Engaging in regular physical activity is one of the most important things people can do to improve their cardiovascular health; however, population levels of physical activity remain low in the ...United States. Effective population-based approaches implemented in communities can help increase physical activity among all Americans. Evidence suggests that built environment interventions offer one such approach. These interventions aim to create or modify community environmental characteristics to make physical activity easier or more accessible for all people in the places where they live. In 2016, the Community Preventive Services Task Force released a recommendation for built environment approaches to increase physical activity. This recommendation is based on a systematic review of 90 studies (search period, 1980-June 2014) conducted using methods outlined by the Guide to Community Preventive Services. The Community Preventive Services Task Force found sufficient evidence of effectiveness to recommend combined built environment strategies. Specifically, these strategies combine interventions to improve pedestrian or bicycle transportation systems with interventions to improve land use and environmental design. Components of transportation systems can include street pattern design and connectivity, pedestrian infrastructure, bicycle infrastructure, and public transit infrastructure and access. Components of land use and environmental design can include mixed land use, increased residential density, proximity to community or neighborhood destinations, and parks and recreational facility access. Implementing this Community Preventive Services Task Force recommendation in communities across the United States can help promote healthy and active living, increase physical activity, and ultimately improve cardiovascular health.
Aorto-atrial fistula is a rare and life-threatening complication of infective endocarditis, classically diagnosed by visualizing a connection between the aorta and atrium with associated continuous ...flow. A patient presented with bioprosthetic and native valve enterococcal endocarditis with multiple complications, including an aorto-atrial fistula that was diagnosed by color M-mode on transesophageal echocardiography. We review the features of aorto-atrial fistula and utilize this case to demonstrate how M-mode can be leveraged to provide improved temporal resolution in the setting of diagnostic uncertainty.
Patients with Eisenmenger syndrome do much better than patients with all other etiologies of severe pulmonary hypertension. The primary reason, and a major focus of this review, is the right ...ventricle, a remarkable chamber with preserved systolic function despite a lifetime of systemic level pulmonary hypertension.
Small-molecule probes can illuminate biological processes and aid in the assessment of emerging therapeutic targets by perturbing biological systems in a manner distinct from other experimental ...approaches. Despite the tremendous promise of chemical tools for investigating biology and disease, small-molecule probes were unavailable for most targets and pathways as recently as a decade ago. In 2005, the NIH launched the decade-long Molecular Libraries Program with the intent of innovating in and broadening access to small-molecule science. This Perspective describes how novel small-molecule probes identified through the program are enabling the exploration of biological pathways and therapeutic hypotheses not otherwise testable. These experiences illustrate how small-molecule probes can help bridge the chasm between biological research and the development of medicines but also highlight the need to innovate the science of therapeutic discovery.
The Molecular Libraries Project began in 2005 to develop small-molecule tools to promote biological and biomedical discoveries. This Perspective highlights the last decade’s advances and looks at opportunities ahead for informed innovation in small-molecule drug discovery.
The authors of prior small studies raised the hypothesis that symptoms in veterans of the 1991 Gulf War, such as chronic diarrhea, dizziness, fatigue, and sexual dysfunction, are due to cholinergic ...autonomic dysfunction.
To perform a confirmatory test of this prestated hypothesis in a larger, representative sample of Gulf War veterans.
Nested case-control study.
Clinical and Translational Research Center, University of Texas Southwestern Medical Center, Dallas.
Representative samples of Gulf War veterans meeting a validated case definition of Gulf War illness with 3 variants (called syndromes 1-3) and a control group, all selected randomly from the US Military Health Survey.
Validated domain scales from the Autonomic Symptom Profile questionnaire, the Composite Autonomic Severity Score, and high-frequency heart rate variability from a 24-hour electrocardiogram.
The Autonomic Symptom Profile scales were significantly elevated in all 3 syndrome groups (P< .001), primarily due to elevation of the orthostatic intolerance, secretomotor, upper gastrointestinal dysmotility, sleep dysfunction, urinary, and autonomic diarrhea symptom domains. The Composite Autonomic Severity Score was also higher in the 3 syndrome groups (P= .045), especially in syndrome 2, primarily due to a significant reduction in sudomotor function as measured by the Quantitative Sudomotor Axon Reflex Test, most significantly in the foot; the score was intermediate in the ankle and upper leg and was nonsignificant in the arm, indicating a peripheral nerve length-related deficit. The normal increase in high-frequency heart rate variability at night was absent or blunted in all 3 syndrome groups (P< .001).
Autonomic symptoms are associated with objective, predominantly cholinergic autonomic deficits in the population of Gulf War veterans.
Outbreaks of human salmonella infections are increasingly associated with contact with live poultry, but effective control measures are elusive. In 2005, a cluster of human salmonella Montevideo ...infections with a rare pattern on pulsed-field gel electrophoresis (the outbreak strain) was identified by PulseNet, a national subtyping network.
In cooperation with public health and animal health agencies, we conducted multistate investigations involving patient interviews, trace-back investigations, and environmental testing at a mail-order hatchery linked to the outbreak in order to identify the source of infections and prevent additional illnesses. A case was defined as an infection with the outbreak strain between 2004 and 2011.
From 2004 through 2011, we identified 316 cases in 43 states. The median age of the patient was 4 years. Interviews were completed with 156 patients (or their caretakers) (49%), and 36 of these patients (23%) were hospitalized. Among the 145 patients for whom information was available, 80 (55%) had bloody diarrhea. Information on contact with live young poultry was available for 159 patients, and 122 of these patients (77%) reported having such contact. A mail-order hatchery in the western United States was identified in 81% of the trace-back investigations, and the outbreak strain was isolated from samples collected at the hatchery. After interventions at the hatchery, the number of human infections declined, but transmission continued.
We identified a prolonged multistate outbreak of salmonellosis, predominantly affecting young children and associated with contact with live young poultry from a mail-order hatchery. Interventions performed at the hatchery reduced, but did not eliminate, associated human infections, demonstrating the difficulty of eliminating salmonella transmission from live poultry.
Why adults with the Eisenmenger syndrome fare so much better than other patients with severe pulmonary hypertension is not known, but may be related to unique hemodynamics found only in these ...patients and in normal fetuses. We used echocardiography to evaluate ventricular morphology and function in 80 subjects: 45 cyanotic adults and 5 cyanotic adolescents with Eisenmenger syndrome, 10 infants with nonrestrictive ventricular septal defect and left-to-right shunt flow (pre-Eisenmenger phase), and 20 fetuses with structurally normal hearts. Cross-sectional morphology of the hearts was the same in all 4 groups with a flat ventricular septum throughout the cardiac cycle and equal thickness of the right and left ventricular free walls (regression slope 0.98, r = 0.97, p <0.0001). This morphology was the same in patients independent of age, defect type, and ventricular function. Right ventricular fractional area change was slightly inferior to that of the left ventricle but normal in most patients with Eisenmenger syndrome (0.47 ± 0.14 vs 0.51 ± 0.13, p <0.01). Overall, there was a highly significant linear relation between right and left ventricular function (r = 0.81, p <0.0001). The hearts of patients with Eisenmenger syndrome are more like normal fetal hearts than normal adult hearts. Because of the unique cardiovascular hemodynamics, regression of right ventricular wall thickness does not occur and is likely the reason that patients with Eisenmenger syndrome fare so much better than other adults with severe pulmonary hypertension.
Brain natriuretic peptide (BNP) levels are used in the evaluation of patients with heart disease, yet there is little understanding of the effect of hypoxia on natriuretic peptide secretion. ...Furthermore, recent data suggest that oxytocin may mediate stretch-induced atrial natriuretic peptide (ANP) secretion.
Ten patients with cyanotic congenital heart defects and 10 control subjects were studied. N-terminal proatrial natriuretic peptide and N-terminal probrain natriuretic peptide levels were 4-fold (P=0.02) and 12-fold (P=0.03) greater in cyanotic patients than in control subjects. Cyanotic patients had reduced body water compared with control subjects, although the difference did not reach statistical significance (P=0.22). In a separate group of patients, cardiac myocytes were isolated from the right atrial appendage during CABG. The amount of oxygen in the buffered saline was varied to simulate hypoxia. Isolated hypoxic atrial myocytes had 43% fewer dense surface secretory granules compared with normoxic myocytes (P<0.0001). Immunohistochemical staining demonstrated decreased ANP and BNP in hypoxic compared with normoxic right atrial tissue. Isolated myocytes also degranulated when incubated with oxytocin (P<0.0001), but there was no difference in oxytocin levels in cyanotic patients compared with control subjects (P=0.49).
ANP and BNP are markedly elevated in adults with cyanotic congenital heart disease despite reduced body water. Our results show that hypoxia is a direct stimulus for ANP and BNP secretion in human cardiac myocytes. These findings may have implications for the interpretation of BNP levels in the assessment of patients with heart and lung disease.
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