Echocardiographic evaluation of diastolic function in the setting of pulmonary hypertension.

Heart failure due to diastolic dysfunction and pulmonary hypertension are frequent comorbid conditions with significant morbidity and mortality. Identifying the presence and etiology of diastolic dysfunction in the setting of pulmonary hypertension remains challenging despite profound therapeutic and prognostic implications. Additionally, there is little guidance in identifying and parsing etiology of diastolic dysfunction in patients found to have pulmonary hypertension. This review discusses the complex interplay between left ventricular diastolic dysfunction and pulmonary hypertension. With an explicit focus on the use of echocardiography for determination of diastolic dysfunction and etiology of pulmonary hypertension, this review also provides a comprehensive review of the literature and provides a framework by which to assess diastolic dysfunction echocardiographically in the setting of pulmonary hypertension.

A Summary of the American Society of Echocardiography Foundation Value-Based Healthcare: Summit 2014: The Role of Cardiovascular Ultrasound in the New Paradigm.

Value-Based Healthcare: Summit 2014 clearly achieved the three goals set forth at the beginning of this document. First, the live event informed and educated attendees through a discussion of the evolving value-based healthcare environment, including a collaborative effort to define the important role of cardiovascular ultrasound in that environment. Second, publication of these Summit proceedings in the Journal of the American Society of Echocardiography will inform a wider audience of the important insights gathered. Third, moving forward, the ASE will continue to build a ''living resource'' on its website, http://www.asecho.org, for clinicians, researchers, and administrators to use in advocating for the value of cardiovascular ultrasound in the new value-based healthcare environment. The ASE looks forward to incorporating many of the Summit recommendations as it works with its members, legislators, payers, hospital administrators, and researchers to demonstrate and increase the value of cardiovascular ultrasound. All Summit attendees shared in the infectious enthusiasm generated by this proactive approach to ensuring cardiovascular ultrasound's place as ''The Value Choice'' in cardiac imaging.

Feasibility and Diagnostic Potential of Pulmonary Transit Time Measurement by Contrast Echocardiography: A Pilot Study.

AIMS: Pulmonary transit time (PTT; the time for ultrasound contrast to travel from the right ventricle [RV] to the left atrium) may provide a single metric that reports on cardiopulmonary function while overcoming some of the challenges of standard echocardiographic measures. We conducted a pilot study to test the feasibility and reproducibility of echocardiographically derived PTT and to determine its association with established measures of cardiopulmonary function. METHODS AND RESULTS: A total of 39 patients receiving clinically indicated ultrasound contrast were prospectively enrolled. PTT was measured in the apical four-chamber view using commercially available software. Reproducibility and inter-observer agreement were assessed in 9 patients. PTT was correlated with established measures of left ventricular systolic and diastolic function, RV function, and pulmonary vascular status. PTT could be measured in 89% (33/37) of patients without a contraindication to ultrasound contrast; all measurements from the last 20 patients were interpretable and obtained independently by a sonographer. Reproducibility and inter-observer agreement were excellent. PTT correlated well with standard echocardiographic indicators of cardiac status. A PTT >4.5 seconds accurately identified all but 1 patient with cardiopulmonary dysfunction. CONCLUSIONS: This pilot study demonstrates that measurement of PTT using ultrasound contrast is highly reproducible, accurately reflects global cardiopulmonary function across a range of cardiopulmonary disease, and can be readily obtained by an independent sonographer. Further studies are needed to determine whether PTT has incremental value in diagnosis and prognosis compared to conventional echocardiographic parameters.

Right ventricular plasticity and functional imaging.

Right ventricular (RV) function is a strong independent predictor of outcome in a number of distinct cardiopulmonary diseases. The RV has a remarkable ability to sustain damage and recover function which may be related to unique anatomic, physiologic, and genetic factors that differentiate it from the left ventricle. This capacity has been described in patients with RV myocardial infarction, pulmonary arterial hypertension, and chronic thromboembolic disease as well as post-lung transplant and post-left ventricular assist device implantation. Various echocardiographic and magnetic resonance imaging parameters of RV function contribute to the clinical assessment and predict outcomes in these patients; however, limitations remain with these techniques. Early diagnosis of RV function and better insight into the mechanisms of RV recovery could improve patient outcomes. Further refinement of established and emerging imaging techniques is necessary to aid subclinical diagnosis and inform treatment decisions.

Strand-specific RNA-seq reveals ordered patterns of sense and antisense transcription in Bacillus anthracis.

BACKGROUND: Although genome-wide transcriptional analysis has been used for many years to study bacterial gene expression, many aspects of the bacterial transcriptome remain undefined. One example is antisense transcription, which has been observed in a number of bacteria, though the function of antisense transcripts, and their distribution across the bacterial genome, is still unclear. METHODOLOGY/PRINCIPAL FINDINGS: Single-stranded RNA-seq results revealed a widespread and non-random pattern of antisense transcription covering more than two thirds of the B. anthracis genome. Our analysis revealed a variety of antisense structural patterns, suggesting multiple mechanisms of antisense transcription. The data revealed several instances of sense and antisense expression changes in different growth conditions, suggesting that antisense transcription may play a role in the ways in which B. anthracis responds to its environment. Significantly, genome-wide antisense expression occurred at consistently higher levels on the lagging strand, while the leading strand showed very little antisense activity. Intrasample gene expression comparisons revealed a gene dosage effect in all growth conditions, where genes farthest from the origin showed the lowest overall range of expression for both sense and antisense directed transcription. Additionally, transcription from both strands was verified using a novel strand-specific assay. The variety of structural patterns we observed in antisense transcription suggests multiple mechanisms for this phenomenon, suggesting that some antisense transcription may play a role in regulating the expression of key genes, while some may be due to chromosome replication dynamics and transcriptional noise. CONCLUSIONS/SIGNIFICANCE: Although the variety of structural patterns we observed in antisense transcription suggest multiple mechanisms for antisense expression, our data also clearly indicate that antisense transcription may play a genome-wide role in regulating the expression of key genes in Bacillus species. This study illustrates the surprising complexity of prokaryotic RNA abundance for both strands of a bacterial chromosome.

Nitrate reductase activity of bacteria in saliva of term and preterm infants.

The salivary glands of adults concentrate nitrate from plasma into saliva where it is converted to nitrite by bacterial nitrate reductases. Nitrite can play a beneficial role in adult gastrointestinal and cardiovascular physiology. When nitrite is swallowed, some of it is converted to nitric oxide (NO) in the stomach and may then exert protective effects in the gastrointestinal tract and throughout the body. It has yet to be determined either when newborn infants acquire oral nitrate reducing bacteria or what the effects of antimicrobial therapy or premature birth may be on the bacterial processing of nitrate to nitrite. We measured nitrate and nitrite levels in the saliva of adults and both preterm and term human infants in the early weeks of life. We also measured oral bacterial reductase activity in the saliva of both infants and adults, and characterized the species of nitrate reducing bacteria present. Oral bacterial conversion of nitrate to nitrite in infants was either undetectable or markedly lower than the conversion rates of adults. No measurable reductase activity was found in infants within the first two weeks of life, despite the presence of oral nitrate reducing bacteria such as Actinomyces odontolyticus, Veillonella atypica, and Rothia mucilaginosa. We conclude that relatively little nitrite reaches the infant gastrointestinal tract due to the lack of oral bacterial nitrate reductase activity. Given the importance of the nitrate-nitrite-NO axis in adults, the lack of oral nitrate-reducing bacteria in infants may be relevant to the vulnerability of newborns to hypoxic stress and gastrointestinal tract pathologies.

Utilizing community-based participatory research to adapt a mental health intervention for African American emerging adults.

BACKGROUND: Adapting mental health interventions to heighten their cultural and contextual appropriateness may be critical for engaging ethnic/racial groups that have been traditionally excluded or marginalized. Community-based participatory research (CBPR) is a collaborative research approach that highlights unique strengths and expertise of those involved. Although intervention adaptations have garnered much attention there is little previous work specifically describing the adaptation process of mental health interventions using CBPR. OBJECTIVE: This article summarizes the use of a CBPR approach to adapt a mental health intervention for urban adolescents and young adults disconnected from school and work, a population at elevated risk for poor mental health owing to the presence of numerous chronic stressors. METHODS: We describe the process undertaken to modify the content and delivery format of an evidence-based intervention. LESSONS LEARNED: Unique challenges of working with urban African American adolescents and young adults in a job training program are highlighted. By incorporating principles of co-learning and shared responsibility, this partnership was able to achieve positive outcomes. CONCLUSION: Our experience suggests that a CBPR approach can be used effectively to adapt a mental health intervention in collaboration with African American adolescents and emerging adults in a job training program.

Herpes simplex virus type 2 tegument proteins contain subdominant T-cell epitopes detectable in BALB/c mice after DNA immunization and infection.

Cytotoxic T cells are important in controlling herpes simplex virus type 2 (HSV-2) reactivation and peripheral lesion resolution. Humans latently infected with HSV-2 have cytotoxic T cells directed against epitopes present in tegument proteins. Studies in mice of immunity to HSV have commonly focused on immunodominant responses in HSV envelope glycoproteins. These antigens have not proved to be an effective prophylactic vaccine target for most of the human population. The murine immune response against HSV tegument proteins has not been explored. We analysed cellular responses in BALB/c mice directed against the tegument proteins encoded by UL46, UL47 and UL49 and against the envelope glycoprotein gD after DNA vaccination or HSV-2 infection. After DNA vaccination, the splenocyte T-cell response to overlapping peptides from UL46 and UL47 was more than 500 gamma interferon spot-forming units per 10(6) responder cells. Peptide truncation studies, responder cell fractionation and major histocompatibility complex binding studies identified several CD8(+) and CD4(+) epitopes. Cellular responses to tegument protein epitopes were also detected after HSV-2 infection. Tegument proteins are rational candidates for further HSV-2 vaccine research.

Comparative transcriptional profiling of Bacillus cereus sensu lato strains during growth in CO2-bicarbonate and aerobic atmospheres.

BACKGROUND: Bacillus species are spore-forming bacteria that are ubiquitous in the environment and display a range of virulent and avirulent phenotypes. This range is particularly evident in the Bacillus cereus sensu lato group; where closely related strains cause anthrax, food-borne illnesses, and pneumonia, but can also be non-pathogenic. Although much of this phenotypic range can be attributed to the presence or absence of a few key virulence factors, there are other virulence-associated loci that are conserved throughout the B. cereus group, and we hypothesized that these genes may be regulated differently in pathogenic and non-pathogenic strains. METHODOLOGY/PRINCIPAL FINDINGS: Here we report transcriptional profiles of three closely related but phenotypically unique members of the Bacillus cereus group--a pneumonia-causing B. cereus strain (G9241), an attenuated strain of B. anthracis (Sterne 34F(2)), and an avirulent B. cereus strain (10987)--during exponential growth in two distinct atmospheric environments: 14% CO(2)/bicarbonate and ambient air. We show that the disease-causing Bacillus strains undergo more distinctive transcriptional changes between the two environments, and that the expression of plasmid-encoded virulence genes was increased exclusively in the CO(2) environment. We observed a core of conserved metabolic genes that were differentially expressed in all three strains in both conditions. Additionally, the expression profiles of putative virulence genes in G9241 suggest that this strain, unlike Bacillus anthracis, may regulate gene expression with both PlcR and AtxA transcriptional regulators, each acting in a different environment. CONCLUSIONS/SIGNIFICANCE: We have shown that homologous and even identical genes within the genomes of three closely related members of the B. cereus sensu lato group are in some instances regulated very differently, and that these differences can have important implications for virulence. This study provides insights into the evolution of the B. cereus group, and highlights the importance of looking beyond differences in gene content in comparative genomics studies.

Prevalence of valvular heart disease in a cohort of patients taking cabergoline for management of hyperprolactinemia.

OBJECTIVE: To determine the prevalence of valvular heart disease in a cohort of patients taking cabergoline for the management of hyperprolactinemia. METHODS: A retrospective review of medical records identified patients with hyperprolactinemia who underwent evaluation at Vanderbilt University Medical Center between January and June 2007. The medical records of those patients who were prescribed cabergoline and who underwent elective echocardiography were reviewed for details pertaining to cardiac valvular abnormalities and cabergoline use. RESULTS: Forty-five patients (mean age, 41 +/- 10 years [SD]) taking 0.91 +/- 0.96 mg of cabergoline per week for a mean duration of 39 +/- 29 months underwent echocardiography. Abnormalities of the cardiac valves were present in 3 patients (7%): 1 patient exhibited mild mitral regurgitation, 1 patient had focal aortic valve thickening, and 1 patient demonstrated mitral valve thickening. We found no significant difference in either the cumulative dose of cabergoline (P = .800) or the duration of cabergoline therapy (P = .745) between those patients with and those without these echocardiographic abnormalities. CONCLUSION: We found echocardiographic valve abnormalities in 3 of 45 patients (7%) who had been prescribed cabergoline for the management of hyperprolactinemia. This prevalence of valvular heart disease after approximately 3 years of cabergoline treatment is no different from that previously reported in normal populations as determined by echocardiography.