A parental communication assessment initiative in the paediatric cardiovascular ICU.

OBJECTIVE: Challenges to communication between families and care providers of paediatric patients in intensive care units (ICU) include variability of communication preferences, mismatched goals of care, and difficulties carrying forward family preferences from provider to provider. Our objectives were to develop and test an assessment tool that queries parents of children requiring cardiac intensive care about their communication preferences and to determine if this tool facilitates patient-centred care and improves families' ICU experience. DESIGN: In this quality improvement initiative, a novel tool was developed, the Parental Communication Assessment (PCA), which asked parents with children hospitalised in the cardiac ICU about their communication preferences. Participants were prospectively randomised to the intervention group, which received the PCA, or to standard care. All participants completed a follow-up survey evaluating satisfaction with communication. MAIN RESULTS: One hundred thirteen participants enrolled and 56 were randomised to the intervention group. Participants who received the PCA preferred detail-oriented communication over big picture. Most parents understood the daily discussions on rounds (64%) and felt comfortable expressing concerns (68%). Eighty-six percent reported the PCA was worthwhile. Parents were generally satisfied with communication. However, an important proportion felt unprepared for difficult decisions or setbacks, inadequately included or supported in decision-making, and that they lacked control over their child's care. There were no significant differences between the intervention and control groups in their communication satisfaction results. CONCLUSIONS: Parents with children hospitalised in the paediatric ICU demonstrated diverse communication preferences. Most participants felt overall satisfied with communication, but individualising communication with patients' families according to their preferences may improve their experience.

Association Between Vertebral Bone Quality Score and Dual-Energy X-ray Absorptiometry for the Assessment of Bone Mineral Density in Adolescent Patients.

BACKGROUND: The MRI-based vertebral bone quality (VBQ) score is an assessment tool for bone mineral density (BMD) that has been validated in adults against the clinical standard of dual-energy X-ray absorptiometry (DEXA). However, VBQ has yet to be validated against DEXA for use in adolescents. This study evaluated the associations between adolescent VBQ scores, DEXA Z-scores, and BMD values. METHODS: The radiographic records of 63 consecutive patients between the ages of 11 and 21 who underwent MRI of the abdomen and pelvis and DEXA of the spine and hip were retrieved. The collected radiographic data consisted of the MRI-based VBQ score, DEXA Z-score, and BMD values of the femoral neck, L1-4 vertebrae, and total body. The VBQ score was calculated by taking the median signal intensity (MSI) from L1-L4 and the SI of the L3 cerebrospinal fluid (CSF). The VBQ score was derived as the quotient of MSIL1-L4 divided by SICSF. RESULTS: A mean VBQ score of 2.41 ± 0.29 was observed. Strong correlations of -0.749 (p<0.0001) and -0.780 (p<0.0001) were detected between the VBQ score and DEXA femoral neck and spine Z-scores, respectively. Correlations between VBQ score and DEXA femoral neck, spine, and total body BMD scores were -0.559 (p<0.0001), -0.611 (p<0.0001), and -0.516 (p<.0001), respectively. No significant correlations were found between the VBQ score and age, BMI, weight, or height. A mean difference in VBQ score of -0.155 (p=0.035) was observed between sexes. VBQ demonstrated moderate predictive ability for DEXA-derived Z-scores and BMD scores. CONCLUSIONS: VBQ scores were strongly correlated with DEXA Z-scores and moderately correlated with BMD values. The VBQ score can also be used by adolescent patients as an accessory tool to assess bone health.

Yoga vs Cognitive Processing Therapy for Military Sexual Trauma-Related Posttraumatic Stress Disorder: A Randomized Clinical Trial.

Importance: First-line treatment for posttraumatic stress disorder (PTSD) in the US Department of Veterans Affairs (VA), ie, trauma-focused therapy, while effective, is limited by low treatment initiation, high dropout, and high treatment refraction. Objective: To evaluate the effectiveness of Trauma Center Trauma-Sensitive Yoga (TCTSY) vs first-line cognitive processing therapy (CPT) in women veterans with PTSD related to military sexual trauma (MST) and the hypothesis that PTSD outcomes would differ between the interventions. Design, Setting, and Participants: This multisite randomized clinical trial was conducted from December 1, 2015, to April 30, 2022, within 2 VA health care systems located in the southeast and northwest. Women veterans aged 22 to 71 years with MST-related PTSD were enrolled and randomized to TCTSY or CPT. Interventions: The TCTSY intervention (Hatha-style yoga focusing on interoception and empowerment) consisted of 10 weekly, 60-minute group sessions, and the CPT intervention (cognitive-based therapy targeting modification of negative posttraumatic thoughts) consisted of 12 weekly, 90-minute group sessions. Main Outcome and Measures: Sociodemographic data were collected via self-report survey. The primary outcome, PTSD symptom severity, was assessed using the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and PTSD Checklist for DSM-5 (PCL-5). Assessments were conducted at baseline, midintervention, 2 weeks post intervention, and 3 months post intervention. Results: Of 200 women veterans who consented to participate, the intent-to-treat sample comprised 131 participants (mean [SD] age, 48.2 [11.2] years), with 72 randomized to TCTSY and 59 randomized to CPT. Treatment was completed by 47 participants (65.3%) in the TCTSY group and 27 (45.8%) in the CPT group, a 42.6% higher treatment completion rate in the TCTSY group (P = .03). Both treatment groups improved over time on the CAPS-5 (mean [SD] scores at baseline: 36.73 [8.79] for TCTSY and 35.52 [7.49] for CPT; mean [SD] scores at 3 months: 24.03 [11.55] for TCTSY and 22.15 [13.56]) and the PCL-5 (mean [SD] scores at baseline: 49.62 [12.19] for TCTSY and 48.69 [13.62] for CPT; mean [SD] scores at 3 months: 36.97 [17.74] for TCTSY and 31.76 [12.47]) (P < .001 for time effects). None of the group effects or group-by-time effects were significant. Equivalence analyses of change scores were not significantly different between the TCTSY and CPT groups, and the two one-sided test intervals fell within the equivalence bounds of plus or minus 10 for CAPS-5 for all follow-up time points. Conclusions and Relevance: In this comparative effectiveness randomized clinical trial, TCTSY was equivalent to CPT in reducing PTSD symptom severity, with both groups improving significantly. The higher treatment completion rate for TCTSY indicates its higher acceptability as an effective and acceptable PTSD treatment for women veterans with PTSD related to MST that could address current VA PTSD treatment limitations. Trial Registration: ClinicalTrials.gov Identifier: NCT02640690.

A Lung Cancer Screening Education Program Impacts both Referral Rates and Provider and Medical Assistant Knowledge at Two Federally Qualified Health Centers.

BACKGROUND: Federally Qualified Health Centers (FQHCs) serve minority and low-socioeconomic populations and provide care to high-risk smokers. These centers frequently experience barriers, including low provider and medical assistant (MA) knowledge around lung cancer screening (LCS). Subsequent low LCS referral rates by providers at FQHCs limit utilization of LCS in eligible, high-risk, underserved patients. METHODS: Providers and MAs from two FQHCs participated in a LCS educational session. A pre-educational survey was administered at the start of the session and a post-educational survey at the end. The intervention included a presentation with education around non-small cell lung cancer, LCS, tobacco cessation, and shared-decision making. Both surveys were used to evaluate changes in provider and MA ability to determine eligible patients for LCS. The Pearson's Chi-squared test with Yates' continuity correction was used to measure the impact. RESULTS: A total of 29 providers and 28 MAs enrolled in the study from two FQHCs. There was an improvement, P < .009 and P < .015 respectively, in provider and MA confidence in identifying patients for LCS. Additionally, one year prior to the program, 9 low-dose computed tomography (LDCTs) were ordered at one of the FQHCs and 0 at the other. After the program, over 100 LDCTs were ordered at each FQHC. CONCLUSIONS: A targeted LCS educational program improves provider and MAs' ability to identify eligible LCS patients and is associated with an increase in the number of patients referred to LDCT at FQHCs.

Health Disparities in Recruitment and Enrollment in Research.

Despite advances in thoracic oncology research, the benefits of new discoveries are not universally experienced. A lack of representation of racial/ethnic minorities and individuals of low socioeconomic status in clinical trials and thoracic research contributes to persistent health care disparities. It is critical that improved racial, ethnic, and socioeconomic diversity is achieved in our trials and research, if we are to attain generalizability of findings and reduction of health care disparities. Culturally tailored and community-based approaches can help improve recruitment and enrollment of marginalized groups in thoracic research, which is an essential step toward achieving health equity and advancing medical science.

Nanoparticles Mediated Target-specific Drug Delivery in Prostate Cancer: An In-depth Review.

Nanotechnology has been extensively exploited for its enormous therapeutic and diagnostic potential in the management of multiple disorders. It employs nanomaterials as drug carriers with enhanced efficacy and limited side effects on normal tissues. A lot of nanomaterials have been studied and produced, imminently reforming the treatment and diagnostics of numerous malignancies, including cancer. The purpose of the present study is to explore the role of nanotechnology-based devices/therapies that have a vital function in the therapeutics and diagnostics of cancer with potential impact at three levels: early detection, tumor imaging, and drug delivery methods. Concentrating on cancer, promising nanotechnology-based approaches have been planned to satisfy the need for targeted specificity of traditional agents of chemotherapeutics, in addition to early recognition of malignant and precancerous lesions. Prostate cancer is the fifth most wellknown cancer worldwide and the second most usually detected cancer in men. Therefore, there is a crucial need to improve therapeutic prospects for the diagnosis and treatment of prostate cancer via the exploitation of the potential of nanomaterials for cell-targeted specificity and improved primary diagnosis of precancerous tumors. The present review, therefore, focuses on summarizing all prospective applications of nanotechnology in the prognosis and diagnosis of prostate cancer, which would further help researchers to elucidate a more potent therapeutic approach for the better management of prostate cancer in the days ahead.

Maturational patterns of left ventricular rotational mechanics in pre-term infants through 1 year of age.

BACKGROUND: Pre-mature birth impacts left ventricular development, predisposing this population to long-term cardiovascular risk. The aims of this study were to investigate maturational changes in rotational properties from the neonatal period through 1 year of age and to discern the impact of cardiopulmonary complications of pre-maturity on these measures. METHODS: Pre-term infants (<29 weeks at birth, n = 117) were prospectively enrolled and followed to 1-year corrected age. Left ventricular basal and apical rotation, twist, and torsion were measured by two-dimensional speckle-tracking echocardiography and analysed at 32 and 36 weeks post-menstrual age and 1-year corrected age. A mixed random effects model with repeated measures analysis was used to compare rotational mechanics over time. Torsion was compared in infants with and without complications of cardiopulmonary diseases of pre-maturity, specifically bronchopulmonary dysplasia, pulmonary hypertension, and patent ductus arteriosus. RESULTS: Torsion decreased from 32 weeks post-menstrual age to 1-year corrected age in all pre-term infants (p < 0.001). The decline from 32 to 36 weeks post-menstrual age was more pronounced in infants with cardiopulmonary complications, but was similar to healthy pre-term infants from 36 weeks post-menstrual age to 1-year corrected age. The decline was due to directional and magnitude changes in apical rotation over time (p < 0.05). CONCLUSION: This study tracks maturational patterns of rotational mechanics in pre-term infants and reveals torsion declines from the neonatal period through 1 year. Cardiopulmonary diseases of pre-maturity may negatively impact rotational mechanics during the neonatal period, but the myocardium recovers by 1-year corrected age.

Cardiac Dysfunction Identified by Strain Echocardiography Is Associated With Illness Severity in Pediatric Sepsis.

OBJECTIVES: Sepsis-induced myocardial dysfunction has been associated with illness severity and mortality in pediatrics. Although early sepsis-induced myocardial dysfunction diagnosis could aid in hemodynamic management, current echocardiographic metrics for assessing biventricular function are limited in detecting early impairment. Strain echocardiography is a validated quantitative measure that can detect subtle perturbations in left ventricular and right ventricular function. This investigation evaluates the utility of strain echocardiography in pediatric sepsis and compares with to conventional methods. DESIGN: Retrospective, observational study comparing left ventricular and right ventricular strain. Strain was compared with ejection fraction and fractional shortening and established sepsis severity of illness markers. SETTING: Tertiary care medical-surgical PICU from July 2013 to January 2018. PATIENTS: Seventy-nine septic children and 28 healthy controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Compared with healthy controls, patients with severe sepsis demonstrated abnormal left ventricular strain (left ventricular longitudinal strain: -13.0% ± 0.72; p = 0.04 and left ventricular circumferential strain: -16.5% ± 0.99; p = 0.046) and right ventricular (right ventricular longitudinal strain = -14.3% ± 6.3; p < 0.01) despite normal fractional shortening (36.0% ± 1.6 vs 38.1% ± 1.1; p = 0.5129) and ejection fraction (60.7% ± 2.2 vs 65.3% ± 1.5; p = 0.33). There was significant association between depressed left ventricular longitudinal strain and increased Vasotrope-Inotrope Score (r = 0.52; p = 0.034). Worsening left ventricular circumferential strain was correlated with higher lactate (r = 0.31; p = 0.03) and higher Pediatric Risk of Mortality-III score (r = 0.39; p < 0.01). Depressed right ventricular longitudinal strain was associated with elevated pediatric multiple organ dysfunction score (r = 0.44; p < 0.01) CONCLUSIONS:: Compared with healthy children, pediatric septic patients demonstrated abnormal left ventricular and right ventricular strain concerning for early signs of cardiac dysfunction. This was despite having normal ejection fraction and fractional shortening. Abnormal strain was associated with abnormal severity of illness markers. Strain echocardiography may have utility as an early indicator of sepsis-induced myocardial dysfunction in pediatric sepsis.

Two-Dimensional Strain is more Precise than Conventional Measures of Left Ventricular Systolic Function in Pediatric Patients.

Ejection fraction (EF) and fractional shortening (FS) are standard methods of quantifying left ventricular (LV) systolic function. 2D global longitudinal strain (2D GLS) is a well-established, but underutilized method for LV function quantification. The aim of this study was to assess precision of GLS compared to EF & FS in pediatrics. Echocardiograms were prospectively analyzed by 2 blinded observers. FS, EF, and GLS were calculated following standard methods. Bland-Altman was applied to assess agreement. Intraclass correlation coefficient (ICC) was used to measure reliability. Coefficient of variation was used to demonstrate relative variability between methods. 103 pediatric echos were evaluated for inter-observer reproducibility, and 15 patients for intra-observer reproducibility. GLS had higher inter-observer agreement and reliability (bias 7%, 95% LOA - 3.4 to + 3.5, ICC 0.86 CI 0.80-0.90) compared to EF (bias 27%, 95% LOA - 18.9 to + 19.5; ICC 0.25 CI 0.07-0.43) and FS (bias 12%, 95% LOA - 11.9 to + 12.2; ICC 0.53 CI 0.38-0.66). GLS also had higher intra-observer agreement (bias 4%, 95% LOA - 3.6 to + 3.7; ICC 0.87 CI 0.66-0.96) compared to EF (bias 11%, 95% LOA - 14.9 to + 15.1; ICC 0.26 CI - 0.28-0.67) and FS (bias 12%, 95% LOA - 12.2 to + 12.5; ICC 0.38 CI - 0.15-0.74). GLS is a more precise method for quantifying LV function in pediatrics, with lower variability compared to EF and FS. GLS provides a more reliable evaluation of LV systolic function and should be utilized more widely in pediatrics.

Persistence of right ventricular dysfunction and altered morphometry in asymptomatic preterm Infants through one year of age: Cardiac phenotype of prematurity.

INTRODUCTION: Prematurity impacts myocardial development and may determine long-term outcomes. The objective of this study was to test the hypothesis that preterm neonates develop right ventricle dysfunction and adaptive remodelling by 32 weeks post-menstrual age that persists through 1 year corrected age. MATERIALS AND METHODS: A subset of 80 preterm infants (born <29 weeks) was selected retrospectively from a prospectively enrolled cohort and measures of right ventricle systolic function and morphology by two-dimensional echocardiography were assessed at 32 weeks post-menstrual age and at 1 year of corrected age. Comparisons were made to 50 term infants at 1 month and 1 year of age. Sub-analyses were performed in preterm-born infants with bronchopulmonary dysplasia and/or pulmonary hypertension. RESULT: In both term and preterm infants, right ventricle function and morphology increased over the first year (p < 0.01). The magnitudes of right ventricle function measures were lower in preterm-born infants at each time period (p < 0.01 for all) and right ventricle morphology indices were wider in all preterm infants by 1 year corrected age, irrespective of lung disease. Measures of a) right ventricle function were further decreased and b) morphology increased through 1 year in preterm infants with bronchopulmonary dysplasia and/or pulmonary hypertension (p < 0.01). CONCLUSION: Preterm infants exhibit abnormal right ventricle performance with remodelling at 32 weeks post-menstrual age that persists through 1 year corrected age, suggesting a less developed intrinsic myocardial function response following preterm birth. The development of bronchopulmonary dysplasia and pulmonary hypertension leave a further negative impact on right ventricle mechanics over the first year of age.

Echocardiographic Assessment of Right Ventricular Afterload in Preterm Infants: Maturational Patterns of Pulmonary Artery Acceleration Time Over the First Year of Age and Implications for Pulmonary Hypertension.

BACKGROUND: Assessment of pulmonary hemodynamics is critical in the diagnosis and management of cardiopulmonary disease of premature infants, but reliable noninvasive indices of pulmonary hemodynamics in preterm infants are lacking. Because pulmonary artery acceleration time (PAAT) is a validated noninvasive method to assess right ventricular (RV) afterload in infants and children, the aim of this study was to investigate the maturational changes of PAAT measures in preterm infants over the first year of age and to discern the impact of typical cardiopulmonary abnormalities on these measures. METHODS: In a prospective multicenter study of 239 preterm infants (<29 weeks at birth), PAAT was assessed at days 1, 2, and 5 to 7, at 32 and 36 weeks' postmenstrual age, and at 1-year corrected age. To account for heart rate variability, PAAT was adjusted for RV ejection time. Premature infants who developed bronchopulmonary dysplasia or had echocardiographic findings of pulmonary hypertension were analyzed separately. Intra- and interobserver reproducibility analysis was performed. RESULTS: PAAT was feasible in 95% of the image acquisitions, and there was high intra- and interobserver agreement (intraclass correlation coefficients > 0.9 and coefficients of variation < 6%). In uncomplicated preterm infants (n = 103 [48%]) PAAT and PAAT adjusted for RV ejection time increased longitudinally from birth to 1-year corrected age (P < .001) and were linearly associated with gestational age at birth (r = 0.81 and r = 0.82, P < .001) and increasing postnatal weight and postnatal age (r > 0.81, P < .001). PAAT measures were significantly reduced (P < .001) in infants with bronchopulmonary dysplasia and/or pulmonary hypertension (n = 119 [51%]) beyond 1 week of age. CONCLUSIONS: PAAT measures increase in preterm infants from birth to 1-year corrected age, reflective of the physiologic postnatal drop in RV afterload. Bronchopulmonary dysplasia and pulmonary hypertension have a negative impact on PAAT measures. By demonstrating excellent reliability and establishing reference patterns of PAAT in preterm infants, this study suggests that PAAT and PAAT adjusted for RV ejection time can be used as complementary parameters to assess physiologic and pathologic changes in pulmonary hemodynamics in neonates.

Evidence of Echocardiographic Markers of Pulmonary Vascular Disease in Asymptomatic Infants Born Preterm at One Year of Age.

OBJECTIVE: To test the hypothesis that echocardiographic markers of pulmonary vascular disease (PVD) exist in asymptomatic infants born preterm at 1-year corrected age. STUDY DESIGN: We conducted a prospective cohort study of 80 infants born preterm (<29 weeks of gestation) and 100 age- and weight-matched infants born at term and compared broad-based conventional and quantitative echocardiographic measures of pulmonary hemodynamics at 1-year corrected age. Pulmonary artery acceleration time (PAAT), a validated index of pulmonary vascular resistance, arterial pressure, and compliance, was used to assess pulmonary hemodynamics. Lower PAAT is indicative of PVD. Subanalyses were performed in infants with bronchopulmonary dysplasia (BPD, n = 48, 59%) and/or late-onset pulmonary hypertension (n = 12, 15%). RESULTS: At 1 year, there were no differences between conventional measures of pulmonary hypertension in the infants born at term and preterm. All infants born preterm had significantly lower values of PAAT than infants born at term (73 ± 8 milliseconds vs 98 ± 5 milliseconds, P < .001). Infants born preterm with BPD had even lower PAAT than those without BPD (69 ± 5 milliseconds vs 79 ± 4 milliseconds, P < .01). The degree of PVD at 1-year corrected age was inversely related to gestation in all infants born preterm. Data analysis included adjustment for ventricular function and other confounding factors. CONCLUSIONS: In comparison with infants born at term, infants born preterm exhibit abnormal PAAT at 1-year corrected age irrespective of neonatal lung disease status, suggesting the existence of PVD beyond infancy. PAAT measurements offer a reliable, noninvasive tool for screening and longitudinal monitoring of pulmonary hemodynamics in infants.

Pediatric and adult dilated cardiomyopathy represent distinct pathological entities.

Pediatric dilated cardiomyopathy (DCM) is the most common indication for heart transplantation in children. Despite similar genetic etiologies, medications routinely used in adult heart failure patients do not improve outcomes in the pediatric population. The mechanistic basis for these observations is unknown. We hypothesized that pediatric and adult DCM comprise distinct pathological entities, in that children do not undergo adverse remodeling, the target of adult heart failure therapies. To test this hypothesis, we examined LV specimens obtained from pediatric and adult donor controls and DCM patients. Consistent with the established pathophysiology of adult heart failure, adults with DCM displayed marked cardiomyocyte hypertrophy and myocardial fibrosis compared with donor controls. In contrast, pediatric DCM specimens demonstrated minimal cardiomyocyte hypertrophy and myocardial fibrosis compared with both age-matched controls and adults with DCM. Strikingly, RNA sequencing uncovered divergent gene expression profiles in pediatric and adult patients, including enrichment of transcripts associated with adverse remodeling and innate immune activation in adult DCM specimens. Collectively, these findings reveal that pediatric and adult DCM represent distinct pathological entities, provide a mechanistic basis to explain why children fail to respond to adult heart failure therapies, and suggest the need to develop new approaches for pediatric DCM.

Maturational Patterns of Systolic Ventricular Deformation Mechanics by Two-Dimensional Speckle-Tracking Echocardiography in Preterm Infants over the First Year of Age.

BACKGROUND: The aim of this study was to determine the maturational changes in systolic ventricular strain mechanics by two-dimensional speckle-tracking echocardiography in extremely preterm neonates from birth to 1 year of age and discern the impact of common cardiopulmonary abnormalities on the deformation measures. METHODS: In a prospective multicenter study of 239 extremely preterm infants (<29 weeks gestation at birth), left ventricular (LV) global longitudinal strain (GLS) and global longitudinal systolic strain rate (GLSRs), interventricular septal wall (IVS) GLS and GLSRs, right ventricular (RV) free wall longitudinal strain and strain rate, and segmental longitudinal strain in the RV free wall, LV free wall, and IVS were serially measured on days 1, 2, and 5 to 7, at 32 and 36 weeks postmenstrual age, and at 1 year corrected age (CA). Premature infants who developed bronchopulmonary dysplasia or had echocardiographic findings of pulmonary hypertension were analyzed separately. RESULTS: In uncomplicated preterm infants (n = 103 [48%]), LV GLS and GLSRs remained unchanged from days 5 to 7 to 1 year CA (P = .60 and P = .59). RV free wall longitudinal strain, RV free wall longitudinal strain rate, and IVS GLS and GLSRs significantly increased over the same time period (P < .01 for all measures). A significant base-to-apex (highest to lowest) segmental longitudinal strain gradient (P < .01) was seen in the RV free wall and a reverse apex-to-base gradient (P < .01) in the LV free wall. In infants with bronchopulmonary dysplasia and/or pulmonary hypertension (n = 119 [51%]), RV free wall longitudinal strain and IVS GLS were significantly lower (P < .01), LV GLS and GLSRs were similar (P = .56), and IVS segmental longitudinal strain persisted as an RV-dominant base-to-apex gradient from 32 weeks postmenstrual age to 1 year CA. CONCLUSIONS: This study tracks the maturational patterns of global and regional deformation by two-dimensional speckle-tracking echocardiography in extremely preterm infants from birth to 1 year CA. The maturational patterns are ventricular specific. Bronchopulmonary dysplasia and pulmonary hypertension leave a negative impact on RV and IVS strain, while LV strain remains stable.

Pulmonary Artery Acceleration Time Provides a Reliable Estimate of Invasive Pulmonary Hemodynamics in Children.

BACKGROUND: Pulmonary artery acceleration time (PAAT) is a noninvasive method to assess pulmonary hemodynamics, but it lacks validity in children. The aim of this study was to evaluate the accuracy of Doppler echocardiography-derived PAAT in predicting right heart catheterization (RHC)-derived pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR), and compliance in children. METHODS: Prospectively acquired and retrospectively measured Doppler echocardiography-derived PAAT and RHC-derived systolic PAP, mean PAP (mPAP), indexed PVR (PVRi), and compliance were compared using regression analysis in a derivation cohort of 75 children (median age, 5.3 years; interquartile range, 1.3-12.6 years) with wide ranges of pulmonary hemodynamics. To account for heart rate variability, PAAT was adjusted for right ventricular ejection time and corrected by the RR interval. Regression equations incorporating PAAT and PAAT/right ventricular ejection time from the derivation cohort were then evaluated for the accuracy of their predictive values for invasive pulmonary hemodynamics in a validation cohort of 50 age- and weight-matched children with elevated PAP and PVR. RESULTS: There were significant inverse correlations between PAAT and RHC-derived mPAP (r = -0.82) and PVRi (r = -0.78) and a direct correlation (r = 0.78) between PAAT and pulmonary compliance in the derivation cohort. For detection of pulmonary hypertension (PRVi > 3 Wood units · m2 and mPAP > 25 mm Hg), PAAT < 90 msec and PAAT/right ventricular ejection time < 0.31 resulted in sensitivity of 97% and specificity of 95%. In the derivation cohort, the regression equations relating PAAT with mPAP and PVRi were mPAP = 48 - 0.28 × PAAT and PVRi = 9 - 0.07 × PAAT. These PAAT-integrated equations predicted RHC-measured pulmonary hemodynamics in the validation cohort with good correlations (r = 0.88 and r = 0.83, respectively), small biases (<10%), and minimal coefficients of variation (<8%). CONCLUSIONS: PAAT inversely correlates with RHC-measured pulmonary hemodynamics and directly correlates with pulmonary arterial compliance in children. The study established PAAT-based regression equations in children to accurately predict RHC-derived PAP and PVR.

Gia/Mthl5 is an aorta specific GPCR required for Drosophila heart tube morphology and normal pericardial cell positioning.

G-protein signaling is known to be required for cell-cell contacts during the development of the Drosophila dorsal vessel. However, the identity of the G protein-coupled receptor (GPCR) that regulates this signaling pathway activity is unknown. Here we describe the identification of a novel cardiac specific GPCR, called Gia, for "GPCR in aorta". Gia is the only heart-specific GPCR identified in Drosophila to date and it is specifically expressed in cardioblasts that fuse at the dorsal midline to become the aorta. Gia is the only Drosophila gene so far identified for which expression is entirely restricted to cells of the aorta. Deletion of Gia led to a broken-hearted phenotype, characterized by pericardial cells dissociated from cardioblasts and abnormal distribution of cell junction proteins. Both phenotypes were similar to those observed in mutants of the heterotrimeric cardiac G proteins. Lack of Gia also led to defects in the alignment and fusion of cardioblasts in the aorta. Gia forms a protein complex with G-αo47A, the alpha subunit of the heterotrimeric cardiac G proteins and interacts genetically with G-αo47A during cardiac morphogenesis. Our study identified Gia as an essential aorta-specific GPCR that functions upstream of cardiac heterotrimeric G proteins and is required for morphological integrity of the aorta during heart tube formation. These studies lead to a redefinition of the bro phenotype, to encompass morphological integrity of the heart tube as well as cardioblast-pericardial cell spatial interactions.

Reference Ranges of Left Ventricular Strain Measures by Two-Dimensional Speckle-Tracking Echocardiography in Children: A Systematic Review and Meta-Analysis.

BACKGROUND: Establishment of the range of reference values and associated variations of two-dimensional speckle-tracking echocardiography (2DSTE)-derived left ventricular (LV) strain is a prerequisite for its routine clinical adoption in pediatrics. The aims of this study were to perform a meta-analysis of normal ranges of LV global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) measurements derived by 2DSTE in children and to identify confounding factors that may contribute to variance in reported measures. METHODS: A systematic review was launched in MEDLINE, Embase, Scopus, the Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library. Search hedges were created to cover the concepts of pediatrics, STE, and left-heart ventricle. Two investigators independently identified and included studies if they reported 2DSTE-derived LV GLS, GCS, or GRS. The weighted mean was estimated by using random effects models with 95% CIs, heterogeneity was assessed using the Cochran Q statistic and the inconsistency index (I(2)), and publication bias was evaluated using the Egger test. Effects of demographic (age), clinical, and vendor variables were assessed in a metaregression. RESULTS: The search identified 2,325 children from 43 data sets. The reported normal mean values of GLS among the studies varied from -16.7% to -23.6% (mean, -20.2%; 95% CI, -19.5% to -20.8%), GCS varied from -12.9% to -31.4% (mean, -22.3%; 95% CI, -19.9% to -24.6%), and GRS varied from 33.9% to 54.5% (mean, 45.2%; 95% CI, 38.3% to 51.7%). Twenty-six studies reported longitudinal strain only from the apical four-chamber view, with a mean of -20.4% (95% CI, -19.8% to -21.7%). Twenty-three studies reported circumferential strain (mean, -20.3%; 95% CI, -19.4% to -21.2%) and radial strain (mean, 46.7%; 95% CI, 42.3% to 51.1%) from the short-axis view at the midventricular level. A significant apex-to-base segmental longitudinal strain gradient (P < .01) was observed in the LV free wall. There was significant between-study heterogeneity and inconsistency (I(2) > 94% and P < .001 for each strain measure), which was not explained by age, gender, body surface area, blood pressure, heart rate, frame rate, frame rate/heart rate ratio, tissue-tracking methodology, location of reported strain value along the strain curve, ultrasound equipment, or software. The metaregression showed that these effects were not significant determinants of variations among normal ranges of strain values. There was no evidence of publication bias (P = .40). CONCLUSIONS: This study defines reference values of 2DSTE-derived LV strain in children on the basis of a meta-analysis. In healthy children, mean LV GLS was -20.2% (95% CI, -19.5% to -20.8%), mean GCS was -22.3% (95% CI, -19.9% to -24.6%), and mean GRS was 45.2% (95% CI, 38.3% to 51.7%). LV segmental longitudinal strain has a stable apex-to-base gradient that is preserved throughout maturation. Although variations among different reference ranges in this meta-analysis were not dependent on differences in demographic, clinical, or vendor parameters, age- and vendor-specific referenced ranges were established as well.

Regulation of Mutagenic DNA Polymerase V Activation in Space and Time.

Spatial regulation is often encountered as a component of multi-tiered regulatory systems in eukaryotes, where processes are readily segregated by organelle boundaries. Well-characterized examples of spatial regulation are less common in bacteria. Low-fidelity DNA polymerase V (UmuD'2C) is produced in Escherichia coli as part of the bacterial SOS response to DNA damage. Due to the mutagenic potential of this enzyme, pol V activity is controlled by means of an elaborate regulatory system at transcriptional and posttranslational levels. Using single-molecule fluorescence microscopy to visualize UmuC inside living cells in space and time, we now show that pol V is also subject to a novel form of spatial regulation. After an initial delay (~ 45 min) post UV irradiation, UmuC is synthesized, but is not immediately activated. Instead, it is sequestered at the inner cell membrane. The release of UmuC into the cytosol requires the RecA* nucleoprotein filament-mediated cleavage of UmuD→UmuD'. Classic SOS damage response mutants either block [umuD(K97A)] or constitutively stimulate [recA(E38K)] UmuC release from the membrane. Foci of mutagenically active pol V Mut (UmuD'2C-RecA-ATP) formed in the cytosol after UV irradiation do not co-localize with pol III replisomes, suggesting a capacity to promote translesion DNA synthesis at lesions skipped over by DNA polymerase III. In effect, at least three molecular mechanisms limit the amount of time that pol V has to access DNA: (1) transcriptional and posttranslational regulation that initially keep the intracellular levels of pol V to a minimum; (2) spatial regulation via transient sequestration of UmuC at the membrane, which further delays pol V activation; and (3) the hydrolytic activity of a recently discovered pol V Mut ATPase function that limits active polymerase time on the chromosomal template.