were sacrificed after 24 hours for functional studies or followed 7 days for survival. Honokiol treatment after sepsis increased the frequency of CD4 T cells and increased activation of CD4 T cells as measured by the activation marker CD69. Honokiol also increased splenic dendritic cells. Honokiol simultaneously decreased frequency and number of CD8 T cells. Honokiol decreased systemic TNF without impacting other systemic cytokines. Honokiol did not have a detectable effect on kidney function, lung physiology, liver function or intestinal integrity. In contrast to prior studies of Honokiol in a lethal model of sepsis, Honokiol did not alter survival at seven days (70% mortality for Honokiol vs. 60% mortality for vehicle). Honokiol is thus effective in modulating the host immune response and inflammation following a clinically relevant model of sepsis but is not sufficient to alter survival.

  13. Supplementation with turmeric residue increased survival of the Chinese soft-shelled turtle (Pelodiscus sinensis) under high ambient temperatures.

    Science.gov (United States)

    Chen, Yong; Zhang, Yi-Fan; Qian, Hao-Cheng; Wang, Jing-Liang; Chen, Zhe; Ordovas, Jose M; Lai, Chao-Qiang; Shen, Li-Rong

    Turmeric residue (TR), containing residual levels of curcumin, is a solid by-product waste generated after the extraction and separation of curcumin from turmeric root. A feeding trial was conducted to evaluate the effects of TR on the survival of Chinese soft-shelled turtles (SSTs), Pelodiscus sinensis, under a high ambient temperature. A total of 320 female SSTs were assigned randomly to two diets: basal diet (the control group, n=160) and an interventional diet supplemented with 10% TR (the TR group, n=160). Our results demonstrated that supplementation of TR increased the SST survival rate by 135.5%, and superoxide dismutase (SOD) activity of SST liver by 112.8%, and decreased the malondialdehyde (MDA) content of SST liver by 36.4%, compared to the control group. The skin of the SST fed TR showed a golden color. High-performance liquid chromatography (HPLC) analysis indicated that the concentrations of curcumin in TR and the skin of the SST fed TR were (1.69±0.30) and (0.14±0.03) μg/g, respectively. Our observation suggests that supplementation of TR increased the survival rate of SST under high ambient temperatures. We speculated that the increased survival rate and tolerance at the high ambient temperature were associated with the anti-oxidation activity of curcumin from TR. Moreover, curcumin in TR could be deposited in SST skin, which made it more favored in the market of China. Our findings provide new knowledge and evidence to effectively reuse TR as a feed additive in animal and aquatic farming.

  14. Increased p53 immunopositivity in anaplastic medulloblastoma and supratentorial PNET is not caused by JC virus

    International Nuclear Information System (INIS)

    Eberhart, Charles G; Chaudhry, Aneeka; Daniel, Richard W; Khaki, Leila; Shah, Keerti V; Gravitt, Patti E

    2005-01-01

    p53 mutations are relatively uncommon in medulloblastoma, but abnormalities in this cell cycle pathway have been associated with anaplasia and worse clinical outcomes. We correlated p53 protein expression with pathological subtype and clinical outcome in 75 embryonal brain tumors. The presence of JC virus, which results in p53 protein accumulation, was also examined. p53 protein levels were evaluated semi-quantitatively in 64 medulloblastomas, 3 atypical teratoid rhabdoid tumors (ATRT), and 8 supratentorial primitive neuroectodermal tumors (sPNET) using immunohistochemistry. JC viral sequences were analyzed in DNA extracted from 33 frozen medulloblastoma and PNET samples using quantitative polymerase chain reaction. p53 expression was detected in 18% of non-anaplastic medulloblastomas, 45% of anaplastic medulloblastomas, 67% of ATRT, and 88% of sPNET. The increased p53 immunoreactivity in anaplastic medulloblastoma, ATRT, and sPNET was statistically significant. Log rank analysis of clinical outcome revealed significantly shorter survival in patients with p53 immunopositive embryonal tumors. No JC virus was identified in the embryonal brain tumor samples, while an endogenous human retrovirus (ERV-3) was readily detected. Immunoreactivity for p53 protein is more common in anaplastic medulloblastomas, ATRT and sPNET than in non-anaplastic tumors, and is associated with worse clinical outcomes. However, JC virus infection is not responsible for increased levels of p53 protein

  15. Collapse of a historic oyster fishery: diagnosing causes and identifying paths toward increased resilience

    Directory of Open Access Journals (Sweden)

    Edward V. Camp

    2015-09-01

    Full Text Available Diagnosing causal factors of change at the ecosystem level is challenging because multiple drivers often interact at various spatial and temporal scales. We employ an integrated natural and social science approach to assess potential mechanisms leading to the collapse of an estuarine social-ecological system, and recommend future paths to increased system resilience. Our case study is the collapse of the eastern oyster (Crassostrea virginica fishery in Apalachicola Bay, Florida, USA, and the associated impacts on local resource dependent communities. The oyster fishery collapse is the most recent in a series of environmental stressors to this region, which have included hurricanes and tropical storms, drought, and the Deepwater Horizon oil spill. We found it likely that the oyster collapse was not related to contamination from the recent oil spill, but rather to factors affecting oyster recruitment and survival, which may have been mediated by both human, e.g., fishing-related habitat alteration, and environmental, e.g., increased natural mortality from predators and disease, factors. The relative impact of each of these factors is likely to increase in the future because of changing climate and increased demand for fishery, water, and petroleum resources. Successful restoration and persistence of a viable oyster fishery will depend on: (1 implementation of some minimal best management practices, e.g., extensive habitat restoration via shell addition, and some spatial closures to harvest, (2 improving environmental knowledge and promoting episodic learning through enhanced monitoring and experimental management, and (3 continued community engagement necessary to produce adaptable governance suitable to responding to future unexpected challenges.

  16. [Multi-profile analysis of survival rate and cause of death in patients with non-Hodgkin's lymphoma].

    Science.gov (United States)

    Broun, G A; Babicheva, S Sh; Eremina, G N; Sal'nikova, M M; Smagliĭ, N P; Spektor, M I

    1992-01-01

    A relationship has been established between the survival rate of 378 patients who had died of non-Hodgkin's lymphoma (NHL) and their sex, age, ABO- and Rh-factors of the blood, primary focus of the tumor lesion, morphological variant, diagnostic period duration, and the treatment intensity. A higher incidence rate and a higher mean survival were recorded in 222 males, as compared to 156 females. Favourable and unfavourable for survival age interval has been distinguished for NHL disease. Patients with Rh+ showed a higher survival rate, although the incidence rate among Rh+ and Rh- subjects was similar. Prognostically favourable and unfavourable sites of the primary tumor and morphological variants of NHL were specified. The time spent for detailed verification of the diagnosis has been justified, and the presence of a direct proportional relationship between the intensity of the treatment and the mean survival of patients with varying forms of NHL has been proved.

  17. Increased all-cause mortality with use of psychotropic medication in dementia patients and controls

    DEFF Research Database (Denmark)

    Jennum, Poul; Baandrup, Lone; Ibsen, Rikke

    2015-01-01

    We aimed to evaluate all-cause mortality of middle-aged and elderly subjects diagnosed with dementia and treated with psychotropic drugs as compared with controls subjects. Using data from the Danish National Patient Registry, n=26,821 adults with a diagnosis of dementia were included. They were...... compared with 44,286 control subjects with a minimum follow-up of four years and matched on age, gender, marital status, and community location. Information about psychotropic medication use (benzodiazepines, antidepressants, antipsychotics) was obtained from the Danish Medicinal Product Statistics. All......-cause mortality was higher in patients with dementia as compared to control subjects. Mortality hazard ratios were increased for subjects prescribed serotonergic antidepressant drugs (respectively, HR=1.355 (SD=0.023), P=0.001 in patients; HR=1.808 (0.033), P

  18. Progress to extinction: increased specialisation causes the demise of animal clades

    Science.gov (United States)

    Raia, P.; Carotenuto, F.; Mondanaro, A.; Castiglione, S.; Passaro, F.; Saggese, F.; Melchionna, M.; Serio, C.; Alessio, L.; Silvestro, D.; Fortelius, M.

    2016-08-01

    Animal clades tend to follow a predictable path of waxing and waning during their existence, regardless of their total species richness or geographic coverage. Clades begin small and undifferentiated, then expand to a peak in diversity and range, only to shift into a rarely broken decline towards extinction. While this trajectory is now well documented and broadly recognised, the reasons underlying it remain obscure. In particular, it is unknown why clade extinction is universal and occurs with such surprising regularity. Current explanations for paleontological extinctions call on the growing costs of biological interactions, geological accidents, evolutionary traps, and mass extinctions. While these are effective causes of extinction, they mainly apply to species, not clades. Although mass extinctions is the undeniable cause for the demise of a sizeable number of major taxa, we show here that clades escaping them go extinct because of the widespread tendency of evolution to produce increasingly specialised, sympatric, and geographically restricted species over time.

  19. Lovastatin delays infection and increases survival rates in AG129 mice infected with dengue virus serotype 2.

    Directory of Open Access Journals (Sweden)

    Marlen Martinez-Gutierrez

    Full Text Available BACKGROUND: It has been reported that treatment of DENV-infected cultures with Lovastatin (LOV, can affect viral assembly. The objective of this study was to evaluate the effect of LOV on the survival rate and viremia levels of DENV-2-infected AG129 mice. METHODOLOGY/PRINCIPAL FINDINGS: Mice were inoculated with 1 × 10(6 plaque-forming units (PFU/ml of DENV-2 and treated with LOV (200 mg/kg/day. Pre-treatment with one or three doses of LOV increased the survival rate compared to untreated mice (7.3 and 7.1 days, respectively, compared to 4.8 days. Viremia levels also decreased by 21.8% compared to untreated mice, but only in the group administered three doses prior to inoculation. When LOV was administered after viral inoculation, the survival rate increased (7.3 days in the group treated at 24 hpi, 6.8 days in the group treated at 48 hpi and 6.5 days in the group treated with two doses compared to the untreated group (4.8 days. Interestingly, the serum viral titer increased by 24.6% in mice treated at 48 hpi with a single dose of LOV and by 21.7% in mice treated with two doses (at 24 and 48 hpi of LOV compared to untreated mice. Finally histopathological changes in the liver and spleen in infected and untreated mice included massive extramedullary erythropoiesis foci and inflammatory filtration, and these characteristics were decreased or absent in LOV-treated mice. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the effect of LOV on viremia depends on the timing of treatment and on the number of doses administered. We observed a significant increase in the survival rate in both schemes due to a delay in the progression of the disease. However, the results obtained in the post-treatment scheme must be handled carefully because this treatment scheme increases viremia and we do not know how this increase could affect disease progression in humans.

  20. Declines in Malaria Burden and All-Cause Child Mortality following Increases in Control Interventions in Senegal, 2005-2010.

    Science.gov (United States)

    Thwing, Julie; Eckert, Erin; Dione, Demba Anta; Tine, Roger; Faye, Adama; Yé, Yazoume; Ndiop, Medoune; Cisse, Moustapha; Ndione, Jacques Andre; Diouf, Mame Birame; Ba, Mady

    2017-09-01

    Malaria is endemic in Senegal. The national malaria control strategy focuses on achieving universal coverage for major interventions, with a goal of reaching preelimination status by 2018. Senegal began distribution of insecticide-treated nets (ITNs) and introduced artemisinin-based combination therapy in 2006, then introduced rapid diagnostic tests in 2007. We evaluated the impact of these efforts using a plausibility design based on malaria's contribution to all-cause under-five mortality (ACCM) and considering other contextual factors which may influence ACCM. Between 2005 and 2010, household ownership of ITNs increased from 20% to 63%, and the proportion of people sleeping under an ITN the night prior to the survey increased from 6% to 29%. Malaria parasite prevalence declined from 6% to 3% from 2008 to 2010 among children under five. Some nonmalaria indicators of child health improved, for example, increase of complete vaccination coverage from 58% to 64%; however, nutritional indicators deteriorated, with an increase in stunting from 16% to 26%. Although economic indicators improved, environmental conditions favored an increase in malaria transmission. ACCM decreased 40% between 2005 and 2010, from 121 (95% confidence interval [CI] 113-129) to 72 (95% CI 66-77) per 1,000, and declines were greater among age groups, epidemiologic zones, and wealth quintiles most at risk for malaria. After considering coverage of malaria interventions, trends in malaria morbidity, effects of contextual factors, and trends in ACCM, it is plausible that malaria control interventions contributed to a reduction in malaria mortality and to the impressive gains in child survival in Senegal.

  1. Agrochemicals indirectly increase survival of E. coli O157:H7 and indicator bacteria by reducing ecosystem services.

    Science.gov (United States)

    Staley, Zachery R; Rohr, Jason R; Senkbeil, Jacob K; Harwood, Valerie J

    Storm water and agricultural runoff frequently contain agrochemicals, fecal indicator bacteria (FIB), and zoonotic pathogens. Entry of such contaminants into aquatic ecosystems may affect ecology and human health. This study tested the hypothesis that the herbicide atrazine and the fungicide chlorothalonil indirectly affect the survival of FIB (Escherichia coli and Enterococcus faecalis) and a pathogen (E. coli O157:H7) by altering densities of protozoan predators or by altering competition from autochthonous bacteria. Streptomycin-resistant E. coli, En. faecalis, and E. coli O157:H7 were added to microcosms composed of Florida river water containing natural protozoan and bacterial populations. FIB, pathogen, and protozoan densities were monitored over six days. Known metabolic inhibitors, cycloheximide and streptomycin, were used to inhibit autochthonous protozoa or bacteria, respectively. The inhibitors made it possible to isolate the effects of predation or competition on survival of allochthonous bacteria, and each treatment increased the survival of FIB and pathogens. Chlorothalonil's effect was similar to that of cycloheximide, significantly reducing protozoan densities and elevating densities of FIB and pathogens relative to the control. Atrazine treatment did not affect protozoan densities, but, through an effect on competition, resulted in significantly greater densities of En. faecalis and E. coli O157:H7. Hence, by reducing predaceous protozoa and bacterial competitors that facilitate purifying water bodies of FIBs and human pathogens, chlorothalonil and atrazine indirectly diminished an ecosystem service of fresh water.

  2. Melatonin increases survival of HaCaT keratinocytes by suppressing UV-induced apoptosis.

    Science.gov (United States)

    Fischer, T W; Zbytek, B; Sayre, R M; Apostolov, E O; Basnakian, A G; Sweatman, T W; Wortsman, J; Elsner, P; Slominski, A

    2006-01-01

    Melatonin is a potent antioxidant and direct radical scavenger. As keratinocytes represent the major population in the skin and UV light causes damage to these cells, the possible protective effects of melatonin against UV-induced cell damage in HaCaT keratinocytes were investigated in vitro. Cells were preincubated with melatonin at graded concentrations from 10(-9) to 10(-3) m for 30 min prior to UV irradiation at doses of 25 and 50 mJ/cm2. Biological markers of cellular viability such as DNA synthesis and colony-forming efficiency as well as molecular markers of apoptosis were measured. DNA synthesis was determined by [3H]-thymidine incorporation into insoluble cellular fraction, clonogenicity through plating efficiency experiments and apoptosis by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. DNA synthesis experiments showed a strong protective effect by preincubation with melatonin at concentrations of 10(-4) m (P UV incubation protective effect. These results indicate that preincubation is a requirement for melatonin to exert its protective effects. The mechanism of melatonin's protective effect (10(-6) to 10(-3) m) includes inhibition of apoptosis as measured by TUNEL assay. Moreover, the biological significance of these effects is supported by clonogenic studies showing a significantly higher number of colonies in cultures treated with melatonin compared to controls. Thus, pretreatment with melatonin led to strong protection against UVB-induced damage in keratinocytes.

  3. IDO1 inhibition synergizes with radiation and PD-1 blockade to durably increase survival against advanced glioblastoma.

    Science.gov (United States)

    Ladomersky, Erik; Zhai, Lijie; Lenzen, Alicia; Lauing, Kristen L; Qian, Jun; Scholtens, Denise M; Gritsina, Galina; Sun, Xuebing; Liu, Ye; Yu, Fenglong; Gong, Wenfeng; Liu, Yong; Jiang, Beibei; Tang, Zhiyu; Patel, Ricky; Platanias, Leonidas C; James, C David; Stupp, Roger; Lukas, Rimas V; Binder, David C; Wainwright, Derek A

    2018-03-02

    Glioblastoma (GBM) is the most aggressive primary brain tumor in adults with a median survival of 15-20 months. Numerous approaches and novel therapeutics for treating GBM have been investigated in the setting of phase III clinical trials, including a recent analysis of the immune checkpoint inhibitor, Nivolumab (anti-PD-1), which failed to improve recurrent GBM patient survival. However, rather than abandoning immune checkpoint inhibitor treatment for GBM, which has shown promise in other types of cancer, ongoing studies are currently evaluating this therapeutic class when combined with other agents. Here, we investigated immunocompetent orthotopic mouse models of GBM treated with the potent CNS-penetrating IDO1 enzyme inhibitor, BGB-5777, combined with anti-PD1 mAb, as well as radiation therapy (RT), based on our recent observation that tumor-infiltrating T cells directly increase immunosuppressive IDO1 levels in human GBM, the previously-described enhancement of immune cell functions after PD-1 blockade, as well as the pro-inflammatory effects of radiation. Our results demonstrate a durable survival benefit from this novel three-agent treatment, but not for any single- or dual-agent combination. Unexpectedly, treatment efficacy required IDO1 enzyme inhibition in non-GBM cells, rather than tumor cells. Timing of effector T cell infiltration, animal subject age and usage of systemic chemotherapy, all directly impacted therapy-mediated survival benefit.  These data highlight a novel and clinically-relevant immunotherapeutic approach with associated mechanistic considerations that have formed the basis of a newly-initiated phase I/II trial for GBM patients. Copyright ©2018, American Association for Cancer Research.

  4. Malnutrition is associated with increased mortality in older adults regardless of the cause of death.

    Science.gov (United States)

    Söderström, Lisa; Rosenblad, Andreas; Thors Adolfsson, Eva; Bergkvist, Leif

    2017-02-01

    Malnutrition predicts preterm death, but whether this is valid irrespective of the cause of death is unknown. The aim of the present study was to determine whether malnutrition is associated with cause-specific mortality in older adults. This cohort study was conducted in Sweden and included 1767 individuals aged ≥65 years admitted to hospital in 2008-2009. On the basis of the Mini Nutritional Assessment instrument, nutritional risk was assessed as well nourished (score 24-30), at risk of malnutrition (score 17-23·5) or malnourished (score malnutrition, and 9·4 % of the participants were malnourished. During a median follow-up of 5·1 years, 839 participants (47·5 %) died. The multiple Cox regression model identified significant associations (hazard ratio (HR)) between malnutrition and risk of malnutrition, respectively, and death due to neoplasms (HR 2·43 and 1·32); mental or behavioural disorders (HR 5·73 and 5·44); diseases of the nervous (HR 4·39 and 2·08), circulatory (HR 1·95 and 1·57) or respiratory system (HR 2·19 and 1·49); and symptoms, signs and abnormal clinical and laboratory findings, not elsewhere classified (HR 2·23 and 1·43). Malnutrition and risk of malnutrition are associated with increased mortality regardless of the cause of death, which emphasises the need for nutritional screening to identify older adults who may require nutritional support in order to avoid preterm death.

  5. Captopril Increases Survival after Whole-Body Ionizing Irradiation but Decreases Survival when Combined with Skin-Burn Trauma in Mice.

    Science.gov (United States)

    Islam, Aminul; Bolduc, David L; Zhai, Min; Kiang, Juliann G; Swift, Joshua M

    2015-09-01

    Past and recent radiation events have involved a high incidence of radiation combined injury where victims often succumb to serious infections as a consequence of bacterial translocation and subsequent sepsis. The risk of infection is exacerbated in radiation combined skin-burn injury (RCI), which increase vulnerability. Furthermore, no suitable countermeasures for radiation combined skin-burn injury have been established. In this study, we evaluated captopril as a potential countermeasure to radiation combined skin-burn injury. Captopril is an FDA-approved angiotensin-converting enzyme inhibitor that was previously reported to stimulate hematopoietic recovery after exposure to ionizing radiation. Female B6D2F1/J mice were whole-body bilateral (60)Co gamma-photon irradiated (dose rate of 0.4 Gy/min) with 9.5 Gy (LD70/30 for RCI), followed by nonlethal dorsal skin-burn injury under anesthesia (approximately 15% total-body surface-area burn). Mice were provided with acidified drinking water with or without dissolved captopril (0.55 g/l) for 30 days immediately after injury and were administered topical gentamicin (0.1% cream; day 1-10) and oral levofloxacin (90-100 mg/kg; day 3-16). Surviving mice were euthanized on day 30 after analyses of water consumption, body weight and survival. Our data demonstrate that, while treatment with captopril did mitigate mortality induced by radiation injury (RI) alone (55% captopril vs. 80% vehicle; n = 20, P captopril vs. 41% vehicle; n = 22, P captopril administration via drinking water produced an uneven dosage pattern among the different injury groups ranging from 74 ± 5.4 to 115 ± 2.2 mg/kg/day. Captopril treatment also did not counteract the negative alterations in hematology, splenocytes or bone marrow cellularity after either radiation injury or radiation combined skin-burn injury. These data suggest that captopril may exert its actions differently between the two injury models (RI vs. RCI) and that captopril dosing, when

  6. Sodium chloride inhibits the growth and infective capacity of the amphibian chytrid fungus and increases host survival rates.

    Directory of Open Access Journals (Sweden)

    Michelle Pirrie Stockwell

    Full Text Available The amphibian chytrid fungus Batrachochytrium dendrobatidis is a recently emerged pathogen that causes the infectious disease chytridiomycosis and has been implicated as a contributing factor in the global amphibian decline. Since its discovery, research has been focused on developing various methods of mitigating the impact of chytridiomycosis on amphibian hosts but little attention has been given to the role of antifungal agents that could be added to the host's environment. Sodium chloride is a known antifungal agent used routinely in the aquaculture industry and this study investigates its potential for use as a disease management tool in amphibian conservation. The effect of 0-5 ppt NaCl on the growth, motility and survival of the chytrid fungus when grown in culture media and its effect on the growth, infection load and survivorship of infected Peron's tree frogs (Litoria peronii in captivity, was investigated. The results reveal that these concentrations do not negatively affect the survival of the host or the pathogen. However, concentrations greater than 3 ppt significantly reduced the growth and motility of the chytrid fungus compared to 0 ppt. Concentrations of 1-4 ppt NaCl were also associated with significantly lower host infection loads while infected hosts exposed to 3 and 4 ppt NaCl were found to have significantly higher survival rates. These results support the potential for NaCl to be used as an environmentally distributed antifungal agent for the prevention of chytridiomycosis in susceptible amphibian hosts. However, further research is required to identify any negative effects of salt exposure on both target and non-target organisms prior to implementation.

  7. Evidence of increasing drought severity caused by temperature rise in southern Europe

    International Nuclear Information System (INIS)

    Vicente-Serrano, Sergio M; Lopez-Moreno, Juan-I; Lorenzo-Lacruz, Jorge; García-Ruiz, José M; Azorin-Molina, Cesar; Morán-Tejeda, Enrique; Revuelto, Jesús; Beguería, Santiago; Sanchez-Lorenzo, Arturo; Trigo, Ricardo; Coelho, Fatima; Espejo, Francisco

    2014-01-01

    We use high quality climate data from ground meteorological stations in the Iberian Peninsula (IP) and robust drought indices to confirm that drought severity has increased in the past five decades, as a consequence of greater atmospheric evaporative demand resulting from temperature rise. Increased drought severity is independent of the model used to quantify the reference evapotranspiration. We have also focused on drought impacts to drought-sensitive systems, such as river discharge, by analyzing streamflow data for 287 rivers in the IP, and found that hydrological drought frequency and severity have also increased in the past five decades in natural, regulated and highly regulated basins. Recent positive trend in the atmospheric water demand has had a direct influence on the temporal evolution of streamflows, clearly identified during the warm season, in which higher evapotranspiration rates are recorded. This pattern of increase in evaporative demand and greater drought severity is probably applicable to other semiarid regions of the world, including other Mediterranean areas, the Sahel, southern Australia and South Africa, and can be expected to increasingly compromise water supplies and cause political, social and economic tensions among regions in the near future. (paper)

  8. Precise Temperature Measurement for Increasing the Survival of Newborn Babies in Incubator Environments

    Directory of Open Access Journals (Sweden)

    Robert Frischer

    2014-12-01

    Full Text Available Precise temperature measurement is essential in a wide range of applications in the medical environment, however the regarding the problem of temperature measurement inside a simple incubator, neither a simple nor a low cost solution have been proposed yet. Given that standard temperature sensors don’t satisfy the necessary expectations, the problem is not measuring temperature, but rather achieving the desired sensitivity. In response, this paper introduces a novel hardware design as well as the implementation that increases measurement sensitivity in defined temperature intervals at low cost.

  9. Increased all-cause mortality with psychotropic medication in Parkinson's disease and controls

    DEFF Research Database (Denmark)

    Frandsen, Rune; Baandrup, Lone; Kjellberg, Jakob

    2014-01-01

    AIM: Use of medication and polypharmacy is common as the population ages and its disease burden increases. We evaluated the association of antidepressants, benzodiazepines, antipsychotics and combinations of psychotropic drugs with all-cause mortality in patients with Parkinson's disease (PD...... of psychotropic medication in PD patients and controls. Hazard ratios were as follows for the medication types: selective serotonin reuptake inhibitors or serotonin-noradrenalin reuptake inhibitors, PD HR = 1.19, 95% CI = 1.04-1.36; Control HR = 1.77, 95% CI = 1.64-1.91; benzodiazepines, PD HR = 1.17, 95% CI = 0.......20-1.76; Control HR = 2.00, 95% CI 1.66-2.43; and combinations of these drugs compared with non-medicated PD patients and controls. Discontinuation of medication was associated with decreased mortality in both groups. CONCLUSIONS: The use of psychotropic medication in the elderly is associated with increased...

  10. Increase of Power System Survivability with the Decision Support Tool CRIPS Based on Network Planning and Simulation Program PSS®SINCAL

    Science.gov (United States)

    Schwaegerl, Christine; Seifert, Olaf; Buschmann, Robert; Dellwing, Hermann; Geretshuber, Stefan; Leick, Claus

    The increased interconnection and automation of critical infrastructures enlarges the complexity of the dependency structures and - as consequence - the danger of cascading effects, e.g. causing area-wide blackouts in power supply networks that are currently after deregulation operated closer to their limits. New tools or an intelligent combination of existing approaches are required to increase the survivability of critical infrastructures. Within the IRRIIS project the expert system CRIPS was developed based on network simulations realised with PSS®SINCAL, an established tool to support the analysis and planning of electrical power, gas, water or heat networks. CRIPS assesses the current situation in power supply networks analysing the simulation results of the physical network behaviour and recommends corresponding decisions.

  11. Sumatran tiger survival threatened by deforestation despite increasing densities in parks.

    Science.gov (United States)

    Luskin, Matthew Scott; Albert, Wido Rizki; Tobler, Mathias W

    2017-12-05

    The continuing development of improved capture-recapture (CR) modeling techniques used to study apex predators has also limited robust temporal and cross-site analyses due to different methods employed. We develop an approach to standardize older non-spatial CR and newer spatial CR density estimates and examine trends for critically endangered Sumatran tigers (Panthera tigris sumatrae) using a meta-regression of 17 existing densities and new estimates from our own fieldwork. We find that tiger densities were 47% higher in primary versus degraded forests and, unexpectedly, increased 4.9% per yr from 1996 to 2014, likely indicating a recovery from earlier poaching. However, while tiger numbers may have temporarily risen, the total potential island-wide population declined by 16.6% from 2000 to 2012 due to forest loss and degradation and subpopulations are significantly more fragmented. Thus, despite increasing densities in smaller parks, we conclude that there are only two robust populations left with >30 breeding females, indicating Sumatran tigers still face a high risk of extinction unless deforestation can be controlled.

  12. Excessive blood pressure increase with exercise and risk of all-cause mortality and cardiac events.

    Science.gov (United States)

    Bouzas-Mosquera, María C; Bouzas-Mosquera, Alberto; Peteiro, Jesús

    2016-10-01

    The association of an excessive blood pressure increase with exercise (EBPIE) on cardiovascular outcomes remains controversial. We sought to assess its impact on the risk of all-cause mortality and major cardiac events in patients with known or suspected coronary artery disease (CAD) referred for stress testing. Exercise echocardiography was performed in 10 047 patients with known or suspected CAD. An EBPIE was defined as an increase in systolic blood pressure with exercise ≥ 80 mmHg. The endpoints were all-cause mortality and major cardiac events (MACE), including cardiac death or nonfatal myocardial infarction (MI). Overall, 573 patients exhibited an EBPIE during the tests. Over a mean follow-up of 4·8 years, there were 1950 deaths (including 725 cardiac deaths), 1477 MI and 1900 MACE. The cumulative 10-year rates of all-cause mortality, cardiac death, nonfatal MI and MACE were 32·9%, 13·1%, 26·9% and 33% in patients who did not develop an EBPIE vs. 18·9%, 4·7%, 17·5% and 20·7% in those experiencing an EBPIE, respectively (P mortality (hazard ratio [HR] 0·73, 95% confidence interval [CI] 0·59-0·91, P = 0·004), cardiac death (HR 0·67, 95% CI 0·46-0·98, P = 0·04), MI (HR 0·67, 95% CI 0·52-0·86, P = 0·002) and MACE (HR 0·69, 95% CI 0·56-0·86, P = 0·001). An EBPIE was associated with a significantly lower risk of mortality and MACE in patients with known or suspected CAD referred for stress testing. © 2016 Stichting European Society for Clinical Investigation Journal Foundation.

  13. Increased thermohaline stratification as a possible cause for an ocean anoxic event in the Cretaceous period.

    Science.gov (United States)

    Erbacher, J; Huber, B T; Norris, R D; Markey, M

    2001-01-18

    Ocean anoxic events were periods of high carbon burial that led to drawdown of atmospheric carbon dioxide, lowering of bottom-water oxygen concentrations and, in many cases, significant biological extinction. Most ocean anoxic events are thought to be caused by high productivity and export of carbon from surface waters which is then preserved in organic-rich sediments, known as black shales. But the factors that triggered some of these events remain uncertain. Here we present stable isotope data from a mid-Cretaceous ocean anoxic event that occurred 112 Myr ago, and that point to increased thermohaline stratification as the probable cause. Ocean anoxic event 1b is associated with an increase in surface-water temperatures and runoff that led to decreased bottom-water formation and elevated carbon burial in the restricted basins of the western Tethys and North Atlantic. This event is in many ways similar to that which led to the more recent Plio-Pleistocene Mediterranean sapropels, but the greater geographical extent and longer duration (approximately 46 kyr) of ocean anoxic event 1b suggest that processes leading to such ocean anoxic events in the North Atlantic and western Tethys were able to act over a much larger region, and sequester far more carbon, than any of the Quaternary sapropels.

  14. Mesenterico-portal vein resection in patients with pancreatico-duodenal cancer is safe and may increase survival

    DEFF Research Database (Denmark)

    Storkholm, Jan Henrik; Hansen, Carsten Palnæs

    2014-01-01

    and 25 women. RESULTS: A total of 44 patients (93.7%) had ductal adenocarcinomas. In all, 39 patients (83%) had T3 tumours, and 38 patients (80.9%) had involvement of lymph nodes. Furthermore, 29 patients (62%) had a pancreaticoduodenectomy, 15 patients (32%) a total pancreatectomy and three patients (6......INTRODUCTION: Pancreatic cancer is one of the most serious gastrointestinal cancers, and in the US and Europe it is a leading cause of cancer-related mortality. Radical surgery is the only option available for long-term survival. The aim of this study was to describe the surgical technique...... and the results of portal vein/superior mesenteric vein resection in patients with pancreatic cancer. MATERIAL AND METHODS: Between 1 April 2009 and 1 April 2013, 354 patients underwent resection for pancreatic malignancy. A total of 47 portal vein/superior mesenteric vein resections were performed in 22 men...

  15. Aire deficiency causes increased susceptibility to streptozotocin-induced murine type 1 diabetes.

    Science.gov (United States)

    Hässler, S; Peltonen, L; Sandler, S; Winqvist, O

    2008-06-01

    Aire-deficient mice are a model of the human monogenic disorder autoimmune polyendocrine syndrome type I (APS I) characterized by a progressive autoimmune destruction of multiple endocrine glands such as the adrenal cortex, the parathyroids and the beta-cells of the pancreas. The disease is caused by mutations in the autoimmune regulator (AIRE) gene, a putative transcription factor expressed in thymic medullary epithelial cells and in antigen-presenting cells of the myeloid lineage in peripheral lymphoid organs. As Aire(-/-) mice do not spontaneously develop endocrinopathies, we wanted to evaluate the autoimmune multiple low-dose streptozotocin (MLDSTZ) diabetes model in Aire(-/-) mice. Surprisingly, Aire heterozygote mice were most susceptible to MLDSTZ-induced diabetes, whereas Aire(-/-) mice displayed an intermediate sensitivity to diabetes. Furthermore, Aire(-/-) macrophages produced higher levels of TNF-alpha and lower levels of IL-10 following streptozotocin stimulation, and Aire(-/-) mice developed a higher frequency of islet cells autoantibodies as a sign of increased activation. However, the number of islet infiltrating F4/80(+) Aire(-/-) macrophages was significantly decreased which was attributed to an increased susceptibility to streptozotocin cytotoxicity of Aire(-/-) macrophages. In conclusion, Aire(-/-) macrophages display an increased activation after STZ stimuli, but suffer from increased susceptibility to STZ cytotoxicity. These results support an important function of Aire in the control of peripheral tolerance through myeloid antigen-presenting cells.

  16. Decreased Polyunsaturated Fatty Acid Content Contributes to Increased Survival in Human Colon Cancer

    Directory of Open Access Journals (Sweden)

    Manuela Oraldi

    2009-01-01

    Full Text Available Among diet components, some fatty acids are known to affect several stages of colon carcinogenesis, whereas others are probably helpful in preventing tumors. In light of this, our aim was to determine the composition of fatty acids and the possible correlation with apoptosis in human colon carcinoma specimens at different Duke's stages and to evaluate the effect of enriching human colon cancer cell line with the possible reduced fatty acid(s. Specimens of carcinoma were compared with the corresponding non-neoplastic mucosa: a significant decrease of arachidonic acid, PPARα, Bad, and Bax and a significant increase of COX-2, Bcl-2, and pBad were found. The importance of arachidonic acid in apoptosis was demonstrated by enriching a Caco-2 cell line with this fatty acid. It induced apoptosis in a dose- and time-dependent manner via induction of PPARα that, in turn, decreased COX-2. In conclusion, the reduced content of arachidonic acid is likely related to carcinogenic process decreasing the susceptibility of cancer cells to apoptosis.

  17. Conditional Deletion of PDK1 in the Forebrain Causes Neuron Loss and Increased Apoptosis during Cortical Development

    Directory of Open Access Journals (Sweden)

    Congyu Xu

    2017-10-01

    Full Text Available Decreased expression but increased activity of PDK1 has been observed in neurodegenerative disease. To study in vivo function of PDK1 in neuron survival during cortical development, we generate forebrain-specific PDK1 conditional knockout (cKO mice. We demonstrate that PDK1 cKO mice display striking neuron loss and increased apoptosis. We report that PDK1 cKO mice exhibit deficits on several behavioral tasks. Moreover, PDK1 cKO mice show decreased activities for Akt and mTOR. These results highlight an essential role of endogenous PDK1 in the maintenance of neuronal survival during cortical development.

  18. Flexible Survival Strategies of Pseudomonas aeruginosa in Biofilms Result in Increased Fitness Compared with Candida albicans *

    Science.gov (United States)

    Purschke, Frauke Gina; Hiller, Ekkehard; Trick, Iris; Rupp, Steffen

    2012-01-01

    The majority of microorganisms persist in nature as surface-attached communities often surrounded by an extracellular matrix, called biofilms. Most natural biofilms are not formed by a single species but by multiple species. Microorganisms not only cooperate as in some multispecies biofilms but also compete for available nutrients. The Gram-negative bacterium Pseudomonas aeruginosa and the polymorphic fungus Candida albicans are two opportunistic pathogens that are often found coexisting in a human host. Several models of mixed biofilms have been reported for these organisms showing antagonistic behavior. To investigate the interaction of P. aeruginosa and C. albicans in more detail, we analyzed the secretome of single and mixed biofilms of both organisms using MALDI-TOF MS/MS at several time points. Overall 247 individual proteins were identified, 170 originated from P. aeruginosa and 77 from C. albicans. Only 39 of the 131 in mixed biofilms identified proteins were assigned to the fungus whereby the remaining 92 proteins belonged to P. aeruginosa. In single-species biofilms, both organisms showed a higher diversity of proteins with 73 being assigned to C. albicans and 154 to P. aeruginosa. Most interestingly, P. aeruginosa in the presence of C. albicans secreted 16 proteins in significantly higher amounts or exclusively among other virulence factors such as exotoxin A and iron acquisition systems. In addition, the high affinity iron-binding siderophore pyoverdine was identified in mixed biofilms but not in bacterial biofilms, indicating that P. aeruginosa increases its capability to sequester iron in competition with C. albicans. In contrast, C. albicans metabolism was significantly reduced, including a reduction in detectable iron acquisition proteins. The results obtained in this study show that microorganisms not only compete with the host for essential nutrients but also strongly with the present microflora in order to gain a competitive advantage. PMID

  19. Cause marketing for tissue and organ donation to increase public awareness

    International Nuclear Information System (INIS)

    Strong, M.; Neely, D.; Warnack, K.; Willits, M.; Yriondo, L.

    1999-01-01

    Today the science of marketing is being applied more and more to increase the rate of tissue and organ donation in the United States. To benefit from the proven tools and techniques of successful marketing in the for-profit world transplantation agencies across the country are turning to integrated marketing communications strategies and strategic partnerships to help achieve their goals.The methods used in cause marketing include: Establishing clear and measurable outcomes and goals; building a marketing plan and timeline to achieve the goals; gathering resources (funding, personnel, organizations, partnerships) to execute the plan, implementation, and measurement of outcomes. This session will review the Tissue and Organ Donation campaign implemented in the Northwest and will touch on the national awareness program developed by United Network for Organ Sharing (UNOS) in the United States. Segments of the Northwest's integrated campaign will include market segmentation strategies and targeted marketing, campaign development, public service advertising and public education campaigns. Media utilized include print, bus signs and billboards, broadcast (radio and TV), video and the internet. Strategies include public service advertising, paid advertising through sponsorships, direct mail, workshops and public speaking. The success of traditional product marketing can be achieved in cause marketing with a long-term, focused public education campaign. The potential benefit to the international community warrants exploration of similar strategies to overcome cultural resistance to life saving transplantation

  20. Aortic Valve Cyclic Stretch Causes Increased Remodeling Activity and Enhanced Serotonin Receptor Responsiveness

    Science.gov (United States)

    Balachandran, Kartik; Bakay, Marina A.; Connolly, Jeanne M.; Zhang, Xuemei; Yoganathan, Ajit P.; Levy, Robert J.

    2011-01-01

    Background Increased serotonin(5HT) receptor(5HTR) signaling has been associated with cardiac valvulopathy. Prior cell culture studies of 5HTR signaling in heart valve interstitial cells have provided mechanistic insights concerning only static conditions. We investigated the hypothesis that aortic valve biomechanics participate in the regulation of both 5HTR expression and inter-related extracellular matrix remodeling events. Methods The effects of cyclic-stretch on aortic valve 5HTR, expression, signaling and extracellular matrix remodeling were investigated using a tensile stretch bioreactor in studies which also compared the effects of adding 5HT and/or the 5HT-transporter inhibitor, Fluoxetine. Results Cyclic-stretch alone increased both proliferation and collagen in porcine aortic valve cusp samples. However, with cyclic-stretch, unlike static conditions, 5HT plus Fluoxetine caused the greatest increase in proliferation (p4.5 fold) for cyclic-stretch versus static (p<0.001), while expression of the 5HT transporter was not changed significantly. Extracellular matrix genes (eg. Collagen Types I,II,III, and proteoglycans) were also upregulated by cyclic-stretch. Conclusions Porcine aortic valve cusp samples subjected to cyclic stretch upregulate 5HTR2A and 2B, and also initiate remodeling activity characterized by increased proliferation and collagen production. Importantly, enhanced 5HTR responsiveness, due to increased 5HTR2A and 2B expression, results in a significantly greater response in remodeling endpoints (proliferation, collagen and GAG production) to 5HT in the presence of 5HT transporter blockade. PMID:21718840

  1. Wasps are the cause of an increasing mastitis problem in dairy cattle in Israel.

    Science.gov (United States)

    Yeruham, I; Braverman, Y; Schwimmer, A

    1998-07-01

    The German wasp Vespula germanica (Fabr.) (Hymenoptera: Vespidae) has been observed to injure dairy cows teats, causing lesions which can lead to mastitis. The number of dairy herds in Israel reported to be affected in this way has increased from five prior to 1989 to 32 from 1989 to 1993. Likewise, the geographical distribution of the colonies of these wasps has expanded from the Galilee to the northern Negev. Most cases of mastitis appeared during August and September when the wasps were most active; the predominant organism isolated was Streptococcus dysgalactiae. Apparently the wasps served as a vector in spreading S. dysgalactiae infection in the herds. More adult cows than first-calving cows were affected. The teats of the front quarters were more affected than those of the hind quarters.

  2. InSAR detects increase in surface subsidence caused by an Arctic tundra fire

    Science.gov (United States)

    Liu, Lin; Jafarov, Elchin E.; Schaefer, Kevin M.; Jones, Benjamin M.; Zebker, Howard A.; Williams, Christopher A.; Rogan, John; Zhang, Tingjun

    2014-01-01

    Wildfire is a major disturbance in the Arctic tundra and boreal forests, having a significant impact on soil hydrology, carbon cycling, and permafrost dynamics. This study explores the use of the microwave Interferometric Synthetic Aperture Radar (InSAR) technique to map and quantify ground surface subsidence caused by the Anaktuvuk River fire on the North Slope of Alaska. We detected an increase of up to 8 cm of thaw-season ground subsidence after the fire, which is due to a combination of thickened active layer and permafrost thaw subsidence. Our results illustrate the effectiveness and potential of using InSAR to quantify fire impacts on the Arctic tundra, especially in regions underlain by ice-rich permafrost. Our study also suggests that surface subsidence is a more comprehensive indicator of fire impacts on ice-rich permafrost terrain than changes in active layer thickness alone.

  3. InSAR detects increase in surface subsidence caused by an Arctic tundra fire

    Science.gov (United States)

    Liu, Lin; Jafarov, Elchin E.; Schaefer, Kevin M.; Jones, Benjamin M.; Zebker, Howard A.; Williams, Christopher A.; Rogan, John; Zhang, Tingjun

    2014-06-01

    Wildfire is a major disturbance in the Arctic tundra and boreal forests, having a significant impact on soil hydrology, carbon cycling, and permafrost dynamics. This study explores the use of the microwave Interferometric Synthetic Aperture Radar (InSAR) technique to map and quantify ground surface subsidence caused by the Anaktuvuk River fire on the North Slope of Alaska. We detected an increase of up to 8 cm of thaw-season ground subsidence after the fire, which is due to a combination of thickened active layer and permafrost thaw subsidence. Our results illustrate the effectiveness and potential of using InSAR to quantify fire impacts on the Arctic tundra, especially in regions underlain by ice-rich permafrost. Our study also suggests that surface subsidence is a more comprehensive indicator of fire impacts on ice-rich permafrost terrain than changes in active layer thickness alone.

  4. Extreme Wildlife Declines and Concurrent Increase in Livestock Numbers in Kenya: What Are the Causes?

    Directory of Open Access Journals (Sweden)

    Joseph O Ogutu

    Full Text Available There is growing evidence of escalating wildlife losses worldwide. Extreme wildlife losses have recently been documented for large parts of Africa, including western, Central and Eastern Africa. Here, we report extreme declines in wildlife and contemporaneous increase in livestock numbers in Kenya rangelands between 1977 and 2016. Our analysis uses systematic aerial monitoring survey data collected in rangelands that collectively cover 88% of Kenya's land surface. Our results show that wildlife numbers declined on average by 68% between 1977 and 2016. The magnitude of decline varied among species but was most extreme (72-88% and now severely threatens the population viability and persistence of warthog, lesser kudu, Thomson's gazelle, eland, oryx, topi, hartebeest, impala, Grevy's zebra and waterbuck in Kenya's rangelands. The declines were widespread and occurred in most of the 21 rangeland counties. Likewise to wildlife, cattle numbers decreased (25.2% but numbers of sheep and goats (76.3%, camels (13.1% and donkeys (6.7% evidently increased in the same period. As a result, livestock biomass was 8.1 times greater than that of wildlife in 2011-2013 compared to 3.5 times in 1977-1980. Most of Kenya's wildlife (ca. 30% occurred in Narok County alone. The proportion of the total "national" wildlife population found in each county increased between 1977 and 2016 substantially only in Taita Taveta and Laikipia but marginally in Garissa and Wajir counties, largely reflecting greater wildlife losses elsewhere. The declines raise very grave concerns about the future of wildlife, the effectiveness of wildlife conservation policies, strategies and practices in Kenya. Causes of the wildlife declines include exponential human population growth, increasing livestock numbers, declining rainfall and a striking rise in temperatures but the fundamental cause seems to be policy, institutional and market failures. Accordingly, we thoroughly evaluate wildlife

  5. Pacemaker lead fracture without an increase in lead impedance caused by cardiac fibroma

    Directory of Open Access Journals (Sweden)

    Daisuke Sato

    2013-12-01

    Full Text Available We report the case of a 64-year-old man who had a permanent pacemaker with a unipolar silicone electrode positioned in the right ventricle in 1989 for sinus node dysfunction. On a routine checkup in June 2011, a 28-mm-diameter mass was discovered, which appeared to adhere to the tricuspid valve and the ventricular lead. The size of the mass did not change for the next 6 months, and the lead impedance was maintained at around 500–600 Ω. Because pacing failure was observed in January 2012, he underwent an urgent pacemaker check; however, the lead impedance was found not to have increased greatly (689 Ω. Nevertheless, the pacemaker lead was noted to be fractured at the tricuspid level. His echocardiogram showed new severe tricuspid regurgitation and a floating mass around the lead. We extracted the fractured lead, enucleated the tumor, replaced the tricuspid valve, and placed an epicardial lead. Macroscopic examination revealed that the tumor surrounded the fractured lead and covered the stump. Pathological examination revealed that the tumor was composed of fibrous connective tissue. We presumed that electric current continued to flow through the stump of the fractured unipolar lead to the generator, and this might have caused the limited increase in lead impedance.

  6. Smoking Prevalence Among Mugla School of Health Sciences Students and Causes of Leading Increase in Smoking

    Directory of Open Access Journals (Sweden)

    Metin Picakciefe

    2007-08-01

    Full Text Available The purpose of this study was to determine the smoking prevalence among Mugla School of Health Sciences students, to determine the effects the increasing causes of smoking and their education about adverse health outcome of smoking. A cross-sectional study was performed among Mugla School of Health Sciences students in Mugla University. All students (417 in Mugla School of Health Sciences included in the study. The participation rates was 85.1%. Data were obtained by the self-administered questionnaire without teachers in classes. SPSS 11.0 was used for data analysis, and the differentiation was assessed by Chi-square analysis. P < 0.05 was accepted statistically significant. The prevalence of current smokers was 25.3% among students in Mugla School of Health Sciences. The students stated that the most important factor of smoking initiation was stress (59.2%. The univariable analysis showed that the friends’ smoking (p: 0.000 , having knowledge about smoking habits of teachers (p: 0.020 , alcohol consumption (p: 0.000, and other smokers out of parent in the home (p: 0.000 was significantly associated with increasing rate of smoking prevalence. The smoking prevalence was quite high (25.3% among Mugla School of Health Sciences students in Mugla University. It is needed to decreasing smoking prevalence among students that antismoking education should be reevaluated, that antismoking campaign should be administered in schools. [TAF Prev Med Bull 2007; 6(4.000: 267-272

  7. Immunization against recombinant bovine inhibin alpha subunit causes increased ovulation rates in gilts.

    Science.gov (United States)

    Brown, R W; Hungerford, J W; Greenwood, P E; Bloor, R J; Evans, D F; Tsonis, C G; Forage, R G

    1990-09-01

    Immunization of gilts in a commercial piggery against a fusion protein of the alpha subunit of bovine inhibin, produced by recombinant DNA methods, resulted in mean ovulation rate increases of 35% at the oestrus at which, under the piggery's management practices, they would have been mated. Sera from two immunized groups showed mean binding of 6.6% and 4.9% when assayed, at 1:800 final dilution, against iodinated bovine inhibin (Mr 31,000). Ovulation rates of immunized gilts were highly correlated with the ability of serum to bind iodinated native inhibin (r = 0.62; P less than 0.001), particularly when weight and age were included in the correlation (r = 0.72; P = 0.001), and inhibin binding accounted for 38% of the total variation in ovulation rate. Immunization caused no deleterious effects on growth rate or onset of oestrus. These results demonstrate the potential for use of such immunization to increase prolificacy in gilts and young sows.

  8. Increased pulmonary vascular permeability as a cause of re-expansion edema in rabbits

    International Nuclear Information System (INIS)

    Pavlin, D.J.; Nessly, M.L.; Cheney, F.W.

    1981-01-01

    In order to study the mechanism(s) underlying re-expansion edema, we measured the concentration of labeled albumin (RISA) in the extravascular, extracellular water (EVECW) of the lung as a measure of pulmonary vascular permeability. Re-expansion edema was first induced by rapid re-expansion of rabbit lungs that had been collapsed for 1 wk by pneumothorax. The RISA in EVECW was expressed as a fraction of its plasma concentration: (RISA)L/(RISA)PL. The volume of EVECW (ml/gm dry lung) was measured using a 24 Na indicator. Results in re-expansion edema were compared with normal control lungs and with oleic acid edema as a model of permeability edema. In re-expanded lungs, EVECW (3.41 +/- SD 1.24 ml/g) and (RISA)L/(RISA)PL 0.84 +/- SD 0.15) were significantly increased when compared with normal control lungs (2.25 +/- 0.41 ml/g and 0.51 +/- 0.20, respectively). Results in oleic acid edema (5.66 +/- 2.23 ml/g and 0.84 +/- 0.23) were similar to re-expansion edema. This suggested that re-expansion edema is due to increased pulmonary vascular permeability caused by mechanical stresses applied to the lung during re-expansion

  9. The public's belief in climate change and its human cause are increasing over time.

    Science.gov (United States)

    Milfont, Taciano L; Wilson, Marc S; Sibley, Chris G

    2017-01-01

    Polls examining public opinion on the subject of climate change are now commonplace, and one-off public opinion polls provide a snapshot of citizen's opinions that can inform policy and communication strategies. However, cross-sectional polls do not track opinions over time, thus making it impossible to ascertain whether key climate change beliefs held by the same group of individuals are changing or not. Here we examine the extent to which individual's level of agreement with two key beliefs ("climate change is real" and "climate change is caused by humans") remain stable or increase/decrease over a six-year period in New Zealand using latent growth curve modelling (n = 10,436). Data were drawn from the New Zealand Attitudes and Values Study, a probabilistic national panel study, and indicated that levels of agreement to both beliefs have steadily increased over the 2009-2015 period. Given that climate change beliefs and concerns are key predictors of climate change action, our findings suggest that a combination of targeted endeavors, as well as serendipitous events, may successfully convey the emergency of the issue.

  10. Outcomes of different bearings in total hip arthroplasty - implant survival, revision causes, and patient-reported outcome

    DEFF Research Database (Denmark)

    Varnum, Claus

    2017-01-01

    and mortality rates, and implant survival. As patients and surgeons may assess outcome after THA differently, patient-reported outcomes (PROMs) have gained much more interest and are today recognized as very important tools for evaluating the outcome and satisfaction after THA. One of the prognostic factors...

  11. Mandible-Powered Escape Jumps in Trap-Jaw Ants Increase Survival Rates during Predator-Prey Encounters.

    Directory of Open Access Journals (Sweden)

    Fredrick J Larabee

    Full Text Available Animals use a variety of escape mechanisms to increase the probability of surviving predatory attacks. Antipredator defenses can be elaborate, making their evolutionary origin unclear. Trap-jaw ants are known for their rapid and powerful predatory mandible strikes, and some species have been observed to direct those strikes at the substrate, thereby launching themselves into the air away from a potential threat. This potential escape mechanism has never been examined in a natural context. We studied the use of mandible-powered jumping in Odontomachus brunneus during their interactions with a common ant predator: pit-building antlions. We observed that while trap-jaw ant workers escaped from antlion pits by running in about half of interactions, in 15% of interactions they escaped by mandible-powered jumping. To test whether escape jumps improved individual survival, we experimentally prevented workers from jumping and measured their escape rate. Workers with unrestrained mandibles escaped from antlion pits significantly more frequently than workers with restrained mandibles. Our results indicate that some trap-jaw ant species can use mandible-powered jumps to escape from common predators. These results also provide a charismatic example of evolutionary co-option, where a trait that evolved for one function (predation has been co-opted for another (defense.

  12. Mandible-Powered Escape Jumps in Trap-Jaw Ants Increase Survival Rates during Predator-Prey Encounters.

    Science.gov (United States)

    Larabee, Fredrick J; Suarez, Andrew V

    2015-01-01

    Animals use a variety of escape mechanisms to increase the probability of surviving predatory attacks. Antipredator defenses can be elaborate, making their evolutionary origin unclear. Trap-jaw ants are known for their rapid and powerful predatory mandible strikes, and some species have been observed to direct those strikes at the substrate, thereby launching themselves into the air away from a potential threat. This potential escape mechanism has never been examined in a natural context. We studied the use of mandible-powered jumping in Odontomachus brunneus during their interactions with a common ant predator: pit-building antlions. We observed that while trap-jaw ant workers escaped from antlion pits by running in about half of interactions, in 15% of interactions they escaped by mandible-powered jumping. To test whether escape jumps improved individual survival, we experimentally prevented workers from jumping and measured their escape rate. Workers with unrestrained mandibles escaped from antlion pits significantly more frequently than workers with restrained mandibles. Our results indicate that some trap-jaw ant species can use mandible-powered jumps to escape from common predators. These results also provide a charismatic example of evolutionary co-option, where a trait that evolved for one function (predation) has been co-opted for another (defense).

  13. Beliefs of people taking antidepressants about causes of depression and reasons for increased prescribing rates.

    Science.gov (United States)

    Read, John; Cartwright, Claire; Gibson, Kerry; Shiels, Christopher; Haslam, Nicholas

    2014-10-01

    Public beliefs about the causes of mental health problems are related to desire for distance and pessimism about recovery, and are therefore frequently studied. The beliefs of people receiving treatment are researched less often. An online survey on causal beliefs about depression and experiences with antidepressants was completed by 1829 New Zealand adults prescribed anti-depressants in the preceding five years, 97.4% of whom proceeded to take antidepressants. The most frequently endorsed of 17 causal beliefs were family stress, relationship problems, loss of loved one, financial problems, isolation, and abuse or neglect in childhood. Factor analysis produced three factors: 'bio-genetic', 'adulthood stress' and 'childhood adversity'. The most strongly endorsed explanations for increases in antidepressant prescribing invoked improved identification, reduced stigma and drug company marketing. The least strongly endorsed was 'Anti-depressants are the best treatment'. Regression analyses revealed that self-reported efficacy of the antidepressants was positively associated with bio-genetic causal beliefs, negatively associated with childhood adversity beliefs and unrelated to adulthood stress beliefs. The belief that 'People cannot׳ get better by themselves even if they try' was positively associated with bio-genetic beliefs. The convenience sample may have been biased towards a favourable view of bio-genetic explanations, since 83% reported that the medication reduced their depression. Clinicians׳ should consider exploring patients׳ causal beliefs. The public, even when taking antidepressants, continues to hold a multi-factorial causal model of depression with a primary emphasis on psycho-social causes. A three factor model of those beliefs may lead to more sophisticated understandings of relationships with stigma variables. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Survival Impact of Increasing Time to Treatment Initiation for Patients With Head and Neck Cancer in the United States.

    Science.gov (United States)

    Murphy, Colin T; Galloway, Thomas J; Handorf, Elizabeth A; Egleston, Brian L; Wang, Lora S; Mehra, Ranee; Flieder, Douglas B; Ridge, John A

    2016-01-10

    To estimate the overall survival (OS) impact from increasing time to treatment initiation (TTI) for patients with head and neck squamous cell carcinoma (HNSCC). Using the National Cancer Data Base (NCDB), we examined patients who received curative therapy for the following sites: oral tongue, oropharynx, larynx, and hypopharynx. TTI was the number of days from diagnosis to initiation of curative treatment. The effect of TTI on OS was determined by using Cox regression models (MVA). Recursive partitioning analysis (RPA) identified TTI thresholds via conditional inference trees to estimate the greatest differences in OS on the basis of randomly selected training and validation sets, and repeated this 1,000 times to ensure robustness of TTI thresholds. A total of 51,655 patients were included. On MVA, TTI of 61 to 90 days versus less than 30 days (hazard ratio [HR], 1.13; 95% CI, 1.08 to 1.19) independently increased mortality risk. TTI of 67 days appeared as the optimal threshold on the training RPA, statistical significance was confirmed in the validation set (P < .001), and the 67-day TTI was the optimal threshold in 54% of repeated simulations. Overall, 96% of simulations validated two optimal TTI thresholds, with ranges of 46 to 52 days and 62 to 67 days. The median OS for TTI of 46 to 52 days or fewer versus 53 to 67 days versus greater than 67 days was 71.9 months (95% CI, 70.3 to 73.5 months) versus 61 months (95% CI, 57 to 66.1 months) versus 46.6 months (95% CI, 42.8 to 50.7 months), respectively (P < .001). In the most recent year with available data (2011), 25% of patients had TTI of greater than 46 days. TTI independently affects survival. One in four patients experienced treatment delay. TTI of greater than 46 to 52 days introduced an increased risk of death that was most consistently detrimental beyond 60 days. Prolonged TTI is currently affecting survival. © 2015 by American Society of Clinical Oncology.

  15. Increased cell survival by inhibition of BRCA1 using an antisense approach in an estrogen responsive ovarian carcinoma cell line

    International Nuclear Information System (INIS)

    Annab, Lois A; Hawkins, Rebecca E; Solomon, Greg; Barrett, J Carl; Afshari, Cynthia A

    2000-01-01

    phosphoprotein that is regulated in response to DNA damaging agents [5,6,7] and in response to estrogen-induced growth [8,9,10,11]. Germline mutations that cause breast and ovarian cancer predisposition frequently result in truncated and presumably inactive BRCA1 protein [12]. BG-1 cells were derived from a patient with stage III, poorly differentiated ovarian adenocarcinoma [13]. This cell line, which expresses wild-type BRCA1, is estrogen responsive and withdrawal of estrogen results in eventual cell death. Previous studies suggest that BRCA1 is stimulated as a result of estrogen treatment [8,9,10,11], and also that BRCA1 may be involved in the cell death process [14]. Therefore, we examined the effect of reduction of BRCA1 levels in BG-1 cells on the cellular response to hormone depletion as well as estrogen stimulation. The results suggest that reduced levels of BRCA1 correlates with a survival advantage when BG-1 cells are placed under growth-restrictive and hormone-depleted conditions. In optimum growth conditions, significantly reduced levels of BRCA1 correlates with enhanced growth both in vitro and in vivo. To test the hypothesis that BRCA1 may play a role in the regulation of ovarian tumor cell death as well as in the inhibition of ovarian cell proliferation. The estrogen receptor-positive, BG-1 cell line [13], which contains an abundant amount of estrogen receptors (600 fmoles/100 μg DNA), was infected using a pLXSN retroviral vector (provided by AD Miller) containing an inverted partial human cDNA 900-base-pair sequence of BRCA1 (from nucleotide 121 in exon 1 to nucleotide 1025 in exon 11, accession #U14680). After 2 weeks of selection in 800 μg/ml of geneticin-G418 (Gibco/Life Technologies, Gaithersburg, MD, USA), BG-1 G418-resistant colonies were pooled, or individually isolated, and assayed for growth in the presence or absence of supplemented estrogen. Virally infected pooled populations of BG-1 cells were examined for BRCA1 message levels by ribonuclease

  16. The Effect of Early Detection of Occult Brain Metastases in HER2-Positive Breast Cancer Patients on Survival and Cause of Death

    International Nuclear Information System (INIS)

    Niwinska, Anna; Tacikowska, Malgorzata; Murawska, Magdalena

    2010-01-01

    Purpose: The aim of the study is to evaluate disease-free survival, survival from the detection of brain metastases, overall survival, and cause of death in patients with occult brain metastases (Group I) vs. patients with symptomatic brain metastases (Group II). Methods and Materials: In 80 HER2-positive breast cancer patients, treated with trastuzumab and cytostatic agents for metastatic disease, magnetic resonance imaging screening of the brain was performed, and in 29 patients (36%) occult brain metastasis was detected (Group I). Whole-brain radiotherapy was delivered to Group I. This first group was compared with 52 patients who had symptomatic brain metastases (Group II) and was treated the same way, at the same clinic, during the same time period. Results: Median disease-free survival was 17 months in Group I and 19.9 months in Group II (p = 0.58). The median time interval between the dissemination of the disease and the detection of occult or symptomatic brain metastases was 9 and 15 months, respectively (p = 0.11). When the brain metastases were detected, the median survival was 9 and 8.78 months, respectively (p = 0.80). The median overall survival was 53 and 51 months, respectively (p = 0.94). In the group with occult brain metastases (Group I) 16% of patients died because of progression within the brain. In the group with symptomatic brain metastases (Group II) the rate of cerebral death was 48% (p = 0.009). Conclusions: Whole-brain radiotherapy of occult brain metastases in HER2-positive breast cancer patients with visceral dissemination produces a three-fold decrease in cerebral deaths but does not prolong survival.

  17. Patient Survival Periods and Death Causes Following Surgical Treatment of Mammary Gland Tumours Depending on Histological Type of Tumour: Retrospective Study of 221 Cases

    Directory of Open Access Journals (Sweden)

    Jana Lorenzová

    2010-01-01

    Full Text Available This retrospective study evaluated a canine patient group operated on for mammary neoplasms (221 females. After surgical treatment, the animals were divided based on histological findings into groups and subgroups according to the WHO system. In the individual groups and subgroups the length of their survival following a mammary tumour surgery and death causes were followed. Of their total number, 164 tumours were malignant, 39 were benign and 18 were mammary hyperplasias. With regard to malignant tumours, invasive tubular carcinoma (20.81% was identified most frequently; fibroadenoma reached the highest occurrence (10.41% as regards benign tumours. The length of survival in females with malignant tumours ranged from 12 to 37.4 months, depending on histological subtypes. In females with benign mammary neoplasms the length of survival ranged from 39.1 to 59.3 months and in animals with hyperplasia it was 50.2 months. As a result of mammary tumour, 41 females (25% died in the malignant tumour group, none died in the benign tumour group and 2 females (11.1% died in the hyperplasia group. The survival periods in surgically treated patients with mammary tumours were shorter for solid and complex carcinomas, compared to patients affected with the remainder of the histological subtypes. The longest survival period following operation was recorded in the group suffering from adenoma. The least favourable illness prognosis for patients with mammary tumours in respect to linking the death cause to the mammary tumour was for those having invasive papillary carcinoma. The most favourable illness prognosis was for patients with benign tumours and non-invasive tubular carcinoma. A frequent death cause in females with mammary tumours was another illness unrelated to mammary tumours.

  18. Increased sediment loads cause non-linear decreases in seagrass suitable habitat extent

    Science.gov (United States)

    Atkinson, Scott; Klein, Carissa Joy; Weber, Tony; Possingham, Hugh P.

    2017-01-01

    Land-based activities, including deforestation, agriculture, and urbanisation, cause increased erosion, reduced inland and coastal water quality, and subsequent loss or degradation of downstream coastal marine ecosystems. Quantitative approaches to link sediment loads from catchments to metrics of downstream marine ecosystem state are required to calculate the cost effectiveness of taking conservation actions on land to benefits accrued in the ocean. Here we quantify the relationship between sediment loads derived from landscapes to habitat suitability of seagrass meadows in Moreton Bay, Queensland, Australia. We use the following approach: (1) a catchment hydrological model generates sediment loads; (2) a statistical model links sediment loads to water clarity at monthly time-steps; (3) a species distribution model (SDM) factors in water clarity, bathymetry, wave height, and substrate suitability to predict seagrass habitat suitability at monthly time-steps; and (4) a statistical model quantifies the effect of sediment loads on area of seagrass suitable habitat in a given year. The relationship between sediment loads and seagrass suitable habitat is non-linear: large increases in sediment have a disproportionately large negative impact on availability of seagrass suitable habitat. Varying the temporal scale of analysis (monthly vs. yearly), or varying the threshold value used to delineate predicted seagrass presence vs. absence, both affect the magnitude, but not the overall shape, of the relationship between sediment loads and seagrass suitable habitat area. Quantifying the link between sediment produced from catchments and extent of downstream marine ecosystems allows assessment of the relative costs and benefits of taking conservation actions on land or in the ocean, respectively, to marine ecosystems. PMID:29125843

  19. Tight Skin 2 Mice Exhibit Delayed Wound Healing Caused by Increased Elastic Fibers in Fibrotic Skin.

    Science.gov (United States)

    Long, Kristen B; Burgwin, Chelsea M; Huneke, Richard; Artlett, Carol M; Blankenhorn, Elizabeth P

    2014-09-01

    Rationale: The Tight Skin 2 (Tsk2) mouse model of systemic sclerosis (SSc) has many features of human disease, including tight skin, excessive collagen deposition, alterations in the extracellular matrix (ECM), increased elastic fibers, and occurrence of antinuclear antibodies with age. A tight skin phenotype is observed by 2 weeks of age, but measurable skin fibrosis is only apparent at 10 weeks. We completed a series of wound healing experiments to determine how fibrosis affects wound healing in Tsk2/+ mice compared with their wild-type (WT) littermates. Method: We performed these experiments by introducing four 4 mm biopsy punched wounds on the back of each mouse, ventral of the midline, and observed wound healing over 10 days. Tsk2/+ mice showed significantly delayed wound healing and increased wound size compared with the WT littermates at both 5 and 10 weeks of age. We explored the potential sources of this response by wounding Tsk2/+ mice that were genetically deficient either for the NLRP3 inflammasome (a known fibrosis mediator), or for elastic fibers in the skin, using a fibulin-5 knockout. Conclusion: We found that the loss of elastic fibers restores normal wound healing in the Tsk2/+ mouse and that the loss of the NLRP3 inflammasome had no effect. We conclude that elastic fiber dysregulation is the primary cause of delayed wound healing in the Tsk2/+ mouse and therapies that promote collagen deposition in the tissue matrix in the absence of elastin deposition might be beneficial in promoting wound healing in SSc and other diseases.

  20. Increased sediment loads cause non-linear decreases in seagrass suitable habitat extent.

    Directory of Open Access Journals (Sweden)

    Megan Irene Saunders

    Full Text Available Land-based activities, including deforestation, agriculture, and urbanisation, cause increased erosion, reduced inland and coastal water quality, and subsequent loss or degradation of downstream coastal marine ecosystems. Quantitative approaches to link sediment loads from catchments to metrics of downstream marine ecosystem state are required to calculate the cost effectiveness of taking conservation actions on land to benefits accrued in the ocean. Here we quantify the relationship between sediment loads derived from landscapes to habitat suitability of seagrass meadows in Moreton Bay, Queensland, Australia. We use the following approach: (1 a catchment hydrological model generates sediment loads; (2 a statistical model links sediment loads to water clarity at monthly time-steps; (3 a species distribution model (SDM factors in water clarity, bathymetry, wave height, and substrate suitability to predict seagrass habitat suitability at monthly time-steps; and (4 a statistical model quantifies the effect of sediment loads on area of seagrass suitable habitat in a given year. The relationship between sediment loads and seagrass suitable habitat is non-linear: large increases in sediment have a disproportionately large negative impact on availability of seagrass suitable habitat. Varying the temporal scale of analysis (monthly vs. yearly, or varying the threshold value used to delineate predicted seagrass presence vs. absence, both affect the magnitude, but not the overall shape, of the relationship between sediment loads and seagrass suitable habitat area. Quantifying the link between sediment produced from catchments and extent of downstream marine ecosystems allows assessment of the relative costs and benefits of taking conservation actions on land or in the ocean, respectively, to marine ecosystems.

  1. Ecological causes of multilevel covariance between size and first-year survival in a wild bird population

    NARCIS (Netherlands)

    Bouwhuis, Sandra; Vedder, Oscar; Garroway, Colin J.; Sheldon, Ben C.

    Estimates of selection in natural populations are frequent but our understanding of ecological causes of selection, and causes of variation in the direction, strength and form of selection is limited. Here, we apply a multilevel framework to partition effects of great tit fledging mass on first-year

  2. A possible cause of epistaxis: increased masked hypertension prevalence in patients with epistaxis.

    Science.gov (United States)

    Acar, Baran; Yavuz, Bunyamin; Yıldız, Erdem; Ozkan, Selcuk; Ayturk, Mehmet; Sen, Omer; Deveci, Onur Sinan

    Epistaxis and hypertension are frequent conditions in the adult population. Masked hypertension is defined as a clinical condition in which a patient's office blood pressure level is epistaxis. The prevalence of this condition in patients with epistaxis is not well defined. This study aimed to evaluate the prevalence of masked hypertension using the results of office blood pressure measurement compared with the results of ambulatory blood pressure monitoring. Sixty patients with epistaxis and 60 control subjects were enrolled in the study. All patients with epistaxis and controls without history of hypertension underwent physical examination, including office blood pressure measurement, ambulatory or home blood pressure, and measurement of anthropometric parameters. Mean age was similar between the epistaxis group and the controls - 21-68 years (mean 42.9) for the epistaxis group and 18-71 years (mean 42.2) for the control group. A total of 20 patients (33.3%) in the epistaxis group and 7 patients (11.7%) in the control group (p=0.004) had masked hypertension. Night-time systolic blood pressure was significantly higher in patients with epistaxis than in the control group (pepistaxis (p=0.517). This study demonstrates increased masked hypertension prevalence in patients with epistaxis. We suggest that all patients with epistaxis should undergo ambulatory or home blood pressure to detect masked hypertension, which could be a possible cause of epistaxis. Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  3. Survival among children with "Lethal" congenital contracture syndrome 11 caused by novel mutations in the gliomedin gene (GLDN).

    Science.gov (United States)

    Wambach, Jennifer A; Stettner, Georg M; Haack, Tobias B; Writzl, Karin; Škofljanec, Andreja; Maver, Aleš; Munell, Francina; Ossowski, Stephan; Bosio, Mattia; Wegner, Daniel J; Shinawi, Marwan; Baldridge, Dustin; Alhaddad, Bader; Strom, Tim M; Grange, Dorothy K; Wilichowski, Ekkehard; Troxell, Robin; Collins, James; Warner, Barbara B; Schmidt, Robert E; Pestronk, Alan; Cole, F Sessions; Steinfeld, Robert

    2017-11-01

    Biallelic GLDN mutations have recently been identified among infants with lethal congenital contracture syndrome 11 (LCCS11). GLDN encodes gliomedin, a protein required for the formation of the nodes of Ranvier and development of the human peripheral nervous system. We report six infants and children from four unrelated families with biallelic GLDN mutations, four of whom survived beyond the neonatal period into infancy, childhood, and late adolescence with intensive care and chronic respiratory and nutritional support. Our findings expand the genotypic and phenotypic spectrum of LCCS11 and demonstrate that the condition may not necessarily be lethal in the neonatal period. © 2017 Wiley Periodicals, Inc.

  4. Novel Oncogenic Mutations of CBL in Human Acute Myeloid Leukemia That Activate Growth and Survival Pathways Depend on Increased Metabolism*

    Science.gov (United States)

    Fernandes, Margret S.; Reddy, Mamatha M.; Croteau, Nicole J.; Walz, Christoph; Weisbach, Henry; Podar, Klaus; Band, Hamid; Carroll, Martin; Reiter, Andreas; Larson, Richard A.; Salgia, Ravi; Griffin, James D.; Sattler, Martin

    2010-01-01

    Acute myeloid leukemia (AML) is characterized by multiple mutagenic events that affect proliferation, survival, as well as differentiation. Recently, gain-of-function mutations in the α helical structure within the linker sequence of the E3 ubiquitin ligase CBL have been associated with AML. We identified four novel CBL mutations, including a point mutation (Y371H) and a putative splice site mutation in AML specimens. Characterization of these two CBL mutants revealed that coexpression with the receptor tyrosine kinases FLT3 (Fms-like tyrosine kinase 3) or KIT-induced ligand independent growth or ligand hyperresponsiveness, respectively. Growth of cells expressing mutant CBL required expression and kinase activity of FLT3. In addition to the CBL-dependent phosphorylation of FLT3 and CBL itself, transformation was associated with activation of Akt and STAT5 and required functional expression of the small GTPases Rho, Rac, and Cdc42. Furthermore, the mutations led to constitutively elevated intracellular reactive oxygen species levels, which is commonly linked to increased glucose metabolism in cancer cells. Inhibition of hexokinase with 2-deoxyglucose blocked the transforming activity of CBL mutants and reduced activation of signaling mechanisms. Overall, our data demonstrate that mutations of CBL alter cellular biology at multiple levels and require not only the activation of receptor proximal signaling events but also an increase in cellular glucose metabolism. Pathways that are activated by CBL gain-of-function mutations can be efficiently targeted by small molecule drugs. PMID:20622007

  5. Depletion of intrinsic expression of Interleukin-8 in prostate cancer cells causes cell cycle arrest, spontaneous apoptosis and increases the efficacy of chemotherapeutic drugs

    Directory of Open Access Journals (Sweden)

    Lokeshwar Bal L

    2009-07-01

    Full Text Available Abstract Background The progression of all cancers is characterized by increased-cell proliferation and decreased-apoptosis. The androgen-independent prostate cancer (AIPC is the terminal stage of the disease. Many chemokines and cytokines are suspects to cause this increased tumor cell survival that ultimately leads to resistance to therapy and demise of the host. The AIPC cells, but not androgen-responsive cells, constitutively express abundant amount of the pro-inflammatory chemokine, Interleukin-8 (IL-8. The mechanism of IL-8 mediated survival and therapeutic resistance in AIPC cells is unclear at present. The purpose of this report is to show the pervasive role of IL-8 in malignant progression of androgen-independent prostate cancer (AIPC and to provide a potential new therapeutic avenue, using RNA interference. Results The functional consequence of IL-8 depletion in AIPC cells was investigated by RNA interference in two IL-8 secreting AIPC cell lines, PC-3 and DU145. The non-IL-8 secreting LNCaP and LAPC-4 cells served as controls. Cells were transfected with RISC-free siRNA (control or validated-pool of IL-8 siRNA. Transfection with 50 nM IL-8 siRNA caused >95% depletion of IL-8 mRNA and >92% decrease in IL-8 protein. This reduction in IL-8 led to cell cycle arrest at G1/S boundary and decreases in cell cycle-regulated proteins: Cyclin D1 and Cyclin B1 (both decreased >50% and inhibition of ERK1/2 activity by >50%. Further, the spontaneous apoptosis was increased by >43% in IL-8 depleted cells, evidenced by increases in caspase-9 activation and cleaved-PARP. IL-8 depletion caused significant decreases in anti-apoptotic proteins, BCL-2, BCL-xL due to decrease in both mRNA and post-translational stability, and increased levels of pro-apoptotic BAX and BAD proteins. More significantly, depletion of intracellular IL-8 increased the cytotoxic activity of multiple chemotherapeutic drugs. Specifically, the cytotoxicity of Docetaxel

  6. CAUSE OF A MULTI-SPECIES RADIOIODINE PLUME THAT IS INCREASING IN CONCENTRATION

    Energy Technology Data Exchange (ETDEWEB)

    Kaplan, D.

    2010-09-30

    Field and laboratory studies were carried out to understand the cause for steady increases in {sup 129}I concentrations emanating from radiological seepage basins located on the Savannah River Site. The basins were closed in 1988 by adding limestone and blast furnace slag and then capping with a RCRA low permeability engineered cover. Groundwater {sup 129}I concentrations in a well near the seepage basin in 1993 were 200 pCi L{sup -1} and are presently between 400 and 1000 pCi L{sup -1}. Iodine speciation in the plume was not uniform. Near the source, the iodine was comprised of 86% iodide, 2% iodate, and 12% organo-iodine (total activity = 178 pCi L{sup -1}). Whereas, groundwater iodine speciation 365 m down stream (25 m up stream from a wetland) was 0% iodide, 93% iodate, and 7% organo iodine. Batch desorption studies demonstrated that high concentrations of {sup 129}I could be incrementally desorbed from an archived seepage basin sediment sample by raising the pH. Batch sorption studies showed that iodate, IO{sub 3}{sup -}, sorbed more strongly than iodide, I{sup -}, to a subsurface clayey sediment, but equally well as iodide to a subsurface sandy sediment and a wetland sediment. Placing an organic-rich wetland sediment, but not nearby mineral sediments, under reducing (or microaerobic) conditions resulted in a large decrease in iodide K{sub d} values (from 73 to 10 mL g{sup -1}) and iodate K{sub d} values (from 80 to 7 mL g{sup -1}). Between pH and reduction-oxidation potential, it appears that pH seems to have a stronger influence on iodide and iodate sorption to mineral sediment. This may not be true for sediments containing higher concentrations of organic matter, such as the 7.6% organic matter sediment used in this study. First order calculations based on desorption studies with seepage basin sediments indicate that the modest increase of 0.7 pH units detected in the study site groundwater over the last 17 years since closure of the seepage basin may be

  7. An incomplete TCA cycle increases survival of Salmonella Typhimurium during infection of resting and activated murine macrophages.

    Science.gov (United States)

    Bowden, Steven D; Ramachandran, Vinoy K; Knudsen, Gitte M; Hinton, Jay C D; Thompson, Arthur

    2010-11-08

    In comparison to the comprehensive analyses performed on virulence gene expression, regulation and action, the intracellular metabolism of Salmonella during infection is a relatively under-studied area. We investigated the role of the tricarboxylic acid (TCA) cycle in the intracellular replication of Salmonella Typhimurium in resting and activated macrophages, epithelial cells, and during infection of mice. We constructed deletion mutations of 5 TCA cycle genes in S. Typhimurium including gltA, mdh, sdhCDAB, sucAB, and sucCD. We found that the mutants exhibited increased net intracellular replication in resting and activated murine macrophages compared to the wild-type. In contrast, an epithelial cell infection model showed that the S. Typhimurium ΔsucCD and ΔgltA strains had reduced net intracellular replication compared to the wild-type. The glyoxylate shunt was not responsible for the net increased replication of the TCA cycle mutants within resting macrophages. We also confirmed that, in a murine infection model, the S. Typhimurium ΔsucAB and ΔsucCD strains are attenuated for virulence. Our results suggest that disruption of the TCA cycle increases the ability of S. Typhimurium to survive within resting and activated murine macrophages. In contrast, epithelial cells are non-phagocytic cells and unlike macrophages cannot mount an oxidative and nitrosative defence response against pathogens; our results show that in HeLa cells the S. Typhimurium TCA cycle mutant strains show reduced or no change in intracellular levels compared to the wild-type. The attenuation of the S. Typhimurium ΔsucAB and ΔsucCD mutants in mice, compared to their increased net intracellular replication in resting and activated macrophages suggest that Salmonella may encounter environments within the host where a complete TCA cycle is advantageous.

  8. Cucurbitacin B Causes Increased Radiation Sensitivity of Human Breast Cancer Cells via G2/M Cell Cycle Arrest

    Directory of Open Access Journals (Sweden)

    Suwit Duangmano

    2012-01-01

    Full Text Available Purpose. To explore the effects of cucurbitacin B on the radiation survival of human breast cancer cells and to elucidate the cellular mechanism of radiosensitization if any. Materials and Methods. Human breast carcinoma cell lines were treated with cucurbitacin B before irradiation with 0–10 Gy of C137s gamma rays. The effect of cucurbitacin B on cell-survival following irradiation was evaluated by colony-forming assay. Cell cycle distributions were investigated using flow cytometry. Real-time PCR and western blots were performed to investigate the expression of cell cycle checkpoints. Results. Cucurbitacin B inhibited breast cancer cell proliferation in a dose-dependent manner. Only MDA-MB-231 and MCF7:5C cells but not SKBR-3 cells were radiosensitized by cucurbitacin B. Flow cytometric analysis for DNA content indicated that cucurbitacin B resulted in G2/M arrest in MDA-MB-231 and MCF7:5C but not SKBR-3 cells. Moreover, Real-time PCR and western blot analysis demonstrated upregulated p21 expression before irradiation, a likely cause of the cell cycle arrest. Conclusion. Taken together, these findings suggest that cucurbitacin B causes radiosensitization of some breast cancer cells, and that cucurbitacin B induced G2/M arrest is an important mechanism. Therefore, combinations of cucurbitacin B with radiotherapy may be appropriate for experimental breast cancer treatment.

  9. Increased cell survival and cytogenetic integrity by spatial dose redistribution at a compact synchrotron X-ray source

    Science.gov (United States)

    Ilicic, Katarina; Dierolf, Martin; Günther, Benedikt; Walsh, Dietrich W. M.; Schmid, Ernst; Eggl, Elena; Achterhold, Klaus; Gleich, Bernhard; Combs, Stephanie E.; Molls, Michael; Schmid, Thomas E.; Pfeiffer, Franz; Wilkens, Jan J.

    2017-01-01

    X-ray microbeam radiotherapy can potentially widen the therapeutic window due to a geometrical redistribution of the dose. However, high requirements on photon flux, beam collimation, and system stability restrict its application mainly to large-scale, cost-intensive synchrotron facilities. With a unique laser-based Compact Light Source using inverse Compton scattering, we investigated the translation of this promising radiotherapy technique to a machine of future clinical relevance. We performed in vitro colony-forming assays and chromosome aberration tests in normal tissue cells after microbeam irradiation compared to homogeneous irradiation at the same mean dose using 25 keV X-rays. The microplanar pattern was achieved with a tungsten slit array of 50 μm slit size and a spacing of 350 μm. Applying microbeams significantly increased cell survival for a mean dose above 2 Gy, which indicates fewer normal tissue complications. The observation of significantly less chromosome aberrations suggests a lower risk of second cancer development. Our findings provide valuable insight into the mechanisms of microbeam radiotherapy and prove its applicability at a compact synchrotron, which contributes to its future clinical translation. PMID:29049300

  10. Increased cell survival and cytogenetic integrity by spatial dose redistribution at a compact synchrotron X-ray source.

    Directory of Open Access Journals (Sweden)

    Karin Burger

    Full Text Available X-ray microbeam radiotherapy can potentially widen the therapeutic window due to a geometrical redistribution of the dose. However, high requirements on photon flux, beam collimation, and system stability restrict its application mainly to large-scale, cost-intensive synchrotron facilities. With a unique laser-based Compact Light Source using inverse Compton scattering, we investigated the translation of this promising radiotherapy technique to a machine of future clinical relevance. We performed in vitro colony-forming assays and chromosome aberration tests in normal tissue cells after microbeam irradiation compared to homogeneous irradiation at the same mean dose using 25 keV X-rays. The microplanar pattern was achieved with a tungsten slit array of 50 μm slit size and a spacing of 350 μm. Applying microbeams significantly increased cell survival for a mean dose above 2 Gy, which indicates fewer normal tissue complications. The observation of significantly less chromosome aberrations suggests a lower risk of second cancer development. Our findings provide valuable insight into the mechanisms of microbeam radiotherapy and prove its applicability at a compact synchrotron, which contributes to its future clinical translation.

  11. Factors associated with local recurrence and cause-specific survival in patients with ductal carcinoma in situ of the breast treated with breast-conserving therapy or mastectomy

    International Nuclear Information System (INIS)

    Vargas, Carlos; Kestin, Larry; Go, Nel; Krauss, Daniel; Chen, Peter; Goldstein, Neal; Martinez, Alvaro; Vicini, Frank A.

    2005-01-01

    Purpose: We reviewed our institution's experience treating patients with ductal carcinoma in situ (DCIS) of the breast to determine risk factors for ipsilateral breast tumor recurrence (IBTR) and cause-specific survival (CSS) after breast-conserving therapy (BCT) or mastectomy. Materials and Methods: Between 1981 and 1999, 410 cases of DCIS (405 patients) were treated at our institution; 367 were managed with breast-conserving surgery (54 with lumpectomy alone and 313 with adjuvant radiation therapy (RT) [median dose, 45 Gy]). Of these 313 patients, 298 received also a supplemental boost of RT to the lumpectomy cavity (median dose, 16 Gy). Forty-three patients underwent mastectomy; 2 (5%) received adjuvant RT to the chest wall. A true recurrence/marginal miss (TR/MM) IBTR was defined as failure within or adjacent to the tumor bed in patients undergoing BCT. Median follow-up for all patients was 7 years (mean: 6.1 years). Results: Thirty patients (8.2%) experienced an IBTR after BCT (25 [8%] after RT, 5 [9.3%] after no RT), and 2 patients (4.7%) developed a chest wall recurrence after mastectomy. Of the 32 local failures, 20 (63%) were invasive (18/30 [60%] after BCT and 2/2 [100%] after mastectomy), and 37% were DCIS alone. Twenty-four (80%) of the IBTRs were classified as TR/MM. The 10-year freedom from local failure, CSS, and overall survival after BCT or mastectomy were 89% vs. 90% (p = 0.4), 98% vs. 100% (p = 0.7), and 89% vs. 100% (p = 0.3), respectively. Factors associated with IBTR on Cox multivariate analysis were younger age (p = 0.02, hazard ratio [HR] 1.06 per year), electron boost energy ≤9 MeV (p = 0.03, HR 1.41), final margins ≤2 mm (p = 0.007; HR, 3.65), and no breast radiation (p = 0.002, HR 5.56). On Cox univariate analysis for BCT patients, IBTR, TR/MM failures, and predominant nuclear Grade 3 were associated with an increased risk of distant metastases and a reduced CSS. Conclusions: After treatment for DCIS, 10-year rates of local control

  12. Violent video games cause an increase in aggression long after the game has been turned off

    NARCIS (Netherlands)

    Bushman, B.J.; Gibson, B

    2011-01-01

    Experimental studies show that violent video games cause people to behave more aggressively, but how long does the effect last? In most experiments, aggression is measured immediately after gameplay. The present experiment is the first to test the long-term causal effects of violent video games on

  13. Increased cytotoxicity and streptolysin O activity in group G streptococcal strains causing invasive tissue infections

    DEFF Research Database (Denmark)

    Siemens, Nikolai; Kittang, Bård R; Chakrakodi, Bhavya

    2015-01-01

    Streptococcus dysgalactiae subsp. equisimilis (SDSE) has emerged as an important cause of severe skin and soft tissue infections, but little is known of the pathogenic mechanisms underlying tissue pathology. Patient samples and a collection of invasive and non-invasive group G SDSE strains (n = 69...

  14. Myiasis caused by Dermatobia hominis: countries with increased risk for travelers going to neotropic areas.

    Science.gov (United States)

    Villalobos, Guiehdani; Vega-Memije, Maria Elisa; Maravilla, Pablo; Martinez-Hernandez, Fernando

    2016-10-01

    Here, we review the human botfly (Dermatobia hominis), which belongs to a group of Diptera generically known as "myiasis-causing flies," characterized by the ability of their larvae to develop in animal flesh. In addition to its medical and economic importance, there is an academic interest in this botfly because of its peculiar biology, particularly because a phoretic diptera is needed to complete the life cycle. The larvae penetrate the host's skin, causing furuncle-like lesions that are pruritic, painful, and resemble subcutaneous nodules, producing irreversible perforations in the skin. Although D. hominis is distributed from Mexico to Argentina, a review performed by our working group from 1999 to 2015 determined that the countries with the highest infection rates in travelers are Belize, Bolivia, and Brazil. Interestingly, infected men show a higher variation in the distribution of the lesions than in women. Many treatment schemes have been suggested, including the application of highly dense liquids to the lesion to cause anoxia in the D. hominis larvae. We showed, for the first time, a Bayesian inference between D. hominis and other myiasis-causing flies. The flies grouped into two main clusters according to their capacity to produce facultative and obligatory myiasis, and D. hominis was phylogenetically close to Cuterebra spp. © 2016 The International Society of Dermatology.

  15. Associations of all-cause mortality with census-based neighbourhood deprivation and population density in Japan: a multilevel survival analysis.

    Directory of Open Access Journals (Sweden)

    Tomoki Nakaya

    Full Text Available BACKGROUND: Despite evidence that neighbourhood conditions affect residents' health, no prospective studies of the association between neighbourhood socio-demographic factors and all-cause mortality have been conducted in non-Western societies. Thus, we examined the effects of areal deprivation and population density on all-cause mortality in Japan. METHODS: We employed census and survival data from the Japan Public Health Center-based Prospective Study, Cohort I (n = 37,455, consisting of middle-aged residents (40 to 59 years at the baseline in 1990 living in four public health centre districts. Data spanned between 1990 and 2010. A multilevel parametric proportional-hazard regression model was applied to estimate the hazard ratios (HRs of all-cause mortality by two census-based areal variables--areal deprivation index and population density--as well as individualistic variables such as socioeconomic status and various risk factors. RESULTS: We found that areal deprivation and population density had moderate associations with all-cause mortality at the neighbourhood level based on the survival data with 21 years of follow-ups. Even when controlling for individualistic socio-economic status and behavioural factors, the HRs of the two areal factors (using quartile categorical variables significantly predicted mortality. Further, this analysis indicated an interaction effect of the two factors: areal deprivation prominently affects the health of residents in neighbourhoods with high population density. CONCLUSIONS: We confirmed that neighbourhood socio-demographic factors are significant predictors of all-cause death in Japanese non-metropolitan settings. Although further study is needed to clarify the cause-effect relationship of this association, the present findings suggest that health promotion policies should consider health disparities between neighbourhoods and possibly direct interventions towards reducing mortality in densely

  16. Pioglitazone treatment increases survival and prevents body weight loss in tumor-bearing animals: possible anti-cachectic effect.

    Directory of Open Access Journals (Sweden)

    Mércia Beluzi

    Full Text Available Cachexia is a multifactorial syndrome characterized by profound involuntary weight loss, fat depletion, skeletal muscle wasting, and asthenia; all symptoms are not entirely attributable to inadequate nutritional intake. Adipose tissue and skeletal muscle loss during cancer cachexia development has been described systematically. The former was proposed to precede and be more rapid than the latter, which presents a means for the early detection of cachexia in cancer patients. Recently, pioglitazone (PGZ was proposed to exhibit anti-cancer properties, including a reduction in insulin resistance and adipose tissue loss; nevertheless, few studies have evaluated its effect on survival. For greater insight into a potential anti-cachectic effect due to PGZ, 8-week-old male Wistar rats were subcutaneously inoculated with 1 mL (2×107 of Walker 256 tumor cells. The animals were randomly assigned to two experimental groups: TC (tumor + saline-control and TP5 (tumor + PGZ/5 mg. Body weight, food ingestion and tumor growth were measured at baseline and after removal of tumor on days 7, 14 and 26. Samples from different visceral adipose tissue (AT depots were collected on days 7 and 14 and stored at -80o C (5 to 7 animals per day/group. The PGZ treatment showed an increase in the survival average of 27.3% (P< 0.01 when compared to TC. It was also associated with enhanced body mass preservation (40.7 and 56.3%, p< 0.01 on day 14 and 26 compared with the TC group. The treatment also reduced the final tumor mass (53.4%, p<0.05 and anorexia compared with the TC group during late-stage cachexia. The retroperitoneal AT (RPAT mass was preserved on day 7 compared with the TC group during the same experimental period. Such effect also demonstrates inverse relationship with tumor growth, on day 14. Gene expression of PPAR-γ, adiponectin, LPL and C/EBP-α from cachectic rats was upregulated after PGZ. Glucose uptake from adipocyte cells (RPAT was entirely re

  17. Effects of increased alcohol availability during adolescence on the risk of all-cause and cause-specific disability pension: a natural experiment.

    Science.gov (United States)

    Thern, Emelie; de Munter, Jeroen; Hemmingsson, Tomas; Davey Smith, George; Ramstedt, Mats; Tynelius, Per; Rasmussen, Finn

    2017-06-01

    To test if being exposed to increased alcohol availability during adolescence is associated with an increased risk of receiving disability pension due to all-cause, alcohol use disorders and mental disorders. Register-based population-based study using a natural experiment setting, the alcohol policy change in Sweden (1967-68), with increased access to strong beer in a narrow time window and geographical area. The individuals exposed to the policy change were compared with non-exposed individuals living in the rest of Sweden, excluding a border area. Sweden. A total of 518 810 individuals (70 761 in the intervention group; 448 049 in the control group) born 1948-1953, aged 14-20 years during the policy change. Date and diagnosis of the outcome variable of disability pension due to all-cause, alcohol use disorders and mental disorders were obtained from the Swedish National Social Insurance Agency database from 1971 to 2013. Individual and family level socio-demographic and health-related covariates, as well as a regional level covariate, were included. Compared with the control group, adolescents exposed to the alcohol policy change were at an increased risk of receiving disability pension due to all-causes [hazard ratio (HR) = 1.09, 95% confidence interval (CI) = 1.07-1.11], alcohol use disorders (HR = 1.17, 95% CI = 1.05-1.30) and mental disorders (HR = 1.19, 95% CI = 1.15-1.23). In Sweden, a natural experiment with a 43-year follow-up suggests that exposure to increased alcohol availability during adolescence is associated with an increased risk of receiving a disability pension due to all-cause, alcohol use disorder and mental disorder diagnoses. © 2017 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

  18. Calcineurin inhibition at the clinical phase of prion disease reduces neurodegeneration, improves behavioral alterations and increases animal survival.

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    Abhisek Mukherjee

    2010-10-01

    Full Text Available Prion diseases are fatal neurodegenerative disorders characterized by a long pre-symptomatic phase followed by rapid and progressive clinical phase. Although rare in humans, the unconventional infectious nature of the disease raises the potential for an epidemic. Unfortunately, no treatment is currently available. The hallmark event in prion diseases is the accumulation of a misfolded and infectious form of the prion protein (PrP(Sc. Previous reports have shown that PrP(Sc induces endoplasmic reticulum stress and changes in calcium homeostasis in the brain of affected individuals. In this study we show that the calcium-dependent phosphatase Calcineurin (CaN is hyperactivated both in vitro and in vivo as a result of PrP(Sc formation. CaN activation mediates prion-induced neurodegeneration, suggesting that inhibition of this phosphatase could be a target for therapy. To test this hypothesis, prion infected wild type mice were treated intra-peritoneally with the CaN inhibitor FK506 at the clinical phase of the disease. Treated animals exhibited reduced severity of the clinical abnormalities and increased survival time compared to vehicle treated controls. Treatment also led to a significant increase in the brain levels of the CaN downstream targets pCREB and pBAD, which paralleled the decrease of CaN activity. Importantly, we observed a lower degree of neurodegeneration in animals treated with the drug as revealed by a higher number of neurons and a lower quantity of degenerating nerve cells. These changes were not dependent on PrP(Sc formation, since the protein accumulated in the brain to the same levels as in the untreated mice. Our findings contribute to an understanding of the mechanism of neurodegeneration in prion diseases and more importantly may provide a novel strategy for therapy that is beneficial at the clinical phase of the disease.

  19. (+)-Nootkatone and (+)-valencene from rhizomes of Cyperus rotundus increase survival rates in septic mice due to heme oxygenase-1 induction.

    Science.gov (United States)

    Tsoyi, Konstantin; Jang, Hwa Jin; Lee, Young Soo; Kim, Young Min; Kim, Hye Jung; Seo, Han Geuk; Lee, Jae Heun; Kwak, Jong Hwan; Lee, Dong-Ung; Chang, Ki Churl

    2011-10-11

    The rhizomes of Cyperus rotundus have been used as traditional folk medicine for the treatment of inflammatory diseases. However, the mechanism by which extract of rhizomes of Cyperus rotundus (ECR) elicits anti-inflammation has not been extensively investigated so far. The aim of the present study was to test whether heme oxygenase (HO)-1 induction is involved in the anti-inflammatory action of ECR. Induction of HO-1 and inhibition of inducible nitric oxide synthase (iNOS)/NO production by ECR and its 12 constituents (3 monoterpenes, 5 sesquiterpenes, and 4 aromatic compounds) were investigated using RAW264.7 cells in vitro. In addition, anti-inflammatory action of ECR and its two active ingredients (nookkatone, valencene) were confirmed in sepsis animal model in vivo. ECR increased HO-1 expression in a concentration-dependent manner, which was correlated with significant inhibition of iNOS/NO production in LPS-activated RAW264.7 cells. Among 12 compounds isolated from ECR, mostly sesquiterpenes induced stronger HO-1 expression than monoterpenes in macrophage cells. Nootkatone and valencene (sesquiterpenes) significantly inhibited iNOS expression and NO production in LPS-simulated RAW264.7 cells. Inhibition of iNOS expression by nootkatone, valencene, and ECR were significantly reduced in siHO-1 RNA transfected cells. Furthermore, all three showed marked inhibition of high mobility group box-1 (HMGB1) in LPS-activated macrophages and increased survival rates in cecal ligation and puncture (CLP)-induced sepsis in mice. Taken together, we concluded that possible anti-inflammatory mechanism of ECR is, at least, due to HO-1 induction, in which sesquiterpenes such as nootkatone and valencene play a crucial role. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  20. Evaluation Of Factors Influencing On Causes Of Prosthetic Valve Re-operation And Early Postoperative Survival Tehran Emam hospital (1991-2001

    Directory of Open Access Journals (Sweden)

    Rahmani Reaza

    2003-06-01

    Full Text Available Prosthetic valve re-operation has greater mortality and morbidity than primary valve replacement. By recognition of factors influencing on causes of redo operation and preoperative survival, one can select appropriate prosthesis at primary valve replacement and when operation performed at appropriate time, surgical risk can be reduced."nMethods and Materials: Two hundred patients that underwent prosthetic valve re-operation from October 1991 through November 2001 were included in this study. There were 68 men and 132 women with the mean age of 42:tl 1.8 years. Structural failure was the commonest cause of bio-prosthesis replacement (93%. Valve thrombosis was the common cause of mechanical valve replacement (32%. Age younger Than 50 (P= 0.01 and interval after the first implantation more than 10 years (P= 0.01 affected bio-prosthesis degeneration."nResults: Atrial fibrillation (P<0.01, Older age especially more than 40 (P<0.05 and mitral position (P<0.01 affected mechanical valve thrombosis. Cross clamp time (P= 0.005, Tricuspid insufficiency (P = 0.001, NYHA IV (P = 0.005 and emergent operation (P= 0.001 were independent determinants of hospital mortality."nConclusion: In conclusion, in patients with more than 10-years life expectancy and age younger than 50, mechanical valve can be selected for primary valve replacement. If operation performed before patients reach deteriorated condition, preoperative survival would be excellent.

  1. Mortality in over 350,000 Insured Swedish Dogs from 1995–2000: II. Breed-Specific Age and Survival Patterns and Relative Risk for Causes of Death

    Directory of Open Access Journals (Sweden)

    Olson P

    2005-09-01

    Full Text Available Abstract This study continues analysis from a companion paper on over 350,000 insured Swedish dogs up to 10 years of age contributing to more than one million dog-years at risk during 1995–2000. The age patterns for total and diagnostic mortality and for general causes of death (trauma, tumour, locomotor, heart and neurological are presented for numerous breeds. Survival estimates at five, eight and 10 years of age are calculated. Survival to 10 years of age was 75% or more in Labrador and golden retrievers, miniature and toy poodles and miniature dachshunds and lowest in Irish wolfhounds (91% dead by 10 years. Multivariable analysis was used to estimate the relative risk for general and more specific causes of death between breeds accounting for gender and age effects, including two-way interactions. Older females had tumour as a designated cause of death more often than males in most breeds, but not in the Bernese mountain dog. Information presented in this and the companion paper inform our understanding of the population level burden of disease, and support decision-making at the population and individual level about health promotion efforts and treatment and prognosis of disease events.

  2. Increased reactive oxygen species levels cause ER stress and cytotoxicity in andrographolide treated colon cancer cells

    OpenAIRE

    Banerjee, Aditi; Banerjee, Vivekjyoti; Czinn, Steven; Blanchard, Thomas

    2017-01-01

    Chemotherapy continues to play an essential role in the management of many cancers including colon cancer, the third leading cause of death due to cancer in the United States. Many naturally occurring plant compounds have been demonstrated to possess anti-cancer cell activity and have the potential to supplement existing chemotherapy strategies. The plant metabolite andrographolide induces cell death in cancer cells and apoptosis is dependent upon the induction of endoplasmic reticulum stress...

  3. Increased mortality among HIV-positive men on antiretroviral therapy: survival differences between sexes explained by late initiation in Uganda

    Directory of Open Access Journals (Sweden)

    Kanters S

    2013-05-01

    Full Text Available Steve Kanters,1,3 Margaret Nansubuga,2 Daniel Mwehire,2 Mary Odiit,2 Margaret Kasirye,2 William Musoke,2 Eric Druyts,3 Sanni Yaya,3 Anna Funk,3 Nathan Ford,4,5 Edward J Mills3,61Faculty of Health Science, Simon Fraser University, Burnaby, BC, Canada, 2Mildmay Uganda, Kampala, Uganda; 3Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada; 4Médecins Sans Frontières, Geneva, Switzerland; 5Centre for Infectious Disease Epidemiology and Research, University of Cape Town, South Africa; 6Stanford Prevention Research Center, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USABackground: We aimed to assess the relationship between gender and survival among adult patients newly enrolled on antiretroviral therapy (ART in Uganda. We also specifically examined the role of antenatal services in favoring women's access to HIV care.Methods: From an observational cohort study, we assessed survival and used logistic regression and differences in means to compare men and women who did not access care through antenatal services. Differences were assessed on measures of disease progression (WHO stage and CD4 count and demographic (age, marital status, and education, behavioral (sexual activity, disclosure to partner, and testing, and clinical variables (hepatitis B and C, syphilis, malaria, and anemia. A mediational analysis that considered gender as the initial variable, time to death as the outcome, initial CD4 count as the mediator, and age as a covariate was performed using an accelerated failure time model with a Weibull distribution.Results: Between 2004 and 2011, a total of 4775 patients initiated ART, and after exclusions 4537 (93.2% were included in analysis. Men initiating ART were more likely to have a WHO disease stage III or IV (odds ratio: 1.46, 95% confidence interval [CI]: 1.29–1.66, and lower CD4 cell counts compared to women (median baseline CD4 124 cells/mm3, interquartile range [IQR]: 43–205

  4. LIGHT (TNFSF14 Increases the Survival and Proliferation of Human Bone Marrow-Derived Mesenchymal Stem Cells.

    Directory of Open Access Journals (Sweden)

    Sook-Kyoung Heo

    Full Text Available LIGHT (HVEM-L, TNFSF14, or CD258, an entity homologous to lymphotoxins, with inducible nature and the ability to compete with herpes simplex virus glycoprotein D for herpes virus entry mediator (HVEM/tumor necrosis factor (TNF-related 2, is a member of the TNF superfamily. It is expressed as a homotrimer on activated T cells and dendritic cells (DCs, and has three receptors: HVEM, LT-β receptor (LTβR, and decoy receptor 3 (DcR3. So far, three receptors with distinct cellular expression patterns are known to interact with LIGHT. Follicular DCs and stromal cells bind LIGHT through LTβR. We monitored the effects of LIGHT on human bone marrow-derived mesenchymal stem cells (BM-MSCs. At first, we checked the negative and positive differentiation markers of BM-MSCs. And we confirmed the quality of MSCs by staining cells undergoing adipogenesis (Oil Red O staining, chondrogenesis (Alcian blue staining, and osteogenesis (Alizarin red staining. After rhLIGHT treatment, we monitored the count, viability, and proliferation of cells and cell cycle distribution. PDGF and TGFβ production by rhLIGHT was examined by ELISA, and the underlying biological mechanisms were studied by immunoblotting by rhLIGHT treatment. LTβR was constitutively expressed on the surface of human BM-MSCs. Cell number and viability increased after rhLIGHT treatment. BM-MSC proliferation was induced by an increase in the S/G2/M phase. The expression of not only diverse cyclins such as cyclin B1, D1, D3, and E, but also CDK1 and CDK2, increased, while that of p27 decreased, after rhLIGHT treatment. RhLIGHT-induced PDGF and TGFβ production mediated by STAT3 and Smad3 activation accelerated BM-MSC proliferation. Thus, LIGHT and LTβR interaction increases the survival and proliferation of human BM-MSCs, and therefore, LIGHT might play an important role in stem cell therapy.

  5. Causes for the recent increase in sea surface salinity in the north ...

    African Journals Online (AJOL)

    ... salinity budget was used to identify the mechanisms responsible for the increase. When comparing the period 2002–2009 with the period 1993–2001, significant changes in the salt budget were identified. The increase in SSS in the more recent period appeared to be driven by changes in the atmospheric freshwater flux, ...

  6. Increasing Reliability by Means of Root Cause Aware HARQ and Interference Coordination

    DEFF Research Database (Denmark)

    Soret, Beatriz; Gerardino, Guillermo Andrés Pocovi; Pedersen, Klaus I.

    2015-01-01

    of the network. Combined with a ROot Cause Aware HARQ (ROCA-HARQ), which provides additional information when a transmission fails, the joint mechanism is relevant for any LTE/LTE-A deployment and can be easily implemented in a real network. System-level simulations show attractive BLER reductions up to 80......The arrival of mission critical applications in the context of vehicular, medical and industrial wireless communications calls for reliability constraints never seen before in cellular systems. Enhanced Inter-Cell Interference Coordination (eICIC) has been widely investigated in the context of LTE...

  7. Fetal infusions of plasma cause an increase in umbilical vascular resistance in sheep.

    Science.gov (United States)

    Faber, J J; Anderson, D F; Jonker, S S; Davis, L E; Giraud, G D

    2006-08-01

    Earlier studies suggested that the fetal placental circulation is relatively inert with fetal placental flow increasing or decreasing with perfusion pressure. Subsequent studies have demonstrated that the placenta may not be an unreactive vascular bed. The present study was undertaken to determine if plasma infusion-induced hypertension increased fetal placental flow in proportion to the driving pressure across the fetal placental circulation. Six fetal sheep were operated on at 118-122 days to place intravascular catheters and a flow sensor on the common umbilical artery. Starting 6 days later, the fetuses were infused with adult sheep plasma. During the 7-day-long infusion period, they received a total of 1515+/-217 (SD) ml of fluid and 93.2+/-12.0 g of protein. Fetal plasma protein concentrations increased from 34.2+/-2.3 to 77.0+/-9.7 g/l (Pblood pressures rose from 42+/-3 to 59+/-4 mmHg (Ppressures rose from 2.2+/-0.5 to 4.8+/-0.8 mmHg (Ppressure, fetal placental blood flow remained (statistically) constant (627+/-299 ml/min and 552+/-221 ml/min) while fetal umbilical resistance increased from 0.077+/-0.038 to 0.115+/-0.053 mmHg min/ml (Ppressure across the fetal placental circulation. The increase in fetal placental resistance may be a response to the increase in arterial pressure since there was no increase in flow.

  8. Is Global Warming likely to cause an increased incidence of Malaria?

    OpenAIRE

    Nabi, SA; Qader, SS

    2009-01-01

    Abstract: The rise in the average temperature of earth has been described as global warming which is mainly attributed to the increasing phenomenon of the greenhouse effect. It is believed that global warming can have several harmful effects on human health, both directly and indirectly. Since malaria is greatly influenced by climatic conditions because of its direct relationship with the mosquito population, it is widely assumed that its incidence is likely to increase in a future warmer wor...

  9. Effect of Increased Radiotoxicity on Survival of Patients with Non-small Cell Lung Cancer Treated with Curatively Intended Radiotherapy.

    Science.gov (United States)

    Holgersson, Georg; Bergström, Stefan; Liv, Per; Nilsson, Jonas; Edlund, Per; Blomberg, Carl; Nyman, Jan; Friesland, Signe; Ekman, Simon; Asklund, Thomas; Henriksson, Roger; Bergqvist, Michael

    2015-10-01

    To elucidate the impact of different forms of radiation toxicities (esophagitis, radiation pneumonitis, mucositis and hoarseness), on the survival of patients treated with curatively intended radiotherapy for non-small cell lung cancer (NSCLC). Data were individually collected retrospectively for all patients diagnosed with NSCLC subjected to curatively intended radiotherapy (≥50 Gy) in Sweden during the time period 1990 to 2000. Esophagitis was the only radiation-induced toxicity with an impact on survival (hazard ratio=0.83, p=0.016). However, in a multivariate model, with clinical- and treatment-related factors taken into consideration, the impact of esophagitis on survival was no longer statistically significant (hazard ratio=0.88, p=0.17). The effect on survival seen in univariate analysis may be related to higher radiation dose and to the higher prevalence of chemotherapy in this group. The results do not suggest that the toxicities examined have any detrimental effect on overall survival. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  10. [Increasing incidence of community-acquired pneumonia caused by atypical microorganisms].

    Science.gov (United States)

    Tazón-Varela, M A; Alonso-Valle, H; Muñoz-Cacho, P; Gallo-Terán, J; Piris-García, X; Pérez-Mier, L A

    2017-09-01

    Knowing the most common microorganisms in our environment can help us to make proper empirical treatment decisions. The aim is to identify those microorganisms causing community-acquired pneumonia. An observational, descriptive and prospective study was conducted, including patients over 14 years with a clinical and radiographic diagnosis of community-acquired pneumonia during a 383 consecutive day period. A record was made of sociodemographic variables, personal history, prognostic severity scales, progress, and pathogenic agents. The aetiological diagnosis was made using blood cultures, detection of Streptococcus pneumoniae and Legionella pneumophila urinary antigens, sputum culture, influenza virus and Streptococcus pyogenes detection. Categorical variables are presented as absolute values and percentages, and continuous variables as their means and standard deviations. Of the 287 patients included in the study (42% women, mean age 66±22 years), 10.45% died and 70% required hospital admission. An aetiological diagnosis was achieved in 43 patients (14.98%), with 16 microorganisms found in 59 positive samples. The most frequently isolated pathogen was Streptococcus pneumonia (24/59, 41%), followed by gram-negative enteric bacilli, Klebsiella pneumonia, Escherichia coli, Serratia marcescens and Enterobacter cloacae isolated in 20% of the samples (12/59), influenza virus (5/59, 9%), methicillin-resistant Staphylococcus aureus (3/59, 5%), Pseudomonas aeruginosa (2/59, 3%), Moraxella catarrhalis (2/59, 3%), Legionella pneumophila (2/59, 3%), and Haemophilus influenza (2/59, 3%). Polymicrobial infections accounted for 14% (8/59). A high percentage of atypical microorganisms causing community-acquired pneumonia were found. Copyright © 2016 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Losing the battle of the bulge: causes and consequences of increasing obesity.

    Science.gov (United States)

    Eckersley, R M

    2001-06-04

    Increasing proportions of Australians are overweight or obese, a problem shared by all developed and, increasingly, developing nations. Now as many people in the world are overweight as underweight. Increasing obesity is a serious public health as well as economic problem. Its associated greater risks of high blood pressure, heart disease, osteoarthritis, type 2 diabetes, some cancers and other health problems consume considerable proportions of healthcare budgets. Health inequalities often reflect social inequalities, but with overweight there is also a male-female difference in the relationship between overweight and socioeconomic status. Health promotion campaigns are underestimating the social determinants of health, and "risk fatigue" is affecting attitudes to complying with healthy lifestyle standards. Proposals to reverse the obesity trend, such as taxing or restricting the advertising of unhealthy foods, raise contentious issues of choice and regulation.

  12. Effectiveness of mouse interferon alpha/beta compared to single-agent chemotherapy in increasing survival time of mice after intravenous inoculation of Friend erythroleukemia cells.

    Science.gov (United States)

    Gresser, I; Maury, C; Belardelli, F; Maunoury, M T; Machover, D

    1988-03-16

    DBA/2 mice received an iv injection of 2 X 10(6) Friend erythroleukemia cells (FLCs; approximately equal to 4 X 10(5) lethal dose50), which multiplied rapidly in the liver and spleen and killed all untreated or control treated mice between 7 and 12 days. Daily interferon (IFN) treatment resulted in a very marked increase in survival time and apparent cure of 4 of 22 tumor-inoculated mice. In contrast, treatment of tumor-injected (iv) mice with cyclophosphamide, 5-fluorouracil, and methotrexate increased survival time by only a few days; and treatment of mice with cisplatin, vincristine, doxorubicin, bleomycin, or etoposide was ineffective. However, when FLCs were injected ip, both cytostatic drugs and IFN exerted an antitumor effect. We conclude that IFN alpha/beta was particularly effective in inhibiting the development of liver and spleen metastases and in increasing mouse survival time after iv inoculation of FLCs.

  13. Rapid Adjustments Cause Weak Surface Temperature Response to Increased Black Carbon Concentrations

    Science.gov (United States)

    Stjern, Camilla Weum; Samset, Bjørn Hallvard; Myhre, Gunnar; Forster, Piers M.; Hodnebrog, Øivind; Andrews, Timothy; Boucher, Olivier; Faluvegi, Gregory; Iversen, Trond; Kasoar, Matthew; Kharin, Viatcheslav; Kirkevâg, Alf; Lamarque, Jean-François; Olivié, Dirk; Richardson, Thomas; Shawki, Dilshad; Shindell, Drew; Smith, Christopher J.; Takemura, Toshihiko; Voulgarakis, Apostolos

    2017-11-01

    We investigate the climate response to increased concentrations of black carbon (BC), as part of the Precipitation Driver Response Model Intercomparison Project (PDRMIP). A tenfold increase in BC is simulated by nine global coupled-climate models, producing a model median effective radiative forcing of 0.82 (ranging from 0.41 to 2.91) W m-2, and a warming of 0.67 (0.16 to 1.66) K globally and 1.24 (0.26 to 4.31) K in the Arctic. A strong positive instantaneous radiative forcing (median of 2.10 W m-2 based on five of the models) is countered by negative rapid adjustments (-0.64 W m-2 for the same five models), which dampen the total surface temperature signal. Unlike other drivers of climate change, the response of temperature and cloud profiles to the BC forcing is dominated by rapid adjustments. Low-level cloud amounts increase for all models, while higher-level clouds are diminished. The rapid temperature response is particularly strong above 400 hPa, where increased atmospheric stabilization and reduced cloud cover contrast the response pattern of the other drivers. In conclusion, we find that this substantial increase in BC concentrations does have considerable impacts on important aspects of the climate system. However, some of these effects tend to offset one another, leaving a relatively small median global warming of 0.47 K per W m-2—about 20% lower than the response to a doubling of CO2. Translating the tenfold increase in BC to the present-day impact of anthropogenic BC (given the emissions used in this work) would leave a warming of merely 0.07 K.

  14. Is Global Warming likely to cause an increased incidence of Malaria?

    Science.gov (United States)

    Nabi, Sa; Qader, Ss

    2009-03-01

    The rise in the average temperature of earth has been described as global warming which is mainly attributed to the increasing phenomenon of the greenhouse effect. It is believed that global warming can have several harmful effects on human health, both directly and indirectly. Since malaria is greatly influenced by climatic conditions because of its direct relationship with the mosquito population, it is widely assumed that its incidence is likely to increase in a future warmer world.This review article discusses the two contradictory views regarding the association of global warming with an increased incidence of malaria. On one hand, there are many who believe that there is a strong association between the recent increase in malaria incidence and global warming. They predict that as global warming continues, malaria is set to spread in locations where previously it was limited, due to cooler climate. On the other hand, several theories have been put forward which are quite contrary to this prediction. There are multiple other factors which are accountable for the recent upsurge of malaria: for example drug resistance, mosquito control programs, public health facilities, and living standards.

  15. Is Global Warming Likely to Cause an Increased Incidence of Malaria?

    African Journals Online (AJOL)

    The rise in the average temperature of earth has been described as global warming which is mainly attributed to the increasing phenomenon of the greenhouse effect. It is believed that global warming can have several harmful effects on human health, both directly and indirectly. Since malaria is greatly influenced by ...

  16. Motion in images is essential to cause motion sickness symptoms, but not to increase postural sway

    NARCIS (Netherlands)

    Lubeck, A.J.A.; Bos, J.E.; Stins, J.F.

    2015-01-01

    Abstract Objective It is generally assumed that motion in motion images is responsible for increased postural sway as well as for visually induced motion sickness (VIMS). However, this has not yet been tested. To that end, we studied postural sway and VIMS induced by motion and still images. Method

  17. Is Global Warming Likely to Cause an Increased Incidence of Malaria?

    African Journals Online (AJOL)

    Administratör

    2008-12-17

    Dec 17, 2008 ... reality, like the melting of polar ice caps and glaciers, rising sea levels, changing weather systems, and climate changes [6]. There also have been reports of freshwater shortages, coral reef bleaching, and an increase in surface temperatures [7]. Patz and Kovats have identified six major areas of concern to.

  18. Is Global Warming likely to cause an increased incidence of Malaria?

    Science.gov (United States)

    Nabi, SA; Qader, SS

    2009-01-01

    The rise in the average temperature of earth has been described as global warming which is mainly attributed to the increasing phenomenon of the greenhouse effect. It is believed that global warming can have several harmful effects on human health, both directly and indirectly. Since malaria is greatly influenced by climatic conditions because of its direct relationship with the mosquito population, it is widely assumed that its incidence is likely to increase in a future warmer world. This review article discusses the two contradictory views regarding the association of global warming with an increased incidence of malaria. On one hand, there are many who believe that there is a strong association between the recent increase in malaria incidence and global warming. They predict that as global warming continues, malaria is set to spread in locations where previously it was limited, due to cooler climate. On the other hand, several theories have been put forward which are quite contrary to this prediction. There are multiple other factors which are accountable for the recent upsurge of malaria: for example drug resistance, mosquito control programs, public health facilities, and living standards. PMID:21483497

  19. Probable causes of increasing brucellosis in free-ranging elk of the Greater Yellowstone Ecosystem

    Science.gov (United States)

    Cross, P.C.; Cole, E.K.; Dobson, A.P.; Edwards, W.H.; Hamlin, K.L.; Luikart, G.; Middleton, A.D.; Scurlock, B.M.; White, P.J.

    2010-01-01

    While many wildlife species are threatened, some populations have recovered from previous overexploitation, and data linking these population increases with disease dynamics are limited. We present data suggesting that free-ranging elk (Cervus elaphus) are a maintenance host for Brucella abortus in new areas of the Greater Yellowstone Ecosystem (GYE). Brucellosis seroprevalence in free-ranging elk increased from 0-7% in 1991-1992 to 8-20% in 2006-2007 in four of six herd units around the GYE. These levels of brucellosis are comparable to some herd units where elk are artificially aggregated on supplemental feeding grounds. There are several possible mechanisms for this increase that we evaluated using statistical and population modeling approaches. Simulations of an age-structured population model suggest that the observed levels of seroprevalence are unlikely to be sustained by dispersal from supplemental feeding areas with relatively high seroprevalence or an older age structure. Increases in brucellosis seroprevalence and the total elk population size in areas with feeding grounds have not been statistically detectable. Meanwhile, the rate of seroprevalence increase outside the feeding grounds was related to the population size and density of each herd unit. Therefore, the data suggest that enhanced elk-to-elk transmission in free-ranging populations may be occurring due to larger winter elk aggregations. Elk populations inside and outside of the GYE that traditionally did not maintain brucellosis may now be at risk due to recent population increases. In particular, some neighboring populations of Montana elk were 5-9 times larger in 2007 than in the 1970s, with some aggregations comparable to the Wyoming feeding-ground populations. Addressing the unintended consequences of these increasing populations is complicated by limited hunter access to private lands, which places many ungulate populations out of administrative control. Agency-landowner hunting access

  20. Human papillomavirus-16 infection in advanced oral cavity cancer patients is related to an increased risk of distant metastases and poor survival.

    Directory of Open Access Journals (Sweden)

    Li-Ang Lee

    Full Text Available BACKGROUND: Human papillomavirus (HPV is an oncogenic virus causing oropharyngeal cancers and resulting in a favorable outcome after the treatment. The role of HPV in oral cavity squamous cell carcinoma (OSCC remains ambiguous. OBJECTIVE: This study aimed to examine the effect of HPV infection on disease control among patients with OSCC following radical surgery with radiation-based adjuvant therapy. PATIENTS AND METHOD: We prospectively followed 173 patients with advanced OSCC (96% were stage III/IV who had undergone radical surgery and adjuvant therapy between 2004 and 2006. They were followed between surgery and death or up to 60 months. Surgical specimens were examined using a PCR-based HPV blot test. The primary endpoints were the risk of relapse and the time to relapse; the secondary endpoints were disease-free survival, disease-specific survival, and overall survival. RESULTS: The prevalence of HPV-positive OSCC was 22%; HPV-16 (9% and HPV-18 (7% were the genotypes most commonly encountered. Solitary HPV-16 infection was a poor predictor of 5-year distant metastases (hazard ratio, 3.4; 95% confidence interval, 1.4-8.0; P = 0.005, disease-free survival (P = 0.037, disease-specific survival (P = 0.006, and overall survival (P = 0.010, whereas HPV-18 infection had no impact on 5-year outcomes. The rate of 5-year distant metastases was significantly higher in the HPV-16 or level IV/V metastasis group compared with both the extracapsular spread or tumor depth ≥ 11-mm group and patients without risk factors (P<0.001. CONCLUSIONS: HPV infections in advanced OSCC patients are not uncommon and clinically relevant. Compared with HPV-16-negative advanced OSCC patients, those with a single HPV-16 infection are at higher risk of distant metastases and poor survival despite undergoing radiation-based adjuvant therapy and require a more aggressive adjuvant treatment and a more thorough follow-up.

  1. Pretreatment with Cry1Ac Protoxin Modulates the Immune Response, and Increases the Survival of Plasmodium-Infected CBA/Ca Mice

    Directory of Open Access Journals (Sweden)

    Martha Legorreta-Herrera

    2010-01-01

    Full Text Available Malaria is a major global health problem that kills 1-2 million people each year. Despite exhaustive research, naturally acquired immunity is poorly understood. Cry1A proteins are potent immunogens with adjuvant properties and are able to induce strong cellular and humoral responses. In fact, it has been shown that administration of Cry1Ac protoxin alone or with amoebic lysates induces protection against the lethal infection caused by the protozoa Naegleria fowleri. In this work, we studied whether Cry1Ac is able to activate the innate immune response to induce protection against Plasmodium berghei ANKA (lethal and P. chabaudi AS (nonlethal parasites in CBA/Ca mice. Treatment with Cry1Ac induced protection against both Plasmodium species in terms of reduced parasitaemia, longer survival time, modulation of pro- and anti-inflammatory cytokines, and increased levels of specific antibodies against Plasmodium. Understanding how to boost innate immunity to Plasmodium infection should lead to immunologically based intervention strategies.

  2. Carotenoid crystal formation in Arabidopsis and carrot roots caused by increased phytoene synthase protein levels.

    Directory of Open Access Journals (Sweden)

    Dirk Maass

    Full Text Available BACKGROUND: As the first pathway-specific enzyme in carotenoid biosynthesis, phytoene synthase (PSY is a prime regulatory target. This includes a number of biotechnological approaches that have successfully increased the carotenoid content in agronomically relevant non-green plant tissues through tissue-specific PSY overexpression. We investigated the differential effects of constitutive AtPSY overexpression in green and non-green cells of transgenic Arabidopsis lines. This revealed striking similarities to the situation found in orange carrot roots with respect to carotenoid amounts and sequestration mechanism. METHODOLOGY/PRINCIPAL FINDINGS: In Arabidopsis seedlings, carotenoid content remained unaffected by increased AtPSY levels although the protein was almost quantitatively imported into plastids, as shown by western blot analyses. In contrast, non-photosynthetic calli and roots overexpressing AtPSY accumulated carotenoids 10 and 100-fold above the corresponding wild-type tissues and contained 1800 and 500 microg carotenoids per g dry weight, respectively. This increase coincided with a change of the pattern of accumulated carotenoids, as xanthophylls decreased relative to beta-carotene and carotene intermediates accumulated. As shown by polarization microscopy, carotenoids were found deposited in crystals, similar to crystalline-type chromoplasts of non-green tissues present in several other taxa. In fact, orange-colored carrots showed a similar situation with increased PSY protein as well as carotenoid levels and accumulation patterns whereas wild white-rooted carrots were similar to Arabidopsis wild type roots in this respect. Initiation of carotenoid crystal formation by increased PSY protein amounts was further confirmed by overexpressing crtB, a bacterial PSY gene, in white carrots, resulting in increased carotenoid amounts deposited in crystals. CONCLUSIONS: The sequestration of carotenoids into crystals can be driven by the

  3. Ocean Acidification Causes Increased Calcium Carbonate Turnover during Larval Shell Formation

    Science.gov (United States)

    Frieder, C.; Pan, F.; Applebaum, S.; Manahan, D. T.

    2016-02-01

    Mollusca is a major taxon for studies of the evolution and mechanisms of calcification. Under current and future ocean change scenarios, decreases in shell size have been observed in many molluscan species during early development. The mechanistic basis for these decreases are of significant interest. In this study, Pacific oyster larvae (Crassostrea gigas) reared at aragonite undersaturation (Ω > 1). Coupling radioisotope tracer assays with mineral mass measurements allowed calculation of calcification budgets for first shell formation in veliger stage larvae. Three primary mechanisms (in order of increasing effect) contributed to the change in shell mass at undersaturation: delayed onset of calcification, increased dissolution rates, and decreased net calcification rates. The observation of dissolution indicates turnover of the newly formed shell, and physicochemical constraints of undersaturation provide a mechanistic basis for decreased calcification.

  4. [Light pollution increases morbidity and mortality rate from different causes in male rats].

    Science.gov (United States)

    Bukalev, A V; Vinogradova, I A; Zabezhinskiĭ, M A; Semenchenko, A V; Anisimov, V N

    2012-01-01

    The influence of different light regimes (constant light--LL; constant darkness--DD; standard light regime--LD, 12 hours light 12 hours darkness; natural lightening of the North-West of Russia--NL) on the dynamics of life's morbidity rate, spontaneous tumorigenesis and frequency of some kinds of non-tumor pathology revealed at the post-mortem examination of male rats was studied. It was found out that the maintenance of animals at LL and NL conditions led to the increase of the number of infectious diseases, substantially faster development of spontaneous tumors and the increase of non-tumor diseases in comparison with the animals kept at LD (standard light) regime. Light deprivation (DD) led to substantial reduction of development of new growth, of non-tumor and infectious diseases in comparison with the similar parameters in standard light regime.

  5. Increased alcohol consumption as a cause of alcoholism, without similar evidence for depression

    DEFF Research Database (Denmark)

    Wium-Andersen, Marie Kim; Orsted, David Dynnes; Tolstrup, Janne Schurmann

    2015-01-01

    BACKGROUND: Increased alcohol consumption has been associated with depression and alcoholism, but whether these associations are causal remains unclear. We tested whether alcohol consumption is causally associated with depression and alcoholism. METHODS: We included 78 154 men and women aged 20.......04 (1.03-1.06) observational for prescription antidepressant use, and 4.52 (0.99-20.5) causal and 0.98 (0.94-1.03) observational for hospitalization/death with depression. CONCLUSIONS: These data indicate that the association between increased alcohol consumption and alcoholism is causal, without......-100 years randomly selected in 1991-2010 from the general population of Copenhagen, Denmark, and genotyped 68 486 participants for two genetic variants in two alcohol dehydrogenase (ADH) genes, ADH-1B (rs1229984) and ADH-1C (rs698). We performed observational and causal analyses using a Mendelian...

  6. Sources of Increased Spring and Streamflow Caused by the 2014 South Napa Earthquake

    Science.gov (United States)

    Rytuba, J. J.; Holzer, T. L.

    2014-12-01

    Seasonally dry springs and creeks began flowing over a broad region in the hills around Napa following the M6.0 South Napa earthquake on August 24, 2014. Flows in hillside creek beds, which were dry before the earthquake, were reported from 19 km west, to 6 km east, and 18 km north of Napa and the epicenter, an area that shook at MMI≥VI. The exact timing of the increased flow is unknown because the earthquake occurred at 3:20 AM PDT. A gaging station on the Napa River, which is downstream from several tributaries that began flowing after the earthquake, showed a sudden increase of flow rate within 45 minutes following the earthquake. The sudden increase at the gaging station suggests flows initiated either contemporaneously with or very soon after the strong shaking. This timing is consistent with eyewitness accounts of other streams and springs at daylight, a few hours after the earthquake. One of the largest increases of streamflow was in Green Valley, where a streamflow rate of about 100 cubic hectometers per day was measured in Wild Horse Creek. Two types of waters are being discharged in the Wild Horse Creek drainage: 1) water with low iron concentration that has exchanged with rhyolitic flows and tuffs in the upper part of the drainage; and 2) high iron concentration water that has exchanged with basaltic andesite in the middle part of drainage (vertical interval of about 75 meters). The high iron waters are depositing FeOOH other iron phases. Mixing of the two water types results in water with pH 6.9 and conductivity of 0.197 mS. This water is used by the Vallejo Water District for domestic purposes after it is mixed with recent surface water runoff stored in Lake Frey reservoir in order to improve its quality. Other drainages that have increased flow since the earthquake have water chemistry consistent with exchange with rhyolitic flows and tuffs that are the dominant rock type in these drainages.

  7. Absence of Protoheme IX Farnesyltransferase CtaB Causes Virulence Attenuation but Enhances Pigment Production and Persister Survival in MRSA.

    Science.gov (United States)

    Xu, Tao; Han, Jian; Zhang, Jia; Chen, Jiazhen; Wu, Nan; Zhang, Wenhong; Zhang, Ying

    2016-01-01

    The membrane protein CtaB in S. aureus is a protoheme IX farnesyltransferase involved in the synthesis of the heme containing terminal oxidases of bacterial respiratory chain. In this study, to assess the role of CtaB in S. aureus virulence, pigment production, and persister formation, we constructed a ctaB mutant in the methicillin-resistant Staphylococcus aureus (MRSA) strain USA500. We found that deletion of ctaB attenuated growth and virulence in mice but enhanced pigment production and formation of quinolone tolerant persister cells in stationary phase. RNA-seq analysis showed that deletion of ctaB caused decreased transcription of several virulence genes including RNAIII which is consistent with its virulence attenuation. In addition, transcription of 20 ribosomal genes and 24 genes involved in amino acid biosynthesis was significantly down-regulated in the ctaB knockout mutant compared with the parent strain. These findings suggest the importance of heme biosynthesis in virulence and persister formation of S. aureus .

  8. Nonalcoholic fatty liver disease and increased risk of 1-year all-cause and cardiac hospital readmissions in elderly patients admitted for acute heart failure.

    Science.gov (United States)

    Valbusa, Filippo; Bonapace, Stefano; Agnoletti, Davide; Scala, Luca; Grillo, Cristina; Arduini, Pietro; Turcato, Emanuela; Mantovani, Alessandro; Zoppini, Giacomo; Arcaro, Guido; Byrne, Christopher; Targher, Giovanni

    2017-01-01

    Nonalcoholic fatty liver disease (NAFLD) is an emerging risk factor for heart failure (HF). Although some progress has been made in improving survival among patients admitted for HF, the rates of hospital readmissions and the related costs continue to rise dramatically. We sought to examine whether NAFLD and its severity (diagnosed at hospital admission) was independently associated with a higher risk of 1-year all-cause and cardiac re-hospitalization in patients admitted for acute HF. We studied 212 elderly patients who were consecutively admitted with acute HF to the Hospital of Negrar (Verona) over a 1-year period. Diagnosis of NAFLD was based on ultrasonography, whereas the severity of advanced NAFLD fibrosis was based on the fibrosis (FIB)-4 score and other non-invasive fibrosis scores. Patients with acute myocardial infarction, severe valvular heart diseases, end-stage renal disease, cancer, known liver diseases or decompensated cirrhosis were excluded. Cox regression was used to estimate hazard ratios (HR) for the associations between NAFLD and the outcome(s) of interest. The cumulative rate of 1-year all-cause re-hospitalizations was 46.7% (n = 99, mainly due to cardiac causes). Patients with NAFLD (n = 109; 51.4%) had remarkably higher 1-year all-cause and cardiac re-hospitalization rates compared with their counterparts without NAFLD. Both event rates were particularly increased in those with advanced NAFLD fibrosis. NAFLD was associated with a 5-fold increased risk of 1-year all-cause re-hospitalization (adjusted-hazard ratio 5.05, 95% confidence intervals 2.78-9.10, pacute HF.

  9. Increased toxic urinary cations in males with interstitial cystitis: a possible cause of bladder symptoms.

    Science.gov (United States)

    Argade, Sulabha; Berecz, Zoltan; Su, Yongxuan; Parsons, C Lowell

    2016-12-01

    To identify and quantify toxic urinary cations in male patients with bladder pain syndrome/interstitial cystitis versus male controls, to compare them in symptomatic patients to those significantly improved, and to evaluate cytotoxicity of these cations to cultured urothelial cells to determine whether Tamm-Horsfall protein (THP) can neutralize the cations. Isolation of cationic fraction (CFs) was achieved by solid phase extraction on urine specimens of 51 male patients with IC and 33 male controls. C 18 reverse-phase high-performance liquid chromatography was used to profile and quantify cationic metabolites. Major CF peaks were identified by liquid chromatography-tandem mass spectrometry. HTB-4 urothelial cells were used to determine the cytotoxicity of CFs, individual metabolites, and of metabolite mixture with THP of patient versus THP of control subject. CF content was significantly higher in patients compared to controls (p < 0.001). Patients had higher levels of modified nucleosides, amino acids, and their derivatives compared to controls. Cytotoxicity for control versus patient mean (SEM) percent was 1.7 (2.9) % versus 63.0 (3.7) %, respectively, (p < 0.001). Cytotoxicity of metabolites was reduced in the presence of THP of control compared to THP of patient (p < 0.001). Patients with IC had significantly higher levels of cationic metabolites with higher cytotoxicity compared to controls. THP of these patients had reduced ability to sequester cytotoxicity of cationic metabolites. Patients who significantly improved on therapy had the same levels and toxicity of cationic metabolites as symptomatic males, suggesting that these cations may be the cause of epithelial dysfunction in IC.

  10. Aging as an evolvability-increasing program which can be switched off by organism to mobilize additional resources for survival.

    Science.gov (United States)

    Skulachev, Maxim V; Severin, Fedor F; Skulachev, Vladimir P

    2015-01-01

    During the last decade, several pieces of convincing evidence were published indicating that aging of living organisms is programmed, being a particular case of programmed death of organism (phenoptosis). Among them, the following observations can be mentioned. (1) Species were described that show negligible aging. In mammals, the naked mole rat is the most impressive example. This is a rodent of mouse size living at least 10-fold longer than a mouse and having fecundity higher than a mouse and no agerelated diseases. (2) In some species with high aging rate, genes responsible for active organization of aging by poisoning of the organism with endogenous metabolites have been identified. (3) In women, standard deviations divided by the mean are the same for age of menarche (an event controlled by the ontogenetic program) and for age of menopause (an aging-related event). (4) Inhibitors of programmed cell death (apoptosis and necrosis) retard and in certain cases even reverse the development of age-dependent pathologies. (5) In aging species, the rate of aging is regulated by the individual which responds by changes in this rate to changes in the environmental conditions. In this review, we consider point (5) in detail. Data are summarized suggesting that inhibition of aging rate by moderate food restriction can be explained assuming that such restriction is perceived by the organism as a signal of future starvation. In response to this dramatic signal, the organism switches off such an optional program as aging, mobilizing in such a way additional reserves for survival. A similar explanation is postulated for geroprotective effects of heavy muscle work, a lowering or a rise in the external temperature, small amounts of metabolic poisons (hormesis), low doses of radiation, and other deleterious events. On the contrary, sometimes certain positive signals can prolong life by inhibiting the aging program in individuals who are useful for the community (e

  11. Hepatic radiofrequency ablation causes an increase of circulating histones in patients with hepatocellular carcinoma.

    Science.gov (United States)

    Gu, Tao; Ge, Yang; Song, Yuezhang; Fu, Zhanzhao; Zhang, Yunjie; Wang, Guangxia; Shao, Shasha; Wen, Tao

    2015-11-01

    Radiofrequency ablation (RFA) has been increasingly accepted for the treatment of hepatocellular carcinoma (HCC). However, RFA has been associated with an obvious systemic inflammatory response, but little is known about the underlying mechanisms. Circulating histones are recently identified as pivotal inflammatory mediators. Hence, we investigated whether circulating histones are involved in RFA-related inflammation. Serial blood samples were collected from 42 HCC patients undergoing RFA at 3 time points: pre-RFA, post-RFA (within 24 h), and in 4-week follow up after RFA. Plasma histones, myeloperoxidase (MPO), inflammatory cytokines (IL-1β, IL-6, IL-10, TNF-α), liver damage parameters (ALT, AST), and creatinine were measured. Compared to pre-RFA (0.837 μg/ml), there was a significant increase in the levels of circulating histones within 24 h post-RFA (4.576 μg/ml, p histones decreased to pre-RFA levels in 4-week follow up after RFA. Meanwhile, MPO, IL-6, and IL-10 were elevated remarkably within 24 h post-RFA, indicative of an occurrence of the inflammatory response. Notably, histone levels correlated well with MPO (r = 0.5678), IL-6 (r = 0.4851), and IL-10 (r = 0.3574), respectively. In addition, there was a significant damage of liver function in patients within 24 h post-RFA, evidenced by the increased levels of ALT and AST. No changes in creatinine levels were observed. These data demonstrate that circulating histones are excessively released in HCC patients treated with RFA, which may lead to systemic inflammation by stimulating neutrophil activation and promoting cytokine production. Circulating histones may act as a novel marker to indicate the extent of inflammation related to RFA.

  12. Atypical celiac disease as cause of increased need for thyroxine: a systematic study.

    Science.gov (United States)

    Virili, Camilla; Bassotti, Giulia; Santaguida, Maria Giulia; Iuorio, Raffaella; Del Duca, Susanna Carlotta; Mercuri, Valeria; Picarelli, Antonio; Gargiulo, Patrizia; Gargano, Lucilla; Centanni, Marco

    2012-03-01

    Replacement T4 dose in hypothyroid patients bearing both chronic autoimmune thyroiditis and atypical celiac disease (CD) has been analyzed. Replacement T4 dose has been analyzed in 35 hypothyroid patients with Hashimoto's thyroiditis (HT) and atypical CD, as defined by the American Gastroenterological Association. We have evaluated the ability of the same dose of T4 to reach target TSH in 21 patients before and during gluten-free diet (GFD). In the remaining 14 patients, noncompliant with GFD, we analyzed replacement T4 dose and compared it with that in a similar group consisting of 68 patients with hypothyroid HT but no evidence of celiac sprue or other conditions interfering with T4 absorption. In patients with isolated HT, the desired serum TSH (median=1.02 mU/liter) was reached in all patients after 5±2 months of treatment at a median T4 dose of 1.31 μg/kg·d. After a similar period and dose of T4, higher levels of TSH (median=4.20 mU/liter) were observed in patients with HT and CD. In 21 CD patients, target TSH (median TSH=1.25 mU/liter) has been attained after 11±3 months of GFD without increasing T4 dose (1.32 μg/kg·d). In the remaining 14 patients, who were noncompliant with GFD, target TSH has also been achieved but at a higher T4 dose (median=1.96 μg/kg·d; +49%; P=0.0002) than in hypothyroid patients without CD. Atypical CD increases the need for T4. The effect was reversed by GFD or by increasing T4 dose. Malabsorption of T4 may provide the opportunity to detect CD that was overlooked until the patients were put under T4 therapy.

  13. Systematic appraisal of lactose intolerance as cause of increased need for oral thyroxine.

    Science.gov (United States)

    Cellini, Miriam; Santaguida, Maria Giulia; Gatto, Ilenia; Virili, Camilla; Del Duca, Susanna Carlotta; Brusca, Nunzia; Capriello, Silvia; Gargano, Lucilla; Centanni, Marco

    2014-08-01

    An increased need for T4 has been described in patients with different gastrointestinal disorders. However, there is a lack of systematic studies assessing the need for T4 in hypothyroid patients with lactose intolerance, a widespread and often occult disorder. The objective of the study was to assess the replacement T4 dose required in hypothyroid patients with lactose intolerance. This was a cohort study. The study was conducted at an outpatient endocrinology unit in a University Hospital. The replacement T4 dose has been analyzed, from 2009 to 2012, in 34 hypothyroid patients due to Hashimoto's thyroiditis and lactose intolerance and being noncompliant with a lactose-free diet. An individually tailored T4 dose was measured. In all patients with isolated Hashimoto's thyroiditis, target TSH (median TSH 1.02 mU/L) was obtained at a median T4 dose of 1.31 μg/kg/d. In patients with lactose intolerance, only five of 34 patients reached the desired TSH (median TSH 0.83 mU/L) with a similar T4 dose (1.29 μg/kg/d). In the remaining 29 patients, the T4 dose was progressively increased and the target TSH (median TSH 1.21 mU/L) was attained at a median T4 dose of 1.81 μg/kg/d (+38%, P lactose intolerance, a median T4 dose of 1.72 μg/kg/d (+31% P lactose intolerance significantly increased the need for oral T4 in hypothyroid patients.

  14. Modern Electronic Devices: An Increasingly Common Cause of Skin Disorders in Consumers.

    Science.gov (United States)

    Corazza, Monica; Minghetti, Sara; Bertoldi, Alberto Maria; Martina, Emanuela; Virgili, Annarosa; Borghi, Alessandro

    2016-01-01

    : The modern conveniences and enjoyment brought about by electronic devices bring with them some health concerns. In particular, personal electronic devices are responsible for rising cases of several skin disorders, including pressure, friction, contact dermatitis, and other physical dermatitis. The universal use of such devices, either for work or recreational purposes, will probably increase the occurrence of polymorphous skin manifestations over time. It is important for clinicians to consider electronics as potential sources of dermatological ailments, for proper patient management. We performed a literature review on skin disorders associated with the personal use of modern technology, including personal computers and laptops, personal computer accessories, mobile phones, tablets, video games, and consoles.

  15. Combined exposure to anti-androgens causes markedly increased frequencies of hypospadias in the rat

    DEFF Research Database (Denmark)

    Christiansen, Sofie; Scholze, M.; Petersen, Marta Axelstad

    2008-01-01

    of several anti-androgenic chemicals. In a mixture (MIX) study with three androgen receptor antagonists, vinclozolin, flutamide and procymidone, rats were gavaged during gestation and lactation with several doses of a MIX of the three chemicals or the chemicals alone. External malformations of the male...... reproductive organs were assessed on PND 47 using a score from 0 to 3 (normal to marked) for hypospadias. Markedly increased frequencies were observed after exposure to a MIX of the three chemicals compared to administration of the three chemicals alone. Anogenital distance at PND 1, nipple retention at PND 13...

  16. Reduced knee flexion is a possible cause of increased loading rates in individuals with patellofemoral pain.

    Science.gov (United States)

    Silva, Danilo de Oliveira; Briani, Ronaldo Valdir; Pazzinatto, Marcella Ferraz; Ferrari, Deisi; Aragão, Fernando Amâncio; Azevedo, Fábio Mícolis de

    2015-11-01

    Stair ascent is an activity that exacerbates symptoms of individuals with patellofemoral pain. The discomfort associated with this activity usually results in gait modification such as reduced knee flexion in an attempt to reduce pain. Although such compensatory strategy is a logical approach to decrease pain, it also reduces the normal active shock absorption increasing loading rates and may lead to deleterious and degenerative changes of the knee joint. Thus, the aims of this study were (i) to investigate whether there is reduced knee flexion in adults with PFP compared to healthy controls; and (ii) to analyze loading rates in these subjects, during stair climbing. Twenty-nine individuals with patellofemoral pain and twenty-five control individuals (18-30 years) participated in this study. Each subject underwent three-dimensional kinematic and kinetic analyses during stair climbing on two separate days. Between-groups analyses of variance were performed to identify differences in peak knee flexion and loading rates. Intraclass correlation coefficient was performed to verify the reliability of the variables. On both days, the patellofemoral pain group demonstrated significantly reduced peak knee flexion and increased loading rates. In addition, the two variables obtained high to very high reliability. Reduced knee flexion during stair climbing as a strategy to avoid anterior knee pain does not seem to be healthy for lower limb mechanical distributions. Repeated loading at higher loading rates may be damaging to lower limb joints. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Increasing temperature causes flowering onset time changes of alpine ginger Roscoea in the Central Himalayas

    Directory of Open Access Journals (Sweden)

    Dharmalingam Mohandass

    2015-09-01

    Full Text Available Recent herbarium-based phenology assessments of many plant species have found significant responses to global climate change over the previous century. In this study, we investigate how the flowering phenology of three alpine ginger Roscoea species responses to climate change over the century from 1913 to 2011, by comparing between herbarium-based phenology records and direct flowering observations. According to the observations, flowering onset of the three alpine ginger species occurred either 22 days earlier or was delayed by 8–30 days when comparing the mean peak flowering date between herbarium-based phenology records and direct flowering observations. It is likely that this significant change in flowering onset is due to increased annual minimum and maximum temperatures and mean annual temperature by about 0.053°C per year. Our results also show that flowering time changes occurred due to an increasing winter–spring minimum temperature and monsoon minimum temperature, suggesting that these Roscoea species respond greatly to climate warming resulting in changes on flowering times.

  18. The Internet and Video Games: Causes of Increased Aggressiveness Among Young People

    Directory of Open Access Journals (Sweden)

    Nataša Ružić

    2011-12-01

    Full Text Available The increase in youth violence is among the most serious problems facing modern society. Many experts adhere to the opinion that responsibility for this phenomenon is borne by families, schools, and the media. The so-called digital generation spends much of its free time on the Internet and accepts the values imposed by the media. The modern criterion of success is to reach glory by any means necessary. As such, it is understandable that young people, eager for publicity, look for creative ways to attract attention. One of the most expedient ways to achieve fame and prove their ‘originality’ is by posting videos of violent behavior on websites like YouTube. The Internet has brought limitless freedom in the exposure of inappropriate content and has thus contributed to an increase in violence among the young, primarily through the video games industry. Based on all the above, we argue that the Internet has spurred and intensified the development of cyberbullying.

  19. A macro-enzyme cause of an isolated increase of alkaline phosphatase.

    Science.gov (United States)

    Cervinski, Mark A; Lee, Hong Kee; Martin, Isabella W; Gavrilov, Dimitar K

    2015-02-02

    Macroenzyme complexes of serum enzymes and antibody can increase the circulating enzymatic activity and may lead to unnecessary additional testing and procedures. Laboratory physicians and scientists need to be aware of techniques to identify macroenzyme complexes when suspected. To investigate the possibility of a macro-alkaline phosphatase in the serum of a 74 year old male with persistently increased alkaline phosphatase we coupled a protein A/G agarose affinity chromatography technique with isoenzyme electrophoresis to look for the presence of macro-alkaline phosphatase. The majority of the alkaline phosphatase activity in the patient's serum sample was bound to the column and only a minor fraction (25%) of alkaline phosphatase activity was present in the column flow-through. The alkaline phosphatase activity was also found to co-elute with the immunoglobulins in the patient sample. The alkaline phosphatase activity in a control serum sample concurrently treated in the same manner did not bind to the column and was found in the column flow-through. The use of protein A/G agarose affinity chromatography is a rapid and simple method that can be applied to the investigation of other macro-enzyme complexes. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Peritoneal Dialysis Catheter Increases Leukocyte Recruitment in the Mouse Parietal Peritoneum Microcirculation and Causes Fibrosis.

    Science.gov (United States)

    Kowalewska, Paulina M; Margetts, Peter J; Fox-Robichaud, Alison E

    2016-01-01

    ♦ The objective of this study was to examine the effects of a conventional dialysis solution and peritoneal catheter on leukocyte-endothelial cell interactions in the microcirculation of the parietal peritoneum in a subacute peritoneal dialysis (PD) mouse model. ♦ An intraperitoneal (IP) catheter with a subcutaneous injection port was implanted into mice and, after a 2-week healing period, the animals were injected daily for 6 weeks with a 2.5% dextrose solution. Intravital microscopy (IVM) of the parietal peritoneum microcirculation was performed 4 hours after the last injection of the dialysis solution. Leukocyte-endothelial cell interactions were quantified and compared with catheterized controls without dialysis treatment and naïve mice. ♦ The number of rolling and extravascular leukocytes along with peritoneal fibrosis and neovascularization were significantly increased in the catheterized animals compared with naïve mice but did not significantly differ between the 2 groups of catheterized animals with sham injections or dialysis solution treatment. ♦ The peritoneal catheter implant increased leukocyte rolling and extravasation, peritoneal fibrosis and vascularization in the parietal peritoneum independently from the dialysis solution treatment. Copyright © 2016 International Society for Peritoneal Dialysis.

  1. Do magnetic fields cause increased risk of childhood leukemia via melatonin disruption?

    Science.gov (United States)

    Henshaw, Denis L; Reiter, Russel J

    2005-01-01

    Epidemiological studies have reported associations between exposure to power frequency magnetic fields and increased risk of certain cancer and noncancer illnesses. For childhood leukemia, a doubling of risk has been associated with exposures above 0.3/0.4 microT. Here, we propose that the melatonin hypothesis, in which power frequency magnetic fields suppress the nocturnal production of melatonin in the pineal gland, accounts for the observed increased risk of childhood leukemia. Such melatonin disruption has been shown in animals, especially with exposure to electric and/or rapid on/off magnetic fields. Equivocal evidence has been obtained from controlled laboratory magnetic field exposures of volunteers, although the exposure conditions are generally atypical of neighborhood exposures. In contrast, support for the hypothesis is found in the body of studies showing magnetic field disruption of melatonin in human populations chronically exposed to both electric and magnetic fields associated with electricity distribution. Further support comes from the observation that melatonin is highly protective of oxidative damage to the human haemopoietic system. Aspects of the hypothesis are amenable to further investigation. Copyright 2005 Wiley-Liss, Inc

  2. New treatment options for infections caused by increasingly antimicrobial-resistant Neisseria gonorrhoeae.

    Science.gov (United States)

    Lee, Hyukmin; Lee, Kyungwon; Chong, Yunsop

    2016-01-01

    The emergence of high-level resistance to ceftriaxone is giving rise to serious concern about absence of effective treatment options to cure gonococcal infections. Increasing the dosage regimen can be applied to ceftriaxone and azithromycin, but the emergence of high-level resistance has already been reported. Spectinomycin is another active drug but has low efficacy in the treatment of pharyngeal gonorrhoea. Conventional antibiotics could be introduced for gonococcal treatment, but they have some limitations, such as the absence of clinical trials and breakpoint. Combining antibiotics is another promising method to cure patients and to prevent the emergence of resistance. The most important strategy to maintain the efficacy of antibiotics is rapid detection and dissemination control of novel resistant isolate.

  3. Prostaglandin E1 causes sedation and increases 5-hydroxytryptamine turnover in rat brain

    Science.gov (United States)

    Haubrich, D. R.; Perez-Cruet, J.; Reid, W. D.

    1973-01-01

    1. Administration of prostaglandin E1 (1 mg/kg, i.p.) to rats induced sedation and a decrease in muscular tone. Prostaglandin E1-induced sedation was accompanied by the low voltage-high frequency E.E.G. pattern characteristic of the waking animal. 2. Administration of prostaglandin E1 also increased the turnover rate of 5-hydroxytryptamine and raised the concentration of acetylcholine in brain. 3. The behavioural effects of prostaglandin were blocked by prior administration of p-chlorophenylalanine or pargyline, drugs which lowered the brain concentration of 5-hydroxyindoleacetic acid (5-HIAA), and was potentiated by pretreatment with probenecid, which elevated the 5-HIAA concentration. Pretreatment with atropine sulphate failed to alter prostaglandin E1-induced sedation. 4. The results are compatible with the possibility that prostaglandin E1 induces a state resembling paradoxical sleep through an action on 5-hydroxytryptamine metabolism in brain. PMID:4269288

  4. Spaceflight and clinorotation cause cytoskeleton and mitochondria changes and increases in apoptosis in cultured cells

    Science.gov (United States)

    Schatten, H.; Lewis, M. L.; Chakrabarti, A.

    2001-01-01

    The cytoskeleton is a complex network of fibers that is sensitive to environmental factors including microgravity and altered gravitational forces. Cellular functions such as transport of cell organelles depend on cytoskeletal integrity; regulation of cytoskeletal activity plays a role in cell maintenance, cell division, and apoptosis. Here we report cytoskeletal and mitochondria alterations in cultured human lymphocyte (Jurkat) cells after exposure to spaceflight and in insect cells of Drosophila melanogaster (Schneider S-1) after exposure to conditions created by clinostat rotation. Jurkat cells were flown on the space shuttle in Biorack cassettes while Schneider S-1 cells were exposed to altered gravity forces as produced by clinostat rotation. The effects of both treatments were similar in the different cell types. Fifty percent of cells displayed effects on the microtubule network in both cell lines. Under these experimental conditions mitochondria clustering and morphological alterations of mitochondrial cristae was observed to various degrees after 4 and 48 hours of culture. Jurkat cells underwent cell divisions during exposure to spaceflight but a large number of apoptotic cells was also observed. Similar results were obtained in Schneider S-1 cells cultured under clinostat rotation. Both cell lines displayed mitochondria abnormalities and mitochondria clustering toward one side of the cells which is interpreted to be the result of microtubule disruption and failure of mitochondria transport along microtubules. The number of mitochondria was increased in cells exposed to altered gravity while cristae morphology was severely affected indicating altered mitochondria function. These results show that spaceflight as well as altered gravity produced by clinostat rotation affects microtubule and mitochondria organization and results in increases in apoptosis. Grant numbers: NAG 10-0224, NAG2-985. c 2001. Elsevier Science Ltd. All rights reserved.

  5. Increased Denitrification Rates Associated with Shifts in Prokaryotic Community Composition Caused by Varying Hydrologic Connectivity

    Directory of Open Access Journals (Sweden)

    Abigail Tomasek

    2017-11-01

    Full Text Available While modern developments in agriculture have allowed for increases in crop yields and rapid human population growth, they have also drastically altered biogeochemical cycles, including the biotransformation of nitrogen. Denitrification is a critical process performed by bacteria and fungi that removes nitrate in surface waters, thereby serving as a potential natural remediation strategy. We previously reported that constant inundation resulted in a coupling of denitrification gene abundances with denitrification rates in sediments, but these relationships were not maintained in periodically-inundated or non-inundated environments. In this study, we utilized Illumina next-generation sequencing to further evaluate how the microbial community responds to these hydrologic regimes and how this community is related to denitrification rates at three sites along a creek in an agricultural watershed over 2 years. The hydrologic connectivity of the sampling location had a significantly greater influence on the denitrification rate (P = 0.010, denitrification gene abundances (P < 0.001, and the prokaryotic community (P < 0.001, than did other spatiotemporal factors (e.g., creek sample site or sample month within the same year. However, annual variability among denitrification rates was also observed (P < 0.001. Furthermore, the denitrification rate was significantly positively correlated with water nitrate concentration (Spearman's ρ = 0.56, P < 0.0001, denitrification gene abundances (ρ = 0.23–0.47, P ≤ 0.006, and the abundances of members of the families Burkholderiaceae, Anaerolinaceae, Microbacteriaceae, Acidimicrobineae incertae sedis, Cytophagaceae, and Hyphomicrobiaceae (ρ = 0.17–0.25, P ≤ 0.041. Prokaryotic community composition accounted for the least amount of variation in denitrification rates (22%, while the collective influence of spatiotemporal factors and gene abundances accounted for 37%, with 40% of the variation related to

  6. Polyplex exposure inhibits cell cycle, increases inflammatory response, and can cause protein expression without cell division.

    Science.gov (United States)

    Matz, Rebecca L; Erickson, Blake; Vaidyanathan, Sriram; Kukowska-Latallo, Jolanta F; Baker, James R; Orr, Bradford G; Banaszak Holl, Mark M

    2013-04-01

    We sought to evaluate the relationship between cell division and protein expression when using commercial poly(ethylenimine) (PEI)-based polyplexes. The membrane dye PKH26 was used to assess cell division, and cyan fluorescent protein (CFP) was used to monitor protein expression. When analyzed at the whole population level, a greater number of cells divided than expressed protein, regardless of the level of protein expression observed, giving apparent consistency with the hypothesis that protein expression requires cells to pass through mitosis in order for the transgene to overcome the nuclear membrane. However, when the polyplex-exposed population was evaluated for the amount of division in the protein-expressing subpopulation, it was observed that substantial amounts of expression had occurred in the absence of division. Indeed, in HeLa S3 cells, this represented the majority of expressing cells. Of interest, the doubling time for both cell lines was slowed by ~2-fold upon exposure to polyplexes. This change was not altered by the origin of the plasmid DNA (pDNA) transgene promoter (cytomegalovirus (CMV) or elongation factor-1 alpha (EF1α)). Gene expression arrays in polyplex-exposed HeLa S3 cells showed upregulation of cell cycle arrest genes and downregulation of genes related to mitosis. Chemokine, interleukin, and toll-like receptor genes were also upregulated, suggesting activation of proinflammatory pathways. In summary, we find evidence that a cell division-independent expression pathway exists, and that polyplex exposure slows cell division and increases inflammatory response.

  7. Acanthamoeba castellanii metabolites increase the intracellular calcium level and cause cytotoxicity in wish cells.

    Science.gov (United States)

    Mattana, A; Bennardini, F; Usai, S; Fiori, P L; Franconi, F; Cappuccinelli, P

    1997-08-01

    Previous studies have shown that trophozoites of the pathogenic free-living amoeba Acanthamoeba castellanii rapidly lyse a variety of cells in vitro. However, the role played by cytolitic molecules that may participate in Acanthamoebal cytopathogenicity has yet to be completely elucidated. The aim of this work was to study whether soluble molecules released by A. castellanii trophozoites could induce cytopathic effect in human epithelial cells in vitro. The results obtained indicate that A. castellanii trophozoites constitutively elaborate and release soluble factors that immediately elicit a cytosolic free-calcium increase in target cells. This phenomenon is induced by low molecular weight amoebic metabolites and depends on a transmembrane influx of extracellular calcium. Morphological changes, cytoskeletal damage, cell death and cytolysis followed the elevation of cytosolic free-calcium levels. Calcium ions are very important for cell homeostasis, in fact, they control the functions of a variety of cellular responses, including secretion, cell proliferation and apoptosis. Our results suggest that the substained elevation of the cytosolic free-calcium in response to A. castellanii metabolites might play a fundamental role in target cell damage during Acanthamoeba infections.

  8. Combination of hydrostatic pressure and lacticin 3147 causes increased killing of Staphylococcus and Listeria.

    Science.gov (United States)

    Morgan, S M; Ross, R P; Beresford, T; Hill, C

    2000-03-01

    The use of hydrostatic pressure and lacticin 3147 treatments were evaluated in milk and whey with a view to combining both treatments for improving the quality of minimally processed dairy foods. The system was evaluated using two foodborne pathogens: Staphylococcus aureus ATCC6538 and Listeria innocua DPC1770. Trials against Staph. aureus ATCC6538 were performed using concentrated lacticin 3147 prepared from culture supernatant. The results demonstrated a more than additive effect when both treatments were used in combination. For example, the combination of 250 MPa (2.2 log reduction) and lacticin 3147 (1 log reduction) resulted in more than 6 logs of kill. Similar results were obtained when a foodgrade powdered form of lacticin 3147 (developed from a spray dried fermentatation of reconstituted demineralized whey powder) was evaluated for the inactivation of L. innocua DPC1770. Furthermore, it was observed that treatment of lacticin 3147 preparations with pressures greater than 400 MPa yielded an increase in bacteriocin activity (equivalent to a doubling of activity). These results indicate that a combination of high pressure and lacticin 3147 may be suitable for improving the quality of minimally processed foods at lower hydrostatic pressure levels.

  9. Acute primary angle closure attack does not cause an increased cup-to-disc ratio.

    Science.gov (United States)

    Chew, Shenton S L; Vasudevan, Sushil; Patel, Hussain Y; Gurria, Lulu U; Kerr, Nathan M; Gamble, Greg; Crowston, Jonathan G; Danesh-Meyer, Helen V

    2011-02-01

    To determine if an increased cup-to-disc ratio (CDR) and retinal nerve fiber layer (RNFL) loss occur after acute primary angle closure (APAC). Prospective, observational case series. Twenty participants with unilateral APAC provided 20 affected eyes and 20 fellow eyes (controls) for analysis. After initial presentation, participants attended 3 further assessments over a 12-month period (visit 2, within 2 weeks; visit 3, 2-3 months; and visit 4, 6-12 months), in which they underwent the following investigations: Heidelberg Retinal Tomography (Heidelberg Engineering, Dossenheim, Germany), optical coherence tomography of the RNFL and macula, and automated perimetry. Cup-to-disc ratio, optic cup area, neuroretinal rim area, RNFL thickness, macular thickness, and volume. There was no change from visits 2 to 4 in CDR (0.46 ± 0.17 vs. 0.47 ± 0.20; P = 0.94), neuroretinal rim area (1.64 ± 0.55 vs. 1.64 ± 0.57; P = 0.96), or other optic nerve head parameters analyzed in eyes with APAC. The mean overall RNFL thickness decreased from 106.6 ± 17.9 μm to 92.9 ± 18.3 μm between visits 2 and 3 (PAPAC that is treated promptly, although RNFL loss does occur. Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  10. Iron overload alters glucose homeostasis, causes liver steatosis, and increases serum triacylglycerols in rats.

    Science.gov (United States)

    Silva, Maísa; Silva, Marcelo E; de Paula, Heberth; Carneiro, Cláudia Martins; Pedrosa, Maria Lucia

    2008-06-01

    The objective of this study was to investigate the effect of iron overload with a hyperlipidemic diet on the histologic feature of hepatic tissue, the lipid and glycemic serum profiles, and the markers of oxidative damage and stress in a rat model. Twenty-four male Fischer rats, purchased from Experimental Nutrition Laboratory, Federal University of Ouro Preto, were assigned to 4 equal groups, 2 were fed a standard cholesterol-free diet (group C or control and CI or control with iron) containing 8.0% soybean oil and 2 were fed a hyperlipidemic diet (group H or hyperlipidemic and HI or hyperlipidemic with iron) containing 1.0% cholesterol and 25.0% soybean oil. A total of 50 mg of iron was administered to rats in groups CI and HI in 5 equal doses (1 every 3 weeks for a 16-week period) by intraperitoneal injections of 0.1 mL of iron dextran solution (100 g Fe(2+)/L; Sigma, St Louis, Mo). The other rats in groups C and H were treated in a similar manner but with sterile saline (0.1 mL). Irrespective of the diet, iron excess enhanced serum triacylglycerols (P .05) were observed in paraoxonase activities or in serum levels of free or total sulfhydryl radicals, malondialdehyde, or total antioxidants. The findings suggest that iron excess in the rat probably modifies lipid metabolism and, as a consequence, alters glucose homeostasis and increases the level of serum triacylglycerols but not of cholesterol.

  11. Pd-nanoparticles cause increased toxicity to kiwifruit pollen compared to soluble Pd(II)

    International Nuclear Information System (INIS)

    Speranza, Anna; Leopold, Kerstin; Maier, Marina; Taddei, Anna Rita; Scoccianti, Valeria

    2010-01-01

    In the present study, endpoints including in vitro pollen performance (i.e., germination and tube growth) and lethality were used as assessments of nanotoxicity. Pollen was treated with 5-10 nm-sized Pd particles, similar to those released into the environment by catalytic car exhaust converters. Results showed Pd-nanoparticles altered kiwifruit pollen morphology and entered the grains more rapidly and to a greater extent than soluble Pd(II). At particulate Pd concentrations well below those of soluble Pd(II), pollen grains experienced rapid losses in endogenous calcium and pollen plasma membrane damage was induced. This resulted in severe inhibition and subsequent cessation of pollen tube emergence and elongation at particulate Pd concentrations as low as 0.4 mg L -1 . Particulate Pd emissions related to automobile traffic have been increasing and are accumulating in the environment. This could seriously jeopardize in vivo pollen function, with impacts at an ecosystem level. - Nanoparticulate Pd - which resembles emissions from automobile catalysts - affects pollen to a higher extent than soluble Pd.

  12. Pd-nanoparticles cause increased toxicity to kiwifruit pollen compared to soluble Pd(II)

    Energy Technology Data Exchange (ETDEWEB)

    Speranza, Anna, E-mail: anna.speranza@unibo.i [Dipartimento di Biologia, Universita di Bologna, via Irnerio 42, 40126 Bologna (Italy); Leopold, Kerstin, E-mail: kerstin.leopold@lrz.tu-muenchen.d [Arbeitsgruppe fuer Analytische Chemie, Technische Universitaet Muenchen, Garching (Germany); Maier, Marina, E-mail: marina.maier@ch.tum.d [Arbeitsgruppe fuer Analytische Chemie, Technische Universitaet Muenchen, Garching (Germany); Taddei, Anna Rita, E-mail: artaddei@unitus.i [CIME, Universita della Tuscia, Viterbo (Italy); Scoccianti, Valeria, E-mail: valeria.scoccianti@uniurb.i [Dipartimento di Scienze dell' Uomo, dell' Ambiente e della Natura, Universita di Urbino ' Carlo Bo' , Urbino (Italy)

    2010-03-15

    In the present study, endpoints including in vitro pollen performance (i.e., germination and tube growth) and lethality were used as assessments of nanotoxicity. Pollen was treated with 5-10 nm-sized Pd particles, similar to those released into the environment by catalytic car exhaust converters. Results showed Pd-nanoparticles altered kiwifruit pollen morphology and entered the grains more rapidly and to a greater extent than soluble Pd(II). At particulate Pd concentrations well below those of soluble Pd(II), pollen grains experienced rapid losses in endogenous calcium and pollen plasma membrane damage was induced. This resulted in severe inhibition and subsequent cessation of pollen tube emergence and elongation at particulate Pd concentrations as low as 0.4 mg L{sup -1}. Particulate Pd emissions related to automobile traffic have been increasing and are accumulating in the environment. This could seriously jeopardize in vivo pollen function, with impacts at an ecosystem level. - Nanoparticulate Pd - which resembles emissions from automobile catalysts - affects pollen to a higher extent than soluble Pd.

  13. Handling may cause increased shedding of Escherichia coli and total coliforms in pigs.

    Science.gov (United States)

    Dowd, Scot E; Callaway, Todd R; Morrow-Tesch, Julie

    2007-01-01

    Many common management practices such as transportation, weaning, handling, and changes in social groups are stressful to animals. The effects of stressors on the intestinal microbial ecosystem are still being investigated. This study was designed to evaluate the effect of handling on naturally occurring intestinal populations of Escherichia coli and total coliforms in swine. Finishing pigs were subjected to repeated handling, in which they were removed from their pens each day, moved down an alley to a scale, weighed individually, and moved back to their pens. This procedure was performed with the control groups once at the beginning and once at the end of the study, while treatment groups were herded and weighed each day for 8 days. Most probable numbers (MPN)/g of E. coli (a subset of the coliform group) and total coliforms were measured daily for treatment and control groups. Using repeated measures analyses, increased MPN/g of feces, for both E. coli and total coliforms, were seen in the treatment groups compared to the control groups (P coliforms, possibly due to stress, and these populations of bacteria may have potential utility as inexpensive, noninvasive indicators of handling-related stress in pigs.

  14. Acute cannabis use causes increased psychotomimetic experiences in individuals prone to psychosis.

    Science.gov (United States)

    Mason, O; Morgan, C J A; Dhiman, S K; Patel, A; Parti, N; Patel, A; Curran, H V

    2009-06-01

    Epidemiological evidence suggests a link between cannabis use and psychosis. A variety of factors have been proposed to mediate an individual's vulnerability to the harmful effects of the drug, one of which is their psychosis proneness. We hypothesized that highly psychosis-prone individuals would report more marked psychotic experiences under the acute influence of cannabis. A group of cannabis users (n=140) completed the Psychotomimetic States Inventory (PSI) once while acutely intoxicated and again when free of cannabis. A control group (n=144) completed the PSI on two parallel test days. All participants also completed a drug history and the Schizotypal Personality Questionnaire (SPQ). Highly psychosis-prone individuals from both groups were then compared with individuals scoring low on psychosis proneness by taking those in each group scoring above and below the upper and lower quartiles using norms for the SPQ. Smoking cannabis in a naturalistic setting reliably induced marked increases in psychotomimetic symptoms. Consistent with predictions, highly psychosis-prone individuals experienced enhanced psychotomimetic states following acute cannabis use. These findings suggest that an individual's response to acute cannabis and their psychosis-proneness scores are related and both may be markers of vulnerability to the harmful effects of this drug.

  15. Is disomic homozygosity at the APECED locus the cause of increased autoimmunity in Down's syndrome?

    Science.gov (United States)

    Shield, J.; Wadsworth, E.; Hassold, T.; Judis, L. A.; Jacobs, P.

    1999-01-01

    AIMS—To examine the age of onset of insulin dependent diabetes mellitus (IDDM) in children with Down's syndrome compared with non-trisomic individuals, and to assess whether differences might be related to disomic homozygosity at the autoimmune polyglandular disease type 1 (APECED) gene locus.
METHODS—Children with Down's syndrome and IDDM were identified through the Down's syndrome association newsletter and from paediatricians. DNA was extracted from mouthbrush preparations provided by the parents and patients using standard techniques. Mapping techniques were then used to identify areas of reduction to homozygosity, including a marker that overlaps the locus for APECED. The frequency of disomic homozygosity for all markers (n = 18) was compared with a control group of 99 patients with Down's syndrome and their parents. The families also answered a questionnaire concerning diabetes and related autoimmune conditions in the family. Details were compared with the British Paediatric Surveillance Group 1988diabetes study.
RESULTS—Children with Down's syndrome and IDDM were diagnosed significantly earlier than the general population (6.7 v 8.0 years) with a far higher proportion diagnosed in the first 2 years of life (22% v 7%). There was no evidence of increased disomic homozygosity in the region of the APECED locus in Down's syndrome patients with IDDM compared with simple Down's syndrome.
CONCLUSIONS—The natural history of IDDM in Down's syndrome is different from that of the general population. Although children with Down's syndrome have features similar to cases of APECED, disomic homozygosity in this region does not explain the predilection for autoimmune disease.

 PMID:10490523

  16. Spaceflight Causes Increased Virulence of Serratia Marcescens on a Drosophila Melanogaster Host

    Science.gov (United States)

    Bhattacharya, Sharmila; Wade, William; Clemens-Grisham, Rachel; Hosamani, Ravikumar; Bhardwaj, Shilpa R.; Lera, Matthew P.; Gresser, Amy L.

    2015-01-01

    Drosophila melanogaster, or the fruit fly, has long been an important organism for Earth-based research, and is now increasingly utilized as a model system to understand the biological effects of spaceflight. Studies in Drosophila melanogaster have shown altered immune responses in 3rd instar larvae and adult males following spaceflight, changes similar to those observed in astronauts. In addition, spaceflight has also been shown to affect bacterial physiology, as evidenced by studies describing altered virulence of Salmonella typhimurium following spaceflight and variation in biofilm growth patterns for the opportunistic pathogen Pseudomonas aeruginosa during flight. We recently sent Serratia marcescens Db11, a Drosophila pathogen and an opportunistic human pathogen, to the ISS on SpaceX-5 (Fruit Fly Lab-01). S. marcescens samples were stored at 4degC for 24 days on-orbit and then allowed to grow for 120 hours at ambient station temperature before being returned to Earth. Upon return, bacteria were isolated and preserved in 50% glycerol or RNAlater. Storage, growth, and isolation for ground control samples were performed using the same procedures. Spaceflight and ground samples stored in 50% glycerol were diluted and injected into 5-7-day-old ground-born adult D. melanogaster. Lethality was significantly greater in flies injected with the spaceflight samples compared to those injected with ground bacterial samples. These results indicate a shift in the virulence profile of the spaceflight S. marcescens Db11 and will be further assessed with molecular biological analyses. Our findings strengthen the conclusion that spaceflight impacts the virulence of bacterial pathogens on model host organisms such as the fruit fly. This research was supported by NASA's ISS Program Office (ISSPO) and Space Life and Physical Sciences Research and Applications (SLPSRA).

  17. Splenectomy Causes 10-Fold Increased Risk of Portal Venous System Thrombosis in Liver Cirrhosis Patients.

    Science.gov (United States)

    Qi, Xingshun; Han, Guohong; Ye, Chun; Zhang, Yongguo; Dai, Junna; Peng, Ying; Deng, Han; Li, Jing; Hou, Feifei; Ning, Zheng; Zhao, Jiancheng; Zhang, Xintong; Wang, Ran; Guo, Xiaozhong

    2016-07-19

    BACKGROUND Portal venous system thrombosis (PVST) is a life-threatening complication of liver cirrhosis. We conducted a retrospective study to comprehensively analyze the prevalence and risk factors of PVST in liver cirrhosis. MATERIAL AND METHODS All cirrhotic patients without malignancy admitted between June 2012 and December 2013 were eligible if they underwent contrast-enhanced CT or MRI scans. Independent predictors of PVST in liver cirrhosis were calculated in multivariate analyses. Subgroup analyses were performed according to the severity of PVST (any PVST, main portal vein [MPV] thrombosis >50%, and clinically significant PVST) and splenectomy. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported. RESULTS Overall, 113 cirrhotic patients were enrolled. The prevalence of PVST was 16.8% (19/113). Splenectomy (any PVST: OR=11.494, 95%CI=2.152-61.395; MPV thrombosis >50%: OR=29.987, 95%CI=3.247-276.949; clinically significant PVST: OR=40.415, 95%CI=3.895-419.295) and higher hemoglobin (any PVST: OR=0.974, 95%CI=0.953-0.996; MPV thrombosis >50%: OR=0.936, 95%CI=0.895-0.980; clinically significant PVST: OR=0.935, 95%CI=0.891-0.982) were the independent predictors of PVST. The prevalence of PVST was 13.3% (14/105) after excluding splenectomy. Higher hemoglobin was the only independent predictor of MPV thrombosis >50% (OR=0.952, 95%CI=0.909-0.997). No independent predictors of any PVST or clinically significant PVST were identified in multivariate analyses. Additionally, PVST patients who underwent splenectomy had a significantly higher proportion of clinically significant PVST but lower MELD score than those who did not undergo splenectomy. In all analyses, the in-hospital mortality was not significantly different between cirrhotic patient with and without PVST. CONCLUSIONS Splenectomy may increase by at least 10-fold the risk of PVST in liver cirrhosis independent of severity of liver dysfunction.

  18. Selective pressure causes an RNA virus to trade reproductive fitness for increased structural and thermal stability of a viral enzyme.

    Directory of Open Access Journals (Sweden)

    Moshe Dessau

    Full Text Available The modulation of fitness by single mutational substitutions during environmental change is the most fundamental consequence of natural selection. The antagonistic tradeoffs of pleiotropic mutations that can be selected under changing environments therefore lie at the foundation of evolutionary biology. However, the molecular basis of fitness tradeoffs is rarely determined in terms of how these pleiotropic mutations affect protein structure. Here we use an interdisciplinary approach to study how antagonistic pleiotropy and protein function dictate a fitness tradeoff. We challenged populations of an RNA virus, bacteriophage Φ6, to evolve in a novel temperature environment where heat shock imposed extreme virus mortality. A single amino acid substitution in the viral lysin protein P5 (V207F favored improved stability, and hence survival of challenged viruses, despite a concomitant tradeoff that decreased viral reproduction. This mutation increased the thermostability of P5. Crystal structures of wild-type, mutant, and ligand-bound P5 reveal the molecular basis of this thermostabilization--the Phe207 side chain fills a hydrophobic cavity that is unoccupied in the wild-type--and identify P5 as a lytic transglycosylase. The mutation did not reduce the enzymatic activity of P5, suggesting that the reproduction tradeoff stems from other factors such as inefficient capsid assembly or disassembly. Our study demonstrates how combining experimental evolution, biochemistry, and structural biology can identify the mechanisms that drive the antagonistic pleiotropic phenotypes of an individual point mutation in the classic evolutionary tug-of-war between survival and reproduction.

  19. [Analysis of the causes of cancer negligence and low survival in the patients with malignant neoplasms of ENT and oral cavity in the city of Moscow].

    Science.gov (United States)

    Sdvizhkov, A M; Kozhanov, L G; Shatskaia, N Kh; Belov, E N

    2014-01-01

    The objective of the present study was to elucidate the causes of late detection of malignant neoplasms of ENT and oral cavity and low survival of the patents with these tumours in Moscow. The secondary objective was to elaborate the organizational measures for reducing the level of negligence and mortality from these malignancies among the city population. It was shown that the main cause behind the negligence is the late application of the patients for the medical assistance. Next in importance are asymptomatic clinical course of the disease in the absence of the pathognomonic and early signs of malignant neoplasms, a combination of several pathologies, imperfection of medical knowledge, and the poor resolving power of the modern methods. It is emphasized that the lack of vigilance against cancer among the practicing health providers is one of the main causes of medical errors. A few ways to address the problem of negligence with respect to malignant neoplasms of ENT and oral cavity in Moscow are proposed.

  20. The influence of increased hepatic sequestration after splenectomy on the survival and osmotic fragility of red cells in rats, with reference to protein levels in diets

    International Nuclear Information System (INIS)

    Hisaoka, Fumiko; Shiraki, Keizo; Sagawa, Sueko

    1977-01-01

    The sequestration of erythrocytes in rats was studied using an isologous 51-Cr labeled population of either normal or N-ethyl-maleimide treated red cells. Experiments were performed for observing the effects of the change in the hepatic sequestration of altered red cells on the osmotic fragility and the survival time of circulating red cells. The rate of sequestration in liver at different period after splenectomy was measured with respect to the survival time and osmotic fragility of red cells. The parameters of the proliferative response imposed on liver were also observed. The spleen sequestered selectively damaged red cells, while the liver compensated and overshot the sequestration for spleen after splenectomy. The sequestering response in liver increased gradually and reached the maximum level around 8 weeks after splenectomy, and then declined toward the control level. This compensatory response in liver was not observed in the rats fed with low protein diet. Therefore, the proliferative response imposed on liver by an extra work after splenectomy was not stimulated in the rats fed with low protein diet. Splenectomy prolonged erythrocyte survival and reduced the osmotic fragility of normal red cells, but the compensatory increase in the sequestration of damaged red cells in liver did not alter the survival and osmotic fragility of normal red cells. This fact indicates that the increased sequestration of reticuloendothelial cells in liver is basically reparative, and it is impossible to compensate for the absence of the spleen because of the inability to duplicate certain anatomic features peculiar to the spleen. (Iwakiri, K.)

  1. Ketogenic diet improves the spatial memory impairment caused by exposure to hypobaric hypoxia through increased acetylation of histones in rats.

    Science.gov (United States)

    Zhao, Ming; Huang, Xin; Cheng, Xiang; Lin, Xiao; Zhao, Tong; Wu, Liying; Yu, Xiaodan; Wu, Kuiwu; Fan, Ming; Zhu, Lingling

    2017-01-01

    Exposure to hypobaric hypoxia causes neuron cell damage, resulting in impaired cognitive function. Effective interventions to antagonize hypobaric hypoxia-induced memory impairment are in urgent need. Ketogenic diet (KD) has been successfully used to treat drug-resistant epilepsy and improves cognitive behaviors in epilepsy patients and other pathophysiological animal models. In the present study, we aimed to explore the potential beneficial effects of a KD on memory impairment caused by hypobaric hypoxia and the underlying possible mechanisms. We showed that the KD recipe used was ketogenic and increased plasma levels of ketone bodies, especially β-hydroxybutyrate. The results of the behavior tests showed that the KD did not affect general locomotor activity but obviously promoted spatial learning. Moreover, the KD significantly improved the spatial memory impairment caused by hypobaric hypoxia (simulated altitude of 6000 m, 24 h). In addition, the improving-effect of KD was mimicked by intraperitoneal injection of BHB. The western blot and immunohistochemistry results showed that KD treatment not only increased the acetylated levels of histone H3 and histone H4 compared to that of the control group but also antagonized the decrease in the acetylated histone H3 and H4 when exposed to hypobaric hypoxia. Furthermore, KD-hypoxia treatment also promoted PKA/CREB activation and BDNF protein expression compared to the effects of hypoxia alone. These results demonstrated that KD is a promising strategy to improve spatial memory impairment caused by hypobaric hypoxia, in which increased modification of histone acetylation plays an important role.

  2. Hydroxyurea-Increased Fetal Hemoglobin Is Associated with Less Organ Damage and Longer Survival in Adults with Sickle Cell Anemia.

    Science.gov (United States)

    Fitzhugh, Courtney D; Hsieh, Matthew M; Allen, Darlene; Coles, Wynona A; Seamon, Cassie; Ring, Michael; Zhao, Xiongce; Minniti, Caterina P; Rodgers, Griffin P; Schechter, Alan N; Tisdale, John F; Taylor, James G

    2015-01-01

    Adults with sickle cell anemia (HbSS) are inconsistently treated with hydroxyurea. We retrospectively evaluated the effects of elevating fetal hemoglobin with hydroxyurea on organ damage and survival in patients enrolled in our screening study between 2001 and 2010. An electronic medical record facilitated development of a database for comparison of study parameters based on hydroxyurea exposure and dose. This study is registered with ClinicalTrials.gov, number NCT00011648. Three hundred eighty-three adults with homozygous sickle cell disease were analyzed with 59 deaths during study follow-up. Cox regression analysis revealed deceased subjects had more hepatic dysfunction (elevated alkaline phosphatase, Hazard Ratio = 1.005, 95% CI 1.003-1.006, phydroxyurea, although only 66% of those received a dose within the recommended therapeutic range. Hydroxyurea use was associated with improved survival (Hazard Ratio = 0.58, 95% CI 0.34-0.97, p = 0.040). This effect was most pronounced in those taking the recommended dose of 15-35 mg/kg/day (Hazard Ratio 0.36, 95% CI 0.17-0.73, p = 0.0050). Hydroxyurea use was not associated with changes in organ function over time. Further, subjects with higher fetal hemoglobin responses to hydroxyurea were more likely to survive (p = 0.0004). While alkaline phosphatase was lowest in patients with the best fetal hemoglobin response (95.4 versus 123.6, p = 0.0065 and 96.1 versus 113.6U/L, p = 0.041 at first and last visits, respectively), other markers of organ damage were not consistently improved over time in patients with the highest fetal hemoglobin levels. Our data suggest that adults should be treated with the maximum tolerated hydroxyurea dose, ideally before organ damage occurs. Prospective studies are indicated to validate these findings.

  3. First feeding of Eugerres brasilianus (Carapeva larvae with Acartia tonsa (Copepod nauplii increases survival and resistance to acute stress

    Directory of Open Access Journals (Sweden)

    Wanessa de Melo Costa

    2016-01-01

    Full Text Available The rotifer Brachionus sp. is commonly used for larval feeding in marine fish hatcheries. The aim of this study was to evaluate whether the inclusion of Acartia tonsa nauplii in the initial diet of carapeva larvae improves their survival, growth and resistance to stress when compared to the regimen containing only rotifers. Adult copepods were collected in the wild and cultured with the microalgae Chaetoceros muelleri, Isochrysis galbana and Nannochloropsis oculata to obtain nauplii. Carapeva larvae were grown for 15 days using four treatments and three replicates: 1 Brachionus plicatilis rotifers (10 to 15/mL; 2 A. tonsa nauplii (0.25 to 0.5/mL; 3 Brachionus plicatilis rotifers (5 to 7.5/mL + A. tonsa nauplii (0.12 to 0.25/mL, and 4 no supply of live feed. After 15 days, the carapeva larvae were subjected to stress by exposure to air for 10 seconds and then returned to the source tank to evaluate survival after 24 h. Survival and stress resistance were higher in carapeva larvae fed B. plicatilis + A. tonsa nauplii (P<0.05, 20.9 ± 11.2% and 88.9%, respectively. These results confirm the positive effect of the inclusion of copepod nauplii in the diet of fish larvae. However, more research is needed to validate these results.

  4. Evidence for Increased Aggressiveness in a Recent Widespread Strain of Puccinia striiformis f. sp. tritici Causing Stripe Rust of Wheat

    DEFF Research Database (Denmark)

    Milus, Eugene A; Kristensen, Kristian; Hovmøller, Mogens S

    2009-01-01

    Stripe rust (yellow rust) of wheat, caused by Puccinia striiformis f. sp. tritici, has become more severe in eastern United States, Australia, and elsewhere since 2000. Recent research has shown that this coincided with a global spread of two closely related strains that were similar based...... to the warm temperature regime for all variables. Based on these results and previously published models for stripe rust epidemics, recent severe stripe rust epidemics were most likely enhanced by the pathogen's increased aggressiveness, especially at higher temperature. Furthermore, these results demonstrate...... that wheat rust fungi can adapt to warmer temperatures and cause severe disease in previously unfavorable environments...

  5. Escin Increases the Survival Rate of LPS-Induced Septic Mice Through Inhibition of HMGB1 Release from Macrophages

    Directory of Open Access Journals (Sweden)

    Yajun Cheng

    2015-07-01

    Full Text Available Background: Previous studies have described the effects of Escin on improving the survival rate of endotoxemic animals. The purpose of this study was to explore the molecular mechanisms of this potentially beneficial treatment. Methods: First, the survival rate of endotoxemic mice was monitored for up to 2 weeks after Escin pretreatment, Escin post-treatment, or Escin post-treatment + rHMGB1. The effects of Escin on the release of pro-inflammatory cytokines such as TNF-a, IL-1ß, IL-6 and HMGB1 in the serum of endotoxemic mice and LPS-induced macrophages were evaluated by ELISA. Furthermore, the mRNA and protein levels of HMGB1 in LPS-induced macrophages were measured by qRT-PCR and Western blot, respectively. Additionally, the release of pro-inflammatory cytokines such as TNF-a, IL-1ß, IL-6 was evaluated by ELISA in rHMGB1-induced macrophages. Finally, the protein levels and the activity of NF-κB in macrophages were checked by Western blot and ELISA, respectively. Results: Both pretreatment and post-treatment with Escin could improve the survival rate of endotoxemic mice, while exogenous rHMGB1 reversed this effect. In addition, Escin decreased the level of the pro-inflammatory cytokines TNF-a, IL-1ß, IL-6 and HMGB1 in endotoxemic mice and in LPS-induced macrophages. Escin could also inhibit the mRNA levels and activity of HMGB1. The release of the pro-inflammatory cytokines TNF-a, IL-1ß, IL-6 could be suppressed in rHMGB1-induced macrophages by Escin. Finally, Escin could suppress the activation of NF-κB in LPS-induced macrophages. Conclusion: Escin could improve the survival of mice with LPS-induced endotoxemia. This effect maybe meditated by reducing the release of HMGB1, resulting in the suppression of the release of pro-inflammatory cytokines.

  6. Escin Increases the Survival Rate of LPS-Induced Septic Mice Through Inhibition of HMGB1 Release from Macrophages.

    Science.gov (United States)

    Cheng, Yajun; Wang, Hongrui; Mao, Min; Liang, Chao; Zhang, Yu; Yang, Deijun; Wei, Ziran; Gao, Shunxiang; Hu, Bo; Wang, Lianghua; Cai, Qingping

    2015-01-01

    Previous studies have described the effects of Escin on improving the survival rate of endotoxemic animals. The purpose of this study was to explore the molecular mechanisms of this potentially beneficial treatment. First, the survival rate of endotoxemic mice was monitored for up to 2 weeks after Escin pretreatment, Escin post-treatment, or Escin post-treatment + rHMGB1. The effects of Escin on the release of pro-inflammatory cytokines such as TNF-α, IL-1β, IL-6 and HMGB1 in the serum of endotoxemic mice and LPS-induced macrophages were evaluated by ELISA. Furthermore, the mRNA and protein levels of HMGB1 in LPS-induced macrophages were measured by qRT-PCR and Western blot, respectively. Additionally, the release of pro-inflammatory cytokines such as TNF-α, IL-1β, IL-6 was evaluated by ELISA in rHMGB1-induced macrophages. Finally, the protein levels and the activity of NF-κB in macrophages were checked by Western blot and ELISA, respectively. Both pretreatment and post-treatment with Escin could improve the survival rate of endotoxemic mice, while exogenous rHMGB1 reversed this effect. In addition, Escin decreased the level of the pro-inflammatory cytokinesTNF-α,IL-1β, IL-6 and HMGB1 in endotoxemic mice and in LPS-induced macrophages. Escin could also inhibit the mRNA levels and activity of HMGB1. The release of the pro-inflammatory cytokinesTNF-α,IL-1β, IL-6 could be suppressed in rHMGB1-induced macrophages by Escin. Finally, Escin could suppress the activation of NF- κB in LPS-induced macrophages. Escin could improve the survival of mice with LPS-induced endotoxemia. This effect maybe meditated by reducing the release of HMGB1, resulting in the suppression of the release of pro-inflammatory cytokines. © 2015 S. Karger AG, Basel.

  7. Nonalcoholic fatty liver disease and increased risk of 1-year all-cause and cardiac hospital readmissions in elderly patients admitted for acute heart failure.

    Directory of Open Access Journals (Sweden)

    Filippo Valbusa

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is an emerging risk factor for heart failure (HF. Although some progress has been made in improving survival among patients admitted for HF, the rates of hospital readmissions and the related costs continue to rise dramatically. We sought to examine whether NAFLD and its severity (diagnosed at hospital admission was independently associated with a higher risk of 1-year all-cause and cardiac re-hospitalization in patients admitted for acute HF. We studied 212 elderly patients who were consecutively admitted with acute HF to the Hospital of Negrar (Verona over a 1-year period. Diagnosis of NAFLD was based on ultrasonography, whereas the severity of advanced NAFLD fibrosis was based on the fibrosis (FIB-4 score and other non-invasive fibrosis scores. Patients with acute myocardial infarction, severe valvular heart diseases, end-stage renal disease, cancer, known liver diseases or decompensated cirrhosis were excluded. Cox regression was used to estimate hazard ratios (HR for the associations between NAFLD and the outcome(s of interest. The cumulative rate of 1-year all-cause re-hospitalizations was 46.7% (n = 99, mainly due to cardiac causes. Patients with NAFLD (n = 109; 51.4% had remarkably higher 1-year all-cause and cardiac re-hospitalization rates compared with their counterparts without NAFLD. Both event rates were particularly increased in those with advanced NAFLD fibrosis. NAFLD was associated with a 5-fold increased risk of 1-year all-cause re-hospitalization (adjusted-hazard ratio 5.05, 95% confidence intervals 2.78-9.10, p<0.0001 after adjustment for established risk factors and potential confounders. Similar results were found for 1-year cardiac re-hospitalization (adjusted-hazard ratio 8.05, 95% confidence intervals 3.77-15.8, p<0.0001. In conclusion, NAFLD and its severity were strongly and independently associated with an increased risk of 1-year all-cause and cardiac re-hospitalization in

  8. Hemangiosarcoma in a Dog: Unusual Presentation and Increased Survival Using a Complementary/Holistic Approach Combined with Metronomic Chemotherapy

    Directory of Open Access Journals (Sweden)

    Philip Chaikin

    2018-01-01

    Full Text Available This case report documents the clinical and pathologic findings in a 12-year-old terrier mix with intraocular and splenic hemangiosarcoma. Pathologic findings in both the spleen and globe were consistent with hemangiosarcoma with a low mitotic count. Initial treatment consisted of enucleation and then splenectomy followed by one cycle of conventional doxorubicin chemotherapy. Due to poor tolerance, a subsequent treatment regimen consisted of metronomic chemotherapy with chlorambucil combined with an alternative/complementary regimen of I’m-Yunity (polysaccharopeptide and Yunnan Baiyao. Follow-up thoracic radiographs and abdominal ultrasounds over a period of 24 months showed no evidence of pulmonary, hepatic, or right atrial metastases, during which time the patient had an excellent quality of life. However, shortly after achieving two-year survival, the patient developed new onset seizures unresponsive to anticonvulsant therapy. Therefore, a decision was made to euthanize the dog given that the most likely etiology of the seizures was a brain tumor. Overall, this is an exceptional treatment response given the poor survival statistics of hemangiosarcoma even with conventional chemotherapy. However, additional clinical pharmacology and clinical trial data are needed to further support the use of a complementary/holistic approach in combination with metronomic chemotherapy.

  9. Statin treatment prevents increased cardiovascular and all-cause mortality associated with clarithromycin in patients with stable coronary heart disease

    DEFF Research Database (Denmark)

    Jensen, Gorm B; Hilden, Jørgen; Als-Nielsen, Bodil

    2010-01-01

    In the CLARICOR trial, significantly increased cardiovascular (CV) and all-cause mortality in stable patients with coronary heart disease were observed after a short course of clarithromycin. We report on the impact of statin treatment at entry on the CV and all-cause mortality. The multicenter...... CLARICOR trial randomized patients to oral clarithromycin (500 mg daily; n = 2172) versus matching placebo (daily; n = 2201) for 2 weeks. Patients were followed through public databases. In the 41% patients on statin treatment at entry, no significant effect of clarithromycin was observed on CV (hazard.......0003; statin-clarithromycin interaction P = 0.0029) and all-cause mortality (HR, 1.33; 95% CI, 1.05-1.67; P = 0.016; statin-clarithromycin interaction P = 0.41). Multivariate analysis and 6-year follow up confirmed these results. Concomitant statin treatment in stable patients with coronary heart disease...

  10. Distinct Effects of miR-210 Reduction on Neurogenesis: Increased Neuronal Survival of Inflammation But Reduced Proliferation Associated with Mitochondrial Enhancement.

    Science.gov (United States)

    Voloboueva, Ludmila A; Sun, Xiaoyun; Xu, Lijun; Ouyang, Yi-Bing; Giffard, Rona G

    2017-03-15

    Neurogenesis is essential to brain development and plays a central role in the response to brain injury. Stroke and head trauma stimulate proliferation of endogenous neural stem cells (NSCs); however, the survival of young neurons is sharply reduced by postinjury inflammation. Cellular mitochondria are critical to successful neurogenesis and are a major target of inflammatory injury. Mitochondrial protection was shown to improve survival of young neurons. This study tested whether reducing cellular microRNA-210 (miR-210) would enhance mitochondrial function and improve survival of young murine neurons under inflammatory conditions. Several studies have demonstrated the potential of miR-210 inhibition to enhance and protect mitochondrial function through upregulation of mitochondrial proteins. Here, miR-210 inhibition significantly increased neuronal survival and protected the activity of mitochondrial enzymes cytochrome c oxidase and aconitase in differentiating NSC cultures exposed to inflammatory mediators. Unexpectedly, we found that reducing miR-210 significantly attenuated NSC proliferation upon induction of differentiation. Further investigation revealed that increased mitochondrial function suppressed the shift to primarily glycolytic metabolism and reduced mitochondrial length characteristic of dividing cells. Activation of AMP-regulated protein kinase-retinoblastoma signaling is important in NSC proliferation and the reduction of this activation observed by miR-210 inhibition is one mechanism contributing to the reduced proliferation. Postinjury neurogenesis occurs as a burst of proliferation that peaks in days, followed by migration and differentiation over weeks. Our studies suggest that mitochondrial protective miR-210 inhibition should be delayed until after the initial burst of proliferation, but could be beneficial during the prolonged differentiation stage. SIGNIFICANCE STATEMENT Increasing the success of endogenous neurogenesis after brain injury

  11. Low Serum Potassium Levels Increase the Infectious-Caused Mortality in Peritoneal Dialysis Patients: A Propensity-Matched Score Study.

    Science.gov (United States)

    Ribeiro, Silvia Carreira; Figueiredo, Ana Elizabeth; Barretti, Pasqual; Pecoits-Filho, Roberto; de Moraes, Thyago Proenca

    2015-01-01

    Hypokalemia has been consistently associated with high mortality rate in peritoneal dialysis. However, studies investigating if hypokalemia is acting as a surrogate marker of comorbidities or has a direct effect in the risk for mortality have not been studied. Thus, the aim of this study was to analyze the effect of hypokalemia on overall and cause-specific mortality. This is an analysis of BRAZPD II, a nationwide prospective cohort study. All patients on PD for longer than 90 days with measured serum potassium levels were used to verify the association of hypokalemia with overall and cause-specific mortality using a propensity match score to reduce selection bias. In addition, competing risks were also taken into account for the analysis of cause-specific mortality. There was a U-shaped relationship between time-averaged serum potassium and all-cause mortality of PD patients. Cardiovascular disease was the main cause of death in the normokalemic group with 133 events (41.8%) followed by PD-non related infections, n=105 (33.0%). Hypokalemia was associated with a 49% increased risk for CV mortality after adjustments for covariates and the presence of competing risks (SHR 1.49; CI95% 1.01-2.21). In contrast, in the group of patients with K mortality even after adjustments for competing risks. The causative nature of this association suggested by our study raises the need for intervention studies looking at the effect of potassium supplementation on clinical outcomes of PD patients.

  12. Survival and cause of death after transcatheter aortic valve replacement as compared to an age- and sex-matched background population

    DEFF Research Database (Denmark)

    Theut, Marie; Thygesen, Julie B; De Backer, Ole

    2017-01-01

    AIMS: This study aimed to assess survival and causes of death in a real-world TAVR population as compared to an age- and sex-matched background population. METHODS AND RESULTS: Each aortic stenosis (AS) patient treated with TAVR in Eastern Denmark between 2007 and 2014 (n=617) was matched with 25...... age- and sex-matched controls (n=15,425) randomly drawn from the general Danish population. In the total TAVR population, early mortality (≤90 days) was significantly higher (hazard ratio [HR] 3.90 [2.82-5.39]; ppopulation, driven mainly by cardiovascular (CV......) mortality. Late mortality (>90 days) was not different between the TAVR and background population (HR 1.16 [0.96-1.40]; p=0.126), causes of death being mainly non-CV. In subgroup analysis, the HR for late mortality was 0.98, 1.11, and 1.90 for the low-, intermediate-, and high-risk TAVR groups, respectively...

  13. Hydroxyurea-Increased Fetal Hemoglobin Is Associated with Less Organ Damage and Longer Survival in Adults with Sickle Cell Anemia.

    Directory of Open Access Journals (Sweden)

    Courtney D Fitzhugh

    Full Text Available Adults with sickle cell anemia (HbSS are inconsistently treated with hydroxyurea.We retrospectively evaluated the effects of elevating fetal hemoglobin with hydroxyurea on organ damage and survival in patients enrolled in our screening study between 2001 and 2010.An electronic medical record facilitated development of a database for comparison of study parameters based on hydroxyurea exposure and dose. This study is registered with ClinicalTrials.gov, number NCT00011648.Three hundred eighty-three adults with homozygous sickle cell disease were analyzed with 59 deaths during study follow-up. Cox regression analysis revealed deceased subjects had more hepatic dysfunction (elevated alkaline phosphatase, Hazard Ratio = 1.005, 95% CI 1.003-1.006, p<0.0.0001, kidney dysfunction (elevated creatinine, Hazard Ratio = 1.13, 95% CI 1.00-1.27, p = 0.043, and cardiopulmonary dysfunction (elevated tricuspid jet velocity on echocardiogram, Hazard Ratio = 2.22, 1.23-4.02, p = 0.0082. Sixty-six percent of subjects were treated with hydroxyurea, although only 66% of those received a dose within the recommended therapeutic range. Hydroxyurea use was associated with improved survival (Hazard Ratio = 0.58, 95% CI 0.34-0.97, p = 0.040. This effect was most pronounced in those taking the recommended dose of 15-35 mg/kg/day (Hazard Ratio 0.36, 95% CI 0.17-0.73, p = 0.0050. Hydroxyurea use was not associated with changes in organ function over time. Further, subjects with higher fetal hemoglobin responses to hydroxyurea were more likely to survive (p = 0.0004. While alkaline phosphatase was lowest in patients with the best fetal hemoglobin response (95.4 versus 123.6, p = 0.0065 and 96.1 versus 113.6U/L, p = 0.041 at first and last visits, respectively, other markers of organ damage were not consistently improved over time in patients with the highest fetal hemoglobin levels.Our data suggest that adults should be treated with the maximum tolerated hydroxyurea dose

  14. Sulphur deficiency causes a reduction in antimicrobial potential and leads to increased disease susceptibility of oilseed rape

    OpenAIRE

    Dubuis, Pierre-Henri; Marazzi, Cristina; Städler, Erich; Mauch, Felix

    2005-01-01

    The reduction of atmospheric sulphur dioxide pollution is causing increasing problems of sulphur deficiency in sulphur-demanding crop plants in northern Europe. Elemental sulphur and many sulphur containing compounds such as cysteine-rich antifungal proteins, glucosinolates (GSL) and phytoalexins play important roles in plant disease resistance. The aim of this work was to analyse the effect of inadequate sulphur supply on disease resistance of oilseed rape (Brassica napus). Compared with fer...

  15. Xenoestrogens may be the cause of high and increasing rates of hormone receptor positive breast cancer in the world.

    Science.gov (United States)

    Dey, Subhojit; Soliman, Amr S; Merajver, Sofia D

    2009-06-01

    Breast cancer rates are higher in the Western or industrialized world when compared to Africa or Asia. Within the developing world, breast cancer rates are higher in urban areas where people have a more Westernized lifestyle. In addition, there has been a steady increase in the breast cancer incidence across the world. It is already a known fact that the proportion of hormone receptor positive breast cancer cases is higher in the developed world. Evidence from developed countries also shows that most of the increase in breast cancer incidence has been due to an increase in hormone receptor positive breast cancer. Most of the breast cancer incidence can be explained by environmental factors and genetic causes. However, all known risk factors of breast cancer can explain only 30-50% of breast cancer incidence. In the past decade, a number of compounds that affect female hormone homeostasis have been discovered. These xenoestrogens have been shown to cause breast cancer and also induce the expression of hormone receptors in vitro and in vivo. Given the high use of substances containing xenoestrogens in developed regions of the world and their increasing use in urban parts of the developing world, xenoestrogens could be the important cause of high and increasing rates of hormone receptor positive breast cancer across the world. New research in the area of mammary stem cells provides added indication of the probable time period of exposure to xenoestrogens with chronic exposure later in life leading to hormone receptor positive breast cancer and most probable reason behind increasing breast cancer incidence.

  16. Is Increased Intracellular Calcium in Red Blood Cells a Common Component in the Molecular Mechanism Causing Anemia?

    Directory of Open Access Journals (Sweden)

    Laura Hertz

    2017-09-01

    Full Text Available For many hereditary disorders, although the underlying genetic mutation may be known, the molecular mechanism leading to hemolytic anemia is still unclear and needs further investigation. Previous studies revealed an increased intracellular Ca2+ in red blood cells (RBCs from patients with sickle cell disease, thalassemia, or Gardos channelopathy. Therefore we analyzed RBCs' Ca2+ content from 35 patients with different types of anemia (16 patients with hereditary spherocytosis, 11 patients with hereditary xerocytosis, 5 patients with enzymopathies, and 3 patients with hemolytic anemia of unknown cause. Intracellular Ca2+ in RBCs was measured by fluorescence microscopy using the fluorescent Ca2+ indicator Fluo-4 and subsequent single cell analysis. We found that in RBCs from patients with hereditary spherocytosis and hereditary xerocytosis the intracellular Ca2+ levels were significantly increased compared to healthy control samples. For enzymopathies and hemolytic anemia of unknown cause the intracellular Ca2+ levels in RBCs were not significantly different. These results lead us to the hypothesis that increased Ca2+ levels in RBCs are a shared component in the mechanism causing an accelerated clearance of RBCs from the blood stream in channelopathies such as hereditary xerocytosis and in diseases involving defects of cytoskeletal components like hereditary spherocytosis. Future drug developments should benefit from targeting Ca2+ entry mediating molecular players leading to better therapies for patients.

  17. The small-molecule TNF-α inhibitor, UTL-5g, delays deaths and increases survival rates for mice treated with high doses of cisplatin.

    Science.gov (United States)

    Shaw, Jiajiu; Media, Joseph; Chen, Ben; Valeriote, Fredrick

    2013-09-01

    UTL-5g is a novel small-molecule chemoprotector that lowers hepatotoxicity, nephrotoxicity, and myelotoxicity induced by cisplatin through TNF-α inhibition among other factors. The objective of this study was to investigate whether UTL-5g can reduce the overall acute toxicity of cisplatin and increase cisplatin tolerability in mice. BDF1 female mice were treated individually with UTL-5g (suspended in Ora-Plus) by oral gavage at 60 mg/kg, 30 min before i.p. injection of cisplatin at 10, 15, and 20 mg/kg, respectively, on Day 0. Starting from Day 1, individual mice were again treated daily by the same dose of UTL-5g for 4 consecutive days. Survivals and body weights were monitored. UTL-5g treatment increased the survival rate and delayed the time to death for mice treated with 150 % of the maximum tolerated dose (MTD) of cisplatin (15 mg/kg). Likewise, at 200 % of the MTD of cisplatin (20 mg/kg), treatment of UTL-5g increased the survival rate and delayed the time to death. Treatment of UTL-5g did not have a significant effect on weight loss induced by cisplatin, indicating that body weight may not be a sensitive-enough measure for chemoprotection of UTL-5g against cisplatin. In summary, UTL-5g delayed deaths and increased survival rates of mice treated by high doses of cisplatin, indicating that UTL-5g is capable of reducing the overall acute toxicity of cisplatin and increased cisplatin tolerability in mice; this is in line with the specific chemoprotective effects of UTL-5g previously reported. Further investigation of UTL-5g in combination with cisplatin is warranted.

  18. RNAi-mediated knockdown of catalase causes cell cycle arrest in SL-1 cells and results in low survival rate of Spodoptera litura (Fabricius.

    Directory of Open Access Journals (Sweden)

    Haiming Zhao

    Full Text Available Deregulated reactive oxygen species (ROS production can lead to the disruption of structural and functional integrity of cells as a consequence of reactive interaction between ROS and various biological components. Catalase (CAT is a common enzyme existing in nearly all organisms exposed to oxygen, which decomposes harmful hydrogen peroxide, into water and oxygen. In this study, the full length sequence that encodes CAT-like protein from Spodoptera litura named siltCAT (GenBank accession number: JQ_663444 was cloned and characterized. Amino acid sequence alignment showed siltCAT shared relatively high conservation with other insect, especially the conserved residues which defined heme and NADPH orientation. Expression pattern analysis showed that siltCAT mRNA was mainly expressed in the fat body, midgut, cuticle and malpighian tube, and as well as over last instar larvae, pupa and adult stages. RNA interference was used to silence CAT gene in SL-1 cells and the fourth-instar stage of S. litura larvae respectively. Our results provided evidence that CAT knockdown induced ROS generation, cell cycle arrest and apoptosis in SL-1 cells. It also confirmed the decrease in survival rate because of increased ROS production in experimental groups injected with double-stranded RNA of CAT (dsCAT. This study implied that ROS scavenging by CAT is important for S. litura survival.

  19. Muscle disuse caused by botulinum toxin injection leads to increased central gain of the stretch reflex in the rat.

    Science.gov (United States)

    Pingel, Jessica; Hultborn, Hans; Näslund-Koch, Lui; Jensen, Dennis B; Wienecke, Jacob; Nielsen, Jens Bo

    2017-10-01

    Botulinum toxin (Btx) is used in children with cerebral palsy and in other neurological patients to diminish spasticity and reduce the risk of development of contractures. We investigated changes in the central gain of the stretch reflex circuitry in response to Btx injection in the triceps surae muscle in rats. Experiments were performed in 21 rats. Eight rats were a control group, and 13 rats were injected with 6 IU of Btx in the left triceps surae muscle. Two weeks after Btx injection, larger monosynaptic reflexes (MSR) were recorded from the left (injected) than the right (noninjected) L4 + L5 ventral roots following stimulation of the corresponding dorsal roots. A similar increase on the left side was observed in response to stimulation of descending motor tracts, suggesting that increased excitability of spinal motor neurons may at least partly explain the increased reflexes. However, significant changes were also observed in postactivation depression of the MSR, suggesting that plastic changes in transmission from Ia afferent to the motor neurons also may be involved. The data demonstrate that muscle paralysis induced by Btx injection is accompanied by plastic adaptations in the central stretch reflex circuitry, which counteract the antispastic effect of Btx. NEW & NOTEWORTHY Injection of botulinum toxin into ankle muscles causes increased gain of stretch reflex. This is caused by adaptive changes in regulation of transmitter release from Ia afferents and increased excitability of spinal motor neurons. Copyright © 2017 the American Physiological Society.

  20. Increased susceptibility for superinfection with Streptococcus pneumoniae during influenza virus infection is not caused by TLR7-mediated lymphopenia.

    Directory of Open Access Journals (Sweden)

    Sabine Stegemann

    Full Text Available Influenza A virus (IAV causes respiratory tract infections leading to recurring epidemics with high rates of morbidity and mortality. In the past century IAV induced several world-wide pandemics, the most aggressive occurring in 1918 with a death toll of 20-50 million cases. However, infection with IAV alone is rarely fatal. Instead, death associated with IAV is usually mediated by superinfection with bacteria, mainly Streptococcus pneumoniae. The reasons for this increased susceptibility to bacterial superinfection have not been fully elucidated. We previously demonstrated that triggering of TLR7 causes immune incompetence in mice by induction of lymphopenia. IAV is recognized by TLR7 and infections can lead to lymphopenia. Since lymphocytes are critical to protect from S. pneumoniae it has long been speculated that IAV-induced lymphopenia might mediate increased susceptibility to superinfection. Here we show that sub-lethal pre-infections of mice with IAV-PR8/A/34 strongly increased their mortality in non-lethal SP infections, surprisingly despite the absence of detectable lymphopenia. In contrast to SP-infection alone co-infected animals were unable to control the exponential growth of SP. However, lymphopenia forced by TLR7-triggering or antibody-mediated neutropenia did not increase SP-susceptibility or compromise the ability to control SP growth. Thus, the immune-incompetence caused by transient lympho- or leukopenia is not sufficient to inhibit potent antibacterial responses of the host and mechanisms distinct from leukodepletion must account for increased bacterial superinfection during viral defence.

  1. Honey bee (Apis mellifera) drones survive oxidative stress due to increased tolerance instead of avoidance or repair of oxidative damage

    Science.gov (United States)

    Oxidative stress can lead to premature aging symptoms and cause acute mortality at higher doses in a range of organisms. Oxidative stress resistance and longevity are mechanistically and phenotypically linked: considerable variation in oxidative stress resistance exists among and within species and ...

  2. Ketogenic diet improves the spatial memory impairment caused by exposure to hypobaric hypoxia through increased acetylation of histones in rats.

    Directory of Open Access Journals (Sweden)

    Ming Zhao

    Full Text Available Exposure to hypobaric hypoxia causes neuron cell damage, resulting in impaired cognitive function. Effective interventions to antagonize hypobaric hypoxia-induced memory impairment are in urgent need. Ketogenic diet (KD has been successfully used to treat drug-resistant epilepsy and improves cognitive behaviors in epilepsy patients and other pathophysiological animal models. In the present study, we aimed to explore the potential beneficial effects of a KD on memory impairment caused by hypobaric hypoxia and the underlying possible mechanisms. We showed that the KD recipe used was ketogenic and increased plasma levels of ketone bodies, especially β-hydroxybutyrate. The results of the behavior tests showed that the KD did not affect general locomotor activity but obviously promoted spatial learning. Moreover, the KD significantly improved the spatial memory impairment caused by hypobaric hypoxia (simulated altitude of 6000 m, 24 h. In addition, the improving-effect of KD was mimicked by intraperitoneal injection of BHB. The western blot and immunohistochemistry results showed that KD treatment not only increased the acetylated levels of histone H3 and histone H4 compared to that of the control group but also antagonized the decrease in the acetylated histone H3 and H4 when exposed to hypobaric hypoxia. Furthermore, KD-hypoxia treatment also promoted PKA/CREB activation and BDNF protein expression compared to the effects of hypoxia alone. These results demonstrated that KD is a promising strategy to improve spatial memory impairment caused by hypobaric hypoxia, in which increased modification of histone acetylation plays an important role.

  3. Endovascular Thrombectomy for Ischemic Stroke Increases Disability-Free Survival, Quality of Life, and Life Expectancy and Reduces Cost

    Directory of Open Access Journals (Sweden)

    Bruce C. V. Campbell

    2017-12-01

    Full Text Available BackgroundEndovascular thrombectomy improves functional outcome in large vessel occlusion ischemic stroke. We examined disability, quality of life, survival and acute care costs in the EXTEND-IA trial, which used CT-perfusion imaging selection.MethodsLarge vessel ischemic stroke patients with favorable CT-perfusion were randomized to endovascular thrombectomy after alteplase versus alteplase-only. Clinical outcome was prospectively measured using 90-day modified Rankin scale (mRS. Individual patient expected survival and net difference in Disability/Quality-adjusted life years (DALY/QALY up to 15 years from stroke were modeled using age, sex, 90-day mRS, and utility scores. Level of care within the first 90 days was prospectively measured and used to estimate procedure and inpatient care costs (US$ reference year 2014.ResultsThere were 70 patients, 35 in each arm, mean age 69, median NIHSS 15 (IQR 12–19. The median (IQR disability-weighted utility score at 90 days was 0.65 (0.00–0.91 in the alteplase-only versus 0.91 (0.65–1.00 in the endovascular group (p = 0.005. Modeled life expectancy was greater in the endovascular versus alteplase-only group (median 15.6 versus 11.2 years, p = 0.02. The endovascular thrombectomy group had fewer simulated DALYs lost over 15 years [median (IQR 5.5 (3.2–8.7 versus 8.9 (4.7–13.8, p = 0.02] and more QALY gained [median (IQR 9.3 (4.2–13.1 versus 4.9 (0.3–8.5, p = 0.03]. Endovascular patients spent less time in hospital [median (IQR 5 (3–11 days versus 8 (5–14 days, p = 0.04] and rehabilitation [median (IQR 0 (0–28 versus 27 (0–65 days, p = 0.03]. The estimated inpatient costs in the first 90 days were less in the thrombectomy group (average US$15,689 versus US$30,569, p = 0.008 offsetting the costs of interhospital transport and the thrombectomy procedure (average US$10,515. The average saving per patient treated with thrombectomy was US$4

  4. Predominance of Th1 response, increase of megakaryocytes and Kupffer cells are related to survival in Trypanosoma cruzi infected mice treated with Lycopodium clavatum.

    Science.gov (United States)

    Falkowski-Temporini, Gislaine Janaina; Lopes, Carina Ribeiro; Massini, Paula Fernanda; Brustolin, Camila Fernanda; Sandri, Patricia Flora; Ferreira, Érika Cristina; Aleixo, Denise Lessa; Pala, Nelson Roberto; de Araújo, Silvana Marques

    2016-12-01

    We investigated the number of megakaryocytes, Kupffer cells and ratios of Th1/Th2 and Th1/Th17 cytokines in survival of mice infected with Y strain of Trypanosoma cruzi and treated with Lycopodium clavatum. In a blind, randomized and controlled assay, Swiss male mice, 8weeks-old, infected with 1400 trypomastigotes (Y strain) were divided into groups and treated with: GLy - Lycopodium clavatum dynamization13c and GCI - alcohol solution 7° GL (vehicle medicine). The treatment was offered two days before infection and on the 2nd, 4th and 6th days after infection, overnight (1mL/100mL) and ad libitum. Parameters assessed were: survival rate, number of megakaryocytes and Kupffer cells, cytokines dosage (TNF-α, IFN-γ, IL-2, IL-4, IL-6, IL-10, IL-17), Th1/Th2 and Th1/Th17 ratios. The increase in megakaryocytes, Kupffer cells, predominance of Th1 response, with increased TNF-α, IL-10, TNF-α/IL-4, TNF-α/IL-17 and decreased IL-6 IL-6/IL-4, are related to increased survival in mice infected with T. cruzi and treated with Lycopodium clavatum 13c. This result demonstrates the possibility of an alternative approach for the treatment of Chagas disease with dynamized drugs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Postoperative Delirium After Liver Transplantation is Associated With Increased Length of Stay and Lower Survival in a Prospective Cohort.

    Science.gov (United States)

    Beckmann, Sonja; Schubert, Maria; Burkhalter, Hanna; Dutkowski, Philipp; De Geest, Sabina

    2017-03-01

    Although postoperative delirium (POD) is a common in-hospital complication associated with negative outcomes, evidence in liver transplantation (LT) is scarce. We examined the incidence and duration of POD, its impact on outcomes and health-care utilization, and described predisposing and precipitating factors favoring POD development. This prospective cohort study included adults undergoing transplantation in a tertiary hospital. Postoperative delirium was assessed 3 times daily until 24 days post-LT, with the Intensive Care Delirium Screening Checklist on the intensive care unit (ICU) and the Delirium Observation Screening Scale on the ward. Postoperative delirium was noted if any of the daily measurements was positive. Forty-two patients (69% male, mean age 55 years, median Model for End-Stage Liver Disease score 15 [interquartile range 8-26]) were included. The incidence of POD was 45.2%, with a median duration of 5 days. Patients with POD had longer ICU (median 8 vs 2 days, P = .000) and hospital stays (median 32 vs 14 days, P = .000) as well as shorter survival (Breslow test P = .045, log-rank test P = .150). Pre-LT comorbidities and perioperative factors might be related to POD development. Nurses are key persons in the detection of POD in the daily clinical routine. The high incidence of POD and its negative association with patient outcomes highlight not only the relevance of systematic assessment of POD after LT but also the need for preventive interventions.

  6. Colon cancer-associated mutator DNA polymerase δ variant causes expansion of dNTP pools increasing its own infidelity.

    Science.gov (United States)

    Mertz, Tony M; Sharma, Sushma; Chabes, Andrei; Shcherbakova, Polina V

    2015-05-12

    Defects in DNA polymerases δ (Polδ) and ε (Polε) cause hereditary colorectal cancer and have been implicated in the etiology of some sporadic colorectal and endometrial tumors. We previously reported that the yeast pol3-R696W allele mimicking a human cancer-associated variant, POLD1-R689W, causes a catastrophic increase in spontaneous mutagenesis. Here, we describe the mechanism of this extraordinary mutator effect. We found that the mutation rate increased synergistically when the R696W mutation was combined with defects in Polδ proofreading or mismatch repair, indicating that pathways correcting DNA replication errors are not compromised in pol3-R696W mutants. DNA synthesis by purified Polδ-R696W was error-prone, but not to the extent that could account for the unprecedented mutator phenotype of pol3-R696W strains. In a search for cellular factors that augment the mutagenic potential of Polδ-R696W, we discovered that pol3-R696W causes S-phase checkpoint-dependent elevation of dNTP pools. Abrogating this elevation by strategic mutations in dNTP metabolism genes eliminated the mutator effect of pol3-R696W, whereas restoration of high intracellular dNTP levels restored the mutator phenotype. Further, the use of dNTP concentrations present in pol3-R696W cells for in vitro DNA synthesis greatly decreased the fidelity of Polδ-R696W and produced a mutation spectrum strikingly similar to the spectrum observed in vivo. The results support a model in which (i) faulty synthesis by Polδ-R696W leads to a checkpoint-dependent increase in dNTP levels and (ii) this increase mediates the hypermutator effect of Polδ-R696W by facilitating the extension of mismatched primer termini it creates and by promoting further errors that continue to fuel the mutagenic pathway.

  7. Inhibition of human Chk1 causes increased initiation of DNA replication, phosphorylation of ATR targets, and DNA breakage

    DEFF Research Database (Denmark)

    Syljuåsen, Randi G; Sørensen, Claus Storgaard; Hansen, Lasse Tengbjerg

    2005-01-01

    by increased amounts of nonextractable RPA protein, formation of single-stranded DNA, and induction of DNA strand breaks. Moreover, these responses were prevented by siRNA-mediated downregulation of Cdk2 or the replication initiation protein Cdc45, or by addition of the CDK inhibitor roscovitine. We propose......-nuclear phosphorylation of histone H2AX, p53, Smc1, replication protein A, and Chk1 itself in human S-phase cells. These phosphorylations were inhibited by ATR siRNA and caffeine, but they occurred independently of ATM. Chk1 inhibition also caused an increased initiation of DNA replication, which was accompanied...... that Chk1 is required during normal S phase to avoid aberrantly increased initiation of DNA replication, thereby protecting against DNA breakage. These results may help explain why Chk1 is an essential kinase and should be taken into account when drugs to inhibit this kinase are considered for use...

  8. Why is tick-borne encephalitis increasing? A review of the key factors causing the increasing incidence of human TBE in Swedena

    Directory of Open Access Journals (Sweden)

    Jaenson Thomas GT

    2012-08-01

    Full Text Available Abstract The highest annual incidence of human tick-borne encephalitis (TBE in Sweden ever recorded by the Swedish Institute for Communicable Disease Control (SMI occurred last year, 2011. The number of TBE cases recorded during 2012 up to 6th August 2012 indicates that the incidence for 2012 could exceed that of 2011. In this review of the ecology and epidemiology of TBE in Sweden our main aim is to analyse the possible reasons behind the gradually increasing incidence of human TBE during the last 20 years. The main TBE virus (TBEV vector to humans in Sweden is the nymphal stage of the common tick Ixodes ricinus. The main mode of transmission and maintenance of TBEV in the tick population is considered to be when infective nymphs co-feed with uninfected but infectible larvae on rodents. In most locations the roe deer, Capreolus capreolus is the main host for the reproducing adult I. ricinus ticks. The high number of roe deer for more than three decades has resulted in a very large tick population. Deer numbers have, however, gradually declined from the early 1990s to the present. This decline in roe deer numbers most likely made the populations of small rodents, which are reservoir-competent for TBEV, gradually more important as hosts for the immature ticks. Consequently, the abundance of TBEV-infected ticks has increased. Two harsh winters in 2009–2011 caused a more abrupt decline in roe deer numbers. This likely forced a substantial proportion of the “host-seeking” ticks to feed on bank voles (Myodes glareolus, which at that time suddenly had become very numerous, rather than on roe deer. Thus, the bank vole population peak in 2010 most likely caused many tick larvae to feed on reservoir-competent rodents. This presumably resulted in increased transmission of TBEV among ticks and therefore increased the density of infected ticks the following year. The unusually warm, humid weather and the prolonged vegetation period in 2011 permitted

  9. Combination of aging and dimethylhydrazine treatment causes an increase in cancer-stem cell population of rat colonic crypts.

    Science.gov (United States)

    Levi, Edi; Misra, Sandhya; Du, Jianhua; Patel, Bhaumik B; Majumdar, Adhip P N

    2009-07-31

    Aging is associated with increased incidence of colon cancers. It is also becoming evident that cancer stem cells (CSC) play a vital role in the pathogenesis and prognosis of colon cancer. Recently, we reported the presence of colon cancer stem-like cells in macroscopically normal mucosa in patients with adenomatous polyps and that they increase with aging, suggesting that aging may predispose the colon to carcinogenesis. In the current study we have examined the combined effects of aging and carcinogen exposure on the status of colon CSCs in an experimental model. We used young (4-6 months) and aged (22-24 months) rats and exposed them to the carcinogen, dimethylhydroxide (DMH). We investigated the expression of colon cancer stem cell markers, CD44, CD166, EpCam, and ALDH1 as well as EGFR expression in normal colonic crypt epithelium following carcinogen treatment. Our results demonstrate that aging per se or carcinogen treatment alone causes an increase in the number of colon cancer stems cells, as evidenced by increased immunoreactive-CSC-markers positive cells in the colonic mucosa. In aged rats, carcinogen exposure results in a more pronounced increase in colon cancer stem cells. Our study shows that in aging colon the effects of carcinogens are more pronounced, and an increase in colon CSCs is one of the earliest changes preceding tumor development. Moreover, the current investigation of the use of a panel of immunohistochemical markers of colon CSC can potentially serve as a prognostic marker during screening for colon cancer.

  10. Elevated plasma YKL-40 predicts increased risk of gastrointestinal cancer and decreased survival after any cancer diagnosis in the general population

    DEFF Research Database (Denmark)

    Johansen, J.S.; Bojesen, S.E.; Mylin, A.K.

    2009-01-01

    PURPOSE: Elevated plasma YKL-40 is a biomarker of poor prognosis in cancer patients. We tested the hypotheses that elevated plasma YKL-40 predicts risk of cancer as well as survival after a cancer diagnosis in the general population. PATIENTS AND METHODS: A prospective cohort study of 8......,899 subjects (20 to 95 years) from the Danish general population, the Copenhagen City Heart Study, observed for 11 years for cancer incidence and 14 years for death: 1,432 participants had a first incident cancer, 968 of these died. Hazard ratios (HRs) for cancer events and death after events according......) after any cancer and 2.4 (95% CI, 1.3 to 4.3; P = .005) after gastrointestinal cancer in participants with YKL-40 category 91% to 100% versus 0% to 33%. CONCLUSION: In the general population, elevated plasma YKL-40 predicts increased risk of gastrointestinal cancer and decreased survival after any...

  11. Racemic oleracein E increases the survival rate and attenuates memory impairment in D-galactose/NaNO₂-induced senescent mice.

    Science.gov (United States)

    Wang, Pei-Pei; Sun, Hong-Xiang; Liu, Ce-Jia; Hu, Ming-Hong; He, Xiu-Quan; Yue, Su; Jiao, Ze-Zhao; Xiang, Lan

    2016-05-15

    Compounds that possess a pyrrolidone skeleton are a rich resource for the discovery of nootropic drugs. Oleracein E (OE), which possesses both tetrahydroisoquinoline and pyrrolidone skeletons, was first isolated from the medicinal plant Portulaca oleracea L. and was thought to be an active component in the cognition-improvement effect induced by this herb. The aim of this study was to investigate the effect of OE on cognitive impairment in senescent mice and its underlying mechanism of action. Senescent Kunming mice were established by the intraperitoneal injection of D-galactose (D-gal, 1250 mg/kg/d) and NaNO2 (90 mg/kg/d) for 8 weeks. OE (3 mg/kg/d, 15 mg/kg/d) was orally administered for 8 weeks, and the nootropic drug piracetam (PA, 400 mg/kg/d) was used as a positive control. A Morris water maze was used to assess cognitive ability. GSH and MDA levels and T-AOC, SOD, and CAT activities in the brain or plasma were determined. Hippocampal morphology was observed by HE staining, and expression of the anti-apoptotic protein Bcl-2 and the pro-apoptotic proteins Bax and Caspase-3 was observed by immunohistochemical staining. Large-dosage treatments with D-gal/NaNO2 for 8 weeks significantly reduced survival, impaired spatial memory capacity, compensatorily up-regulated GSH level and T-AOC and SOD activities, decreased CAT activity, and induced hippocampal neuronal damage and apoptosis as reflected by the apparent low expression of Bcl-2 and high expression of Bax and Caspase-3. OE significantly prolonged lifespan and was more potent than PA. Similar to PA, OE at 15 mg/kg/d improved memory capacity. The underlying mechanism of action was related to the reversal of abnormal brain antioxidant biomarkers (GSH, T-AOC, and SOD) to normal levels and the inhibition of hippocampal neuronal apoptosis. OE from P. oleracea is an active compound for improving cognitive function and is also a candidate nootropic drug for the treatment of age-related dementia. Copyright © 2016

  12. A mutation in the centriole-associated protein centrin causes genomic instability via increased chromosome loss in Chlamydomonas reinhardtii

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    Marshall Wallace F

    2005-05-01

    Full Text Available Abstract Background The role of centrioles in mitotic spindle function remains unclear. One approach to investigate mitotic centriole function is to ask whether mutation of centriole-associated proteins can cause genomic instability. Results We addressed the role of the centriole-associated EF-hand protein centrin in genomic stability using a Chlamydomonas reinhardtii centrin mutant that forms acentriolar bipolar spindles and lacks the centrin-based rhizoplast structures that join centrioles to the nucleus. Using a genetic assay for loss of heterozygosity, we found that this centrin mutant showed increased genomic instability compared to wild-type cells, and we determined that the increase in genomic instability was due to a 100-fold increase in chromosome loss rates compared to wild type. Live cell imaging reveals an increased rate in cell death during G1 in haploid cells that is consistent with an elevated rate of chromosome loss, and analysis of cell death versus centriole copy number argues against a role for multipolar spindles in this process. Conclusion The increased chromosome loss rates observed in a centrin mutant that forms acentriolar spindles suggests a role for centrin protein, and possibly centrioles, in mitotic fidelity.

  13. Increased heart rate caused by atrial pacing with the closed-loop stimulation function prevented micturition syncope

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    Tatsuo Haraki, MD,PhD

    2013-10-01

    Full Text Available A 70-year-old man had been experiencing syncope several times a year. We implanted a DDD pacemaker with closed-loop stimulation (CLS function. When he urinated early in the morning, his increased atrial pacing rates elevated his heart rate (HR during and after micturition. After implantation of the DDD-CLS mode, he did not experience symptoms. In contrast, in the DDD-R mode, his intrinsic HR changed to atrial pacing after micturition but decreased to the basal rate within 2 min, and he experienced a sense of cold perspiration and presyncope. Increased HRs caused by atrial pacing with the CLS function were useful in the prevention of micturition syncope.

  14. Hybrid and electric low-noise cars cause an increase in traffic accidents involving vulnerable road users in urban areas.

    Science.gov (United States)

    Brand, Stephan; Petri, Maximilian; Haas, Philipp; Krettek, Christian; Haasper, Carl

    2013-01-01

    Due to resource scarcity, the number of low-noise and electric cars is expected to increase rapidly. The frequent use of these cars will lead to a significant reduction of traffic related noise and pollution. On the other hand, due to the adaption and conditioning of vulnerable road users the number of traffic accidents involving pedestrians and bicyclists is postulated to increase as well. Children, older people with reduced eyesight and the blind are especially reliant on a combination of acoustic and visual warning signals with approaching or accelerating vehicles. This is even more evident in urban areas where the engine sound is the dominating sound up to 30 kph (kilometres per hour). Above this, tyre-road interaction is the main cause of traffic noise. With the missing typical engine sound a new sound design is necessary to prevent traffic accidents in urban areas. Drivers should not be able to switch the sound generator off.

  15. Hypertension and hyperglycemia synergize to cause incipient renal tubular alterations resulting in increased NGAL urinary excretion in rats.

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    Ana M Blázquez-Medela

    Full Text Available Hypertension and diabetes are the two leading causes of chronic kidney disease (CKD eventually leading to end stage renal disease (ESRD and the need of renal replacement therapy. Mortality among CKD and ESRD patients is high, mostly due to cardiovascular events. New early markers of risk are necessary to better anticipate the course of the disease, to detect the renal affection of additive risk factors, and to appropriately handle patients in a pre-emptive and personalized manner.Renal function and NGAL urinary excretion was monitored in rats with spontaneous (SHR or L-NAME induced hypertension rendered hyperglycemic (or not as controls.Combination of hypertension and hyperglycemia (but not each of these factors independently causes an increased urinary excretion of neutrophil gelatinase-associated lipocalin (NGAL in the rat, in the absence of signs of renal damage. Increased NGAL excretion is observed in diabetic animals with two independent models of hypertension. Elevated urinary NGAL results from a specific alteration in its tubular handling, rather than from an increase in its renal expression. In fact, when kidneys of hyperglycaemic-hypertensive rats are perfused in situ with Krebs-dextran solution containing exogenous NGAL, they excrete more NGAL in the urine than hypertensive rats. We also show that albuminuria is not capable of detecting the additive effect posed by the coexistence of these two risk factors.Our results suggest that accumulation of hypertension and hyperglycemia induces an incipient and quite specific alteration in the tubular handling of NGAL resulting in its increased urinary excretion.

  16. Road traffic noise is associated with increased cardiovascular morbidity and mortality and all-cause mortality in London.

    Science.gov (United States)

    Halonen, Jaana I; Hansell, Anna L; Gulliver, John; Morley, David; Blangiardo, Marta; Fecht, Daniela; Toledano, Mireille B; Beevers, Sean D; Anderson, Hugh Ross; Kelly, Frank J; Tonne, Cathryn

    2015-10-14

    Road traffic noise has been associated with hypertension but evidence for the long-term effects on hospital admissions and mortality is limited. We examined the effects of long-term exposure to road traffic noise on hospital admissions and mortality in the general population. The study population consisted of 8.6 million inhabitants of London, one of Europe's largest cities. We assessed small-area-level associations of day- (7:00-22:59) and nighttime (23:00-06:59) road traffic noise with cardiovascular hospital admissions and all-cause and cardiovascular mortality in all adults (≥25 years) and elderly (≥75 years) through Poisson regression models. We adjusted models for age, sex, area-level socioeconomic deprivation, ethnicity, smoking, air pollution, and neighbourhood spatial structure. Median daytime exposure to road traffic noise was 55.6 dB. Daytime road traffic noise increased the risk of hospital admission for stroke with relative risk (RR) 1.05 [95% confidence interval (CI): 1.02-1.09] in adults, and 1.09 (95% CI: 1.04-1.14) in the elderly in areas >60 vs. 60 vs. road traffic noise was associated with small increased risks of all-cause mortality and cardiovascular mortality and morbidity in the general population, particularly for stroke in the elderly. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

  17. Colon cancer-associated mutator DNA polymerase δ variant causes expansion of dNTP pools increasing its own infidelity

    Science.gov (United States)

    Mertz, Tony M.; Sharma, Sushma; Chabes, Andrei; Shcherbakova, Polina V.

    2015-01-01

    Defects in DNA polymerases δ (Polδ) and ε (Polε) cause hereditary colorectal cancer and have been implicated in the etiology of some sporadic colorectal and endometrial tumors. We previously reported that the yeast pol3-R696W allele mimicking a human cancer-associated variant, POLD1-R689W, causes a catastrophic increase in spontaneous mutagenesis. Here, we describe the mechanism of this extraordinary mutator effect. We found that the mutation rate increased synergistically when the R696W mutation was combined with defects in Polδ proofreading or mismatch repair, indicating that pathways correcting DNA replication errors are not compromised in pol3-R696W mutants. DNA synthesis by purified Polδ-R696W was error-prone, but not to the extent that could account for the unprecedented mutator phenotype of pol3-R696W strains. In a search for cellular factors that augment the mutagenic potential of Polδ-R696W, we discovered that pol3-R696W causes S-phase checkpoint-dependent elevation of dNTP pools. Abrogating this elevation by strategic mutations in dNTP metabolism genes eliminated the mutator effect of pol3-R696W, whereas restoration of high intracellular dNTP levels restored the mutator phenotype. Further, the use of dNTP concentrations present in pol3-R696W cells for in vitro DNA synthesis greatly decreased the fidelity of Polδ-R696W and produced a mutation spectrum strikingly similar to the spectrum observed in vivo. The results support a model in which (i) faulty synthesis by Polδ-R696W leads to a checkpoint-dependent increase in dNTP levels and (ii) this increase mediates the hypermutator effect of Polδ-R696W by facilitating the extension of mismatched primer termini it creates and by promoting further errors that continue to fuel the mutagenic pathway. PMID:25827231

  18. Transient Oxygen/Glucose Deprivation Causes a Delayed Loss of Mitochondria and Increases Spontaneous Calcium Signaling in Astrocytic Processes

    Science.gov (United States)

    O'Donnell, John C.; Jackson, Joshua G.

    2016-01-01

    Recently, mitochondria have been localized to astrocytic processes where they shape Ca2+ signaling; this relationship has not been examined in models of ischemia/reperfusion. We biolistically transfected astrocytes in rat hippocampal slice cultures to facilitate fluorescent confocal microscopy, and subjected these slices to transient oxygen/glucose deprivation (OGD) that causes delayed excitotoxic death of CA1 pyramidal neurons. This insult caused a delayed loss of mitochondria from astrocytic processes and increased colocalization of mitochondria with the autophagosome marker LC3B. The losses of neurons in area CA1 and mitochondria in astrocytic processes were blocked by ionotropic glutamate receptor (iGluR) antagonists, tetrodotoxin, ziconotide (Ca2+ channel blocker), two inhibitors of reversed Na+/Ca2+ exchange (KB-R7943, YM-244769), or two inhibitors of calcineurin (cyclosporin-A, FK506). The effects of OGD were mimicked by NMDA. The glutamate uptake inhibitor (3S)-3-[[3-[[4-(trifluoromethyl)benzoyl]amino]phenyl]methoxy]-l-aspartate increased neuronal loss after OGD or NMDA, and blocked the loss of astrocytic mitochondria. Exogenous glutamate in the presence of iGluR antagonists caused a loss of mitochondria without a decrease in neurons in area CA1. Using the genetic Ca2+ indicator Lck-GCaMP-6S, we observed two types of Ca2+ signals: (1) in the cytoplasm surrounding mitochondria (mitochondrially centered) and (2) traversing the space between mitochondria (extramitochondrial). The spatial spread, kinetics, and frequency of these events were different. The amplitude of both types was doubled and the spread of both types changed by ∼2-fold 24 h after OGD. Together, these data suggest that pathologic activation of glutamate transport and increased astrocytic Ca2+ through reversed Na+/Ca2+ exchange triggers mitochondrial loss and dramatic increases in Ca2+ signaling in astrocytic processes. SIGNIFICANCE STATEMENT Astrocytes, the most abundant cell type in the

  19. Survival analysis of increases in care needs associated with dementia and living alone among older long-term care service users in Japan.

    Science.gov (United States)

    Lin, Huei-Ru; Otsubo, Tetsuya; Imanaka, Yuichi

    2017-08-15

    Japan is known for its long life expectancy and rapidly aging society that there are various demands of older adults need to be fulfilled with, and one of them is long-term care needs. Therefore, Japan implemented the Long-Term Care Insurance in year 2000 for citizens who are above 65-year old and citizens who are above 40-year old in needs of long-term care services. This study was undertaken to longitudinally examine the influence of dementia and living alone on care needs increases among older long-term care insurance service users in Japan. Long-term care insurance claims data were used to identify enrollees who applied for long-term care services between October 2010 and September 2011, and subjects were tracked until March 2015. A Kaplan-Meier survival analysis was conducted to examine increases in care needs over time in months. Cox regression models were used to examine the effects of dementia and living alone on care needs increases. The cumulative survival rates before care needs increased over the 4.5-year observation period were 17.6% in the dementia group and 31.9% in the non-dementia group. After adjusting for age, sex, care needs level, and status of living alone, the risk of care needs increases was found to be 1.5 times higher in the dementia group. Living alone was not a significant risk factor of care needs increases, but people with dementia who lived alone had a higher risk of care needs increases than those without dementia. Dementia, older age, the female sex, and lower care needs levels were associated with a higher risk of care needs increases over the study period. Among these variables, dementia had the strongest impact on care needs increases, especially in persons who lived alone.

  20. Abrupt onset of large scale nonproton ion release in purple membranes caused by increasing pH or ionic strength.

    Science.gov (United States)

    Marinetti, T

    1987-06-01

    The abrupt onset of large scale nonproton ion release by photo-excited purple membrane suspensions has been observed near neutral pH using transient conductivity measurements. At pH 7 and low ionic strength, the conductivity transients due to proton and nonproton ions are of comparable magnitude but of opposite sign: fast proton release and ion uptake, followed by slow proton uptake and ion release. By increasing either the pH or the NaCl concentration, the amplitude of the conductivity transient increases sharply and the signal is then dominated by nonproton ion release. These results can be understood in terms of light-induced changes in the population of counterions condensed at the purple membrane surface caused by changes in the surface charge density. The critical charge density required for condensation to occur is evidently achieved near neutral pH by ionizing dissociable groups on the membrane by either titration (increasing the pH) or shifting their pKs (increasing the ionic strength).

  1. Decreased miR-128 and increased miR-21 synergistically cause podocyte injury in sepsis.

    Science.gov (United States)

    Wang, Shanshan; Wang, Jun; Zhang, Zengdi; Miao, Hongjun

    2017-08-01

    Glomerular podocytes are injured in sepsis. We studied, in a sepsis patient, whether microRNAs (miRNAs) play a role in the podocyte injury. Podocytes were cultured and treated with lipopolysaccharide (LPS). Filtration barrier function of podocyte was analyzed with albumin influx assay. Nephrin level was analyzed with reverse transcription polymerase chain reaction (RT-PCR) and western blot. MiRNAs were detected using miRNAs PCR Array and in situ hybridization. MiRNA target sites were evaluated with luciferase reporter assays. LPS impaired the filtration barrier function of podocytes. MiR-128 level was decreased and miR-21 level was increased in podocytes in vitro and in the sepsis patient. The decrease in miR-128 was sufficient to induce the loss of nephrin and the impairment of filtration barrier function, while the increase of miR-21 exacerbated the process. Snail and phosphatase and tensin homolog (PTEN) were identified as the targets of miR-128 and miR-21. Decreased miR-128 induced Snail expression, and the increased miR-21 stabilized Snail by regulating the PTEN/Akt/GSK3β pathway. Supplementation of miR-128 and inhibition of miR-21 suppressed Snail expression and prevented the podocyte injury induced by LPS. Our study suggests that decreased miR-128 and increased miR-21 synergistically cause podocyte injury and are the potential therapeutic targets in sepsis.

  2. Increased Effectiveness of Microbiological Verification by Concentration-Dependent Neutralization of Sanitizers Used in Poultry Slaughter and Fabrication Allowing Salmonella enterica Survival

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    Zahra H. Mohammad

    2018-03-01

    Full Text Available Sanitizer neutralizers can assist foodborne pathogen detection during routine testing by counteracting sanitizer residues carried over into fluids collected and tested from food samples. This study tested sanitizer-matched neutralizers applied at increasing concentrations to facilitate Salmonella enterica survival following exposure to cetylpyridinium chloride (CPC or peracetic acid (PAA, identifying minimum required concentrations of neutralizers to facilitate pathogen survival. Salmonella isolates were individually inoculated into a non-selective medium followed immediately by CPC (0.1 to 0.8% v/v or PAA (0.0125 to 0.2% v/v application, followed by neutralizers application. CPC was neutralized by lecithin and polysorbate 80, each supplemented into buffered peptone water (BPW at 0.125 to 2.0X its respective content in Dey-Engley (D/E neutralizing buffer. PAA was neutralized in BPW supplemented with disodium phosphate, potassium monophosphate, and sodium thiosulfate, each at 0.25 to 3.0X its respective concentration in BPW (phosphates or D/E buffer (thiosulfate. Addition of neutralizers at 1X their respective concentrations in D/E buffer was required to allow Salmonella growth at the maximum CPC concentration (0.8%, while 2X neutralizer addition was required for Salmonella growth at the maximum PAA level (0.2%. Sanitizer neutralizers can assist pathogen survival and detection during routine food product testing.

  3. Increased tolerance and resistance to virus infections: a possible factor in the survival of Varroa destructor-resistant honey bees (Apis mellifera).

    Science.gov (United States)

    Locke, Barbara; Forsgren, Eva; de Miranda, Joachim R

    2014-01-01

    The honey bee ectoparasitic mite, Varroa destructor, has a world-wide distribution and inflicts more damage than all other known apicultural diseases. However, Varroa-induced colony mortality is more accurately a result of secondary virus infections vectored by the mite. This means that honey bee resistance to Varroa may include resistance or tolerance to virus infections. The aim of this study was to see if this is the case for a unique population of mite-resistant (MR) European honey bees on the island of Gotland, Sweden. This population has survived uncontrolled mite infestation for over a decade, developing specific mite-related resistance traits to do so. Using RT-qPCR techniques, we monitored late season virus infections, Varroa mite infestation and honey bee colony population dynamics in the Gotland MR population and compared this to mite-susceptible (MS) colonies in a close by apiary. From summer to autumn the deformed wing virus (DWV) titres increased similarly between the MR and MS populations, while the black queen cell virus (BQCV) and sacbrood virus (SBV) titres decreased substantially in the MR population compared to the MS population by several orders of magnitude. The MR colonies all survived the following winter with high mite infestation, high DWV infection, small colony size and low proportions of autumn brood, while the MS colonies all perished. Possible explanations for these changes in virus titres and their relevance to Varroa resistance and colony winter survival are discussed.

  4. Increased tolerance and resistance to virus infections: a possible factor in the survival of Varroa destructor-resistant honey bees (Apis mellifera.

    Directory of Open Access Journals (Sweden)

    Barbara Locke

    Full Text Available The honey bee ectoparasitic mite, Varroa destructor, has a world-wide distribution and inflicts more damage than all other known apicultural diseases. However, Varroa-induced colony mortality is more accurately a result of secondary virus infections vectored by the mite. This means that honey bee resistance to Varroa may include resistance or tolerance to virus infections. The aim of this study was to see if this is the case for a unique population of mite-resistant (MR European honey bees on the island of Gotland, Sweden. This population has survived uncontrolled mite infestation for over a decade, developing specific mite-related resistance traits to do so. Using RT-qPCR techniques, we monitored late season virus infections, Varroa mite infestation and honey bee colony population dynamics in the Gotland MR population and compared this to mite-susceptible (MS colonies in a close by apiary. From summer to autumn the deformed wing virus (DWV titres increased similarly between the MR and MS populations, while the black queen cell virus (BQCV and sacbrood virus (SBV titres decreased substantially in the MR population compared to the MS population by several orders of magnitude. The MR colonies all survived the following winter with high mite infestation, high DWV infection, small colony size and low proportions of autumn brood, while the MS colonies all perished. Possible explanations for these changes in virus titres and their relevance to Varroa resistance and colony winter survival are discussed.

  5. Systemic Administration of Mesenchymal Stem Cells Increases Neuron Survival after Global Cerebral Ischemia In Vivo (2VO

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    Luisa Perasso

    2010-01-01

    Full Text Available Although many studies have shown that administration of stem cells after focal cerebral ischemia improves brain damage, very little data are available concerning the damage induced by global cerebral ischemia. The latter causes neuronal death in selectively vulnerable areas, including the hippocampal CA1 region. We tested the hypothesis that intravenous infusion of bone marrowderived stromal cells (mesenchimal stem cells, MSC reduce brain damage after transient global ischemia. In adult male Sprague-Dawley rats transient global ischemia was induced using bilateral common carotid artery occlusion for 20 min in addition to controlled hypotension. Five days after, the animals were anaesthetized with urethane and the brain was fixed, sectioned and stained with hematoxylin-eosin to investigate histological damage. MSC did not fully protect against ischemic damage, as the number of viable neurons in this group was lower than in normal (sham-operated rats. However, in MSC-treated rats the number of viable CA1 pyramidal neurons was significally higher than in rats that had been subjected to ischemia but not treated with MSC. We conclude that intravenous administration of MSC after transient global ischemia reduces hippocampal damage.

  6. TV viewing time is associated with increased all-cause mortality in Brazilian adults independent of physical activity.

    Science.gov (United States)

    Turi, B C; Monteiro, H L; Lemes, Í R; Codogno, J S; Lynch, K R; Asahi Mesquita, C A; Fernandes, R A

    2018-02-01

    The purpose of this study was to investigate the association between television (TV) viewing and all-cause mortality among Brazilian adults after 6 years of follow-up. This longitudinal study started in 2010 in the city of Bauru, SP, Brazil, and involved 970 adults aged ≥50 years. Mortality was reported by relatives and confirmed in medical records of the Brazilian National Health System. Physical activity (PA) and TV viewing were assessed by the Baecke questionnaire. Health status, sociodemographic and behavioral covariates were considered as potential confounders. After 6 years of follow-up, 89 deaths were registered (9.2% [95% CI=7.4%-11%]). Type 2 diabetes mellitus was associated with higher risk of mortality (P-value=.012). Deaths correlated significantly with age (ρ=.188; P-value=.001), overall PA score (ρ=-.128; P-value=.001) and TV viewing (ρ=.086; P-value=.007). Lower percentage of participants reported TV viewing time as often (16%) and very often (5.7%), but there was an association between higher TV viewing time ("often" and "very often" grouped together) and increased mortality after 6 years of follow-up (P-value=.006). The higher TV viewing time was associated with a 44.7% increase in all-cause mortality (HR=1.447 [1.019-2.055]), independently of other potential confounders. In conclusion, the findings from this cohort study identified increased risk of mortality among adults with higher TV viewing time, independently of PA and other variables. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Ciprofloxacin Enhances Stress Erythropoiesis in Spleen and Increases Survival after Whole-Body Irradiation Combined with Skin-Wound Trauma

    Science.gov (United States)

    2014-02-28

    rheumatoid arthritis [10], and chemotherapy-induced neutropenia [11]. These observations convincingly demonstrate that immunomodulation is a result of...Introduction Victims of nuclear disasters often suffer from a combination of radiation injury (RI) along with other insults such as physical wounds and...from 40% to 50%, but the increase was not significant (Figure 1A top left panel). In addition, none of the CI mice died after completion of CIP therapy

  8. Increased neutrophil-to-lymphocyte ratio after neoadjuvant therapy is associated with worse survival after resection of borderline resectable pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Glazer, Evan S; Rashid, Omar M; Pimiento, Jose M; Hodul, Pamela J; Malafa, Mokenge P

    2016-11-01

    The neutrophil-to-lymphocyte ratio (neutrophil count divided by lymphocyte count) is a marker of inflammation associated with poor cancer outcomes. The role of neutrophil-to-lymphocyte ratio in borderline resectable pancreatic ductal adenocarcinoma is unknown. We hypothesized that increased neutrophil-to-lymphocyte ratio in patients with borderline resectable pancreatic ductal adenocarcinoma after neoadjuvant therapy is inversely associated with survival. We used our borderline resectable pancreatic ductal adenocarcinoma database to identify patients who had completed neoadjuvant therapy and underwent resection. The neutrophil-to-lymphocyte ratio difference was calculated as the neutrophil-to-lymphocyte ratio after neoadjuvant therapy minus the neutrophil-to-lymphocyte ratio before neoadjuvant therapy. Patients were assigned to the increased neutrophil-to-lymphocyte ratio cohort if the difference was ≥2.5 units; all others were assigned to the stable neutrophil-to-lymphocyte ratio cohort. Statistical analyses were performed with t test and regression. Of 62 patients identified, 43 were assigned to the stable neutrophil-to-lymphocyte ratio cohort, and 19 to the increased neutrophil-to-lymphocyte ratio cohort. There were no differences in stage, age, or sex. The preneoadjuvant neutrophil-to-lymphocyte ratio was 3.1 ± 2.4, whereas the postneoadjuvant neutrophil-to-lymphocyte ratio was 4.4 ± 3.5 (P = .002). Overall survival was worse in the increased neutrophil-to-lymphocyte ratio cohort compared with the stable neutrophil-to-lymphocyte ratio cohort (P = .009) with a Cox hazard ratio of 2.9 (P = .02). N0 disease conferred a survival advantage over N1 disease (Cox hazard ratio = 0.3, P = .01). On multivariate Cox hazard regression analysis, both increased neutrophil-to-lymphocyte ratio and N1 stage were associated with worse survival (P ratio in patients with borderline resectable pancreatic ductal adenocarcinoma. These findings support exploring

  9. Population density, socioeconomic environment and all-cause mortality: a multilevel survival analysis of 2.7 million individuals in Denmark.

    Science.gov (United States)

    Meijer, Mathias; Kejs, Anne Mette; Stock, Christiane; Bloomfield, Kim; Ejstrud, Bo; Schlattmann, Peter

    2012-03-01

    This study examines the relative effects of population density and area-level SES on all-cause mortality in Denmark. A shared frailty model was fitted with 2.7 million persons aged 30-81 years in 2,121 parishes. Residence in areas with high population density increased all-cause mortality for all age groups. For older age groups, residence in areas with higher proportions of unemployed persons had an additional effect. Area-level factors explained considerably more variation in mortality among the elderly than among younger generations. Overall this study suggests that structural prevention efforts in neighborhoods could help reduce mortality when mediating processes between area-level socioeconomic status, population density and mortality are found. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. BDNF Increases Survival and Neuronal Differentiation of Human Neural Precursor Cells Cotransplanted with a Nanofiber Gel to the Auditory Nerve in a Rat Model of Neuronal Damage

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    Yu Jiao

    2014-01-01

    Full Text Available Objectives. To study possible nerve regeneration of a damaged auditory nerve by the use of stem cell transplantation. Methods. We transplanted HNPCs to the rat AN trunk by the internal auditory meatus (IAM. Furthermore, we studied if addition of BDNF affects survival and phenotypic differentiation of the grafted HNPCs. A bioactive nanofiber gel (PA gel, in selected groups mixed with BDNF, was applied close to the implanted cells. Before transplantation, all rats had been deafened by a round window niche application of β-bungarotoxin. This neurotoxin causes a selective toxic destruction of the AN while keeping the hair cells intact. Results. Overall, HNPCs survived well for up to six weeks in all groups. However, transplants receiving the BDNF-containing PA gel demonstrated significantly higher numbers of HNPCs and neuronal differentiation. At six weeks, a majority of the HNPCs had migrated into the brain stem and differentiated. Differentiated human cells as well as neurites were observed in the vicinity of the cochlear nucleus. Conclusion. Our results indicate that human neural precursor cells (HNPC integration with host tissue benefits from additional brain derived neurotrophic factor (BDNF treatment and that these cells appear to be good candidates for further regenerative studies on the auditory nerve (AN.

  11. Increasing the cracking resistance and the survivability of the elements the joints of the sections of the jib crane-manipulating installations of mobile machines

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    Lagerev I.A.

    2015-12-01

    Full Text Available The new constructive method of increasing the cracking resistance and survivability of eyes swivel boom crane with hydraulic cylinders. Analysis of its efficiency on the basis of predicting the growth of fatigue cracks for the conven-tional and modified variants of the constructive execution of the connection nodes of the cylinders with the boom sec-tions. This research was supported by the grant no. MK-92.2014.8 of the President of Russian Federation for young scientist support.

  12. Progranulin causes adipose insulin resistance via increased autophagy resulting from activated oxidative stress and endoplasmic reticulum stress.

    Science.gov (United States)

    Guo, Qinyue; Xu, Lin; Li, Huixia; Sun, Hongzhi; Liu, Jiali; Wu, Shufang; Zhou, Bo

    2017-01-31

    Progranulin (PGRN) has recently emerged as an important regulator for insulin resistance. However, the direct effect of progranulin in adipose insulin resistance associated with the autophagy mechanism is not fully understood. In the present study, progranulin was administered to 3T3-L1 adipocytes and C57BL/6 J mice with/without specific inhibitors of oxidative stress and endoplasmic reticulum stress, and metabolic parameters, oxidative stress, endoplasmic reticulum stress and autophagy markers were assessed. Progranulin treatment increased iNOS expression, NO synthesis and ROS generation, and elevated protein expressions of CHOP, GRP78 and the phosphorylation of PERK, and caused a significant increase in Atg7 and LC3-II protein expression and a decreased p62 expression, and decreased insulin-stimulated tyrosine phosphorylation of IRS-1 and glucose uptake, demonstrating that progranulin activated oxidative stress and ER stress, elevated autophagy and induced insulin insensitivity in adipocytes and adipose tissue of mice. Interestingly, inhibition of iNOS and ER stress both reversed progranulin-induced stress response and increased autophagy, protecting against insulin resistance in adipocytes. Furthermore, the administration of the ER stress inhibitor 4-phenyl butyric acid reversed the negative effect of progranulin in vivo. Our findings showed the clinical potential of the novel adipokine progranulin in the regulation of insulin resistance, suggesting that progranulin might mediate adipose insulin resistance, at least in part, by inducing autophagy via activated oxidative stress and ER stress.

  13. Diet-induced obesity causes visceral, but not subcutaneous, lymph node hyperplasia via increases in specific immune cell populations.

    Science.gov (United States)

    Magnuson, A M; Regan, D P; Fouts, J K; Booth, A D; Dow, S W; Foster, M T

    2017-10-01

    The spatial proximity of adipose depots to secondary lymph nodes allows a unique relation between the two systems. Obesity, predominately visceral adiposity, links to numerous diseases; hence, we postulate that secondary lymphatics within this region contributes to disease risk. Male C57BL/6 mice were fed standard CHOW (18% kcal fat) or Western diet (45% kcal fat) for 7 weeks. Visceral and subcutaneous lymph nodes and associated adipose depots they occupy were excised. Lymph node morphology and resident immune cell populations were characterized via histopathology, immunofluorescence and flow cytometry. Adipose tissue immune cell populations were also characterized. Obesity caused lymph node expansion, increased viable cell number and deviations in immune cell populations. These alterations were exclusive to visceral lymph nodes. Notably, pro-inflammatory antigen presenting cells and regulatory T cells increased in number in the visceral lymph node. Obesity, however, reduced T regulatory cells in visceral lymph nodes. The visceral adipose depot also had greater reactivity towards HFD than subcutaneous, with a greater percent of macrophages, dendritic and CD8 + T cells. Immune cell number, in both the visceral and subcutaneous, however decreased as adipose depots enlarged. Overall, HFD has a greater influence on visceral cavity than the subcutaneous. In the visceral lymph node, but not subcutaneous, HFD-induced obesity decreased cell populations that suppressed immune function while increasing those that regulate/activate immune response. © 2017 John Wiley & Sons Ltd.

  14. Heterosis Increases Fertility, Fecundity, and Survival of Laboratory-Produced F1 Hybrid Males of the Malaria Mosquito Anopheles coluzzii.

    Science.gov (United States)

    Ekechukwu, Nkiru E; Baeshen, Rowida; Traorè, Sékou F; Coulibaly, Mamadou; Diabate, Abdoulaye; Catteruccia, Flaminia; Tripet, Frédéric

    2015-10-23

    The success of vector control strategies aiming to decrease disease transmission via the release of sterile or genetically-modified male mosquitoes critically depends on mating between laboratory-reared males and wild females. Unfortunately, mosquito colonization, laboratory rearing, and genetic manipulations can all negatively affect male competitiveness. Heterosis is commonly used to produce domestic animals with enhanced vigor and homogenous genetic background and could therefore potentially improve the mating performance of mass-reared male mosquitoes. Here, we produced enhanced hybrid males of the malaria mosquito Anopheles coluzzii by crossing two strains colonized >35 and 8 years ago. We compared the amount of sperm and mating plug proteins they transferred to females, as well as their insemination rate, reproductive success and longevity under various experimental conditions. Across experiments, widespread adaptations to laboratory mating were detected in the older strain. In large-group mating experiments, no overall hybrid advantage in insemination rates and the amount of sperm and accessory gland proteins transferred to females was detected. Despite higher sperm activity, hybrid males did not appear more fecund. However, individual-male mating and laboratory-swarm experiments revealed that hybrid males, while inseminating fewer females than older inbred males, were significantly more fertile, producing larger mating plugs and drastically increasing female fecundity. Heterotic males also showed increased longevity. These results validate the use of heterosis for creating hybrid males with improved fitness from long-established inbred laboratory strains. Therefore, this simple approach could facilitate disease control strategies based on male mosquito releases with important ultimate benefits to human health. Copyright © 2015 Ekechukwu et al.

  15. Contribution of adenosine to the increase in skeletal muscle blood flow caused by manual acupuncture in rats.

    Science.gov (United States)

    Shinbara, Hisashi; Nagaoka, Satomi; Izutani, Yasuyuki; Okubo, Masamichi; Kimura, Keisaku; Mizunuma, Kunio; Sumiya, Eiji

    2017-08-01

    Adenosine is believed to play an important role in local acupuncture analgesia. The aim of this study was to investigate the contribution of adenosine to the increase in skeletal muscle blood flow (MBF) caused by manual acupuncture (MA). Thirty-two male Sprague-Dawley rats (310-360 g) were anaesthetised and divided into four equal groups (n=8 each): Saline, Saline+MA, Theophylline, and Theophylline+MA. In the two MA groups, the sparrow-pecking MA technique was applied at 30 repetitions per min for 1 min to a depth of 15-18 mm using a stainless steel acupuncture needle (0.20×40 mm). The stimulus point was located on the right tibialis anterior (TA) muscle 7-8 mm below the knee. Animals in the two theophylline groups were intra-arterially injected with 8-(p-sulphophenyl) theophylline, a non-selective adenosine receptor antagonist, at a dose of 30 mg/kg before MA. Animals in the two saline groups received control saline. Fluorescent microspheres (15 µm in diameter, yellow-green fluorescent) were used for MBF measurement in all four groups. MA of the TA muscle significantly increased MBF (Saline+MA vs Saline: p=0.001; Saline+MA vs Theophylline: p=0.008). Pre-treatment with theophylline appeared to inhibit this increase (Theophylline vs Theophylline+MA; p=1.000). MBF in the Theophylline+MA group was 43% lower than in the Saline+MA group, although this was not significantly different (p=0.104). The results suggest that adenosine leads to an increase in MBF caused by MA. Adenosine may play a role in acupuncture analgesia by washing out algesic substances. Further studies are needed in order to elucidate the precise mechanism. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  16. Impact of chemotherapy relative dose intensity on cause-specific and overall survival for stage I-III breast cancer: ER+/PR+, HER2- vs. triple-negative.

    Science.gov (United States)

    Zhang, Lu; Yu, Qingzhao; Wu, Xiao-Cheng; Hsieh, Mei-Chin; Loch, Michelle; Chen, Vivien W; Fontham, Elizabeth; Ferguson, Tekeda

    2018-05-01

    To investigate the impact of chemotherapy relative dose intensity (RDI) on cause-specific and overall survival for stage I-III breast cancer: estrogen receptor or progesterone receptor positive, human epidermal-growth factor receptor negative (ER+/PR+ and HER2-) vs. triple-negative (TNBC) and to identify the optimal RDI cut-off points in these two patient populations. Data were collected by the Louisiana Tumor Registry for two CDC-funded projects. Women diagnosed with stage I-III ER+/PR+, HER2- breast cancer, or TNBC in 2011 with complete information on RDI were included. Five RDI cut-off points (95, 90, 85, 80, and 75%) were evaluated on cause-specific and overall survival, adjusting for multiple demographic variables, tumor characteristics, comorbidity, use of granulocyte-growth factor/cytokines, chemotherapy delay, chemotherapy regimens, and use of hormone therapy. Cox proportional hazards models and Kaplan-Meier survival curves were estimated and adjusted by stabilized inverse probability treatment weighting (IPTW) of propensity score. Of 494 ER+/PR+, HER2- patients and 180 TNBC patients, RDI PR+, HER2- patients, 85% was the only cut-off point at which the low RDI was significantly associated with worse overall survival (HR = 1.93; 95% CI 1.09-3.40). Among TNBC patients, 75% was the cut-off point at which the high RDI was associated with better cause-specific (HR = 2.64; 95% CI 1.09, 6.38) and overall survival (HR = 2.39; 95% CI 1.04-5.51). Higher RDI of chemotherapy is associated with better survival for ER+/PR+, HER2- patients and TNBC patients. To optimize survival benefits, RDI should be maintained ≥ 85% in ER+/PR+, HER2- patients, and ≥ 75% in TNBC patients.

  17. Addition of Cardiorespiratory Fitness Within an Obesity Risk Classification Model Identifies Men at Increased Risk of All-Cause Mortality.

    Science.gov (United States)

    Ricketts, T Alexander; Sui, Xuemei; Lavie, Carl J; Blair, Steven N; Ross, Robert

    2016-05-01

    Guidelines for identification of obesity-related risk which stratify disease risk using specific combinations of body mass index and waist circumference. Whether the addition of cardiorespiratory fitness, an independent predictor of disease risk, provides better risk prediction of all-cause mortality within current body mass index and waist circumference categories is unknown. The study objective was to determine whether the addition of cardiorespiratory fitness improves prediction of all-cause mortality risk classified by the combination of body mass index and waist circumference. We performed a prospective observational study using data from the Aerobics Center Longitudinal Study. A total of 31,267 men (mean age, 43.9 years; standard deviation, 9.4 years) who completed a baseline medical examination between 1974 and 2002 were included. The main outcome measure was all-cause mortality. Participants were grouped using body mass index- and waist circumference-specific threshold combinations: normal body mass index: 18.5 to 24.9 kg/m(2), waist circumference threshold of 90 cm; overweight body mass index: 25.0 to 29.9 kg/m(2), waist circumference threshold of 100 cm, and obese body mass index: 30.0 to 34.9 kg/m(2), waist circumference threshold of 110 cm. Participants were classified using cardiorespiratory fitness as unfit or fit, where unfit was the lowest fifth of the age-specified distribution of maximal exercise test time on the treadmill among the entire Aerobics Center Longitudinal Study population. A total of 1399 deaths occurred over a follow-up of 14.1 ± 7.4 years, for a total of 439,991 person-years of observation. Men who were unfit and had normal body mass index with waist circumference men who were fit, respectively (P Men who were unfit and overweight had 41% (HR, 1.41; 95% CI, 1.04-1.90) higher mortality risk with a waist circumference Men who were unfit and obese were not at increased mortality risk (HR, 1.37; 95% CI, 0.90-2.09) with a waist

  18. Surviving workplace adversity: a qualitative study of nurses and midwives and their strategies to increase personal resilience.

    Science.gov (United States)

    Mcdonald, Glenda; Jackson, Debra; Vickers, Margaret H; Wilkes, Lesley

    2016-01-01

    To explore the experiences of Australian nurses and midwives who perceived themselves as resilient. The focus of this paper is to report the strategies used by a group of nurses and midwives to develop and maintain their resilience, despite encountering serious workplace adversity. Despite the potentially adverse effects of nursing work, many nurses and midwives thrive through exercising self-efficacy and coping skills. The relationship between thriving and resilience is clear, as resilience refers to the ability to cope well with adversity and change. The participants were part of an instrumental, collective case study investigation of personal resilience amongst nurses and midwives. Prior to an innovative, work-based intervention including workshops and mentoring, participants were interviewed to collect baseline perceptions and experiences of personal resilience and workplace adversity. Interview transcripts were analysed thematically. Participants attributed their ability to thrive in the workplace to three major influences: support networks, personal characteristics and ability to organise work for personal resilience. Participant insights contributed to a deeper understanding of personal resilience and highlight future initiatives to enhance the ability of nurses and midwives to thrive within health organisations and systems. It is vital that resilience-enhancing initiatives, such as peer mentoring and tailored work options to increase autonomy, are implemented at earlier career phases. © 2015 John Wiley & Sons Ltd.

  19. Hypoxic Preconditioning Increases Survival and Pro-Angiogenic Capacity of Human Cord Blood Mesenchymal Stromal Cells In Vitro.

    Directory of Open Access Journals (Sweden)

    Andreas Matthäus Bader

    preconditioning might be a translationally relevant strategy to increase the tolerance of cord blood MSCs to ischemia and improve their therapeutic efficacy in clinical applications.

  20. Increasing N-acetylaspartate in the Brain during Postnatal Myelination Does Not Cause the CNS Pathologies of Canavan Disease

    Directory of Open Access Journals (Sweden)

    Abhilash P. Appu

    2017-06-01

    Full Text Available Canavan disease is caused by mutations in the gene encoding aspartoacylase (ASPA, a deacetylase that catabolizes N-acetylaspartate (NAA. The precise involvement of elevated NAA in the pathogenesis of Canavan disease is an ongoing debate. In the present study, we tested the effects of elevated NAA in the brain during postnatal development. Mice were administered high doses of the hydrophobic methyl ester of NAA (M-NAA twice daily starting on day 7 after birth. This treatment increased NAA levels in the brain to those observed in the brains of Nur7 mice, an established model of Canavan disease. We evaluated various serological parameters, oxidative stress, inflammatory and neurodegeneration markers and the results showed that there were no pathological alterations in any measure with increased brain NAA levels. We examined oxidative stress markers, malondialdehyde content (indicator of lipid peroxidation, expression of NADPH oxidase and nuclear translocation of the stress-responsive transcription factor nuclear factor (erythroid-derived 2-like 2 (NRF-2 in brain. We also examined additional pathological markers by immunohistochemistry and the expression of activated caspase-3 and interleukin-6 by Western blot. None of the markers were increased in the brains of M-NAA treated mice, and no vacuoles were observed in any brain region. These results show that ASPA expression prevents the pathologies associated with excessive NAA concentrations in the brain during postnatal myelination. We hypothesize that the pathogenesis of Canavan disease involves not only disrupted NAA metabolism, but also excessive NAA related signaling processes in oligodendrocytes that have not been fully determined and we discuss some of the potential mechanisms.

  1. Association with pregnancy increases the risk of local recurrence but does not impact overall survival in breast cancer: A case-control study of 87 cases.

    Science.gov (United States)

    Genin, A S; De Rycke, Y; Stevens, D; Donnadieu, A; Langer, A; Rouzier, R; Lerebours, F

    2016-12-01

    Pregnancy-associated breast cancer (PABC) constitutes 7% of all BCs in young women. The prognosis of PABC remains controversial. In this study, we evaluated the impact of the association of pregnancy with BC on the rates of overall survival (OS), disease free survival (DFS), and distant and local recurrence-free survival. We conducted a retrospective unicenter case-control study. We enrolled PABC patients treated at our institution between 1992 and 2009. For each case, 2 BC controls were matched for age and year of diagnosis. Univariate and multivariate analyses were performed to assess the parameters associated with prognosis. Eighty-seven PABC patients were enrolled and matched with 174 controls. The univariate analysis did not reveal any significant differences in OS, DFS or distant recurrence rates between the 2 groups. Pregnancy associated status, a tumor larger than T2 and neoadjuvant chemotherapy as the primary treatment were significantly associated with an increased risk of local relapse. The multivariate analysis showed that the pregnancy associated status and the tumor size were strong prognostic factors of local recurrence. Pregnancy associated status negates the prognostic value of tumor size, as both T0-T2 and T3-T4 PABC patients have the same poor prognosis as control BC patients with T3-T4 tumors. Interestingly, although PABC patients have more locally advanced tumors, they did not have a higher rate of radical surgery than the control BC patients. Pregnancy associated status is a strong prognostic factor of local relapse in BC. In PABC patients, when possible, radical surgery should be the preferred first treatment step. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. The modified 2VO ischemia protocol causes cognitive impairment similar to that induced by the standard method, but with a better survival rate

    Directory of Open Access Journals (Sweden)

    F. Cechetti

    2010-12-01

    Full Text Available Permanent bilateral occlusion of the common carotid arteries (2VO in the rat has been established as a valid experimental model to investigate the effects of chronic cerebral hypoperfusion on cognitive function and neurodegenerative processes. Our aim was to compare the cognitive and morphological outcomes following the standard 2VO procedure, in which there is concomitant artery ligation, with those of a modified protocol, with a 1-week interval between artery occlusions to avoid an abrupt reduction of cerebral blood flow, as assessed by animal performance in the water maze and damage extension to the hippocampus and striatum. Male Wistar rats (N = 47 aged 3 months were subjected to chronic hypoperfusion by permanent bilateral ligation of the common carotid arteries using either the standard or the modified protocol, with the right carotid being the first to be occluded. Three months after the surgical procedure, rat performance in the water maze was assessed to investigate long-term effects on spatial learning and memory and their brains were processed in order to estimate hippocampal volume and striatal area. Both groups of hypoperfused rats showed deficits in reference (F(8,172 = 7.0951, P < 0.00001 and working spatial memory [2nd (F(2,44 = 7.6884, P < 0.001, 3rd (F(2,44 = 21.481, P < 0.00001 and 4th trials (F(2,44 = 28.620, P < 0.0001]; however, no evidence of tissue atrophy was found in the brain structures studied. Despite similar behavioral and morphological outcomes, the rats submitted to the modified protocol showed a significant increase in survival rate, during the 3 months of the experiment (P < 0.02.

  3. Effect of pimozide on the increase of muscarinic receptors caused by mazindol and apomorphine in the rat cerebral motor cortex.

    Science.gov (United States)

    de-Sousa, F C; Marinho, M M; Aguiar, G V; Viana, G S

    1995-01-01

    The effects of pimozide, mazindol and apomorphine on muscarinic receptors in homogenates of rat cerebral motor cortex were measured by binding assays, using 3H-N-methylscopolamine (3H-NMS) alone as ligand (for the measurement of M1- and M2-like receptors) or in the presence of carbachol or pirenzepine for determination of M1- and M2-like receptors, respectively. Female Wistar rats (150 g) were treated daily for one week with pimozide, a dopaminergic antagonist (10 and 20 mg/kg, po, by gavage), or with apomorphine (1 mg/kg, ip). In another set of experiments, animals were treated with pimozide and 30 min later with mazindol (10 mg/kg, po, by gavage) or apomorphine. The drugs were administered daily for one week. Controls received the same volume of saline. 3H-NMS binding was increased from the control value of 418 +/- 17 to 548 +/- 42 fmol/mg protein by administration of mazindol (10 mg/kg) but binding was reduced to 360 +/- 11 fmol/mg protein upon administration of pimozide (20 mg/kg) plus mazindol (10 mg/kg). Similarly 10 mg/kg pimozide reduced the increase in M1-like receptors caused by mazindol from 262 +/- 31 to 220 +/- 20 fmol/mg protein. Although 20 mg/kg pimozide alone produced a decrease in M1- plus M2-like receptors (from 418 +/- 17 to 348 +/- 22 fmol/mg protein), its action was preferentially on M2-like receptors, decreasing them from 148 +/- 10 to 111 +/- 15 fmol/mg protein in the control and treated groups, respectively. At the higher dose, 20 mg/kg pimozide also inhibited the 3H-NMS binding (M1- plus M2-like receptors) in the presence of apomorphine (263 +/- 25 vs 418 +/- 17 fmol/mg protein.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Age-related increase in Wnt inhibitor causes a senescence-like phenotype in human cardiac stem cells.

    Science.gov (United States)

    Nakamura, Tamami; Hosoyama, Tohru; Murakami, Junichi; Samura, Makoto; Ueno, Koji; Kurazumi, Hiroshi; Suzuki, Ryo; Mikamo, Akihito; Hamano, Kimikazu

    2017-06-03

    Aging of cardiac stem/progenitor cells (CSCs) impairs heart regeneration and leads to unsatisfactory outcomes of cell-based therapies. As the precise mechanisms underlying CSC aging remain unclear, the use of therapeutic strategies for elderly patients with heart failure is severely delayed. In this study, we used human cardiosphere-derived cells (CDCs), a subtype of CSC found in the postnatal heart, to identify secreted factor(s) associated with CSC aging. Human CDCs were isolated from heart failure patients of various ages (2-83 years old). Gene expression of key soluble factors was compared between CDCs derived from young and elderly patients. Among these factors, SFRP1, a gene encoding a Wnt antagonist, was significantly up-regulated in CDCs from elderly patients (≥65 years old). sFRP1 levels was increased significantly also in CDCs, whose senescent phenotype was induced by anti-cancer drug treatment. These results suggest the participation of sFRP1 in CSC aging. We show that the administration of recombinant sFRP1 induced cellular senescence in CDCs derived from young patients, as indicated by increased levels of markers such as p16, and a senescence-associated secretory phenotype. In addition, co-administration of recombinant sFRP1 could abrogate the accelerated CDC proliferation induced by Wnt3A. Taken together, our results suggest that canonical Wnt signaling and its antagonist, sFRP1, regulate proliferation of human CSCs. Furthermore, excess sFRP1 in elderly patients causes CSC aging. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Goat milk feeding causes an increase in biliary secretion of cholesterol and a decrease in plasma cholesterol levels in rats.

    Science.gov (United States)

    López-Aliaga, I; Alférez, M J M; Nestares, M T; Ros, P B; Barrionuevo, M; Campos, M S

    2005-03-01

    The hypocholesterolemic effect of goat milk with respect to cow milk observed in a previous study led us to examine the influence of goat and cow milk in the diet on certain aspects of biliary physiology in normal rats. The fat content in all diets was 10% but the lipid quality was varied: the standard diet was based on virgin olive oil, and the other 2 diets included fat obtained from lyophilized cow milk and goat milk. We characterized the bile secretion, including biliary phospholipid, cholesterol, and bile acid outputs, the interrelation between bile acids and bile lipids, and the lithogenic index. The consumption of goat milk in the diet, compared with that of cow milk, caused an increase in the biliary secretion of cholesterol together with a decrease in plasma cholesterol concentration, whereas values for bile phospholipids, biliary acid concentrations, and the lithogenic index remained normal. Moreover, consumption of this type of milk decreased plasma triglyceride concentration and therefore had a positive effect, similar to that of olive oil (standard diet), on the lipid metabolism; hence, it may be recommended for consumption by the general population.

  6. Transition in Survival From Low-Dose Hyper-Radiosensitivity to Increased Radioresistance Is Independent of Activation of ATM SER1981 Activity

    International Nuclear Information System (INIS)

    Krueger, Sarah A.; Collis, Spencer J.; Joiner, Michael C.; Wilson, George D.; Marples, Brian

    2007-01-01

    Purpose: The molecular basis of low-dose hyper-radiosensitivity (HRS) is only partially understood. The aim of this study was to define the roles of ataxia telangiectasia mutated (ATM) activity and the downstream ATM-dependent G 2 -phase cell cycle checkpoint in overcoming HRS and triggering radiation resistance. Methods and Materials: Survival was measured using a high-resolution clonogenic assay. ATM Ser1981 activation was measured by Western blotting. The role of ATM was determined in survival experiments after molecular (siRNA) and chemical (0.4 mM caffeine) inhibition and chemical (20 μg/mL chloroquine, 15 μM genistein) activation 4-6 h before irradiation. Checkpoint responsiveness was assessed in eight cell lines of differing HRS status using flow cytometry to quantify the progression of irradiated (0-2 Gy) G 2 -phase cells entering mitosis, using histone H3 phosphorylation analysis. Results: The dose-response pattern of ATM activation was concordant with the transition from HRS to radioresistance. However, ATM activation did not play a primary role in initiating increased radioresistance. Rather, a relationship was discovered between the function of the downstream ATM-dependent early G 2 -phase checkpoint and the prevalence and overcoming of HRS. Four cell lines that exhibited HRS failed to show low-dose ( 2 -phase checkpoint. These data suggest that clinical exploitation of HRS could be achieved by combining radiotherapy with chemotherapeutic agents that modulate this cell cycle checkpoint

  7. Survival after blood transfusion

    DEFF Research Database (Denmark)

    Kamper-Jørgensen, Mads; Ahlgren, Martin; Rostgaard, Klaus

    2008-01-01

    of transfusion recipients in Denmark and Sweden followed for up to 20 years after their first blood transfusion. Main outcome measure was all-cause mortality. RESULTS: A total of 1,118,261 transfusion recipients were identified, of whom 62.0 percent were aged 65 years or older at the time of their first...... the SMR remained significantly 1.3-fold increased. CONCLUSION: The survival and relative mortality patterns among blood transfusion recipients were characterized with unprecedented detail and precision. Our results are relevant to assessments of the consequences of possible transfusion-transmitted disease......BACKGROUND: Long-term survival of transfusion recipients has rarely been studied. This study examines short- and long-term mortality among transfusion recipients and reports these as absolute rates and rates relative to the general population. STUDY DESIGN AND METHODS: Population-based cohort study...

  8. Increasing levels of wild-type CREB up-regulates several activity-regulated inhibitor of death (AID genes and promotes neuronal survival

    Directory of Open Access Journals (Sweden)

    Tan Yan-Wei

    2012-05-01

    Full Text Available Abstract Background CREB (cAMP-response element binding protein is the prototypical signal-regulated transcription factor. In neurons, it is the target of the synaptic activity-induced nuclear calcium-calcium/calmodulin dependent protein kinase (CaMK IV signaling pathway that controls the expression of genes important for acquired neuroprotection as well as other long-lasting adaptive processes in the nervous system. The function of CREB as a transcriptional activator is controlled by its phosphorylation on serine 133, which can be catalyzed by CaMKIV and leads to the recruitment of the co-activator, CREB binding protein (CBP. Activation of CBP function by nuclear calcium-CaMKIV signaling is a second regulatory step required for CREB/CBP-mediated transcription. Results Here we used recombinant adeno-associated virus (rAAV to increase the levels of wild type CREB or to overexpress a mutant version of CREB (mCREB containing a serine to alanine mutation at position amino acid 133 in mouse hippocampal neurons. Increasing the levels of CREB was sufficient to boost neuroprotective activity even under basal conditions (i.e., in the absence of stimulation of synaptic activity. In contrast, overexpression of mCREB increased cell death. The ratio of phospho(serine 133CREB to CREB immunoreactivity in unstimulated hippocampal neurons was similar for endogenous CREB and overexpressed wild type CREB and, as expected, dramatically reduced for overexpressed mCREB. A gene expression analysis revealed that increased expression of CREB but not that of mCREB in hippocampal neurons led to elevated expression levels of bdnf as well as that of several members of a previously characterized set of Activity-regulated Inhibitor of Death (AID genes, which include atf3, btg2, gadd45β, and gadd45γ. Conclusions Our findings indicate that the expression levels of wild type CREB are a critical determinant of the ability of hippocampal neurons to survive harmful conditions

  9. Intermittent hypoxia causes histological kidney damage and increases growth factor expression in a mouse model of obstructive sleep apnea.

    Directory of Open Access Journals (Sweden)

    Bisher Abuyassin

    have an increased glomerular area (by 1.13 fold, p< 0.001 and expansion of mesangial matrix (by 1.8 fold, p< 0.01. Moreover, the glomerular expressions of TGF-β1, CTGF and VEGF-A proteins were 2.7, 2.2 and 3.8-fold higher in mice exposed to IH (p< 0.05 for all. Furthermore, western blotting protein analysis demonstrates that IH-exposed mice express higher levels of TGF-β1, CTGF and VEGF-A proteins by 1.9, 4.0 and 1.6-fold (p< 0.05 for all respectively. Renal cellular apoptosis was greater in the IH group as shown by an increased cortical Bax/Bcl-2 protein ratio (p< 0.01 and higher fluorometric TUNEL staining (p< 0.001. Finally, 24-hr urinary albumin levels were higher in mice exposed to IH (43.4 μg vs 9.7 μg, p< 0.01, while there were no differences in serum creatinine levels between the two groups. We conclude that IH causes kidney injury that is accompanied by glomerular hypertrophy, mesangial matrix expansion, increased expression of glomerular growth factors and an increased cellular apoptosis.

  10. Ketogenic diet improves the spatial memory impairment caused by exposure to hypobaric hypoxia through increased acetylation of histones in rats

    OpenAIRE

    Zhao, Ming; Huang, Xin; Cheng, Xiang; Lin, Xiao; Zhao, Tong; Wu, Liying; Yu, Xiaodan; Wu, Kuiwu; Fan, Ming; Zhu, Lingling

    2017-01-01

    Exposure to hypobaric hypoxia causes neuron cell damage, resulting in impaired cognitive function. Effective interventions to antagonize hypobaric hypoxia-induced memory impairment are in urgent need. Ketogenic diet (KD) has been successfully used to treat drug-resistant epilepsy and improves cognitive behaviors in epilepsy patients and other pathophysiological animal models. In the present study, we aimed to explore the potential beneficial effects of a KD on memory impairment caused by hypo...

  11. Increased circulating VCAM-1 correlates with advanced disease and poor survival in patients with multiple myeloma: reduction by post-bortezomib and lenalidomide treatment.

    Science.gov (United States)

    Terpos, E; Migkou, M; Christoulas, D; Gavriatopoulou, M; Eleutherakis-Papaiakovou, E; Kanellias, N; Iakovaki, M; Panagiotidis, I; Ziogas, D C; Fotiou, D; Kastritis, E; Dimopoulos, M A

    2016-05-27

    Circulating vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and selectins were prospectively measured in 145 newly-diagnosed patients with symptomatic myeloma (NDMM), 61 patients with asymptomatic/smoldering myeloma (SMM), 47 with monoclonal gammopathy of undetermined significance (MGUS) and 87 multiple myeloma (MM) patients at first relapse who received lenalidomide- or bortezomib-based treatment (RD, n=47; or VD, n=40). Patients with NDMM had increased VCAM-1 and ICAM-1 compared with MGUS and SMM patients. Elevated VCAM-1 correlated with ISS-3 and was independently associated with inferior overall survival (OS) (45 months for patients with VCAM-1 >median vs 75 months, P=0.001). MM patients at first relapse had increased levels of ICAM-1 and L-selectin, even compared with NDMM patients and had increased levels of VCAM-1 compared with MGUS and SMM. Both VD and RD reduced dramatically serum VCAM-1 after four cycles of therapy, but only VD reduced serum ICAM-1, irrespective of response to therapy. The reduction of VCAM-1 was more pronounced after RD than after VD. Our study provides evidence for the prognostic value of VCAM-1 in myeloma patients, suggesting that VCAM-1 could be a suitable target for the development of anti-myeloma therapies. Furthermore, the reduction of VCAM-1 and ICAM-1 by RD and VD supports the inhibitory effect of these drugs on the adhesion of MM cells to stromal cells.

  12. Low-Dose Aspirin Use Does Not Increase Survival in 2 Independent Population-Based Cohorts of Patients With Esophageal or Gastric Cancer.

    Science.gov (United States)

    Spence, Andrew D; Busby, John; Johnston, Brian T; Baron, John A; Hughes, Carmel M; Coleman, Helen G; Cardwell, Chris R

    2018-03-01

    esophageal cancer (pooled adjusted HR, 1.03; 95% CI, 0.85-1.25) or gastric cancer (pooled adjusted HR, 1.06; 95% CI, 0.85-1.32). In analyses of 2 large independent cohorts in the United Kingdom, low-dose aspirin usage was not associated with increased survival of patients diagnosed with esophageal or gastric cancer. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

  13. Structural modification of resveratrol leads to increased anti-tumor activity, but causes profound changes in the mode of action

    Energy Technology Data Exchange (ETDEWEB)

    Scherzberg, Maria-Christina; Kiehl, Andreas; Zivkovic, Aleksandra; Stark, Holger [Institute of Pharmaceutical Chemistry, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany); Stein, Jürgen [Institute of Pharmaceutical Chemistry, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany); Department of Internal Medicine, Sachsenhausen Hospital, Frankfurt am Main (Germany); Fürst, Robert [Institute of Pharmaceutical Biology, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany); Steinhilber, Dieter [Institute of Pharmaceutical Chemistry, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany); Ulrich-Rückert, Sandra, E-mail: sandra.ulrich@em.uni-frankfurt.de [Institute of Pharmaceutical Chemistry, Biozentrum, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main (Germany)

    2015-08-15

    (Z)-3,5,4′-Trimethoxystilbene (Z-TMS) is a resveratrol analog with increased antiproliferative activity towards a number of cancer cell lines compared to resveratrol, which has been shown to inhibit tubulin polymerization in vitro. The purpose of this study was to investigate if Z-TMS still shows potential for the prevention of metabolic diseases as known for resveratrol. Cell growth inhibition was determined with IC{sub 50} values for Z-TMS between 0.115 μM and 0.473 μM (resveratrol: 110.7 μM to 190.2 μM). Flow cytometric analysis revealed a G{sub 2}/M arrest after Z-TMS treatment, whereas resveratrol caused S phase arrest. Furthermore, Z-TMS was shown to impair microtubule polymerization. Beneficial effects on lipid accumulation were observed for resveratrol, but not for Z-TMS in an in vitro steatosis model. (E)-Resveratrol was confirmed to elevate cAMP levels, and knockdown of AMPK attenuated the antiproliferative activity, while Z-TMS did not show significant effects in these experiments. SIRT1 and AMPK activities were further measured indirectly via induction of the target gene small heterodimer partner (SHP). Thereby, (E)-resveratrol, but not Z-TMS, showed potent induction of SHP mRNA levels in an AMPK- and SIRT1-dependent manner, as confirmed by knockdown experiments. We provide evidence that Z-TMS does not show beneficial metabolic effects, probably due to loss of activity towards resveratrol target genes. Moreover, our data support previous findings that Z-TMS acts as an inhibitor of tubulin polymerization. These findings confirm that the methylation of resveratrol leads to profound changes in the mode of action, which should be taken into consideration when conducting lead structure optimization approaches. - Highlights: • Methylation of resveratrol leads to profound changes in biologic activity. • Z-TMS does not prevent hepatic steatosis, but inhibits tubulin polymerization. • Resveratrol analog Z-TMS does not influence known targets like

  14. Splenic vein thrombosis is associated with an increase in pancreas-specific complications and reduced survival in patients undergoing distal pancreatectomy for pancreatic exocrine cancer.

    Science.gov (United States)

    Dedania, Nishi; Agrawal, Nidhi; Winter, Jordan M; Koniaris, Leonidas G; Rosato, Ernest L; Sauter, Patricia K; Leiby, Ben; Pequignot, Edward; Yeo, Charles J; Lavu, Harish

    2013-08-01

    Distal pancreatectomy and splenectomy (DPS) is the procedure of choice for the surgical treatment of pancreatic exocrine cancer localized to the body and tail of the pancreas. Splenic vein thrombosis (SVT) can occur in patients with malignant pancreatic exocrine tumors secondary to direct tumor invasion or compression of the splenic vein by mass effect. This study examines the effect of preoperative SVT on postoperative outcomes. In this retrospective cohort study, we queried our pancreatic surgery database to identify patients who underwent DPS from October 2005 to June 2011. These cases were evaluated for evidence of preoperative SVT on clinical records and cross-sectional imaging (CT,MRI, endoscopic US). Outcomes for patients with and without SVT were compared. From an overall cohort of 285 consecutive patients who underwent DPS during the study period, data were evaluated for 70 subjects who underwent surgery for pancreatic exocrine cancer (27 with SVT, 43 without SVT). The preoperative demographics and co-morbidities were similar between the groups, except the average age was higher for those without SVT (pSVT group (675 versus 250 ml, p=SVT versus 56% no SVT, p=NS), the group with SVT had a significantly higher rate of pancreas-specific complications, including pancreatic fistula (33 versus 7 %,pSVT had a trend toward longer median survival (40 versus 20.8 months),although the difference was not statistically significant (p=0.1). DPS for pancreatic ductal adenocarcinoma can be performed safely in patients with SVT, but with higher intraoperative blood loss, increased pancreas-specific complications, and a trend towards lower long-term survival rates. This paper was presented as a poster at the 53rd annual meeting of the Society for Surgery of the Alimentary Tract and at the 46th annual meeting of the Pancreas Club, San Diego, CA, May 2012.

  15. Laninamivir octanoate and artificial surfactant combination therapy significantly increases survival of mice infected with lethal influenza H1N1 Virus.

    Directory of Open Access Journals (Sweden)

    Masaya Fukushi

    Full Text Available BACKGROUND: Patients with influenza virus infection can develop severe pneumonia and acute respiratory distress syndrome (ARDS which have a high mortality. Influenza virus infection is treated worldwide mainly by neuraminidase inhibitors (NAIs. However, monotherapy with NAIs is insufficient for severe pneumonia secondary to influenza virus infection. We previously demonstrated that mice infected with a lethal dose of influenza virus develop diffuse alveolar damage (DAD with alveolar collapse similar to that seen in ARDS in humans. Additionally, pulmonary surfactant proteins were gradually increased in mouse serum, suggesting a decrease in pulmonary surfactant in the lung. Therefore, the present study examined whether combination therapy of NAI with exogenous artificial surfactant affects mortality of influenza virus-infected mice. METHODOLOGY/PRINCIPAL FINDINGS: BALB/c mice were inoculated with several viral doses of influenza A/Puerto Rico/8/34 (PR8 virus (H1N1. The mice were additionally administered exogenous artificial surfactant in the presence or absence of a new NAI, laninamivir octanoate. Mouse survival, body weight and general condition were observed for up to 20 days after inoculation. Viral titer and cytokine/chemokine levels in the lungs, lung weight, pathological analysis, and blood O(2 and CO(2 pressures were evaluated. Infected mice treated with combination therapy of laninamivir octanoate with artificial surfactant showed a significantly higher survival rate compared with those that received laninamivir octanoate monotherapy (p = 0.003. However, virus titer, lung weight and cytokine/chemokine responses were not different between the groups. Histopathological examination, a hydrostatic lung test and blood gas analysis showed positive results in the combination therapy group. CONCLUSIONS/SIGNIFICANCE: Combination therapy of laninamivir octanoate with artificial surfactant reduces lethality in mice infected with influenza virus, and

  16. Nation-Scale Adoption of Shorter Breast Radiation Therapy Schedules Can Increase Survival in Resource Constrained Economies: Results From a Markov Chain Analysis

    International Nuclear Information System (INIS)

    Khan, Atif J.; Rafique, Raza; Zafar, Waleed; Shah, Chirag; Haffty, Bruce G.; Vicini, Frank; Jamshed, Arif; Zhao, Yao

    2017-01-01

    Purpose: Hypofractionated whole breast irradiation and accelerated partial breast irradiation (APBI) offer women options for shorter courses of breast radiation therapy. The impact of these shorter schedules on the breast cancer populations of emerging economies with limited radiation therapy resources is unknown. We hypothesized that adoption of these schedules would improve throughput in the system and, by allowing more women access to life-saving treatments, improve patient survival within the system. Methods and Materials: We designed a Markov chain model to simulate the different health states that a postlumpectomy or postmastectomy patient could enter over the course of a 20-year follow-up period. Transition rates between health states were adapted from published data on recurrence rates. We used primary data from a tertiary care hospital in Lahore, Pakistan, to populate the model with proportional use of mastectomy versus breast conservation and to estimate the proportion of patients suitable for APBI. Sensitivity analyses on the use of APBI and relative efficacy of APBI were conducted to study the impact on the population. Results: The shorter schedule resulted in more women alive and more women remaining without evidence of disease (NED) compared with the conventional schedule, with an absolute difference of about 4% and 7% at 15 years, respectively. Among women who had lumpectomies, the chance of remaining alive and with an intact breast was 62% in the hypofractionation model and 54% in the conventional fractionation model. Conclusions: Increasing throughput in the system can result in improved survival, improved chances of remaining without evidence of disease, and improved chances of remaining alive with a breast. These findings are significant and suggest that adoption of hypofractionation in emerging economies is not simply a question of efficiency and cost but one of access to care and patient survivorship.

  17. Nation-Scale Adoption of Shorter Breast Radiation Therapy Schedules Can Increase Survival in Resource Constrained Economies: Results From a Markov Chain Analysis.

    Science.gov (United States)

    Khan, Atif J; Rafique, Raza; Zafar, Waleed; Shah, Chirag; Haffty, Bruce G; Vicini, Frank; Jamshed, Arif; Zhao, Yao

    2017-02-01

    Hypofractionated whole breast irradiation and accelerated partial breast irradiation (APBI) offer women options for shorter courses of breast radiation therapy. The impact of these shorter schedules on the breast cancer populations of emerging economies with limited radiation therapy resources is unknown. We hypothesized that adoption of these schedules would improve throughput in the system and, by allowing more women access to life-saving treatments, improve patient survival within the system. We designed a Markov chain model to simulate the different health states that a postlumpectomy or postmastectomy patient could enter over the course of a 20-year follow-up period. Transition rates between health states were adapted from published data on recurrence rates. We used primary data from a tertiary care hospital in Lahore, Pakistan, to populate the model with proportional use of mastectomy versus breast conservation and to estimate the proportion of patients suitable for APBI. Sensitivity analyses on the use of APBI and relative efficacy of APBI were conducted to study the impact on the population. The shorter schedule resulted in more women alive and more women remaining without evidence of disease (NED) compared with the conventional schedule, with an absolute difference of about 4% and 7% at 15 years, respectively. Among women who had lumpectomies, the chance of remaining alive and with an intact breast was 62% in the hypofractionation model and 54% in the conventional fractionation model. Increasing throughput in the system can result in improved survival, improved chances of remaining without evidence of disease, and improved chances of remaining alive with a breast. These findings are significant and suggest that adoption of hypofractionation in emerging economies is not simply a question of efficiency and cost but one of access to care and patient survivorship. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Nation-Scale Adoption of Shorter Breast Radiation Therapy Schedules Can Increase Survival in Resource Constrained Economies: Results From a Markov Chain Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Khan, Atif J., E-mail: atif.j.khan@rutgers.edu [Department of Radiation Oncology, Robert Wood Johnson Medical School/Cancer Institute of New Jersey, New Brunswick, New Jersey (United States); Rafique, Raza [Suleman Dawood School of Business, Lahore University of Management Sciences, Lahore (Pakistan); Zafar, Waleed [Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore (Pakistan); Shah, Chirag [Department of Radiation Oncology, Cleveland Clinic, Cleveland, Ohio (United States); Haffty, Bruce G. [Department of Radiation Oncology, Robert Wood Johnson Medical School/Cancer Institute of New Jersey, New Brunswick, New Jersey (United States); Vicini, Frank [Michigan HealthCare Professionals, Farmington Hills, Michigan (United States); Jamshed, Arif [Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore (Pakistan); Zhao, Yao [Rutgers University School of Business, Newark, New Jersey (United States)

    2017-02-01

    Purpose: Hypofractionated whole breast irradiation and accelerated partial breast irradiation (APBI) offer women options for shorter courses of breast radiation therapy. The impact of these shorter schedules on the breast cancer populations of emerging economies with limited radiation therapy resources is unknown. We hypothesized that adoption of these schedules would improve throughput in the system and, by allowing more women access to life-saving treatments, improve patient survival within the system. Methods and Materials: We designed a Markov chain model to simulate the different health states that a postlumpectomy or postmastectomy patient could enter over the course of a 20-year follow-up period. Transition rates between health states were adapted from published data on recurrence rates. We used primary data from a tertiary care hospital in Lahore, Pakistan, to populate the model with proportional use of mastectomy versus breast conservation and to estimate the proportion of patients suitable for APBI. Sensitivity analyses on the use of APBI and relative efficacy of APBI were conducted to study the impact on the population. Results: The shorter schedule resulted in more women alive and more women remaining without evidence of disease (NED) compared with the conventional schedule, with an absolute difference of about 4% and 7% at 15 years, respectively. Among women who had lumpectomies, the chance of remaining alive and with an intact breast was 62% in the hypofractionation model and 54% in the conventional fractionation model. Conclusions: Increasing throughput in the system can result in improved survival, improved chances of remaining without evidence of disease, and improved chances of remaining alive with a breast. These findings are significant and suggest that adoption of hypofractionation in emerging economies is not simply a question of efficiency and cost but one of access to care and patient survivorship.

  19. Insights on the antitumor effects of kahweol on human breast cancer: Decreased survival and increased production of reactive oxygen species and cytotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Cárdenas, Casimiro [Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, E-29071 Málaga (Spain); IBIMA (Biomedical Research Institute of Málaga), E-29071 Málaga (Spain); Research Support Central Services (SCAI) of the University of Málaga, E-29071 Málaga (Spain); Quesada, Ana R. [Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, E-29071 Málaga (Spain); IBIMA (Biomedical Research Institute of Málaga), E-29071 Málaga (Spain); CIBER de Enfermedades Raras (CIBERER), E-29071 Málaga (Spain); Medina, Miguel Ángel, E-mail: medina@uma.es [Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, E-29071 Málaga (Spain); IBIMA (Biomedical Research Institute of Málaga), E-29071 Málaga (Spain); CIBER de Enfermedades Raras (CIBERER), E-29071 Málaga (Spain)

    2014-05-09

    Highlights: • Kahweol inhibits growth and attachment-independent proliferation of tumor cells. • Kahweol induces apoptosis in MDA-MB231 human breast cancer cells. • Kahweol-induced apoptosis involves caspase activation and cytochrome c release. • Kahweol does not protect against hydrogen peroxide cytotoxicity. • Kahweol increases hydrogen peroxide production by human breast cancer cells. - Abstract: The present study aims to identify the modulatory effects of kahweol, an antioxidant diterpene present in coffee beans, on a panel of human tumor cell lines. Kahweol inhibits tumor cell proliferation and clonogenicity and induces apoptosis in several kinds of human tumor cells. In the estrogen receptor-negative MDA-MB231 human breast cancer, the mentioned effects are accompanied by caspases 3/7 and 9 activation and cytochrome c release. On the other hand, kahweol increases the production of reactive oxygen species and their cytotoxicity in human breast cancer cells but not in normal cells. Taken together, our data suggest that kahweol is an antitumor compound with inhibitory effects on tumor cell growth and survival, especially against MDA-MB231 breast cancer cells.

  20. Increase of autophagy and attenuation of apoptosis by Salvigenin promote survival of SH-SY5Y cells following treatment with H₂O₂.

    Science.gov (United States)

    Rafatian, Ghazaleh; Khodagholi, Fariba; Farimani, Mahdi Moridi; Abraki, Shahnaz Babaei; Gardaneh, Mossa

    2012-12-01

    Oxidative stress is a major component of harmful cascades activated in neurodegenerative disorders. Here, we tried to elucidate the possible neuroprotective effect of Salvigenin, a natural polyphenolic compound, on oxidative stress-induced apoptosis and autophagy in human neuroblastoma SH-SY5Y cells. We measured cell viability by MTT test and found that 25 μM is the best protective concentration of Salvigenin. GSH and SOD assays suggested that Salvigenin activates antioxidant factors. At the same time, measurement of ER stress-associated proteins including calpain and caspase-12 showed the ability of Salvigenin to decrease ER stress. We found that Salvigenin could decrease the apoptotic factors. Salvigenin inhibited H(2)O(2)-induced caspase-3 which is a hallmark of apoptosis in addition to reducing Bax\\Bcl-2 ratio by 1.45 fold. Additionally, Salvigenin increased the levels of autophagic factors. Our results showed an increase in LC3-II/LC3-I ratio, Atg7, and Atg12 in the presence of 25 μM of Salvigenin by about 1.28, 1.25, and 1.54 folds, respectively, compared to H(2)O(2)-treated cells. So it seems that H(2)O(2) cytotoxicity mainly results from apoptosis. Besides, Salvigenin helps cells to survive by inhibiting apoptosis and enhancing autophagy that opens a new horizon for the future experiments.

  1. Is increase in bone mineral content caused by increase in skeletal muscle mass/strength in adult patients with GH-treated GH deficiency?

    DEFF Research Database (Denmark)

    Klefter, Oliver; Feldt-Rasmussen, Ulla

    2009-01-01

    OBJECTIVE: Adult patients with GH deficiency (GHD) are characterized by a reduced muscle mass, but also reduced bone mineral density (BMD) and content (BMC), which have been ascribed to GHD per se. The aim of this study was to investigate if changes in BMD/BMC in adult GHD patients could be due...... to a muscle modulating effect, and if treatment with GH would primarily increase muscle mass and strength with a secondary increase in BMD/BMC, thus supporting the present physiological concept that mass and strength of bones are mainly determined by dynamic loads from the skeletal muscles. METHOD: We...... studied both muscle and bone variables concomitantly. No trials studied the relationship between the changes in muscle and bone measurements. CONCLUSION: Although in vitro studies have shown that GH has a direct effect on bone remodeling, present physiological concepts and the results of clinical trials...

  2. The bioefficacy of crude extracts of Azadirachta indica (Meliaceae) on the survival and development of myiasis-causing larvae of Chrysomya bezziana (Diptera: Calliphoridae).

    Science.gov (United States)

    Singh, Amandeep; Kaur, Jasneet

    2016-01-01

    Myiasis is a type of parasitosis originating from the invasion of tissues of live humans and other vertebrates by dipteran larvae. The Old World screwworm fly—Chrysomya bezziana—is known worldwide in the tropical regions for causing myiasis among man and domestic animals, thereby leading to health hazards and severe economic losses to the dairy farmers. Management techniques for controlling populations of the fly are needed to minimize these losses. Plant-derived materials have been increasingly evaluated these days in controlling the insects of medical and veterinary importance. This study evaluated the efficacy of crude extracts of the plant neem, Azadirachta indica, against C. bezziana. The dried leaves of the plant were extracted successively with four different solvents viz. petroleum ether, chloroform, ethyl acetate and methanol and were evaluated against the third instar larvae of C. bezziana using dipping method and thin film application technique. In the dipping method, larvae were dipped in four different concentrations of plant extracts for 30 s, whereas in the thin film application, they were exposed to a thin film of plant extracts. The results showed that all the extracts had toxic effect on the larvae in both the techniques. In the dipping method, the highest mortalities were recorded in methanol extract followed by chloroform, petroleum ether and ethyl acetate extracts with LC50 values 1.07 g/100 ml, 1.7 g/100 ml, 3.39 g/100 ml and 4.9 g/100 ml, respectively. In the thin film application method, methanol extract showed the highest mortalities followed by chloroform, ethyl acetate and petroleum ether with LC50 values 0.4 mg/cm2, 0.6 mg/cm2, 2.1 mg/cm2 and 2.5 mg/cm2. It is concluded that the crude extracts of A. indica can be used in controlling the larvae of C. bezziana by using the dipping as well as thin film application technique.

  3. Is increase in bone mineral content caused by increase in skeletal muscle mass/strength in adult patients with GH-treated GH deficiency? A systematic literature analysis

    DEFF Research Database (Denmark)

    Klefter, O.; Feldt-Rasmussen, U.

    2009-01-01

    OBJECTIVE: Adult patients with GH deficiency (GHD) are characterized by a reduced muscle mass, but also reduced bone mineral density (BMD) and content (BMC), which have been ascribed to GHD per se. The aim of this study was to investigate if changes in BMD/BMC in adult GHD patients could be due...... performed a systematic literature analysis, including 51 clinical trials published between 1996 and 2008, which had studied the development in muscle mass, muscle strength, BMD, and/or BMC in GH-treated adult GHD patients. RESULTS: GH therapy had an anabolic effect on skeletal muscle. The largest increase...

  4. Bt Toxin Cry1Ie Causes No Negative Effects on Survival, Pollen Consumption, or Olfactory Learning in Worker Honey Bees (Hymenoptera: Apidae).

    Science.gov (United States)

    Dai, Ping-Li; Jia, Hui-Ru; Geng, Li-Li; Diao, Qing-Yun

    2016-04-27

    The honey bee (Apis mellifera L.) is a key nontarget insect in environmental risk assessments of insect-resistant genetically modified crops. In controlled laboratory conditions, we evaluated the potential effects of Cry1Ie toxin on survival, pollen consumption, and olfactory learning of young adult honey bees. We exposed worker bees to syrup containing 20, 200, or 20,000 ng/ml Cry1Ie toxin, and also exposed some bees to 48 ng/ml imidacloprid as a positive control for exposure to a sublethal concentration of a toxic product. Results suggested that Cry1Ie toxin carries no risk to survival, pollen consumption, or learning capabilities of young adult honey bees. However, during oral exposure to the imidacloprid treatments, honey bee learning behavior was affected and bees consumed significantly less pollen than the control and Cry1Ie groups. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Microencapsulation increases survival of the probiotic Lactobacillus plantarum IS-10506, but not Enterococcus faecium IS-27526 in a dynamic, computer-controlled in vitro model of the upper gastrointestinal tract.

    Science.gov (United States)

    Surono, I; Verhoeven, J; Verbruggen, S; Venema, K

    2018-02-23

    To test the effect of microencapsulation on the survival of two probiotic strains isolated from Dadih, Indonesian fermented buffalo milk, in a dynamic, computer-controlled in vitro model of the upper gastrointestinal (GI) tract (TIM-1), simulating human adults. Free or microencapsulated probiotics, Lactobacillus plantarum IS-10506 or Enterococcus faecium IS-27526, resuspended in milk were studied for survival in the complete TIM-1 system (stomach + small intestine) or in the gastric compartment of TIM-1 only. Hourly samples collected after the ileal-caecal valve or after the pylorus were plated on MRS agar (for Lactobacillus) or S&B agar (for Enterococcus). Survival of the free cells after transit through the complete TIM-1 system was on average for the E. faecium and L. plantarum 15·0 and 18·5% respectively. Survival of the microencapsulated E. faecium and L. plantarum was 15·7 and 84·5% respectively. The free cells were further assessed in only the gastric compartment of TIM-1. E. faecium and L. plantarum showed an average survival of 39 and 32%, respectively, after gastric passage. There is similar sensitivity to gastric acid as well as survival after complete upper GI tract transit of free cells, but microencapsulation only protected L. plantarum. Survival of microencapsulated L. plantarum IS-10506 is increased compared to free cells in a validated in vitro model of the upper GI tract. It increases its use as an ingredient of functional foods. © 2018 The Society for Applied Microbiology.

  6. Hypoxia inhibits mineralization ability of human dental pulp cells treated with TEGDMA but increases cell survival in accordance with the culture time.

    Science.gov (United States)

    Öncel Torun, Zeynep; Torun, Deniz; Demirkaya, Kadriye; Yavuz, Süleyman Tolga; Sarper, Meral; Avcu, Ferit

    2016-11-01

    To evaluate the cytotoxicity and mineralization effects of TEGDMA in human dental pulp cells (hDPCs) under hypoxic and normoxic culture conditions. Cell viability was evaluated using XTT assay after incubation periods of 24, 48, or 72h. The expression of mineralization-related genes (osteonectin, osteopontin, dentin sialophosphoprotein, collagen type 1) and heme oxygenase 1 (HO-1) was assessed by quantitative real-time polymerase chain reaction at 24 and 72h. In XTT assay, viability was higher in 0.3, 1, 2, 4, and 5mM groups in the presence of 21% O 2 after 24h (p0.05). In the gene expression study, TEGDMA-treated hDPCs showed lower mineralization potential in the presence of 3% than with 21% O 2 (p<0.05). hDPCs revealed higher HO 1 expression in 0.3 and 1mM groups under hypoxic than under normoxic conditions after a 72-h time period (p<0.001). Hypoxic conditions increased cell survival in accordance with the culture period but inhibited the odontoblastic differentiation of hDPCs treated with TEGDMA. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Increased Circulating Level of the Survival Factor GP88 (Progranulin in the Serum of Breast Cancer Patients When Compared to Healthy Subjects

    Directory of Open Access Journals (Sweden)

    Katherine Rak Tkaczuk

    2011-01-01

    Full Text Available Introduction GP88 (PC-Cell Derived Growth Factor, progranulin is a glycoprotein overexpressed in breast tumors and involved in their proliferation and survival. Since GP88 is secreted, an exploratory study was established to compare serum GP88 level between breast cancer patients (BC and healthy volunteers (HV. Methods An IRB approved prospective study enrolled 189 stage 1–4 BC patients and 18 HV. GP88 serum concentration was determined by immunoassay. Results Serum GP88 level was 28.7+ 5.8 ng/ml in HV and increased to 40.7+ 16.0 ng/ml ( P = 0.007 for stage 1-3 and 45.3 +23.3 ng/ml ( P = 0.0007 for stage 4 BC patients. There was no correlation between the GP88 level and BC characteristics such as age, race, tumor grade, ER, PR and HER-2 expression. Conclusion These data suggest that serial testing of serum GP88 levels may have value as a circulating biomarker for detection, monitoring and follow up of BC.

  8. Increased expression of (pro)renin receptor does not cause hypertension or cardiac and renal fibrosis in mice

    NARCIS (Netherlands)

    Rosendahl, Alva; Niemann, Gianina; Lange, Sascha; Ahadzadeh, Erfan; Krebs, Christian; Contrepas, Aurelie; van Goor, Harry; Wiech, Thorsten; Bader, Michael; Schwake, Michael; Peters, Judith; Stahl, Rolf; Nguyen, Genevieve; Wenzel, Ulrich

    Binding of renin and prorenin to the (pro)renin receptor (PRR) increases their enzymatic activity and upregulates the expression of pro-fibrotic genes in vitro. Expression of PRR is increased in the heart and kidney of hypertensive and diabetic animals, but its causative role in organ damage is

  9. High serum YKL-40 level in a cohort of octogenarians is associated with increased risk of all-cause mortality

    DEFF Research Database (Denmark)

    Johansen, J. S.; Pedersen, Agnes Nadelmann; Schroll, M.

    2007-01-01

    = 151) and serum YKL-40 in 18-30-year-olds (n = 89). Fifty-one of the octogenarians died during the 6-year follow-up. Serum YKL-40 in octogenarians was higher compared to the level in young people (median 116 versus 31 microg/l, P ... of serum YKL-40 (logarithmically transformed and divided by tertiles) showed significant association with all-cause mortality [tertile 3: hazard ratio (HR) = 2.38, 95% confidence interval (CI): 1.19-4.78, P = 0.02]. The effect persisted after adjusting for potential confounders (sex, smoking, body mass...

  10. Protein-Energy Malnutrition (PEM is Believed to Lead to an Increased Susceptibility to Infection, or cause Impaired Immunity

    Directory of Open Access Journals (Sweden)

    Mellova Amir Masrizal

    2003-08-01

    Full Text Available Infection, occurring with malnutrition, is a major cause of morbidity in all age groups and is responsible for two-thirds of all death under 5 yr of age in developing countries. Many cells of the immune system are known to depend for their function on metabolic pathways that employ various nutrients as critical factors. The most consistent changes in immune competence in PEM are in cell-mediated immunity, the bactericidal function of neutrophils, the complement system, the secretory immunoglobin A, and antibody response.

  11. Increased All-Cause Mortality in Patients With Type 1 Diabetes and High-Expression Mannan-Binding Lectin Genotypes

    DEFF Research Database (Denmark)

    Østergaard, Jakob A; Thiel, Steffen; Lajer, Maria

    2015-01-01

    normoalbuminuric patients (103 men, age 43 years [95% CI 41-44], eGFR 93 mL/min/1.73 m(2) [95% CI 91-95]). Mortality rates were compared according to the concentration-determining MBL2 genotype or the MBL concentration. Patients were classified as having high or low MBL expression genotypes. The effect of MBL...... concentration was estimated by comparing patients with MBL concentrations above or below the median. RESULTS: Ninety-eight patients died during follow-up. The unadjusted hazard ratio (HR) for all-cause mortality was 1.61 (95% CI 1.07-2.43) for patients with high MBL expression genotypes versus patients with low...... MBL expression genotypes (P = 0.023). All-cause mortality was higher in patients with MBL concentrations above the median than in patients with MBL concentrations below the median (unadjusted HR 1.90 [95% CI 1.26-2.87], P = 0.002). CONCLUSIONS: High MBL expression genotypes and high MBL concentrations...

  12. Co-exposure to ultrafine particulate matter and ozone causes electrocardiogram changes indicative of increased arrhythmia risk in mice

    Science.gov (United States)

    Numerous studies have shown a relationship between acute air pollution exposure and increased risk for cardiovascular morbidity and mortality. Due to the inherent complexity of air pollution, recent studies have focused on co-exposures to better understand potential interactions....

  13. Combination Of Aging And Dimethylhydrazine Treatment Causes An Increase In The Stem Cell Population Of Rat Colonic Crypts

    OpenAIRE

    Levi, Edi; Misra, Sandhya; Du, Jianhua; Patel, Bhaumik B.; Majumdar, Adhip P. N.

    2009-01-01

    Aging is associated with increased incidence of colon cancers. It is also becoming evident that cancer stem cells (CSC) play a vital role in the pathogenesis and prognosis of colon cancer. Recently, we reported the presence of colon cancer stem-like cells in macroscopically normal mucosa in patients with adenomatous polyps and that they increase with aging, suggesting that aging may predispose the colon to carcinogenesis. In the current study we have examined the combined effects of aging and...

  14. The role of population change in the increased economic differences in mortality: a study of premature death from all causes and major groups of causes of death in Spain, 1980-2010.

    Science.gov (United States)

    Martínez, David; Giráldez-García, Carolina; Miqueleiz, Estrella; Calle, María E; Santos, Juana M; Regidor, Enrique

    2015-04-02

    An increase has been observed in differences in mortality between the richest and poorest areas of rich countries. This study assesses whether one of the proposed explanations, i.e., population change, might be responsible for this increase in Spain. Observational study based on average income, population change and mortality at provincial level. The premature mortality rate (ages 0-74 years) was estimated for all causes and for cancer, cardiovascular disease and external causes across the period 1980-2010. In the years analysed, provinces were grouped into tertiles based on provincial income, with the mortality rate ratio (MMR) being estimated by taking the tertile of highest-income provinces as reference. Population change was then controlled for to ascertain whether it would modify the rate ratio. In all-cause mortality, the magnitude of the MRR for provinces in the poorest versus the richest tertile was 1.01 in 1980 and 1.12 in 2010; in cardiovascular mortality, the MMRs for these same years were 1.08 and 1.31 respectively; and in the case of cancer and external-cause mortality, MMR magnitude was similar in 1980 and 2010. The magnitude of the MMR remained unchanged in response to adjustment for population change, with the single exception of 1980, when it increased in all-cause and cardiovascular mortality. The increase in the difference in premature mortality between the richest and poorest areas in Spain is due to the increased difference in cardiovascular mortality. This increase is not accounted for by population change. In rich countries, more empirical evidence is thus needed to test other alternative explanations for the increase in economic differences in mortality.

  15. Periconceptional alcohol consumption causes fetal growth restriction and increases glycogen accumulation in the late gestation rat placenta.

    Science.gov (United States)

    Gårdebjer, E M; Cuffe, J S M; Pantaleon, M; Wlodek, M E; Moritz, K M

    2014-01-01

    Alcohol consumption is a common social practice among women of childbearing age. With 50% of pregnancies being unplanned, many embryos are exposed to alcohol prior to pregnancy recognition and formation of the placenta. The effects of periconceptional (PC) alcohol exposure on the placenta are unknown. Sprague-Dawley rats were exposed to alcohol (12.5% v/v ad libitum) from 4 days prior to 4 days after conception and effects on placental growth, morphology and gene/protein expression examined at embryonic day (E) 20. PC ethanol (EtOH)-exposed fetuses were growth restricted and their placental/body weight ratio and placental cross-sectional area were increased. This was associated with an increase in cross-sectional area of the junctional zone and glycogen cells, especially in PC EtOH-exposed placentas from female fetuses. Junctional Glut1 and Igf2 mRNA levels were increased. Labyrinth Igf1 mRNA levels were decreased in placentas from both sexes, but protein IGF1R levels were decreased in placentas from male fetuses only. Labyrinth mRNA levels of Slc38a2 were decreased and Vegfa were increased in placentas following PC EtOH-exposure but only placentas from female fetuses exhibited increased Kdr expression. Augmented expression of the protective enzyme 11βHsd2 was found in PC EtOH-exposed labyrinth. These observations are consistent with a stress response, apparent well beyond the period of EtOH-exposure and demonstrate that PC EtOH alters placental development in a sex specific manner. Public awareness should be increased to educate women about how excessive drinking even before falling pregnant may impact on placental development and fetal health. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Increasing severity of damage caused by floods in the Spanish Mediterranean coast (1960-2014), climate change or vulnerability?

    Science.gov (United States)

    Perez, Alfredo; Gil, Salvador; Lopez, Francisco; Barriendos, Mariano

    2016-04-01

    In recent decades, there has been an increase in physical and economic losses (WMO, CRED and UCL, 2014) that raises serious concerns in society. Climate change projections may explain the rise in flood losses; however, these shouldn't be considered yet (Bouwer, 2011). According to IPCC (2014), there is low confidence in anthropogenic climate change affecting the frequency and magnitude of fluvial floods on a global scale. In other words, this increase in flood events is not completely related to the higher frequency of heavy rainfall. To illustrate the aforementioned, a spatial example can be seen in the study area. In the Spanish Mediterranean coast, we see an increase in economic losses within the last 50 years due to flood events (Gil et al., 2014). It seems that the socio-economic growth and the rise of housing construction (Gaja, 2008) have led to an increase in vulnerability and exposure which are mainly responsible for those losses and the increase in severity of flood events (Pérez et al., 2015). Furthermore, this situation will probably become more precarious if some climate forecasts are met [IPCC, 2014; AEMET, 2015], and if the economic model fails to adopt efficient adaptive measures. Therefore, it is interesting to focus attention on social factors either within the present or future scenario in order to minimise the potential consequences and improve the adaptation. The main objective of this work focuses on the study of the evolution of the severity of the floods in the Spanish Mediterranean coast for the period (1960-2015). To do that, a statistical analysis of the data base [Gil et al., 2014; extended to the entire Spanish Mediterranean coast (MEDIFLOOD)] and a multiscale mapping (local, provincial and regional level) of the frequency of these events will take place in order to make comparisons and show spatiotemporal patterns according to the severity events evolution. Preliminary results show some interesting statistically significant

  17. Marble industry effluents cause an increased bioaccumulation of heavy metals in Mahaseer (Tor putitora) in Barandu River, district Buner, Pakistan.

    Science.gov (United States)

    Mulk, Shahi; Korai, Abdul Latif; Azizullah, Azizullah; Shahi, Lubna; Khattak, Muhammad Nasir Khan

    2017-10-01

    The present study was conducted to evaluate the impact of marble industry effluents on the accumulation of heavy metals in selected tissues of mahaseer (Tor putitora) in Barandu River. Fish samples were collected from three selected sites (upstream (US), effluents/industrial (IS), and downstream (DS) sites) on monthly basis for 8 months. Heavy metal concentrations were determined in fish tissues using Atomic Absorption Spectrophotometer. Liver accumulated the highest level of metal concentrations while the lowest concentrations were found in muscles in T. putitora. Among metals, Fe was reported in the highest amount whereas the lowest was Cd in all the fish organs. In all the months, the metal concentrations were significantly higher (P metal concentrations at DS were found significantly higher (P metals in fish tissues at IS compared to US and DS. Furthermore, in many cases, the concentrations at DS were also found significantly higher (P < 0.05) compared to US. It is further confirmed by skewness z-score which was found to be higher than 1.96 suggesting the hazardous effects of marble industries on the collective health of the river. It is therefore recommended that all these industries either should be moved away from the bank of River Barandu or must be bound to properly treat their effluents prior to discharge into the river in order to protect the biota of River Barandu from the pollution caused by these marble industries.

  18. Survival analysis

    International Nuclear Information System (INIS)

    Badwe, R.A.

    1999-01-01

    The primary endpoint in the majority of the studies has been either disease recurrence or death. This kind of analysis requires a special method since all patients in the study experience the endpoint. The standard method for estimating such survival distribution is Kaplan Meier method. The survival function is defined as the proportion of individuals who survive beyond certain time. Multi-variate comparison for survival has been carried out with Cox's proportional hazard model

  19. Increase in dermcidin-derived peptides in sweat of patients with atopic eczema caused by a humorous video.

    Science.gov (United States)

    Kimata, Hajime

    2007-01-01

    Dermcidin (DCD)-derived peptide is an antimicrobial peptide produced by the sweat glands. However, the levels of DCD-derived peptide in sweat were decreased in patients with atopic eczema (AE). The effect of viewing a humorous video on the levels of DCD-derived peptide was studied. Twenty patients with AE viewed an 87-min humorous video (Modern Times, featuring Charlie Chaplin). Just before and immediately after viewing, sweat was collected, and the levels of DCD-derived peptide and total protein in sweat were measured. Viewing a humorous video increased the levels of DCD-derived peptide without affecting the levels of total protein in sweat. Viewing a humorous video increased DCD-derived peptide in sweat of patients with AE, and thus, it may be helpful in the treatment of skin infection of AE.

  20. Possible causes of the recent rapid increase in the radial increment of silver fir in the Western Carpathians.

    Science.gov (United States)

    Bošela, Michal; Petráš, Rudolf; Sitková, Zuzana; Priwitzer, Tibor; Pajtík, Jozef; Hlavatá, Helena; Sedmák, Róbert; Tobin, Brian

    2014-01-01

    Silver fir is one of the most productive and ecologically valuable native European tree species, however, it has been experiencing decline which has periodically occurred over its natural range. This paper aims to investigate the recent climate-growth relationships of silver fir (Abies alba Mill.) and its temporal change along the course of its life. Long-term tree-ring databases, as well as records on climate, atmospheric SO2, NO3 and acid concentrations from four different regions in the Western Carpathians were used. The results provide clear evidence of significant increase of silver fir's radial increment over the entire Western Carpathian area since 1970-1980. The results indicated that the most probable factors behind the rapid recovery of tree radial increment were reductions in emissions of NO3 and SO2, alongside a significant increase in mean June, July and April temperatures. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Early vascular injury and increased vascular permeability in gastric mucosal injury caused by ethanol in the rat.

    Science.gov (United States)

    Szabo, S; Trier, J S; Brown, A; Schnoor, J

    1985-01-01

    The hypothesis that vascular injury contributes to the development of hemorrhagic erosions after intragastric administration of ethanol has been examined in the rat using vascular tracers. Extravasation of intravenously injected Evans blue into the gastric wall and into gastric contents was used as an indicator of vascular permeability. India ink and monastral blue, which label damaged blood vessels, were used to demonstrate vascular injury morphologically. Intragastric instillation of 75% and 100% ethanol induced increased vascular permeability within 1-3 min and resulted in monastral blue labeling of vessels in 13% and 17%, respectively, of the glandular mucosa within 1 min. After 1 h of 100% ethanol exposure, the areal density of monastral blue-stained blood vessels did not increase compared with that seen at 1 min, but the areal density of grossly visible hemorrhagic lesions increased strikingly and approximated that of vessel staining. The hemorrhagic erosions consistently occurred in regions of glandular mucosa where vessels were stained with monastral blue. Pretreatment with prostaglandin F2 beta or cysteamine reduced ethanol-induced Evans blue extravasation and monastral blue staining of mucosal blood vessels but did not reduce histologic evidence of gastric surface cell damage in the glandular mucosa. As increased vascular permeability and morphologically detectable vascular lesions consistently preceded the development of grossly visible hemorrhagic erosions in the glandular mucosa, we suggest that vascular injury is an early pathogenetic factor in the development of ethanol-induced gastric hemorrhagic erosions. The data also indicate that the degree of vascular damage, unlike the injury to surface epithelial cells, is reduced by pretreatment with prostaglandin F2 beta or the sulfhydryl cysteamine.

  2. Voriconazole more likely than posaconazole increases plasma exposure to sublingual buprenorphine causing a risk of a clinically important interaction.

    Science.gov (United States)

    Fihlman, Mari; Hemmilä, Tuija; Hagelberg, Nora M; Kuusniemi, Kristiina; Backman, Janne T; Laitila, Jouko; Laine, Kari; Neuvonen, Pertti J; Olkkola, Klaus T; Saari, Teijo I

    2016-11-01

    This study aimed to determine possible effects of voriconazole and posaconazole on the pharmacokinetics and pharmacological effects of sublingual buprenorphine. We used a randomized, placebo-controlled crossover study design with 12 healthy male volunteers. Subjects were given a dose of 0.4 mg (0.6 mg during placebo phase) sublingual buprenorphine after a 5-day oral pretreatment with either (i) placebo, (ii) voriconazole 400 mg twice daily on the first day and 200 mg twice daily thereafter or (iii) posaconazole 400 mg twice daily. Plasma and urine concentrations of buprenorphine and its primary active metabolite norbuprenorphine were monitored over 18 h and pharmacological effects were measured. Compared to placebo, voriconazole increased the mean area under the plasma concentration-time curve (AUC 0-∞ ) of buprenorphine 1.80-fold (90 % confidence interval 1.45-2.24; P Voriconazole, unlike posaconazole, increased the urinary excretion of norbuprenorphine 1.58-fold (90 % confidence interval 1.18-2.12; P Voriconazole, and to a minor extent posaconazole, increase plasma exposure to sublingual buprenorphine, probably via inhibition of cytochrome P450 3 A and/or P-glycoprotein. Care should be exercised in the combined use of buprenorphine with triazole antimycotics, particularly with voriconazole, because their interaction can be of clinical importance.

  3. Ghrelin treatment causes increased food intake and retention of lean body mass in a rat model of cancer cachexia.

    Science.gov (United States)

    DeBoer, Mark D; Zhu, Xin Xia; Levasseur, Peter; Meguid, Michael M; Suzuki, Susumu; Inui, Akio; Taylor, John E; Halem, Heather A; Dong, Jesse Z; Datta, Rakesh; Culler, Michael D; Marks, Daniel L

    2007-06-01

    Cancer cachexia is a debilitating syndrome of anorexia and loss of lean body mass that accompanies many malignancies. Ghrelin is an orexigenic hormone with a short half-life that has been shown to improve food intake and weight gain in human and animal subjects with cancer cachexia. We used a rat model of cancer cachexia and administered human ghrelin and a synthetic ghrelin analog BIM-28131 via continuous infusion using sc osmotic minipumps. Tumor-implanted rats receiving human ghrelin or BIM-28131 exhibited a significant increase in food consumption and weight gain vs. saline-treated animals. We used dual-energy x-ray absorptiometry scans to show that the increased weight was due to maintenance of lean mass vs. a loss of lean mass in saline-treated animals. Also, BIM-28131 significantly limited the loss of fat mass normally observed in tumor-implanted rats. We further performed real-time PCR analysis of the hypothalami and brainstems and found that ghrelin-treated animals exhibited a significant increase in expression of orexigenic peptides agouti-related peptide and neuropeptide Y in the hypothalamus and a significant decrease in the expression of IL-1 receptor-I transcript in the hypothalamus and brainstem. We conclude that ghrelin and a synthetic ghrelin receptor agonist improve weight gain and lean body mass retention via effects involving orexigenic neuropeptides and antiinflammatory changes.

  4. Surgery in high-volume hospitals not commission on cancer accreditation leads to increased cancer-specific survival for early-stage lung cancer.

    Science.gov (United States)

    David, Elizabeth A; Cooke, David T; Chen, Yingjia; Perry, Andrew; Canter, Robert J; Cress, Rosemary

    2015-10-01

    Quality of oncologic outcomes is of paramount importance in the care of patients with non-small cell lung cancer (NSCLC). We sought to evaluate the relationship of hospital volume for lobectomy on cancer-specific survival in NSCLC patients treated in California, as well as the influence of Commission on Cancer (CoC) accreditation. The California Cancer Registry was queried from 2004 to 2011 for cases of Stage I NSCLC and 8,345 patients were identified. Statistical analysis was used to determine prognostic factors for cancer-specific survival. A total of 7,587 patients were treated surgically. CoC accreditation was not significant for cancer-specific survival, but treatment in high-volume centers was associated with longer survival when compared with low- and medium-volume centers (hazard ratio 1.77, 1.474 to 2.141 and hazard ratio 1.23, 1.058 to 1.438). These data suggest that surgical treatment in high-volume hospitals is associated with longer cancer-specific survival for early-stage NSCLC, but that CoC accreditation is not. Published by Elsevier Inc.

  5. Individual social capital and survival

    DEFF Research Database (Denmark)

    Ejlskov, Linda; Mortensen, Rikke N; Overgaard, Charlotte

    2014-01-01

    BACKGROUND: The concept of social capital has received increasing attention as a determinant of population survival, but its significance is uncertain. We examined the importance of social capital on survival in a population study while focusing on gender differences. METHODS: We used data from...... a Danish regional health survey with a five-year follow-up period, 2007-2012 (n = 9288, 53.5% men, 46.5% women). We investigated the association between social capital and all-cause mortality, performing separate analyses on a composite measure as well as four specific dimensions of social capital while...... controlling for covariates. Analyses were performed with Cox proportional hazard models by which hazard ratios and 95% confidence intervals were calculated. RESULTS: For women, higher levels of social capital were associated with lower all-cause mortality regardless of age, socioeconomic status, health...

  6. Increasing obesity in treated female HIV patients from Sub-Saharan Africa: Potential causes and possible targets for intervention

    Directory of Open Access Journals (Sweden)

    Claire eMcCormick

    2014-11-01

    Full Text Available Objectives To investigate changing nutritional demographics of treated HIV-1-infected patients and explore causes of obesity, particularly in women of African origin.Methods We prospectively reviewed nutritional demographics of clinic attenders at an urban European HIV clinic during four one-month periods at 3-yearly intervals (2001, 2004, 2007, and 2010 and in two consecutive whole-year reviews (2010-11 and 2011-12. Risk-factors for obesity were assessed by multiple linear regression. A sub-study of 50 HIV-positive African female patients investigated body-size/shape perception using numerical, verbal and pictorial cues. Results We found a dramatic rise in the prevalence of obesity (BMI >30 kg/m2, from 8.5% (2001 to 28% (2011-12 for all clinic attenders, of whom 86% were on antiretroviral treatment. Women of African origin were most affected, 49% being obese, with a further 32% overweight (BMI 25-30 kg/m2, in 2012. Clinical factors strongly associated with obesity included female gender, black African ethnicity, non-smoking, age and CD4 count (all P<0.001; greater duration of cART did not predict obesity. Individual weight-time trends mostly showed slow long-term progressive weight gain. Investigating body weight perception, we found that weight and adiposity were underestimated by obese subjects, who showed a greater disparity between perceived and actual adiposity (P<0.001. Obese subjects targeted more obese target ideal body shapes (P<0.01, but were less satisfied with their body shape overall (P=0.02. Conclusions Seropositive African women on antiretroviral treatment are at heightened risk of obesity. Although multifactorial, bodyweight perception represents a potential target for intervention.

  7. Increased alcohol consumption as a cause of alcoholism, without similar evidence for depression: a Mendelian randomization study.

    Science.gov (United States)

    Wium-Andersen, Marie Kim; Ørsted, David Dynnes; Tolstrup, Janne Schurmann; Nordestgaard, Børge Grønne

    2015-04-01

    Increased alcohol consumption has been associated with depression and alcoholism, but whether these associations are causal remains unclear. We tested whether alcohol consumption is causally associated with depression and alcoholism. We included 78,154 men and women aged 20-100 years randomly selected in 1991-2010 from the general population of Copenhagen, Denmark, and genotyped 68,486 participants for two genetic variants in two alcohol dehydrogenase (ADH) genes, ADH-1B (rs1229984) and ADH-1C (rs698). We performed observational and causal analyses using a Mendelian randomization design with antidepressant medication use and hospitalization/death, with depression and alcoholism as outcomes. In prospective analyses, the multifactorially adjusted hazard ratio for participants reporting >6 drinks/day vs participants reporting 0.1-1 drinks/day was 1.28 (95% confidence interval, 1.00-1.65) for prescription antidepressant use, with a corresponding hazard ratio of 0.80 (0.45-1.45) for hospitalization/death with depression and of 11.7 (8.77-15.6) for hospitalization/death with alcoholism. For hospitalization/death with alcoholism, instrumental variable analysis yielded a causal odds ratio of 28.6 (95 % confidence interval 6.47-126) for an increase of 1 drink/day estimated from the combined genotype combination, whereas the corresponding multifactorially adjusted observational odds ratio was 1.28 (1.25-1.31). Corresponding odds ratios were 1.11 (0.67-1.83) causal and 1.04 (1.03-1.06) observational for prescription antidepressant use, and 4.52 (0.99-20.5) causal and 0.98 (0.94-1.03) observational for hospitalization/death with depression. These data indicate that the association between increased alcohol consumption and alcoholism is causal, without similar strong evidence for depression. © The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

  8. Long-term increased carnitine palmitoyltransferase 1A expression in ventromedial hypotalamus causes hyperphagia and alters the hypothalamic lipidomic profile.

    Directory of Open Access Journals (Sweden)

    Paula Mera

    Full Text Available Lipid metabolism in the ventromedial hypothalamus (VMH has emerged as a crucial pathway in the regulation of feeding and energy homeostasis. Carnitine palmitoyltransferase (CPT 1A is the rate-limiting enzyme in mitochondrial fatty acid β-oxidation and it has been proposed as a crucial mediator of fasting and ghrelin orexigenic signalling. However, the relationship between changes in CPT1A activity and the intracellular downstream effectors in the VMH that contribute to appetite modulation is not fully understood. To this end, we examined the effect of long-term expression of a permanently activated CPT1A isoform by using an adeno-associated viral vector injected into the VMH of rats. Peripherally, this procedure provoked hyperghrelinemia and hyperphagia, which led to overweight, hyperglycemia and insulin resistance. In the mediobasal hypothalamus (MBH, long-term CPT1AM expression in the VMH did not modify acyl-CoA or malonyl-CoA levels. However, it altered the MBH lipidomic profile since ceramides and sphingolipids increased and phospholipids decreased. Furthermore, we detected increased vesicular γ-aminobutyric acid transporter (VGAT and reduced vesicular glutamate transporter 2 (VGLUT2 expressions, both transporters involved in this orexigenic signal. Taken together, these observations indicate that CPT1A contributes to the regulation of feeding by modulating the expression of neurotransmitter transporters and lipid components that influence the orexigenic pathways in VMH.

  9. Increased signal intensity in the normal glenoid labrum in MR imaging. Diagnostic pitfalls caused by the magic-angle effect

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, Taisuke; Yodono, Hiraku; Prado, G.L.M.; Saito, Yoko; Miura, Hiroyuki; Itabashi, Yoko; Ootsuka, Hironori; Ishibashi, Yasuyuki [Hirosaki Univ., Aomori (Japan). School of Medicine

    2002-11-01

    The purpose of this study was to determine the effect of the magic-angle effect on the MR signal in the posterosuperior portion of the glenoid labrum. MR imaging of 15 arthroscopically evaluated shoulders, five with posterosuperior labrum injury and ten intact, was retrospectively reviewed. In the first part of the study, the signal intensity of the posterosuperior labrum on gradient-recalled echo (GRE) T{sub 2}-weighted axial images was correlated with the arthroscopy findings. The second part of the study was designed to illustrate the orientation-dependent signal that occurs in the posterosuperior labrum of three asymptomatic volunteers when imaged in the conventional supine position and in a position similar to Trendelenburg's. Another three volunteers were examined with GRE T{sub 2}-weighted axial images to assess the echo-time (TE)-dependent signal in the labrum. The signal increase in the posterosuperior labrum was identified not only in the injured labra but also in nine of 10 intact labra. In the volunteers' studies, the signal in the posterosuperior labrum changed according to the examinees' positions (conventional supine or similar to Trendelenburg's) and according to TE. Increased signal intensity due to the magic-angle effect may be misdiagnosed as a labrum injury. Awareness of this pitfall is particularly important in MR imaging of throwing athletes whose posterosuperior labra are frequently injured by posterosuperior glenoid impingement. (author)

  10. Moderate intensity supine exercise causes decreased cardiac volumes and increased outer volume variations: a cardiovascular magnetic resonance study.

    Science.gov (United States)

    Steding-Ehrenborg, Katarina; Jablonowski, Robert; Arvidsson, Per M; Carlsson, Marcus; Saltin, Bengt; Arheden, Håkan

    2013-10-24

    The effects on left and right ventricular (LV, RV) volumes during physical exercise remains controversial. Furthermore, no previous study has investigated the effects of exercise on longitudinal contribution to stroke volume (SV) and the outer volume variation of the heart. The aim of this study was to determine if LV, RV and total heart volumes (THV) as well as cardiac pumping mechanisms change during physical exercise compared to rest using cardiovascular magnetic resonance (CMR). 26 healthy volunteers (6 women) underwent CMR at rest and exercise. Exercise was performed using a custom built ergometer for one-legged exercise in the supine position during breath hold imaging. Cardiac volumes and atrio-ventricular plane displacement were determined. Heart rate (HR) was obtained from ECG. HR increased during exercise from 60±2 to 94±2 bpm, (pexercise although not statistically significant (p=0.18). Longitudinal contribution to RVSV decreased during exercise by -6±15% (pexercise by -4±1%, (pexercise from 5.9±0.5% to 9.7±0.6% (pexercise. THV becomes significantly smaller due to decreases in RVEDV whilst LVEDV remains unchanged. THVV and consequently radial pumping increases during exercise which may improve diastolic suction during the rapid filling phase.

  11. Growth hormone inhibition causes increased selenium levels in Duchenne muscular dystrophy: a possible new approach to therapy.

    Science.gov (United States)

    Collipp, P J; Kelemen, J; Chen, S Y; Castro-Magana, M; Angulo, M; Derenoncourt, A

    1984-01-01

    Nine children with Duchenne muscular dystrophy were given Sanorex (mazindol), a growth hormone inhibitor, daily for 6 months. There was no significant change in their muscle function, but there was a significant reduction in weight gain and in levels of growth hormone, somatomedin C, hair zinc, serum zinc, and serum LDH. Selenium and glutathione peroxidase in the serum increased significantly. Thirteen other children with growth hormone deficiency had a significant reduction in hair selenium following growth hormone administration. These results show a significant relationship between growth hormone and selenium nutritional status and confirm our previous reports indicating an effect of growth hormone on zinc nutritional status. It is possible that prolonged therapy with a growth hormone inhibitor would attenuate the course and improve the longevity of patients with muscular dystrophy. PMID:6492089

  12. Increased F-18 FDG uptake on positron emission tomography/computed tomography imaging caused by plantar fibromatosis.

    Science.gov (United States)

    Scheler, Jennifer; Rehani, Bhavya; Percy, Thomas; Pelstring, Richard; Bharija, Ankur; Ames, Donald; Mantil, Joseph

    2008-04-01

    We detail the history and evaluation of a 68-year-old man who had head-to-toe PET/CT scanning that showed a focal area of increased FDG uptake in the left medial foot. This was thought to be recurrence of his melanoma. The patient was asymptomatic. He had a history of malignant melanoma of the right ear, which was removed in 2001. On biopsy, the foot lesion was diagnosed as plantar fibromatosis. Plantar fibromatosis is a benign fibroblastic condition, which can be indistinguishable from malignancy in head-to-toe PET/CT scans. Awareness of their potential appearance on PET and PET/CT will aid in the appropriate staging of oncology patients.

  13. Mutation of the key residue for extraribosomal function of ribosomal protein S19 cause increased grooming behaviors in mice.

    Science.gov (United States)

    Chen, Jun; Kaitsuka, Taku; Fujino, Rika; Araki, Kimi; Tomizawa, Kazuhito; Yamamoto, Tetsuro

    2016-08-26

    Ribosomal protein S19 (RP S19) possesses ribosomal function as RP S19 monomer and extraribosomal function as cross-linked RP S19 oligomers which function as a ligand of the complement 5a (C5a) receptor (CD88). We have generated a Gln137Glu-RP S19 knock-in (KI) mouse, which is shown to possess the weakened extraribosomal function of RP S19. Because whether the extraribosomal function of RP S19 has a role in brain function had been unclear, we performed behavioral analysis on these mice and demonstrated that KI mice displayed an increased grooming behavior during open-field test and elevated plus maze test and an enhanced freezing behavior in contextual fear conditioning test. These results suggest an involvement of RP S19 oligomers in some anxiety-like behavior, especially grooming behavior. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. High Insulin Levels in KK-Ay Diabetic Mice Cause Increased Cortical Bone Mass and Impaired Trabecular Micro-Structure

    Directory of Open Access Journals (Sweden)

    Cen Fu

    2015-04-01

    Full Text Available Type 2 diabetes mellitus (T2DM is a chronic disease characterized by hyperglycemia, hyperinsulinemia and complications, including obesity and osteoporosis. Rodents have been widely used to model human T2DM and investigate its effect on the skeleton. We aimed to investigate skeletal alterations in Yellow Kuo Kondo (KK-Ay diabetic mice displaying high insulin and glucose levels. Bone mineral density (BMD, micro-architecture and bone metabolism-related genes were analyzed. The total femoral areal BMD (aBMD, cortical volumetric BMD (vBMD and thickness were significantly increased in KK-Ay mice, while the trabecular vBMD and mineralized bone volume/tissue volume (BV/TV, trabecular thickness and number were decreased compared to C57BL mice. The expression of both osteoblast-related genes, such as osteocalcin (OC, bone sialoprotein, Type I Collagen, osteonectin, RUNX2 and OSX, and osteoclast-related genes, such as TRAP and TCIRG, were up-regulated in KK-Ay mice. Correlation analyses showed that serum insulin levels were positively associated with aBMD, cortical vBMD and thickness and negatively associated with trabecular vBMD and micro-architecture. In addition, serum insulin levels were positively related to osteoblast-related and osteoclast-related gene expression. Our data suggest that high insulin levels in KK-Ay diabetic mice may increase cortical bone mass and impair trabecular micro-structure by up-regulating osteoblast-and osteoclast-related gene expression.

  15. Gugulipid causes hypercholesterolemia leading to endothelial dysfunction, increased atherosclerosis, and premature death by ischemic heart disease in male mice.

    Directory of Open Access Journals (Sweden)

    Andrea Leiva

    Full Text Available For proper cholesterol metabolism, normal expression and function of scavenger receptor class B type I (SR-BI, a high-density lipoprotein (HDL receptor, is required. Among the factors that regulate overall cholesterol homeostasis and HDL metabolism, the nuclear farnesoid X receptor plays an important role. Guggulsterone, a bioactive compound present in the natural product gugulipid, is an antagonist of this receptor. This natural product is widely used globally as a natural lipid-lowering agent, although its anti-atherogenic cardiovascular benefit in animal models or humans is unknown. The aim of this study was to determine the effects of gugulipid on cholesterol homeostasis and development of mild and severe atherosclerosis in male mice. For this purpose, we evaluated the impact of gugulipid treatment on liver histology, plasma lipoprotein cholesterol, endothelial function, and development of atherosclerosis and/or ischemic heart disease in wild-type mice; apolipoprotein E knockout mice, a model of atherosclerosis without ischemic complications; and SR-B1 knockout and atherogenic-diet-fed apolipoprotein E hypomorphic (SR-BI KO/ApoER61h/h mice, a model of lethal ischemic heart disease due to severe atherosclerosis. Gugulipid administration was associated with histological abnormalities in liver, increased alanine aminotransferase levels, lower hepatic SR-BI content, hypercholesterolemia due to increased HDL cholesterol levels, endothelial dysfunction, enhanced atherosclerosis, and accelerated death in animals with severe ischemic heart disease. In conclusion, our data show important adverse effects of gugulipid intake on HDL metabolism and atherosclerosis in male mice, suggesting potential and unknown deleterious effects on cardiovascular health in humans. In addition, these findings reemphasize the need for rigorous preclinical and clinical studies to provide guidance on the consumption of natural products and regulation of their use in the

  16. Snake venom causes apoptosis by increasing the reactive oxygen species in colorectal and breast cancer cell lines

    Directory of Open Access Journals (Sweden)

    Al-Asmari AK

    2016-10-01

    Full Text Available Abdulrahman Khazim Al-Asmari,1 Anvarbatcha Riyasdeen,1 Mohammad Hamed Al-Shahrani,2 Mozaffarul Islam1 1Research Center, 2Pediatric Hematology/Oncology and Bone Marrow Transplant Unit, Prince Sultan Military Medical City, Riyadh, Kingdom of Saudi Arabia Abstract: Snake venom possesses various kinds of proteins and neurotoxic polypeptides, which can negatively interfere with the neurotransmitter signaling cascade. This phenomenon occurs mainly due to the blocking of ion channels in the body system. Envenomation prevents or severely interrupts nerve impulses from being transmitted, inhibition of adenosine triphosphate synthesis, and proper functioning of the cardiac muscles. However, some beneficial properties of venoms have also been reported. The aim of this study was to examine the snake venom as an anticancer agent due to its inhibitory effects on cancer progression such as cell motility, cell invasion, and colony formation. In this study, the effect of venoms on phenotypic changes and the change on molecular level in colorectal and breast cancer cell lines were examined. A reduction of 60%–90% in cell motility, colony formation, and cell invasion was observed when these cell lines were treated with different concentrations of snake venom. In addition, the increase in oxidative stress that results in an increase in the number of apoptotic cancer cells was significantly higher in the venom-treated cell lines. Further analysis showed that there was a decrease in the expression of pro-inflammatory cytokines and signaling proteins, strongly suggesting a promising role for snake venom against breast and colorectal cancer cell progression. In conclusion, the snake venoms used in this study showed significant anticancer properties against colorectal and breast cancer cell lines. Keywords: colorectal cancer, breast cancer, cell motility, colony formation, oxidative stress, apoptosis, IL-8, IL-6, RhoC, p-Erk1/2

  17. Increased temperature causes different carbon and nitrogen processing patterns in two common intertidal foraminifera (Ammonia tepida and Haynesina germanica)

    Science.gov (United States)

    Wukovits, Julia; Enge, Annekatrin Julie; Wanek, Wolfgang; Watzka, Margarete; Heinz, Petra

    2017-06-01

    Benthic foraminifera are highly abundant heterotrophic protists in marine sediments, but future environmental changes will challenge the tolerance limits of intertidal species. Metabolic rates and physiological processes in foraminifera are strongly dependent on environmental temperatures. Temperature-related stress could therefore impact foraminiferal food source processing efficiency and might result in altered nutrient fluxes through the intertidal food web. In this study, we performed a laboratory feeding experiment on Ammonia tepida and Haynesina germanica, two dominant foraminiferal species of the German Wadden Sea/Friedrichskoog, to test the effect of temperature on phytodetritus retention. The specimens were fed with 13C and 15N labelled freeze-dried Dunaliella tertiolecta (green algae) at the start of the experiment and were incubated at 20, 25 and 30 °C respectively. Dual labelling was applied to observe potential temperature effects on the relation of phytodetrital carbon and nitrogen retention. Samples were taken over a period of 2 weeks. Foraminiferal cytoplasm was isotopically analysed to investigate differences in carbon and nitrogen uptake derived from the food source. Both species showed a positive response to the provided food source, but carbon uptake rates of A. tepida were 10-fold higher compared to those of H. germanica. Increased temperatures had a far stronger impact on the carbon uptake of H. germanica than on A. tepida. A distinct increase in the levels of phytodetrital-derived nitrogen (compared to more steady carbon levels) could be observed over the course of the experiment in both species. The results suggest that higher temperatures have a significant negative effect on the carbon exploitation of H. germanica. For A. tepida, higher carbon uptake rates and the enhanced tolerance range for higher temperatures could outline an advantage in warmer periods if the main food source consists of chlorophyte phytodetritus. These conditions are

  18. Overexpression of eIF-5A2 in mice causes accelerated organismal aging by increasing chromosome instability

    Directory of Open Access Journals (Sweden)

    Chen Leilei

    2011-05-01

    Full Text Available Abstract Background Amplification of 3q26 is one of the most frequent genetic alterations in many human malignancies. Recently, we isolated a novel oncogene eIF-5A2 within the 3q26 region. Functional study has demonstrated the oncogenic role of eIF-5A2 in the initiation and progression of human cancers. In the present study, we aim to investigate the physiological and pathological effect of eIF-5A2 in an eIF-5A2 transgenic mouse model. Methods An eIF-5A2 transgenic mouse model was generated using human eIF-5A2 cDNA. The eIF-5A2 transgenic mice were characterized by histological and immunohistochemistry analyses. The aging phenotypes were further characterized by wound healing, bone X-ray imaging and calcification analysis. Mouse embryo fibroblasts (MEF were isolated to further investigate molecular mechanism of eIF-5A2 in aging. Results Instead of resulting in spontaneous tumor formation, overexpression of eIF-5A2 accelerated the aging process in adult transgenic mice. This included decreased growth rate and body weight, shortened life span, kyphosis, osteoporosis, delay of wound healing and ossification. Investigation of the correlation between cellular senescence and aging showed that cellular senescence is not required for the aging phenotypes in eIF-5A2 mice. Interestingly, we found that activation of eIF-5A2 repressed p19 level and therefore destabilized p53 in transgenic mouse embryo fibroblast (MEF cells. This subsequently allowed for the accumulation of chromosomal instability, such as errors in cell dividing during metaphase and anaphase. Additionally, a significantly increase in number of aneuploidy cells (p Conclusion These observations suggest that eIF-5A2 mouse models could accelerate organismal aging by increasing chromosome instability.

  19. Does Residual Varus Alignment Cause Increasing Varus Laxity at a Minimum of Five Years After Total Knee Arthroplasty?

    Science.gov (United States)

    Hatayama, Kazuhisa; Terauchi, Masanori; Saito, Kenichi; Higuchi, Hiroshi

    2017-06-01

    The purpose of this study is to investigate whether varus-valgus laxity of cruciate-retaining (CR) total knee arthroplasty (TKA) changes between 1 year and >5 years after surgery based on postoperative limb alignment. One hundred twenty-one varus osteoarthritic knees that underwent CR TKA were included. The minimum follow-up was 5 years. Weight-bearing full-leg radiographs were obtained postoperatively and the hip-knee-ankle (HKA) angle was measured. Knees were grouped in varus (HKA angle ≤ -3°, 47 knees) and neutral groups (-3° Varus-valgus laxity at 15° of knee flexion was measured with stress radiographs after 1 year and at the last follow-up. No knees required revision surgery. The mean knee flexion angle (121.0° vs 117.1°) and Hospital for Special Surgery score (90.3 vs 90.4) at the last follow-up were not significantly different between the varus and neutral groups. In both groups, there was no significant change in varus or valgus laxity between 1 year and at the last follow-up. Postoperative residual varus limb alignment did not lead to increasing varus laxity after CR TKA in the mid-term. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Increased evapotranspiration demand in a Mediterranean climate might cause a decline in fungal yields under global warming.

    Science.gov (United States)

    Ágreda, Teresa; Águeda, Beatriz; Olano, José M; Vicente-Serrano, Sergio M; Fernández-Toirán, Marina

    2015-09-01

    Wild fungi play a critical role in forest ecosystems, and its recollection is a relevant economic activity. Understanding fungal response to climate is necessary in order to predict future fungal production in Mediterranean forests under climate change scenarios. We used a 15-year data set to model the relationship between climate and epigeous fungal abundance and productivity, for mycorrhizal and saprotrophic guilds in a Mediterranean pine forest. The obtained models were used to predict fungal productivity for the 2021-2080 period by means of regional climate change models. Simple models based on early spring temperature and summer-autumn rainfall could provide accurate estimates for fungal abundance and productivity. Models including rainfall and climatic water balance showed similar results and explanatory power for the analyzed 15-year period. However, their predictions for the 2021-2080 period diverged. Rainfall-based models predicted a maintenance of fungal yield, whereas water balance-based models predicted a steady decrease of fungal productivity under a global warming scenario. Under Mediterranean conditions fungi responded to weather conditions in two distinct periods: early spring and late summer-autumn, suggesting a bimodal pattern of growth. Saprotrophic and mycorrhizal fungi showed differences in the climatic control. Increased atmospheric evaporative demand due to global warming might lead to a drop in fungal yields during the 21st century. © 2015 John Wiley & Sons Ltd.

  1. Increased localization of APP-C99 in mitochondria-associated ER membranes causes mitochondrial dysfunction in Alzheimer disease.

    Science.gov (United States)

    Pera, Marta; Larrea, Delfina; Guardia-Laguarta, Cristina; Montesinos, Jorge; Velasco, Kevin R; Agrawal, Rishi R; Xu, Yimeng; Chan, Robin B; Di Paolo, Gilbert; Mehler, Mark F; Perumal, Geoffrey S; Macaluso, Frank P; Freyberg, Zachary Z; Acin-Perez, Rebeca; Enriquez, Jose Antonio; Schon, Eric A; Area-Gomez, Estela

    2017-11-15

    In the amyloidogenic pathway associated with Alzheimer disease (AD), the amyloid precursor protein (APP) is cleaved by β-secretase to generate a 99-aa C-terminal fragment (C99) that is then cleaved by γ-secretase to generate the β-amyloid (Aβ) found in senile plaques. In previous reports, we and others have shown that γ-secretase activity is enriched in mitochondria-associated endoplasmic reticulum (ER) membranes (MAM) and that ER-mitochondrial connectivity and MAM function are upregulated in AD We now show that C99, in addition to its localization in endosomes, can also be found in MAM, where it is normally processed rapidly by γ-secretase. In cell models of AD, however, the concentration of unprocessed C99 increases in MAM regions, resulting in elevated sphingolipid turnover and an altered lipid composition of both MAM and mitochondrial membranes. In turn, this change in mitochondrial membrane composition interferes with the proper assembly and activity of mitochondrial respiratory supercomplexes, thereby likely contributing to the bioenergetic defects characteristic of AD. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

  2. An evaluation of surface-dose increase caused by the thermoplastic shell in head and neck radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Wada, Shin-ichi; Hayama, Kazuhide; Toyama, Michio; Ninomiya, Shuichi; Eguchi, Toru; Takase, Hiroshi; Maeda, Kadzuo (Nippon Dental Univ., Niigata (Japan) Faculty of Dentistry (Niigata))

    1992-10-01

    Some kinds of the thermoplastic shells have been developed to improve the reproducibility of patient immobilization in head and neck radiotherapy treatment. Due to a build-up layer of high energy photons, the consideration of the surface-dose under the shell is important in radiotherapy treatment planning. This paper presents the precise evaluation of the surface-dose affected by the shell. The therapy machine used was 2.8 MV linac X-ray. The shell used was mesh sheet type thermoplastic shell. The TPR (tissue peak ratio) in the build-up layer was measured in various irradiation fields under the conditions with or without a wedge filter. The coefficients m' and K's of the power function of the build-up region were obtained from the relation between TPR and the irradiation fields. As a result, the coefficients were approximately intermediate values between cobalt-60 [gamma]-ray and 4.3 MV X-ray. When a wedge filter was used, the coefficients shifted toward those of higher energy. Before obtaining the dose distribution under the thermoplastic shell, film response was tested under the conditions of various irradiation fields and use of a wedge filter. The results showed that the film response was constant enough for dosimetry in the build-up region. Digital surface-absorbed dose distribution images under the shell were obtained using the microphotometer-microcomputer system. The digital image demonstrated a meshy dose pattern under the shell. In the area of a higher absorbed dose, the dose increases were in the range of 40-50%. The differences depended on not only the irradiation field and presence of a wedge-filter, but especially on the extent of expansion of the thermoplastic material in making the shell mask. (author).

  3. Understanding the Patterns and Causes of Variability in Distribution, Habitat use, Abundance, Survival and Reproductive Rates of Three Species of Cetacean in the Alboran Sea, Western Mediterranean

    Science.gov (United States)

    2013-09-30

    cetaceans can serve as indicators of environmental change in the marine environment and of “ocean health ” generally. APPROACH To achieve the...the summer months, an increase of proportion of groups with calves was observed coinciding with the first inmigration event between 1997 and 2001...There is also an increase in 2005- 2006 coinciding with the second inmigration event (according to field observations, this second event started in

  4. Increased litter survival rates, reduced clinical illness and better lactogenic immunity against TGEV in gilts that were primed as neonates with porcine respiratory coronavirus (PRCV).

    Science.gov (United States)

    Wesley, Ronald D; Lager, Kelly M

    2003-09-01

    Establishing immunological memory in female piglets at a young age with PRCV was effective in inducing a secondary immune response to a limiting dose of virulent TGEV given orally 13-18 days prior to farrowing. Subsequently, because of passive antibody transfer, the offspring of these primed gilts were more efficient in surviving a lethal TGEV challenge. An average survival rate of 89% occurred in 6 litters of piglets from primed gilts that were boosted with 2.8 x 10(6) plaque forming units (PFU) of TGEV whereas 76% of the piglets survived in three litters that suckled primed gilts boosted with 3.0 x 10(5)PFU of TGEV. Non-primed gilts given identical pre-farrowing doses of TGEV had litter survival rates of 63 and 55%, respectively. Moreover, both groups of litters from primed gilts suffered less clinical illness (as measured by the extent of weight loss post-challenge) than control litters. Priming of the piglets as neonates and boosting the pregnant gilts produced an anamnestic systemic immune response and correspondingly higher milk titers in the primed gilts compared to control animals. Thus, priming piglets with PRCV was beneficial in providing resistance to TGEV and could be incorporated into a vaccine strategy that yields better protection against TGEV.

  5. Procalcitonin-guided interventions against infections to increase early appropriate antibiotics and improve survival in the intensive care unit: a randomized trial

    DEFF Research Database (Denmark)

    Jensen, Jens U; Hein, Lars; Lundgren, Bettina

    2011-01-01

    For patients in intensive care units, sepsis is a common and potentially deadly complication and prompt initiation of appropriate antimicrobial therapy improves prognosis. The objective of this trial was to determine whether a strategy of antimicrobial spectrum escalation, guided by daily...... measurements of the biomarker procalcitonin, could reduce the time to appropriate therapy, thus improving survival....

  6. High tobacco consumption is causally associated with increased all-cause mortality in a general population sample of 55 568 individuals, but not with short telomeres

    DEFF Research Database (Denmark)

    Rode, Line; Bojesen, Stig E; Weischer, Maren

    2014-01-01

    randomization study, we conducted observational, genetic, and mediation analyses. RESULTS: First, tobacco consumption was 21.1 pack-years in non-carriers, 22.8 in heterozygotes and 24.8 in homozygotes (P-trendcause mortality was 1......BACKGROUND: High cumulative tobacco consumption is associated with short telomeres and with increased all-cause mortality. We tested the hypothesis that high tobacco consumption is causally associated with short telomeres and with increased all-cause mortality. METHODS: We studied 55...... in tobacco consumption. In Mendelian randomization analysis, the estimate was +3 base pairs (-10, +15) per minor CHRNA3 allele. Finally, individuals with the shortest vs longest telomeres had a multivariable adjusted hazard ratio of 1.30 (1.13, 1.50) for all-cause mortality; however, in mediation analysis...

  7. A Novel FOXE1 Mutation (R73S) in Bamforth–Lazarus Syndrome Causing Increased Thyroidal Gene Expression

    Science.gov (United States)

    Carré, Aurore; Hamza, Rasha T.; Kariyawasam, Dulanjalee; Guillot, Loïc; Teissier, Raphaël; Tron, Elodie; Castanet, Mireille; Dupuy, Corinne; El Kholy, Mohamed; Polak, Michel

    2014-01-01

    Background: Homozygous loss-of-function mutations in the FOXE1 gene have been reported in several patients with partial or complete Bamforth–Lazarus syndrome: congenital hypothyroidism (CH) with thyroid dysgenesis (usually athyreosis), cleft palate, spiky hair, with or without choanal atresia, and bifid epiglottis. Here, our objective was to evaluate potential functional consequences of a FOXE1 mutation in a patient with a similar clinical phenotype. Methods: FOXE1 was sequenced in eight patients with thyroid dysgenesis and cleft palate. Transient transfection was performed in HEK293 cells using the thyroglobulin (TG) and thyroid peroxidase (TPO) promoters in luciferase reporter plasmids to assess the functional impact of the FOXE1 mutations. Primary human thyrocytes transfected with wild type and mutant FOXE1 served to assess the impact of the mutation on endogenous TG and TPO expression. Results: We identified and characterized the function of a new homozygous FOXE1 missense mutation (p.R73S) in a boy with a typical phenotype (athyreosis, cleft palate, and partial choanal atresia). This new mutation located within the forkhead domain was inherited from the heterozygous healthy consanguineous parents. In vitro functional studies in HEK293 cells showed that this mutant gene enhanced the activity of the TG and TPO gene promoters (1.5-fold and 1.7-fold respectively vs. wild type FOXE1; p<0.05), unlike the five mutations previously reported in Bamforth–Lazarus syndrome. The gain-of-function effect of the FOXE1-p.R73S mutant gene was confirmed by an increase in endogenous TG production in primary human thyrocytes. Conclusion: We identified a new homozygous FOXE1 mutation responsible for enhanced expression of the TG and TPO genes in a boy whose phenotype is similar to that reported previously in patients with loss-of-function FOXE1 mutations. This finding further delineates the role for FOXE1 in both thyroid and palate development, and shows that enhanced gene

  8. After accounting for competing causes of death and more advanced stage, do Aboriginal and Torres Strait Islander peoples with cancer still have worse survival? A population-based cohort study in New South Wales.

    Science.gov (United States)

    Tervonen, Hanna E; Walton, Richard; You, Hui; Baker, Deborah; Roder, David; Currow, David; Aranda, Sanchia

    2017-06-02

    Aboriginal and Torres Strait Islander peoples in Australia have been found to have poorer cancer survival than non-Aboriginal people. However, use of conventional relative survival analyses is limited due to a lack of life tables. This cohort study examined whether poorer survival persist after accounting for competing risks of death from other causes and disparities in cancer stage at diagnosis, for all cancers collectively and by cancer site. People diagnosed in 2000-2008 were extracted from the population-based New South Wales Cancer Registry. Aboriginal status was multiply imputed for people with missing information (12.9%). Logistic regression models were used to compute odds ratios (ORs) with 95% confidence intervals (CIs) for 'advanced stage' at diagnosis (separately for distant and distant/regional stage). Survival was examined using competing risk regression to compute subhazard ratios (SHRs) with 95%CIs. Of the 301,356 cases, 2517 (0.84%) identified as Aboriginal (0.94% after imputation). After adjusting for age, sex, year of diagnosis, socio-economic status, remoteness, and cancer site Aboriginal peoples were more likely to be diagnosed with distant (OR 1.30, 95%CI 1.17-1.44) or distant/regional stage (OR 1.29, 95%CI 1.18-1.40) for all cancers collectively. This applied to cancers of the female breast, uterus, prostate, kidney, others (those not included in other categories) and cervix (when analyses were restricted to cases with known stages/known Aboriginal status). Aboriginal peoples had a higher hazard of death than non-Aboriginal people after accounting for competing risks from other causes of death, socio-demographic factors, stage and cancer site (SHR 1.40, 95%CI 1.31-1.50 for all cancers collectively). Consistent results applied to colorectal, lung, breast, prostate and other cancers. Aboriginal peoples with cancer have an elevated hazard of cancer death compared with non-Aboriginal people, after accounting for more advanced stage and competing

  9. Increased tumour ascorbate is associated with extended disease-free survival and decreased hypoxia-inducible factor-1 activation in human colorectal cancer

    Directory of Open Access Journals (Sweden)

    Caroline eKuiper

    2014-02-01

    Full Text Available Ascorbate is a co-factor for the hydroxylases that regulate the transcription factor hypoxia-inducible factor (HIF-1, which provides cancer cells with a metabolic and survival advantage in the hypoxic environment of solid tumors. However, whether ascorbate affects tumor development is a highly debated issue. We aimed to determine whether tumor ascorbate was associated with HIF-1 activation and patient disease-free survival. In this study we undertook a retrospective observational analysis of tissue-banked tumor and paired normal tissue from 49 colorectal cancer patients, measuring ascorbate levels, HIF-1α and its downstream gene products BNIP3 and VEGF. Patient survival was monitored for the first six years after surgery. We found that ascorbate levels were lower in tumor tissue compared to normal tissue (p< 0.001 but overall levels varied considerably. HIF-1α, VEGF and BNIP3 were elevated in tumor samples (p< 0.01. There was an inverse relationship between tumor ascorbate content and HIF-1 pathway activation (p=0.002 and tumor size (p=0.018. Higher tumor ascorbate content was associated with significantly improved disease-free survival in the first 6 years after surgery (p=0.006, with 141 - 1,094 additional disease free days. This was independent of tumor grade and stage. Survival advantage was associated with the amount of ascorbate in the tumor, but not with the amount in adjacent normal tissue. Our results demonstrate that higher tumor ascorbate content is associated decreased HIF-1 activation, most likely due to the co-factor activity of ascorbate for the regulatory HIF hydroxylases. Our findings support the need for future studies to determine whether raising tumor ascorbate is possible with clinical intervention and whether this results in modification of hydroxylase-dependent pathways in the tumor.

  10. Increasing CPR duration prior to first defibrillation does not improve return of spontaneous circulation or survival in a swine model of prolonged ventricular fibrillation

    Science.gov (United States)

    Rittenberger, Jon C.; Suffoletto, Brian; Salcido, David; Logue, Eric; Menegazzi, James J.

    2008-01-01

    Introduction The optimum duration of cardiopulmonary resuscitation (CPR) prior to first rescue shock is unknown. Clinical trials have used 90s and 180s. Neither of these durations may be optimal. We sought to determine the optimum duration of CPR prior to first defibrillation attempt and whether this varied depending on the duration of ventricular fibrillation (VF). In this porcine model of basic life support, our outcomes were rates of return of spontaneous circulation (ROSC), survival, and coronary perfusion pressure (CPP). Methods We anesthetized and instrumented 45 swine and then induced VF. After 5 or 8 minutes of untreated VF, we randomized the swine to mechanical CPR for 90, 180, or 300s. A single rescue shock (150J biphasic) was then administered. If this shock failed, 2 minutes of mechanical CPR were completed prior to the next rescue shock. CPP was calculated for each 30 second epoch. ROSC was defined as a blood pressure >80mmHg sustained for 60s. Survival was defined as sustained ROSC for 20 minutes. Data were analyzed with descriptive statistics, Fisher’s exact test, and ANOVA. Results In the 5 minute VF cohort, the rate of ROSC did not differ between the three groups (90s: 25%; 180s: 38%; 300s: 38%, p>.05). Survival rates did not differ (90s: 25%; 180s: 25%; 300s: 25%, p>0.05). In the 8 minute VF cohort, no animals experienced ROSC or survival. CPP were calculated by 30 second epoch and did not differ between the three groups (p>0.05). CPPs decline after 180s of CPR. Conclusions ROSC and survival were equivalent regardless of VF duration and CPR duration. When CPR begins late, CPPs are low, stressing the importance of early CPR. We do not recommend 300s of CPR unless a defibrillator is unavailable. PMID:18620793

  11. Increased orosomucoid in urine is an independent predictor of cardiovascular and all-cause mortality in patients with type 2 diabetes at 10 years of follow-up

    DEFF Research Database (Denmark)

    Svendstrup, Mathilde; Christiansen, Merete Skovdal; Magid, Erik

    2013-01-01

    To evaluate whether increased urinary orosomucoid excretion rate (UOER) is an independent predictor of cardiovascular and all-cause mortality in type 2 diabetes (T2DM) and type 1 diabetes (T1DM) at 10years of follow-up....

  12. The human Cx26-D50A and Cx26-A88V mutations causing keratitis-ichthyosis-deafness syndrome display increased hemichannel activity.

    Science.gov (United States)

    Mhaske, Pallavi V; Levit, Noah A; Li, Leping; Wang, Hong-Zhan; Lee, Jack R; Shuja, Zunaira; Brink, Peter R; White, Thomas W

    2013-06-15

    Mutations in the human gene encoding connexin 26 (Cx26 or GJB2) cause either nonsyndromic deafness or syndromic deafness associated with skin diseases. That distinct clinical disorders can be caused by different mutations within the same gene suggests that different channel activities influence the ear and skin. Here we use three different expression systems to examine the functional characteristics of two Cx26 mutations causing either mild (Cx26-D50A) or lethal (Cx26-A88V) keratitis-ichthyosis-deafness (KID) syndrome. In either cRNA-injected Xenopus oocytes, transfected HeLa cells, or transfected primary human keratinocytes, we show that both Cx26-D50A and Cx26-A88V form active hemichannels that significantly increase membrane current flow compared with wild-type Cx26. This increased membrane current accelerated cell death in low extracellular calcium solutions and was not due to increased mutant protein expression. Elevated mutant hemichannel currents could be blocked by increased extracellular calcium concentration. These results show that these two mutations exhibit a shared gain of functional activity and support the hypothesis that increased hemichannel activity is a common feature of human Cx26 mutations responsible for KID syndrome.

  13. Clarithromycin for stable coronary heart disease increases all-cause and cardiovascular mortality and cerebrovascular morbidity over 10years in the CLARICOR randomised, blinded clinical trial

    DEFF Research Database (Denmark)

    Winkel, Per; Hilden, Jørgen; Hansen, Jørgen Fischer

    2015-01-01

    -cause mortality (hazard ratio (HR): 1.10, 95% confidence interval (CI): 1.00-1.21) and cerebrovascular disease during 10years (HR: 1.19, 95% CI: 1.02-1.38). The increased mortality and morbidity were restricted to patients not on statin at entry (HR: 1.16, 95% CI: 1.04-1.31, and HR: 1.25, 95% CI: 1...... death outside hospital and cerebrovascular morbidity in patients with stable coronary heart disease who were not on statin. The increased cardiovascular mortality was years later compensated, likely through frailty attrition.......BACKGROUND: The CLARICOR trial reported that clarithromycin compared with placebo increased all-cause mortality in patients with stable coronary heart disease. This study investigates the effects of clarithromycin versus placebo during 10years follow up. METHODS: The CLARICOR trial is a randomised...

  14. Up-regulation of cell cycle arrest protein BTG2 correlates with increased overall survival in breast cancer, as detected by immunohistochemistry using tissue microarray

    Directory of Open Access Journals (Sweden)

    Jirström Karin

    2010-06-01

    Full Text Available Abstract Background Previous studies have shown that the ADIPOR1, ADORA1, BTG2 and CD46 genes differ significantly between long-term survivors of breast cancer and deceased patients, both in levels of gene expression and DNA copy numbers. The aim of this study was to characterize the expression of the corresponding proteins in breast carcinoma and to determine their correlation with clinical outcome. Methods Protein expression was evaluated using immunohistochemistry in an independent breast cancer cohort of 144 samples represented on tissue microarrays. Fisher's exact test was used to analyze the differences in protein expression between dead and alive patients. We used Cox-regression multivariate analysis to assess whether the new markers predict the survival status of the patients better than the currently used markers. Results BTG2 expression was demonstrated in a significantly lower proportion of samples from dead patients compared to alive patients, both in overall expression (P = 0.026 and cell membrane specific expression (P = 0.013, whereas neither ADIPOR1, ADORA1 nor CD46 showed differential expression in the two survival groups. Furthermore, a multivariate analysis showed that a model containing BTG2 expression in combination with HER2 and Ki67 expression along with patient age performed better than a model containing the currently used prognostic markers (tumour size, nodal status, HER2 expression, hormone receptor status, histological grade, and patient age. Interestingly, BTG2 has previously been described as a tumour suppressor gene involved in cell cycle arrest and p53 signalling. Conclusions We conclude that high-level BTG2 protein expression correlates with prolonged survival in patients with breast carcinoma.

  15. Data for increase of Lymantria dispar male survival after topical application of single-stranded RING domain fragment of IAP-3 gene of its nuclear polyhedrosis virus

    Science.gov (United States)

    Oberemok, Volodymyr V.; Laikova, Kateryna V.; Zaitsev, Aleksei S.; Gushchin, Vladimir A.; Skorokhod, Oleksii A.

    2016-01-01

    This data article is related to the research article entitled “The RING for gypsy moth control: topical application of fragment of its nuclear polyhedrosis virus anti-apoptosis gene as insecticide” [1]. This article reports on significantly higher survival of gypsy moth Lymantria dispar male individuals in response to topical application of single-stranded DNA, based on RING (really interesting new gene) domain fragment of LdMNPV (L. dispar multicapsid nuclear polyhedrosis virus) IAP-3 (inhibitor of apoptosis) gene and acted as DNA insecticide. PMID:27054151

  16. In situ normoxia enhances survival and proliferation rate of human adipose tissue-derived stromal cells without increasing the risk of tumourigenesis.

    Directory of Open Access Journals (Sweden)

    Jane Ru Choi

    Full Text Available Adipose tissue-derived stromal cells (ASCs natively reside in a relatively low-oxygen tension (i.e., hypoxic microenvironment in human body. Low oxygen tension (i.e., in situ normoxia, has been known to enhance the growth and survival rate of ASCs, which, however, may lead to the risk of tumourigenesis. Here, we investigated the tumourigenic potential of ASCs under their physiological condition to ensure their safe use in regenerative therapy. Human ASCs isolated from subcutaneous fat were cultured in atmospheric O2 concentration (21% O2 or in situ normoxia (2% O2. We found that ASCs retained their surface markers, tri-lineage differentiation potential, and self-renewal properties under in situ normoxia without altering their morphology. In situ normoxia displayed a higher proliferation and viability of ASCs with less DNA damage as compared to atmospheric O2 concentration. Moreover, low oxygen tension significantly up-regulated VEGF and bFGF mRNA expression and protein secretion while reducing the expression level of tumour suppressor genes p16, p21, p53, and pRb. However, there were no significant differences in ASCs telomere length and their relative telomerase activity when cultured at different oxygen concentrations. Collectively, even with high proliferation and survival rate, ASCs have a low tendency of developing tumour under in situ normoxia. These results suggest 2% O2 as an ideal culture condition for expanding ASCs efficiently while maintaining their characteristics.

  17. The Silencing of a 14-3-3ɛ Homolog in Tenebrio molitor Leads to Increased Antimicrobial Activity in Hemocyte and Reduces Larval Survivability.

    Science.gov (United States)

    Seo, Gi Won; Jo, Yong Hun; Seong, Jeong Hwan; Park, Ki Beom; Patnaik, Bharat Bhusan; Tindwa, Hamisi; Kim, Sun-Am; Lee, Yong Seok; Kim, Yu Jung; Han, Yeon Soo

    2016-08-20

    The 14-3-3 family of phosphorylated serine-binding proteins acts as signaling molecules in biological processes such as metabolism, division, differentiation, autophagy, and apoptosis. Herein, we report the requirement of 14-3-3ɛ isoform from Tenebrio molitor (Tm14-3-3ɛ) in the hemocyte antimicrobial activity. The Tm14-3-3ɛ transcript is 771 nucleotides in length and encodes a polypeptide of 256 amino acid residues. The protein has the typical 14-3-3 domain, the nuclear export signal (NES) sequence, and the peptide binding residues. The Tm14-3-3ɛ transcript shows a significant three-fold expression in the hemocyte of T. molitor larvae when infected with Escherichia coli Tm14-3-3ɛ silenced larvae show significantly lower survival rates when infected with E. coli. Under Tm14-3-3ɛ silenced condition, a strong antimicrobial activity is elicited in the hemocyte of the host inoculated with E. coli. This suggests impaired secretion of antimicrobial peptides (AMP) into the hemolymph. Furthermore, a reduction in AMP secretion under Tm14-3-3ɛ silenced condition would be responsible for loss in the capacity to kill bacteria and might explain the reduced survivability of the larvae upon E. coli challenge. This shows that Tm14-3-3ɛ is required to maintain innate immunity in T. molitor by enabling antimicrobial secretion into the hemolymph and explains the functional specialization of the isoform.

  18. The Silencing of a 14-3-3ɛ Homolog in Tenebrio molitor Leads to Increased Antimicrobial Activity in Hemocyte and Reduces Larval Survivability

    Directory of Open Access Journals (Sweden)

    Gi Won Seo

    2016-08-01

    Full Text Available The 14-3-3 family of phosphorylated serine-binding proteins acts as signaling molecules in biological processes such as metabolism, division, differentiation, autophagy, and apoptosis. Herein, we report the requirement of 14-3-3ɛ isoform from Tenebrio molitor (Tm14-3-3ɛ in the hemocyte antimicrobial activity. The Tm14-3-3ɛ transcript is 771 nucleotides in length and encodes a polypeptide of 256 amino acid residues. The protein has the typical 14-3-3 domain, the nuclear export signal (NES sequence, and the peptide binding residues. The Tm14-3-3ɛ transcript shows a significant three-fold expression in the hemocyte of T. molitor larvae when infected with Escherichia coli Tm14-3-3ɛ silenced larvae show significantly lower survival rates when infected with E. coli. Under Tm14-3-3ɛ silenced condition, a strong antimicrobial activity is elicited in the hemocyte of the host inoculated with E. coli. This suggests impaired secretion of antimicrobial peptides (AMP into the hemolymph. Furthermore, a reduction in AMP secretion under Tm14-3-3ɛ silenced condition would be responsible for loss in the capacity to kill bacteria and might explain the reduced survivability of the larvae upon E. coli challenge. This shows that Tm14-3-3ɛ is required to maintain innate immunity in T. molitor by enabling antimicrobial secretion into the hemolymph and explains the functional specialization of the isoform.

  19. Interferon gamma increases survival in urine experimental cryptococcosis El Interferon gamma incrementa la sobrevida de un modelo experimental murino de criptococosis

    Directory of Open Access Journals (Sweden)

    Amadeo J. Bava

    1995-10-01

    Full Text Available Systemic disease by Cryptococcus neoformans (C. neoformans is a common opportunistic infection in immunodeficient patients. Cellular immunity seems to be the most important determinant of resistance. The aim of this study was to assess the effect of recombinant rat interferon gamma (IFN-gamma in murine cryptococcosis (Balb/c mice infected by IP route with the Rivas strain of C. neoformans, evaluating survival time, macroscopic and microscopic examination of the organs, and massive seeding of brain homogenate. IFN-gamma treatment, at a daily dose of 10,000 IU, did not modify significantly these variables when mice were challenged with a high inoculum (10(7 yeasts and treatment was delayed to 5 days after infection (median survival 21 days in control mice vs. 23 days in IFN-treated. Another set of experiments suggested that IFN-gamma treatment, at a dose of 10,000 IU/day, begun at the moment of infection could be useful (it prolonged survival from 20 to 28 days, although the difference did not achieve statistical signification. When used simultaneously with infection by 3.5 x 10(5 yeasts, IFN-gamma at 10,000 IU/day for 15 days significantly prolonged survival of mice (p = 0.004. These results suggest that, depending on the experimental conditions, IFN-gamma can improve survival of mice infected with a lethal dose of C. neoformans.Se evaluó la efectividad del interferon-gamma (IFN-gamma recombinante de rata en un modelo experimental de criptococosis desarollado en ratones Balb/C inoculados por vía intraperitoneal con la cepa Rivas de Cryptococcus neoformans (C. neoformans. Se tuvieron en cuenta el tiempo de sobrevida de los animales, el aspecto macroscópico de los órganos en la autopsia, la presencia de levaduras capsuladas en los tejidos y la siembra masiva de un homogenato de cerebro. El tratamiento con IFN-gamma, en dosis diarias de 10.000 UI, no modificó estos parámetros cuando la dosis infectante fue de 10(7 levaduras y el tratamiento se

  20. Glutamate Increases In Vitro Survival and Proliferation and Attenuates Oxidative Stress-Induced Cell Death in Adult Spinal Cord-Derived Neural Stem/Progenitor Cells via Non-NMDA Ionotropic Glutamate Receptors.

    Science.gov (United States)

    Hachem, Laureen D; Mothe, Andrea J; Tator, Charles H

    2016-08-15

    Traumatic spinal cord injury (SCI) leads to a cascade of secondary chemical insults, including oxidative stress and glutamate excitotoxicity, which damage host neurons and glia. Transplantation of exogenous neural stem/progenitor cells (NSPCs) has shown promise in enhancing regeneration after SCI, although survival of transplanted cells remains poor. Understanding the response of NSPCs to the chemical mediators of secondary injury is essential in finding therapies to enhance survival. We examined the in vitro effects of glutamate and glutamate receptor agonists on adult rat spinal cord-derived NSPCs. NSPCs isolated from the periventricular region of the adult rat spinal cord were exposed to various concentrations of glutamate for 96 h. We found that glutamate treatment (500 μM) for 96 h significantly increased live cell numbers, reduced cell death, and increased proliferation, but did not significantly alter cell phenotype. Concurrent glutamate treatment (500 μM) in the setting of H2O2 exposure (500 μM) for 10 h increased NSPC survival compared to H2O2 exposure alone. The effects of glutamate on NSPCs were blocked by the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor antagonist GYKI-52466, but not by the N-methyl-D-aspartic acid receptor antagonist MK-801 or DL-AP5, or the mGluR3 antagonist LY-341495. Furthermore, treatment of NSPCs with AMPA, kainic acid, or the kainate receptor-specific agonist (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid mimicked the responses seen with glutamate both alone and in the setting of oxidative stress. These findings offer important insights into potential mechanisms to enhance NSPC survival and implicate a potential role for glutamate in promoting NSPC survival and proliferation after traumatic SCI.

  1. The AMP-Dependent Protein Kinase (AMPK Activator A-769662 Causes Arterial Relaxation by Reducing Cytosolic Free Calcium Independently of an Increase in AMPK Phosphorylation

    Directory of Open Access Journals (Sweden)

    Yi Huang

    2017-10-01

    Full Text Available Although recent studies reveal that activation of the metabolic and Ca2+ sensor AMPK strongly inhibits smooth muscle contraction, there is a paucity of information about the potential linkage between pharmacological AMPK activation and vascular smooth muscle (VSM contraction regulation. Our aim was to test the general hypothesis that the allosteric AMPK activator A-769662 causes VSM relaxation via inhibition of contractile protein activation, and to specifically determine which activation mechanism(s is(are affected. The ability of A-769662 to cause endothelium-independent relaxation of contractions induced by several contractile stimuli was examined in large and small musculocutaneous and visceral rabbit arteries. For comparison, the structurally dissimilar AMPK activators MET, SIM, and BBR were assessed. A-769662 displayed artery- and agonist-dependent differential inhibitory activities that depended on artery size and location. A-769662 did not increase AMPK-pT172 levels, but did increase phosphorylation of the downstream AMPK substrate, acetyl-CoA carboxylase (ACC. A-769662 did not inhibit basal phosphorylation levels of several contractile protein regulatory proteins, and did not alter the activation state of rhoA. A-769662 did not inhibit Ca2+- and GTPγS-induced contractions in β-escin-permeabilized muscle, suggesting that A-769662 must act by inhibiting Ca2+ signaling. In intact artery, A-769662 immediately reduced basal intracellular free calcium ([Ca2+]i, inhibited a stimulus-induced increase in [Ca2+]i, and inhibited a cyclopiazonic acid (CPA-induced contraction. MET increased AMPK-pT172, and caused neither inhibition of contraction nor inhibition of [Ca2+]i. Together, these data support the hypothesis that the differential inhibition of stimulus-induced arterial contractions by A-769662 was due to selective inhibition of a Ca2+ mobilization pathway, possibly involving CPA-dependent Ca2+ entry via an AMPK-independent pathway. That

  2. The U-shaped relationship between BMI and all-cause mortality contrasts with a progressive increase in medical expenditure: a prospective cohort study.

    Science.gov (United States)

    Pan, Wen-Harn; Yeh, Wen-Ting; Chen, Hsin-Jen; Chuang, Shao-Yuan; Chang, Hsing-Yi; Chen, Likwang; Wahlqvist, Mark L

    2012-01-01

    The U-shaped relationship between body mass index (BMI) and all-cause mortality has generated uncertainty about optimal BMI. For clarification, we have related BMI to both mortality and medical expenditure. The MJ Health examination cohort of 111,949 examinees established during 1994-1996 was followed with endpoint information derived from death certificates and National Health Insurance records from 1996 to 2007. Age- and gender-specific relative risks between BMI groups were estimated by Cox and logistic regressions. The BMI and all-cause mortality relationship is U-shaped with the concave regions sitting in the region of BMI 22-26, butshifted rightward for the elderly. After excluding smokers and cancer patients at baseline, the low mortality region moved leftward to BMI 20-22. Cause-specific mortalities from respiratory disease, injury, and senility increased in the underweight group (BMI mortality from respiratory diseases and senility, but not with others. In contrast, irrespective of age and gender, the overall median and mean medical expenditures progressively increased with BMI, particularly beyond 22. Expenditures for injury, respiratory, circulatory diseases and senility all increased with BMI. The U-shaped BMI-mortality relation was a result of elevated death rate at both ends of the BMI scale. Increased mortality at the low end did not contribute to higher medical expenditure, maybe because the lean and frail deceased tend to die abruptly before large amount of medical expenditure was consumed. Our findings suggest that current recommendations to maintain BMI at the lower end of the desirable range remain tenable for the apparently healthy general public.

  3. Are sitting occupations associated with increased all-cause, cancer, and cardiovascular disease mortality risk? A pooled analysis of seven British population cohorts.

    Directory of Open Access Journals (Sweden)

    Emmanuel Stamatakis

    Full Text Available There is mounting evidence for associations between sedentary behaviours and adverse health outcomes, although the data on occupational sitting and mortality risk remain equivocal. The aim of this study was to determine the association between occupational sitting and cardiovascular, cancer and all-cause mortality in a pooled sample of seven British general population cohorts.The sample comprised 5380 women and 5788 men in employment who were drawn from five Health Survey for England and two Scottish Health Survey cohorts. Participants were classified as reporting standing, walking or sitting in their work time and followed up over 12.9 years for mortality. Data were modelled using Cox proportional hazard regression adjusted for age, waist circumference, self-reported general health, frequency of alcohol intake, cigarette smoking, non-occupational physical activity, prevalent cardiovascular disease and cancer at baseline, psychological health, social class, and education.In total there were 754 all-cause deaths. In women, a standing/walking occupation was associated with lower risk of all-cause (fully adjusted hazard ratio [HR] = 0.68, 95% CI 0.52-0.89 and cancer (HR = 0.60, 95% CI 0.43-0.85 mortality, compared to sitting occupations. There were no associations in men. In analyses with combined occupational type and leisure-time physical activity, the risk of all-cause mortality was lowest in participants with non-sitting occupations and high leisure-time activity.Sitting occupations are linked to increased risk for all-cause and cancer mortality in women only, but no such associations exist for cardiovascular mortality in men or women.

  4. Diabetes mellitus increased all-cause mortality rate among newly-diagnosed tuberculosis patients in an Asian population: A nationwide population-based study.

    Science.gov (United States)

    Ko, Po-Yen; Lin, Shi-Dou; Hsieh, Ming-Chia; Chen, Yu-Cheng

    2017-11-01

    To investigate the effect of diabetes mellitus (DM) on all-cause mortality among patients with newly-diagnosed tuberculosis (TB) in an Asian population. We also identified risk factors for mortality in these patients. The data were obtained from the National Health Insurance Research Database and included 9831 newly-diagnosed TB individuals and 1627 TB mortality cases in the period of 2000-2010. The mortality data were divided into a DM group and a non-DM group. We measured the incidence density of mortality and identified the risk factors of mortality. The all-cause mortality of newly-diagnosed TB patients progressively increased with an average rate of 16.5% during 2000-2010. DM is an independent risk factor for all-cause mortality with HRs 1.17-1.27 by various models. TB patients with ages above 75years had the highest risk of mortality (HR=11.93) compared with those under 45 years. TB patients with heart failure, peripheral vascular disease, ischemic heart disease, cerebral vascular disease, hypertension, chronic kidney disease, pulmonary disease, liver disease, cancer, peptic ulcer disease, gout, and autoimmune disease had higher mortality compared to those without the aforementioned factors. The one-year all-cause mortality after TB diagnosis was high among TB patients in Taiwan and it tended to increase in the past decade. While treating these newly-diagnosed TB patients, it is crucial to detect the factors predisposing to death, such as old age, male gender, certain kinds of aforementioned factors and diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Agile Objects: Component-Based Inherent Survivability

    National Research Council Canada - National Science Library

    Chien, Andrew

    2003-01-01

    We have developed a framework called Agile Objects which leverages component object models and enables the construction of survivable systems that support increased application survivability through elusive technologies...

  6. Pneumocystis murina infection and cigarette smoke exposure interact to cause increased organism burden, development of airspace enlargement, and pulmonary inflammation in mice.

    Science.gov (United States)

    Christensen, Paul J; Preston, Angela M; Ling, Tony; Du, Ming; Fields, W Bradley; Curtis, Jeffrey L; Beck, James M

    2008-08-01

    Chronic obstructive pulmonary disease (COPD) is characterized by the presence of airflow obstruction and lung destruction with airspace enlargement. In addition to cigarette smoking, respiratory pathogens play a role in pathogenesis, but specific organisms are not always identified. Recent reports demonstrate associations between the detection of Pneumocystis jirovecii DNA in lung specimens or respiratory secretions and the presence of emphysema in COPD patients. Additionally, human immunodeficiency virus-infected individuals who smoke cigarettes develop early emphysema, but a role for P. jirovecii in pathogenesis remains speculative. We developed a new experimental model using immunocompetent mice to test the interaction of cigarette smoke exposure and environmentally acquired Pneumocystis murina infection in vivo. We hypothesized that cigarette smoke and P. murina would interact to cause increases in total lung capacity, airspace enlargement, and pulmonary inflammation. We found that exposure to cigarette smoke significantly increases the lung organism burden of P. murina. Pulmonary infection with P. murina, combined with cigarette smoke exposure, results in changes in pulmonary function and airspace enlargement characteristic of pulmonary emphysema. P. murina and cigarette smoke exposure interact to cause increased lung inflammatory cell accumulation. These findings establish a novel animal model system to explore the role of Pneumocystis species in the pathogenesis of COPD.

  7. Polyphenol Extracts from Punica granatum and Terminalia chebula are anti-inflammatory and increase the survival rate of chickens challenged with Escherichia coli

    Science.gov (United States)

    Avian pathogenic Escherichia coli (APEC) causes avian colibacillosis, inflammation in multi-organs of chickens, and results in serious economic loss to the chicken industry. Polyphenolic compounds possess a wide range of physiological activities that may contribute to their beneficial effects again...

  8. Increased expression of IRF8 in tumor cells inhibits the generation of Th17 cells and predicts unfavorable survival of diffuse large B cell lymphoma patients.

    Science.gov (United States)

    Zhong, Weijie; Xu, Xin; Zhu, Zhigang; Du, Qinghua; Du, Hong; Yang, Li; Ling, Yanying; Xiong, Huabao; Li, Qingshan

    2017-07-25

    The immunological pathogenesis of diffuse large B cell lymphoma (DLBCL) remains elusive. Searching for new prognostic markers of DLBCL is a crucial focal point for clinical scientists. The aim of the present study was to examine the prognostic value of interferon regulatory factor 8 (IRF8) expression and its effect on the development of Th17 cells in the tumor microenvironment of DLBCL patients. Flow cytometry, immunohistochemistry, and quantitative real-time PCR were used to detect the distribution of Th17 cells and related cytokines and IRF8 in tumor tissues from DLBCL patients. Two DLBCL cell lines (OCI-LY10 and OCI-LY1) with IRF8 knockdown or overexpression and two human B lymphoblast cell lines were co-cultured with peripheral blood mononuclear cells (PBMCs) in vitro to determine the effect of IRF8 on the generation of Th17 cells. Quantitative real-time PCR and Western blotting were used to investigate the involvement of retinoic acid receptor-related orphan receptor gamma t (RORγt) in the effect of IRF8 on Th17 cell generation. The survival of 67 DLBCL patients was estimated using the Kaplan-Meier method and log-rank analysis. The percentage of Th17 cells was lower in DLBCL tumor tissues than in PBMCs and corresponding adjacent benign tissues. Relative expression of interleukin (IL)-17A was lower, whereas that of interferon (IFN)-γ was higher in tumor tissues than in benign tissues. Co-culture with DLBCL cell lines inhibited the generation of Th17 cells in vitro. IRF8 upregulation was detected in DLBCL tumor tissues, and it was associated with decreased DLBCL patient survival. Investigation of the underlying mechanism suggested that IRF8 upregulation in DLBCL, through an unknown mechanism, inhibited Th17 cell generation by suppressing RORγt in neighboring CD4+ T cells. Tumor cells may express soluble or membrane-bound factors that inhibit the expression of RORγt in T cells within the tumor microenvironment. Our findings suggest that IRF8 expression could

  9. Intraspinal administration of human spinal cord-derived neural progenitor cells in the G93A-SOD1 mouse model of ALS delays symptom progression, prolongs survival and increases expression of endogenous neurotrophic factors.

    Science.gov (United States)

    Knippenberg, Sarah; Rath, Klaus Jan; Böselt, Sebastian; Thau-Habermann, Nadine; Schwarz, Sigrid C; Dengler, Reinhard; Wegner, Florian; Petri, Susanne

    2017-03-01

    Neural stem or progenitor cells are considered to be a novel therapeutic strategy for amyotrophic lateral sclerosis (ALS), based on their potential to generate a protective environment rather than to replace degenerating motor neurons. Following local injection to the spinal cord, neural progenitor cells may generate glial cells and release neurotrophic factors. In the present study, human spinal cord-derived neural progenitor cells (hscNPCs) were injected into the lumbar spinal cord of G93A-SOD1 ALS transgenic mice. We evaluated the potential effect of hscNPC treatment by survival analysis and behavioural/phenotypic assessments. Immunohistological and real-time PCR experiments were performed at a defined time point to study the underlying mechanisms. Symptom progression in hscNPC-injected mice was significantly delayed at the late stage of disease. On average, survival was only prolonged for 5 days. Animals treated with hscNPCs performed significantly better in motor function tests between weeks 18 and 19. Increased production of GDNF and IGF-1 mRNA was detectable in spinal cord tissue of hscNPC-treated mice. In summary, treatment with hscNPCs led to increased endogenous production of several growth factors and increased the preservation of innervated motor neurons but had only a small effect on overall survival. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  10. Survival of Low-pH Stress by Escherichia coli O157:H7: Correlation between Alterations in the Cell Envelope and Increased Acid Tolerance

    Science.gov (United States)

    Jordan, Kieran N.; Oxford, Lynn; O’Byrne, Conor P.

    1999-01-01

    Survival of a nontoxigenic isolate of Escherichia coli O157:H7 at low pH (pH 3.0) was examined over prolonged time periods for each of three population types: exponential-phase cells, stationary-phase cells, and acid-adapted exponential-phase cells. In each population, approximately 5 × 104 CFU ml−1 were detected after a 24-h incubation at pH 3.0. Even after 3 days at pH 3.0, significant numbers of survivors from each of the three populations could be detected. The high level of acid tolerance exhibited by these survivors was found to be quickly lost once they were transferred to conditions which permitted growth to resume, indicating that they were not mutants. Proton flux measurements on the three populations of cells revealed that the initial rates of viability loss at pH 3.0 correlated well with net proton accumulation. Cells showing a high initial rate of viability loss (exponential-phase cells) accumulated protons at the highest rate, whereas resistant populations (adapted or stationary-phase cells) accumulated protons only slowly. Differences in the protein composition of the cell envelope between the three populations were studied by two-dimensional polyacrylamide gel electrophoresis. Complex differences in the pattern of proteins expressed by each population were uncovered. The implications of these findings are discussed in the context of a possible model accounting for acid tolerance in this important food-borne pathogen. PMID:10388702

  11. The rs16906252:C>T SNP is not associated with increased overall survival or temozolomide response in a Han-Chinese glioma cohort.

    Directory of Open Access Journals (Sweden)

    Kuo-Chen Wei

    Full Text Available The methylation status of O-6-methylguanine-DNA methyltransferase (MGMT is associated with the prognosis in gliomas and in other cancers. Recent studies showed that rs16906252, an SNP in the MGMT promoter, is associated with promoter methylation and is a predictor of the overall survival time (OST and the response to temozolomide (TMZ treatment. However, these findings haven't been systematically investigated in the Han-Chinese population. We analyzed the relevance between rs16906252 polymorphisms, the MGMT methylation status, and the OST in 72 Han-Chinese gliomas patients. The MGMT promoter methylation was measured by bisulfite conversion followed by pyro-sequencing, while rs16906252 was measured by restriction endonuclease digestion. Contrary to the previous findings, we found no association between rs16906252 genotypes and promoter methylation on MGMT. The lower-grade glioma (LGGs patients carrying the C allele with rs16906252 showed a surprisingly better OST (P = 0.04. Furthermore, the LGG patients carrying hypo-methylated MGMT promoter and rs16906252 T allele showed significantly poorer prognosis. The prognostic benefit of MGMT promoter methylation and genotypes on gliomas patients is marginal. A new molecular stratified patient grouping of LGGs is potentially associated with poorer OST. Active MGMT might have a protective role in LGG tumors, enabling evolution to severe malignancy.

  12. [Increase in the incidence of invasive pneumococcal disease caused by serotype 19A prior to the implementation of the expanded pneumococcal vaccines].

    Science.gov (United States)

    González Martínez, F; Saavedra Lozano, J; Navarro Gómez, M L; Santos Sebastián, M M; Rodríguez Fernández, R; González Sánchez, M; Hernández-Sampelayo Matos, T

    2013-11-01

    To describe the epidemiology, clinical syndromes and microbiological characteristics of serotype 19A as the main cause of invasive pneumococcal disease (IPD) in children admitted to a tertiary hospital in Spain. A retrospective (1998-2004) and prospective (2005-2009) study was conducted on children with IPD produced by serotype 19A. The study was divided into three periods (P): P1 (1998-2001) when PCV7 had not been commercialized; P2 (2002-2005) with 40% vaccine coverage among children; and P3 (2006-2009) when the vaccine was added to the Childhood Immunization Schedule in Madrid. A total of 155 isolates of Streptococcus pneumoniae (SP) producing IPD were analysed, with 21 of them being serotype 19A (14%). An increased prevalence of serotype 19A was found: 2/45 cases (4.4%) in P1, 3/41 cases (7.3%) in P2 and 16/69 cases (23.2%) in P3. It occurred mostly in children younger than 2 years (16/21; 76%). This serotype was the main cause of meningitis (5/20; 25%), pleural empyema (3/22; 14%) and bacteraemic mastoiditis (2/4; 50%). Thirteen isolates (61.5%) had an MIC ≥ 0.12μ/ml for penicillin in extra-meningeal infections, and 3 of the 5 isolates causing meningitis (60%) had an MIC ≥ 1μ/ml for cefotaxime. Serotype 19A was the main causal agent of IPD in the PCV7 era (P3), with high antibiotic resistance rates. This serotype was responsible for all types of IPD, being the main cause of meningitis. Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  13. Increased fluoro-deoxy-D-glucose uptake on positron emission tomography-computed tomography postbronchoalveolar lavage: a potential cause of radiologic misinterpretation.

    LENUS (Irish Health Repository)

    Leong, Sum

    2011-08-01

    Cytologic analysis of bronchoalveolar lavage (BAL) fluid is used for lung cancer diagnosis. We describe a patient with a history of rectal carcinoma who presented with a new lung mass. BAL was performed, with positron emission tomography-computed tomography the following day. There was mildly increased fluoro-deoxy-D-glucose uptake in areas of the lung parenchyma with new ground-glass opacification. This created ambiguity in staging, clarified 2 weeks later by a computed tomography showing complete resolution of the ground-glass opacity. Clinicians should be aware that BAL may cause increased pulmonary fluoro-deoxy-D-glucose uptake, making accurate radiologic interpretation problematic. We suggest that to optimize positron emission tomography-computed tomography, studies should not be performed within 24 hours of BAL.

  14. Sensitivity of spiral ganglion neurons to damage caused by mobile phone electromagnetic radiation will increase in lipopolysaccharide-induced inflammation in vitro model.

    Science.gov (United States)

    Zuo, Wen-Qi; Hu, Yu-Juan; Yang, Yang; Zhao, Xue-Yan; Zhang, Yuan-Yuan; Kong, Wen; Kong, Wei-Jia

    2015-05-29

    With the increasing popularity of mobile phones, the potential hazards of radiofrequency electromagnetic radiation (RF-EMR) on the auditory system remain unclear. Apart from RF-EMR, humans are also exposed to various physical and chemical factors. We established a lipopolysaccharide (LPS)-induced inflammation in vitro model to investigate whether the possible sensitivity of spiral ganglion neurons to damage caused by mobile phone electromagnetic radiation (at specific absorption rates: 2, 4 W/kg) will increase. Spiral ganglion neurons (SGN) were obtained from neonatal (1- to 3-day-old) Sprague Dawley® (SD) rats. After the SGN were treated with different concentrations (0, 20, 40, 50, 100, 200, and 400 μg/ml) of LPS, the Cell Counting Kit-8 (CCK-8) and alkaline comet assay were used to quantify cellular activity and DNA damage, respectively. The SGN were treated with the moderate LPS concentrations before RF-EMR exposure. After 24 h intermittent exposure at an absorption rate of 2 and 4 W/kg, DNA damage was examined by alkaline comet assay, ultrastructure changes were detected by transmission electron microscopy, and expression of the autophagy markers LC3-II and Beclin1 were examined by immunofluorescence and confocal laser scanning microscopy. Reactive oxygen species (ROS) production was quantified by the dichlorofluorescin-diacetate assay. LPS (100 μg/ml) induced DNA damage and suppressed cellular activity (P 0.05); therefore, 40 μg/ml was used to pretreat the concentration before exposure to RF-EMR. RF-EMR could not directly induce DNA damage. However, the 4 W/kg combined with LPS (40 μg/ml) group showed mitochondria vacuoles, karyopyknosis, presence of lysosomes and autophagosome, and increasing expression of LC3-II and Beclin1. The ROS values significantly increased in the 4 W/kg exposure, 4 W/kg combined with LPS (40 μg/ml) exposure, and H2O2 groups (P electromagnetic radiation could not directly induce DNA damage in normal spiral ganglion neurons, but

  15. RX-207, a Small Molecule Inhibitor of Protein Interaction with Glycosaminoglycans (SMIGs), Reduces Experimentally Induced Inflammation and Increases Survival Rate in Cecal Ligation and Puncture (CLP)-Induced Sepsis.

    Science.gov (United States)

    Juhas, Stefan; Harris, Nicholas; Il'kova, Gabriela; Rehák, Pavol; Zsila, Ferenc; Yurgenzon Kogan, Faina; Lahmy, Orly; Zhuk, Regina; Gregor, Paul; Koppel, Juraj

    2018-02-01

    The fused quinazolinone derivative, RX-207, is chemically and functionally related to small molecule inhibitors of protein binding to glycosaminoglycans (SMIGs). Composed of a planar aromatic amine scaffold, it inhibits protein binding to glycosaminoglycans (GAGs). RX-207 reduced neutrophil migration in thioglycollate-induced peritonitis (37%), inhibited carrageenan-induced paw edema (32%) and cerulein-induced pancreatitis (28%), and increased animal survival in the mouse model of cecal ligation and puncture (CLP)-induced sepsis (60%). The mechanism of RX-207 action, analyzed by UV spectroscopy, confirmed that which was elucidated for chemically related anti-inflammatory SMIGs. RX-207 binding to cell surface GAGs can account for the inhibition of neutrophil recruitment via the micro-vasculature and as a consequence, the reduction of neutrophil mediated tissue damage in the animal models of inflammation and improved survival of mice in CLP-induced sepsis.

  16. Modelling survival

    DEFF Research Database (Denmark)

    Ashauer, Roman; Albert, Carlo; Augustine, Starrlight

    2016-01-01

    well GUTS, calibrated with short-term survival data of Gammarus pulex exposed to four pesticides, can forecast effects of longer-term pulsed exposures. Thirdly, we tested the ability of GUTS to estimate 14-day median effect concentrations of malathion for a range of species and use these estimates...

  17. Survival Analysis

    CERN Document Server

    Miller, Rupert G

    2011-01-01

    A concise summary of the statistical methods used in the analysis of survival data with censoring. Emphasizes recently developed nonparametric techniques. Outlines methods in detail and illustrates them with actual data. Discusses the theory behind each method. Includes numerous worked problems and numerical exercises.

  18. Rituximab induction therapy, survival benefits, and the increasing selection of radiotherapy as the postinduction treatment in patients with primary mediastinal large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Sheng-Hsiang Yang

    2015-07-01

    Conclusion: Rituximab improved the CR and OS rates of patients with PMBCL, but these improvements may be attributable to the increased use of radiotherapy (which may have also resulted from FDG-PET evaluation.

  19. Ensuring survival.

    Science.gov (United States)

    Sadik, N

    1992-12-01

    The global population growth rate has been 1.7% since 1975, while for developing countries it is 2.1%. UN projections are for population to grow from 5.5 billion in 1992 to 10 billion by 2050. Sustainable development is only possible when population growth is balanced with available resources. UN medium population projections of 7.8 billion by 2050 can be reached with 187 million more couples practicing family planning (FP) by the year 2000. Within the past 20 years, 1 billion people, mostly from developed countries, have enjoyed economic growth, but have contributed polluting technologies, excessive waste, and environmentally dangerous economic practices. The generations to come will be affected by the continuance of these practices by the 1 billion affluent population. The bottom billion are mired in poverty and high population growth and survival, needs that hinder their country's economic development, upset fragile ecosystems, and destroy the balance between human beings and the environment. International migration on a large scale could be the by-product of population growth. Progress has been made since the 1974 UN Conference on Population in Bucharest. There are still, however, vulnerable populations, the poorest households, the landless and small-holder families, urban squatters and slum dwellers, those living in low lying deltas and along coasts, and women. Women control family resources and their micro environment. Sustainable development is not possible without the elimination of prejudice against women. Reproductive freedom for women must be a priority. High quality, readily available FP services are also needed for those desiring this. The difficulty is in providing FP services that conform to a woman's social and cultural background and personal needs; success is dependent on involving women in the process and holding men more responsible for FP. Development means allowing for the legitimate aspirations of the majority not just the specialized

  20. Loss of VPS13C Function in Autosomal-Recessive Parkinsonism Causes Mitochondrial Dysfunction and Increases PINK1/Parkin-Dependent Mitophagy

    Science.gov (United States)

    Lesage, Suzanne; Drouet, Valérie; Majounie, Elisa; Deramecourt, Vincent; Jacoupy, Maxime; Nicolas, Aude; Cormier-Dequaire, Florence; Hassoun, Sidi Mohamed; Pujol, Claire; Ciura, Sorana; Erpapazoglou, Zoi; Usenko, Tatiana; Maurage, Claude-Alain; Sahbatou, Mourad; Liebau, Stefan; Ding, Jinhui; Bilgic, Basar; Emre, Murat; Erginel-Unaltuna, Nihan; Guven, Gamze; Tison, François; Tranchant, Christine; Vidailhet, Marie; Corvol, Jean-Christophe; Krack, Paul; Leutenegger, Anne-Louise; Nalls, Michael A.; Hernandez, Dena G.; Heutink, Peter; Gibbs, J. Raphael; Hardy, John; Wood, Nicholas W.; Gasser, Thomas; Durr, Alexandra; Deleuze, Jean-François; Tazir, Meriem; Destée, Alain; Lohmann, Ebba; Kabashi, Edor; Singleton, Andrew; Corti, Olga; Brice, Alexis; Lesage, Suzanne; Tison, François; Vidailhet, Marie; Corvol, Jean-Christophe; Agid, Yves; Anheim, Mathieu; Bonnet, Anne-Marie; Borg, Michel; Broussolle, Emmanuel; Damier, Philippe; Destée, Alain; Dürr, Alexandra; Durif, Franck; Krack, Paul; Klebe, Stephan; Lohmann, Ebba; Martinez, Maria; Pollak, Pierre; Rascol, Olivier; Tranchant, Christine; Vérin, Marc; Viallet, François; Brice, Alexis; Lesage, Suzanne; Majounie, Elisa; Tison, François; Vidailhet, Marie; Corvol, Jean Christophe; Nalls, Michael A.; Hernandez, Dena G.; Gibbs, J. Raphael; Dürr, Alexandra; Arepalli, Sampath; Barker, Roger A.; Ben-Shlomo, Yoav; Berg, Daniela; Bettella, Francesco; Bhatia, Kailash; de Bie, Rob M.A.; Biffi, Alessandro; Bloem, Bastiaan R.; Bochdanovits, Zoltan; Bonin, Michael; Lesage, Suzanne; Tison, François; Vidailhet, Marie; Corvol, Jean-Christophe; Agid, Yves; Anheim, Mathieu; Bonnet, Anne-Marie; Borg, Michel; Broussolle, Emmanuel; Damier, Philippe; Destée, Alain; Dürr, Alexandra; Durif, Franck; Krack, Paul; Klebe, Stephan; Lohmann, Ebba; Martinez, Maria; Pollak, Pierre; Rascol, Olivier; Tranchant, Christine; Vérin, Marc; Bras, Jose M.; Brockmann, Kathrin; Brooks, Janet; Burn, David J.; Charlesworth, Gavin; Chen, Honglei; Chinnery, Patrick F.; Chong, Sean; Clarke, Carl E.; Cookson, Mark R.; Counsell, Carl; Damier, Philippe; Dartigues, Jean-François; Deloukas, Panos; Deuschl, Günther; Dexter, David T.; van Dijk, Karin D.; Dillman, Allissa; Dong, Jing; Durif, Frank; Edkins, Sarah; Escott-Price, Valentina; Evans, Jonathan R.; Foltynie, Thomas; Gao, Jianjun; Gardner, Michelle; Goate, Alison; Gray, Emma; Guerreiro, Rita; Harris, Clare; van Hilten, Jacobus J.; Hofman, Albert; Hollenbeck, Albert; Holmans, Peter; Holton, Janice; Hu, Michèle; Huang, Xuemei; Huber, Heiko; Hudson, Gavin; Hunt, Sarah E.; Huttenlocher, Johanna; Illig, Thomas; Jónsson, Pálmi V.; Kilarski, Laura L.; Jansen, Iris E.; Lambert, Jean-Charles; Langford, Cordelia; Lees, Andrew; Lichtner, Peter; Limousin, Patricia; Lopez, Grisel; Lorenz, Delia; Lubbe, Steven; Lungu, Codrin; Martinez, María; Mätzler, Walter; McNeill, Alisdair; Moorby, Catriona; Moore, Matthew; Morrison, Karen E.; Mudanohwo, Ese; O’Sullivan, Sean S.; Owen, Michael J.; Pearson, Justin; Perlmutter, Joel S.; Pétursson, Hjörvar; Plagnol, Vincent; Pollak, Pierre; Post, Bart; Potter, Simon; Ravina, Bernard; Revesz, Tamas; Riess, Olaf; Rivadeneira, Fernando; Rizzu, Patrizia; Ryten, Mina; Saad, Mohamad; Simón-Sánchez, Javier; Sawcer, Stephen; Schapira, Anthony; Scheffer, Hans; Schulte, Claudia; Sharma, Manu; Shaw, Karen; Sheerin, Una-Marie; Shoulson, Ira; Shulman, Joshua; Sidransky, Ellen; Spencer, Chris C.A.; Stefánsson, Hreinn; Stefánsson, Kári; Stockton, Joanna D.; Strange, Amy; Talbot, Kevin; Tanner, Carlie M.; Tashakkori-Ghanbaria, Avazeh; Trabzuni, Daniah; Traynor, Bryan J.; Uitterlinden, André G.; Velseboer, Daan; Walker, Robert; van de Warrenburg, Bart; Wickremaratchi, Mirdhu; Williams-Gray, Caroline H.; Winder-Rhodes, Sophie; Wurster, Isabel; Williams, Nigel; Morris, Huw R.; Heutink, Peter; Hardy, John; Wood, Nicholas W.; Gasser, Thomas; Singleton, Andrew B.; Brice, Alexis

    2016-01-01

    Autosomal-recessive early-onset parkinsonism is clinically and genetically heterogeneous. The genetic causes of approximately 50% of autosomal-recessive early-onset forms of Parkinson disease (PD) remain to be elucidated. Homozygozity mapping and exome sequencing in 62 isolated individuals with early-onset parkinsonism and confirmed consanguinity followed by data mining in the exomes of 1,348 PD-affected individuals identified, in three isolated subjects, homozygous or compound heterozygous truncating mutations in vacuolar protein sorting 13C (VPS13C). VPS13C mutations are associated with a distinct form of early-onset parkinsonism characterized by rapid and severe disease progression and early cognitive decline; the pathological features were striking and reminiscent of diffuse Lewy body disease. In cell models, VPS13C partly localized to the outer membrane of mitochondria. Silencing of VPS13C was associated with lower mitochondrial membrane potential, mitochondrial fragmentation, increased respiration rates, exacerbated PINK1/Parkin-dependent mitophagy, and transcriptional upregulation of PARK2 in response to mitochondrial damage. This work suggests that loss of function of VPS13C is a cause of autosomal-recessive early-onset parkinsonism with a distinctive phenotype of rapid and severe progression. PMID:26942284

  1. Prolonged consumption of flaxseed flour increases the 17β-estradiol hormone without causing adverse effects on the histomorphology of Wistar rats' penis.

    Science.gov (United States)

    Cardozo, Ludmila Ferreira Medeiros de França; Boaventura, Gilson Teles; Brant, Lívia Hipólito Cardozo; Pereira, Vivian Alves; Velarde, Luis Guillermo Coca; Chagas, Maurício Alves

    2012-11-01

    Consumption of foods rich in phytoestrogens such as flaxseed has increased due to its chemoprotective effects, especially those related to the cardiovascular system. The flaxseed has components that can interfere with development of male reproductive system. This study aims to investigate the possible effects of prolonged consumption of flaxseed flour on hormonal and histomorphologic penis parameters of adult Wistar rats. Rat dams were divided into two groups during lactation period: the control group that was fed with diet based on casein and the flaxseed group that was fed with diet based on casein containing 25% of flaxseed . At weaning, 10 male offspring from each group continued to receive the experimental diets until 250 days old. Rats fed with diet containing flaxseed showed increased concentrations of 17β-estradiol (p=0.01) but no changes in testosterone concentrations. With regard to histomorphometric analysis of the penis, supplemented rats had lower values for the total area of the corpus spongiosum (p=0.01). All other analyzed parameters wer e similar as the control. Results showed that the use of flaxseed flour did not cause adverse effects on the penis morphology but increases the 17β-estradiol hormone, when consumed in integral form for a prolonged period. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Transiently increasing cAMP levels selectively in hippocampal excitatory neurons during sleep deprivation prevents memory deficits caused by sleep loss.

    Science.gov (United States)

    Havekes, Robbert; Bruinenberg, Vibeke M; Tudor, Jennifer C; Ferri, Sarah L; Baumann, Arnd; Meerlo, Peter; Abel, Ted

    2014-11-19

    The hippocampus is particularly sensitive to sleep loss. Although previous work has indicated that sleep deprivation impairs hippocampal cAMP signaling, it remains to be determined whether the cognitive deficits associated with sleep deprivation are caused by attenuated cAMP signaling in the hippocampus. Further, it is unclear which cell types are responsible for the memory impairments associated with sleep deprivation. Transgenic approaches lack the spatial resolution to manipulate specific signaling pathways selectively in the hippocampus, while pharmacological strategies are limited in terms of cell-type specificity. Therefore, we used a pharmacogenetic approach based on a virus-mediated expression of a Gαs-coupled Drosophila octopamine receptor selectively in mouse hippocampal excitatory neurons in vivo. With this approach, a systemic injection with the receptor ligand octopamine leads to increased cAMP levels in this specific set of hippocampal neurons. We assessed whether transiently increasing cAMP levels during sleep deprivation prevents memory consolidation deficits associated with sleep loss in an object-location task. Five hours of total sleep deprivation directly following training impaired the formation of object-location memories. Transiently increasing cAMP levels in hippocampal neurons during the course of sleep deprivation prevented these memory consolidation deficits. These findings demonstrate that attenuated cAMP signaling in hippocampal excitatory neurons is a critical component underlying the memory deficits in hippocampus-dependent learning tasks associated with sleep deprivation. Copyright © 2014 the authors 0270-6474/14/3415715-07$15.00/0.

  3. Subacute Zinc Administration and L-NAME Caused an Increase of NO, Zinc, Lipoperoxidation, and Caspase-3 during a Cerebral Hypoxia-Ischemia Process in the Rat

    Science.gov (United States)

    Blanco-Alvarez, Victor Manuel; Lopez-Moreno, Patricia; Soto-Rodriguez, Guadalupe; Martinez-Fong, Daniel; Rubio, Hector; Gonzalez-Barrios, Juan Antonio; Piña-Leyva, Celia; Torres-Soto, Maricela; Gomez-Villalobos, María de Jesus; Hernandez-Baltazar, Daniel; Eguibar, José Ramon; Ugarte, Araceli; Cebada, Jorge

    2013-01-01

    Zinc or L-NAME administration has been shown to be protector agents, decreasing oxidative stress and cell death. However, the treatment with zinc and L-NAME by intraperitoneal injection has not been studied. The aim of our work was to study the effect of zinc and L-NAME administration on nitrosative stress and cell death. Male Wistar rats were treated with ZnCl2 (2.5 mg/kg each 24 h, for 4 days) and N-ω-nitro-L-arginine-methyl ester (L-NAME, 10 mg/kg) on the day 5 (1 hour before a common carotid-artery occlusion (CCAO)). The temporoparietal cortex and hippocampus were dissected, and zinc, nitrites, and lipoperoxidation were assayed at different times. Cell death was assayed by histopathology using hematoxylin-eosin staining and caspase-3 active by immunostaining. The subacute administration of zinc before CCAO decreases the levels of zinc, nitrites, lipoperoxidation, and cell death in the late phase of the ischemia. L-NAME administration in the rats treated with zinc showed an increase of zinc levels in the early phase and increase of zinc, nitrites, and lipoperoxidation levels, cell death by necrosis, and the apoptosis in the late phase. These results suggest that the use of these two therapeutic strategies increased the injury caused by the CCAO, unlike the alone administration of zinc. PMID:23997853

  4. Subacute Zinc Administration and L-NAME Caused an Increase of NO, Zinc, Lipoperoxidation, and Caspase-3 during a Cerebral Hypoxia-Ischemia Process in the Rat

    Directory of Open Access Journals (Sweden)

    Victor Manuel Blanco-Alvarez

    2013-01-01

    Full Text Available Zinc or L-NAME administration has been shown to be protector agents, decreasing oxidative stress and cell death. However, the treatment with zinc and L-NAME by intraperitoneal injection has not been studied. The aim of our work was to study the effect of zinc and L-NAME administration on nitrosative stress and cell death. Male Wistar rats were treated with ZnCl2 (2.5 mg/kg each 24 h, for 4 days and N-ω-nitro-L-arginine-methyl ester (L-NAME, 10 mg/kg on the day 5 (1 hour before a common carotid-artery occlusion (CCAO. The temporoparietal cortex and hippocampus were dissected, and zinc, nitrites, and lipoperoxidation were assayed at different times. Cell death was assayed by histopathology using hematoxylin-eosin staining and caspase-3 active by immunostaining. The subacute administration of zinc before CCAO decreases the levels of zinc, nitrites, lipoperoxidation, and cell death in the late phase of the ischemia. L-NAME administration in the rats treated with zinc showed an increase of zinc levels in the early phase and increase of zinc, nitrites, and lipoperoxidation levels, cell death by necrosis, and the apoptosis in the late phase. These results suggest that the use of these two therapeutic strategies increased the injury caused by the CCAO, unlike the alone administration of zinc.

  5. Polyphenol extracts from Punica granatum and Terminalia chebula are anti-inflammatory and increase the survival rate of chickens challenged with Escherichia coli.

    Science.gov (United States)

    Zhong, Xinlu; Shi, Yaran; Chen, Jiajia; Xu, Jianqing; Wang, Lei; Beier, Ross C; Hou, Xiaolin; Liu, Fenghua

    2014-01-01

    Avian pathogenic Escherichia coli (APEC) causes inflammation in multiple organs of chickens called avian colibacillosis, and results in serious economic loss to the chicken industry. Polyphenolic compounds possess a wide range of physiological activities that may contribute to their beneficial effects against inflammation-related diseases. In this study, the curative effect and mechanism of action of the polyphenolic extracts from Punica granatum L. and Terminalia chebula Retz. in chickens challenged with APEC were studied. Specific-pathogen-free white Leghorn chickens (males, 21-d old) were challenged with APEC and then given oral administration of extracts of P. granatum and T. chebula. The extracts decreased the morbidity and inflammation induced by APEC. Data from quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay showed that the extracts of P. granatum and T. chebula polyphenols (GCP) reversed the over-expression genes of the Toll-like receptor (TLR) 2, 4, and 5, down-regulated the activation of nuclear factor-kappa B signal transduction pathways, and inhibited the production of pro-inflammatory cytokines. Naturally occurring GCP may be a potential alternative medicine for the prevention or treatment of avian colibacillosis.

  6. Increases in tibial force imbalance but not changes in tibiofemoral laxities are caused by varus-valgus malalignment of the femoral component in kinematically aligned TKA.

    Science.gov (United States)

    Riley, Jeremy; Roth, Joshua D; Howell, Stephen M; Hull, Maury L

    2018-01-29

    The purposes of this study were to quantify the increase in tibial force imbalance (i.e. magnitude of difference between medial and lateral tibial forces) and changes in laxities caused by 2° and 4° of varus-valgus (V-V) malalignment of the femoral component in kinematically aligned total knee arthroplasty (TKA) and use the results to detemine sensitivities to errors in making the distal femoral resections. Because V-V malalignment would introduce the greatest changes in the alignment of the articular surfaces at 0° flexion, the hypotheses were that the greatest increases in tibial force imbalance would occur at 0° flexion, that primarily V-V laxity would significantly change at this flexion angle, and that the tibial force imbalance would increase and laxities would change in proportion to the degree of V-V malalignment. Kinematically aligned TKA was performed on ten human cadaveric knee specimens using disposable manual instruments without soft tissue release. One 3D-printed reference femoral component, with unmodified geometry, was aligned to restore the native distal and posterior femoral joint lines. Four 3D-printed femoral components, with modified geometry, introduced V-V malalignments of 2° and 4° from the reference component. Medial and lateral tibial forces were measured during passive knee flexion-extension between 0° to 120° using a custom tibial force sensor. Eight laxities were measured from 0° to 120° flexion using a six degree-of-freedom load application system. With the tibial component kinematically aligned, the increase in the tibial force imbalance from that of the reference component at 0° of flexion was sensitive to the degree of V-V malalignment of the femoral component. Sensitivities were 54 N/deg (medial tibial force increasing > lateral tibial force) (p  medial tibial force) (p varus and valgus malalignments, respectively. Varus-valgus malalignment did not significantly change varus, internal-external rotation

  7. Chronic restraint stress causes a delayed increase in responding for palatable food cues during forced abstinence via a dopamine D1-like receptor-mediated mechanism.

    Science.gov (United States)

    Ball, Kevin T; Best, Olivia; Luo, Jonathan; Miller, Leah R

    2017-02-15

    Relapse to unhealthy eating habits in dieters is often triggered by stress. Animal models, moreover, have confirmed a causal role for acute stress in relapse. The role of chronic stress in relapse vulnerability, however, has received relatively little attention. Therefore, in the present study, we used an abstinence-based relapse model in rats to test the hypothesis that exposure to chronic stress increases subsequent relapse vulnerability. Rats were trained to press a lever for highly palatable food reinforcers in daily 3-h sessions and then tested for food seeking (i.e., responding for food associated cues) both before and after an acute or chronic restraint stress procedure (3h/day×1day or 10days, respectively) or control procedure (unstressed). The second food seeking test was conducted either 1day or 7days after the last restraint. Because chronic stress causes dopamine D1-like receptor-mediated alterations in prefrontal cortex (a relapse node), we also assessed dopaminergic involvement by administering either SCH-23390 (10.0μg/kg; i.p.), a dopamine D1-like receptor antagonist, or vehicle prior to daily treatments. Results showed that chronically, but not acutely, stressed rats displayed increased food seeking 7days, but not 1day, after the last restraint. Importantly, SCH-23390 combined with chronic stress reversed this effect. These results suggest that drugs targeting D 1 -like receptors during chronic stress may help to prevent future relapse in dieters. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Disruption of the AMPK-TBC1D1 nexus increases lipogenic gene expression and causes obesity in mice via promoting IGF1 secretion.

    Science.gov (United States)

    Chen, Liang; Chen, Qiaoli; Xie, Bingxian; Quan, Chao; Sheng, Yang; Zhu, Sangsang; Rong, Ping; Zhou, Shuilian; Sakamoto, Kei; MacKintosh, Carol; Wang, Hong Yu; Chen, Shuai

    2016-06-28

    Tre-2/USP6, BUB2, cdc16 domain family member 1 (the TBC domain is the GTPase activating protein domain) (TBC1D1) is a Rab GTPase activating protein that is phosphorylated on Ser(231) by the AMP-activated protein kinase (AMPK) in response to intracellular energy stress. However, the in vivo role and importance of this phosphorylation event remains unknown. To address this question, we generated a mouse model harboring a TBC1D1(Ser231Ala) knockin (KI) mutation and found that the KI mice developed obesity on a normal chow diet. Mechanistically, TBC1D1 is located on insulin-like growth factor 1 (IGF1) storage vesicles, and the KI mutation increases endocrinal and paracrinal/autocrinal IGF1 secretion in an Rab8a-dependent manner. Hypersecretion of IGF1 causes increased expression of lipogenic genes via activating the protein kinase B (PKB; also known as Akt)-mammalian target of rapamycin (mTOR) pathway in adipose tissues, which contributes to the development of obesity, diabetes, and hepatic steatosis as the KI mice age. Collectively, these findings demonstrate that the AMPK-TBC1D1 signaling nexus interacts with the PKB-mTOR pathway via IGF1 secretion, which consequently controls expression of lipogenic genes in the adipose tissue. These findings also have implications for drug discovery to combat obesity.

  9. Increased NT-proANP predicts risk of congestive heart failure in Cavalier King Charles spaniels with mitral regurgitation caused by myxomatous valve disease.

    Science.gov (United States)

    Eriksson, Anders S; Häggström, Jens; Pedersen, Henrik Duelund; Hansson, Kerstin; Järvinen, Anna-Kaisa; Haukka, Jari; Kvart, Clarence

    2014-09-01

    To evaluate the predictive value of plasma N-terminal pro-atrial natriuretic peptide (NT-proANP) and nitric oxide end-products (NOx) as markers for progression of mitral regurgitation caused by myxomatous mitral valve disease. Seventy-eight privately owned Cavalier King Charles spaniels with naturally occurring myxomatous mitral valve disease. Prospective longitudinal study comprising 312 measurements over a 4.5 year period. Clinical values were recorded, NT-proANP concentrations were measured by radioimmunoassay, and NOx were analyzed colorimetrically. To predict congestive heart failure (CHF), Cox proportional hazards models with time-varying covariates were constructed. The hazard ratio for NT-proANP (per 1000 pmol/l increase) to predict future CHF was 6.7 (95% confidence interval, 3.6-12.5; p 1000 pmol/l was 11 months (95% confidence interval, 5.6-12.6 months), compared to 54 months (46 - infinity) for dogs with concentrations ≤ 1000 pmol/l (p 130 beats per minute) and grade of murmur (≥ 3/6). The risk of CHF due to mitral regurgitation is increased in dogs with blood NT-proANP concentrations above 1000 pmol/l. Measurement of NT-proANP can be a valuable tool to identify dogs that may develop CHF within months. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Increasing losses caused by natural disasters: what are the drivers, how is the insurance industry affected, what has to be done?

    Science.gov (United States)

    Hoppe, P.

    2016-12-01

    Losses caused by natural disasters are a major factor influencing the balance sheet of insurers, especially reinsurers. Such events have a high potential of creating extreme accumulation losses by affecting different business lines at the same time. The basis for long term profitable business in the insurance industry is to be able to calculate and also get risk adequate premiums for the covers of natural perils. Risk adequate means that on average over several years the losses occurring can be paid by the premium income. Losses caused by natural disasters have increased tremendously worldwide in the last decades. The main drivers have been changes in the exposed values, i.e. growth of population and wealth in affected regions. For the insurance industry this loss increasing process in general is not a problem as the premiums normally are proportional to the sum insured, i.e. the exposed value. These factors can be quantified and the loss trends can be adjusted for these changes. Munich Re just recently has developed a very sophisticated method for such a normalisation of losses. After this normalization in respect to exposed values a still residual loss trend can be either driven by changes in the vulnerability of assets or on the hazard side. Trends in both factors are not automatically considered in the premiums, they have to be detected, quantified and then built into the risk models of the insurers. Many studies as well as data from the Munich Re NatCatSERVICE suggest that weather related hazards already have changed for some perils and in some regions. Climate research implies that due to global warming such trends will increase in the coming decades. Very little quantitative data, however, on such changes still is available to allow the adjustment of the risk models of insurers. In order to do this, data with high regional resolution and also probabilities of