Fetal diagnosis and management of pulmonary artery sling: A case series.

OBJECTIVE: Pulmonary artery sling is a rare congenital anomaly accounting for 2% of all patients with vascular anomalies that cause airway obstruction. In the normal heart, the left (LPA) and right (RPA) pulmonary arteries arise in the intrapericardial space. However, in the pulmonary artery sling, the LPA trunk arises in the extrapericardial space from the posterior aspect of the mid RPA and courses posterior to the trachea causing tracheal compression and, at times, bronchial compression. While a full spectrum of congenital cardiac pathology can be identified before birth, only a few case reports document the prenatal diagnosis of an Left pulmonary artery sling (LPAS). METHOD: We retrospectively identified all cases of prenatal LPAS from three Canadian fetal cardiology centers (2015-2022). RESULTS: Using the 3-vessel-tracheal view via fetal echocardiography (FE), four fetuses from three pregnancies demonstrated abnormal origin of the LPA from RPA and echogenic trachea. In one of two affected monochorionic twins coronal imaging demonstrated a significant narrowing of the large airways consistent with significant airway obstruction. CONCLUSION: Prenatal detection of LPAS by FE is possible and should prompt an evaluation for airway obstruction in the coronal view. Investigating associated lesions and genetic testing are recommended for informed shared decision making.

A cardiovascular disease risk factor in children with congenital heart disease: unmasking elevated waist circumference - a CHAMPS* study *CHAMPS: Children's Healthy-Heart Activity Monitoring Program in Saskatchewan.

BACKGROUND: Children with congenital heart disease (CHD) have an elevated risk of future cardiovascular disease but the underlying mechanisms are unclear. Abdominal obesity (measured as waist circumference) is a risk factor for adult onset of cardiovascular diseases and is correlated with low physical activity levels, commonly found in children with congenital heart disease. Elevated waist circumference may be a mechanism by which cardiovascular disease risk is elevated in children with CHD. The purpose of this study was to compare waist circumference between children with and without CHD, while considering potential confounders. We hypothesized that children with CHD would have higher measures of waist circumference when controlling for differences in birthweight, lean mass, and physical activity. METHODS: Thirty-two children with CHD (10.9 ± 2.6 years; 12 female) from the Children's Healthy-Heart Activity Monitoring Program in Saskatchewan, and 23 healthy controls (11.7 ± 2.5 years; 10 female) were studied. Waist circumference, physical activity (physical activity questionnaire), body composition (lean mass; dual x-ray absorptiometry), and birthweight were assessed. Analysis of covariance, Mann-Whitney U, and independent sample t-tests were used to assess group differences (p < 0.05). RESULTS: Children with CHD had greater waist circumference than controls, controlling for lean mass, physical activity, birthweight, and sex (F (1, 49) = 4.488, p = 0.039). Physical activity, lean mass, and birthweight were not significantly different between groups (p > 0.05). CONCLUSION: Our findings generate a novel hypothesis-higher waist circumferences in children with CHD compared to age-matched controls, may contribute to an elevated risk of cardiovascular disease.

Health-Related Quality of Life in Children and Young Adults with Marfan Syndrome.

OBJECTIVE: To assess health-related quality of life (HRQOL) in a large multicenter cohort of children and young adults with Marfan syndrome participating in the Pediatric Heart Network Marfan Trial. STUDY DESIGN: The Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales were administered to 321 subjects with Marfan syndrome (5-25 years). PedsQL scores were compared with healthy population norms. The impact of treatment arm (atenolol vs losartan), severity of clinical features, and number of patient-reported symptoms on HRQOL was assessed by general linear models. RESULTS: Mean PedsQL scores in children (5-18 years) with Marfan syndrome were lower than healthy population norms for physical (P ≤ .003) and psychosocial (P < .001) domains; mean psychosocial scores for adults (19-25 years) were greater than healthy norms (P < .001). HRQOL across multiple domains correlated inversely with frequency of patient-reported symptoms (r = 0.30-0.38, P < .0001). Those <18 years of age with neurodevelopmental disorders (mainly learning disability, attention-deficit/hyperactivity disorder) had lower mean PedsQL scores (5.5-7.4 lower, P < .04). A multivariable model found age, sex, patient-reported symptoms, and neurodevelopmental disorder to be independent predictors of HRQOL. There were no differences in HRQOL scores by treatment arm, aortic root z score, number of skeletal features, or presence of ectopia lentis. CONCLUSIONS: Children and adolescents with Marfan syndrome were at high risk for impaired HRQOL. Patient-reported symptoms and neurodevelopmental disorder, but not treatment arm or severity of Marfan syndrome-related physical findings, were associated with lower HRQOL.

Cardiovascular Magnetic Resonance Provides Evidence of Abnormal Myocardial Strain and Primary Cardiomyopathy in Marfan syndrome.

OBJECTIVE: Marfan syndrome is an autosomal-dominant genetic disorder caused by mutations in the fibrillin-1 gene. The condition is a connective tissue disease that frequently involves the cardiovascular system. The existence of a primary cardiomyopathy in Marfan syndrome, however, is controversial. The aims of this study were to investigate the prevalence of left ventricular dysfunction with both transthoracic echocardiography and cardiovascular magnetic resonance (CMR) in a cohort of Marfan syndrome patients and to investigate patterns of myocardial strain across the cohort. METHODS: We used an institutional database to identify all patients with a firm diagnosis of Marfan syndrome based on Ghent criteria. Inclusion required left ventricular ejection fraction (LVEF) to have been measured by both CMR and transthoracic echocardiography within 12 months of each other. Normal LVEF was defined as a value of >55% when measured by CMR. Velocity vector imaging was used to measure left ventricular longitudinal strain patterns by application of feature tracking to cine magnetic resonance images. Results were compared with data from 20 age-matched control subjects. RESULTS: Sixty-nine Marfan syndrome patients met the inclusion criteria. The mean age was 35.4 ± 15.0 years, and 56.5% were male. The mean LVEF was 59.0% ± 7.0% by CMR and 59.1% ± 5.8% by echo. One-fifth of Marfan syndrome patients (15/69; 21.7%) had reduced function with LVEF ≤55% by CMR, but only 5 of these were identified by echo. Furthermore, echo identified 5 Marfan syndrome patients as having reduced LVEF in the presence of a normal LVEF by CMR. Some Marfan syndrome patients had abnormal longitudinal strain patterns even with LVEF within the reference range. CONCLUSIONS: These data provide support for a primary cardiomyopathy in some Marfan syndrome patients. Cardiovascular magnetic resonance is more sensitive than echo for identifying cases with mild systolic dysfunction. Strain analysis may be more sensitive than simple LVEF assessment for identifying at-risk individuals.

Increased Arterial Stiffness Adversely Affects Left Ventricular Mechanics in Patients With Pediatric Takayasu Arteritis From a Toronto Cohort.

BACKGROUND/OBJECTIVE: Takayasu arteritis (TA) is characterized by extensive aortic, large and midsize arterial wall inflammation. The aim of this study was to assess the morphological and elastic properties of the aorta and large arteries and the impact on left ventricular (LV) mechanics in children with TA. METHODS: Seven pediatric TA patients (6 female patients, 13.8 ± 3.2 years) were assessed with magnetic resonance imaging, vascular ultrasound, applanation tonometry, and echocardiography from February 2015 until July 2017 and compared with 7 age- and sex-matched controls. Takayasu arteritis disease activity was assessed clinically by the Pediatric Vasculitis Activity Score (PVAS). RESULTS: Pediatric TA patients showed increased carotid-to-radial artery pulse wave velocity (8.1 ± 1.8 vs. 6.4 ± 0.6 m/s, p = 0.03) and increased carotid-to-femoral artery pulse wave velocity (8.3 ± 1.9 vs. 5.1 ± 0.8 m/s, p < 0.01) when compared with controls. Patients demonstrated increased LV mass index (74.3 ± 18.8 vs. 56.3 ± 10.9 g/m, p = 0.04), altered myocardial deformation with increased basal rotation (-9.8 ± 4.5 vs. -4.0 ± 2.0 degrees, p = 0.01) and torsion (19.9 ± 8.1 vs. 9.1 ± 3.1 degrees, p = 0.01), and impaired LV diastolic function with decreased mitral valve E/A ratio (1.45 ± 0.17 vs. 2.40 ± 0.84, p = 0.01), increased mitral valve E/E' ratio (6.8 ± 1.4 vs. 4.9 ± 0.7, p < 0.01), and increased pulmonary vein A-wave velocity (26.7 ± 5.7 vs. 16.8 ± 3.3 cm/s, p = 0.03). Carotid-to-radial artery pulse wave velocity was associated with systolic (R = 0.94, p < 0.01), diastolic (R = 0.85, p = 0.02), and mean blood pressure (R = 0.91, p < 0.01), as well as disease activity by PVAS (R = 0.75, p = 0.05). The PVAS was associated with carotid-to-radial artery pulse wave velocity (R = 0.75, p = 0.05), as well as systolic (R = 0.84, p = 0.02), diastolic (R = 0.82, p = 0.03), and mean blood pressure (R = 0.84, p = 0.02). CONCLUSIONS: Increased arterial stiffness is present in pediatric TA patients and associated with increased blood pressure and TA disease activity. Pediatric TA patients demonstrate altered LV mechanics, LV hypertrophy, and impaired diastolic function.

Clinical history and management recommendations of the smooth muscle dysfunction syndrome due to ACTA2 arginine 179 alterations.

PURPOSE: Smooth muscle dysfunction syndrome (SMDS) due to heterozygous ACTA2 arginine 179 alterations is characterized by patent ductus arteriosus, vasculopathy (aneurysm and occlusive lesions), pulmonary arterial hypertension, and other complications in smooth muscle-dependent organs. We sought to define the clinical history of SMDS to develop recommendations for evaluation and management. METHODS: Medical records of 33 patients with SMDS (median age 12 years) were abstracted and analyzed. RESULTS: All patients had congenital mydriasis and related pupillary abnormalities at birth and presented in infancy with a patent ductus arteriosus or aortopulmonary window. Patients had cerebrovascular disease characterized by small vessel disease (hyperintense periventricular white matter lesions; 95%), intracranial artery stenosis (77%), ischemic strokes (27%), and seizures (18%). Twelve (36%) patients had thoracic aortic aneurysm repair or dissection at median age of 14 years and aortic disease was fully penetrant by the age of 25 years. Three (9%) patients had axillary artery aneurysms complicated by thromboembolic episodes. Nine patients died between the ages of 0.5 and 32 years due to aortic, pulmonary, or stroke complications, or unknown causes. CONCLUSION: Based on these data, recommendations are provided for the surveillance and management of SMDS to help prevent early-onset life-threatening complications.

Predictors of Rapid Aortic Root Dilation and Referral for Aortic Surgery in Marfan Syndrome.

Few data exist regarding predictors of rapid aortic root dilation and referral for aortic surgery in Marfan syndrome (MFS). To identify independent predictors of the rate of aortic root (AoR) dilation and referral for aortic surgery, we investigated the data from the Pediatric Heart Network randomized trial of atenolol versus losartan in young patients with MFS. Data were analyzed from the echocardiograms at 0, 12, 24, and 36 months read in the core laboratory of 608 trial subjects, aged 6 months to 25 years, who met original Ghent criteria and had an AoR z-score (AoRz) > 3. Repeated measures linear and logistic regressions were used to determine multivariable predictors of AoR dilation. Receiver operator characteristic curves were used to determine cut-points in AoR dilation predicting referral for aortic surgery. Multivariable analysis showed rapid AoR dilation as defined by change in AoRz/year > 90th percentile was associated with older age, higher sinotubular junction z-score, and atenolol use (R2 = 0.01) or by change in AoR diameter (AoRd)/year > 90th percentile with higher sinotubular junction z-score and non-white race (R2 = 0.02). Referral for aortic root surgery was associated with higher AoRd, higher ascending aorta z-score, and higher sinotubular junction diameter:ascending aorta diameter ratio (R2 = 0.17). Change in AoRz of 0.72 SD units/year had 42% sensitivity and 92% specificity and change in AoRd of 0.34 cm/year had 38% sensitivity and 95% specificity for predicting referral for aortic surgery. In this cohort of young patients with MFS, no new robust predictors of rapid AoR dilation or referral for aortic root surgery were identified. Further investigation may determine whether generalized proximal aortic dilation and effacement of the sinotubular junction will allow for better risk stratification. Rate of AoR dilation cut-points had high specificity, but low sensitivity for predicting referral for aortic surgery, limiting their clinical use. Clinical Trial Number ClinicalTrials.gov number, NCT00429364.

The relationship between urinary renin-angiotensin system markers, renal function, and blood pressure in adolescents with type 1 diabetes.

The relationship between the renal renin-angiotensin aldosterone system (RAAS) and cardiorenal pathophysiology is unclear. Our aims were to assess 1) levels of urinary RAAS components and 2) the association between RAAS components and HbA1c, the urine albumin/creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), and blood pressure (BP) in otherwise healthy adolescents with type 1 diabetes mellitus (TID) vs. healthy controls (HC). Urinary angiotensinogen and angtionsin-converting enzyme (ACE) 2 levels, activity of ACE and ACE2, BP, HbA1c, ACR, and eGFR were measured in 65 HC and 194 T1D from the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT). Urinary levels of all RAAS components were higher in T1D vs. HC (P < 0.0001). Higher HbA1c was associated with higher urinary angiotensinogen, ACE2, and higher activity of ACE and ACE2 (P < 0.0001, P = 0.0003, P = 0.003, and P = 0.007 respectively) in T1D. Higher ACR (within the normal range) was associated with higher urinary angiotensinogen (P < 0.0001) and ACE activity (P = 0.007), but not with urinary ACE2 activity or ACE2 levels. These observations were absent in HC. Urinary RAAS components were not associated with BP or eGFR in T1D or HC. Otherwise healthy adolescents with T1D exhibit higher levels of urinary RAAS components compared with HC. While levels of all urinary RAAS components correlate with HbA1c in T1D, only urinary angiotensinogen and ACE activity correlate with ACR, suggesting that these factors reflect an intermediary pathogenic link between hyperglycemia and albuminuria within the normal range.

Atenolol versus losartan in children and young adults with Marfan's syndrome.

BACKGROUND: Aortic-root dissection is the leading cause of death in Marfan's syndrome. Studies suggest that with regard to slowing aortic-root enlargement, losartan may be more effective than beta-blockers, the current standard therapy in most centers. METHODS: We conducted a randomized trial comparing losartan with atenolol in children and young adults with Marfan's syndrome. The primary outcome was the rate of aortic-root enlargement, expressed as the change in the maximum aortic-root-diameter z score indexed to body-surface area (hereafter, aortic-root z score) over a 3-year period. Secondary outcomes included the rate of change in the absolute diameter of the aortic root; the rate of change in aortic regurgitation; the time to aortic dissection, aortic-root surgery, or death; somatic growth; and the incidence of adverse events. RESULTS: From January 2007 through February 2011, a total of 21 clinical centers enrolled 608 participants, 6 months to 25 years of age (mean [±SD] age, 11.5±6.5 years in the atenolol group and 11.0±6.2 years in the losartan group), who had an aortic-root z score greater than 3.0. The baseline-adjusted rate of change in the mean (±SE) aortic-root z score did not differ significantly between the atenolol group and the losartan group (-0.139±0.013 and -0.107±0.013 standard-deviation units per year, respectively; P=0.08). Both slopes were significantly less than zero, indicating a decrease in the aortic-root diameter relative to body-surface area with either treatment. The 3-year rates of aortic-root surgery, aortic dissection, death, and a composite of these events did not differ significantly between the two treatment groups. CONCLUSIONS: Among children and young adults with Marfan's syndrome who were randomly assigned to losartan or atenolol, we found no significant difference in the rate of aortic-root dilatation between the two treatment groups over a 3-year period. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT00429364.).

Aerobic function in mitochondria persists beyond death by heat stress in insects.

The critical thermal maximum (CTmax) of insects can be determined using flow-through thermolimit respirometry. It has been demonstrated that respiratory patterns cease and insects do not recover once the CTmax temperature has been reached. However, if high temperatures are maintained following the CTmax, researchers have observed a curious phenomenon whereby the insect body releases a large burst of carbon dioxide at a rate and magnitude that often exceed that of the live insect. This carbon dioxide release has been termed the post-mortal peak (PMP). We demonstrate here that the PMP is observed only at high temperatures, is oxygen-dependent, is prevented by cyanide exposure, and is associated with concomitant consumption of oxygen. We conclude that the PMP derives from highly active, aerobic metabolism in the mitochondria. The insect tracheal system contains air-filled tubes that reach deep into the tissues and allow mitochondria access to oxygen even upon organismal death. This unique condition permits the investigation of mitochondrial function during thermal failure in a manner that cannot be achieved using vertebrate organisms or in vitro preparations.

Early changes in cardiovascular structure and function in adolescents with type 1 diabetes.

BACKGROUND: Children with type 1 diabetes (T1D) are at higher risk of early adult-onset cardiovascular disease. We assessed cardiovascular structure and function in adolescents with T1D compared with healthy controls and the relationships between peripheral vascular function and myocardial parameters. METHODS AND RESULTS: 199 T1D [14.4 ± 1.6 years, diabetes duration 6.2 (2.0-12.8) years] and 178 controls (14.4 ± 2.1 years) completed endothelial function by flow mediated vasodilatation (FMD), arterial stiffness using pulse wave velocity (PWV) along with M-mode, pulse wave and tissue Doppler, and myocardial deformation echocardiographic imaging. Systolic (113 ± 10 vs. 110 ± 9 mmHg; p = 0.0005) and diastolic (62 ± 7 vs. 58 ± 7 mmHg; p < 0.0001) blood pressures, carotid femoral PWV and endothelial dysfunction measurements were increased in T1D compared with controls. Systolic and diastolic left ventricular dimensions and function by M-mode and pulse wave Doppler assessment were not significantly different. Mitral valve lateral e' (17.6 ± 2.6 vs. 18.6 ± 2.6 cm/s; p < 0.001) and a' (5.4 ± 1.1 vs. 5.9 ± 1.1 cm/s; p < 0.001) myocardial velocities were decreased and E/e' (7.3 ± 1.2 vs. 6.7 ± 1.3; p = 0.0003) increased in T1D. Left ventricular mid circumferential strain (-20.4 ± 2.3 vs. -19.5 ± 1.7 %; p < 0.001) was higher, whereas global longitudinal strain was lower (-19.0 ± 1.9 vs. -19.8 ± 1.5 % p < 0.001) in T1D. CONCLUSIONS: Adolescents with T1D exhibit early changes in blood pressure, peripheral vascular function and left ventricular myocardial deformation indices with a shift from longitudinal to circumferential shortening. Longitudinal follow-up of these changes in ongoing prospective trials may allow detection of those most at risk for cardiovascular abnormalities including hypertension that could preferentially benefit from early therapeutic interventions.

Exploring Health-Related Quality of Life in Children With Hypertrophic Cardiomyopathy and Relationship to Physical Activity.

BACKGROUND: Hypertrophic cardiomyopathy is a burdensome condition that inflicts both physical and psychological impairment on those with the disease, negatively impacting health-related quality of life (HRQoL). Given the abundance of evidence suggesting a role of physical activity (PA) in modulating HRQoL in healthy populations of children, we sought to determine the relationship between HRQoL and PA in children diagnosed with hypertrophic cardiomyopathy. METHODS AND RESULTS: A multicenter prospective observational cohort study was conducted, with patients with hypertrophic cardiomyopathy aged 10 to 19 years being provided a wrist-worn activity tracker (Fitbit Charge HR) to wear for 14 days. Patients self-reported on Pediatric Quality of Life 4.0 quality of life inventory items, which were associated with PA metrics following covariate adjustment using linear regression. A total of 56 participants were recruited to the study. The median age at enrollment was 15.5 years (interquartile range, 13.8-16.8), and 16 out of 56 (29%) of the cohort were girls. The cohort reported decreased metrics of physical, psychosocial, and total summary scores compared with health reference populations, with scores comparable with that of published populations with chronic disease. Increased physical HRQoL scores were significantly associated with increased daily steps taken, distance traveled, and flights of stairs climbed. CONCLUSIONS: These results show that impaired PA correlates with reduced HRQoL in children with hypertrophic cardiomyopathy, suggesting PA may partially mediate HRQoL in this population.

Characteristics of children and young adults with Marfan syndrome and aortic root dilation in a randomized trial comparing atenolol and losartan therapy.

BACKGROUND: The Pediatric Heart Network designed a clinical trial to compare aortic root growth and other short-term cardiovascular outcomes in children and young adults with Marfan syndrome randomized to receive atenolol or losartan. We report here the characteristics of the screened population and enrolled subjects. METHODS AND RESULTS: Between 2007 and 2011, 21 clinical sites randomized 608 subjects, aged 6 months to 25 years who met the original Ghent criteria and had a body surface area-adjusted aortic root diameter z-score >3.0. The mean age at study entry was 11.2 years, 60% were male, and 25% were older teenagers and young adults. The median aortic root diameter z-score was 4.0. Aortic root diameter z-score did not vary with age. Mitral valve prolapse and mitral regurgitation were more common in females. Among those with a positive family history, 56% had a family member with aortic surgery, and 32% had a family member with a history of aortic dissection. CONCLUSIONS: Baseline demographic, clinical, and anthropometric characteristics of the randomized cohort are representative of patients in this population with moderate to severe aortic root dilation. The high percentage of young subjects with relatives who have had aortic dissection or surgery illustrates the need for more definitive therapy; we expect that the results of the study and the wealth of systematic data collected will make an important contribution to the management of individuals with Marfan syndrome.

An evaluation of early cardiometabolic risk factors in children and adolescents with Turner syndrome.

BACKGROUND AND OBJECTIVES: Turner syndrome (TS) confers increased lifetime risk of type 2 diabetes mellitus and cardiovascular disease. We compared cardiometabolic risk factors and measures of subcutaneous, visceral adipose tissue and intra-myocellular lipid between young TS girls and an age- and BMI-standard deviation scores (SDS)-matched healthy female cohort. PATIENTS AND METHODS: A cross-sectional cohort study was conducted at the Hospital for Sick Children, Toronto. Nineteen TS and 17 control girls (13.7 ± 2.5 vs 12.7 ± 3.4 years of age, respectively, P = 0.30). Multiple-sample oral glucose tolerance test with measurement of fasting insulin, LDL, HDL, triglycerides, adiponectin and highly sensitive C-reactive protein (hsCRP) was performed. Subcutaneous adipose tissue, visceral adipose tissue intramyocellular lipid levels evaluated by magnetic resonance techniques. Insulin secretion (IS), sensitivity (Si) and the insulin secretion-sensitivity index (ISSI-2) were calculated from oral glucose tolerance test data. RESULTS: Five TS and no controls had impaired fasting glucose or impaired glucose tolerance; none had type 2 diabetes mellitus. Insulin sensitivity and insulin secretion were similar between groups; ISSI-2 was lower in TS (923.5 ± 307.3 vs 659.1 ± 387.3; P = 0.03). TS girls had higher blood pressure (82.5 ± 13.6 vs 73.5 ± 5.5 mmHg; P = 0.0146), waist circumference (76.0 ± 11.8 vs 65.9 ± 9.7; P = 0.0087) and subcutaneous adipose tissue (135.6 ± 88.6 vs 69.3 ± 59.9; P = 0.01) than controls. Visceral adipose tissue, intramyocellular lipid levels and adiponectin were not different between groups. TS girls also had higher triglycerides (1.1 ± 0.6 vs 0.7 ± 0.3; P = 0.003), total cholesterol (4.4 ± 0.7 vs 3.9 ± 0.4; P = 0.02) and hsCRP (2.0 ± 1.9 vs 0.8 ± 0.3; P = 0.01). CONCLUSIONS: TS girls exhibit more cardiometabolic risk factors and reduced beta cell function compared with age- and BMI-SDS-matched girls. Increased awareness of early risk of type 2 diabetes mellitus and hypertension in TS girls is needed.

Coordinated ventilation and spiracle activity produce unidirectional airflow in the hissing cockroach, Gromphadorhina portentosa.

Insects exchange respiratory gases via an extensive network of tracheal vessels that open to the surface of the body through spiracular valves. Although gas exchange is known to increase with the opening of these spiracles, it is not clear how this event relates to gas flow through the tracheal system. We examined the relationship between respiratory airflow and spiracle activity in a ventilating insect, the hissing cockroach, Gromphadorhina portentosa, to better understand the complexity of insect respiratory function. Using simultaneous video recordings of multiple spiracular valves, we found that abdominal spiracles open and close in unison during periods of ventilation. Additionally, independent recordings of CO2 release from the abdominal and thoracic regions and observations of hyperoxic tracer gas movement indicate that air is drawn into the thoracic spiracles and expelled from the abdominal spiracles. Our video recordings suggest that this unidirectional flow is driven by abdominal contractions that occur when the abdominal spiracles open. The spiracles then close as the abdomen relaxes and fills with air from the thorax. Therefore, the respiratory system of the hissing cockroach functions as a unidirectional pump through the coordinated action of the spiracles and abdominal musculature. This mechanism may be employed by a broad diversity of large insects that respire by active ventilation.

Evolution of the arterial structure and function from infancy to adolescence is related to anthropometric and blood pressure changes.

OBJECTIVE: To develop a normative data set and to study the relationship among arterial structure, different anthropometric measures, blood pressure, and arterial function during healthy childhood using very-high-resolution ultrasound (25-55 MHz). METHODS AND RESULTS: In 135 healthy children between 0 and 18 years of age, we assessed the structure of the carotid arteries, larger peripheral arteries, aorta, and left ventricle with ultrasound. Arterial stiffness was assessed by pulse wave velocity and endothelial function by brachial flow-mediated dilation. Reference curves adjusted for age and body surface area of arterial lumen diameters, intima-media thickness, and adventitia thickness were developed. Arterial walls thicken during childhood predominantly as a result of a progressive increase in intima-media thickness. There were significant associations among lumen diameter (R(2) range, 0.20-0.88 for different arteries; P<0.001), intima-media thickness (R(2) range, 0.47-0.85; P<0.001), left ventricular mass (R(2)=0.90; P<0.001), and adventitia thickness (R(2) range, 0.15-0.22; P<0.001) with sex, age, body surface, and systolic blood pressure. Arterial wall stress was associated with lumen diameter (R(2) range, 0.52-0.83; P<0.001) and intima-media thickness (R(2) range, 0.53-0.88; P<0.001). Limited relationships were found among arterial wall layer thickness, stiffness, and endothelial function. CONCLUSIONS: In healthy children, the evolution of the arterial structure is mainly related to anthropometrics and blood pressure.

Factors impacting echocardiographic imaging after the Fontan procedure: a report from the pediatric heart network fontan cross-sectional study.

Echocardiographic image quality in Fontan survivors may be limited by a variety of factors. We sought to describe echocardiographic quality and factors associated with study quality in subjects participating in the Pediatric Heart Network Fontan Cross-Sectional Study. Echocardiograms were obtained at 7 clinical sites using a standard protocol. Quality grading and analysis were performed by a core laboratory. Univariate and multivariable modeling were performed to assess factors associated with quality and ability to obtain images sufficient for prespecified quantitative analysis. A total of 543 echocardiograms were obtained. The quality of echocardiograms improved over the duration of the study. The great arteries, systemic veins, and pulmonary veins were less likely to be adequately imaged than other cardiac structures. Quantitative analysis of ventricular volume was possible in 76% overall, but only 41% of those with mixed ventricular morphology. Factors independently associated with better quality included younger age, levocardia, acquisition of the echocardiogram at a longer time since the beginning of enrollment, absence of a pulmonary artery stent, and clinical site. Patient and center-specific factors are associated with echocardiographic quality after the Fontan procedure. Increased familiarity and experience with a standard imaging protocol is likely to result in improved quality.

Health anxiety and associated constructs in school-age children and adolescents with congenital heart disease and their parents: A children's healthy-heart activity monitoring program in Saskatchewan cohort study.

Youth with congenital heart disease (CHD) have been found to experience higher levels of health anxiety and associated constructs than typically developing peers. The association between youth and parent health anxiety has been explored in typically developing youth but this association remains unknown in youth with CHD. This association was explored using a prospective, cross-sectional study that included 36 school-age children and adolescents with CHD (median age =10.5 years, IQR = 4) and 35 parents (median age = 44 years, IQR = 10.5). Participants completed a demographic form and measures of health anxiety, anxiety sensitivity, intolerance of uncertainty, and anxiety disorder symptom categories (youth) or general anxiety (parent). Associations were observed between child and adolescent panic/agoraphobia symptoms and parent state anxiety (r = .41), child and adolescent intolerance of uncertainty and parent state and trait anxiety (r = .37; r = .46, respectively), and child and adolescent anxiety sensitivity and parent state anxiety (r = .40). No association was observed between health anxiety in children and adolescents and parents nor between child and adolescent health anxiety and parent associated constructs. For parents, associations between health anxiety and all measures of associated constructs of interest were observed. Study findings will facilitate improved understanding of the psychological needs of school-age children and adolescents with CHD.

Building Bridges from Genome to Physiology Using Machine Learning and Drosophila Experimental Evolution.

Drosophila experimental evolution, with its well-defined selection protocols, has long supplied useful genetic material for the analysis of functional physiology. While there is a long tradition of interpreting the effects of large-effect mutants physiologically, identifying and interpreting gene-to-phenotype relationships has been challenging in the genomic era, with many labs not resolving how physiological traits are affected by multiple genes throughout the genome. Drosophila experimental evolution has demonstrated that multiple phenotypes change because of the evolution of many loci across the genome, creating the scientific challenge of sifting out differentiated but noncausal loci for individual characters. The fused lasso additive model method allows us to infer some of the differentiated loci that have relatively greater causal effects on the differentiation of specific phenotypes. The experimental material that we use in the present study comes from 50 populations that have been selected for different life histories and levels of stress resistance. Differentiation of cardiac robustness, starvation resistance, desiccation resistance, lipid content, glycogen content, water content, and body masses was assayed among 40-50 of these experimentally evolved populations. Through the fused lasso additive model, we combined physiological analyses from eight parameters with whole-body pooled-seq genomic data to identify potentially causally linked genomic regions. We have identified approximately 2,176 significantly differentiated 50-kb genomic windows among our 50 populations, with 142 of those identified genomic regions that are highly likely to have a causal effect connecting specific genome sites to specific physiological characters.

Differences in critical thermal maxima and mortality across life stages of the mealworm beetle Tenebrio molitor.

Thermal limits to activity profoundly affect the abundance and distribution of ectothermic animals. Upper thermal limits to activity are typically reported as the critical thermal maximum (CT(max)), the temperature at which activity becomes uncontrolled. Thermolimit respirometry is a new technique that allows CT(max) to be quantified in small animals, such as insects, as the point of spiracular failure by measuring CO(2) release from the animal as temperature increases. Although prior studies have reported a characteristic pattern of CO(2) release for insects during thermolimit respirometry trials, no studies have been carried out to determine the universality of this pattern across development, or at what point death occurs along this pattern. Here, we compared the CT(max) and patterns of CO(2) release among three life stages of a beetle species, Tenebrio molitor, and mapped heat death onto these patterns. Our study is the first to report distinct patterns of CO(2) release in different life stages of an insect species during thermolimit respirometry. Our results show that CT(max) was significantly higher in adult beetles than in either larvae or pupae (P<0.001) and, similarly, death occurred at higher temperatures in adults than in larvae and pupae. We also found that death during heating closely follows CT(max) in these animals, which confirms that measuring the loss of spiracular control with thermolimit respirometry successfully identifies the point of physiological limitation during heat stress.