Context and Considerations for the Development of Community-Informed Health Communication Messaging to Support Equitable Uptake of COVID-19 Vaccines Among Communities of Color in Washington, DC.

BACKGROUND: Communities of color have been disproportionately impacted by COVID-19. We explored barriers and facilitators to COVID-19 vaccine uptake among African American, Latinx, and African immigrant communities in Washington, DC. METHODS: A total of 76 individuals participated in qualitative interviews and focus groups, and 208 individuals from communities of color participated in an online crowdsourcing contest. RESULTS: Findings documented a lack of sufficient, accurate information about COVID-19 vaccines and questions about the science. African American and African immigrant participants spoke about the deeply rooted historical underpinnings to their community's vaccine hesitancy, citing the prior and ongoing mistreatment of people of color by the medical community. Latinx and African immigrant participants highlighted how limited accessibility played an important role in the slow uptake of COVID-19 vaccines in their communities. Connectedness and solidarity were found to be key assets that can be drawn upon through community-driven responses to address social-structural challenges to COVID-19 related vaccine uptake. CONCLUSIONS: The historic and ongoing socio-economic context and realities of communities of color must be understood and respected to inform community-based health communication messaging to support vaccine equity for COVID-19 and other infectious diseases.

"Direct to Drug" screening as a precision medicine tool in multiple myeloma.

Seventy-six FDA-approved oncology drugs and emerging therapeutics were evaluated in 25 multiple myeloma (MM) and 15 non-Hodgkin's lymphoma cell lines and in 113 primary MM samples. Ex vivo drug sensitivities were mined for associations with clinical phenotype, cytogenetic, genetic mutation, and transcriptional profiles. In primary MM samples, proteasome inhibitors, dinaciclib, selinexor, venetoclax, auranofin, and histone deacetylating agents had the broadest cytotoxicity. Of interest, newly diagnosed patient samples were globally less sensitive especially to bromodomain inhibitors, inhibitors of receptor tyrosine kinases or non-receptor kinases, and DNA synthesis inhibitors. Clustering demonstrated six broad groupings of drug sensitivity linked with genomic biomarkers and clinical outcomes. For example, our findings mimic clinical observations of increased venetoclax responsiveness in t(11;14) patients but also identify an increased sensitivity profile in untreated patients, standard genetic risk, low plasma cell S-Phase, and in the absence of Gain(1q) and t(4;14). In contrast, increased ex vivo responsiveness to selinexor was associated with biomarkers of poor prognosis and later relapse patients. This "direct to drug" screening resource, paired with functional genomics, has the potential to successfully direct appropriate individualized therapeutic approaches in MM and to enrich clinical trials for likely responders.

Microbiota-driven interleukin-17-producing cells and eosinophils synergize to accelerate multiple myeloma progression.

The gut microbiota has been causally linked to cancer, yet how intestinal microbes influence progression of extramucosal tumors is poorly understood. Here we provide evidence implying that Prevotella heparinolytica promotes the differentiation of Th17 cells colonizing the gut and migrating to the bone marrow (BM) of transgenic Vk*MYC mice, where they favor progression of multiple myeloma (MM). Lack of IL-17 in Vk*MYC mice, or disturbance of their microbiome delayed MM appearance. Similarly, in smoldering MM patients, higher levels of BM IL-17 predicted faster disease progression. IL-17 induced STAT3 phosphorylation in murine plasma cells, and activated eosinophils. Treatment of Vk*MYC mice with antibodies blocking IL-17, IL-17RA, and IL-5 reduced BM accumulation of Th17 cells and eosinophils and delayed disease progression. Thus, in Vk*MYC mice, commensal bacteria appear to unleash a paracrine signaling network between adaptive and innate immunity that accelerates progression to MM, and can be targeted by already available therapies.

Antibiotic stewardship in the retail clinic setting: Implementation in 1100 clinics nationwide.

In light of increasing antibiotic resistance and a slowed antibiotic development pipeline, stewardship is more urgent than ever. To date, most stewardship guidelines and best practice recommendations for implementation focus on local or regional health care organizations. CVS MinuteClinic has implemented a consistent, evidence-based stewardship approach in its >1100 clinics in 33 states. The approach is associated with higher quality antibiotic use than that in primary care practices and emergency departments. Given MinuteClinic's scale, sharing this approach and lessons learned may assist other organizations in implementing large-scale stewardship programs that foster judicious use of antibiotics for the public's health.

Activation of the EIF2α/ATF4 and ATF6 Pathways in DU-145 Cells by Boric Acid at the Concentration Reported in Men at the US Mean Boron Intake.

Fruits, nuts, legumes, and vegetables are rich sources of boron (B), an essential plant nutrient with chemopreventive properties. Blood boric acid (BA) levels reflect recent B intake, and men at the US mean intake have a reported non-fasting level of 10 µM. Treatment of DU-145 prostate cancer cells with physiological concentrations of BA inhibits cell proliferation without causing apoptosis and activates eukaryotic initiation factor 2 (eIF2α). EIF2α induces cell differentiation and protects cells by redirecting gene expression to manage endoplasmic reticulum stress. Our objective was to determine the temporal expression of endoplasmic reticulum (ER) stress-activated genes in DU-145 prostate cells treated with 10 µM BA. Immunoblots showed post-treatment increases in eIF2α protein at 30 min and ATF4 and ATF6 proteins at 1 h and 30 min, respectively. The increase in ATF4 was accompanied by an increase in the expression of its downstream genes growth arrest and DNA damage-induced protein 34 (GADD34) and homocysteine-induced ER protein (Herp), but a decrease in GADD153/CCAAT/enhancer-binding protein homologous protein (CHOP), a pro-apoptotic gene. The increase in ATF6 was accompanied by an increase in expression of its downstream genes GRP78/BiP, calreticulin, Grp94, and EDEM. BA did not activate IRE1 or induce cleavage of XBP1 mRNA, a target of IRE1. Low boron status has been associated with increased cancer risk, low bone mineralization, and retinal degeneration. ATF4 and BiP/GRP78 function in osteogenesis and bone remodeling, calreticulin is required for tumor suppressor p53 function and mineralization of teeth, and BiP/GRP78 and EDEM prevent the aggregation of misfolded opsins which leads to retinal degeneration. The identification of BA-activated genes that regulate its phenotypic effects provides a molecular underpinning for boron nutrition and biology.

Boric acid induces cytoplasmic stress granule formation, eIF2α phosphorylation, and ATF4 in prostate DU-145 cells.

Dietary boron intake is associated with reduced prostate and lung cancer risk and increased bone mass. Boron is absorbed and circulated as boric acid (BA) and at physiological concentrations is a reversible competitive inhibitor of cyclic ADP ribose, the endogenous agonist of the ryanodine receptor calcium (Ca(+2)) channel, and lowers endoplasmic reticulum (ER) [Ca(2+)]. Low ER [Ca(2+)] has been reported to induce ER stress and activate the eIF2α/ATF4 pathway. Here we report that treatment of DU-145 prostate cells with physiological levels of BA induces ER stress with the formation of stress granules and mild activation of eIF2α, GRP78/BiP, and ATF4. Mild activation of eIF2α and its downstream transcription factor, ATF4, enables cells to reconfigure gene expression to manage stress conditions and mild activation of ATF4 is also required for the differentiation of osteoblast cells. Our results using physiological levels of boric acid identify the eIF2α/ATF pathway as a plausible mode of action that underpins the reported health effects of dietary boron.

Dating violence, childhood maltreatment, and BMI from adolescence to young adulthood.

BACKGROUND AND OBJECTIVES: This study tested whether dating violence (DV) victimization is associated with increases in BMI across the transition from adolescence to young adulthood and whether gender and previous exposure to child maltreatment modify such increases. METHODS: Data were from participants (N = 9295; 49.9% female) in the National Longitudinal Study of Adolescent Health. BMI was calculated from measured height and weight at waves 2, 3, and 4 of the study. DV victimization was measured at waves 2, 3, and 4 by using items from the revised Conflict Tactics Scales. Linear regression by using generalized estimating equations with robust SEs was used to test the association. Models were stratified according to gender and history of child maltreatment. RESULTS: From baseline to wave 4, BMI increased on average 6.5 units (95% confidence interval [CI]: 6.2-6.7) and 6.8 units (95% CI: 6.5-7.1) among men and women, respectively, and nearly one-half (45.5% of men; 43.9% of women) reported DV at some point. In stratified models, DV victimization (ß: 0.3 [95% CI: 0.0-0.6]) independently predicted BMI increase over time in women. Exposure to childhood sexual abuse magnified the increase in BMI associated with DV victimization (ß: 1.3 [95% CI: 0.3-2.3]). No other types of childhood maltreatment were significant modifiers of the DV-BMI association. Violence victimization was not associated with BMI among men. CONCLUSIONS: Screening and support for DV victims, especially women who have also experienced childhood maltreatment, may be warranted to reduce the likelihood of health consequences associated with victimization.

Monolayer graphene dispersion and radiative cooling for high power LED.

Molecular fan, a radiative cooling by thin film, has been developed and its application for compact electronic devices has been evaluated. The enhanced surface emissivity and heat dissipation efficiency of the molecular fan coating are shown to correlate with the quantization of lattice modes in active nanomaterials. The highly quantized G and 2D bands in graphene are achieved by our dispersion technique, and then incorporated in an organic-inorganic acrylate emulsion to form a coating assembly on heat sinks (for LED and CPU). This water-based dielectric layer coating has been formulated and applied on metal core printed circuit boards. The heat dissipation efficiency and breakdown voltage are evaluated by a temperature-monitoring system and a high-voltage breakdown tester. The molecular fan coating on heat dissipation units is able to decrease the equilibrium junction temperature by 29.1 ° C, while functioning as a dielectric layer with a high breakdown voltage (>5 kV). The heat dissipation performance of the molecular fan coating applied on LED devices shows that the coated 50 W LED gives an enhanced cooling of 20% at constant light brightness. The schematics of monolayer graphene dispersion, undispersed graphene platelet, and continuous graphene sheet are illustrated and discussed to explain the mechanisms of radiative cooling, radiative/non-radiative, and non-radiative heat re-accumulation.

Effects of tyrosine kinase inhibitors on rat isolated heart function and protein biomarkers indicative of toxicity.

INTRODUCTION: Cardiac toxicity, manifested as diminished contractility, ischemic heart disease, and heart failure is a major issue in drug safety. Concerns revolve around targeted drugs (TKIs) where contractility effects were not anticipated. The ability to predict cardiac toxicity early would help to de-risk drugs in development and prepare physicians to manage risk in the clinic. Issues with current preclinical studies include insufficient testing with informative, translatable models, and predictive biomarkers. The isolated heart model is amenable to multiple assessments which can be combined with current technologies to assess toxicity on a multi-scale level. METHODS: Rat isolated heart model was used to assess changes in left ventricular (LV) contractility and protein biomarkers BNP, IL6, TNFα, and cardiac troponins T (TnT) and I (TnI). Responses were assessed during perfusion with modified Henseleit Krebs (MHK), and 20 min concentration escalations of verapamil, carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP), isoproterenol, or 20 min escalations bracketing clinical blood concentrations of sunitinib, sorafenib, and erlotinib. LV parameters and effluent for biomarkers were collected before and during escalating drug concentrations. RESULTS: Verapamil reduced inotropy with no change in biomarkers, FCCP and isoproterenol reduced and increased heart function respectively and increased TnT and TNFα. Erlotinib had no significant effects on function or biomarkers. Sunitinib diminished function, increased TNFα at 0.1 µM, and increased TnT at higher concentrations. Sorafenib dose dependently increased TNFα beginning at 0.1 µM, reducing contractility and flow rate at 0.6 µM. DISCUSSION: The ex-vivo assay is a sensitive and predictive model for assessing changes in heart function and biomarkers of toxicity and injury. This assay demonstrates the potential for sunitinib and sorafenib to cause cardiac toxicity in humans. Also, TNFα appears to be a biomarker in the heart prior to injury. Due to its versatility, the isolated heart assay has potential to fill gaps in cardiac safety testing early in drug development.

Placenta membranacea.

Placenta membranacea is a rare placental disorder characterized by the presence of fetal membranes (complete or partially) covered by chorionic villi. A 35-year-old woman, gravida 1, was admitted for preterm labor at 24 weeks and 5 days. She subsequently developed heavy vaginal bleeding and underwent a classical cesarean delivery for suspected abruption. Postpartum inspection of the placenta demonstrated a small placenta with tan colored membranes, and diffusely scattered placental cotyledons. Histologic examination revealed chorionic villi directly attached to the fetal membranes on the periphery,consistent with the diagnosis of a partial placenta membranacea. Placenta membranacea should be considered in the etiology of painless vaginal bleeding in the second and third trimester. This condition can be associated with other placental abnormalities, such as placenta previa or accreta. Perinatal outcome may include stillbirth, preterm delivery, or neonatal death.

Uncovering the biology of multiple myeloma among African Americans: a comprehensive genomics approach.

Epidemiological data have suggested that African American (AA) persons are twice as likely to be diagnosed with multiple myeloma (MM) compared with European American (EA) persons. Here, we have analyzed a set of cytogenetic and genomic data derived from AA and EA MM patients. We have compared the frequency of IgH translocations in a series of data from 115 AA patients from 3 studies and 353 EA patients from the Eastern Cooperative Oncology Group (ECOG) studies E4A03 and E9487. We have also interrogated tumors from 45 AA and 196 EA MM patients for somatic copy number abnormalities associated with poor outcome. In addition, 35 AA and 178 EA patients were investigated for a transcriptional profile associated with high-risk disease. Overall, based on this cohort, genetic profiles were similar except for a significantly lower frequency of IgH translocations (40% vs 52%; P = .032) in AA patients. Frequency differences of somatic copy number aberrations were not significant after correction for multiple testing. There was also no significant difference in the frequency of high-risk disease based on gene expression profiling. Our study represents the first comprehensive comparisons of the frequency and distribution of molecular alterations in MM tumors between AA and EA patients. ECOG E4A03 is registered with ClinicalTrials.gov, number NCT00098475. ECOG E9487 is a companion validation set to the ECOG study E9486 and is registered with the National Institutes of Health, National Cancer Institute, Clinical Trials (PDQ), number EST-9486.

Psychosocial distress and stroke risk in older adults.

BACKGROUND AND PURPOSE: To investigate the association of psychosocial distress with risk of stroke mortality and incident stroke in older adults. METHODS: Data were from the Chicago Health and Aging Project, a longitudinal population-based study conducted in 3 contiguous neighborhoods on the south side of Chicago, IL. Participants were community-dwelling black and non-Hispanic white adults, aged 65 years and older (n=4120 for stroke mortality; n=2649 for incident stroke). Psychosocial distress was an analytically derived composite measure of depressive symptoms, perceived stress, neuroticism, and life dissatisfaction. Cox proportional hazards models examined the association of distress with stroke mortality and incident stroke over 6 years of follow-up. RESULTS: Stroke deaths (151) and 452 incident strokes were identified. Adjusting for age, race, and sex, the hazard ratio (HR) for each 1-SD increase in distress was 1.47 (95% confidence interval [CI]=1.28-1.70) for stroke mortality and 1.18 (95% CI=1.07-1.30) for incident stroke. Associations were reduced after adjustment for stroke risk factors and remained significant for stroke mortality (HR=1.29; 95% CI=1.10-1.52) but not for incident stroke (HR=1.09; 95% CI=0.98-1.21). Secondary analyses of stroke subtypes showed that distress was strongly related to incident hemorrhagic strokes (HR=1.70; 95% CI=1.28-2.25) but not ischemic strokes (HR=1.02; 95% CI=0.91-1.15) in fully adjusted models. CONCLUSIONS: Increasing levels of psychosocial distress are related to excess risk of both fatal and nonfatal stroke in older black and white adults. Additional research is needed to examine pathways linking psychosocial distress to cerebrovascular disease risk.

Identification of ryanodine receptor isoforms in prostate DU-145, LNCaP, and PWR-1E cells.

The ryanodine receptor (RyR) is a large, intracellular calcium (Ca(2+)) channel that is associated with several accessory proteins and is an important component of a cell's ability to respond to changes in the environment. Three isoforms of the RyR exist and are well documented for skeletal and cardiac muscle and the brain, but the isoforms in non-excitable cells are poorly understood. The aggressiveness of breast cancers in women has been positively correlated with the expression of the RyR in breast tumor tissue, but it is unknown if this is limited to specific isoforms. Identification and characterization of RyRs in cancer models is important in understanding the role of the RyR channel complex in cancer and as a potential therapeutic target. The objective of this report was to identify the RyR isoforms expressed in widely used prostate cancer cell lines, DU-145 and LNCaP, and the non-tumorigenic prostate cell line, PWR-1E. Oligonucleotide primers specific for each isoform were used in semi-quantitative and real-time PCR to determine the identification and expression levels of the RyR isoforms. RyR1 was expressed in the highest amount in DU-145 tumor cells, expression was 0.48-fold in the non-tumor cell line PWR-1E compared to DU-145 cells, and no expression was observed in LNCaP tumor cells. DU-145 cells had the lowest expression of RyR2. The expression was 26- and 15-fold higher in LNCaP and PWR-1E cells, respectively. RyR3 expression was not observed in any of the cell lines. All cell types released Ca(2+) in response to caffeine showing they had functional RyRs. Total cellular RyR-associated Ca(2+) release is determined by both the number of activated RyRs and its accessory proteins which modulate the receptor. Our results suggest that the correlation between the expression of the RyR and tumor aggression is not related to specific RyR isoforms, but may be related to the activity and number of receptors.

Latent constructs in psychosocial factors associated with cardiovascular disease: an examination by race and sex.

This study examines race and sex differences in the latent structure of 10 psychosocial measures and the association of identified factors with self-reported history of coronary heart disease (CHD). Participants were 4,128 older adults from the Chicago Health and Aging Project. Exploratory factor analysis (EFA) with oblique geomin rotation was used to identify latent factors among the psychosocial measures. Multi-group comparisons of the EFA model were conducted using exploratory structural equation modeling to test for measurement invariance across race and sex subgroups. A factor-based scale score was created for invariant factor(s). Logistic regression was used to test the relationship between the factor score(s) and CHD adjusting for relevant confounders. Effect modification of the relationship by race-sex subgroup was tested. A two-factor model fit the data well (comparative fit index = 0.986; Tucker-Lewis index = 0.969; root mean square error of approximation = 0.039). Depressive symptoms, neuroticism, perceived stress, and low life satisfaction loaded on Factor I. Social engagement, spirituality, social networks, and extraversion loaded on Factor II. Only Factor I, re-named distress, showed measurement invariance across subgroups. Distress was associated with a 37% increased odds of self-reported CHD (odds ratio: 1.37; 95% confidence intervals: 1.25, 1.50; p-value < 0.0001). This effect did not differ by race or sex (interaction p-value = 0.43). This study identified two underlying latent constructs among a large range of psychosocial variables; only one, distress, was validly measured across race-sex subgroups. This construct was robustly related to prevalent CHD, highlighting the potential importance of latent constructs as predictors of cardiovascular disease.

Impact of high-risk classification by FISH: an eastern cooperative oncology group (ECOG) study E4A03.

Lenalidomide with dexamethasone is a standard induction treatment regimen for newly diagnosed myeloma (although a Federal Drug Administration indication is still absent). In the context of the Phase 3 clinical trial E4A03 (lenalidomide plus dexamethasone in low or high doses), we queried whether a fluorescence in situ hybridization (FISH)-based genetic classification into high risk (HR) and standard risk (SR) multiple myeloma (MM) would remain clinically significant. Of 445 E4A03 patients, 126 had FISH analysis; 21 were classified HR with t(4;14), t(14;16), or 17p13 deletions. Median survival follow-up approached 3 years. Patients with FISH data tended to be younger and healthier compared to the rest of the study population and, consequently, had superior overall survival (OS) results. Within the FISH cohort, shorter OS in the HR versus SR group (P = 0·004) corresponded to a hazard ratio of 3·48 [95% confidence interval: (1·42-8·53)], an effect also observed in multivariate analysis. Two-year OS rates were 91% for SR MM and 76% for HR MM. There was also evidence of interaction between risk status and treatment (P = 0·026). HR patients were less likely to attain good partial response (SR 46% and HR 30%, Odds Ratio = 2·0 [0·7-5·6]), but overall response rates were not different. FISH-based risk classification retained prognostic significance in patients receiving lenalidomide-based induction.

Effects of a home-based walking intervention on mobility and quality of life in people with diabetes and peripheral arterial disease: a randomized controlled trial.

OBJECTIVE: Determine the efficacy of a home-based walking intervention to improve walking ability and quality of life in people with diabetes and peripheral arterial disease (PAD). RESEARCH DESIGN AND METHODS: We conducted a randomized, controlled, single-blind trial within university-affiliated clinics in our local community. We randomized 145 participants (45 women) with diabetes and PAD to our intervention--a 6-month behavioral intervention targeting levels of readiness to engage in routine walking for exercise--versus attention control. Our primary outcome was 6-month change in maximal treadmill walking distance. Secondary outcomes included 3-month change in maximal walking distance, lower limb function (i.e., walking impairment scores), quality of life (Medical Outcomes Short Form Survey), exercise behaviors, depressive symptoms, and self-efficacy at 3 and 6 months. RESULTS: The mean age of participants was 66.5 (SD 10.1) years. Intervention and control groups did not differ significantly in 6-month change in maximal treadmill walking distance (average [SE] 24.5 [19.6] meters vs. 39.2 [19.6] meters; P = 0.60). Among secondary outcomes, for the intervention and control groups, respectively, average walking speed scores increased by 5.7 [2.2] units and decreased by 1.9 [2.8] units (P = 0.03); the mental health quality of life subscale score increased by 3.2 [1.5] and decreased by 2.4 [1.5] units (P = 0.01). CONCLUSIONS: A home-based walking intervention did not improve walking distance but did improve walking speed and quality of life in people with diabetes and PAD. Clinicians should consider recommending home-based walking therapy for such patients.

Impact of gene expression profiling-based risk stratification in patients with myeloma receiving initial therapy with lenalidomide and dexamethasone.

Detection of specific chromosomal abnormalities by FISH and metaphase cytogenetics allows risk stratification in multiple myeloma; however, gene expression profiling (GEP) based signatures may enable more specific risk categorization. We examined the utility of 2 GEP-based risk stratification systems among patients undergoing initial therapy with lenalidomide in the context of a phase 3 trial. Among 45 patients studied at baseline, 7 (16%) and 10 (22%), respectively, were high-risk using the GEP70 and GEP15 signatures. The median overall survival for the GEP70 high-risk group was 19 months versus not reached for the rest (hazard ratio = 14.1). Although the medians were not reached, the GEP15 also predicted a poor outcome among the high-risk patients. The C-statistic for the GEP70, GEP15, and FISH based risk stratification systems was 0.74, 0.7, and 0.7, respectively. Here we demonstrate the prognostic value for GEP risk stratification in a group of patients primarily treated with novel agents. This trial was registered at www.clinicaltrials.gov as #NCT00098475.

Individual differences in vagal regulation moderate associations between daily affect and daily couple interactions.

Previous research suggests that cardiac vagal regulation (indexed by respiratory sinus arrhythmia, or RSA) provides a physiological substrate for affect regulation, which presumably underlies adaptive interpersonal functioning.The authors tested these associations in the context of daily interactions between 68 cohabiting couples. Participants underwent a laboratory assessment of RSA during rest and also during a series of psychological stressors. Subsequently, they kept daily measures of affect and interaction quality for 21 days. Individual differences in baseline and stress levels of RSA moderated within-person associations between daily affect and the quality of couple interactions. The pattern of results differed for women versus men. Men with lower vagal tone or higher vagal reactivity had stronger associations between daily negative affect and daily negative interactions, and men with higher vagal tone had more positive daily interactions overall. Women with higher vagal tone had stronger associations between daily positive affect and daily positive interactions.

Receptor activated Ca(2+) release is inhibited by boric acid in prostate cancer cells.

BACKGROUND: The global disparity in cancer incidence remains a major public health problem. We focused on prostate cancer since microscopic disease in men is common, but the incidence of clinical disease varies more than 100 fold worldwide. Ca(2+) signaling is a central regulator of cell proliferation, but has received little attention in cancer prevention. We and others have reported a strong dose-dependent reduction in the incidence of prostate and lung cancer within populations exposed to boron (B) in drinking water and food; and in tumor and cell proliferation in animal and cell culture models. METHODS/PRINCIPAL FINDINGS: We examined the impact of B on Ca(2+) stores using cancer and non-cancer human prostate cell lines, Ca(2+) indicators Rhod-2 AM and Indo-1 AM and confocal microscopy. In DU-145 cells, inhibition of Ca(2+) release was apparent following treatment with Ringers containing RyR agonists cADPR, 4CmC or caffeine and respective levels of BA (50 microM), (1, 10 microM) or (10, 20, 50,150 microM). Less aggressive LNCaP cancer cells required 20 microM BA and the non-tumor cell line PWR1E required 150 microM BA to significantly inhibit caffeine stimulated Ca(2+) release. BA (10 microM) and the RyR antagonist dantroline (10 microM) were equivalent in their ability to inhibit ER Ca(2+) loss. Flow cytometry and confocal microscopy analysis showed exposure of DU-145 cells to 50 microM BA for 1 hr decreased stored [Ca(2+)] by 32%. CONCLUSION/SIGNIFICANCE: We show B causes a dose dependent decrease of Ca(2+) release from ryanodine receptor sensitive stores. This occurred at BA concentrations present in blood of geographically disparate populations. Our results suggest higher BA blood levels lower the risk of prostate cancer by reducing intracellular Ca(2+) signals and storage.