Glucose-6-Phosphate Dehydrogenase Deficiency and Haemoglobin Drop after Sulphadoxine-Pyrimethamine Use for Intermittent Preventive Treatment of Malaria during Pregnancy in Ghana - A Cohort Study.

BACKGROUND: Sulphadoxine-Pyrimethamine (SP) is still the only recommended antimalarial for use in intermittent preventive treatment of malaria during pregnancy (IPTp) in some malaria endemic countries including Ghana. SP has the potential to cause acute haemolysis in G6PD deficient people resulting in significant haemoglobin (Hb) drop but there is limited data on post SP-IPTp Hb drop. This study determined the difference, if any in proportions of women with significant acute haemoglobin drop between G6PD normal, partial deficient and full deficient women after SP-IPTp. METHODS AND FINDINGS: Prospectively, 1518 pregnant women who received SP for IPTp as part of their normal antenatal care were enrolled. Their G6PD status were determined at enrollment followed by assessments on days 3, 7,14 and 28 to document any adverse effects and changes in post-IPTp haemoglobin (Hb) levels. The three groups were comparable at baseline except for their mean Hb (10.3 g/dL for G6PD normal, 10.8 g/dL for G6PD partial deficient and 10.8 g/dL for G6PD full defect women).The prevalence of G6PD full defect was 2.3% and 17.0% for G6PD partial defect. There was no difference in the proportions with fractional Hb drop ≥ 20% as compared to their baseline value post SP-IPTp among the 3 groups on days 3, 7, 14. The G6PD full defect group had the highest median fractional drop at day 7. There was a weak negative correlation between G6PD activity and fractional Hb drop. There was no statistical difference between the three groups in the proportions of those who started the study with Hb ≥ 8g/dl whose Hb level subsequently fell below 8g/dl post-SP IPTp. No study participant required transfusion or hospitalization for severe anaemia. CONCLUSIONS: There was no significant difference between G6PD normal and deficient women in proportions with significant acute haemoglobin drop post SP-IPTp and lower G6PD enzyme activity was not strongly associated with significant acute drug-induced haemoglobin drop post SP-IPTp but a larger study is required to confirm consistency of findings

Adapting the Community-based Health Planning and Services (CHPS) to engage poor urban communities in Ghana: protocol for a participatory action research study

Introduction: With rapid urbanisation in low-income and middle-income countries, health systems are struggling to meet the needs of their growing populations. Community-based Health Planning and Services (CHPS) in Ghana have been effective in improving maternal and child health in rural areas; however, implementation in urban areas has proven challenging. This study aims to engage key stakeholders in urban communities to understand how the CHPS model can be adapted to reach poor urban communities.Methods and analysis: A Participatory Action Research (PAR) will be used to develop an urban CHPS model with stakeholders in three selected CHPS zones: (a) Old Fadama (Yam and Onion Market community), (b) Adedenkpo and (c) Adotrom 2, representing three categories of poor urban neighbourhoods in Accra, Ghana. Two phases will be implemented: phase 1 (‘reconnaissance phase) will engage and establish PAR research groups in the selected zones, conduct focus groups and individual interviews with urban residents, households vulnerable to ill-health and CHPS staff and key stakeholders. A desk review of preceding efforts to implement CHPS will be conducted to understand what worked (or not), how and why. Findings from phase 1 will be used to inform and co-create an urban CHPS model in phase 2, where PAR groups will be involved in multiple recurrent stages (cycles) of community-based planning, observation, action and reflection to develop and refine the urban CHPS model. Data will be managed using NVivo software and coded using the domains of community engagement as a framework to understand community assets and potential for engagement

Adapting the Community-based Health Planning and Services (CHPS) to engage poor urban communities in Ghana: protocol for a participatory action research study

Introduction: With rapid urbanisation in low-income and middle-income countries, health systems are struggling to meet the needs of their growing populations. Community-based Health Planning and Services (CHPS) in Ghana have been effective in improving maternal and child health in rural areas; however, implementation in urban areas has proven challenging. This study aims to engage key stakeholders in urban communities to understand how the CHPS model can be adapted to reach poor urban communities.Methods and analysis: A Participatory Action Research (PAR) will be used to develop an urban CHPS model with stakeholders in three selected CHPS zones: (a) Old Fadama (Yam and Onion Market community), (b) Adedenkpo and (c) Adotrom 2, representing three categories of poor urban neighbourhoods in Accra, Ghana. Two phases will be implemented: phase 1 (‘reconnaissance phase) will engage and establish PAR research groups in the selected zones, conduct focus groups and individual interviews with urban residents, households vulnerable to ill-health and CHPS staff and key stakeholders. A desk review of preceding efforts to implement CHPS will be conducted to understand what worked (or not), how and why. Findings from phase 1 will be used to inform and co-create an urban CHPS model in phase 2, where PAR groups will be involved in multiple recurrent stages (cycles) of community-based planning, observation, action and reflection to develop and refine the urban CHPS model. Data will be managed using NVivo software and coded using the domains of community engagement as a framework to understand community assets and potential for engagement

Chemical genetic dissection of aurora a kinase in breast cancer

Aurora A kinase is a mitotic protein which is overexpressed in a variety of cancer and plays a significant role in tumorigenesis. Our goal is to identify Aurora A kinase substrates in metastatic breast cancer cell lines. These substrates will be used as cues to unravel the molecular mechanism by which Aurora A promotes breast malignancy. We employed a chemical genetic technique to identify direct substrates of Aurora A kinase in breast cancer. It involves a space-creating mutation at the kinase ATP binding pocket, which renders it sensitive to orthogonal ATP analogs. The chemical genetic technique which has been applied to over 50 different kinases, did not work for the Aurora A kinase. Using modeling, we identified a new residue, which was less than 5 angstroms away from the N-6 group of the adenine ring of ATP. This single mutation along with the mutation at the gate keeper residue made the kinase susceptible to N6(phenethyl)-ATP. Using the engineered Aurora A kinase and mass spectrometry we have identified several direct substrates in breast cancer cells. Two of the identified substrates were chosen for further validation: Pleckstrin homology-like domain family A member 1 (PHLDA1) and Lim kinase 2 (LIMK2). PHLDA1 encodes a protein of 262 amino acids and has recently been suggested to be a tumor suppressor. Loss of PHLDA1 mRNA and protein has been correlated with breast adenocarcinoma and melanoma progression in clinical samples. The exact mechanism as to how PHLDA1 mediates its role as a tumor suppressor is still not known. Our data shows Aurora A kinase directly phosphorylates and interacts with PHLDA1. Phosphorylation of PHLDA1 by Aurora A on residue S98 facilitates its degradation. On the other hand, overexpression of PHLDA1 downregulates Aurora A mediated breast cancer cell invasion, proliferation and migration to suppress it oncogenic activity. Taken together, our data indicate that deregulation of the functional balance between Aurora A and PHLDA1 could be another mechanism in Aurora A mediated tumorigenesis and metastasis. In contrast to PHLDA1, LIMK2 a serine/threonine kinase have recently been shown to have an essential role in the migration and metastatic behavior of pancreatic cancer cells. However, LIMK2 has not been analyzed in breast cancer. We report for the first time, the importance of LIMK2 in Aurora A mediated transformation and tumorigenesis in breast cancer. Aurora A positively regulates LIMK2 protein levels by phosphorylating at S283, T494 and T505. We further observed that LIMK2 also positively regulates Aurora A levels. Ablation of LIMK2 abrogate Aurora A mediated cell migration and colony formation in soft agar. Most importantly, in nude mouse xenografts, ablation of LIMK2 completely abrogates tumor formation, suggesting that LIMK2 is an important therapeutic target in breast cancer

Design, construction and evaluation of an evaporative cooler for the storage of sweet potatoes in the north Ghana

A 14.4 × 86.0 × 70.0 cm mud evaporative cooler was designed and constructed for the storage of sweet potato roots to evaluate its performance in storing orange fleshed sweet potato variety (Apomuden) roots.  The investigation lasted for 14 weeks, from November 2014 to February, 2015.  The dry bulb (Tdb) and wet bulb temperatures (Twb) for the ambient storage ranged between 27.600C to 26.900C and 22.500C to 20.100C respectively with their corresponding RH of 64.00%, 77.00% respectively, while Tdb and Twb within the cooler ranged between 25.940C to 24.860C and 21.940C to 20.610C with corresponding R.H of 89.00% to 92.00% respectively.  The efficiency of the constructed evaporative cooler was 87.17%. From an initial weight of 2000 g, roots weight decreased to 1298.3 g during the storage period, while the weight loss within the cooler was from 2000 g to 1570.65 g over the same period. Also, the moisture content of the roots stored under ambient conditions declined from 68.9% to 48.35%.  Roots stored in the evaporative cooler declined from 68.9% to 60.80%.  As mc decreased from 68.9% to 48.35%, energy content increased from an initial of 501 to 858.677 kJ/100g under ambient storage while in the evaporative cooler, as mc declined, from 68.9% to 60.8%, energy content increased from an initial of 501.518 to 642.296 kJ/100g.  The evaporative cooler maintained the quality of the sweet potato roots by fourteen weeks while those stored in the ambient storage lasted for eight weeks

Correlation between G6PD activity (U/gHb) and fractional Hb drops in study participants with a decline in Hb from baseline post SP-IPTp.

<p>Correlation between G6PD activity (U/gHb) and fractional Hb drops in study participants with a decline in Hb from baseline post SP-IPTp.</p

Map of Ghana showing the three study areas.

<p>Map of Ghana showing the three study areas.</p

Baseline demographic characteristics of study participants by G6PD status^*.

<p>*G6PD status was available for 1507 study women.</p><p>Baseline demographic characteristics of study participants by G6PD status^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0136828#t001fn001" target="_blank">*</a>}.</p