QUANTITATIVE PROTEOMIC ANALYSES OF HUMAN PLASMA: APPLICATION OF MASS SPECTROMETRY FOR THE DISCOVERY OF CLINICAL DELIRIUM BIOMARKERS

The biomarker discovery pipeline is a multi-step endeavor to identify potential diagnostic or prognostic markers of a disease. Although the advent of modern mass spectrometers has revolutionized the initial discovery phase, a significant bottleneck still exists when validating discovered biomarkers. In this doctoral research, I demonstrate that the discovery, verification and validation of biomarkers can all be performed using mass spectrometry and apply the biomarker pipeline to the context of clinical delirium. First, a systematic review of recent literature provided a birds-eye view of untargeted, discovery proteomic attempts for biomarkers of delirium in the geriatric population. Here, a comprehensive search from five databases yielded 1172 publications, from which eight peer-reviewed studies met our defined inclusion criteria. Despite the paucity of published studies that applied systems- biology approaches for biomarker discovery on the subject, lessons learned and insights from this review was instrumental in the study designing and proteomics analyses of plasma sample in our cohort. We then performed a targeted study on four biomarkers for their potential mediation role in the occurrence of delirium after high-dose intra-operative oxygen treatment. Although S100B calcium binding protein (S100B), gamma enolase (ENO2), chitinase-3-like protein 1 (CHI3L1) and ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1) have well-documented associations with delirium, we did not find any such associations in our cohort. Of note, this study demonstrates that the use of targeted approaches for the purposes of biomarker discovery, rather than an untargeted, systems-biology approach, is unavoidably biased and may lead to misleading conclusions. Lastly, we applied lessons learned and comprehensively profiled the plasma samples of delirium cases and non-delirium cases, at both pre- and post-surgical timepoints. We found 16 biomarkers as signatures of cardiopulmonary bypass, and 11 as potential diagnostic candidates of delirium (AuROC = 93%). We validated the discovered biomarkers on the same mass spectrometry platform without the use of traditional affinity-based validation methods. Our discovery of novel biomarkers with no know association with delirium such as serum amyloid A1 (SAA1) and A2 (SAA2), pepsinogen A3 (PEPA3) and cathepsin B (CATB) shed new lights on possible neuronal pathomechanisms

Monetary policy and microfinance in Sub-Sahara Africa: Ghana’s perspective

Ghana, like many other developing countries in Sub-Sahara Africa, recognises the important role that the micro, small and medium-sized enterprises (MSMEs) play in economic development. These enterprises need an environment conducive to thriving and growth, to contribute to employment and overall output. A key pillar to this is access to affordable credit. Credit in itself is thought to be affected by monetary policy formulated and put forth by the central bank, on behalf of government. The pass-through effect of monetary policy on commercial banking rates, as charged by bank and non-bank financial institutions (NBFIs), is a concern for MSMEs. Therefore, this study sought to highlight cause and effects relationship between monetary policy, the lending rate and private sector credit, and also sought to find a possible cushion for MSMEs through the microfinance targeting approach. Annual aggregate monetary time series data from the Bank of Ghana (BoG) was analysed. Multiple linear regression and analysis of variance test results reveal evidence of a significant and proportional effect of both the monetary policy rate and commercial banking rate on credit to the private sector. The key implication of the findings is that the pass-through effect of monetary policy negatively affects MSMEs. The study recommends that governments in Sub-Sahara Africa (SSA), and particularly the government of Ghana, should take into consideration the effects of monetary policy on MSMEs, when formulating monetary policies. It is also recommended that governments in SSA should formulate policies that enhance MSMEs access to adequate and affordable credit to enable it contribute more to economic growth. Perhaps, this can be done through microfinance

The rental system in Ghana’s low-income housing communities, challenges and adaptation strategies

Shelter is one of the fundamental needs of human survival aside food and clothing. However, provision of adequate housing to accommodate people in urban areas has been a challenge in developing countries, including Ghana. This has caused many Ghanaians, especially the low-income group, to resort to the rental sector for their housing needs. It is widely discussed in the literature that each city user is to be accorded the needed right to utilise what exists in the city, including decent accommodation. This article examines the strategies put in place by low-income house tenants to cope with the challenges of renting houses in the Wenchi Municipality, in order to rightly utilise urban housing. The study used a quantitative approach and a questionnaire survey to collect data from 245 tenant household heads. Purposive and systematic sampling techniques were used to select the respondents for the study. The data was analysed using SPSS. The study revealed that rental problems faced by tenants and adaptation measures developed to cope in cities and bigger towns are not different from what exists in the smaller towns. The study recommended that rent control should be strengthened to perform its duties in the rental sector well enough to protect the interest of the urban low-income renters

Does Access to Market Information Determine the Choice of Marketing Channel among Smallholder Yam Farmers in the Brong Ahafo Region of Ghana? A Multinomial Logit Regression Analysis

Asymmetric or missing information is likely to cause market failure and greater access of farmers to knowledge about markets and prices, is a key element in the efforts of breaking the cycle of poverty. This study describes the yam marketing distribution channel in Brong-Ahafo region. It also quantifies the magnitude and direction of the effect of market information access on the choice of yam marketing channel using the Multinomial Logit regression analysis. The study is cross sectional in designs. A total of 250 smallholder yam farmers participated in the survey. Data collected was analyzed using StataSE 11. Results indicate that there are six main channels of yam distribution comprising of producers, assemblers, wholesalers and retailers. The study observes, inter alia, that age of household head, access to cell phone, farm size and output price determine the choice of rural market relative to urban market whilst gender of household head, number of years of formal education and distance to tarred road significantly influences the choice of cooperative market relative to urban market. Access to cell phone and the interactive term (cell phone access*location of household head) are the most influential determinants of rural market and market cooperative choice both statistically and numerically respectively. These results have implications for agricultural policy in Ghana. Key words: Multinomial Logit, Brong-Ahafo, Market channel, Cell Phone, Market informatio

Are Farmers Surviving the Level of Seasonal Cultivation of Tomatoes in Ghana? A Tobit Regression Analysis

Tomato is an important vegetable in the cultivation and diet of Ghanaians. However, statistics have shown that domestic production of fresh tomato is on the decline. As an important traded commodity, the research wonders if the decline is due to lower farm land devoted to its cultivation.The paper therefore, seeks to identify factors that influence the seasonal farm size devoted to tomato cultivation. A total of 159 farmers in three regions in Ghana were purposively and randomly sampled and interviewed. Results from thetobitregression model suggests that approaching the dry season, farmers using any irrigation technology tend to allocate smaller proportion of farmland to tomato. It was also realised that as farmers acquire additional farmland for crop production, they are likely to reduce the level of tomato cultivation. This could mean that farmers are only surviving the cultivation of tomato as they are unlikely to increase its cultivation. Strategies that reduce the cost of irrigation especially in the drier seasons and enhance access is critical for increasing tomato production in Ghana. Training of farmers must target good storage and use of seeds from formal sources. Key words: Seasonal, Tomato, Cultivation, Tobit Model, Ghan

Reversion of Sulfenamide Prodrugs in the Presence of Free Thiol Containing Proteins

The purpose of this work was to study the reaction kinetics between two model sulfenamide prodrugs of linezolid, N-(phenylthio)linezolid and N-((2-ethoxycarbonyl)ethylthio)linezolid, with free thiol containing proteins; human serum albumin (HSA); a constitutively active mutant of theprotein tyrosine phosphatase PRL-1, PRL-1-C170-171S, a model protein; and diluted fresh human plasma. The reaction was followed by HPLC, both for the loss of prodrug and appearance of linezolid, and at different pH values with molar excess of the proteins relative to the prodrugs. Pseudo first-order kinetics were observed. Consistent with earlier findings for the reaction between similar sulfenamides and small molecule thiols, the reaction kinetics appeared to be consistent with thiolate attack at the sulfenamide bond to release the parent drug. The proteins reacted significantly slower on a molar basis than their small molecule counterparts. It appears that proteins such as HSA may play a role in the in vivo conversion of sulfenamide prodrugs to their parent drug

Anaemia in pregnant adolescent girls with malaria and practicing pica

Introduction: pregnancy during the adolescent period is challenging mainly because of the nutritional demands of both the adolescent and pregnancy period. The risk for anaemia increases especially in developing countries such as Ghana where malaria is endemic and the practice of pica is common. In this study, we sought to determine the prevalence of anaemia, pica practice and malaria infection among pregnant adolescent girls and assess the extent to which these factors are associated. Methods: two hundred and sixty five (265) pregnant adolescent girls were recruited from three hospitals in Accra. Haemoglobin levels, malaria infection and the practice of pica were assessed. Pearson’s Chi squared tests were used to determine associations and logistic regression analysis was used to determine the odds of being anaemic. Significance was set at p≤0.05. Results: anaemia prevalence was 76% with severity ranging from mild (47.8%) to severe (0.8%). About 27.5% were moderately anaemic. Pica was practiced in only 9.1% of the girls. Malaria infection was prevalent in 17.7% of the girls. The logistic regression analysis indicated that pregnant girls with malaria infection were 3.56 times more likely to be anaemic when compared to those without malaria. Also, those who practiced pica were 1.23 times more likely to be anaemic when compared to those who did not practice pica. Conclusion: anaemia is very prevalent in pregnant adolescent  girls and is a public health problem. Drastic measures should be taken to reduce the high prevalence.The Pan African Medical Journal 2016;2

Performance and Constraints of Small Scale Enterprises in the Accra Metropolitan Area of Ghana

Small Scale Enterprises play a crucial role in the development of entrepreneurial capabilities and indigenous technology which generate employment. Promotion of such enterprises in developing economies like Ghana is of paramount importance as it brings about a great distribution of benefits. The study seeks to quantify the determinants of the factors influencing performance of small scale enterprises in Accra Metropolitan Area of Ghana. Kendall’s coefficient of concordance was used to test the agreement between the ranked constraints of the small scale enterprises in relation to performance. The study uses structured questionnaire to interview 150 small scale entrepreneurs in Accra Metropolitan Area (AMA). Data collected was analyzed using Statistical Package for Social Science (SPSS) and Econometric views (E-views). Results of the analysis indicate that age of entrepreneur is the most influential determinant of performance of small scale enterprises. The Kendall’s coefficient of concordance indicates that there is 91 percent agreement between the respondents in the ranking of the constraints in relation to performance. High cost of borrowing is the most important constraint faced by the small scale entrepreneurs. Based on the results, we recommend a flexible policy geared towards helping young entrepreneurs, as well as reducing the high interest charges on loans. Key words: Performance, Constraint, Small Scale Enterprise, Accra Metropolitan Area, Ghan

Susceptibility pattern of uropathogens to ciprofloxacin at the Ghana police hospital

Introduction: Reports of increasing resistance of uropathogens to antimicrobials is of global concern. Culture and drug susceptibility tests remain a vital guide to effective therapy. The aim of this study was to determine the susceptibility pattern of isolated uropathogens to ciprofloxacin at the Ghana Police Hospital. Methods: A total of 705 mid-stream urine samples were collected from patients suspected of having  urinary tract infection, and visited the Ghana Police Hospital's laboratory from December 2013 to March  2014. Samples were cultured and isolates identified by standard methods, after which isolates  susceptibility to ciprofloxacin was determined. Results: Prevalence of urinary tract infection among patients' whose samples were analyzed was 15.9%. Predominant uropathogens isolated were E .coli (46.4%), Coliform (41.1%) and Coliform spp. with Candida (6.2%). Other isolates were Pseudomonas spp. (2.7%), Salmonella spp. (1.8%), Candida spp. (0.9%) and Klebsiella spp (0.9%). The overall resistance among the top three isolated uropathogens to ciprofloxacin was 35.9%. Resistance pattern demonstrated by  respective isolates to ciprofloxacin were: E. coli (38.5%), Coliform (54.3%), and Coliform spp. with Candida (15%). The other isolates showed 100% sensitivity.Conclusion: This study revealed a relatively high ciprofloxacin resistance among isolated uropathogens,  hence, the need for prudent prescribing and use of  ciprofloxacin in urinary tract infection management.Key words: Urinary tract infection, isolates, susceptibility, antibiotics, uropathogen