Aortic stenosis (AS) is among the most common valvular heart diseases encountered in the United States. In this review the authors examine differences between racial and ethnic groups in the ...epidemiology and management of severe AS, explore potential explanations for these findings, and discuss the implications for improving the delivery of care to racially and ethnically diverse populations. Underrepresented racial and ethnic groups experience a paradoxically lower prevalence or incidence of AS relative to white subjects, despite having a higher prevalence of traditional risk factors. Historically, UREGs with severe AS have had lower rates of both surgical and transcatheter aortic valve replacement and experienced more post-surgical complications, including, bleeding, worsening heart failure, and rehospitalization. Last, UREGs with severe AS have an increased risk for morbidity and mortality relative to white patients. To date much of the research on AS has examined black-white differences, so there is a need to understand how other racial and ethnic groups with severe AS are diagnosed and treated, with examination of their resulting outcomes. Overall, racial and ethnic disparities in health care access and care delivery are a public health concern given the changing demographics of the U.S. population. These differences in AS management and outcomes highlight the need for additional research into contributing factors and appropriate interventions to address the lower rates of aortic valve replacement and higher morbidity and mortality among UREGs.
Postmenopausal estrogen depletion is a major contributing factor to bone loss. Soy isoflavones have variable effects on the prevention of postmenopausal bone loss, which is possibly related to the ...specific isoflavone content or the variable equol-producing capacity of individuals.
We aimed to determine the effects of the content of isoflavones in a soy supplement and the equol-producing ability of the individual on postmenopausal bone calcium retention.
The study was a blinded, randomized, crossover intervention trial in 24 postmenopausal women who were prescreened for their ability to convert daidzein to equol. Women were equilibrated with (41)Ca before the intervention. Interventions were 5 soy isoflavone oral supplements (2 doses of a genistein-rich soy supplement and 3 doses of mixed isoflavones in various proportions) and a bisphosphonate (risedronate). Each intervention was given sequentially for 50 d followed by a 50-d washout period. The percentage of bone calcium retention was determined from the change in urinary (41)Ca:calcium.
Interventions that ranged from 52 to 220 mg total isoflavones/d increased bone calcium retention between 3.4% and 7.6% (P < 0.05), which was a moderate effect compared with that of risedronate at 15.3% (95% CI: 7.1%, 22.7%; P = 0.0014). The most-effective soy intervention delivered 105.23 mg total isoflavones/d as genistein, daidzein, and glycitein in their natural ratios and increased bone calcium retention by 7.6% (95% CI: 4.9%, 10.2%; P < 0.0001). Genistein, at 52.85 mg/d, increased bone calcium retention by 3.4% (95% CI: 0.5%, 6.2%; P = 0.029); but there was no benefit at higher amounts (113.52 mg/d). There was no difference (P = 0.5) in bone calcium retention between equol producers and nonproducers.
Soy isoflavones, although not as potent as risedronate, are effective bone-preserving agents in postmenopausal women regardless of their equol-producing status, and mixed isoflavones in their natural ratios are more effective than enriched genistein. This trial was registered at clinicaltrials.gov as NCT00244907.
Among patients with severe aortic stenosis (AS), there are limited data on aortic valve replacement (AVR), reasons for nonreceipt and mortality by race.
Utilizing the Duke Echocardiography Laboratory ...Database, we analyzed data from 110,711 patients who underwent echocardiography at Duke University Medical Center between 1999 and 2013. We identified 1,111 patients with severe AS who met ≥1 of 3 criteria for AVR: ejection fraction ≤50%, diagnosis of heart failure, or need for coronary artery bypass surgery. Logistic regression models were used to assess the association between race, AVR and 1-year mortality. χ2 testing was used to assess potential racial differences in reasons for AVR nonreceipt.
Among the 1,111 patients (143 AA and 968 CA) eligible for AVR, AA were more often women, had more diabetes, renal insufficiency, aortic regurgitation and left ventricular hypertrophy. CA were more often smokers, had more ischemic heart disease, hyperlipidemia and higher median income levels. There were no racial differences in surgical risk utilizing logistic euroSCORES. Relative to CA, AA had lower rates of AVR (adjusted odds ratio 0.46, 95% CI 0.3-0.71, P < .001) yet similar 1-year mortality (aHR 0.81, 95% CI 0.57-1.17, P = .262). There were no significant differences in reasons for AVR nonreceipt.
We identified 143 African Americans (AA) and 968 Caucasian Americans(CA) with severe AS who met prespecified criteria for AVR.. AA relative to CA were more often women, had more diabetes, renal insufficiency, and left ventricular hypertrophy, however had less tobacco use, ischemic heart disease, hyperlipidemia and lower median income levels. Among patients with severe AS, AA relative to CA had lower rates of AVR (adjusted odds ratio 0.46, 95% CI 0.3-0.71, P < .001) without significant differences in reasons for AVR nonreceipt and similar 1-year mortality.
The accurate measurement of blood pressure (BP) is essential for the diagnosis and management of hypertension. Restricted use of mercury devices, increased use of oscillometric devices, discrepancies ...between clinic and out-of-clinic BP, and concerns about measurement error with manual BP measurement techniques have resulted in uncertainty for clinicians and researchers. The National Heart, Lung, and Blood Institute of the U.S. National Institutes of Health convened a working group of clinicians and researchers in October 2017 to review data on BP assessment among adults in clinical practice and clinic-based research. In this report, the authors review the topics discussed during a 2-day meeting including the current state of knowledge on BP assessment in clinical practice and clinic-based research, knowledge gaps pertaining to current BP assessment methods, research and clinical needs to improve BP assessment, and the strengths and limitations of using BP obtained in clinical practice for research and quality improvement activities.
Neuromodulation plays a critical role in brain function in both health and disease, and new tools that capture neuromodulation with high spatial and temporal resolution are needed. Here, we introduce ...a synthetic catecholamine nanosensor with fluorescent emission in the near infrared range (1000-1300 nm), near infrared catecholamine nanosensor (nIRCat). We demonstrate that nIRCats can be used to measure electrically and optogenetically evoked dopamine release in brain tissue, revealing hotspots with a median size of 2 µm. We also demonstrated that nIRCats are compatible with dopamine pharmacology and show D2 autoreceptor modulation of evoked dopamine release, which varied as a function of initial release magnitude at different hotspots. Together, our data demonstrate that nIRCats and other nanosensors of this class can serve as versatile synthetic optical tools to monitor neuromodulatory neurotransmitter release with high spatial resolution.
Studies of visit-to-visit office blood pressure (BP) variability (OBPV) as a predictor of cardiovascular events and death in high-risk patients treated to lower BP targets are lacking. We conducted a ...post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial), a well-characterized cohort of participants randomized to intensive (<120 mm Hg) or standard (<140 mm Hg) systolic BP targets. We defined OBPV as the coefficient of variation of the systolic BP using measurements taken during the 3-,6-, 9-, and 12-month study visits. In our cohort of 7879 participants, older age, female sex, black race, current smoking, chronic kidney disease, and coronary disease were independent determinants of higher OBPV. Use of thiazide-type diuretics or dihydropyridine calcium channel blockers was associated with lower OBPV whereas angiotensin-converting enzyme inhibitors or angiotensin receptor blocker use was associated with higher OBPV. There was no difference in OBPV in participants randomized to standard or intensive treatment groups. We found that OBPV had no significant associations with the composite end point of fatal and nonfatal cardiovascular events (n=324 primary end points; adjusted hazard ratio, 1.20; 95% confidence interval, 0.85-1.69, highest versus lowest quintile) nor with heart failure or stroke. The highest quintile of OBPV (versus lowest) was associated with all-cause mortality (adjusted hazard ratio, 1.92; confidence interval, 1.22-3.03) although the association of OBPV overall with all-cause mortality was marginal (
=0.07). Our results suggest that clinicians should continue to focus on office BP control rather than on OBPV unless definitive benefits of reducing OBPV are shown in prospective trials.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01206062.
Preclinical studies suggest that blueberry consumption is associated with improved bone health.
We conducted a blueberry dose-response study in ovariectomized (OVX)-rats that informed a study in ...postmenopausal women using the urinary appearance of calcium (Ca) tracers from prelabeled bone to reflect changes in bone balance. We hypothesized that blueberry consumption would reduce bone loss in a dose-dependent manner compared with no treatment.
OVX rats were fed 4 doses of blueberry powder (2.5%, 5%, 10%, and 15%) in randomized order to determine bone 45Ca retention. Fourteen healthy, nonosteoporotic women ≥4 y past menopause were dosed with 50 nCi of 41Ca, a long-lived radioisotope, and equilibrated for 5 mo to allow 41Ca deposition in bone. Following a 6-wk baseline period, participants were assigned to a random sequence of 3 6-wk interventions, a low (17.5 g/d), medium (35 g/d), or high (70 g/d) dose of freeze-dried blueberry powder equivalent to 0.75, 1.5, or 3 cups of fresh blueberries incorporated into food and beverage products. Urinary 41Ca:Ca ratio was measured by accelerator mass spectrometry. Serum bone resorption biomarkers and urinary polyphenols were measured at the end of each control and intervention period. Data were analyzed using a linear mixed model and repeated measures analysis of variance.
In both OVX rats and postmenopausal women, blueberry interventions benefited net bone calcium balance at lower but not at higher doses. In women, net bone calcium retention increased by 6% with the low (95% CI: 2.50, 8.60; P < 0.01) and 4% with the medium (95% CI: 0.96, 7.90; P < 0.05) dose compared with no treatment. Urinary excretion of hippuric acid increased dose-dependently with blueberry consumption. No significant relationships were found between bone resorption biomarkers, 25-hydroxyvitamin D, and interventions.
Moderate consumption (<1 cup/d) of blueberries may be an effective strategy to attenuate bone loss in healthy postmenopausal women.
This trial was registered at clinicaltrials.gov as NCT02630797.
A model for statewide dissemination of evidence-based treatment (EBT) for traumatized youth was piloted and taken to scale across North Carolina (NC). This article describes the implementation ...platform developed, piloted, and evaluated by the NC Child Treatment Program to train agency providers in Trauma-Focused Cognitive Behavioral Therapy using the National Center for Child Traumatic Stress Learning Collaborative (LC) Model on Adoption & Implementation of EBTs. This type of LC incorporates adult learning principles to enhance clinical skills development as part of training and many key implementation science strategies while working with agencies and clinicians to implement and sustain the new practice.
Clinicians (n = 124) from northeastern NC were enrolled in one of two TF-CBT LCs that lasted 12 months each. During the LC clinicians were expected to take at least two clients through TF-CBT treatment with fidelity and outcomes monitoring by trainers who offered consultation by phone and during trainings. Participating clinicians initiated treatment with 281 clients. The relationship of clinician and client characteristics to treatment fidelity and outcomes was examined using hierarchical linear regression.
One hundred eleven clinicians completed general training on trauma assessment batteries and TF-CBT. Sixty-five clinicians met all mastery and fidelity requirements to meet roster criteria. One hundred fifty-six (55%) clients had fidelity-monitored assessment and TF-CBT. Child externalizing, internalizing, and post-traumatic stress symptoms, as well as parent distress levels, decreased significantly with treatment fidelity moderating child PTSD outcomes. Since this pilot, 11 additional cohorts of TF-CBT providers have been trained to these roster criteria.
Scaling up or outcomes-oriented implementation appears best accomplished when training incorporates: 1) practice-based learning, 2) fidelity coaching, 3) clinical assessment and outcomes-oriented treatment, 4) organizational skill-building to address barriers for agencies, and 5) linking clients to trained clinicians via an online provider roster. Demonstrating clinician performance and client outcomes in this pilot and subsequent cohorts led to legislative support for dissemination of a service array of EBTs by the NC Child Treatment Program.
Ribonuclease H2 (RNase H2) is the major nuclear enzyme involved in the degradation of RNA/DNA hybrids and removal of ribonucleotides misincorporated in genomic DNA. Mutations in each of the three ...RNase H2 subunits have been implicated in a human auto-inflammatory disorder, Aicardi-Goutières Syndrome (AGS). To understand how mutations impact on RNase H2 function we determined the crystal structure of the human heterotrimer. In doing so, we correct several key regions of the previously reported murine RNase H2 atomic model and provide biochemical validation for our structural model. Our results provide new insights into how the subunits are arranged to form an enzymatically active complex. In particular, we establish that the RNASEH2A C terminus is a eukaryotic adaptation for binding the two accessory subunits, with residues within it required for enzymatic activity. This C-terminal extension interacts with the RNASEH2C C terminus and both are necessary to form a stable, enzymatically active heterotrimer. Disease mutations cluster at this interface between all three subunits, destabilizing the complex and/or impairing enzyme activity. Altogether, we locate 25 out of 29 residues mutated in AGS patients, establishing a firm basis for future investigations into disease pathogenesis and function of the RNase H2 enzyme.
Context:
Citrus fruits contain unique flavanones. One of the most abundant of the flavanones, hesperidin, has been shown to prevent bone loss in ovariectomized rats.
Objective:
The objective of the ...study was to measure the effect of hesperidin with or without calcium supplementation on bone calcium retention in postmenopausal women.
Design:
The study was a double-blind, placebo-controlled, randomized-order crossover design of 500 g hesperidin with or without 500 mg calcium supplement in 12 healthy postmenopausal women. Bone calcium retention was determined from urinary excretion of the rare isotope, 41Ca, from bone.
Results:
Calcium plus hesperidin, but not hesperidin alone, improved bone calcium retention by 5.5% (P < .04).
Conclusion:
Calcium supplementation (Calcilock), in combination with hesperidin, is effective at preserving bone in postmenopausal women.
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