Deliberate and natural outbreaks of infectious disease underscore the necessity of effective vaccines and antimicrobial/antiviral therapeutics. The prevalence of antibiotic resistant strains and the ease by which antibiotic resistant bacteria can be intentionally engineered further highlights the need for continued development of novel antibiotics against new bacterial targets. Isoprenes are a class of molecules fundamentally involved in a variety of crucial biological functions. Mammalian cells utilize the mevalonic acid pathway for isoprene biosynthesis, whereas many bacteria utilize the methylerythritol phosphate (MEP) pathway, making the latter an attractive target for antibiotic development. In this report we describe the cloning and characterization of Francisella tularensis MEP synthase, a MEP pathway enzyme and potential target for antibiotic development. In vitro growth-inhibition assays using fosmidomycin, an inhibitor of MEP synthase, illustrates the effectiveness of MEP pathway inhibition with F. tularensis. To facilitate drug development, F. tularensis MEP synthase was cloned, expressed, purified, and characterized. Enzyme assays produced apparent kinetic constants (KMDXP = 104 µM, KMNADPH = 13 µM, kcatDXP = 2 s−1, kcatNADPH = 1.3 s−1), an IC50 for fosmidomycin of 247 nM, and a Ki for fosmidomycin of 99 nM. The enzyme exhibits a preference for Mg+2 as a divalent cation. Titanium dioxide chromatography-tandem mass spectrometry identified Ser177 as a site of phosphorylation. S177D and S177E site-directed mutants are inactive, suggesting a mechanism for post-translational control of metabolic flux through the F. tularensis MEP pathway. Overall, our study suggests that MEP synthase is an excellent target for the development of novel antibiotics against F. tularensis.
Bullying, especially in developing countries, has not been much examined, especially the influence of parents on the risk of being bullied. The aim of this study was to determine whether active parenting is associated with reduced peer victimization among middle-school students in North Africa. A secondary analysis of data from more than 13 000 middle-school students who participated in the Global School-based Student Health Survey (GSHS) in Egypt, Libya, Morocco and Tunisia between 2006 and 2008, was conducted using multiple logistic regression models. About 60% of students in Egypt and one-third of students in Libya, Morocco and Tunisia reported having been bullied in the past month. In all 4 countries, boys reported more peer victimization than girls. In Egypt, Morocco and Tunisia, students who reported that their parents checked their homework, were understanding, and knew how the student spent free time had a reduced likelihood of peer victimization but this association was not significant in Libya. Interventions for reducing bullying should consider the positive impact of involved parents.
Objective: To examine the relationships between peer victimization, mental health, and parental involvement among middle school students in the Caribbean.
The factors that influence the selection of a healthcare provider once the decision to seek care has been made can be summarized using a triad of cost, location and reputation. The goal of this study was to identify which of these factors is the primary consideration when women in urban Bo, Sierra Leone, select a healthcare provider for themselves or their children. We interviewed 1091 mothers during a household census of two neighbourhoods of Bo in April 2010. Reputation was the top consideration for about half of the women, cost was the second most common priority, and the location of the healthcare facility was the primary consideration for less than 7% of the participants. The majority of women said they would select a new provider if cost was not a barrier. Socioeconomic characteristics were not significant predictors of whether cost, location or reputation was selected as the highest-ranked consideration. This evidence for the importance of reputation in healthcare decision-making even in low-resource areas highlights the need for health systems to address issues of quality and responsiveness, and not just cost, in order to increase access to and utilization of health services.
As of April 2010, all maternity care at government healthcare facilities in Sierra Leone is provided at no cost to patients. In late 2010, we conducted a community health census of 18 sections of the city of Bo (selected via randomized cluster sampling from 68 total sections). Among the 3421 women with a history of pregnancy who participated in the study, older women most often reported having a history of both home and hospital deliveries, while younger women showed a preference for hospital births. The proportion of lastborn children delivered at a healthcare facility increased from 71.8% of offspring 10-14 years old to 81.1% of those one to nine years old and 87.3% of infants born after April 2010. These findings suggest that the new maternal healthcare initiative has accelerated an existing trend toward a preference for healthcare facility births, at least in some urban parts of Sierra Leone.
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