Synthesis of Tridecacene by Multistep Single-Molecule Manipulation.

Acenes represent a unique class of polycyclic aromatic hydrocarbons that have fascinated chemists and physicists due to their exceptional potential for use in organic electronics. While recent advances in on-surface synthesis have resulted in higher acenes up to dodecacene, a comprehensive understanding of their fundamental properties necessitates their expansion toward even longer homologues. Here, we demonstrate the on-surface synthesis of tridecacene via atom-manipulation-induced conformational preparation and dissociation of a trietheno-bridged precursor on a Au(111) surface. The generated tridecacene has been investigated by scanning tunneling microscopy and spectroscopy (STM/STS), combined with first-principles calculations. We observe that the STS transport gap (1.09 eV) shrinks again following the gap reopening of dodecacene (1.4 eV). Spin-polarized density functional theory calculations confirm an antiferromagnetic open-shell ground-state electronic configuration for tridecacene in the gas phase. Interestingly, tridecacene's open-shell character is significantly reduced upon interaction with the Au(111) surface despite being only physisorbed. The interaction with the surface leads to a lowering of the magnetization of tridecacene, a reduced gap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO), compared to the gas phase, and a reduced relative energy to the nonmagnetic state, making it nearly isoenergetic. These observations show qualitatively that the influence of the Au(111) substrate on the properties of long acenes is significant, which is important for interpreting the measured STS transport gaps. Our work contributes to a fundamental understanding of the electronic properties of long acenes, confirming a nonmonotonous length-dependent HOMO-LUMO gap, and to the development of multistep tip-assisted synthesis of elusive compounds.

Impact of burnout and professional fulfillment on intent to leave among pediatric physicians: The findings of a quality improvement initiative.

BACKGROUND AND OBJECTIVES: Physician burnout is rampant, and physician retention is increasingly hard. It is unclear how burnout impacts intent to leave an organization. We sought to determine how physician burnout and professional fulfillment impact pediatric physicians' intent to leave (ITL) an organization. DESIGN AND METHODS: We performed 120, 1:1 semi-structured interviews of our pediatric faculty and used the themes therefrom to develop a Likert-scale based, 22-question battery of their current work experience. We created a faculty climate survey by combining those questions with a standardized instrument that assesses burnout and professional fulfillment. We surveyed pediatric and pediatric-affiliated (e.g. pediatric surgery, pediatric psychiatry, etc.) physicians between November 2 and December 9, 2022. We used standard statistical methods to analyze the data. An alpha-level of 0.05 was used to determine significance. RESULTS: A total of 142 respondents completed the survey, 129 (91%) were Department of Pediatrics faculty. Burnout was present in 41% (58/142) of respondents, whereas 30% (42/142) were professionally fulfilled. There was an inverse relationship between professional fulfillment and ITL, p < 0.001 for the trend. Among those who were not professionally fulfilled, the odds ratio of ITL in the next three years was 3.826 [95% CI 1.575-9.291], p = 0.003. There was a direct relationship between burnout and ITL, p < 0.001 for the trend. CONCLUSIONS: Among pediatric physicians, professional fulfillment is strongly, inversely related with ITL in the next three years. Similarly, burnout is directly related with ITL. These data suggest a lack of professional fulfillment and high burnout are strong predictors of pediatric physician turnover.

Activation of the Renin-Angiotensin-Aldosterone System Is Attenuated in Hypertensive Compared with Normotensive Pregnancy.

Hypertension during pregnancy increases the risk of adverse maternal and fetal outcomes, but the mechanisms of pregnancy hypertension are not precisely understood. Elevated plasma renin activity and aldosterone concentrations play an important role in the normal physiologic adaptation to pregnancy. These effectors are reduced in patients with pregnancy hypertension, creating an opportunity to define the features of the renin-angiotensin-aldosterone system (RAAS) that are characteristic of this disorder. In the current study, we used a novel LC-MS/MS-based methodology to develop comprehensive profiles of RAAS peptides and effectors over gestation in a cohort of 74 pregnant women followed prospectively for the development of gestational hypertension and pre-eclampsia (HYP, 27 patients) versus those remaining normotensive (NT, 47 patients). In NT pregnancy, the plasma renin activity surrogate, (PRA-S, calculated from the sum of Angiotensin I + Angiotensin II) and aldosterone concentrations significantly increased from the first to the third trimester, accompanied by a modest increase in the concentrations of angiotensin peptide metabolites. In contrast, in HYP pregnancies, PRA-S and angiotensin peptides were largely unchanged over gestation, and third-trimester aldosterone concentrations were significantly lower compared with those in NT pregnancies. The results indicated that the predominant features of pregnancies that develop HYP are stalled or waning activation of the RAAS in the second half of pregnancy (accompanied by unchanging levels of angiotensin peptides) and the attenuated secretion of aldosterone.

Intermittent Hypoxemia in Preterm Infants: A Potential Proinflammatory Process.

OBJECTIVE: A major consequence of prematurity is intermittent hypoxemia (IH). Data from both adult studies and neonatal animal models suggest that IH is proinflammatory; however, there is limited data in preterm infants. Here, we assess the relationship between IH and systemic inflammation, namely, serum C-reactive protein (CRP) in preterm infants. STUDY DESIGN: Serum CRP was measured at 30 days of life, at the time of peak IH frequency. IH measures (e.g., per cent time in hypoxemia, frequency, duration) were calculated the week prior to CRP collection. Statistical analyses were based on Spearman's correlation. RESULTS: A total of 26 infants were included. Median gestational age and birth weight were 274/7 weeks and 980 g, respectively. There were positive correlations between primary IH measures and CRP levels, especially for events longer than 1-minute duration (r range: 0.56-0.74, all p < 0.01). CONCLUSION: We demonstrate that IH is associated with increased CRP for the first time in preterm infants. Our findings are consistent with studies from adults and neonatal animal models suggesting that IH is a proinflammatory process. KEY POINTS: · IH events are common.. · IH is associated with elevated C-reactive protein.. · Longer IH events (>1 min) are of most significance..

Synthesis of the [11]Cyclacene Framework by Repetitive Diels-Alder Cycloadditions.

The Diels-Alder cycloaddition between bisdienes and bisdienophile incorporating the 7-oxa-bicyclo[2.2.1]heptane unit are well known to show high diastereoselectivity that can be exploited for the synthesis of molecular belts. The related bisdiene 5,6,7,8-tetramethylidene-2-bicyclo[2.2.2]octene is a valuable building block for the synthesis of photoprecursors for acenes, but it has not been employed for the synthesis of molecular belts. The present work investigates by computational means the Diels-Alder reaction between these bisdiene building blocks with syn-1,4,5,8-tetrahydro-1,4:5,8-diepoxyanthracene, which shows that the diastereoselectivity of the Diels-Alder reaction of the etheno-bridged bisdiene is lower than that of the epoxy-bridged bisdiene. The reaction of the etheno-bridged bisdiene and syn-1,4,5,8-tetrahydro-1,4:5,8-diepoxyanthracene in 2:1 ratio yields two diastereomers that differ in the orientation of the oxa and etheno bridges based on NMR and X-ray crystallography. The all-syn diastereomer can be transformed into a molecular belt by inter- and intramolecular Diels-Alder reactions with a bifunctional building block. The molecular belt could function as a synthetic intermediate en route to a [11]cyclacene photoprecursor.

Case series of therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy during extracorporeal life support.

Therapeutic hypothermia initiated within 6 hours of birth is currently the standard of care for the management of neonates with hypoxic-ischemic encephalopathy. Neonates undergoing therapeutic hypothermia for hypoxic-ischemic encephalopathy are also at risk for severe respiratory failure and need for extracorporeal life support. The risks and benefits of therapeutic hypothermia for hypoxic-ischemic encephalopathy during extracorporeal life support are still not well defined. We report our experience of a case series of six neonates who underwent therapeutic hypothermia for hypoxic-ischemic encephalopathy during extracorporeal life support. We also report long-term neurodevelopmental follow-up from 6 to 24 months and add to the current body of evidence regarding feasibility, clinical experience, and short-term complications.

CANDLE/Supervisor: a workflow framework for machine learning applied to cancer research.

BACKGROUND: Current multi-petaflop supercomputers are powerful systems, but present challenges when faced with problems requiring large machine learning workflows. Complex algorithms running at system scale, often with different patterns that require disparate software packages and complex data flows cause difficulties in assembling and managing large experiments on these machines. RESULTS: This paper presents a workflow system that makes progress on scaling machine learning ensembles, specifically in this first release, ensembles of deep neural networks that address problems in cancer research across the atomistic, molecular and population scales. The initial release of the application framework that we call CANDLE/Supervisor addresses the problem of hyper-parameter exploration of deep neural networks. CONCLUSIONS: Initial results demonstrating CANDLE on DOE systems at ORNL, ANL and NERSC (Titan, Theta and Cori, respectively) demonstrate both scaling and multi-platform execution.

Secondhand Smoke Exposure and Preclinical Markers of Cardiovascular Risk in Toddlers.

OBJECTIVE: To investigate relationships between secondhand smoke exposure in young children and several preclinical markers of cardiovascular risk that have been established as relevant to adult populations. STUDY DESIGN: There were 139 children, 2-5 years of age, enrolled in a cross-sectional study. Secondhand smoke exposure was objectively determined by hair nicotine level; a comprehensive panel of clinical markers (morning blood pressure, fasting glucose and insulin, lipid profiles, inflammation) and research markers (markers of oxidation, endothelial stress, and endothelial repair) of cardiovascular risk status were assessed. Univariate and multivariate linear regression were used to evaluate relationships between secondhand smoke exposure and cardiovascular risk markers. RESULTS: Hair nicotine levels were correlated directly with blood pressure and serum C-reactive protein, and inversely correlated with serum high-density lipoprotein cholesterol and endothelial cell progenitor cell prevalence. In multivariate analyses, these relationships remained when controlled for age, sex, body mass index z-score, maternal education, and method of payment. Additionally, in multivariate analyses, hair nicotine level was significantly negatively correlated with total antioxidant capacity. CONCLUSIONS: These results support the view that secondhand smoke exposure in the very young has a detectable relationship with several markers of cardiovascular risk, long before the emergence of clinical disease. Further studies to define mechanisms and strategies to prevent and mitigate these risks early in life are warranted.

Renal injury in neonates: use of "omics" for developing precision medicine in neonatology.

Preterm birth is associated with increased risks of morbidity and mortality along with increased healthcare costs. Advances in medicine have enhanced survival for preterm infants but the overall incidence of major morbidities has changed very little. Abnormal renal development is an important consequence of premature birth. Acute kidney injury (AKI) in the neonatal period is multifactorial and may increase lifetime risk of chronic kidney disease.Traditional biomarkers in newborns suffer from considerable confounders, limiting their use for early identification of AKI. There is a need to develop novel biomarkers that can identify, in real time, the evolution of renal dysfunction in an early diagnostic, monitoring and prognostic fashion. Use of "omics", particularly metabolomics, may provide valuable information regarding functional pathways underlying AKI and prediction of clinical outcomes.The emerging knowledge generated by the application of "omics" (genomics, proteomics, metabolomics) in neonatology provides new insights that can help to identify markers of early diagnosis, disease progression, and identify new therapeutic targets. Additionally, omics will have major implications in the field of personalized healthcare in the future. Here, we will review the current knowledge of different omics technologies in neonatal-perinatal medicine including biomarker discovery, defining as yet unrecognized biologic therapeutic targets, and linking of omics to relevant standard indices and long-term outcomes.

Deletion of Galgt2 (B4Galnt2) reduces muscle growth in response to acute injury and increases muscle inflammation and pathology in dystrophin-deficient mice.

Transgenic overexpression of Galgt2 (official name B4Galnt2) in skeletal muscle stimulates the glycosylation of α dystroglycan (αDG) and the up-regulation of laminin α2 and dystrophin surrogates known to inhibit muscle pathology in mouse models of congenital muscular dystrophy 1A and Duchenne muscular dystrophy. Skeletal muscle Galgt2 gene expression is also normally increased in the mdx mouse model of Duchenne muscular dystrophy compared with the wild-type mice. To assess whether this increased endogenous Galgt2 expression could affect disease, we quantified muscular dystrophy measures in mdx mice deleted for Galgt2 (Galgt2(-/-)mdx). Galgt2(-/-) mdx mice had increased heart and skeletal muscle pathology and inflammation, and also worsened cardiac function, relative to age-matched mdx mice. Deletion of Galgt2 in wild-type mice also slowed skeletal muscle growth in response to acute muscle injury. In each instance where Galgt2 expression was elevated (developing muscle, regenerating muscle, and dystrophic muscle), Galgt2-dependent glycosylation of αDG was also increased. Overexpression of Galgt2 failed to inhibit skeletal muscle pathology in dystroglycan-deficient muscles, in contrast to previous studies in dystrophin-deficient mdx muscles. This study demonstrates that Galgt2 gene expression and glycosylation of αDG are dynamically regulated in muscle and that endogenous Galgt2 gene expression can ameliorate the extent of muscle pathology, inflammation, and dysfunction in mdx mice.

Early urinary biomarkers of acute kidney injury in preterm infants.

BACKGROUND: Acute kidney injury (AKI) in the neonatal intensive care setting is multifactorial and is associated with significant morbidity and mortality. This study evaluates the utility of novel urinary biomarkers to predict the development and/or severity AKI in preterm infants. METHODS: We performed a case-control study on a prospective cohort of preterm infants (<32 wk), to compare seven urine biomarkers between 25 infants with AKI and 20 infants without AKI. RESULTS: Infants with AKI had significantly higher neutrophil gelatinase-associated lipocalin (NGAL) (median, control (CTRL) vs. AKI; 0.598 vs. 4.24 µg/ml; P < 0.0001). In contrast, urinary epidermal growth factor (EGF) levels were significantly lower in infants who developed AKI compared to controls (median, CTRL vs. AKI; 0.016 vs. 0.006 µg/ml; P < 0.001). The area under the curve (AUC) for NGAL for prediction of stage I AKI on the day prior to AKI diagnosis (day-1) was 0.91, and for the prediction of stage II/III, AKI was 0.92. Similarly, urine EGF was a predictor of renal injury on day -1 (AUC: 0.97 for stage I and 0.86 for stage II/III AKI). CONCLUSION: Urinary biomarkers may be useful to predict AKI development prior to changes in serum creatinine (SCr) in preterm infants.

Oxidative Stress in Youth and Adolescents With Elevated Body Mass Index Exposed to Secondhand Smoke.

INTRODUCTION: Our objective was to investigate the relationships between secondhand smoke (SHS) exposure and oxidative stress in a group of youth and adolescents with elevated body mass index. METHODS: Participants in this cross sectional study were healthy nonsmoking youth and adolescents ages 9 to 18 years old. Three-quarters of the participants were either overweight or obese. SHS exposure was determined by survey and hair nicotine level. Markers of oxidation were total antioxidant capacity and protein malondialdehyde adducts (MDA). RESULTS: Ninety subjects were studied; adequate hair samples were available for 86. The mean hair nicotine level was 0.75ng/mg, the median was 0.58ng/mg and the range was 0.09-2.88ng/mg. There was a significant relationship between MDA and the three survey questions regarding smoke exposure ([mother smokes, r = 0.29, P = .006], [smoker lives in the home, r = 0.31, P = .004], and [number of smokers in the home, r = 0.36, P = .002]). There was a significant positive relationship between log-hair nicotine and MDA (Pearson r = 0.233, P = .031), which remained significant after controlling for age, sex, race, and method of insurance. No relationship was found between log-hair nicotine and total antioxidant capacity. However, there was a significant relationship between number of smokers in the home (r = 0.24, P = .042) and total antioxidant capacity. CONCLUSIONS: We have demonstrated a significant positive relationship hair nicotine level and MDA in a group of youth with a high proportion of overweight/obese subjects. IMPLICATIONS: We have shown a significant relationship between objectively measured SHS exposure and one marker of oxidative stress in a sample of youth and adolescents with a high proportion of overweight/obese subjects, and who were nonsmokers with relatively low tobacco exposure. This finding remains significant after controlling for age, sex, race, and type of medical insurance. Since the cardiovascular effects of SHS exposure are related to oxidative stress, this finding adds to our knowledge that the sequence of deleterious effects of tobacco exposure on the cardiovascular system begins long before clinical disease is evident.

Lung development alterations in newborn mice after recovery from exposure to sublethal hyperoxia.

Exposure of newborn mice to hyperoxia arrests lung development, with resultant pathological characteristics similar to bronchopulmonary dysplasia in infants born prematurely. We tested the hypothesis that aberrations in lung development caused by 14 days of sublethal hyperoxia would be reversed during 14 days of recovery to room air (RA) when the concentration of oxygen exposure was weaned gradually. Newborn FVB mice were exposed to 85% oxygen or RA for 14 days. Weaning from hyperoxia was by either transfer directly into RA or a decrease in the concentration of oxygen by 10% per days. At 28 days, pups were euthanized, and the lungs were inflation fixed and assessed. At postnatal day 28, lungs of mice weaned abruptly from hyperoxia had fewer (6 ± 0.6 versus 10 ± 0.7; P < 0.001) alveoli per high-powered field and larger alveoli (4050 ± 207 versus 2305 ± 182 µm(2)) than animals weaned gradually; both hyperoxia-exposed groups were different from lungs obtained from air-breathing controls (20 ± 0.5 alveoli per high-powered field; P < 0.001). The results are consistent with the absence of catch-up alveolarization in this model and indicate that the long-term consequences of early exposures to hyperoxia merit closer examination. The effects of abrupt weaning to RA observed further suggest that weaning should be considered in experimental models of newborn exposure to hyperoxia.

Ultrasonographic characteristics of lipiduria in clinically normal cats.

Echoes are frequently seen in the urinary bladder of cats during abdominal ultrasound. These have been attributed to hematuria, pyuria, crystalluria, and lipid. However, sonographic findings have not been previously correlated with urinalysis. We prospectively evaluated 40 clinically normal cats via ultrasound, serum chemistry, and urinalysis. Thin layer chromatography was performed on the urine to determine the amount (mg) of lipid subfractions including diacylglycerol, triglyceride, phospholipid, free fatty acid, cholesterol, and cholesterol ester. Ninety percent (36/40) of the cats in our population had sonographic echoes suspended in the urinary bladder, with most having a subjective score of mild echoes (n = 20). None of the sonographic echoes were gravity dependent or caused distal acoustic shadowing, reverberation, or twinkle artifact. Of the cats with sonographic echoes in the urine, 66% (24/36) had no significant findings on urinalysis other than the presence of lipid. The total amount of subjective sonographic echoes was not significantly related to the total amount of fat measured on thin layer chromatography or the number of lipid droplets seen on urinalysis. An increased amount of urine diacylglycerol was significantly associated with clumping of echoes (P = 0.02) and the amount of lipid droplets seen on urinalysis (P = 0.04). An association between increased amounts of urine diacylglycerol and the amount of echoes seen on ultrasound approached significance (P = 0.05). Findings from this study support previously published theories that sonographic echoes within the urinary bladder of clinically normal cats may be due to urine lipid.

Ultrasound-Guided Transfemoral Access for Coronary Procedures: A Pooled Learning Curve Analysis From the FAUST and UNIVERSAL Trials.

BACKGROUND: The learning curve for new operators performing ultrasound-guided transfemoral access (TFA) remains uncertain. METHODS: We performed a pooled analysis of the FAUST (Femoral Arterial Access With Ultrasound Trial) and UNIVERSAL (Routine Ultrasound Guidance for Vascular Access for Cardiac Procedures) trials, both multicenter randomized controlled trials of 1:1 ultrasound-guided versus non-ultrasound-guided TFA for coronary procedures. Outcomes included the composite of major bleeding or vascular complications and successful common femoral artery cannulation. Participants were stratified by the operators' accrued case volume. We used adjusted repeated-measurement logistic regression, with random intercepts for operator clustering, for comparison against the non-ultrasound-guided TFA group and to model the learning curve. RESULTS: The FAUST and UNIVERSAL trials randomized a total of 1624 patients, of which 810 were randomized to non-ultrasound-guided TFA and 814 to ultrasound-guided TFA (cases 1-10, 391; 11-20, 183; and >20, 240). Participants who had operators who performed >20 ultrasound-guided TFAs had a decreased risk for the primary end point (5/240 [2.1%] versus 64/810 [7.9%]; adjusted odds ratio, 0.26 [95% CI, 0.09-0.61]) compared with non-ultrasound-guided TFA. Operators who performed >20 ultrasound-guided procedures had increased odds of successfully cannulating the common femoral artery (224/246 [91.1%] versus 327/382 [85.6%]; adjusted odds ratio, 1.76 [95% CI, 1.08-2.89]) compared with non-ultrasound-guided TFA. The learning curve plots demonstrated growing competence with increasing accrued cases. CONCLUSIONS: New operators should perform at least 20 ultrasound-guided TFA to decrease access site complications and increase proper cannulation compared with non-ultrasound-guided TFA. Additional accrued cases may lead to increased proficiency. Training programs should consider these findings in the transradial era.

Functional relevance of genetic variations of endothelial nitric oxide synthase and vascular endothelial growth factor in diabetic coronary microvessel dysfunction.

The prevalence of type 1 diabetes (T1D) is increasing worldwide and is associated with significant microvessel complications, of which nephropathy, retinopathy and neuropathy are the most commonly studied. Although clinically evident microvascular complications of diabetes are rarely seen in childhood, early vascular abnormalities develop during childhood and accelerate during puberty. Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis, which is regulated by endothelial nitric oxide synthase (NOS3) at several levels. Together, VEGF and NOS3 play an important role in the pathogenesis of the microvascular complications of diabetes. Genetic variations in NOS3 and VEGF critically regulate endothelial survival and function and increase the susceptibility of patients to develop severe microvessel complications. Identification of the risk factors for and improved understanding of the subclinical signs of these diabetic microvascular complications will enable implementation of therapeutic strategies, potentially changing the course of vascular complications and improving the prognosis of children, adolescents and young adults with diabetes. Moreover, early detection of these variations may have a prognostic value or may suggest interventional approaches to regulate these proteins in patients with diabetes.

Impact of in utero drug exposure on neonates requiring ECMO: A retrospective cohort study.

The incidence of in utero drug exposure (IUDE) and neonatal extracorporeal membrane oxygenation (ECMO) utilization have both increased over the past decade. However, there are no studies to date that examine the impact that IUDE has on neonates requiring ECMO. In this retrospective cohort study, we compared the clinic course and outcomes of neonates who were placed on ECMO with IUDE vs. neonates without IUDE. Analysis included data extracted from medical records from all neonatal ECMO runs between January 2014 and January 2021 at the University of Kentucky Children's Hospital. A total of 56 neonatal patients were placed on ECMO during this time period and there were a total of 57 ECMO runs. Nearly one-third of neonates (16) had documented IUDE. There were no differences in gestational age, length of ECMO run, survival to discharge, or number of major complications while on ECMO in the neonates with IUDE compared to those without. In contrast, greater use of sedative and analgesic adjuvant medications during ECMO was required for IUDE-ECMO cases (p < 0.01). Trending results indicated that post-ECMO feeding complications and total hospitalization length were also greater in the IUDE-ECMO group. These findings illustrate the complex influence of prenatal drug exposures on neonatal patient care and warrant the development of clinical care strategies optimized for this unique patient group.

Body mass index percentiles versus body composition assessments: Challenges for disease risk classifications in children.

Background: Identifying at-risk children with optimal specificity and sensitivity to allow for the appropriate intervention strategies to be implemented is crucial to improving the health and well-being of children. We determined relationships of body mass indexes for age and sex percentile (BMI%) classifications to actual body composition using validated and convenient methodologies and compared fat and non-fat mass estimates to normative cut-off reference values to determine guideline reliability. We hypothesized that we would achieve an improved ability to identify at-risk children using simple, non-invasive body composition and index measures. Methods: Cross-sectional study of a volunteer convenience sample of 1,064 (537 boys) young children comparing Body Fat Percentage (BF%), Fat Mass Index (FMI), Fat-Free Mass Index (FFMI), determined via rapid bioimpedance methods vs. BMI% in children. Comparisons determined among weight classifications and boys vs. girls. Results: Amongst all subjects BMI% was generally correlated to body composition measures and indexes but nearly one quarter of children in the low-risk classifications (healthy weight or overweight BMI%) had higher BF% and/or lower FFMI than recommended standards. Substantial evidence of higher than expected fatness and or sarcopenia was found relative to risk status. Inaccuracies were more common in girls than boys and girls were found to have consistently higher BF% at any BMI%. Conclusions: The population studied raises concerns regarding actual risks for children of healthy or overweight categorized BMI% since many had higher than expected BF% and potential sarcopenia. When body composition and FMI and FFMI are used in conjunction with BMI% improved sensitivity, and accuracy of identifying children who may benefit from appropriate interventions results. These additional measures could help guide clinical decision making in settings of disease-risks stratifications and interventions.

Association of Elevated Serum Aldosterone Concentrations in Pregnancy with Hypertension.

Emerging evidence indicates a previously unrecognized, clinically relevant spectrum of abnormal aldosterone secretion associated with hypertension severity. It is not known whether excess aldosterone secretion contributes to hypertension during pregnancy. We quantified aldosterone concentrations and angiotensin peptides in serum (using liquid chromatography with tandem mass spectrometry) in a cohort of 128 pregnant women recruited from a high-risk obstetrics clinic and followed prospectively for the development of gestational hypertension, pre-eclampsia, superimposed pre-eclampsia, chronic hypertension, or remaining normotensive. The cohort was grouped by quartile of aldosterone concentration in serum measured in the first trimester, and blood pressure, angiotensin peptides, and hypertension outcomes compared across the four quartiles. Blood pressures and body mass index were greatest in the top and bottom quartiles, with the top quartile having the highest blood pressure throughout pregnancy. Further stratification of the top quartile based on increasing (13 patients) or decreasing (19 patients) renin activity over gestation revealed that the latter group was characterized by the highest prevalence of chronic hypertension, use of anti-hypertensive agents, pre-term birth, and intrauterine growth restriction. Serum aldosterone concentrations greater than 704 pmol/L, the 75th percentile defined within the cohort, were evident across all categories of hypertension in pregnancy, including normotensive. These findings suggest that aldosterone excess may underlie the development of hypertension in pregnancy in a significant subpopulation of individuals.

Ultrasound-guided femoral access in patients with vascular closure devices: a prespecified analysis of the randomised UNIVERSAL trial.

BACKGROUND: Whether ultrasound (US)-guided femoral access compared to femoral access without US guidance decreases access site complications in patients receiving a vascular closure device (VCD) is unclear. AIMS: We aimed to compare the safety of VCD in patients undergoing US-guided versus non-US-guided femoral arterial access for coronary procedures. METHODS: We performed a prespecified subgroup analysis of the UNIVERSAL trial, a multicentre randomised controlled trial of 1:1 US-guided femoral access versus non-US-guided femoral access, stratified for planned VCD use, for coronary procedures on a background of fluoroscopic landmarking. The primary endpoint was a composite of major Bleeding Academic Research Consortium 2, 3 or 5 bleeding and vascular complications at 30 days. RESULTS: Of 621 patients, 328 (52.8%) received a VCD (86% ANGIO-SEAL, 14% ProGlide). In patients who received a VCD, those randomised to US-guided femoral access compared to non-US-guided femoral access experienced a reduction in major bleeding or vascular complications (20/170 [11.8%] vs 37/158 [23.4%], odds ratio [OR] 0.44, 95% confidence interval [CI]: 0.23-0.82). In patients who did not receive a VCD, there was no difference between the US- and non-US-guided femoral access groups, respectively (20/141 [14.2%] vs 13/152 [8.6%], OR 1.76, 95% CI: 0.80-4.03; interaction p=0.004). CONCLUSIONS: In patients receiving a VCD after coronary procedures, US-guided femoral access was associated with fewer bleeding and vascular complications compared to femoral access without US guidance. US guidance for femoral access may be particularly beneficial when VCD are used.