Background
It is known that respiration modulates cavopulmonary flows, but little data compare mean flows under breath-holding and free-breathing conditions to isolate the respiratory effects and effects of exercise on the respiratory modulation. Methods Real-time phase-contrast magnetic resonance combined with a novel method to track respiration on the same image acquisition was used to investigate respiratory effects on Fontan caval and aortic flows under breath-holding, free-breathing, and exercise conditions. Respiratory phasicity indices that were based on beat-averaged flow were used to quantify the respiratory effect. Results Flow during inspiration was substantially higher than expiration under the free-breathing and exercise conditions for both inferior vena cava (inspiration/expiration: 1.6 ± 0.5 and 1.8 ± 0.5, respectively) and superior vena cava (inspiration/expiration: 1.9 ± 0.6 and 2.6 ± 2.0, respectively). Changes from rest to exercise in the respiratory phasicity index for these vessels further showed the impact of respiration. Total systemic venous flow showed no significant statistical difference between the breath-holding and free-breathing conditions. In addition, no substantial difference was found between the descending aorta and inferior vena cava mean flows under either resting or exercise conditions. Conclusions This study demonstrated that inferior vena cava and superior vena cava flow time variance is dominated by respiratory effects, which can be detected by the respiratory phasicity index. However, the minimal respiration influence on net flow validates the routine use of breath-holding techniques to measure mean flows in Fontan patients. Moreover, the mean flows in the inferior vena cava and descending aorta are interchangeable.
by
Jacob P. Brunner;
Joshua Michael Levy;
Melissa L. Ada;
Kiranya E. Tipirneni;
Henry P. Barham;
Gretchen M. Oakley;
Daniel Cox;
Bobby D. Nossaman;
Edward D. McCoul
Background: Total intravenous anesthesia (TIVA) has been proposed as a method to reduce blood loss during endoscopic sinus surgery (ESS). Impaired sinonasal visualization due to mucosal bleeding may be burdensome in cases of chronic rhinosinusitis (CRS) with high-grade inflammatory disease, suggesting a role for TIVA in that disease subgroup.
Methods: A double-blind, randomized controlled trial was conducted of adults undergoing ESS at a tertiary medical center. Patients considered for inclusion had high-grade CRS defined as either sinonasal polyposis or a preoperative Lund-Mackay score of ≥12. Subjects were randomized to receive either TIVA or inhaled anesthesia (IA) during ESS. The primary outcome measure was intraoperative visibility as rated by 3 blinded reviewers utilizing the 10-point Wormald Surgical Field Grading Scale. Secondary outcomes included operative blood loss, complications, and change in quality of life evaluated by the 22-item Sino-Nasal Outcome Test (SNOT-22).
Results: A total of 72 patients were randomized into TIVA (n = 37) and IA (n = 35) study arms. Aggregate median (interquartile range) Wormald scores across all reviewers demonstrated a more favorable visual field with TIVA compared to IA (3.5 [2.4-3.9] vs IA 4.1[3.0-5.8], p = 0.0089). There was significantly less blood loss in the TIVA group compared to the IA group (200 mL [100-450] vs 300 mL [200-500], p = 0.046). Baseline patient characteristics were comparable between cohorts with no significant postoperative complications. No significant changes were detected between postoperative SNOT-22 scores at 3 months (p = 0.278) and at 6 months (p = 0.396) following ESS.
Conclusion: TIVA contributes to improved intraoperative visualization and decreased blood loss in patients undergoing ESS for high-grade inflammatory sinus disease.
by
Maisam Abu-El-Haija;
Soma Kumar;
J. Antonio Quiros;
Keshawadhana Balakrishnan;
Bradley Barth;
Samuel Bitton;
John F. Eisses;
Elsie Jazmin Foglio;
Victor Fox;
Denease Francis;
Alvin Jay Freeman;
Tanja Gonska;
Amit S. Grover;
Sohail Z. Husain;
Rakesh Kumar;
Sameer Lapsia;
Tom Lin;
Quin Y. Liu;
Asim Maqbool;
Zachary M. Sellers;
Flora Szabo;
Aliye Uc;
Steven L. Werlin;
Veronique D. Morinville
Background: Although the incidence of acute pancreatitis (AP) in children is increasing, management recommendations rely on adult published guidelines. Pediatric-specific recommendations are needed. Methods: The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Pancreas committee performed a MEDLINE review using several preselected key terms relating to management considerations in adult and pediatric AP. The literature was summarized, quality of evidence reviewed, and statements of recommendations developed. The authorship met to discuss the evidence, statements, and voted on recommendations. A consensus of at least 75% was required to approve a recommendation. Results: The diagnosis of pediatric AP should follow the published INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE definitions (by meeting at least 2 out of 3 criteria: (1) abdominal pain compatible with AP, (2) serum amylase and/or lipase values ≥3 times upper limits of normal, (3) imaging findings consistent with AP). Adequate fluid resuscitation with crystalloid appears key especially within the first 24 hours. Analgesia may include opioid medications when opioid-sparing measures are inadequate. Pulmonary, cardiovascular, and renal status should be closely monitored particularly within the first 48 hours. Enteral nutrition should be started as early as tolerated, whether through oral, gastric, or jejunal route. Little evidence supports the use of prophylactic antibiotics, antioxidants, probiotics, and protease inhibitors. Esophago-gastroduodenoscopy, endoscopic retrograde cholangiopancreatography, and endoscopic ultrasonography have limited roles in diagnosis and management. Children should be carefully followed for development of early or late complications and recurrent attacks of AP. Conclusions: This clinical report represents the first English-language recommendations for the management of pediatric AP. Future aims should include prospective multicenter pediatric studies to further validate these recommendations and optimize care for children with AP.
The mechanism of permanganate-mediated dual C-H oxidation of complex diketopiperazines has been examined with density functional theory computations. The products of these oxidations are enabling intermediates in the synthesis of structurally diverse ETP natural products. We evaluated, for the first time, the impact of ion-pairing and aggregation states of the permanganate ion and counter-cations, such as bis(pyridine)-silver(I) (Ag+) and tetra-n-butylammonium (TBA+), on the C-H oxidation mechanism. The C-H abstraction occurs through an open shell singlet species, as noted previously, followed by O-rebound and a competing OH-rebound pathway. The second C-H oxidation proceeds with a second equivalent of oxidant with lower free energy barriers than the first C-H oxidation due to directing effects and the generation of a more reactive oxidant species after the first C-H oxidation. The success and efficiency of the second C-H oxidation are found to be critically dependent on the presence of an ion-paired oxidant. We used the developed mechanistic knowledge to rationalize an experimentally observed oxidation pattern for C3-indole-substituted diketopiperazine (+)-5 under optimal oxidation conditions: namely, the formation of diol (-)-6 as a single diastereomer and lack of the ketone products. We proposed two factors that may impede the ketone formation: (i) the conformational flexibility of the diketopiperazine ring, and (ii) hindrance of this site, making it less accessible to the ion-paired oxidant species.
Despite the large number of reports on colloidal nanocrystals, very little is known about the mechanistic details in terms of nucleation and growth at the atomistic level. Taking bimetallic core-shell nanocrystals as an example, here we integrate in situ liquid-cell transmission electron microscopy with first-principles calculations to shed light on the atomistic details involved in the nucleation and growth of Pt on Pd cubic seeds. We elucidate the roles played by key synthesis parameters, including capping agent and precursor concentration, in controlling the nucleation site, diffusion path, and growth pattern of the Pt atoms. When the faces of a cubic seed are capped by Br−, Pt atoms preferentially nucleate from corners and then diffuse to edges and faces for the creation of a uniform shell. The diffusion does not occur until the Pt deposited at the corner has reached a threshold thickness. At a high concentration of the precursor, self-nucleation takes place and the Pt clusters then randomly attach to the surface of a seed for the formation of a non-uniform shell. These atomistic insights offer a general guideline for the rational synthesis of nanocrystals with diverse compositions, structures, shapes, and related properties.
Ionized Mg (iMg) is considered the biologically active fraction of circulating total Mg (tMg). It is possible that iMg may be a more physiologically relevant marker than tMg. Using data from a double-blind pilot randomized controlled trial, we tested (1) whether oral Mg supplementation will increase iMg concentrations compared with placebo and (2) the relationship between iMg and tMg at baseline. Additionally, we evaluated the agreement between iMg measured in fresh whole blood versus stored samples. A total of fifty-nine participants were randomized 1:1 to oral Mg supplementation (400 mg/day, Mg Oxide) or placebo for 10 weeks. Fasting blood samples were obtained at baseline and follow-up. The analysis used linear regression and an intent-to-treat approach.
Participants were generally healthy, the mean age was 62, and 73% were female. The baseline iMg and tMg were modestly and positively associated (r = 0.50). The ratio of baseline iMg to tMg was 64%. The mean supplement effect on iMg was 0.03 mmol/L (95% CI:0.01, 0.05) for Mg supplementation versus placebo. The supplement effect on iMg was not statistically significantly different according to baseline iMg status (above/below median). Compared to fresh blood, iMg was consistently higher in refrigerated and frozen samples by 0.14 and 0.20 mmol/L, respectively. In this relatively healthy adult population, Mg supplementation over 10 weeks resulted in increased iMg concentrations. Whether iMg is a more appropriate measure of Mg status than tMg, and the public health or clinical utility of measuring iMg remains to be determined.
by
Melinda C. Power;
Andreea Rawlings;
A. Richey Sharrett;
Karen Bandeen-Roche;
Josef Coresh;
Christie Ballantyne;
Yashashwi Pokharel;
Erin D. Michos;
Alan Penman;
Alvaro Alonso;
David Knopman;
Thomas H. Mosley;
Rebecca F. Gottesman
Introduction Existing studies predominantly consider the association of late-life lipid levels and subsequent cognitive change. However, midlife rather than late-life risk factors are often most relevant to cognitive health. Methods We quantified the association between measured serum lipids in midlife and subsequent 20-year change in performance on three cognitive tests in 13,997 participants of the Atherosclerosis Risk in Communities study. Results Elevated total cholesterol, low-density lipoprotein cholesterol, and triglycerides were associated with greater 20-year decline on a test of executive function, sustained attention, and processing speed. Higher total cholesterol and triglycerides were also associated with greater 20-year decline in memory scores and a measure summarizing performance on all three tests. High-density lipoprotein cholesterol was not associated with cognitive change. Results were materially unchanged in sensitivity analyses addressing informative missingness. Discussion Elevated total cholesterol, low-density lipoprotein cholesterol, and triglycerides in midlife were associated with greater 20-year cognitive decline.
Background: Analytic methods are available to acquire extensive metabolic information in a cost-effective manner for personalized medicine, yet disease risk and diagnosis mostly rely upon individual biomarkers based on statistical principles of false discovery rate and correlation. Due to functional redundancies and multiple layers of regulation in complex biologic systems, individual biomarkers, while useful, are inherently limited in disease characterization. Data reduction and discriminant analysis tools such as principal component analysis (PCA), partial least squares (PLS), or orthogonal PLS (O-PLS) provide approaches to separate the metabolic phenotypes, but do not offer a statistical basis for selection of group-wise metabolites as contributors to metabolic phenotypes. Methods: We present a dimensionality-reduction based approach termed 'biplot correlation range (BCR)' that uses biplot correlation analysis with direct orthogonal signal correction and PLS to provide the group-wise selection of metabolic markers contributing to metabolic phenotypes. Results: Using a simulated multiple-layer system that often arises in complex biologic systems, we show the feasibility and superiority of the proposed approach in comparison of existing approaches based on false discovery rate and correlation. To demonstrate the proposed method in a real-life dataset, we used LC-MS based metabolomics to determine spectrum of metabolites present in liver mitochondria from wild-type (WT) mice and thioredoxin-2 transgenic (TG) mice. We select discriminatory variables in terms of increased score in the direction of class identity using BCR. The results show that BCR provides means to identify metabolites contributing to class separation in a manner that a statistical method by false discovery rate or statistical total correlation spectroscopy can hardly find in complex data analysis for predictive health and personalized medicine.
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Michelle Daya;
Nicholas Rafaels;
Tonya M. Brunetti;
Sameer Chavan;
Albert M. Levin;
Aniket Shetty;
Christopher R. Gignoux;
Meher Preethi Boorgula;
Genevieve Wojcik;
Monica Campbell;
Candelaria Vergara;
Dara G. Torgerson;
Victor E. Ortega;
Ayo Doumatey;
Henry Richard Johnston;
Nathalie Acevedo;
Maria Ilma Araujo;
Zhaohui Qin;
Adolfo Correa;
Yijuan Hu
Asthma is a complex disease with striking disparities across racial and ethnic groups. Despite its relatively high burden, representation of individuals of African ancestry in asthma genome-wide association studies (GWAS) has been inadequate, and true associations in these underrepresented minority groups have been inconclusive. We report the results of a genome-wide meta-analysis from the Consortium on Asthma among African Ancestry Populations (CAAPA; 7009 asthma cases, 7645 controls). We find strong evidence for association at four previously reported asthma loci whose discovery was driven largely by non-African populations, including the chromosome 17q12–q21 locus and the chr12q13 region, a novel (and not previously replicated) asthma locus recently identified by the Trans-National Asthma Genetic Consortium (TAGC). An additional seven loci reported by TAGC show marginal evidence for association in CAAPA. We also identify two novel loci (8p23 and 8q24) that may be specific to asthma risk in African ancestry populations.