Atrioventricular Longitudinal Mechanics Using Novel Speckle-Tracking Improved Risk Stratification Beyond Baseline Thyroid Hormone in Asymptomatic Subclinical Hypothyroidism.

BACKGROUND: Hypothyroidism is reportedly associated with increased cardiovascular risk and heart failure. We aimed to elucidate the mechanistic influence of atrio-ventricular deformations and their prognostic utilizations in asymptomatic subclinical hypothyroidism (SCH). METHODS: We assessed speckle-tracking of deformations among 4173 population-based asymptomatic individuals classified as euthyroid (0.25< thyroid-stimulating hormone [TSH] ≤4.0 µIU/mL, n=3799) or having mild (4< TSH ≤10.0 µIU/mL, n=349) or marked (TSH >10 µIU/mL, n=25) SCH. We further related deformational indices to outcomes of atrial fibrillation and heart failure. RESULTS: Despite borderline differences in indexed left ventricular mass and left atrial volume (P=0.054 and 0.051), those classified as mild and marked SCH presented with modest but significant reductions of global longitudinal strain, and showed elevated E/tissue Doppler imaging (TDI)-e', markedly diminished peak atrial longitudinal strain and higher left atrial stiffness (all P<0.05) when compared with euthyroid subjects. A higher TSH level was independently associated with reduced TDI-s'/TDI-e', worse global atrio-ventricular strains (global longitudinal strain/peak atrial longitudinal strain), elevated E/TDI-e', and worsened left atrial strain rate components (all P<0.05). Over a median 5.6 years (interquartile range, 4.7-6.5 years) follow-up, myocardial deformations yielded independent risk prediction using Cox regression in models adjusted for baseline covariates, N-terminal pro-brain natriuretic peptide, E/e', and treatment effect. Incorporation of global atrio-ventricular strain (global longitudinal strain/peak atrial longitudinal strain) and strain rates further showed improved risk reclassification when added to the baseline TSH strata (classified as euthyroid and mild and marked SCH; all P<0.05). Cox regression models remained significant with improved risk reclassification beyond TSH-based strata by using slightly different deformational cutoffs after excluding marked SCH group. CONCLUSIONS: Hypothyroidism, even when asymptomatic, may widely influence subclinical atrio-ventricular mechanical functions that may lead to higher heart failure and atrial fibrillation risk. We proposed the potential usefulness and prognostic utilization of myocardial strains in such population.

Effect of a Six-Week Core Conditioning as a Warm-Up Exercise in Physical Education Classes on Physical Fitness, Movement Capability, and Balance in School-Aged Children.

Whether the implementation of feasible, equipment-free, and simple core exercises in warm-up routines in physical education classes for school-aged children is beneficial remains unclear. Therefore, this study investigated the effects of a core conditioning in the warm-up routine of physical education classes on trunk muscular endurance, movement capability, and flexibility in this population. In these pre- and post-test control group experiments, 52 healthy, school-aged children (aged 10-11 years) were cluster randomized allocated to either the dynamic core exercise (DCE) group or general physical education (GPE) group. The DCE group performed a 10-min core exercise routine twice per week for six consecutive weeks; the GPE group performed traditional physical education warm-up exercises regularly. The children were assessed by conducting the trunk muscular endurance test (i.e., dynamic curl-up, static curl-up, plank, and lateral plank), functional movement screen (FMS), and single-leg balance test before and after the intervention. At the end of the intervention, the DCE group demonstrated a significant effect on trunk muscular endurance, movement capability (i.e., FMS scores), flexibility, and balance (each p < 0.001, effect size: 0.38-1.3). Furthermore, the DCE group showed significant improvements in all outcome measurements compared with the GPE group (p < 0.05, effect size: 0.29-1.68). These data may provide a reference for incorporating additional core stability exercises in the warm-up routine of physical education classes in school-aged children in the future.

Visceral Adiposity, Pro-Inflammatory Signaling and Vasculopathy in Metabolically Unhealthy Non-Obesity Phenotype.

The debate regarding the actual cardiovascular burden in metabolically healthy obese or metabolically unhealthy non-obesity individuals is ongoing. Accumulating data have suggested a unique pathophysiological role of pro-inflammatory cytokines in mediating metabolic and cardiovascular disorders by dysregulated visceral adiposity. To compare the burden of visceral adiposity, the inflammatory marker high-sensitivity C-reactive protein (hs-CRP) and the prevalent atherosclerotic burden in metabolically healthy obese (MHO) or metabolically unhealthy (MU) populations, were compared to those of metabolically healthy non-obesity subjects (MHNO). Coronary artery calcification score (CACS) and visceral fat, including pericardial fat (PCF)/thoracic peri-aortic fat (TAT), were quantified in 2846 asymptomatic subjects using a CT dataset. A cross-sectional analysis comparing CACS, inflammatory marker hs-CRP, and visceral fat burden among four obesity phenotypes (MHNO, metabolically unhealthy non-obesity (MUNO), MHO, and metabolically unhealthy obese (MUO)) was performed. Both MUNO and MUO demonstrated significantly higher hs-CRP and greater CACS than MHNO/MHO (adjusted coefficient: 25.46, 95% confidence interval (CI): 5.29-45.63; 43.55, 95% CI: 23.38-63.73 for MUNO and MUO (MHNO as reference); both p < 0.05). Visceral fat (PCF/TAT) was an independent determinant of MU and was similarly higher in the MUNO/MHO groups than in the MHNO group, with the MUO group having the largest amount. PCF/TAT, obesity, and MU remained significantly associated with higher CACS even after adjustment, with larger PCF/TAT modified effects for MU and diabetes in CACS (both pinteraction < 0.05). MU tightly linked to excessive visceral adiposity was a strong and independent risk factor for coronary atherosclerosis even in lean individuals, which could be partially explained by its coalignment with pathological pro-inflammatory signaling.

Malnutrition in acute heart failure with preserved ejection fraction: clinical correlates and prognostic implications.

AIMS: This study aimed to evaluate the prognostic significance of nutritional status in post-discharge Asians with heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: We examined the prognostic implications of body mass index (BMI) and nutritional markers among consecutive patients hospitalized for HFpEF. Nutritional metrics were estimated by serum albumin (SA), prognostic nutritional index (PNI), Controlling Nutritional Status (CONUT) score, and geriatric nutritional risk index. Among 1120 patients (mean age: 77.2 ± 12.6 years, 39.4% men), mean SA levels, PNI, CONUT scores, and geriatric nutritional risk index were 3.3 ± 0.6 g/dL, 40.2 ± 8.7, 5.5 ± 2.1, and 95.9 ± 14.5, respectively. Lean body size, higher white blood cell counts and C-reactive protein levels, anaemia, and lack of angiotensin blocker use were independently associated with malnutrition (defined by SA < 3.5 g/dL). Higher SA levels [hazard ratio (HR): 0.67 (95% confidence interval, CI: 0.53-0.85)], higher PNI [HR: 0.97 (95% CI: 0.95-0.99)], and higher geriatric nutritional risk index [HR: 0.98 (95% CI: 0.97-0.99)] (all P < 0.05) were all associated with longer survival, with higher CONUT score [HR: 1.08 (95% CI: 1.02-1.13)] exhibited higher mortality in Cox regression models and with higher SA levels/PNI but not BMI further contributing to the reduced rate of re-hospitalization (both P < 0.05). Categorizing BMI (25 kg/m2 as cut-off) and nutritional status showed significantly higher mortality rates among patients with lower BMI/malnutrition than among those with BMI/better nutrition (SA level, PNI, and CONUT score, all P < 0.01). Restricted cubic spline regression revealed a marked survival benefit of better nutrition with increasing BMI (adjusted Pinteraction for both SA level and PNI: <0.001; adjusted Pinteraction for CONUT score: 0.046). CONCLUSIONS: Malnutrition was frequently and strongly associated with systemic inflammation in Asian patients hospitalized for acute HFpEF. Our findings also indicate that nutrition may play a pivotal role in metabolic protection in this population.

Elucidating Potential Energy Surfaces for Singlet O2 Reactions with Protonated, Deprotonated, and Di-Deprotonated Cystine Using a Combination of Approximately Spin-Projected Density Functional Theory and Guided-Ion-Beam Mass Spectrometry.

The reactivity of cystine toward electronically excited singlet O2 (a1Δg) has been long debated, despite the fact that most organic disulfides are susceptible to oxidation by singlet O2. We report a combined experimental and computational study on reactions of singlet O2 with gas-phase cystine at different ionization and hydration states, aimed to determine reaction outcomes, mechanisms, and potential energy surfaces (PESs). Ion-molecule collisions of protonated and di-deprotonated cystine ions with singlet O2, in both the absence and the presence of a water ligand, were measured over a center-of-mass collision energy (Ecol) range from 0.1 to 1.0 eV, using a guided-ion-beam scattering tandem mass spectrometer. No oxidation was observed for these reactant ions except collision-induced dissociation at high energies. Guided by density functional theory (DFT)-calculated PESs, reaction coordinates were established to unravel the origin of the nonreactivity of cystine ions toward singlet O2. To account for mixed open- and closed-shell characters, singlet O2 and critical structures along reaction coordinates were evaluated using broken-symmetry, open-shell DFT with spin contamination errors removed by an approximate spin-projection method. It was found that collision of protonated cystine with singlet O2 follows a repulsive potential surface and possesses no chemically significant interaction and that collision-induced dissociation of protonated cystine is dominated by loss of water and CO. Collision of di-deprotonated cystine with singlet O2, on the other hand, forms a short-lived electrostatically bonded precursor complex at low Ecol. The latter may evolve to a covalently bonded persulfoxide, but the conversion is blocked by an activation barrier lying 0.39 eV above reactants. At high Ecol, C-S bond cleavage dominates the collision-induced dissociation of di-deprotonated cystine, leading to charge-separated fragmentation. Cross section for the ensuing fragment ion H2NCH(CO2-)CH2SS• was measured as a function of Ecol, and the mechanism of charge-separated fragmentation was discussed. It was also found that the reaction of deprotonated cystine with singlet O2 follows a similar mechanism as that of di-deprotonated cystine, but with an even higher activation barrier (0.72 eV).

Associations of the pre-pregnancy body mass index and gestational weight gain with pregnancy outcomes in Taiwanese women.

BACKGROUND: Pre-pregnancy weight and gestational weight gain (GWG) are important factors in both maternal and infant outcomes. Little information is available in relation to different levels of pre-pregnancy body mass index (BMI) and body weight gain on obstetric outcomes in Taiwan. This study investigated the associations between pregnancy complications with pre-pregnant BMI and GWG, in Taiwanese women. METHODS: Data were extracted from a delivery room information bank on all women delivering singleton babies in a medical center. Eight hundred and sixty pregnant women were included. The collected variables included basic information, GWG, and pregnancy and neonatal outcomes. Pregnant women were categorized according to their pre-pregnant BMI and GWG to evaluate the impacts of pre-pregnant BMI and maternal weight gain on the risk of pregnancy complications. Univariate and multivariable logistic regression analyses were performed, and odds ratios were calculated. RESULTS: Pre-pregnancy BMI>=24 kg/m2 increased the risks of gestational diabetes mellitus, preeclampsia, and preterm labor. Preeclampsia and Cesarean delivery were positively associated with high weight gains (>18 kg), whereas a low birth weight and preterm labor were strongly associated with low weight gains (<10 kg). A higher birth weight was found with a GWG of >14 kg in women who were underweight and normal weight before pregnancy. CONCLUSION: An appropriate maternal BMI (18.5-24 kg/m2) at conception followed by a suitable gestational weight gain (10-14 kg) has substantial impact on the overall health of pregnant women and would lead to better obstetric management for Taiwanese women.

J-coupling constants for a trialanine peptide as a function of dihedral angles calculated by density functional theory over the full Ramachandran space.

We present 13 (3)J, seven (2)J and four (1)J coupling constants (24 in all) calculated using B3LYP/D95** as a function of the φ and ψ Ramachandran dihedral angles of the acetyl(Ala)(3)NH(2) capped trialanine peptide over the entire Ramachandran space. With the exception of three of these J couplings, all show significant dependence upon both dihedral angles. For each J coupling considered, a two dimensional grid with respect to φ and ψ angles can be used to interpolate the values for any pair of φ and ψ values. Such simple interpolation is shown to be very accurate. Most of these calculated J couplings should prove useful for improving the accuracy of the determination of peptide and protein structures from NMR measurements in solution over that provided by the common procedure of treating the J couplings as functions of a single dihedral angle by means of Karplus-type fittings.