Functional Assessment of Cancer-Linked Mutations in Sensitive Regions of Regulators of G Protein Signaling Predicted by Three-Dimensional Missense Tolerance Ratio Analysis.

Regulators of G protein signaling (RGS) proteins modulate G protein-coupled receptor (GPCR) signaling by acting as negative regulators of G proteins. Genetic variants in RGS proteins are associated with many diseases, including cancers, although the impact of these mutations on protein function is uncertain. Here we analyze the RGS domains of 15 RGS protein family members using a novel bioinformatic tool that measures the missense tolerance ratio (MTR) using a three-dimensional (3D) structure (3DMTR). Subsequent permutation analysis can define the protein regions that are most significantly intolerant (P < 0.05) in each dataset. We further focused on RGS14, RGS10, and RGS4. RGS14 exhibited seven significantly tolerant and seven significantly intolerant residues, RGS10 had six intolerant residues, and RGS4 had eight tolerant and six intolerant residues. Intolerant and tolerant-control residues that overlap with pathogenic cancer mutations reported in the COSMIC cancer database were selected to define the functional phenotype. Using complimentary cellular and biochemical approaches, proteins were tested for effects on GPCR-Gα activation, Gα binding properties, and downstream cAMP levels. Identified intolerant residues with reported cancer-linked mutations RGS14-R173C/H and RGS4-K125Q/E126K, and tolerant RGS14-S127P and RGS10-S64T resulted in a loss-of-function phenotype in GPCR-G protein signaling activity. In downstream cAMP measurement, tolerant RGS14-D137Y and RGS10-S64T and intolerant RGS10-K89M resulted in change of function phenotypes. These findings show that 3DMTR identified intolerant residues that overlap with cancer-linked mutations cause phenotypic changes that negatively impact GPCR-G protein signaling and suggests that 3DMTR is a potentially useful bioinformatics tool for predicting functionally important protein residues. SIGNIFICANCE STATEMENT: Human genetic variant/mutation information has expanded rapidly in recent years, including cancer-linked mutations in regulator of G protein signaling (RGS) proteins. However, experimental testing of the impact of this vast catalogue of mutations on protein function is not feasible. We used the novel bioinformatics tool three-dimensional missense tolerance ratio (3DMTR) to define regions of genetic intolerance in RGS proteins and prioritize which cancer-linked mutants to test. We found that 3DMTR more accurately classifies loss-of-function mutations in RGS proteins than other databases thereby offering a valuable new research tool.

RGS14 regulates PTH- and FGF23-sensitive NPT2A-mediated renal phosphate uptake via binding to the NHERF1 scaffolding protein.

Phosphate homeostasis, mediated by dietary intake, renal absorption, and bone deposition, is incompletely understood because of the uncharacterized roles of numerous implicated protein factors. Here, we identified a novel role for one such element, regulator of G protein signaling 14 (RGS14), suggested by genome-wide association studies to associate with dysregulated Pi levels. We show that human RGS14 possesses a carboxy-terminal PDZ ligand required for sodium phosphate cotransporter 2a (NPT2A) and sodium hydrogen exchanger regulatory factor-1 (NHERF1)-mediated renal Pi transport. In addition, we found using isotope uptake measurements combined with bioluminescence resonance energy transfer assays, siRNA knockdown, pull-down and overlay assays, and molecular modeling that secreted proteins parathyroid hormone (PTH) and fibroblast growth factor 23 inhibited Pi uptake by inducing dissociation of the NPT2A-NHERF1 complex. PTH failed to affect Pi transport in cells expressing RGS14, suggesting that it suppresses hormone-sensitive but not basal Pi uptake. Interestingly, RGS14 did not affect PTH-directed G protein activation or cAMP formation, implying a postreceptor site of action. Further pull-down experiments and direct binding assays indicated that NPT2A and RGS14 bind distinct PDZ domains on NHERF1. We showed that RGS14 expression in human renal proximal tubule epithelial cells blocked the effects of PTH and fibroblast growth factor 23 and stabilized the NPT2A-NHERF1 complex. In contrast, RGS14 genetic variants bearing mutations in the PDZ ligand disrupted RGS14 binding to NHERF1 and subsequent PTH-sensitive Pi transport. In conclusion, these findings identify RGS14 as a novel regulator of hormone-sensitive Pi transport. The results suggest that changes in RGS14 function or abundance may contribute to the hormone resistance and hyperphosphatemia observed in kidney diseases.

RGS14 expression in CA2 hippocampus, amygdala, and basal ganglia: Implications for human brain physiology and disease.

RGS14 is a multifunctional scaffolding protein that is highly expressed within postsynaptic spines of pyramidal neurons in hippocampal area CA2. Known roles of RGS14 in CA2 include regulating G protein, H-Ras/ERK, and calcium signaling pathways to serve as a natural suppressor of synaptic plasticity and postsynaptic signaling. RGS14 also shows marked postsynaptic expression in major structures of the limbic system and basal ganglia, including the amygdala and both the ventral and dorsal subdivisions of the striatum. In this review, we discuss the signaling functions of RGS14 and its role in postsynaptic strength (long-term potentiation) and spine structural plasticity in CA2 hippocampal neurons, and how RGS14 suppression of plasticity impacts linked behaviors such as spatial learning, object memory, and fear conditioning. We also review RGS14 expression in the limbic system and basal ganglia and speculate on its possible roles in regulating plasticity in these regions, with a focus on behaviors related to emotion and motivation. Finally, we explore the functional implications of RGS14 in various brain circuits and speculate on its possible roles in certain disease states such as hippocampal seizures, addiction, and anxiety disorders.

Are committee experiences of minoritized family medicine faculty part of the minority tax? a qualitative study.

BACKGROUND AND OBJECTIVES: Because much of the work in academic medicine is done by committee, early career URiM faculty, are often asked to serve on multiple committees, including diversity work that may not be recognized as important. They may also be asked to serve on committees to satisfy a diversity "check box," and may be asked more often than their non-URiM peers to serve in this capacity. We sought to describe the committee experiences of early career URiM faculty, hypothesizing that they may see committee service as a minority tax. METHODS: Participants in the Leadership through Scholarship Fellowship (LTSF) were asked to share their experiences with committee service in their careers after participating in a faculty development discussion. Their responses were analyzed and reported using qualitative, open, axial, and abductive reasoning methods. RESULTS: Four themes, with eight sub-themes (in parenthesis), emerged from the content analysis of the LTSF fellows responses to the prompt: Time commitment (Timing of committee work and lack of protected time for research and scholarship), URiM Committee service (Expectation that URiM person will serve on committees and consequences for not serving), Mentoring issues (no mentoring regarding committee service, faculty involvement is lacking and the conflicting nature of committee work) and Voice (Lack of voice or acknowledgement). CONCLUSIONS: Early career URiM faculty reported an expectation of serving on committees and consequences for not serving related to their identity, but other areas of committee service they shared were not connected to their URiM identity. Because most of the experiences were not connected to the LTSF fellows' URiM identity, this group has identified areas of committee service that may affect all early career faculty. More research is necessary to determine how committee service affects URiM and non-URiM faculty in academic family medicine.

Human genetic variants disrupt RGS14 nuclear shuttling and regulation of LTP in hippocampal neurons.

The human genome contains vast genetic diversity as naturally occurring coding variants, yet the impact of these variants on protein function and physiology is poorly understood. RGS14 is a multifunctional signaling protein that suppresses synaptic plasticity in dendritic spines of hippocampal neurons. RGS14 also is a nucleocytoplasmic shuttling protein, suggesting that balanced nuclear import/export and dendritic spine localization are essential for RGS14 functions. We identified genetic variants L505R (LR) and R507Q (RQ) located within the nuclear export sequence (NES) of human RGS14. Here we report that RGS14 encoding LR or RQ profoundly impacts protein functions in hippocampal neurons. RGS14 membrane localization is regulated by binding Gαi-GDP, whereas RGS14 nuclear export is regulated by Exportin 1 (XPO1). Remarkably, LR and RQ variants disrupt RGS14 binding to Gαi1-GDP and XPO1, nucleocytoplasmic equilibrium, and capacity to inhibit long-term potentiation (LTP). Variant LR accumulates irreversibly in the nucleus, preventing RGS14 binding to Gαi1, localization to dendritic spines, and inhibitory actions on LTP induction, while variant RQ exhibits a mixed phenotype. When introduced into mice by CRISPR/Cas9, RGS14-LR protein expression was detected predominantly in the nuclei of neurons within hippocampus, central amygdala, piriform cortex, and striatum, brain regions associated with learning and synaptic plasticity. Whereas mice completely lacking RGS14 exhibit enhanced spatial learning, mice carrying variant LR exhibit normal spatial learning, suggesting that RGS14 may have distinct functions in the nucleus independent from those in dendrites and spines. These findings show that naturally occurring genetic variants can profoundly alter normal protein function, impacting physiology in unexpected ways.

First Evidence of Gastroprotection by Schinus molle: Roles of Nitric Oxide, Prostaglandins, and Sulfhydryls Groups in Its Mechanism of Action.

Schinus molle is a plant traditionally used in Mexico to treat gastric disorders. However, no scientific evidence has been reported on its gastroprotective effect. The aim of the current contribution was to conduct a bioassay-guided study on S. molle to evaluate its gastroprotective activity in a model of Wistar rats given ethanol orally to induce gastric lesions. The hexane and dichloromethane extracts from the tested plant showed over 99% gastroprotection at a dose of 100 mg/kg. From the hexane extract, two of the three fractions (F1 and F2) afforded over 99% gastroprotection. The F1 fraction was subjected to column chromatography, which revealed a white solid. Based on the ESI-MS analysis, the two main compounds in this solid were identified. The predominant compound was probably a triterpene. This mixture of compounds furnished about 67% gastroprotection at a dose of 100 mg/kg. Pretreatment with L-NAME, indomethacin, and NEM was carried out to explore the possible involvement of nitric oxide, prostaglandins, and/or sulfhydryl groups, respectively, in the gastroprotective activity of the white solid. We found evidence for the participation of all three factors. No antisecretory activity was detected (tested by pylorus ligation). In conclusion, evidence is herein provided for the first time of the gastroprotective effect of S. molle.

Genetic Analysis of Rare Human Variants of Regulators of G Protein Signaling Proteins and Their Role in Human Physiology and Disease.

Regulators of G protein signaling (RGS) proteins modulate the physiologic actions of many neurotransmitters, hormones, and other signaling molecules. Human RGS proteins comprise a family of 20 canonical proteins that bind directly to G protein-coupled receptors/G protein complexes to limit the lifetime of their signaling events, which regulate all aspects of cell and organ physiology. Genetic variations account for diverse human traits and individual predispositions to disease. RGS proteins contribute to many complex polygenic human traits and pathologies such as hypertension, atherosclerosis, schizophrenia, depression, addiction, cancers, and many others. Recent analysis indicates that most human diseases are due to extremely rare genetic variants. In this study, we summarize physiologic roles for RGS proteins and links to human diseases/traits and report rare variants found within each human RGS protein exome sequence derived from global population studies. Each RGS sequence is analyzed using recently described bioinformatics and proteomic tools for measures of missense tolerance ratio paired with combined annotation-dependent depletion scores, and protein post-translational modification (PTM) alignment cluster analysis. We highlight selected variants within the well-studied RGS domain that likely disrupt RGS protein functions and provide comprehensive variant and PTM data for each RGS protein for future study. We propose that rare variants in functionally sensitive regions of RGS proteins confer profound change-of-function phenotypes that may contribute, in newly appreciated ways, to complex human diseases and/or traits. This information provides investigators with a valuable database to explore variation in RGS protein function, and for targeting RGS proteins as future therapeutic targets.

RGS14 Regulation of Post-Synaptic Signaling and Spine Plasticity in Brain.

The regulator of G-protein signaling 14 (RGS14) is a multifunctional signaling protein that regulates post synaptic plasticity in neurons. RGS14 is expressed in the brain regions essential for learning, memory, emotion, and stimulus-induced behaviors, including the basal ganglia, limbic system, and cortex. Behaviorally, RGS14 regulates spatial and object memory, female-specific responses to cued fear conditioning, and environmental- and psychostimulant-induced locomotion. At the cellular level, RGS14 acts as a scaffolding protein that integrates G protein, Ras/ERK, and calcium/calmodulin signaling pathways essential for spine plasticity and cell signaling, allowing RGS14 to naturally suppress long-term potentiation (LTP) and structural plasticity in hippocampal area CA2 pyramidal cells. Recent proteomics findings indicate that RGS14 also engages the actomyosin system in the brain, perhaps to impact spine morphogenesis. Of note, RGS14 is also a nucleocytoplasmic shuttling protein, where its role in the nucleus remains uncertain. Balanced nuclear import/export and dendritic spine localization are likely essential for RGS14 neuronal functions as a regulator of synaptic plasticity. Supporting this idea, human genetic variants disrupting RGS14 localization also disrupt RGS14's effects on plasticity. This review will focus on the known and unexplored roles of RGS14 in cell signaling, physiology, disease and behavior.

Does deferral for high-risk behaviors improve the safety of the blood supply?

BACKGROUND: Predonation donor deferral is used to select donors with presumed lower risk for transfused transmitted infections. The contribution to blood safety from this practice has not been reported previously for Brazil. STUDY DESIGN AND METHODS: At four large Brazilian blood centers from September 2010 to March 2011, donors who were deferred due to responses on eligibility questions were invited to provide a blood sample to test for HIV, hepatitis C virus, hepatitis B virus, human T-lymphotropic virus, syphilis, and Trypanosoma cruzi and complete an audio computer-assisted structured interview on risk behaviors. RESULTS: Of 299,848 potential donors during the study period, 66,870 were deferred with 10,453 (15.6%) for high-risk behaviors. Of those, 4860 (46.5%) were consecutively approached and 4013 (82.5%) participated. Disclosed risk behaviors by audio computer-assisted structured interview included 4 or more sexual partners in the past 12 months (15.0% of females [F] and 34.5% of males [M]), unprotected sex (62.0% F and 44.0% M), other high-risk sexual exposure (85.0% F and 73.0% M), being a person who injects drugs (3.0% F and 10.0% M), and test-seeking (17.0% F and 22.0% M). Eleven percent of deferred males reported male-to-male sex. Individuals who reported other high-risk sexual exposure, sexual partner risk, or male-to-male sex had the highest frequency of confirmed HIV: 1.2, 0.7, and 0.7%, respectively. Individuals who reported male-to-male sex, sexual partner risk, test seeking, and unprotected sex had the highest frequency of confirmed syphilis: 3.8, 3.3, 2.4, and 2.0%, respectively. CONCLUSION: Donor deferral deters donation by individuals with risk behaviors and elevated rates of infectious disease markers.

Social and behavioral characteristics of male blood donors and their sexual partners: an analysis to define risk subsets.

BACKGROUND: Men who have sex with men in Brazil are deferred from donation for 1 year since their last sexual contact. Legal proceedings in front of the Brazilian Supreme Court could compel blood collection agencies to discontinue use of sexual orientation questions. METHODS: Data from male participants in a completed HIV risk factor case-control study were used to evaluate whether it is possible to differentiate donors at lower and higher risk for HIV using two analytical approaches: latent class and random forest analyses. RESULTS: Male blood donors were divided into three distinct risk profile classes. Class 1 includes donors who are heterosexual (96.4%), are HIV negative (88.7%), have a main partner (99.4%), and practice unprotected sex (77.8%). Class 2 includes donors who are men who have sex with men /bisexuals' (100.0%), are HIV positive (97.4%), and were not aware of their sexual partners' HIV status (80.3%). Class 3 includes donors who are heterosexual (84.1%), practice unprotected vaginal/anal heterosexual sex (66.8% vs. 40.9%), and were both HIV positive and HIV negative (49.5% vs. 50.5%). We also found that asking donors about their partner(s)' HIV serostatus could replace asking about donors' sexual orientation and types of partners with relatively minor shifts in sensitivity (0.76 vs. 0.58), specificity (0.89 vs. 0.94), and positive predictive value (0.85 vs. 0.88). CONCLUSION: Sexual orientation questions on the donor questionnaire could be replaced without great loss in the sensitivity, specificity, and positive predictive value. Social and sexual behaviors of donors and their partners are proxies for HIV risk and can help to develop modified questions that will need controlled trials to be validated.

Repercussions of low fructose-drinking water in male rats.

Fructose consumption has increased worldwide, and it has been associated with the development of metabolic diseases such as insulin resistance (IR) and steatosis. The aim was to evaluate if lower fructose concentrations may cause pancreatic structural abnormalities, leading to a glucose intolerance without steatosis in male rats. Young male rats orally received 7% fructose solution for 12 weeks. Body weight, food, water, and energy intake were measured. An oral glucose tolerance test (OGTT) was performed. After final experimental period, all rats were anaesthetized and killed. Blood samples were collected for biochemical analyses and organs (liver and pancreas) were processed for morphological analyses. Fructose consumption was not associated with lipid accumulation in liver. However, fructose administration was associated with an increased area under curve from OGTT and an increased percentage of insulin-positive cells, high beta cell mass and reduced pancreatic islet area. Fructose supplementation (7%) did not cause steatosis, but it led to abnormal morphology and function of pancreatic islet cells, contributing for glucose intolerance development. Our findings demonstrate that even low fructose concentrations may cause deleterious effects in animals.

Differential Transcription of SOCS5 and SOCS7 in Multiple Sclerosis Patients Treated with Interferon Beta or Glatiramer Acetate.

The participation of proinflammatory cytokines in the progression of Multiple Sclerosis (MS) has been well documented. Cytokines activate the JAK-STAT pathway, in which the suppressors of cytokine signaling (SOCS) exert a negative feedback. This paper analyzes the levels of SOCS5 and SOCS7 transcripts, quantified by RT-qPCR, in MS patients, and the concentrations of proinflammatory cytokines, IFN-γ, IL17, and IL6, determined by ELISA. Samples of peripheral blood were obtained from MS patients in the relapsing-remitting phase, treated with IFN-ß or glatiramer acetate (GA), and from healthy individuals. SOCS7 mRNA was significantly higher in patients treated with GA (1.36 ± 0.23) than in those treated with IFN-ß (0.65 ± 0.1). Regarding gender, the level of SOCS5 and SOCS7 transcripts were similar between MS and healthy females; in MS males, the level of SOCS7 transcripts were significantly lower (0.59 ± 0.03) than in healthy males (1.008 ± 0.05). Plasmatic levels of IFN-γ were significantly higher in MS patients (60 pg/mL, range 0-160) than in healthy subjects (0 range, 0-106). The same pattern was observed in MS patients treated with IFN-ß (68 pg/mL, range 0-160) compared to patients treated with GA (51 pg/mL, range 0-114), and in MS females (64 pg/mL, range 0-161) compared to healthy females (0, range 0-99). We hypothesize that the increase in SOCS7 transcription in patients treated with GA could partially explain the action mechanism of this drug, while the increase in the concentration of IFN-γ in MS patients could help elucidate the immunopathology of the disease.

[Submucosal endoscopic dissection in the treatment of early esophageal cancer]. / Disección endoscópica submucosa en el tratamiento del cáncer precoz deesófago.

We report the case of a male patient, 80 years old, with a history of dyspepsia and no family history of neoplasias. In the upper digestive endoscopy in the distal esophagus, a flat depressed lesion with the appearance of early carcinoma, type IIC of Paris classification, was diagnosed by biopsy as a squamous carcinoma in situ, infiltrating, moderately differentiated non-keratinizing grade II carcinoma. He underwent submucosal endoscopic dissection without complications. Histopathology concluded: carcinoma of squamous cells, predominantly in situ of distal esophagus, measuring 0.6 cm, with focus of 0.1 cm of infiltration in the own lamina; absence of angiolymphatic or perineural invasion. The histopathology specimen had margins of surgical resection free of neoplasia. Stage pT1a. Three months later, in the endoscopy control with biopsy of the area, there was no evidence of carcinoma. We present the case because it is still a challenge to establish the diagnosis of esophageal cancer at an early stage, especially in patients without symptoms, highlighting the importance of chromoendoscopy and a good endoscopic examination to reach the diagnosis. Submucosal endoscopy dissection could be considered as a safe and effective alternative treatment to radical surgery.

Hepatitis C: Prevalence of serologic markers and risk factors in blood donors at a large blood centre in South-eastern Brazil (2007-2010).

This study aimed to evaluate the trends of HCV seropositivity rates in first time blood donors from a reference blood centre in Southeast Brazil. Data from the period of 2007-2010 were analysed according to anti-HCV antibodies, donor demographic characteristics and type of donation. There was a marked and continuous decline in prevalence in the analysed period, and in 93,534 first time donors, the prevalence of anti-HCV was 0.09%. Anti-HCV were associated with less education and older age (≥ 35 years). The rates of anti-HCV observed in the present study were lower than in Brazil, but considerably higher than developed countries.

[Presence of Bejing genotype among Mycobacterium tuberculosis strains in two centres of the Region Metropolitana of Chile]. / Presencia del genotipo Beijing entre cepas del complejo Mycobacterium tuberculosis en dos centros de salud de la Región Metropolitana-Chile.

BACKGROUND: Genotyping of Mycobacterium tuberculosis complex (cMtb) allows us to know geographically predominant lineages. Some lineages spread more rapidly and are associated with multidrug resistance, particularly Beijing, which has been reported in Latin America (Peru). There is little information about this topic in Chile and there are no reports of the presence of the Beijing genotype. AIM: To determine the most prevalent lineages in the Metropolitan Region of Chile with emphasis on the search for Beijing in two health centers. METHODS: Two complementary molecular methods were used: spoligotyping, based on the variations of the direct repeat regions in the genome of cMtb and MIRU-VNTR, based in the variable number of tandem repeats of mycobacterial interspersed repetitive units, and subsequent analysis in international databases. A designed lineage was assigned to 37 of the 43 strains studied (86%); 6 isolates could not be assigned to any genotype. LAM and T genotype were the most frequent (39.5 and 32.5%, respectively) followed by Haarlem (7.0%), Beijing (4.7%) and X (2.3%). CONCLUSION: We describe for the first time the presence of the Beijing genotype in Chile. cMtb molecular surveillance should be implemented in our country in order to know the dynamics of its transmission.

Hyperglycemia influences the cell proliferation and death of the rat endocrine pancreas in the neonatal period.

AIMS: To evaluate the cell proliferation and death, and structural morphology of the pancreatic islet cells of the rats with hyperglycemia in the first month of life and compare to those of the control rats. MAIN METHODS: Female Sprague-Dawley newborn rats received Streptozotocin (a beta-cytotoxic drug) at birth for diabetes induction. Control and hyperglycemic animals were euthanized on different days of life: 5, 10, 15, and 30. The pancreas was collected and processed for immunohistochemical analysis of cleaved Caspase-3 (cell death), Ki-67 (cell proliferation), PDX-1 (transcription factor responsible for insulin synthesis), and endocrine hormones (insulin, glucagon, and somatostatin). KEY FINDINGS: Control females showed a higher percentage (%) of Ki-67-positive(+) cells on D10 and D15, a higher % of insulin+ and somatostatin+ cells on D15 and D30, a lower % of PDX-1+ cells on D10, and a higher % of glucagon+ cells on D10 and D30. Hyperglycemic females showed a lower % of Ki-67+ cells on D15, a higher % of cleaved Caspase-3+ cells on D15, and insulin+ cells on D15 and D30. In the comparison among the experimental groups, the hyperglycemic females showed an increased % of cleaved Caspase-3+ and Ki-67+ cells and a lower % of PDX-1+ cells. SIGNIFICANCE: This study enabled a better understanding of the abnormal pancreas development regarding cellular proliferation, apoptosis, and hormonal synthesis in the neonatal period. Thus, the pancreatic islets of hyperglycemic rats do not reestablish the normal endocrine cell population, and cellular apoptosis overcame the proliferative activity of these cells.

Analysis of donor deferral at three blood centers in Brazil.

BACKGROUND: The safety of the blood supply is ensured through several procedures from donor selection to testing of donated units. Examination of the donor deferrals at different centers provides insights into the role that deferrals play in transfusion safety. STUDY DESIGN AND METHODS: A cross-sectional descriptive study of prospective allogeneic blood donors at three large blood centers located in São Paulo, Belo Horizonte, and Recife, Brazil, from August 2007 to December 2009 was conducted. Deferrals were grouped into similar categories across the centers, and within each center frequencies out of all presentations were determined. RESULTS: Of 963,519 prospective blood donors at the three centers, 746,653 (77.5%) were accepted and 216,866 (22.5%) were deferred. Belo Horizonte had the highest overall deferral proportion of 27%, followed by Recife (23%) and São Paulo (19%). Females were more likely to be deferred than males (30% vs. 18%, respectively). The three most common deferral reasons were low hematocrit or hemoglobin, medical diagnoses, and higher-risk behavior. CONCLUSION: The types and frequencies of deferral vary substantially among the three blood centers. Factors that may explain the differences include demographic characteristics, the order in which health history and vital signs are taken, the staff training, and the way deferrals are coded by the centers among other policies. The results indicate that blood donor deferral in Brazil has regional aspects that should be considered when national policies are developed.

Motivation and social capital among prospective blood donors in three large blood centers in Brazil.

BACKGROUND: Studies analyzing motivation factors that lead to blood donation have found altruism to be the primary motivation factor; however, social capital has not been analyzed in this context. Our study examines the association between motivation factors (altruism, self-interest, and response to direct appeal) and social capital (cognitive and structural) across three large blood centers in Brazil. STUDY DESIGN AND METHODS: We conducted a cross-sectional survey of 7635 donor candidates from October 15 through November 20, 2009. Participants completed self-administered questionnaires on demographics, previous blood donation, human immunodeficiency virus testing and knowledge, social capital, and donor motivations. Enrollment was determined before the donor screening process. RESULTS: Among participants, 43.5 and 41.7% expressed high levels of altruism and response to direct appeal, respectively, while only 26.9% expressed high levels of self-interest. More high self-interest was observed at Hemope-Recife (41.7%). Of participants, 37.4% expressed high levels of cognitive social capital while 19.2% expressed high levels of structural social capital. More high cognitive and structural social capital was observed at Hemope-Recife (47.3 and 21.3%, respectively). High cognitive social capital was associated with high levels of altruism, self-interest, and response to direct appeal. Philanthropic and high social altruism were associated with high levels of altruism and response to direct appeal. CONCLUSION: Cognitive and structural social capital and social altruism are associated with altruism and response to direct appeal, while only cognitive social capital is associated with self-interest. Designing marketing campaigns with these aspects in mind may help blood banks attract potential blood donors more efficiently.