Circularly polarised luminescence from intramolecular excimer emission of bis-1,8-naphthalimide derivatives.

Chiral excimers exhibit unique photophysical behaviour. However, further molecular design is required along with systematic studies on the effect of spacer groups and solvent polarity. In this study, we prepared four circularly polarised luminescence (CPL)-active molecules that exhibit intramolecular excimer emission. Bis-1,8-naphthalimide (bNI) derivatives D-LybNI, L-LybNI, D-LyMebNI, and L-LyMebNI were prepared with chiral backbones and alkyl linkages between the NI rings with chain lengths of five carbon atoms, suitable for excimer fluorescence. The fluorescence properties were investigated experimentally and theoretically using density functional theory. The molecules exhibited intramolecular excimer fluorescence in polar organic solvents. Mirror-image circular dichroism and CPL spectra were obtained for the D and L forms. D- and L-LyMebNI exhibited relatively large luminescence dissymmetry factors (|glum|) in acetonitrile of 1.9 × 10-3 and 1.6 × 10-3, respectively. Thus, this study demonstrates chiral bNI derivatives with simple synthesis procedures that emit intramolecular excimer fluorescence and have effective CPL properties. These molecules are promising for developing organic molecular systems with bright, highly polarised emission.

Intramolecular cyclization reactions of arylpropargyl amides of electron-deficient α,ß-alkenyl carboxylates and related compounds.

Intramolecular cyclization reactions of arylpropargyl amides of electron-deficient α,ß-alkenyl carboxylates such as fumarates and ethenetricarboxylates were investigated. The reaction of the fumaramides with a base, Et3N or DBU in xylenes at 140 °C under air gave benz[f]isoindoline derivatives in 21-63% yields. The benz[f]isoindolines may be produced via the formation of an allenic intermediate, intramolecular Diels-Alder reaction, proton transfer, and dehydrogenation by oxygen. The suitable bases and the product yields depend on the substituents on the benzene ring. On the other hand, the reaction of the amides of fumarate and ethenetricarboxylate by heating in DMSO gave aroyl-substituted pyrrolidine derivatives as major products, probably via addition of water under metal-free conditions. Furthermore, cyclization reactions of H and Me substituted alkyne derivatives were investigated for comparison. The selective formation of various types of products, such as ethyl 2-(1-benzyl-4-formyl-2-oxopyrrolidin-3-yl)acetate and diethyl 2-(1-benzyl-2-oxo-4-vinylidenepyrrolidin-3-yl)malonate, was found, depending upon the alkyne substituents and the reaction conditions. The reaction mechanisms have been discussed using density functional theory (DFT) calculations.

Predictors of a non-response to prophylactic indomethacin for patent ductus arteriosus in preterm infants.

BACKGROUND: Preterm infants are recommended for prophylactic indomethacin (PIND) to promote closure of patent ductus arteriosus (PDA) and reduce morbidity and mortality. This study investigated the predictive factors of a non-response to PIND for PDA in preterm-birth infants. METHODS: Consecutive preterm-birth infants (gestational age: < 28 weeks) who received PIND between 2009 and 2019 were retrospectively enrolled. Seventy-six eligible participants were classified as PIND responders (N = 42) or non-responders (N = 34). Information on potential confounders in maternal obstetric and perinatal data were collected from medical records. Multiple logistic regression analysis was carried out to identify the prognostic factors of a PIND response in preterm-birth infants. RESULTS: The prevalence of intrauterine infection and multiple births was significantly different between responders and non-responders to PIND (intrauterine infection: 2 [4.8%] vs. 8 [23.5%], P = 0.036; twins: 3 [7.1%] vs. 9 [ 26.5%], P = 0.029, respectively). In multivariate logistic regression analysis after adjustment for multiple births, intrauterine infection was a significant and independent predictive factor of a non-response to PIND (odds ratio [OR] 5.54, 95% confidence interval [CI] 1.05-29.2, P = 0.044). A remarkable association was also noted for multiple births with a non-response to PIND (OR 4.22, 95% CI 0.99-17.8, P = 0.050). CONCLUSIONS: Intrauterine infection and multiple births were identified as potential risk factors of a non-response to PIND for PDA in preterm infants.

Circularly polarised luminescence from excimer emission of anthracene derivatives complexed with γ-cyclodextrin in the solid state.

In this study, we report circularly polarised luminescence (CPL)-active molecules that exhibit high fluorescence quantum yields in the solid state. We developed anthracene derivatives with substituents at the 9 and 10 positions, such as ethyl(anthracene-9-carbonyl)glycinate (9AnGlyEt), N-butylanthracene-9-carboxamide (9AnB), N-benzylanthracene-9-carboxamide (9AnPh), and N 9,N 10-dibutylanthracene-9,10-dicarboxamide (9,10AnB). These compounds were complexed with γ-cyclodextrin (γ-CD) in the solid state by grinding, and the fluorescence properties of the resulting γ-CD complexes were investigated. The fluorescence quantum yields were enhanced after γ-CD complexation. Among the prepared γ-CD complexes, 9AnGlyEt/γ-CD had the highest fluorescence quantum yield (Φ f = 0.35), which was enhanced up to 5.8 times after γ-CD complexation. This was probably due to the interaction between the two anthracene molecules in the γ-CD cavity, which prevented fluorescence quenching caused by aggregation of the compounds. Positive CPL of g CPL = 1.3 × 10-3 was observed for 9AnGlyEt/γ-CD based on its excimer emission.

Intramolecular Diels-Alder Reactions of α-Bromostyrene-Functionalized Unsaturated Carboxamides.

Intramolecular cycloaddition reactions of α-bromostyrene-functionalized amides of monomethyl fumarate were investigated. The reaction of the amides with Et3N in toluene at 110 °C gave 1,4-dihydronaphthalenes. The 1,4-dihydronaphthalenes may be produced via the intramolecular Diels-Alder reaction, proton transfer, and dehydrobromination by a base, along with C═C bond isomerization by proton transfer. The reaction of amide derivatives with halogen on a benzene ring and alkali metal carbonates in toluene at 110 °C gave naphthalene derivatives directly. Dehydrogenation of various 1,4-dihydronaphthalenes with cesium or rubidium carbonate in toluene at 110 °C gave naphthalene derivatives. The retardation by TEMPO, acceleration by air for some substrates, and density functional theory calculations suggest a radical mechanism caused by intervention of molecular oxygen.

A DFT study of the active role of the phosphate group of an internal aldimine in a transamination reaction.

A transamination reaction from an internal aldimine ([PLP]) and (S)-alanine to pyridoxamine phosphate (PMP) and pyruvic acid was investigated by DFT calculations. As [PLP], a model where the lysine (-Lys) part was approximated by -CH[-NH-C(O)-CH3]-C(O)-NH-CH3 was adopted. (H2O)4 was also included to trace reaction paths involving proton transfers. 13 elementary processes were obtained. For (the external aldimine → quinoid), (quinoid → ketimine) and (ketimine → carbinol amine) processes, the water dimer was found to connect a phosphate-group oxygen with the moving proton. The connection promoted the Grotthuss-type proton transfer in transition states. It was revealed that the phosphate group is not a mere substituent but has the central role in the transfer.

A DFT study on the degradation mechanism of vitamin B2.

Degradation reaction paths starting from riboflavin (RF) were investigated using DFT (density functional theory) as the first attempt to reveal their elementary processes. Photochemical reactions were followed in the lowest triplet spin state, "(T)". Two intermediates [Int1(T) and Int2(T)] were found in the course, RF(T) â†’ FMF (7,8-dimethyl-10-formylflavin, T). From FMF(T), there are two degradation channels. Release of ketene(T) and carbon monoxide leads to LC (lumichrome, S0) and LF (lumiflavin, T), respectively. The base-catalyzed (ground state) degradation of FMF was investigated with HO-(H2O)3. The Grotthuss-type proton transfer along hydrogen bonds controlled the degradation reaction. All the transition states of cleavage of C-C and C-N covalent bonds were determined, and the degradation mechanism was clarified.

Identification of metabolomic profile related to adult Fontan pathophysiology.

BACKGROUND: Metabolic disorders are important pathophysiologies that can cause multiple organ dysfunction and worsen prognosis in Fontan patients. This study aimed to comprehensively evaluate the metabolomic profile of adult Fontan patients and characterize its pathophysiology in relation to 2 control groups. METHODS AND RESULTS: We performed metabolomic analysis of 31 plasma samples using capillary electrophoresis time-of-flight mass spectrometry. This observational cross-sectional study compared plasma metabolites of 14 heterogeneous adult Fontan patients with those of control groups, including 9 patients with congenital heart disease after biventricular repair and 8 normal healthy controls. Fontan patients exhibited significant differences in intermediate metabolite concentrations related to glycolysis, the tricarboxylic acid (TCA) cycle, and the urea cycle. The plasma concentrations of lactic acid, 2-oxoglutarate, isocitric acid, malic acid, cis-aconitic acid, arginine, citrulline, and the ratio of ornithine/citrulline showed significantly differences among the groups. Multiple logistic regression analysis with a stepwise selection-elimination method identified 2-oxoglutaric acid (odds ratio [OR] 1.98, 95% confidence interval [CI] 1.05-3.76) and cis-aconitic acid (OR 2.69, 95% CI 1.04-6.99) as independently associated with Fontan patients. After adjustment for the covariates of age and gender, 2-oxoglutaric acid (OR 1.97, 95% CI 0.98-3.93) and cis-aconitic acid (OR 3.88, 95% CI 0.99-15.2) showed remarkable relationships with Fontan patients. CONCLUSIONS: The present findings suggest that abnormalities in the TCA cycle and amino acid metabolism are distinguishing features in the pathophysiology of Fontan patients. Future metabolomic studies will assist in developing biomarkers for the early prediction of "silent" Fontan pathophysiologies.

Sequential Knoevenagel Condensation/Cyclization for the Synthesis of Indene and Benzofulvene Derivatives.

Sequential Knoevenagel condensation/cyclization leading to indene and benzofulvene derivatives has been developed. The reaction of 2-(1-phenylvinyl)benzaldehyde with malonates gave benzylidene malonates, cyclized indenes, and dehydrogenated benzofulvenes. The product selectivity depends on the reaction conditions. The reaction with piperidine, AcOH in benzene at 80 °C for 1.5 h gave a benzylidene malonate in 75% yield as a major product. The reactions with piperidine, AcOH in benzene at 80 °C for 17 h and with TiCl4-pyridine at room temperature gave an indene derivative in 56 and 79% yields, respectively, as a major product. The reaction with TiCl4-Et3N gave a benzofulvene in 40% yield selectively. Indene was transformed to a benzofulvene derivative using the reagents TiCl4-Et3N and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). The reaction of variously substituted aryl derivatives with dimethyl malonate gave indene and benzofulvene derivatives. The reactions of 2-(1-phenylvinyl)benzaldehyde with Meldrum's acid or malononitrile also gave cyclized compounds in the suitable sequential or stepwise conditions. Furthermore, the reaction of 2-arylbenzaldehydes has been investigated. The limitation and scope have been described. The reaction mechanism of the cyclization steps has been examined by DFT calculations.

How Is the Oxidation Related to the Tautomerization in Vitamin B9?

The relationship between the lactim-lactam tautomerization and the free-radical scavenging reaction in vitamin B9 [folic acid (FA)] was investigated by density functional theory calculations. 6-Methylpterin was also adopted for the detailed analyses of various reaction paths. For pterin, the transition state of the tautomerization with two water molecules (n = 2) was calculated to be of the lowest activation energy. The proton-transfer circuit of n = 2 is retained (not broken) even with the addition of outer water molecules, n = 2 + 2, 2 + 4, 2 + 8, and 2 + 14. At the oxidation of the system composed of 6-methylpterin + (H2O)2 + HO•, the radical character of HO• is directly transmitted to the pterin ring along with the C-O → H → O → H → O → H → OH proton transfer. The patterns of the electron transfer (pterin ring → OX•) and the concomitant proton transfer via the water dimer were commonly obtained for the oxidant (OX•) = HO•, Cl3C-O2•, N3•, or SO4-•. The hydrogen atom transfer mechanism was ruled out. Two conformations of the puckered form with the -C(═O)-OH···N intramolecular hydrogen bonds of FA were found to have the stability similar to that of the linear conformer. Both the tautomerization and the oxidation were calculated to occur competitively in the three conformers.

Ventricular myocardial response to exercise in patients with Fontan circulation.

BACKGROUND: Exercise stress echocardiography has been used to assess myocardial reserve in various heart diseases. This study examined the ventricular myocardial response to exercise in Fontan patients using exercise stress echocardiography. METHODS: Twenty-five Fontan patients and 19 control subjects underwent semi-supine bicycle exercise stress echocardiography in this prospective, single-center, cross-sectional study. Pulsed-wave Doppler tissue imaging peak systolic (s') and diastolic (e') velocities, longitudinal strain and systolic strain rate, and early diastolic strain rate data at rest and at peak exercise were obtained for the systemic ventricle. The myocardial reserve of functional parameters was calculated as the difference between peak exercise and rest. RESULTS: Inter- and intra-observer reliability were both high for exercise stress echocardiography measurements. Compared with controls, Fontan patients had significantly lower s', e', longitudinal systolic strain and strain rate, and early diastolic longitudinal strain rate at rest and at peak exercise as well as reduced myocardial reserve. CONCLUSIONS: Fontan patients have markedly reduced myocardial reserve during exercise. The use of exercise stress echocardiography assessment may improve the clinical management of Fontan patients.

How is vitamin B1 oxidized to thiochrome? Elementary processes revealed by a DFT study.

The oxidation reaction of thiamine (vitamin B1) to thiochrome was investigated by DFT calculations. Three reaction systems, [A] thiamine + methyl peroxy radical + (H2O)8, [B] thiamine + cyanogen bromide + HO-(H2O)8 and [C] thiamine + mercury(ii) chloride + HO-(H2O)8, were investigated. wB97X-D/6-311+G** for [A] and [B] and wB97X-D/SDD&6-311(+)G** for [C] geometry optimizations were carried out with the solvent effect (water). The effect is of the self-consistent reaction field (SCRF) with the polarizable continuum model (PCM). In [A], the H3C-O2˙ adduct of thiamine undergoes simultaneous cleavage of the C-H and O-O bonds, leading to a very stable 2(3H)-thiazolone intermediate. The same intermediate was obtained after the cleavage of the C-H and O-H bonds of the HO adduct of thiamine in [B] and [C]. After the formation of the key intermediate, the N-protonated thiochrome was afforded via three steps. In reflection of the water-soluble character of vitamin B1, proton transfers along hydrogen bonds of the water cluster enhance those steps.

Heart rate variability in the course of chemotherapy and haematopoietic stem cell transplantation for peadiatric patients with haematological malignancies.

BACKGROUND: High-dose chemotherapy and haematopoietic stem cell transplantation are essential for patients with paediatric haematologic diseases, although cardiotoxicity remains a concern. Heart rate variability analysis can evaluate autonomic nervous function interactions with cardiac function. OBJECTIVE: This study aimed to characterise heart rate variability differences between patients undergoing chemotherapy and controls, and the effects of haematopoietic stem cell transplantation on the autonomic nervous system in patients with haematological malignancies. METHODS: Nineteen patients (11 male, median age: 11.6 years) who received conventional chemotherapy followed by transplantation and 19 non-transplant patients (10 male, median age: 11.5 years) receiving chemotherapy only between 2006 and 2018 for haematological malignancies were retrospectively enrolled. Data from 24-hour Holter monitoring were recorded after chemotherapy and before and after transplantation. Heart rate variability was analysed in patients and 32 matched normal controls. RESULTS: There were significant differences between patients and normal controls in all heart rate variability analysis parameters apart from coefficient of variation of RR interval and standard deviation of the average normal RR interval for all 5-minute segments during sleeping. There was a significant difference in the cumulative anthracycline dose and heart rate variability during sleep between the non-transplant and pre-transplant groups. We observed no remarkable differences in time-domain analysis parameters between before and after transplantation, although the low-frequency component of power-spectrum analysis during awake hours was significantly decreased after transplantation. CONCLUSION: Conventional chemotherapy for paediatric haematologic diseases may be a risk factor for autonomic dysfunction. Further declines in heart rate variability after transplantation appear minor.

[Relation between concrete activities and results of activities planned in conferences of the regional and occupational health fields in secondary medical care zones].

Objectives　This study aimed to clarify the current implemented conditions of collaborations between regional and occupational health fields in secondary medical care zones, taking into account the difficulties, and to suggest measures to promote further collaboration.Methods　Self-rating questionnaires were distributed to public health nurses (PHNs) who were responsible for collaboration at 464 regional health care centers (HCCs). We asked for answers on four cases regarding the implementation and results of 22 different collaboration activities.Results　We analyzed 176 questionnaires from PHNs who had been in charge of conferences for an average of two years. We found the implementation rate of conferences promoting collaboration between regional and occupational health fields to be approximately 80%, with an average duration of four years since these conferences began. Collaborative activities between regional and occupational health fields were divided into three categories: A) "Information exchange among the people involved from regional and occupational fields," B) "Collaboration in health education and counseling," and C) "New health projects based on surveys." The first and third categories (A and C) were significantly higher in the "implemented" group than in the "not implemented" group. The results of the collaborations were organized into six categories: a) "PHNs and members of the conferences (members) could learn about various resources in the community," b) "PHNs and members could build a good relationship among one another and understand community health needs appropriately," c) "Sense of accomplishment and forward progress in the construction of information exchange systems as well as improved cost effectiveness," d) "Progress in health promotion efforts was made," e) "Improvement of health literacy," and f) "An increase in the quality and quantity of participants in health services." The first to three categories (a to c) were higher in cases where three or more conferences were held per year. In addition, we found significant associations between "Collaboration in health education and counseling" (B) and "New health projects based on surveys" (C) as well as with most collaboration result categories.Conclusion　This study identified three collaborative activity categories and six cooperative achievement categories. We clarified their relation with the implementation of the council and the number of conferences held. In addition, we demonstrated the possibility that successful cooperation can be realized by active engagement in collaborative activities, such as planning of substantial collaboration and new projects.

DFT Study of the Hydroxyl Radical Addition to 2'-Deoxyguanosine and the Guanine Base in Four Double-Stranded B-Form Dimers.

Density functional theory (DFT) calculations of reactions between 2'-deoxyguanosine (dR-Gua) and hydroxyl radical (HO•) with water molecules (H2O)n, n = 0, 1, and 2, were carried out. The HO• addition to three carbon sites, C(4), C(5), and C(8), and the subsequent ring cleavage of the three HO adducts were investigated. The addition to C(5) is of the smallest activation energy according to the largest lobe of the dR-Gua highest occupied molecular orbital (HOMO) at C(5). However, its adduct has small stability, and the C(8) adduct has the largest one. The C(8) adduct and the ring-opened amide have similar stability, which would lead to the apparent small yield of the former. Calculations were also performed on HO• additions to the C(4) and C(8) sites of the guanine moiety of four dimer sequence models of B-form DNA with nucleotide moieties (a) 5'-GA-3', (b) 5'-GG-3', (c) 5'-GT-3', and (d) 5'-GC-3'. For instance, the (a) 5'-GA-3' model has a molecular formula C39H50N15Na2O21P2. The HO• attack to C(4) is ruled out owing to the reinforced deformation of the parallel stacking of base pairs. The clear selectivity that the (b) 5'-GG-3' sequence is most reactive was found with the inclusion of the water dimer.

Decreased Circulating Insulin-Like Growth Factor 1 Levels Are Associated with Cardiac Diastolic Dysfunction in Small for Gestational Age Infants.

OBJECTIVE: To evaluate the impact of serum insulin-like growth factor-1 (IGF-1) levels on cardiac function in small for gestational age (SGA) infants. STUDY DESIGN: This is a prospective, observational study. Serum IGF-1 levels at birth and echocardiography measurements at 1 week of age were compared between SGA and appropriate for gestational age (AGA) infants. RESULTS: Thirty-one SGA infants and 27 AGA infants were enrolled. Serum IGF-1 levels were lower in the SGA infants than in the AGA infants. SGA infants had lower mitral lateral annular systolic (S') and early diastolic (E') tissue Doppler imaging velocities compared with AGA infants (S', 5.1 ± 0.9 vs 5.7 ± 1.2 cm/s; E', 6.1 ± 1.5 cm/s vs 7.1 ± 1.3 cm/s; p < 0.05). Serum IGF-1 levels positively correlated with E' velocity in the entire population (r = 0.44, p < 0.001) and in SGA infants (r = 0.39, p < 0.05). In multivariate linear regression analysis, serum IGF-1 and S' velocity were independently associated with E' velocity in the entire population and in SGA infants. CONCLUSION: Decreased serum IGF-I levels could account for cardiac diastolic dysfunction in SGA infants.

Lewis Acid Catalyzed Cyclization Reactions of Ethenetricarboxylates via Intramolecular Hydride Transfer.

Catalytic cyclization of amides of ethenetricarboxylate bearing ether and acetal groups has been examined. The reaction of the amides bearing cyclic ether and acetal groups in the presence of Lewis acid such as Sc(OTf)3 gave spirocyclic piperidine derivatives as major products. The cyclized products may be formed via intramolecular hydride transfer. The reaction mechanism was examined by the DFT calculations. The scope and limitations of the hydride transfer/cyclization reactions of amides of ethenetricarboxylates was investigated, and morpholine formation by intramolecular oxy-Michael addition was also found.

Prognostic Significance of QT Interval Dispersion in the Response to Intravenous Immunoglobulin Therapy in Kawasaki Disease.

BACKGROUND: Kawasaki disease (KD) is classified as a systemic vasculitis syndrome and QT interval dispersion (QTD) has been associated with cardiac involvement and disease activity in patients with cardiovasculitis. We examined whether baseline QTD could predict a response to intravenous immunoglobulin (IVIG) in KD.Methods and Results:QTD was recorded in 86 patients with KD before IVIG, who were separated into IVIG responders (R group; n=62) and nonresponders (N group; n=24). The association between baseline QTD and response to IVIG was investigated, and the predictive response value was compared with conventional risk scores from Gunma and Kurume universities. Baseline-corrected QTDs with Bazett's (QTbcD) and Fridericia's (QTfcD) formulae were significantly increased in the N group (R group vs. N group: 31.6 [28.3, 44.0] ms vs. 66.6 [50.5, 76.3] ms and 27.4 [25.2, 39.1] ms vs. 55.2 [42.4, 66.3] ms, respectively, both P<0.001). Multiple logistic regression analysis revealed QTfcD as an independent predictor of a response to IVIG after adjustment for conventional scores (odds ratio: 1.133, 95% confidence interval: 1.061-1.210, P<0.001). Moreover, QTfcD provided incremental predictive value for IVIG nonresponders over Gunma score (increment in global χ2=25.46, P<0.001). CONCLUSIONS: QTD was significantly associated with a response to IVIG in KD patients and may represent a useful identifier of IVIG nonresponders with high risk of coronary aneurysm.

Impact of Decreased Serum Insulin-Like Growth Factor-1 Levels on Central Aortic Compliance in Small-for-Gestational-Age Infants.

BACKGROUND: Intrauterine growth restriction is associated with arterial hypertension in adulthood; however, the underlying mechanism is unclear. OBJECTIVES: We hypothesized that serum insulin-like growth factor-1 (IGF-1) levels affect central aortic elastic properties and structure in small-for-gestational-age (SGA) infants. METHODS: Eighteen SGA infants and 22 appropriate-for-gestational-age (AGA) infants were enrolled in this study. The serum IGF-1 level within 1 h of birth and abdominal aortic echo parameters at 1 week of age were retrospectively compared. RESULTS: In the SGA infants, IGF-1 levels (27.6 ± 17.7 vs. 42.6 ± 15 ng/ml, p = 0.006), aortic strain (10.2 ± 3.1 vs. 12.8 ± 3.1%, p = 0.01), and aortic distensibility (0.73 ± 0.19 vs. 0.92 ± 0.34 cm2/dyn × 10-4, p = 0.05) were significantly lower compared with AGA infants. By contrast, blood pressure, aortic intima-media thickness (aIMT) in relation to body weight (383 ± 163 vs. 256 ± 43 µm/kg, p < 0.001), aortic stiffness index in relation to body weight (2.0 ± 1.7 vs. 1.1 ± 0.4, p = 0.005), and arterial pressure-strain elastic modulus (293 ± 72 vs. 242 ± 78 mm Hg, p = 0.04) were higher compared with AGA infants. In the SGA infants, IGF-1 levels were significantly correlated with aortic strain (r = 0.49, p = 0.04), aIMT in relation to body weight (r = -0.61, p = 0.007), and aortic stiffness index in relation to body weight (r = -0.63, p = 0.005). CONCLUSIONS: Decreased serum IGF-1 levels in SGA infants may affect the vascular compliance and structure of the central aorta.

Decreased Aortic Elasticity in Children With Marfan Syndrome or Loeys-Dietz Syndrome.

BACKGROUND: The characteristics of aortic elasticity are unclear in children with connective tissue disorders (CTDs) such as Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS), especially in those with a non-dilated aortic root (AoR). This study evaluated the aortic elasticity properties of pediatric MFS and LDS patients with either dilated or non-dilated AoR.Methods and Results:The 31 children with MFS or LDS were classified into dilated (Z score of AoR diameter ≥2.5; n=17) or non-dilated (Z score of AoR diameter <2.5; n=14) AoR groups and compared with controls. Using transthoracic echocardiography, we analyzed the aortic elasticity parameters of distensibility, strain, and stiffness index at the levels of the AoR, sinotubular junction, ascending aorta, and descending aorta. Aortic distensibility and strain were significantly lower in both test groups than in controls at the AoR level. The Z score of AoR diameter significantly correlated with aortic distensibility (R=-0.63, P<0.001), strain (R=-0.54, P=0.002), and stiffness index (R=0.52, P=0.002) in the patients' groups. Multivariate analysis revealed that aortic distensibility and the type of CTD were independently associated with AoR dilatation. CONCLUSIONS: Aortic elasticity at the level of the AoR may be decreased in children with MFS or LDS even before AoR dilatation progresses. Less aortic distensibility and CTD type are considered important parameters in estimating AoR dilatation in these patients. (Circ J 2016; 80: 2369-2375).