Towards achieving Abuja targets: identifying and addressing barriers to access and use of insecticides treated nets among the poorest populations in Kenya

<p>Abstract</p> <p>Background</p> <p>Ensuring that the poor and vulnerable population benefit from malaria control interventions remains a challenge for malaria endemic countries. Until recently, ownership and use of insecticides treated nets (ITNs) in most countries was low and inequitable, although coverage has increased in countries where free ITN distribution is integrated into mass vaccination campaigns. In Kenya, free ITNs were distributed to children aged below five years in 2006 through two mass campaigns. High and equitable coverage were reported after the campaigns in some districts, although national level coverage remained low, suggesting that understanding barriers to access remains important. This study was conducted to explore barriers to ownership and use of ITNs among the poorest populations before and after the mass campaigns, to identify strategies for improving coverage, and to make recommendations on how increased coverage levels can be sustained.</p> <p>Methods</p> <p>The study was conducted in the poorest areas of four malaria endemic districts in Kenya. Multiple data collection methods were applied including: cross-sectional surveys (n = 708 households), 24 focus group discussions and semi-structured interviews with 70 ITN suppliers.</p> <p>Results</p> <p>Affordability was reported as a major barrier to access but non-financial barriers were also shown to be important determinants. On the demand side key barriers to access included: mismatch between the types of ITNs supplied through interventions and community preferences; perceptions and beliefs on illness causes; physical location of suppliers and; distrust in free delivery and in the distribution agencies. Key barriers on the supply side included: distance from manufacturers; limited acceptability of ITNs provided through interventions; crowding out of the commercial sector and the price. Infrastructure, information and communication played a central role in promoting or hindering access.</p> <p>Conclusions</p> <p>Significant resources have been directed towards addressing affordability barriers through providing free ITNs to vulnerable groups, but the success of these interventions depends largely on the degree to which other barriers to access are addressed. Only if additional efforts are directed towards addressing non-financial barriers to access, will high coverage levels be achieved and sustained.</p

Safety and Efficacy of Methylene Blue Combined with Artesunate or Amodiaquine for Uncomplicated Falciparum Malaria: A Randomized Controlled Trial from Burkina Faso

Besides existing artemisinin-based combination therapies, alternative safe, effective and affordable drug combinations against falciparum malaria are needed. Methylene blue (MB) was the first synthetic antimalarial drug ever used, and recent studies have been promising with regard to its revival in malaria therapy. The objective of this study was to assess the safety and efficacy of two MB-based malaria combination therapies, MB-artesunate (AS) and MB-amodiaquine (AQ), compared to the local standard of care, AS-AQ, in Burkina Faso.Open-label randomised controlled phase II study in 180 children aged 6-10 years with uncomplicated falciparum malaria in Nouna, north-western Burkina Faso. Follow-up was for 28 days and analysis by intention-to-treat. The treatment groups were similar in baseline characteristics and there was only one loss to follow-up. No drug-related serious adverse events and no deaths occurred. MB-containing regimens were associated with mild vomiting and dysuria. No early treatment failures were observed. Parasite clearance time differed significantly among groups and was the shortest with MB-AS. By day 14, the rates of adequate clinical and parasitological response after PCR-based correction for recrudescence were 87% for MB-AS, 100% for MB-AQ (p = 0.004), and 100% for AS-AQ (p = 0.003). By day 28, the respective figure was lowest for MB-AS (62%), intermediate for the standard treatment AS-AQ (82%; p = 0.015), and highest for MB-AQ (95%; p<0.001; p = 0.03).MB-AQ is a promising alternative drug combination against malaria in Africa. Moreover, MB has the potential to further accelerate the rapid parasite clearance of artemisinin-based combination therapies. More than a century after the antimalarial properties of MB had been described, its role in malaria control deserves closer attention.ClinicalTrials.gov NCT00354380

Regulation of BRCA1 expression and its relationship to sporadic breast cancer

Germ-line mutations in the BRCA1 tumour suppressor gene contribute to familial breast tumour formation, but there is no evidence for direct mutation of the BRCA1 gene in the sporadic form of the disease. In contrast, decreased expression of the BRCA1 gene has been shown to be common in sporadic tumours, and the magnitude of the decrease correlates with disease progression. BRCA1 expression is also tightly regulated during normal breast development. Determining how these developmental regulators of BRCA1 expression are co-opted during breast tumourigenesis could lead to a better understanding of sporadic breast cancer aetiology and the generation of novel therapeutic strategies aimed at preventing sporadic breast tumour progression

Reference genes for gene expression studies in wheat flag leaves grown under different farming conditions

<p>Abstract</p> <p>Background</p> <p>Internal control genes with highly uniform expression throughout the experimental conditions are required for accurate gene expression analysis as no universal reference genes exists. In this study, the expression stability of 24 candidate genes from <it>Triticum aestivum </it>cv. Cubus flag leaves grown under organic and conventional farming systems was evaluated in two locations in order to select suitable genes that can be used for normalization of real-time quantitative reverse-transcription PCR (RT-qPCR) reactions. The genes were selected among the most common used reference genes as well as genes encoding proteins involved in several metabolic pathways.</p> <p>Findings</p> <p>Individual genes displayed different expression rates across all samples assayed. Applying geNorm, a set of three potential reference genes were suitable for normalization of RT-qPCR reactions in winter wheat flag leaves cv. Cubus: <it>TaFNRII </it>(ferredoxin-NADP(H) oxidoreductase; AJ457980.1), <it>ACT2 </it>(actin 2; TC234027), and <it>rrn26 </it>(a putative homologue to RNA 26S gene; AL827977.1). In addition of these three genes that were also top-ranked by NormFinder, two extra genes: <it>CYP18-2 </it>(Cyclophilin A, AY456122.1) and <it>TaWIN1 </it>(14-3-3 like protein, AB042193) were most consistently stably expressed.</p> <p>Furthermore, we showed that <it>TaFNRII, ACT2</it>, and <it>CYP18-2 </it>are suitable for gene expression normalization in other two winter wheat varieties (Tommi and Centenaire) grown under three treatments (organic, conventional and no nitrogen) and a different environment than the one tested with cv. Cubus.</p> <p>Conclusions</p> <p>This study provides a new set of reference genes which should improve the accuracy of gene expression analyses when using wheat flag leaves as those related to the improvement of nitrogen use efficiency for cereal production.</p

Environmental Influences on Mate Preferences as Assessed by a Scenario Manipulation Experiment

Many evolutionary psychology studies have addressed the topic of mate preferences, focusing particularly on gender and cultural differences. However, the extent to which situational and environmental variables might affect mate preferences has been comparatively neglected. We tested 288 participants in order to investigate the perceived relative importance of six traits of an ideal partner (wealth, dominance, intelligence, height, kindness, attractiveness) under four different hypothetical scenarios (status quo/nowadays, violence/post-nuclear, poverty/resource exhaustion, prosperity/global well-being). An equal number of participants (36 women, 36 men) was allotted to each scenario; each was asked to allocate 120 points across the six traits according to their perceived value. Overall, intelligence was the trait to which participants assigned most importance, followed by kindness and attractiveness, and then by wealth, dominance and height. Men appraised attractiveness as more valuable than women. Scenario strongly influenced the relative importance attributed to traits, the main finding being that wealth and dominance were more valued in the poverty and post-nuclear scenarios, respectively, compared to the other scenarios. Scenario manipulation generally had similar effects in both sexes, but women appeared particularly prone to trade off other traits for dominance in the violence scenario, and men particularly prone to trade off other traits for wealth in the poverty scenario. Our results are in line with other correlational studies of situational variables and mate preferences, and represent strong evidence of a causal relationship of environmental factors on specific mate preferences, corroborating the notion of an evolved plasticity to current ecological conditions. A control experiment seems to suggest that our scenarios can be considered as realistic descriptions of the intended ecological conditions

Environmental Influences on Mate Preferences as Assessed by a Scenario Manipulation Experiment

Many evolutionary psychology studies have addressed the topic of mate preferences, focusing particularly on gender and cultural differences. However, the extent to which situational and environmental variables might affect mate preferences has been comparatively neglected. We tested 288 participants in order to investigate the perceived relative importance of six traits of an ideal partner (wealth, dominance, intelligence, height, kindness, attractiveness) under four different hypothetical scenarios (status quo/nowadays, violence/post-nuclear, poverty/resource exhaustion, prosperity/global well-being). An equal number of participants (36 women, 36 men) was allotted to each scenario; each was asked to allocate 120 points across the six traits according to their perceived value. Overall, intelligence was the trait to which participants assigned most importance, followed by kindness and attractiveness, and then by wealth, dominance and height. Men appraised attractiveness as more valuable than women. Scenario strongly influenced the relative importance attributed to traits, the main finding being that wealth and dominance were more valued in the poverty and post-nuclear scenarios, respectively, compared to the other scenarios. Scenario manipulation generally had similar effects in both sexes, but women appeared particularly prone to trade off other traits for dominance in the violence scenario, and men particularly prone to trade off other traits for wealth in the poverty scenario. Our results are in line with other correlational studies of situational variables and mate preferences, and represent strong evidence of a causal relationship of environmental factors on specific mate preferences, corroborating the notion of an evolved plasticity to current ecological conditions. A control experiment seems to suggest that our scenarios can be considered as realistic descriptions of the intended ecological conditions

Matrix Metalloproteinase-Induced Epithelial-Mesenchymal Transition in Breast Cancer

Matrix metalloproteinases (MMPs) degrade and modify the extracellular matrix (ECM) as well as cell-ECM and cell-cell contacts, facilitating detachment of epithelial cells from the surrounding tissue. MMPs play key functions in embryonic development and mammary gland branching morphogenesis, but they are also upregulated in breast cancer, where they stimulate tumorigenesis, cancer cell invasion and metastasis. MMPs have been investigated as potential targets for cancer therapy, but clinical trials using broad-spectrum MMP inhibitors yielded disappointing results, due in part to lack of specificity toward individual MMPs and specific stages of tumor development. Epithelial-mesenchymal transition (EMT) is a developmental process in which epithelial cells take on the characteristics of invasive mesenchymal cells, and activation of EMT has been implicated in tumor progression. Recent findings have implicated MMPs as promoters and mediators of developmental and pathogenic EMT processes in the breast. In this review, we will summarize recent studies showing how MMPs activate EMT in mammary gland development and in breast cancer, and how MMPs mediate breast cancer cell motility, invasion, and EMT-driven breast cancer progression. We also suggest approaches to inhibit these MMP-mediated malignant processes for therapeutic benefit

Network analysis of human glaucomatous optic nerve head astrocytes

<p>Abstract</p> <p>Background</p> <p>Astrocyte activation is a characteristic response to injury in the central nervous system, and can be either neurotoxic or neuroprotective, while the regulation of both roles remains elusive.</p> <p>Methods</p> <p>To decipher the regulatory elements controlling astrocyte-mediated neurotoxicity in glaucoma, we conducted a systems-level functional analysis of gene expression, proteomic and genetic data associated with reactive optic nerve head astrocytes (ONHAs).</p> <p>Results</p> <p>Our reconstruction of the molecular interactions affected by glaucoma revealed multi-domain biological networks controlling activation of ONHAs at the level of intercellular stimuli, intracellular signaling and core effectors. The analysis revealed that synergistic action of the transcription factors AP-1, vitamin D receptor and Nuclear Factor-kappaB in cross-activation of multiple pathways, including inflammatory cytokines, complement, clusterin, ephrins, and multiple metabolic pathways. We found that the products of over two thirds of genes linked to glaucoma by genetic analysis can be functionally interconnected into one epistatic network via experimentally-validated interactions. Finally, we built and analyzed an integrative disease pathology network from a combined set of genes revealed in genetic studies, genes differentially expressed in glaucoma and closely connected genes/proteins in the interactome.</p> <p>Conclusion</p> <p>Our results suggest several key biological network modules that are involved in regulating neurotoxicity of reactive astrocytes in glaucoma, and comprise potential targets for cell-based therapy.</p