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Digital Object Identifier (DOI) Minting Policy

Thu, 07/27/2017 - 6:52pm

This policy articulates the scope of materials that can be assigned a Digital Object Identifier (DOI) through the Lamar Soutter Library and the process of obtaining a DOI.

The Role of Attitude, Control and Intention to Explain Fruit and Vegetable Intake among Racial/Ethnic Minority Women with Low Socioeconomic Status

Mon, 07/24/2017 - 3:41pm

Objective: Fruit and Vegetable (FV) intake-a modifiable risk factor for chronic diseases-is lower among racial/ethnic minorities and low Socio- Economic Status (SES) groups when compared to other populations. The Theory of Planned Behavior (TPB) is one theoretical model studied to explain and influence individual health behaviors, including FV intake, in middle class populations, but not exclusively in diverse, low SES groups. This cross-sectional study evaluated the utility of select TPB variables to explain intention to consume and intake of FV in this population.

Design: Demographics, BMI, select TPB variables, and FV intake were measured via survey. Bivariate analyses were conducted to explore relationships between variables. Hierarchical regression analyses were used to fit two models: one to explain intention and one to explain behavior with regard to FV vegetable intake.

Results: Participants (n=114) age 25-69 years and were mostly African American/Black and Hispanic (21.9% and 73%, respectively). The TPB variable perceived behavioral control was the only significant predictor of intention to consume FV (OR=2.55, 95% CI OR: 1.23, 5.27), and with BMI, FV intake (R2=0.08; F [2,130] =5.72, p=0.0042).

Conclusion: Perceived behavioral control and BMI are the most significant predictors of FV intake but explain only 8% of the variability in intake in our cohort. Our results support prior research which suggests an attenuation of the intention-behavior relationship by SES, and may question the utility of the TPB as it is currently operationalized as a foundational model for future health behavior change research and programs in low SES racial/ethnic minorities.

SlipBuddy: A Mobile Health Intervention to Prevent Overeating

Mon, 07/24/2017 - 3:41pm

Obesity is one of the top health issues around the globe. Rapid adoption of smartphones presents an opportunity for delivering technology-based interventions that are designed to tackle behaviors that contribute to weight gain. Research shows that the vast majority of weight loss apps in the market place do not go beyond deploying tracking based strategies that are burdensome to the users. In this study, we present a new mobile app and an intervention system called SlipBuddy that puts less burden on users and implements stimulus control strategy to help users lose weight. We describe the SlipBuddy system in detail and present the results of the first phase of a pilot study. Our findings indicate that a mobile app that simply helps users identify and track overeating episodes can potentially result in weight loss.

The Feasibility of Incentivizing Participation in an Online Social Network Weight Loss Program

Mon, 07/24/2017 - 3:41pm

Engagement in online social network-delivered weight loss interventions is a predictor of weight loss. Incentivizing engagement in a subset of participants may increase group engagement and subsequent weight loss. In a pilot feasibility trial, 56 adults with obesity were randomized to two Facebook-delivered weight loss interventions, one had 10% users incentivized to engage daily and the other did not. We compared conditions on engagement and weight loss, and then compared incentivized users and natural high engagers on weight loss. Participants were 46.3 (SD: 10.3) years and 89% female. The incentivized user condition had greater total engagement (p=0.0361), but weight loss did not differ (p=0.2096). Three natural superusers emerged in each condition. Natural superusers lost more weight than incentivized users (p=0.0358). Natural superusers’ posts elicited more comments than incentivized superusers (p=0.0107). Incentivized superusers may engage differently than natural superusers. Future studies should explore ways to promote engagement in online interventions.

Racial Differences in Neighborhood Perceptions and their Influences on Physical Activity among Urban Older Women

Mon, 07/24/2017 - 3:41pm

Background: Proper levels of physical activity (PA) are important to healthy aging. Little is known about racial differences in influences of neighborhood perceptions (NP) on PA and use of neighborhood resources among community-dwelling older women.

Materials and methods: In 2014 and 2015, 49 white and 44 black women of age 65 and older living in Washington, DC were queried about their PA, NP, use of neighborhood resources and sociodemographic characteristics. They wore an accelerometer and a Global Positioning System device concurrently for 7 consecutive days. Data were analyzed by race.

Results: Compared to Whites, Blacks had lower NP scores (71% positive vs. 77%, p = 0.01), lower mean daily step counts (mean (SD): 3256 (1918) vs. 5457 (2989), p < 0.001), and lower frequencies of all exercise activities combined (19.7 (8.7) vs. 25.2 (11.8) per week, p = 0.01). For both Whites and Blacks, better NPs were associated with more frequent PA both at (p = 0.05) and away from home (p = 0.01). However, better NPs were associated with higher frequencies of exercise activities, moderate-to-high intensity activities, and utilitarian walking for Whites but not Blacks (p < 0.05 for race-perception interaction terms).

Conclusions: In an urban setting, older Black women were more likely than older White women to have poor NPs, less PA, and weaker or no association of positive NPs with higher levels of certain PAs. Such substantial racial differences warrant further investigation and consideration in health promotion programs.

Racial Differences in Eating Patterns and Food Purchasing Behaviors Among Urban Older Women

Mon, 07/24/2017 - 3:41pm

Objective: To examine differences in diet and food purchasing behaviors between Black and White older women living in urban neighborhoods.

Design: Cross-sectional observational study.

Setting: Urban neighborhoods in Washington, DC, USA.

Participants: Community-dwelling White and Black women of age 65 and older.

Measurements: Participants were queried on diet via 24-hour recalls, food purchasing habits, their use of neighborhood resources and local travel patterns. Frequency and location of self-reported food purchasing and consumption were compared by race.

Results: In 2014 and 2015, 49 White and 44 Black older women were enrolled in the study. Compared to Whites, Blacks reported lower daily caloric intake (mean (SD) 1314 (404) vs. 1529 (448), p=0.02), with a higher percent of calories from protein and fat 1.8 (7.0), p=0.03), and a slightly higher polyunsaturated to saturated fat ratio (p=0.05). Blacks had substantially lower alternate healthy eating index (AHEI) (33.5 (10.2) vs. 43.9 (10.8) of 80 possible points.

Conclusions: In an urban setting, food consumption and purchasing behaviors differed substantially between older Black and White women, which should be further investigated and considered to promote healthy eating in older populations.

Racial Differences in Misclassification of Healthy Eating Based on Food Frequency Questionnaire and 24-Hour Dietary Recalls

Mon, 07/24/2017 - 3:41pm

Objectives: To examine the agreement in nutrient intake and alternate healthy eating indices (AHEI) between a self-administered Food Frequency Questionnaire (FFQ) and 24-hour recall (24HR) measurements of diet by race, among urban older women.

Design: Cross-sectional observational study

Setting: Urban neighborhoods in Washington, DC, USA.

Participants: Community-dwelling White and Black women aged 65 and older.

Measurements: In 2014 and 2015, 49 White and 44 Black older women were queried on diet using both FFQ and 24-hour recalls. The correlation coefficients of 55 nutrient intake measures and agreements on healthy eating classification between the two instruments were compared overall and by race.

Results: The mean correlation coefficient (rho) was 0.46 for Whites and 0.23 for Blacks. For 47 measures, rho was lower for Blacks. Whites had a strong correlation of ≥0.5 for 28 items, while Blacks had strong correlations for only 3 items. Based on FFQ, the mean (SD) of AHEI were 54.0 (10.3) for Whites and 45.9 (8.8) for Blacks (P< 0.001). Based on 24HR, the mean (SD) were 43.9 (10.8) for Whites and 33.2 (9.6) for Blacks (P< 0.001). Using 32 as the cutoff (40% of maximum AHEI score), 50% of Blacks and 14% of Whites were classified as eating unhealthy based on the 24HR, versus 2.6% and 0% based on the FFQ.

Conclusion: The FFQ has limited ability to accurately assess nutrient intake among older Black women, and tends to underestimate racial differences in healthy eating. The FFQ should be further improved for use in racial disparities research of healthy eating in older age, using a larger sample of older women with racial and geographic diversities.

PRIMA: a gene-centered, RNA-to-protein method for mapping RNA-protein interactions

Mon, 07/24/2017 - 11:17am

Interactions between RNA binding proteins (RBPs) and mRNAs are critical to post-transcriptional gene regulation. Eukaryotic genomes encode thousands of mRNAs and hundreds of RBPs. However, in contrast to interactions between transcription factors (TFs) and DNA, the interactome between RBPs and RNA has been explored for only a small number of proteins and RNAs. This is largely because the focus has been on using 'protein-centered' (RBP-to-RNA) interaction mapping methods that identify the RNAs with which an individual RBP interacts. While powerful, these methods cannot as of yet be applied to the entire RBPome. Moreover, it may be desirable for a researcher to identify the repertoire of RBPs that can interact with an mRNA of interest-in a 'gene-centered' manner-yet few such techniques are available. Here, we present Protein-RNA Interaction Mapping Assay (PRIMA) with which an RNA 'bait' can be tested versus multiple RBP 'preys' in a single experiment. PRIMA is a translation-based assay that examines interactions in the yeast cytoplasm, the cellular location of mRNA translation. We show that PRIMA can be used with small RNA elements, as well as with full-length Caenorhabditis elegans 3' UTRs. PRIMA faithfully recapitulated numerous well-characterized RNA-RBP interactions and also identified novel interactions, some of which were confirmed in vivo. We envision that PRIMA will provide a complementary tool to expand the depth and scale with which the RNA-RBP interactome can be explored.

Effect of transcription factor resource sharing on gene expression noise

Mon, 07/24/2017 - 11:17am

Gene expression is intrinsically a stochastic (noisy) process with important implications for cellular functions. Deciphering the underlying mechanisms of gene expression noise remains one of the key challenges of regulatory biology. Theoretical models of transcription often incorporate the kinetics of how transcription factors (TFs) interact with a single promoter to impact gene expression noise. However, inside single cells multiple identical gene copies as well as additional binding sites can compete for a limiting pool of TFs. Here we develop a simple kinetic model of transcription, which explicitly incorporates this interplay between TF copy number and its binding sites. We show that TF sharing enhances noise in mRNA distribution across an isogenic population of cells. Moreover, when a single gene copy shares it's TFs with multiple competitor sites, the mRNA variance as a function of the mean remains unaltered by their presence. Hence, all the data for variance as a function of mean expression collapse onto a single master curve independent of the strength and number of competitor sites. However, this result does not hold true when the competition stems from multiple copies of the same gene. Therefore, although previous studies showed that the mean expression follows a universal master curve, our findings suggest that different scenarios of competition bear distinct signatures at the level of variance. Intriguingly, the introduction of competitor sites can transform a unimodal mRNA distribution into a multimodal distribution. These results demonstrate the impact of limited availability of TF resource on the regulation of noise in gene expression.

Hi-C 2.0: An optimized Hi-C procedure for high-resolution genome-wide mapping of chromosome conformation

Mon, 07/24/2017 - 11:17am

Chromosome conformation capture-based methods such as Hi-C have become mainstream techniques for the study of the 3D organization of genomes. These methods convert chromatin interactions reflecting topological chromatin structures into digital information (counts of pair-wise interactions). Here, we describe an updated protocol for Hi-C (Hi-C 2.0) that integrates recent improvements into a single protocol for efficient and high-resolution capture of chromatin interactions. This protocol combines chromatin digestion and frequently cutting enzymes to obtain kilobase (kb) resolution. It also includes steps to reduce random ligation and the generation of uninformative molecules, such as unligated ends, to improve the amount of valid intra-chromosomal read pairs. This protocol allows for obtaining information on conformational structures such as compartment and topologically associating domains, as well as high-resolution conformational features such as DNA loops.

Targeted Degradation of CTCF Decouples Local Insulation of Chromosome Domains from Genomic Compartmentalization

Mon, 07/24/2017 - 11:17am

The molecular mechanisms underlying folding of mammalian chromosomes remain poorly understood. The transcription factor CTCF is a candidate regulator of chromosomal structure. Using the auxin-inducible degron system in mouse embryonic stem cells, we show that CTCF is absolutely and dose-dependently required for looping between CTCF target sites and insulation of topologically associating domains (TADs). Restoring CTCF reinstates proper architecture on altered chromosomes, indicating a powerful instructive function for CTCF in chromatin folding. CTCF remains essential for TAD organization in non-dividing cells. Surprisingly, active and inactive genome compartments remain properly segregated upon CTCF depletion, revealing that compartmentalization of mammalian chromosomes emerges independently of proper insulation of TADs. Furthermore, our data support that CTCF mediates transcriptional insulator function through enhancer blocking but not as a direct barrier to heterochromatin spreading. Beyond defining the functions of CTCF in chromosome folding, these results provide new fundamental insights into the rules governing mammalian genome organization.

Shelterin components mediate genome reorganization in response to replication stress

Mon, 07/24/2017 - 11:16am

The dynamic nature of genome organization impacts critical nuclear functions including the regulation of gene expression, replication, and DNA damage repair. Despite significant progress, the mechanisms responsible for reorganization of the genome in response to cellular stress, such as aberrant DNA replication, are poorly understood. Here, we show that fission yeast cells carrying a mutation in the DNA-binding protein Sap1 show defects in DNA replication progression and genome stability and display extensive changes in genome organization. Chromosomal regions such as subtelomeres that show defects in replication progression associate with the nuclear envelope in sap1 mutant cells. Moreover, high-resolution, genome-wide chromosome conformation capture (Hi-C) analysis revealed prominent contacts between telomeres and chromosomal arm regions containing replication origins proximal to binding sites for Taz1, a component of the Shelterin telomere protection complex. Strikingly, we find that Shelterin components are required for interactions between Taz1-associated chromosomal arm regions and telomeres. These analyses reveal an unexpected role for Shelterin components in genome reorganization in cells experiencing replication stress, with important implications for understanding the mechanisms governing replication and genome stability.

The Oxidative Stress Response in Caenorhabditis elegans Requires the GATA Transcription Factor ELT-3 and SKN-1/Nrf2

Mon, 07/24/2017 - 11:16am

Cellular damage caused by reactive oxygen species (ROS) is believed to be a major contributor to age-associated diseases. Previously, we characterized the C. elegans Brap2 ortholog (BRAP-2) and found that it is required to prevent larval arrest in response to elevated levels of oxidative stress. Here, we report that C. elegans brap-2 mutants display increased expression of SKN-1-dependent phase II detoxification enzymes that is dependent on PMK-1 (a p38 MAP kinase C. elegans ortholog). An RNAi screen was conducted using a transcription factor library to identify genes required for increased expression of the SKN-1 target gst-4 in brap-2 mutants. We identified ELT-3, a member of the GATA transcription factor family, as a positive regulator of gst-4p::gfp expression. We found that ELT-3 interacts with SKN-1 to activate gst-4 transcription in vitro and that elt-3 is required for enhanced gst-4 expression in the brap-2(ok1492) mutant in vivo Furthermore, nematodes overexpressing SKN-1 required ELT-3 for lifespan extension. Taken together, these results suggest a model where BRAP-2 acts as negative regulator of SKN-1 through inhibition of p38 MAPK activity and that the GATA transcription factor ELT-3 is required along with SKN-1 for the phase II detoxification response in C. elegans.

Self-consistent theory of transcriptional control in complex regulatory architectures

Mon, 07/24/2017 - 11:16am

Individual regulatory proteins are typically charged with the simultaneous regulation of a battery of different genes. As a result, when one of these proteins is limiting, competitive effects have a significant impact on the transcriptional response of the regulated genes. Here we present a general framework for the analysis of any generic regulatory architecture that accounts for the competitive effects of the regulatory environment by isolating these effects into an effective concentration parameter. These predictions are formulated using the grand-canonical ensemble of statistical mechanics and the fold-change in gene expression is predicted as a function of the number of transcription factors, the strength of interactions between the transcription factors and their DNA binding sites, and the effective concentration of the transcription factor. The effective concentration is set by the transcription factor interactions with competing binding sites within the cell and is determined self-consistently. Using this approach, we analyze regulatory architectures in the grand-canonical ensemble ranging from simple repression and simple activation to scenarios that include repression mediated by DNA looping of distal regulatory sites. It is demonstrated that all the canonical expressions previously derived in the case of an isolated, non-competing gene, can be generalised by a simple substitution to their grand canonical counterpart, which allows for simple intuitive incorporation of the influence of multiple competing transcription factor binding sites. As an example of the strength of this approach, we build on these results to present an analytical description of transcriptional regulation of the lac operon.

Generation of Pharyngeal Foregut Endoderm from Pluripotent Stem Cells

Mon, 07/24/2017 - 10:32am

The pharyngeal foregut endoderm (PFE) gives rise to several important organs including the thyroid, thymus and parathyroid glands. In mice and humans, defects in the development of PFE can lead to thymic aplasia and aberrations in thymic epithelial cell (TEC) function can lead to immunodeficiency or autoimmune disease. Successful differentiation of pluripotent stem cells (PSCs) to PFE could provide a renewable cell source that enables the study of human diseases that originate in the PFE.

Here, I identify signaling pathways that influence the differentiation of PSCs to PFE. Firstly, using a novel mouse reporter PSC line we develop a protocol that generates a Pax9 expressing population that is enriched for PFE markers and upon transplantation can form organized epithelial structures. However, since this protocol was inefficient for human PSCs, we subsequently identified additional signaling pathways required for the efficient generation of human PFE and determined a key role for retinoic acid. Upon transplantation, the human PFE gives rise to TECs, a ventral PFE derivative. Finally, to facilitate future investigation into the gene regulatory networks in PFE, we develop a CRISPR-effector system to modulate endogenous gene expression in PSCs. We demonstrate that developmentally relevant genes can be repressed or induced, thereby influencing the cellular state. These data present strategies to generate cells of the PFE lineage from PSCs, facilitating the production of cells for patient-specific disease modeling or cell replacement therapies, and a method to interrogate gene and regulatory element function in PFE and its derivatives.

Augmenting the anisotropic network model with torsional potentials improves PATH performance, enabling detailed comparison with experimental rate data

Fri, 07/21/2017 - 4:25pm

PATH algorithms for identifying conformational transition states provide computational parameters-time to the transition state, conformational free energy differences, and transition state activation energies-for comparison to experimental data and can be carried out sufficiently rapidly to use in the "high throughput" mode. These advantages are especially useful for interpreting results from combinatorial mutagenesis experiments. This report updates the previously published algorithm with enhancements that improve correlations between PATH convergence parameters derived from virtual variant structures generated by RosettaBackrub and previously published kinetic data for a complete, four-way combinatorial mutagenesis of a conformational switch in Tryptophanyl-tRNA synthetase.

High-Grade Partial and Retracted (less than 2 cm) Proximal Hamstring Ruptures: Nonsurgical Treatment Revisited

Fri, 07/21/2017 - 4:25pm

BACKGROUND: High-grade partial proximal hamstring tears and complete tears with retraction less than 2 cm are a subset of proximal hamstring injuries where, historically, treatment has been nonoperative. It is unknown how nonoperative treatment compares with operative treatment.

HYPOTHESIS: The clinical and functional outcomes of nonoperative and operative treatment of partial/complete proximal hamstring tears were compared. We hypothesize that operative treatment of these tears leads to better clinical and functional results.

STUDY DESIGN: Case series; Level of evidence, 4.

METHODS: A retrospective review identified patients with a high-grade partial or complete proximal hamstring rupture with retraction less than 2 cm treated either operatively or nonoperatively from 2007 to 2015. All patients had an initial period of nonoperative treatment. Surgery was offered if patients had continued pain and/or limited function refractory to nonoperative treatment with physical therapy. Outcome measures were each patient's strength perception, ability to return to activity, Lower Extremity Functional Scale (LEFS) score, Short Form-12 (SF-12) physical and mental component outcome scores, distance traversed by a single-leg hop, and Biodex hamstring strength testing.

RESULTS: A total of 25 patients were enrolled in the study. The 15 patients who were treated nonoperatively sustained injuries at a mean age of 55.73 +/- 14.83 years and were evaluated 35.47 +/- 30.35 months after injury. The 10 patients who elected to have surgery sustained injuries at 50.40 +/- 6.31 years of age (P = .23) and were evaluated 30.11 +/- 19.43 months after surgery. LEFS scores were significantly greater for the operative group compared with the nonoperative group (77/80 vs 64.3/80; P = .01). SF-12 physical component scores for the operative group were also significantly greater (P = .03). Objectively, operative and nonoperative treatment modalities showed no significant difference in terms of single-leg hop distance compared with each patient's noninjured leg (P = .26) and torque deficit at isokinetic speeds of 60 and 180 deg/s (P = .46 and .70, respectively).

CONCLUSION: Patients who undergo operative and nonoperative treatment of high-grade partial and/or complete proximal hamstring tears with < 2 cm retraction demonstrate good clinical and functional outcomes. In our series, 40% of patients treated nonoperatively with physical therapy went on to have surgery. For those patients with persistent pain and/or loss of function despite conservative treatment, surgical repair is a viable treatment option that is met with good results.

Missing the target: including perspectives of women with overweight and obesity to inform stigma-reduction strategies

Fri, 07/21/2017 - 4:25pm

OBJECTIVE: Pervasive weight stigma and discrimination have led to ongoing calls for efforts to reduce this bias. Despite increasing research on stigma-reduction strategies, perspectives of individuals who have experienced weight stigma have rarely been included to inform this research. The present study conducted a systematic examination of women with high body weight to assess their perspectives about a broad range of strategies to reduce weight-based stigma.

METHODS: Women with overweight or obesity (N = 461) completed an online survey in which they evaluated the importance, feasibility and potential impact of 35 stigma-reduction strategies in diverse settings. Participants (91.5% who reported experiencing weight stigma) also completed self-report measures assessing experienced and internalized weight stigma.

RESULTS: Most participants assigned high importance to all stigma-reduction strategies, with school-based and healthcare approaches accruing the highest ratings. Adding weight stigma to existing anti-harassment workplace training was rated as the most impactful and feasible strategy. The family environment was viewed as an important intervention target, regardless of participants' experienced or internalized stigma.

CONCLUSION: These findings underscore the importance of including people with stigmatized identities in stigma-reduction research; their insights provide a necessary and valuable contribution that can inform ways to reduce weight-based inequities and prioritize such efforts.

Structural Analysis of the Glycosylated Intact HIV-1 gp120-b12 Antibody Complex Using Hydroxyl Radical Protein Footprinting

Fri, 07/21/2017 - 4:25pm

Glycoprotein gp120 is a surface antigen and virulence factor of human immunodeficiency virus 1. Broadly neutralizing antibodies (bNAbs) that react to gp120 from a variety of HIV isolates offer hope for the development of broadly effective immunogens for vaccination purposes, if the interactions between gp120 and bNAbs can be understood. From a structural perspective, gp120 is a particularly difficult system because of its size, the presence of multiple flexible regions, and the large amount of glycosylation, all of which are important in gp120-bNAb interactions. Here, the interaction of full-length, glycosylated gp120 with bNAb b12 is probed using high-resolution hydroxyl radical protein footprinting (HR-HRPF) by fast photochemical oxidation of proteins. HR-HRPF allows for the measurement of changes in the average solvent accessible surface area of multiple amino acids without the need for measures that might alter the protein conformation, such as mutagenesis. HR-HRPF of the gp120-b12 complex coupled with computational modeling shows a novel extensive interaction of the V1/V2 domain, probably with the light chain of b12. Our data also reveal HR-HRPF protection in the C3 domain caused by interaction of the N330 glycan with the b12 light chain. In addition to providing information about the interactions of full-length, glycosylated gp120 with b12, this work serves as a template for the structural interrogation of full-length glycosylated gp120 with other bNAbs to better characterize the interactions that drive the broad specificity of the bNAb.

Beta-Blocker Use Is Associated With Impaired Left Atrial Function in Hypertension

Fri, 07/21/2017 - 4:25pm

BACKGROUND: Impaired left atrial (LA) mechanical function is present in hypertension and likely contributes to various complications, including atrial arrhythmias, stroke, and heart failure. Various antihypertensive drug classes exert differential effects on central hemodynamics and left ventricular function. However, little is known about their effects on LA function.

METHODS AND RESULTS: We studied 212 subjects with hypertension and without heart failure or atrial fibrillation. LA strain was measured from cine steady-state free-precession cardiac MRI images using feature-tracking algorithms. In multivariable models adjusted for age, sex, race, body mass index, blood pressure, diabetes mellitus, LA volume, left ventricular mass, and left ventricular ejection fraction, beta-blocker use was associated with a lower total longitudinal strain (standardized beta=-0.21; P=0.008), and lower LA expansion index (standardized beta=-0.30; P < 0.001), indicating impaired LA reservoir function. Beta-blocker use was also associated with a lower positive strain (standardized beta=-0.19; P=0.012) and early diastolic strain rate (standardized beta=0.15; P=0.039), indicating impaired LA conduit function. Finally, beta-blocker use was associated with a lower (less negative) late-diastolic strain (standardized beta=0.15; P=0.049), strain rate (standardized beta=0.18; P=0.019), and a lower active LA emptying fraction (standardized beta=-0.27; P< 0.001), indicating impaired booster pump function. Use of other antihypertensive agents was not associated with LA function.

CONCLUSIONS: Beta-blocker use is significantly associated with impaired LA function in hypertension. This association could underlie the increased risk of atrial fibrillation and stroke seen with the use of beta-blockers (as opposed to other antihypertensive agents) demonstrated in recent trials.