Establishment of intestinal infection with Entamoeba histolytica depends on the mouse strain; C57BL/6 mice are highly resistant, and C3H/HeJ mice are relatively susceptible. We found that resistance to intestinal infection was independent of lymphocyte activity or H-2 haplotype and occurred in the first hours to days postchallenge according to in vivo imaging. At 18 h postchallenge, the ceca of resistant C57BL/6 mice were histologically unremarkable, in contrast to the severe inflammation observed in susceptible C3H/HeJ mice. Comparison of cecal gene expression in C3H/HeJ and C57BL/6 mice demonstrated that there was parasiteinduced upregulation of proinflammatory and neutrophil chemotaxis transcripts and there was downregulation of transforming growth factor  signaling molecules. Pretreatment with dexamethasone abrogated the partial resistance of C3H/HeJ or CBA mice through an innate, lymphocyte-independent mechanism, but it had no effect on the high-level resistance of C57BL/6 mice. Similarly, administration of a neutrophil-depleting anti-Gr-1 monoclonal antibody (RB6-8C5) decreased the partial resistance of CBA mice and led to severe pathology compared to control antibody-treated mice, but it had no effect on C57BL/6 resistance. These data indicate that there are discrete mechanisms of innate resistance to E. histolytica depending on the host background and, in contrast to other reports, imply that neutrophils are protective and not damaging in intestinal amebiasis.
IntroductionFollowing twenty years of economic and social growth, Liberia's fourteen-year civil war destroyed its health system, with most of the health workforce leaving the country. Following the inauguration of the Sirleaf administration in 2006, the Ministry of Health & Social Welfare (MOHSW) has focused on rebuilding, with an emphasis on increasing the size and capacity of its human resources for health (HRH). Given resource constraints and the high maternal and neonatal mortality rates, MOHSW concentrated on its largest cadre of health workers: nurses.Case descriptionBased on results from a post-war rapid assessment of health workers, facilities and community access, MOHSW developed the Emergency Human Resources (HR) Plan for 2007-2011. MOHSW established a central HR Unit and county-level HR officers and prioritized nursing cadres in order to quickly increase workforce numbers, improve equitable distribution of workers and enhance performance. Strategies included increasing and standardizing salaries to attract workers and prevent outflow to the private sector; mobilizing donor funds to improve management capacity and fund incentive packages in order to retain staff in hard to reach areas; reopening training institutions and providing scholarships to increase the pool of available workers.Discussion and evaluationMOHSW has increased the total number of clinical health workers from 1396 in 1998 to 4653 in 2010, 3394 of which are nurses and midwives. From 2006 to 2010, the number of nurses has more than doubled. Certified midwives and nurse aides also increased by 28% and 31% respectively. In 2010, the percentage of the clinical workforce made up by nurses and nurse aides increased to 73%. While the nursing cadre numbers are strong and demonstrate significant improvement since the creation of the Emergency HR Plan, equitable distribution, retention and performance management continue to be challenges.ConclusionThis paper illustrates the process, successes, ongoing challenges and current strategies Liberia has used to increase and improve HRH since 2006, particularly the nursing workforce. The methods used here and lessons learned might be applied in other similar settings.
The Entamoeba histolytica transcription factor Upstream Regulatory Element 3-Binding Protein (URE3-BP) is a calcium-responsive regulator of two E. histolytica virulence genes, hgl5 and fdx1. URE3-BP was previously identified by a yeast one-hybrid screen of E. histolytica proteins capable of binding to the sequence TATTCTATT (Upstream Regulatory Element 3 (URE3)) in the promoter regions of hgl5 and fdx1. In this work, precise definition of the consensus URE3 element was performed by electrophoretic mobility shift assays (EMSA) using base-substituted oligonucleotides, and the consensus motif validated using episomal reporter constructs. Transcriptome profiling of a strain induced to produce a dominant-positive URE3-BP was then used to identify additional genes regulated by URE3-BP. Fifty modulated transcripts were identified, and of these the EMSA defined motif T[atg]T[tc][cg]T[at][tgc][tg] was found in over half of the promoters (54% p<0.0001). Fifteen of the URE3-BP regulated genes were potential membrane proteins, suggesting that one function of URE3-BP is to remodel the surface of E. histolytica in response to a calcium signal. Induction of URE3-BP leads to an increase in tranwell migration, suggesting a possible role in the regulation of cellular motility.
A randomized controlled trial of four interventions was conducted using tubewells (n ¼ 2,486), liquid sodium hypochlorite ('Clorin') distributed with an improved water vessel (n ¼ 2,305), hygiene promotion (n ¼ 1,877), and a combination of the three (n ¼ 2,040) to create an evidence- Higher economic status as measured through household assets was associated with lower rates of diarrhoea and greater intervention uptake, excepting Clorin. Use of soap was also associated with lower prevalence of diarrhoea.
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