International Journal of Environmental Research and Public Health
The Research Centers in Minority Institutions (RCMI) Program was congressionally mandated in 1985... more The Research Centers in Minority Institutions (RCMI) Program was congressionally mandated in 1985 to build research capacity at institutions that currently and historically recruit, train, and award doctorate degrees in the health professions and health-related sciences, primarily to individuals from underrepresented and minority populations. RCMI grantees share similar infrastructure needs and institutional goals. Of particular importance is the professional development of multidisciplinary teams of academic and community scholars (the “workforce”) and the harnessing of the heterogeneity of thought (the “thinkforce”) to reduce health disparities. The purpose of this report is to summarize the presentations and discussion at the RCMI Investigator Development Core (IDC) Workshop, held in conjunction with the RCMI Program National Conference in Bethesda, Maryland, in December 2019. The RCMI IDC Directors provided information about their professional development activities and Pilot Pr...
The American Journal of Tropical Medicine and Hygiene
In malaria endemic countries, anemia in pregnant women occurs as a result of erythrocyte destruct... more In malaria endemic countries, anemia in pregnant women occurs as a result of erythrocyte destruction by Plasmodium infections and other causes including malnutrition. Iron supplementation is recommended as treatment of iron-deficiency anemia. Erythrocyte destruction results in increased release of cytotoxic free heme that is scavenged by haptoglobin (Hp), hemopexin (Hx) and heme oxygenase-1 (HO-1). Paradoxically, iron supplementation in pregnant women has been reported to enhance parasitemia and increase levels of free heme. The relationship between free heme, heme scavengers, and birth outcomes has not been investigated, especially in women who are on iron supplementation. We hypothesized that parasite-infected pregnant women on routine iron supplementation have elevated heme and altered expression of heme scavengers. A cross-sectional study was conducted to determine the association between plasma levels of free heme, HO-1, Hp, Hx, and malaria status in pregnant women who received...
BACKGROUND: Vasculogenesis is critically important to restoring and maintaining vascular homeosta... more BACKGROUND: Vasculogenesis is critically important to restoring and maintaining vascular homeostasis in patients who have sickle cell disease. Emerging evidence indicates vasculo-angiogenesis is a complex process involving recruitment of endothelial progenitor cells (EPCs) from the bone marrow and homing of EPCs to sites of vascular injury. Both recruitment and homing of EPCs are intimately regulated by cytokines and growth factors that are released in response to vascular insult. Hitherto, the phenotype of growth factors and cytokines intimately involved in EPC recruitment and homing in patients who have sickle cell disease remains poorly understood. METHODS: A total of 50 children aged 6–18 years were studied, 30 with Hemoglobin SS, including 11 on chronic red blood cell transfusions, and 20 with normal hemoglobin. We measured plasma concentrations of angiogenesis growth factors/cytokines using a multiplex assay, which permitted analysis of nine factors concurrently, and determine...
In Africa, the natural history of SCD is often assumed to be same to the African Diaspora in the ... more In Africa, the natural history of SCD is often assumed to be same to the African Diaspora in the US, Jamaica, Europe or Latin America. Yet the environment can be different, including different pathogen exposure, such as malaria. To help better understand this, over 2000 references were identified using the names of all current or past names of African continent countries and the truncated word sickl$, followed by secondary nested and cross reference searches. Six cases series describing causes of death were identified, representing 182 children (Ndugwa, 1973, Athale, 1994, Koko, 1998, Diagne, 2000, Rahimy, 2003, Van-Dunem, 2007). Gender was reported in 172, 73 were female (42%). Age was reported in 118, 52 were < 5 years (44%). Four studies described some impediment to care or arrival for care in extremis in1/4 to over ½ of patients that died. In Uganda, 9/12 (75%) patient died at home. In Gabon 6/23 (26%) patients died within 4 hours of reaching the hospital and 11/23 (48%) with...
2123 Little is known about the relative rate of pubertal development among children with differen... more 2123 Little is known about the relative rate of pubertal development among children with different phenotypes of sickle cell disease (SCD). This study proposes, for the first time, to compare the influence of SCD phenotypes on pubertal development (PD) and body mass. We hypothesized that differences in pubertal development and body mass index (BMI) are modulated by SCD phenotype and treatment modality. We therefore conducted a cross-sectional study of SCD children and adolescents aged 8 – 18 years old (yo) to determine the impact of SCD phenotype and treatments on pubertal development (according to sexual maturity rating by Tanner stages, TS) and BMI. Participants were recruited from…
BackgroundMalaria mortality is associated with exaggerated host responses to inflammatory factors... more BackgroundMalaria mortality is associated with exaggerated host responses to inflammatory factors such as C-X-C motif chemokine 10 (CXCL10) and host biomarkers such as angiopoietin 1 (Ang-1) and angiopoietin 2 (Ang-2). The aim of this study was to determine saliva levels of CXCL10, Ang-1 and Ang-2 and compare with plasma levels regarding their potential as biomarkers of malaria, which may be useful for further development of highly efficient non-invasive malaria detection methods.MethodsCase control study involving 213 subjects (119 with and 94 without malaria) aged 1–16 years. Haematological determination was done using Haematology Analyser. Plasmodium Lactate Dehydrogenase/Histidine Rich Protein-2 (pLDH/HRP-2) Antigen rapid diagnostic test (RDT) were performed. Plasma and saliva levels of CXCL10, Ang-1 and Ang-2 were measured using Elisa kit. Data was presented as mean ±standard error or median and interquartile range (IQR). A p-value<0.001 was considered statistically signific...
International Journal of Environmental Research and Public Health
Junior investigators often have limited access to networks of scientific experts and resources th... more Junior investigators often have limited access to networks of scientific experts and resources that facilitate competitive grant submissions. Since environments in which scientists are trained are critically important for long-term success, we built and tested a virtual environment for early-stage investigators (ESIs) working on grant proposals. The aim of this study was to evaluate the virtual community’s influence on grant submission patterns among participants from underrepresented groups. As part of a grant writing coaching model, junior investigators were recruited into a professional development program designed to develop competitive grantsmanship skills. Designed by the Research Resources and Outreach Core (RROC) of the National Research Mentoring Network (NRMN), the Health Equity Learning Collaboratory (EQ-Collaboratory) provided a virtual community for social support, accountability, constructive feedback, and access to peer networks to help investigators overcome barriers...
Human cerebral malaria (HCM) is a severe form of malaria characterized by sequestration of infect... more Human cerebral malaria (HCM) is a severe form of malaria characterized by sequestration of infected erythrocytes (IRBCs) in brain microvessels, increased levels of circulating free heme and pro-inflammatory cytokines and chemokines, brain swelling, vascular dysfunction, coma, and increased mortality. Neuregulin-1β (NRG-1) encoded by the gene NRG1, is a member of a family of polypeptide growth factors required for normal development of the nervous system and the heart. Utilizing an experimental cerebral malaria (ECM) model (Plasmodium berghei ANKA in C57BL/6), we reported that NRG-1 played a cytoprotective role in ECM and that circulating levels were inversely correlated with ECM severity. Intravenous infusion of NRG-1 reduced ECM mortality in mice by promoting a robust anti-inflammatory response coupled with reduction in accumulation of IRBCs in microvessels and reduced tissue damage. In the current study, we examined how NRG-1 treatment attenuates pathogenesis and mortality associa...
Effective mentorship is critical to the success of early stage investigators, and has been linked... more Effective mentorship is critical to the success of early stage investigators, and has been linked to enhanced mentee productivity, self-efficacy, and career satisfaction. The mission of the National Research Mentoring Network (NRMN) is to provide all trainees across the biomedical, behavioral, clinical, and social sciences with evidence-based mentorship and professional development programming that emphasizes the benefits and challenges of diversity, inclusivity, and culture within mentoring relationships, and more broadly the research workforce. The purpose of this paper is to describe the structure and activities of NRMN. NRMN serves as a national training hub for mentors and mentees striving to improve their relationships by better aligning expectations, promoting professional development, maintaining effective communication, addressing equity and inclusion, assessing understanding, fostering independence, and cultivating ethical behavior. Training is offered in-person at institu...
Chronic inflammation is a characteristic of sickle cell disease (SCD), and is invariably associat... more Chronic inflammation is a characteristic of sickle cell disease (SCD), and is invariably associated with vascular endothelial injury. Hydroxyurea (HU), a naturally cytotoxic chemotherapeutic agent, is the only FDA drug approved for SCD, and is therefore naturally cytotoxic. Quercetin (QCT) is a dietary flavonoid found ubiquitously in plants and foods that have anti-oxidative and anti-inflammatory characteristics. Our hypothesis is that dietary QCT will decrease cytotoxic effects of lipopolysaccharide (LPS) and HU induced vascular cell damage. Lipopolysaccharide (LPS) was used to induce inflammation in immortalized mouse aortic endothelial cells (iMAECs), providing an in vitro model of inflamed endothelial cells. The cells were exposed to LPS throughout the entire experiment. Interventions included treating the LPS exposed cells with QCT, HU, or QCT + HU over 50 hours. The 50-hour period included 24 hours of varying treatments, followed by two hours of hypoxic exposure and then 24 ho...
Iron supplementation is recommended for pregnant women to meet their iron requirement for a healt... more Iron supplementation is recommended for pregnant women to meet their iron requirement for a healthy pregnancy. The benefits and risks of universal iron supplementation during pregnancy in malaria endemic countries are currently being debated. As part of a broader study that focused on the effect of heme/HO-1 on pregnancy outcomes in malaria in pregnancy, we determined the association between iron supplementation and free heme levels in blood of pregnant women with and without malaria in Ghana. We hypothesized that pregnant women with malaria who took iron supplements will have higher levels of Heme/HO-1 than those who did not take iron supplements. A total of 337 women were recruited for this study. Blood samples were collected for malaria diagnosis and heme/HO-1 measurement. Quantification of heme was done using a heme colorimetric assay kit and HO-1 levels were performed using Enzyme-Linked Immunosorbent Assay (ELISA) on plasma samples. Malaria positive iron supplemented women, in...
Scarce studies have addressed hematological differences of malaria in urban and rural regions. Fu... more Scarce studies have addressed hematological differences of malaria in urban and rural regions. Full or complete blood cell counts from 46 and 75 individuals (age range from < 1 to 92 years) with uncomplicated malaria infection living in urban (Accra) and rural (Dodowa) Ghana, respectively, were assessed. Sickle cell trait and patients were excluded from the study. Between overall groups, patients from Accra had significantly lower parasite count (p < 0.0001) and granulocyte number (p = 0.026). Children in Accra had a significantly lower parasitemia (p = 0.0013), hemoglobin (p = 0.0254), platelet count (p = 0.0148) and red blood cell levels (p = 0.0080) when compared with the children of Dodowa. In adults, mean cell hemoglobin (p = 0.0086) and parasite count (p < 0.0001) were significantly higher in Dodowa. These results indicate that children living in urban setting may experience a greater anemic effect to malaria as compared with those living in a rural setting.
International Journal of Environmental Research and Public Health
The Research Centers in Minority Institutions (RCMI) Program was congressionally mandated in 1985... more The Research Centers in Minority Institutions (RCMI) Program was congressionally mandated in 1985 to build research capacity at institutions that currently and historically recruit, train, and award doctorate degrees in the health professions and health-related sciences, primarily to individuals from underrepresented and minority populations. RCMI grantees share similar infrastructure needs and institutional goals. Of particular importance is the professional development of multidisciplinary teams of academic and community scholars (the “workforce”) and the harnessing of the heterogeneity of thought (the “thinkforce”) to reduce health disparities. The purpose of this report is to summarize the presentations and discussion at the RCMI Investigator Development Core (IDC) Workshop, held in conjunction with the RCMI Program National Conference in Bethesda, Maryland, in December 2019. The RCMI IDC Directors provided information about their professional development activities and Pilot Pr...
The American Journal of Tropical Medicine and Hygiene
In malaria endemic countries, anemia in pregnant women occurs as a result of erythrocyte destruct... more In malaria endemic countries, anemia in pregnant women occurs as a result of erythrocyte destruction by Plasmodium infections and other causes including malnutrition. Iron supplementation is recommended as treatment of iron-deficiency anemia. Erythrocyte destruction results in increased release of cytotoxic free heme that is scavenged by haptoglobin (Hp), hemopexin (Hx) and heme oxygenase-1 (HO-1). Paradoxically, iron supplementation in pregnant women has been reported to enhance parasitemia and increase levels of free heme. The relationship between free heme, heme scavengers, and birth outcomes has not been investigated, especially in women who are on iron supplementation. We hypothesized that parasite-infected pregnant women on routine iron supplementation have elevated heme and altered expression of heme scavengers. A cross-sectional study was conducted to determine the association between plasma levels of free heme, HO-1, Hp, Hx, and malaria status in pregnant women who received...
BACKGROUND: Vasculogenesis is critically important to restoring and maintaining vascular homeosta... more BACKGROUND: Vasculogenesis is critically important to restoring and maintaining vascular homeostasis in patients who have sickle cell disease. Emerging evidence indicates vasculo-angiogenesis is a complex process involving recruitment of endothelial progenitor cells (EPCs) from the bone marrow and homing of EPCs to sites of vascular injury. Both recruitment and homing of EPCs are intimately regulated by cytokines and growth factors that are released in response to vascular insult. Hitherto, the phenotype of growth factors and cytokines intimately involved in EPC recruitment and homing in patients who have sickle cell disease remains poorly understood. METHODS: A total of 50 children aged 6–18 years were studied, 30 with Hemoglobin SS, including 11 on chronic red blood cell transfusions, and 20 with normal hemoglobin. We measured plasma concentrations of angiogenesis growth factors/cytokines using a multiplex assay, which permitted analysis of nine factors concurrently, and determine...
In Africa, the natural history of SCD is often assumed to be same to the African Diaspora in the ... more In Africa, the natural history of SCD is often assumed to be same to the African Diaspora in the US, Jamaica, Europe or Latin America. Yet the environment can be different, including different pathogen exposure, such as malaria. To help better understand this, over 2000 references were identified using the names of all current or past names of African continent countries and the truncated word sickl$, followed by secondary nested and cross reference searches. Six cases series describing causes of death were identified, representing 182 children (Ndugwa, 1973, Athale, 1994, Koko, 1998, Diagne, 2000, Rahimy, 2003, Van-Dunem, 2007). Gender was reported in 172, 73 were female (42%). Age was reported in 118, 52 were < 5 years (44%). Four studies described some impediment to care or arrival for care in extremis in1/4 to over ½ of patients that died. In Uganda, 9/12 (75%) patient died at home. In Gabon 6/23 (26%) patients died within 4 hours of reaching the hospital and 11/23 (48%) with...
2123 Little is known about the relative rate of pubertal development among children with differen... more 2123 Little is known about the relative rate of pubertal development among children with different phenotypes of sickle cell disease (SCD). This study proposes, for the first time, to compare the influence of SCD phenotypes on pubertal development (PD) and body mass. We hypothesized that differences in pubertal development and body mass index (BMI) are modulated by SCD phenotype and treatment modality. We therefore conducted a cross-sectional study of SCD children and adolescents aged 8 – 18 years old (yo) to determine the impact of SCD phenotype and treatments on pubertal development (according to sexual maturity rating by Tanner stages, TS) and BMI. Participants were recruited from…
BackgroundMalaria mortality is associated with exaggerated host responses to inflammatory factors... more BackgroundMalaria mortality is associated with exaggerated host responses to inflammatory factors such as C-X-C motif chemokine 10 (CXCL10) and host biomarkers such as angiopoietin 1 (Ang-1) and angiopoietin 2 (Ang-2). The aim of this study was to determine saliva levels of CXCL10, Ang-1 and Ang-2 and compare with plasma levels regarding their potential as biomarkers of malaria, which may be useful for further development of highly efficient non-invasive malaria detection methods.MethodsCase control study involving 213 subjects (119 with and 94 without malaria) aged 1–16 years. Haematological determination was done using Haematology Analyser. Plasmodium Lactate Dehydrogenase/Histidine Rich Protein-2 (pLDH/HRP-2) Antigen rapid diagnostic test (RDT) were performed. Plasma and saliva levels of CXCL10, Ang-1 and Ang-2 were measured using Elisa kit. Data was presented as mean ±standard error or median and interquartile range (IQR). A p-value<0.001 was considered statistically signific...
International Journal of Environmental Research and Public Health
Junior investigators often have limited access to networks of scientific experts and resources th... more Junior investigators often have limited access to networks of scientific experts and resources that facilitate competitive grant submissions. Since environments in which scientists are trained are critically important for long-term success, we built and tested a virtual environment for early-stage investigators (ESIs) working on grant proposals. The aim of this study was to evaluate the virtual community’s influence on grant submission patterns among participants from underrepresented groups. As part of a grant writing coaching model, junior investigators were recruited into a professional development program designed to develop competitive grantsmanship skills. Designed by the Research Resources and Outreach Core (RROC) of the National Research Mentoring Network (NRMN), the Health Equity Learning Collaboratory (EQ-Collaboratory) provided a virtual community for social support, accountability, constructive feedback, and access to peer networks to help investigators overcome barriers...
Human cerebral malaria (HCM) is a severe form of malaria characterized by sequestration of infect... more Human cerebral malaria (HCM) is a severe form of malaria characterized by sequestration of infected erythrocytes (IRBCs) in brain microvessels, increased levels of circulating free heme and pro-inflammatory cytokines and chemokines, brain swelling, vascular dysfunction, coma, and increased mortality. Neuregulin-1β (NRG-1) encoded by the gene NRG1, is a member of a family of polypeptide growth factors required for normal development of the nervous system and the heart. Utilizing an experimental cerebral malaria (ECM) model (Plasmodium berghei ANKA in C57BL/6), we reported that NRG-1 played a cytoprotective role in ECM and that circulating levels were inversely correlated with ECM severity. Intravenous infusion of NRG-1 reduced ECM mortality in mice by promoting a robust anti-inflammatory response coupled with reduction in accumulation of IRBCs in microvessels and reduced tissue damage. In the current study, we examined how NRG-1 treatment attenuates pathogenesis and mortality associa...
Effective mentorship is critical to the success of early stage investigators, and has been linked... more Effective mentorship is critical to the success of early stage investigators, and has been linked to enhanced mentee productivity, self-efficacy, and career satisfaction. The mission of the National Research Mentoring Network (NRMN) is to provide all trainees across the biomedical, behavioral, clinical, and social sciences with evidence-based mentorship and professional development programming that emphasizes the benefits and challenges of diversity, inclusivity, and culture within mentoring relationships, and more broadly the research workforce. The purpose of this paper is to describe the structure and activities of NRMN. NRMN serves as a national training hub for mentors and mentees striving to improve their relationships by better aligning expectations, promoting professional development, maintaining effective communication, addressing equity and inclusion, assessing understanding, fostering independence, and cultivating ethical behavior. Training is offered in-person at institu...
Chronic inflammation is a characteristic of sickle cell disease (SCD), and is invariably associat... more Chronic inflammation is a characteristic of sickle cell disease (SCD), and is invariably associated with vascular endothelial injury. Hydroxyurea (HU), a naturally cytotoxic chemotherapeutic agent, is the only FDA drug approved for SCD, and is therefore naturally cytotoxic. Quercetin (QCT) is a dietary flavonoid found ubiquitously in plants and foods that have anti-oxidative and anti-inflammatory characteristics. Our hypothesis is that dietary QCT will decrease cytotoxic effects of lipopolysaccharide (LPS) and HU induced vascular cell damage. Lipopolysaccharide (LPS) was used to induce inflammation in immortalized mouse aortic endothelial cells (iMAECs), providing an in vitro model of inflamed endothelial cells. The cells were exposed to LPS throughout the entire experiment. Interventions included treating the LPS exposed cells with QCT, HU, or QCT + HU over 50 hours. The 50-hour period included 24 hours of varying treatments, followed by two hours of hypoxic exposure and then 24 ho...
Iron supplementation is recommended for pregnant women to meet their iron requirement for a healt... more Iron supplementation is recommended for pregnant women to meet their iron requirement for a healthy pregnancy. The benefits and risks of universal iron supplementation during pregnancy in malaria endemic countries are currently being debated. As part of a broader study that focused on the effect of heme/HO-1 on pregnancy outcomes in malaria in pregnancy, we determined the association between iron supplementation and free heme levels in blood of pregnant women with and without malaria in Ghana. We hypothesized that pregnant women with malaria who took iron supplements will have higher levels of Heme/HO-1 than those who did not take iron supplements. A total of 337 women were recruited for this study. Blood samples were collected for malaria diagnosis and heme/HO-1 measurement. Quantification of heme was done using a heme colorimetric assay kit and HO-1 levels were performed using Enzyme-Linked Immunosorbent Assay (ELISA) on plasma samples. Malaria positive iron supplemented women, in...
Scarce studies have addressed hematological differences of malaria in urban and rural regions. Fu... more Scarce studies have addressed hematological differences of malaria in urban and rural regions. Full or complete blood cell counts from 46 and 75 individuals (age range from < 1 to 92 years) with uncomplicated malaria infection living in urban (Accra) and rural (Dodowa) Ghana, respectively, were assessed. Sickle cell trait and patients were excluded from the study. Between overall groups, patients from Accra had significantly lower parasite count (p < 0.0001) and granulocyte number (p = 0.026). Children in Accra had a significantly lower parasitemia (p = 0.0013), hemoglobin (p = 0.0254), platelet count (p = 0.0148) and red blood cell levels (p = 0.0080) when compared with the children of Dodowa. In adults, mean cell hemoglobin (p = 0.0086) and parasite count (p < 0.0001) were significantly higher in Dodowa. These results indicate that children living in urban setting may experience a greater anemic effect to malaria as compared with those living in a rural setting.
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