Association of putative enteroaggregative Escherichia coli virulence genes and biofilm production in isolates from travelers to developing countries.

Enteroaggregative Escherichia coli (EAEC) is an emerging enteric pathogen that causes acute and chronic diarrhea among children, human immunodeficiency virus-infected patients, and travelers to developing regions of the world. The pathogenesis of EAEC strains involves the production of biofilm. In this study, we determined the association between presence of putative EAEC virulence genes and biofilm formation in 57 EAEC isolates (as defined by HEp-2 adherence) from travelers with diarrhea and in 18 EAEC isolates from travelers without diarrhea. Twelve nondiarrheagenic E. coli isolates from healthy travelers were used as controls. Biofilm formation was measured by using a microtiter plate assay with the crystal violet staining method, and the presence of the putative EAEC virulence genes aap, aatA, aggR, astA, irp2, pet, set1A, and shf was determined by PCR. EAEC isolates were more likely to produce biofilm than nondiarrheagenic E. coli isolates (P = 0.027), and the production of biofilm was associated with the virulence genes aggR, set1A, aatA, and irp2, which were found in 16 (40%), 17 (43%), 10 (25%), and 27 (68%) of the biofilm producers versus only 4 (11%), 6 (6%), 2 (6%), and 15 (43%) in non-biofilm producers (P = 0.008 for aggR, P = 0.0004 for set1A, P = 0.029 for aatA, and P = 0.04 for irp2). Although the proportion of EAEC isolates producing biofilm in patients with diarrhea (51%) was similar to that in patients without diarrhea (61%), biofilm production was related to the carriage of aggR (P = 0.015), set1A (P = 0.001), and aatA (P = 0.025). Since aggR is a master regulator of EAEC, the presence of aap (P = 0.004), astA (P = 0.001), irp2 (P = 0.0006), pet (P = 0.002), and set1A (P = 0.014) in an aggR versus an aggR-lacking background was investigated and was also found to be associated with biofilm production. This study suggests that biofilm formation is a common phenomenon among EAEC isolates derived from travelers with or without diarrhea and that multiple genes associated with biofilm formation are regulated by aggR.

STRATEGIES FOR THE TRANSFER OF APPROPRIATE TECHNOLOGY TO DEVELOPING COUNTRIES: THE IMPLEMENTATION AND DEVELOPMENT OF ENVIRONMENTAL HEALTH PROGRAMS IN TUNISIA

This dissertation focuses on Project HOPE, an American medical aid agency, and its work in Tunisia. More specifically this is a study of the implementation strategies of those HOPE sponsored projects and programs designed to solve the problems of high morbidity and infant mortality rates due to environmentally related diarrheal and enteric diseases. Several environmental health programs and projects developed in cooperation with Tunisian counterparts are described and analyzed. These include (1) a paramedical manpower training program; (2) a national hospital sanitation and infection control program; (3) a community sewage disposal project; (4) a well reconstruction project; and (5) a solid-waste disposal project for a hospital.^ After independence, Tunisia, like many developing countries, encountered several difficulties which hindered progress toward solving basic environmental health problems and prompted a request for aid. This study discusses the need for all who work in development programs to recognize and assess those difficulties or constraints which affect the program planning process, including those latent cultural and political constraints which not only exist within the host country but within the aid agency as well. For example, failure to recognize cultural differences may adversely affect the attitudes of the host staff towards their work and towards the aid agency and its task. These factors, therefore, play a significant role in influencing program development decisions and must be taken into account in order to maximize the probability of successful outcomes.^ In 1969 Project HOPE was asked by the Tunisian government to assist the Ministry of Health in solving its health manpower problems. HOPE responded with several programs, one of which concerned the training of public health nurses, sanitary technicians, and aids at Tunisia's school of public health in Nabeul. The outcome of that program as well as the strategies used in its development are analyzed. Also, certain questions are addressed such as, what should the indicators of success be, and when is the time right to phase out?^ Another HOPE program analyzed involved hospital sanitation and infection control. Certain generic aspects of basic hospital sanitation procedures were documented and presented in the form of a process model which was later used as a "microplan" in setting up similar programs in other Tunisian hospitals. In this study the details of the "microplan" are discussed. The development of a nation-wide program without any further need of external assistance illustrated the success of HOPE's implementation strategies.^ Finally, although it is known that the high incidence of enteric disease in developing countries is due to poor environmental sanitation and poor hygiene practices, efforts by aid agencies to correct these conditions have often resulted in failure. Project HOPE's strategy was to maximize limited resources by using a systems approach to program development and by becoming actively involved in the design and implementation of environmental health projects utilizing "appropriate" technology. Three innovative projects and their implementation strategies (including technical specifications) are described.^ It is advocated that if aid agencies are to make any progress in helping developing countries basic sanitation problems, they must take an interdisciplinary approach to progrm development and play an active role in helping counterparts seek and identify appropriate technologies which are socially and economically acceptable. ^

Globesity: Food marketing to children in Asia-Pacific A systematic review

Food advertising and promotion to children has been identified as one possible contributing factor to the childhood obesity pandemic. Food marketing to children in "western" society consists mainly of foods that are high in fat, sugar and salt (HFSS), such as pre-sugared breakfast cereals; sugar sweetened beverages (SSBs); confectionary; savory snacks; and fast food. Of these heavily marketed items consumption of, SSBs, savory snacks and fast foods have been found to contribute to the childhood obesity pandemic. A systematic review was conducted to determine what types of products are being promoted and what types of techniques food marketers are using to promote these foods throughout the Asia-Pacific region. The review of current literature, while not abundant, clearly showed marketing styles and content similar to those in western countries were being employed in the Asia-Pacific. Advertisements in this geographic region often took on a local flair to make them more identifiable to children and adolescents in their respective regions and countries, due to the numerous cultural and traditional differences. Children in these developing parts of the world may be just as, if not more, susceptible to these advertising techniques than their counterparts in the west.^

ROLE OF GSH METABOLISM IN MEDIATING STROMAL-LEUKEMIA INTERACTION AND PROMOTING CELL SURVIVAL AND DRUG RESISTANCE IN CHRONIC LYMPHOCYTIC LEUKEMIA

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the western countries. The interaction between CLL cells and the bone marrow stromal environment is thought to play a major role in promoting the leukemia cell survival and drug resistance. My dissertation works proved a novel biochemical mechanism by which the bone marrow stromal cells exert a profound influence on the redox status of primary CLL cells and enhance their ability to sustain oxidative stress and drug treatment. Fresh leukemia cells isolated from the peripheral blood of CLL patients exhibited two major redox alterations when they were cultured alone: a significant decrease in cellular glutathione (GSH) and an increase in basal ROS levels. However, when cultured in the presence of bone marrow stromal cells, CLL cells restored their redox balance with an increased synthesis of GSH, a decrease in spontaneous apoptosis, and an improved cell survival. Further study showed that CLL cells were under intrinsic ROS stress and highly dependent on GSH for survival, and that the bone marrow stromal cells promoted GSH synthesis in CLL cells through a novel biochemical mechanism. Cysteine is a limiting substrate for GSH synthesis and is chemically unstable. Cells normally obtain cysteine by uptaking the more stable and abundant precursor cystine from the tissue environment and convert it to cysteine intracellularly. I showed that CLL cells had limited ability to take up extracellular cystine for GSH synthesis due to their low expression of the transporter Xc-, but had normal ability to uptake cysteine. In the co-culture system, the bone marrow stromal cells effectively took up cystine and reduced it to cysteine for secretion into the tissue microenvironment to be taken up by CLL cells for GSH synthesis. The elevated GSH in CLL cells in the presence of bone marrow stromal cells significantly protected the leukemia cells from stress-induced apoptosis, and rendered them resistant to standard therapeutic agents such as fludarabine and oxaliplatin. Importantly, disabling of this protective mechanism by depletion of cellular GSH using a pharmacological approach potently sensitized CLL cells to drug treatment, and effectively enhanced the cytotoxic action of fludarabine and oxaliplatin against CLL in the presence of stromal cells. This study reveals a key biochemical mechanism of leukemia-stromal cells interaction, and identifies a new therapeutic strategy to overcome drug resistance in vivo.

Characterization of diabetes risk factors of elementary school children in low income areas of San Antonio, Texas

The number of children developing type-2 diabetes mellitus (T2DM) is increasing globally, especially in Western countries. Previous studies have indicated that low socioeconomic status (SES) is a contributing factor to diabetes. This study of children examined the relationship of socioeconomic status and two physiological measures that are risk factors for diabetes: the level of fasting capillary glucose (FCG) and hyperglycemia, in which there is an elevated amount of glucose in the blood. This study utilized data from the study entitled Bienester: A School-Based Diabetes Mellitus Prevention Program. The sample was 1,426 fourth grade students from 27 San Antonio Independent School District elementary schools. The dependent variable was FCG and the independent variable was the median family income associated with the student's zip code based on Census information. Other variables included body mass index, gender, and ethnicity. The statistical results showed no relationship between FCG, continuously defined, and income. In addition, there was no relationship between hyperglycemia and income. Furthermore, there was no relationship of FCG with BMI, gender, or ethnicity. Income measured at the zip code level is likely too aggregate and distal an influence to demonstrate an impact on FCG. Research should continue to examine risk factors associated with the onset of T2DM.^

Is obesity associated with increased symptoms of psychiatric morbidity among Indian adolescents?

The relationship between obesity and mental health disorders has not been explored among adolescents in India. Although evidence from western countries has failed to demonstrate conclusive associations, a tremendous increase in the prevalence of obesity and overweight among urban adolescents in India, along with an absolute lack of studies into mental health of Indian adolescents, necessitate the need for research in this population. This present study used data collected from 861 urban 6th and 8th graders from Delhi, India and tested for the associations of weight status with psychiatric symptomatology and other weight related behaviors. The Strengths and Difficulties questionnaire (SDQ) was used to collect data on psychiatric symptoms. Falling into the overweight or obese category was hypothesized to be associated with borderline or abnormal scores on the SDQ scales. Results indicated a high prevalence for overweight/obesity among the population (>30%). No significant associations were demonstrated between weight status and borderline/abnormal SDQ scores on all the scales. However, significant associations were found between sedentary behaviors (screen time >2 hrs daily), positive and negative weight-control behaviors and borderline/abnormal SDQ scores on various scales. In light of these new findings, a further exploration of the relationship in this population is indicated.^