Pooled-DNA sequencing identifies genomic regions of selection in Nigerian isolates of Plasmodium falciparum.

BACKGROUND: The burden of falciparum malaria is especially high in sub-Saharan Africa. Differences in pressure from host immunity and antimalarial drugs lead to adaptive changes responsible for high level of genetic variations within and between the parasite populations. Population-specific genetic studies to survey for genes under positive or balancing selection resulting from drug pressure or host immunity will allow for refinement of interventions. METHODS: We performed a pooled sequencing (pool-seq) of the genomes of 100 Plasmodium falciparum isolates from Nigeria. We explored allele-frequency based neutrality test (Tajima's D) and integrated haplotype score (iHS) to identify genes under selection. RESULTS: Fourteen shared iHS regions that had at least 2 SNPs with a score > 2.5 were identified. These regions code for genes that were likely to have been under strong directional selection. Two of these genes were the chloroquine resistance transporter (CRT) on chromosome 7 and the multidrug resistance 1 (MDR1) on chromosome 5. There was a weak signature of selection in the dihydrofolate reductase (DHFR) gene on chromosome 4 and MDR5 genes on chromosome 13, with only 2 and 3 SNPs respectively identified within the iHS window. We observed strong selection pressure attributable to continued chloroquine and sulfadoxine-pyrimethamine use despite their official proscription for the treatment of uncomplicated malaria. There was also a major selective sweep on chromosome 6 which had 32 SNPs within the shared iHS region. Tajima's D of circumsporozoite protein (CSP), erythrocyte-binding antigen (EBA-175), merozoite surface proteins - MSP3 and MSP7, merozoite surface protein duffy binding-like (MSPDBL2) and serine repeat antigen (SERA-5) were 1.38, 1.29, 0.73, 0.84 and 0.21, respectively. CONCLUSION: We have demonstrated the use of pool-seq to understand genomic patterns of selection and variability in P. falciparum from Nigeria, which bears the highest burden of infections. This investigation identified known genomic signatures of selection from drug pressure and host immunity. This is evidence that P. falciparum populations explore common adaptive strategies that can be targeted for the development of new interventions

Reducing Urinary Catheter Use: A Protocol for a Mixed Methods Evaluation of an Electronic Reminder System in Hospitalised Patients in Australia

Introduction: Despite advances in infection prevention and control, catheter-associated urinary tract infections (CAUTIs) are common and remain problematic. Prolonged urinary catheterisation is the main risk factor for development of CAUTIs; hence, interventions that target early catheter removal warrant investigation. The study’s objectives are to examine the efficacy of an electronic reminder system, the CATH TAG, in reducing urinary catheter use (device utilisation ratio) and to determine the effect of the CATH TAG on nurses’ ability to deliver patient care. Methods and analysis: This study uses a mixed methods approach in which both quantitative and qualitative data will be collected. A stepped wedge randomised controlled design in which wards provide before and after observations will be undertaken in one large Australian hospital over 24 weeks. The intervention is the use of the CATH TAG. Eligible hospital wards will receive the intervention and act as their own control, with analysis undertaken of the change within each ward using data collected in control and intervention periods. An online survey will be administered to nurses on study completion, and a focus group for nurses will be conducted 2 months after study completion. The primary outcomes are the urinary catheter device utilisation ratio and perceptions of nurses about ease of use of the CATH TAG. Secondary outcomes include a reduced number of cases of catheter-associated asymptomatic bacteriuria, a reduced number of urinary catheters inserted per 100 patient admissions, perceptions of nurses regarding effectiveness of the CATH TAG, changes in ownership/interest by patients in catheter management, as well as possible barriers to successful implementation of the CATH TAG

Role of Adrenergic Receptors in Glucose, Fructose and Galactose-Induced Increases in Intestinal Glucose Uptake in Dogs

Summary: The study investigated the role of adrenergic receptors in glucose, fructose-, and galactose-induced increases in intestinal glucose uptake. Experiments were carried out on fasted male anaesthetized Nigerian local dogs divided into seven groups (with five dogs per group). Group I dogs were administered normal saline and served as control. Dogs in groups II, III and IV were intravenously infused with glucose (1.1 mg/kg/min), fructose (1.1 mg/kg/min) and galactose (1.1 mg/kg/min) respectively. Another three groups, V, VI and VII were pretreated with prazosin (0.2mg/kg), propranolol (0.5mg/kg) or a combination of prazosin (0.2mg/kg) and propranolol (0.5mg/kg) followed by glucose infusion, frutose infusion or galactose infusion respectively. Through a midline laparatomy, the upper jejunum was cannulated for blood flow measurement and blood samples were obtained for measurement of glucose content of the arterial blood and venous blood from the upper jejunal segment. Glucose uptake was calculated as the product of jejunal blood flow and the difference between arterial and venous glucose levels (A-V glucose). The results showed that pretreatment of the animal with prazosin had no effect on glucose and galactose induced increases in glucose uptake. However, pretreatment with propranolol completely abolished glucose, fructose and galactose-induced increases in intestinal glucose uptake. Prazosin also significantly reduced galactose-induced increase in intestinal glucose uptake. The results suggest that the increases in intestinal glucose uptake induced by glucose and fructose are mediated mostly by beta adrenergic receptors while that of galactose is mediated by both alpha and beta adrenergic receptors

High cases of submicroscopic Plasmodium falciparum infections in a suburban population of Lagos, Nigeria.

BACKGROUND: Asymptomatic malaria parasites are significant sources of infections for onward malaria transmission. Conventional tools for malaria diagnosis such as microscopy and rapid diagnostic test kits (RDT) have relatively low sensitivity, hence the need for alternative tools for active screening of such low-density infections. METHODS: This study tested var acidic terminal sequence-based (varATS) quantitative polymerase chain reaction (qPCR) for screening asymptomatic Plasmodium falciparum infections among dwellers of a sub-urban community in Lagos, Nigeria. Clinically healthy participants were screened for malaria using microscopy, RDT and varATS qPCR techniques. Participants were stratified into three age groups: 1-5, 6-14 and > 14 years old. RESULTS: Of the 316 participants screened for asymptomatic malaria infection, 78 (24.68%) were positive by microscopy, 99 (31.33%) were positive by RDT and 112 (35.44%) by varATS qPCR. Participants aged 6-14 years had the highest prevalence of asymptomatic malaria, with geometric means of ~ 116 parasites/µL and ~ 6689 parasites/µL as detected by microscopy and varATS, respectively. CONCLUSION: This study has revealed high prevalence of asymptomatic malaria in the study population, with varATS detecting additional sub-microscopic infections. The highest concentration of asymptomatic malaria was observed among school-age children between 6 and 14 years old. A large-scale screening to identify other potential hotspots of asymptomatic parasites in the country is recommended

Mechanical and durability assessment of concrete containing seashells: A review

This study reviews recent literature on the mechanical and durability properties of concrete incorporating seashells as partial or full substitutes for conventional materials. The study summarizes various contributions elucidating the various waste seashells utilized, the growing worldwide aquaculture production, seashell material preparation and treatment, chemical composition, physical properties, and different mechanical and durability test methods adopted by previous studies such as compressive strength, split tensile strength, flexural strength, modulus of elasticity, freeze-thaw resistance, water permeability, air content, chemical attack, carbonation, and weight loss. The study showed that mechanical properties indicate reductions of different percentages with increases in substitution ratio at 5% to 75%, compared to control mixes. However, relative increases in mechanical strength were recorded with the increase in curing age up to 90 days. Influence of seashells on durability properties varied across various durability tests at different seashell percentages. In a nutshell, the use of seashells in concreteproduction has a good effect, and further innovative research can solidify its utilization in the drive towards sustainable development

Sustainable use of seashells as binder in concrete production: Prospect and challenges

Cement production has a lot of adverse effects on the environment and the globe at large. With all these negativities, it becomes imperative to find alternative materials that are sustainable and environmentally friendly to reduce some of these adverse effects. Seashells are one of the numerous wastes that are quickly accumulating onshore coasts. Using seashells in cement aids in ridding seashells from seashores and landfills, and transforming these wastes to viable cementitious materials. This review paper summarizes past studies on using seashell ash powder as a partial replacement for cement in several proportions. The workability of concrete reduces with the addition of seashell ash. It also indicates a reduction in compressive strength of concrete whose cement content is partially replaced with seashells as compared to those of ordinary Portland cement (OPC). Also, at low percentages of 5%–15% ranges, the concrete absorption and porosity are less compared to standard. Though, with greater replacement levels of up to 25%–50%, these values are enhanced. The workability of concrete is reduced with the addition of higher percentage of seashell ash. After long curing periods, concrete permeability is also reduced, and the mechanical performance is enhanced

Waste materials in highway applications: An overview on generation and utilization implications on sustainability

The rate at which the construction industry explores and consumes non-renewable natural aggregates and other industrial products such as bitumen, lime, and cement during construction and rehabilitation of road pavements has over time proven to be environmentally degrading and non-sustainable. This, alongside the issues of high solid waste generation and inadequate disposal, has led to series of studies by various researchers to find methods to integrate these solid wastes as alternative materials in road construction and maintenance. This paper provides a simple yet detailed review of recent relevant studies conducted to understand the alarming rate of generation and the effects of reusing these waste materials in both flexible and rigid pavements. The review further outlines the advantages and disadvantages of the selected waste materials and compare the results with that of conventional materials in accordance with relevant standards while highlighting the performance, and life cycle environmental and economic sustainability implications. The study shows that the adoption of these materials offers efficiency in waste disposal while reducing the demand for natural aggregates and consequently, significantly reducing life cycle impacts and costs. The challenges limiting the effective practical implementation of these waste recycling techniques in the construction industry were discussed and possible solutions were suggested to encourage and ensure its utilization in road construction

Financial market development, global financial crisis and economic growth : evidence from developing nations

Emerging and frontier markets in Africa have witnessed various economic and financial reforms aimed at integrating the domestic markets into the global financial market to attract investment. Whether these reforms promote high economic growth remains inconclusive. The paper applies the pooled mean group estimation technique to empirically re-investigate the link between financial market development, global financial crisis, and economic growth in selected African economies. The results strongly support our hypotheses that stock market and banking sector development promotes economic growth in the selected countries. Moreover, financial crisis reduce the positive effects of both the stock market and banking sector developments on economic growth. The study suggests that both the banking sector and stock market are important to deliver the long-run economic growth that the African region desired. Moreover, effort should be made to enact policy measures that would ensure development of the stock market which has received inadequate attention.info:eu-repo/semantics/publishedVersio

In silico characterisation of putative Plasmodium falciparum vaccine candidates in African malaria populations.

Genetic diversity of surface exposed and stage specific Plasmodium falciparum immunogenic proteins pose a major roadblock to developing an effective malaria vaccine with broad and long-lasting immunity. We conducted a prospective genetic analysis of candidate antigens (msp1, ama1, rh5, eba175, glurp, celtos, csp, lsa3, Pfsea, trap, conserved chrom3, hyp9, hyp10, phistb, surfin8.2, and surfin14.1) for malaria vaccine development on 2375 P. falciparum sequences from 16 African countries. We described signatures of balancing selection inferred from positive values of Tajima's D for all antigens across all populations except for glurp. This could be as a result of immune selection on these antigens as positive Tajima's D values mapped to regions with putative immune epitopes. A less diverse phistb antigen was characterised with a transmembrane domain, glycophosphatidyl anchors between the N and C- terminals, and surface epitopes that could be targets of immune recognition. This study demonstrates the value of population genetic and immunoinformatic analysis for identifying and characterising new putative vaccine candidates towards improving strain transcending immunity, and vaccine efficacy across all endemic populations

Micro-epidemiological structuring of Plasmodium falciparum parasite populations in regions with varying transmission intensities in Africa

Background: The first models of malaria transmission assumed a completely mixed and homogeneous population of parasites.  Recent models include spatial heterogeneity and variably mixed populations. However, there are few empiric estimates of parasite mixing with which to parametize such models. Methods: Here we genotype 276 single nucleotide polymorphisms (SNPs) in 5199 P. falciparum isolates from two Kenyan sites (Kilifi county and Rachuonyo South district) and one Gambian site (Kombo coastal districts) to determine the spatio-temporal extent of parasite mixing, and use Principal Component Analysis (PCA) and linear regression to examine the relationship between genetic relatedness and distance in space and time for parasite pairs. Results: Using 107, 177 and 82 SNPs that were successfully genotyped in 133, 1602, and 1034 parasite isolates from The Gambia, Kilifi and Rachuonyo South district, respectively, we show that there are no discrete geographically restricted parasite sub-populations, but instead we see a diffuse spatio-temporal structure to parasite genotypes.  Genetic relatedness of sample pairs is predicted by relatedness in space and time. Conclusions: Our findings suggest that targeted malaria control will benefit the surrounding community, but unfortunately also that emerging drug resistance will spread rapidly through the population