60 research outputs found

    Complexity of the Mycoplasma fermentans M64 Genome and Metabolic Essentiality and Diversity among Mycoplasmas

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    Recently, the genomes of two Mycoplasma fermentans strains, namely M64 and JER, have been completely sequenced. Gross comparison indicated that the genome of M64 is significantly bigger than the other strain and the difference is mainly contributed by the repetitive sequences including seven families of simple and complex transposable elements ranging from 973 to 23,778 bps. Analysis of these repeats resulted in the identification of a new distinct family of Integrative Conjugal Elements of M. fermentans, designated as ICEF-III. Using the concept of “reaction connectivity”, the metabolic capabilities in M. fermentans manifested by the complete and partial connected biomodules were revealed. A comparison of the reported M. pulmonis, M. arthritidis, M. genitalium, B. subtilis, and E. coli essential genes and the genes predicted from the M64 genome indicated that more than 73% of the Mycoplasmas essential genes are preserved in M. fermentans. Further examination of the highly and partly connected reactions by a novel combinatorial phylogenetic tree, metabolic network, and essential gene analysis indicated that some of the pathways (e.g. purine and pyrimidine metabolisms) with partial connected reactions may be important for the conversions of intermediate metabolites. Taken together, in light of systems and network analyses, the diversity among the Mycoplasma species was manifested on the variations of their limited metabolic abilities during evolution

    Effects of Post-Resuscitation Treatment with N-acetylcysteine on Cardiac Recovery in Hypoxic Newborn Piglets

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    AIMS: Although N-acetylcysteine (NAC) can decrease reactive oxygen species and improve myocardial recovery after ischemia/hypoxia in various acute animal models, little is known regarding its long-term effect in neonatal subjects. We investigated whether NAC provides prolonged protective effect on hemodynamics and oxidative stress using a surviving swine model of neonatal asphyxia. METHODS AND RESULTS: Newborn piglets were anesthetized and acutely instrumented for measurement of systemic hemodynamics and oxygen transport. Animals were block-randomized into a sham-operated group (without hypoxia-reoxygenation [H-R, n = 6]) and two H-R groups (2 h normocapnic alveolar hypoxia followed by 48 h reoxygenation, n = 8/group). All piglets were acidotic and in cardiogenic shock after hypoxia. At 5 min after reoxygenation, piglets were given either saline or NAC (intravenous 150 mg/kg bolus + 20 mg/kg/h infusion) via for 24 h in a blinded, randomized fashion. Both cardiac index and stroke volume of H-R controls remained lower than the pre-hypoxic values throughout recovery. Treating the piglets with NAC significantly improved cardiac index, stroke volume and systemic oxygen delivery to levels not different from those of sham-operated piglets. Accompanied with the hemodynamic improvement, NAC-treated piglets had significantly lower plasma cardiac troponin-I, myocardial lipid hydroperoxides, activated caspase-3 and lactate levels (vs. H-R controls). The change in cardiac index after H-R correlated with myocardial lipid hydroperoxides, caspase-3 and lactate levels (all p<0.05). CONCLUSIONS: Post-resuscitation administration of NAC reduces myocardial oxidative stress and caused a prolonged improvement in cardiac function and in newborn piglets with H-R insults

    Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09‐related pneumonia: an individual participant data meta‐analysis

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    BACKGROUND: The impact of neuraminidase inhibitors (NAIs) on influenza‐related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection. METHODS: A worldwide meta‐analysis of individual participant data from 20 634 hospitalised patients with laboratory‐confirmed A(H1N1)pdm09 (n = 20 021) or clinically diagnosed (n = 613) ‘pandemic influenza’. The primary outcome was radiologically confirmed IRP. Odds ratios (OR) were estimated using generalised linear mixed modelling, adjusting for NAI treatment propensity, antibiotics and corticosteroids. RESULTS: Of 20 634 included participants, 5978 (29·0%) had IRP; conversely, 3349 (16·2%) had confirmed the absence of radiographic pneumonia (the comparator). Early NAI treatment (within 2 days of symptom onset) versus no NAI was not significantly associated with IRP [adj. OR 0·83 (95% CI 0·64–1·06; P = 0·136)]. Among the 5978 patients with IRP, early NAI treatment versus none did not impact on mortality [adj. OR = 0·72 (0·44–1·17; P = 0·180)] or likelihood of requiring ventilatory support [adj. OR = 1·17 (0·71–1·92; P = 0·537)], but early treatment versus later significantly reduced mortality [adj. OR = 0·70 (0·55–0·88; P = 0·003)] and likelihood of requiring ventilatory support [adj. OR = 0·68 (0·54–0·85; P = 0·001)]. CONCLUSIONS: Early NAI treatment of patients hospitalised with A(H1N1)pdm09 virus infection versus no treatment did not reduce the likelihood of IRP. However, in patients who developed IRP, early NAI treatment versus later reduced the likelihood of mortality and needing ventilatory support
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