23 research outputs found

    Pattern and determinants of BCG immunisation delays in a sub-Saharan African community

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Childhood immunisation is recognised worldwide as an essential component of health systems and an indispensable indicator of quality of care for vaccine-preventable diseases. While performance of immunisation programmes is more commonly measured by coverage, ensuring that every child is immunised at the earliest/appropriate age is an important public health goal. This study therefore set out to determine the pattern and predictors of Bacille de Calmette-Guérin (BCG) immunisation delays in the first three months of life in a Sub-Saharan African community where BCG is scheduled at birth in order to facilitate necessary changes in current policy and practices for improved services.</p> <p>Methods</p> <p>A cross-sectional study in which immunisation delays among infants aged 0-3 months attending community-based BCG clinics in Lagos, Nigeria over a 2-year period from July 2005 to June 2007 were assessed by survival analysis and associated factors determined by multivariable logistic regression. Population attributable risk (PAR) was computed for the predictors of delays.</p> <p>Results</p> <p>BCG was delayed beyond three months in 31.6% of all eligible infants. Of 5171 infants enrolled, 3380 (65.4%) were immunised within two weeks and a further 1265 (24.5%) by six weeks. A significantly higher proportion of infants born in hospitals were vaccinated in the first six weeks compared to those born outside hospitals. Undernourishment was predictive of delays beyond 2 and 6 weeks while treated hyperbilirubinaemia was associated with decreased odds for any delays. Lack of antenatal care and multiple gestations were also predictive of delays beyond 6 weeks. Undernourishment was associated with the highest PAR for delays beyond 2 weeks (18.7%) and 6 weeks (20.8%).</p> <p>Conclusions</p> <p>BCG immunisation is associated with significant delays in this setting and infants at increased risk of delays can be identified and supported early possibly through improved maternal uptake of antenatal care. Combining BCG with subsequent immunisation(s) at 6 weeks for infants who missed the BCG may be considered.</p

    Equine Torovirus (BEV) Induces Caspase-Mediated Apoptosis in Infected Cells

    Get PDF
    Toroviruses are gastroenteritis causing agents that infect different animal species and humans. To date, very little is known about how toroviruses cause disease. Here, we describe for the first time that the prototype member of this genus, the equine torovirus Berne virus (BEV), induces apoptosis in infected cells at late times postinfection. Observation of BEV infected cells by electron microscopy revealed that by 24 hours postinfection some cells exhibited morphological characteristics of apoptotic cells. Based on this finding, we analyzed several apoptotic markers, and observed protein synthesis inhibition, rRNA and DNA degradation, nuclear fragmentation, caspase-mediated cleavage of PARP and eIF4GI, and PKR and eIF2α phosphorylation, all these processes taking place after peak virus production. We also determined that both cell death receptor and mitochondrial pathways are involved in the apoptosis process induced by BEV. BEV-induced apoptosis at late times postinfection, once viral progeny are produced, could facilitate viral dissemination in vivo and contribute to viral pathogenesis

    Nitric Oxide Controls Constitutive Freezing Tolerance in Arabidopsis by Attenuating the Levels of Osmoprotectants, Stress-Related Hormones and Anthocyanins

    Full text link
    [EN] Plant tolerance to freezing temperatures is governed by endogenous constitutive components and environmental inducing factors. Nitric oxide (NO) is one of the endogenous components that participate in freezing tolerance regulation. A combined metabolomic and transcriptomic characterization of NO-deficient nia1,2noa1¿2 mutant plants suggests that NO acts attenuating the production and accumulation of osmoprotective and regulatory metabolites, such as sugars and polyamines, stress-related hormones, such as ABA and jasmonates, and antioxidants, such as anthocyanins and flavonoids. Accordingly, NO-deficient plants are constitutively more freezing tolerant than wild type plants.This work was supported by grants BIO2011-27526 and BIO2014-56067-P from the Spanish Ministry of Economy and Competitiveness and FEDER funds. We thank support and comments from Janice Jones and Danny Alexander (Metabolon Inc., USA) on metabolomic analyses.Costa-Broseta, Á.; Perea-Resa, C.; Castillo López Del Toro, MC.; Ruíz, MF.; Salinas, J.; Leon Ramos, J. (2018). Nitric Oxide Controls Constitutive Freezing Tolerance in Arabidopsis by Attenuating the Levels of Osmoprotectants, Stress-Related Hormones and Anthocyanins. Scientific Reports. 8. https://doi.org/10.1038/s41598-018-27668-8S8Janská, A., Marsík, P., Zelenková, S. & Ovesná, J. Cold stress and acclimation - what is important for metabolic adjustment? Plant Biol (Stuttg) 12, 395–405 (2010).Eremina, M., Rozhon, W. & Poppenberger, B. Hormonal control of cold stress responses in plants. Cell Mol Life Sci 73, 797–810 (2016).Winkel-Shirley, B. Biosynthesis of flavonoids and effects of stress. Curr Opin Plant Biol 5, 218–223 (2002).Cuevas, J. C. et al. Putrescine is involved in Arabidopsis freezing tolerance and cold acclimation by regulating abscisic acid levels in response to low temperature. Plant Physiol 148, 1094–105 (2008).Chen, M. & Thelen, J. J. Acyl-lipid desaturase 1 primes cold acclimation response in Arabidopsis. Physiol Plant 158, 11–22 (2016).Takahashi, D., Kawamura, Y. & Uemura, M. Cold acclimation is accompanied by complex responses of glycosylphosphatidylinositol (GPI)-anchored proteins in Arabidopsis. J Exp Bot 67, 5203–5215 (2016).van Buer, J., Cvetkovic, J. & Baier, M. Cold regulation of plastid ascorbate peroxidases serves as a priming hub controlling ROS signaling in Arabidopsis thaliana. BMC Plant Biol 16(1), 163 (2016).Zhao, M. G., Chen, L., Zhang, L. L. & Zhang, W. H. Nitric reductase dependent nitric oxide production is involved in cold acclimation and freezing tolerance in Arabidopsis. Plant Physiol 151, 755–767 (2009).Puyaubert, J. & Baudouin, E. New clues for a cold case: nitric oxide response to low temperature. Plant Cell & Environ 37, 2623–2630 (2014).Siddiqui, M. H., Al-Whaibi, M. H. & Basalah, M. O. Role of nitric oxide in tolerance of plants to abiotic stress. Protoplasma 248, 447–455 (2011).Arasimowicz-Jelonek, M. & Floryszak-Wieczorek, J. Nitric oxide: an effective weapon of the plant or the pathogen? Mol. Plant Pathol. 15, 406–416 (2014).Gupta, K. J., Fernie, A. R., Kaiser, W. M. & van Dongen, J. T. On the origins of nitric oxide. Trends Plant Sci. 16, 160–168 (2011).Mur, L. A. et al. Nitric oxide in plants: an assessment of the current state of knowledge. AoB Plants 5, pls052 (2013).Thomas, D. D. Breathing new life into nitric oxide signaling: A brief overview of the interplay between oxygen and nitric oxide. Redox Biol. 5, 225–33 (2015).Correa-Aragunde, N., Foresi, N. & Lamattina, L. Nitric oxide is a ubiquitous signal for maintaining redox balance in plant cells: regulation of ascorbate peroxidase as a case study. J. Exp. Bot. 66, 2913–2921 (2015).Groβ, F., Durner, J. & Gaupels, F. Nitric oxide, antioxidants and prooxidants in plant defence responses. Front. Plant Sci. 4, 419 (2013).Astier, J. & Lindermayr, C. Nitric oxide-dependent posttranslational modification in plants: an update. Int. J. Mol. Sci. 13, 15193–15208 (2012).Hess, D. T. & Stamler, J. S. Regulation by S-nitrosylation of protein post-translational modification. J. Biol. Chem. 287, 4411–4418 (2012).Guerra, D. D. & Callis, J. Ubiquitin on the move: the ubiquitin modification system plays diverse roles in the regulation of endoplasmic reticulum- and plasma membrane-localized proteins. Plant Physiol. 160, 56–64 (2012).Cantrel, C. et al. Nitric oxide participates in cold-responsive phosphosphingolipid formation and gene expression in Arabidopsis thaliana. New Phytol. 189, 415–427 (2011).Lozano-Juste, J. & León, J. Enhanced abscisic acid-mediated responses innia1,2noa1-2 triple mutant impaired in NIA/NR- and AtNOA1-dependent nitric oxide biosynthesis in Arabidopsis. Plant Physiol. 152, 891–903 (2010).Gibbs, D. J. et al. Nitric oxide sensing in plants is mediated by proteolytic control of group VII ERF transcription factors. Mol. Cell 53, 369–379 (2014).Lee, B. H., Henderson, D. A. & Zhu, J. K. The Arabidopsis cold-responsive transcriptome and its regulation by ICE1. Plant Cell 17, 3155–3175 (2005).Kilian, J. et al. The AtGenExpress global stress expression data set: protocols, evaluation and model data analysis of UV-B light, drought and cold stress responses. Plant J. 50, 347–363 (2007).Hu, Y., Jiang, L., Wang, F. & Yu, D. Jasmonate regulates the inducer of cbf expression-C-repeat binding factor/DRE binding factor1 cascade and freezing tolerance in Arabidopsis. Plant Cell 25, 2907–2924 (2013).Lee, H. G. & Seo, P. J. The MYB96-HHP module integrates cold and abscisic acid signaling to activate the CBF-COR pathway in Arabidopsis. Plant J. 82, 962–977 (2015).Kasukabe, Y. et al. Overexpression of spermidine synthase enhances tolerance to multiple environmental stresses and up-regulates the expression of various stress-regulated genes in transgenic Arabidopsis thaliana. Plant & Cell Physiol 45, 712–722 (2004).Korn, M., Peterek, S., Mock, H. P., Heyer, A. G. & Hincha, D. K. Heterosis in the freezing tolerance, and sugar and flavonoid contents of crosses between Arabidopsis thaliana accessions of widely varying freezing tolerance. Plant Cell & Environ. 31, 813–827 (2008).Guy, C., Kaplan, F., Kopka, J., Selbig, J. & Hincha, D. K. Metabolomics of temperature stress. Physiol. Plant. 132, 220–235 (2008).Berger, S. et al. Enzymatic and non enzymatic lipid peroxidation in leaf development. Biochem. Biophys. Acta 1533, 266–276 (2001).Yoshida, Y., Umeno, A. & Shichiri, M. Lipid peroxidation biomarkers for evaluating oxidative stress and assessing antioxidant capacity in vivo. J Clin. Biochem. Nutr. 52, 9–16 (2013).Catalá, R. et al. The Arabidopsis 14-3-3 protein RARE COLD INDUCIBLE 1A links low-temperature response and ethylene biosynthesis to regulate freezing tolerance and cold acclimation. Plant Cell 26, 3326–3342 (2014).Tähtiharju, S. & Palva, T. Antisense inhibition of protein phosphatase 2C accelerates cold acclimation in Arabidopsis thaliana. Plant J. 26, 461–470 (2001).Kawamura, Y. & Uemura, M. Mass spectrometric approach for identifying putative plasma membrane proteins of Arabidopsis leaves associated with cold acclimation. Plant J. 36, 141–154 (2003).Xin, Z. & Browse, J. Eskimo1 mutants of Arabidopsis are constitutively freezing-tolerant. Proc. Natl. Acad. Sci. USA 95, 7799–7804 (1998).Nanjo, T. et al. Antisense suppression of proline degradation improves tolerance to freezing and salinity in Arabidopsis thaliana. FEBS Lett. 461, 205–210 (1999).Zuther, E., Schulz, E., Childs, L. H. & Hincha, D. K. Clinal variation in the non-acclimated and cold-acclimated freezing tolerance of Arabidopsis thaliana accessions. Plant Cell & Environ. 35, 1860–1878 (2012).Alcázar, R., García-Martínez, J. L., Cuevas, J. C., Tiburcio, A. F. & Altabella, T. Overexpression of ADC2 in Arabidopsis induces dwarfism and late-flowering through GA deficiency. Plant J. 43, 425–436 (2005).Alet, A. I. et al. Putrescine accumulation in Arabidopsis thaliana transgenic lines enhances tolerance to dehydration and freezing stress. Plant Signal. & Behav. 6, 278–286 (2011).Nägele, T., Stutz, S., Hörmiller, I. I. & Heyer, A. G. Identification of a metabolic bottleneck for cold acclimation in Arabidopsis thaliana. Plant J. 72, 102–114 (2012).Krol, M. et al. Low-temperature stress and photoperiod affect an increased tolerance to photoinhibition in Pinus banksiana seedlings. Canadian Journal of Botany 73, 1119–1127 (1995).Harvaux, M. & Kloppstech, K. The protective functions of carotenoid and flavonoid pigments against excess visible radiation at chilling temperature investigated in Arabidopsis npq and tt mutants. Planta 213, 953–966 (2001).Schulz, E., Tohge, T., Zuther, E., Fernie, A. R. & Hincha, D. K. Flavonoids are determinants of freezing tolerance and cold acclimation in Arabidopsis thaliana. Sci. Rep. 6, 34027 (2016).Llorente, F., Oliveros, J. C., Martínez-Zapater, J. M. & Salinas, J. A freezing-sensitive mutant of Arabidopsis, frs1, is a new aba3 allele. Planta 211, 648–655 (2000).Lozano-Juste, J., Colom-Moreno, R. & León, J. In vivo protein tyrosine nitration in Arabidopsis thaliana. J. Exp. Bot. 62, 3501–3517.Gill, S. S. & Tuteja, N. Reactive oxygen species and antioxidant machinery in abiotic stress tolerance in crop plants. Plant Physiol. Biochem. 48, 909–930 (2010).Begara-Morales, J. C. et al. Antioxidant Systems are Regulated by Nitric Oxide-Mediated Post-translational Modifications (NO-PTMs). Front. Plant Sci. 7, 152 (2016).Castillo, M. C. & León, J. Expression of the beta-oxidation gene 3-ketoacyl-CoA thiolase 2 (KAT2) is required for the timely onset of natural and dark-induced leaf senescence in Arabidopsis. J. Exp. Bot. 59, 2171–2179 (2008).Guo, F. Q., Okamoto, M. & Crawford, N. M. Identification of a plant nitric oxide synthase gene involved in hormonal signaling. Science 302, 100–103 (2003).Solfanelli, C., Poggi, A., Loreti, E., Alpi, A. & Perata, P. Sucrose-specific induction of the anthocyanin biosynthetic pathway in Arabidopsis. Plant Physiol. 140, 637–646 (2006).Seo, M., Jikumaru, Y. & Kamiya, Y. Profiling of Hormones and Related Metabolites in Seed Dormancy and Germination Studies. Meth. Mol. Biol. 773, 99–111 (2011)

    The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

    Get PDF
    AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease
    corecore