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\u00a9 2014 The Authors. Objective: To assess mortality risk among adults presenting to an African teaching hospital with sepsis and severe sepsis in a setting of high HIV prevalence and widespread ART uptake. Methods: Prospective cohort study of adults (age \u226516 years) admitted with clinical suspicion of severe infection between November 2008 and January 2009 to Queen Elizabeth Central Hospital, a 1250-bed government-funded hospital in Blantyre, Malawi. Demographic, clinical and laboratory information, including blood and cerebrospinal fluid cultures were obtained on admission. Results: Data from 213 patients (181 with sepsis and 32 with severe sepsis; M:F=2:3) were analysed. 161 (75.6%) patients were HIV-positive. Overall mortality was 22%, rising to 50% amongst patients with severe sepsis. The mortality of all sepsis patients commenced on antiretroviral therapy (ART) within 90 days was 11/28 (39.3%) compared with 7/42 (16.7%) among all sepsis patients on ART for greater than 90 days (. p=0.050). Independent associations withdeath were hypoxia (OR=2.4; 95% CI, 1.1-5.1) and systolic hypotension (OR 7.0; 95% CI: 2.4-20.4). Conclusions: Sepsis and severe sepsis carry high mortality among hospitalised adults in Malawi. Measures to reduce this, including early identification and targeted intervention in high-risk patients, especially HIV-positive individuals recently commenced on ART, are urgently required.
\n \n\n \n \nDefinitive identification of Angiostrongylus cantonensis parasites from clinical specimens is difficult. As a result, regional epidemiology and burden are poorly characterized. To ascertain presence of this parasite in patients in Laos with eosinophilic meningitis, we performed quantitative PCRs on 36 cerebrospinal fluid samples; 4 positive samples confirmed the parasite's presence.
\n \n\n \n \nBurkholderia pseudomallei is a Gram-negative bacterium that causes melioidosis, an often fatal disease in tropical countries. Burkholderia thailandensis is a non-virulent but closely related species. Both species are soil saprophytes but are almost never isolated together.We identified two mechanisms by which B. pseudomallei affects the growth of B. thailandensis. First, we found that six different isolates of B. pseudomallei inhibited the growth of B. thailandensis on LB agar plates. Second, our results indicated that 55% of isolated strains of B. pseudomallei produced a secreted compound that inhibited the motility but not the viability of B. thailandensis. Analysis showed that the active compound was a pH-sensitive and heat-labile compound, likely a protein, which may affect flagella processing or facilitate their degradation. Analysis of bacterial sequence types (STs) demonstrated an association between this and motility inhibition. The active compound was produced from B. pseudomallei during the stationary growth phase.Taken together, our results indicate that B. pseudomallei inhibits both the growth and motility of its close relative B. thailandensis. The latter phenomenon appears to occur via a previously unreported mechanism involving flagellar processing or degradation.
\n \n\n \n \nDuring eukaryotic cell division, the DNA molecules are partitioned to opposite poles of the cell, ensuring accurate distribution of chromosomes between the dividing cells. In prokaryotes, the mechanism for accurate segregation is unknown. Previous studies have focused on partitioning of a plasmid, Rl, which encodes a stability operon, par, that is required for proper segregation of this low-copy-number plasmid. The par operon of Rl encodes three components: ParM, an actin-like ATPase, ParR, a DNA-bind- ing protein, and parC, a centromere-like DNA sequence element to which ParR binds. In the presence of ATP, ParM polymerizes and then disassembles. Disassembly is prevented, however, by the binding of ParR to parC, which stabilizes the ParM filaments. In the current model for DNA segregation, the ATP-dependent polymerization of ParM is believed to move newly replicated plasmids to the opposite poles. This study therefore determined how the ParM filaments are formed and stabilized and ascertained the sites involved to effect both mechanisms. Mutational studies, pull-down and gel- shift assays for point and deletion mutants of Rl ParR, and electron microscopy at varying concentrations of labeled parC established that the ParR- parC complex forms the clamp that binds at both the C-terminal ends of ParM, forming ring structures that bind ATP and stabilize the ParM filaments. ParR binds through its N-terminus to parC, forming a rigid scaffold of protein (ParR) wrapped by a DNA helix (parC). This binding does not include the Rl promoter region within the parC domain, because the promoter region extends out as a loop from the ParR binding region. Additionally, studies with mutants of ParM also identified the binding sites of the ParR-parC complex on ParM. A model for ParM polymerization consistent with electron micrograph images was thus proposed whereby ATP binding polymerizes ParM. Binding of the ParR-parC complex clamps the C-terminal ParM-ATP complex stabilizing filament formation. Hydrolysis of ATP to ADP dislocates ParR-parC and translocates ParR to one side to allow binding of a new ParM-ATP monomer. ParR translocates back, rocking the clamp, and the cycle of hydrolysis, translocation, and monomer addition is repeated until elongation is completed (Fig. 1). \u00a9 2008 Data Trace Publishing Company.
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