Coronary artery dilation associated with bicuspid and unicuspid aortic valve disease in children: a series of 17 patients.

INTRODUCTION: Coronary artery dilation associated with bicuspid/unicuspid aortic valves is described in adults with limited data in children. We aimed to describe the clinical course of children with bicuspid/unicuspid aortic valves and coronary dilation including coronary Z-score changes over time, association of coronary changes with aortic valve anatomy/function, and complications. MATERIALS AND METHODS: Institutional databases were searched for children ≤18 years with both bicuspid/unicuspid aortic valves and coronary dilation (1/2006-6/2021). Kawasaki disease and isolated supra-/subvalvar aortic stenosis were excluded. Statistics were descriptive with associations measured by Fisher's exact test and overlapping 83.7% confidence intervals. RESULTS: Of 17 children, bicuspid/unicuspid aortic valve was diagnosed at birth in 14 (82%). Median age at coronary dilation diagnosis was 6.4 years (range: 0-17.0). Aortic stenosis was present in 14 (82%) [2 (14%) moderate, 8 (57%) severe]; 10 (59%) had aortic regurgitation; 8 (47%) had aortic dilation. The right coronary was dilated in 15 (88%), left main in 6 (35%), and left anterior descending in 1 (6%) with no relationship between leaflet fusion pattern or severity of aortic regurgitation/stenosis on coronary Z-score. Follow-up evaluations were available for 11 (mean 9.3 years, range 1.1-14.8) with coronary Z-scores increasing in 9/11 (82%). Aspirin was used in 10 (59%). There were no deaths or coronary artery thrombosis. DISCUSSION: In children with bicuspid/unicuspid aortic valves and coronary dilation, the right coronary artery was most frequently involved. Coronary dilation was observed in early childhood and frequently progressed. Antiplatelet medication use was inconsistent, but no child died nor developed thrombosis.

Implications of Changing Z-Score Models for Coronary Artery Dimensions in Kawasaki Disease.

BACKGROUND: Coronary artery abnormalities in Kawasaki disease (KD) are assessed using echocardiographic z-scores. We hypothesized that changing the coronary artery (CA) z-score model would alter diagnosis and management of children with KD. METHODS: In this retrospective single-center study of children treated for KD (9/2007-1/2020), we collected echocardiographic measurements for the left anterior descending (LAD), right (RCA), and left main (LMCA) coronary arteries during 3 illness phases and calculated Boston and Pediatric Heart Network (PHN) z-scores. Agreement between Boston and PHN z-scores was assessed using Kappa (κ) and Lin's Concordance Correlation Coefficients (CCC) and Bland-Altman analysis. RESULTS: For 904 echocardiograms from 357 children, the median Boston LAD z-score was lower than the PHN (0.3 [IQR - 0.6, 1.5] vs 1.6 [IQR 0.7, 2.8], CCC 0.94 [95% CI 0.93, 0.95], moderate agreement), aggregated across all illness phases. RCA and LMCA z-scores showed substantial agreement. With conversion from Boston to PHN models, the percentage of individual LAD z-scores ≥ 2.5 increased (14.6% to 32.1%). At least one CA z-score classification changed in 213 children (59.7%) across all phases, and 48 children (13.4%) had a change that altered recommended antithrombotic strategy. Agreement between models differed by age, sex, and race. CONCLUSIONS: Conversion from Boston to PHN z-scores changed at least 1 CA z-score classification in over half of KD patients and changed recommended antithrombotic management in 13%, largely driven by LAD measurements. Since diagnosis and management of KD and KD-like diseases rely upon CA z-scores, the clinical and research implications of these findings merit further exploration.

Newborn Screening Pulse Oximetry to Detect Critical Congenital Heart Disease: A Follow-Up Survey of Current Practice at Army, Navy and Air Force Hospitals.

INTRODUCTION: The purpose of this study was to assess the evolution of newborn pulse oximetry screening (+POx) among Army, Air Force, and Naval military hospitals (MH), including prevalence, protocol use, quality assurance processes, access to echocardiography, and use of telemedicine. This is a follow-up from a prior study published in 2011. MATERIALS AND METHODS: An Internet-based questionnaire was forwarded to the chief pediatrician at MH worldwide which support newborn deliveries. Descriptive data were reported using percentages. Grouped responses, as applicable, were further compared using the chi-square test. A p-value < 0.05 was considered statistically significant. RESULTS: Seventy-eight percent (36/46) of MH supporting deliveries worldwide responded to the survey (17 Army hospitals, 11 Navy Hospitals, 8 Air Force hospitals). All responding hospitals utilize +POx, of which 94% endorsed protocol compliance with the American Academy of Pediatrics guidelines. Nine (25%) hospitals were located outside of the United States. Delivery volumes (infants per month) range between 1-49 (36%), 50-99 (28%), 100-199 (19%), and 200-300 (17%). Eleven hospitals reported regular review of +POx data, with most reviewing them monthly. Four MH share findings with state institutions. Ten hospitals either have a staff pediatric cardiologist or use tele-echocardiography for on-site evaluations. Ten hospitals are located greater than 60 miles from the nearest center with echocardiography capabilities. Of the five hospitals using tele-echocardiography, four confirmed critical congenital heart disease (CCHD) using this practice, and all five reported averting transfer of an infant using this technology. Of the 22 hospitals lacking the ability to obtain on-site echocardiography, 12 (55%) are interested in implementing a tele-echocardiography protocol. CONCLUSIONS: All responding MH use +POx, representing significant increase from the 30% of MH reporting use of +POx seven years ago. The majority of MH follow AAP +POx guidelines, and though most have providers review results prior to discharge, only one-third report periodic chart review for quality assurance. Most MH transfer infants with positive +POx results for evaluation due to a lack of on-site echocardiography. Tele-echocardiography was reported as a potential solution to diagnose or rule out CCHD. Over half of remaining hospitals without cardiologists are interested in using this technology to evaluate stable infants with positive CCHD screening.

Antiproliferative Effects of a Triterpene-Enriched Extract from Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes), on Human Lung Cancer Cells.

Ganoderma lucidum, a mushroom that has been used to treat disease in East Asia for centuries, has been shown to be effective against many types of tumors, but the exact cellular mechanism of action is unknown. In this study we examined proliferation of a lung cancer cell line after treatment with 12 concentrations of powdered G. lucidum for 24, 48, and 120 hours. Based on half-maximal inhibitory concentrations values, proliferation of the H1793 cell line seemed to be sensitive to the extract in a time- and dose-dependent manner. We used immunoblot analysis to examine the amounts of cell cycle proteins (cyclin D, Cdk4, and Cdc2) and apoptotic proteins (Bcl-xL and Bax) after treatment with a range of G. lucidum concentrations. Changes in amounts of proteins that regulate the cell cycle were consistent with longer G1 and G2 phases. Proapoptotic protein (Bax) levels increased 6.5-fold, with a commensurate increase in the Bax-to-Bcl ratio, especially at 48 and 120 hours. These results suggest that the decrease in cellular proliferation correlated with a change in both cell cycle progression and apoptosis, and that the triterpenoid in G. lucidum is the bioactive component. Further biochemical characterization of this ancient herbal remedy could hold promise for treating lung cancer.

Effectiveness of a cloning and sequencing exercise on student learning with subsequent publication in the National Center for Biotechnology Information GenBank.

With rapid advances in biotechnology and molecular biology, instructors are challenged to not only provide undergraduate students with hands-on experiences in these disciplines but also to engage them in the "real-world" scientific process. Two common topics covered in biotechnology or molecular biology courses are gene-cloning and bioinformatics, but to provide students with a continuous laboratory-based research experience in these techniques is difficult. To meet these challenges, we have partnered with Bio-Rad Laboratories in the development of the "Cloning and Sequencing Explorer Series," which combines wet-lab experiences (e.g., DNA extraction, polymerase chain reaction, ligation, transformation, and restriction digestion) with bioinformatics analysis (e.g., evaluation of DNA sequence quality, sequence editing, Basic Local Alignment Search Tool searches, contig construction, intron identification, and six-frame translation) to produce a sequence publishable in the National Center for Biotechnology Information GenBank. This 6- to 8-wk project-based exercise focuses on a pivotal gene of glycolysis (glyceraldehyde-3-phosphate dehydrogenase), in which students isolate, sequence, and characterize the gene from a plant species or cultivar not yet published in GenBank. Student achievement was evaluated using pre-, mid-, and final-test assessments, as well as with a survey to assess student perceptions. Student confidence with basic laboratory techniques and knowledge of bioinformatics tools were significantly increased upon completion of this hands-on exercise.

In pursuit of knowledge.

This article is based on the proposition that to understand the nature of knowledge, and how best to acquire it, one must look first at how the brain abstracts knowledge from the information provided by sensory receptors. The nature of this biological process of knowledge acquisition is suggested by the necessary conditions for the occurrence of learning, and from consideration of these necessary conditions in terms of what is currently known about the properties and limitations of neural systems. This entails discussion of an important distinction that must be made between "perceptual" and "associative" learning and between the neural systems required to mediate these two kinds of learning. There is also discussion of the manner in which language can overcome the limitations of neurological systems to greatly extend the scope of associative learning. This leads on to discussion of the role of active efferent language systems and temporary memory in the mediation of thinking. Consideration of the main features of the biological process of knowledge acquisition confirms, and extends to perception, Hume's famous conclusion that knowledge derives from the similarity or temporal contiguity of recurring events. New insights are also obtained concerning the biological causes of bias in the knowledge acquisition process, concerning the intellectual process of theory generation, and concerning the role of theory in the conduct of empirical research. Finally, and most importantly, it can be concluded that all knowledge is theory and hence that the ultimate goal of science is the development of better theories.