The Role of PfEMP1 Expression and Immunity in Ugandian Children with Severe Malaria

Indiana University-Purdue University Indianapolis (IUPUI)Severe malaria, primarily caused by Plasmodium falciparum infection, is among the leading causes of childhood mortality globally. A key virulence factor and source of antigenic variation and immune evasion during infection is P. falciparum erythrocyte membrane protein 1 (PfEMP1). Encoded for by approximately 60 var genes, this complex protein mediates cytoadherence of infected erythrocytes to the host endothelium and is a prominent immune target for the anti-malarial immune response in children. During severe malaria, specific domains of PfEMP1 that bind to endothelial protein C receptor (EPCR) and intercellular adhesion molecule-1 (ICAM-1) on host endothelial cells, are more prevalently expressed. The interaction of these proteins and infected erythrocytes mediates the sequestration of infected erythrocytes and plays a role in severe malaria pathogenesis. Antibodies to these domains develop over time with exposure to the parasite and are thought to contribute to immunity against severe malaria in children. In this study, whole blood samples from children with different forms of severe malaria, enrolled in two observational prospective cohort studies were used to quantify the expression of PfEMP1 domains using RT-qPCR and to measure the antibody response to PfEMP1 domains via a bead-based multiplex immunoassay. Using these samples, we demonstrated that although the expression of var transcripts encoding PfEMP1 domains was generally similar across children with different forms of severe malaria, the expression of variants encoding specific EPCR-binding domains was associated with thrombocytopenia and severe anemia. The antibody response to PfEMP1 domains in children with severe malaria was highest in children with SMA and children with asymptomatic parasitemia, but not associated with decreased risk of additional malaria episodes. Overall, the results of this study suggest that PfEMP1 is acting similarly across different forms of severe malaria but that it can be related to pathogenesis and severe malaria immunity

Challenges and Considerations Related to Studying Dementia in Blacks/African Americans

Blacks/African Americans have been reported to be ~2–4 times more likely to develop clinical Alzheimer’s disease (AD) compared to Whites. Unfortunately, study design challenges (e.g., recruitment bias), racism, mistrust of healthcare providers and biomedical researchers, confounders related to socioeconomic status, and other sources of bias are often ignored when interpreting differences in human subjects categorized by race. Failure to account for these factors can lead to misinterpretation of results, reification of race as biology, discrimination, and missed or delayed diagnoses. Here we provide a selected historical background, discuss challenges, present opportunities, and suggest considerations for studying health outcomes among racial/ethnic groups. We encourage neuroscientists to consider shifting away from using biologic determination to interpret data, and work instead toward a paradigm of incorporating both biological and socio-environmental factors known to affect health outcomes with the goal of understanding and improving dementia treatments for Blacks/African Americans and other underserved populations

Racial differences in smoking abstinence rates in a multicenter, randomized, open-label trial in the United States

Background: This study evaluates differences in smoking abstinence between white and minority smokers using pharmaceutical aids. Methods: This is an analysis of data from a multi-center, randomized, clinical trial conducted in the United States. Of the 1,684 subjects randomized to one of three medications (nicotine inhaler, bupropion, or a combination of both), 60% were women and 10% were minority races. Results: Factors associated with a decreased likelihood of smoking at 12 weeks were older age (OR = 0.971, p\u3c 0.0001), being married (OR = 0.678, p= 0.0029), using bupropion SR (OR = 0.480, p∈\u3c∈0.0001), and using combination therapy (OR = 0.328, p∈\u3c∈0.0001). Factors associated with an increased likelihood of smoking were higher tobacco dependence scores (OR = 1.244, p \u3c 0.0001), prior quit attempts (OR = 1.812, p=0.004), and being a minority (OR = 1.849, p=0.0083). Compared to white smokers, minority smokers were significantly older at time of study entry (46 vs. 42 years, p\u3c 0.0001), less likely to be married (35% vs. 59%, p\u3c 0.0001), older at smoking initiation (21 vs. 19 years of age, p\u3c 0.0001), and had a lower abstinence rate (16% vs. 26%, p=0.0065). Conclusion: Regardless of the treatment used, minority smokers in the US have lower smoking abstinence after treatment for tobacco dependence. Future research should focus on the improvement in treatment strategies for minority smokers

The Role of PfEMP1 Expression and Immunity in Ugandian Children with Severe Malaria

Indiana University-Purdue University Indianapolis (IUPUI)Severe malaria, primarily caused by Plasmodium falciparum infection, is among the leading causes of childhood mortality globally. A key virulence factor and source of antigenic variation and immune evasion during infection is P. falciparum erythrocyte membrane protein 1 (PfEMP1). Encoded for by approximately 60 var genes, this complex protein mediates cytoadherence of infected erythrocytes to the host endothelium and is a prominent immune target for the anti-malarial immune response in children. During severe malaria, specific domains of PfEMP1 that bind to endothelial protein C receptor (EPCR) and intercellular adhesion molecule-1 (ICAM-1) on host endothelial cells, are more prevalently expressed. The interaction of these proteins and infected erythrocytes mediates the sequestration of infected erythrocytes and plays a role in severe malaria pathogenesis. Antibodies to these domains develop over time with exposure to the parasite and are thought to contribute to immunity against severe malaria in children. In this study, whole blood samples from children with different forms of severe malaria, enrolled in two observational prospective cohort studies were used to quantify the expression of PfEMP1 domains using RT-qPCR and to measure the antibody response to PfEMP1 domains via a bead-based multiplex immunoassay. Using these samples, we demonstrated that although the expression of var transcripts encoding PfEMP1 domains was generally similar across children with different forms of severe malaria, the expression of variants encoding specific EPCR-binding domains was associated with thrombocytopenia and severe anemia. The antibody response to PfEMP1 domains in children with severe malaria was highest in children with SMA and children with asymptomatic parasitemia, but not associated with decreased risk of additional malaria episodes. Overall, the results of this study suggest that PfEMP1 is acting similarly across different forms of severe malaria but that it can be related to pathogenesis and severe malaria immunity

Assessing the Reliability and Validity of the John Henry Active Coping Scale in an Urban Sample of African Americans and white Americans

Objectives. The primary focus of this study was to examine the psychometric properties of the John Henry Active Coping scale (JHAC12) among an urban middle-aged sample of African Americans and white Americans. Design. The sample consisted of 75 African Americans and 129 white Americans from South Florida ranging in age from 25 to 54 years. Subjects completed the JHAC12, the Life Orientation Test (LOT), Coping Orientation to Problems Encountered (COPE) subscales, and the Marlowe-Crowne Social Desirability scale. Results. Major findings supported the validity and reliability of the JHAC12 among both African Americans and white Americans. For both the African American and white American subsamples, the JHAC12 was correlated with the active coping and suppression of competing activities subscales of the COPE and negatively correlated with the Marlowe-Crowne Social Desirability scale. In the African American subsample the JHAC12 was positively correlated with the LOT. The JHAC12 was also negatively associated with the behavioral disengagement subscale of the COPE among white Americans. Multiple regression analyses revealed that the proportion of variance in the JHAC12 explained by the various subscales of the COPE, Marlowe-Crowne, and the LOT was 43% for African Americans and 20% for white Americans. Factor analyses suggested two similar and meaningful factors among the African American and white American subsamples. Finally, Cronbach alpha reliabilities revealed similar subsample coefficients. Discussion. The implications of the findings are discussed in terms of the JHAC12's ability to assess the construct of active coping among African Americans and white Americans

Exploring the association of John Henry active coping and education on smoking behavior and nicotine dependence among Blacks in the USA

Although smoking is used as a coping tool in response to stress and Blacks have been found to report smoking more in response to stress than Whites, little research exists that has examined ethno-culturally specific constructs of stress and coping as they relate to smoking behavior and nicotine dependence among Blacks in the USA. This study explored the association between the ethno-culturally interactively defined construct of John Henryism, as well as the individual contributions of John Henry active coping and education on smoking behavior and nicotine dependence in a relatively urban-Midwestern Black population. Self-identified Black patients (n=146) who had previously received a clinical intervention for nicotine dependence were followed to assess smoking status and John Henry active coping. Results revealed that patients with low levels of education who had low levels of John Henry active coping reported higher nicotine dependence scores than any other education by John Henry active coping group. Furthermore, low levels of John Henry active coping were associated with the use of menthol cigarettes and lower-educational level was associated with smoking greater than 20 cigarettes per day. Further community-based studies examining this construct among Black smokers in various socio-cultural contexts are needed to clarify the association between John Henry active coping and socioeconomic status on smoking behavior and nicotine dependence among Blacks.John Henry active coping Smoking Blacks Nicotine dependence USA

Evaluating High Resolution Soil Moisture Maps in the Framework of the ESA CCI

International audienc