BACKGROUND: There is evidence that right ventricular (RV) contractile function, especially its coupling with the pulmonary circulation, has an important prognostic value in patients with left ventricular dysfunction.
OBJECTIVE: This study aimed to identify the best echocardiographic parameters of RV function and pulmonary artery systolic pressure (PASP) alone or in the form of the index of right ventricular-pulmonary artery coupling (RV-PA coupling) to determine the best predictor of 1-year major adverse cardiovascular events (MACE), which were defined as cardiovascular death and cardiac decompensation in heart failure patients with reduced ejection fraction (HFrEF).
RESULTS: The study enrolled 191 HFrEF patients (mean age 62.28 ± 12.79 years, 74% males, mean left ventricular ejection fraction (LVEF) 25.53 ± 6.87%). All patients underwent clinical, laboratory, and transthoracic echocardiographic (TTE) evaluation, focusing on assessing RV function and non-invasive parameters of RV-PA coupling. RV function was evaluated using fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE), and peak tricuspid annular systolic velocity (TAS\'). PASP was estimated by peak tricuspid regurgitation velocity (TRVmax) and corrected by assumed right atrial pressure relative to the dimension and collapsibility of the inferior vena cava. The TAPSE/PASP and TAS\'/PASP ratios were taken as an index of RV-PA coupling. During the follow-up (mean period of 340 ± 84 days), 58.1% of patients met the composite endpoint. The independent predictors of one-year outcome were shown to be advanced age, atrial fibrillation, indexed left atrial systolic volume (LAVI), LVEF, TAPSE/PASP, and TAS\'/PASP. TAS\'/PASP emerged as the strongest independent predictor of prognosis, with a hazard ratio (HR) of 0.67 (0.531-0.840), p < 0.001. Reconstructing the ROC curve 0.8 (0.723-0.859), p < 0.001, we obtained a threshold value of TAS\'/PASP ≤ 0.19 (cm/s/mm Hg) (sensitivity 74.0, specificity 75.2). Patients with TAS\'/RVSP ≤ 0.19 have a worse prognosis (Log Rank p < 0.001).
CONCLUSIONS: This study confirmed previously known independent predictors of adverse outcomes in patients with HfrEF-advanced age, atrial fibrillation, LAVI, and LVEF-but non-invasive parameters of RV-PA coupling TAPSE/PASP and TAS\'/PASP improved risk stratification in patients with HFrEF. Variable TAS\'/PASP has been shown to be the most powerful, independent predictor of one-year outcome.

This study aimed to determine the patterns of changes in structure, function, and cognitive ability in early-onset and late-onset older adults with focal epilepsy (OFE). This study first utilized the deformation-based morphometry analysis to identify structural abnormalities, which were used as the seed region to investigate the functional connectivity with the whole brain. Next, a correlation analysis was performed between the altered imaging findings and neuropsychiatry assessments. Finally, the potential role of structural-functional abnormalities in the diagnosis of epilepsy was further explored by using mediation analysis. Compared with healthy controls (n = 28), the area of reduced structural volume was concentrated in the bilateral cerebellum, right thalamus, and right middle cingulate cortex, with frontal, temporal, and occipital lobes also affected in early-onset focal epilepsy (n = 26), while late-onset patients (n = 31) displayed cerebellar, thalamic, and cingulate atrophy. Furthermore, correlation analyses suggest an association between structural abnormalities and cognitive assessments. Dysfunctional connectivity in the cerebellum, cingulate cortex, and frontal gyrus partially mediates the relationship between structural abnormalities and the diagnosis of early-onset focal epilepsy. This study identified structural and functional abnormalities in early-onset and late-onset focal epilepsy and explored characters in cognitive performance. Structural-functional coupling may play a potential role in the diagnosis of epilepsy.

OBJECTIVE: Coupling of sleep spindles with cortical slow waves and hippocampus sharp-waves ripples is crucial for sleep-related memory consolidation. Recent literature evidenced that nasal respiration modulates neural activity in large-scale brain networks. In rodents, this respiratory drive strongly varies according to vigilance states. Whether sleep oscillations are also respiration-modulated in humans remains open. In this work, we investigated the influence of breathing on sleep spindles during non-rapid-eye-movement sleep in humans.
METHODS: Full night polysomnography of twenty healthy participants were analysed. Spindles and slow waves were automatically detected during N2 and N3 stages. Spindle-related sigma power as well as spindle and slow wave events were analysed according to the respiratory phase.
RESULTS: We found a significant coupling between both slow and fast spindles and the respiration cycle, with enhanced sigma activity and occurrence probability of spindles during the middle part of the expiration phase. A different coupling was observed for slow waves negative peaks which were rather distributed around the two respiration phase transitions.
CONCLUSIONS: Our findings suggest that breathing cycle influences the dynamics of brain activity during non-rapid-eye-movement sleep.
CONCLUSIONS: This coupling may enable sleep spindles to synchronize with other sleep oscillations and facilitate information transfer between distributed brain networks.

OBJECTIVE: Spinocerebellar Ataxia Type 3 (SCA3) is a rare genetic ataxia that impacts the entire brain and is characterized as a neurodegenerative disorder affecting the neural network. This study explores how alterations in the functional hierarchy, connectivity, and structural changes within specific brain regions significantly contribute to the heterogeneity of symptom manifestations in patients with SCA3.
METHODS: We prospectively recruited 51 patients with SCA3 and 59 age-and sex-matched healthy controls. All participants underwent comprehensive multimodal neuroimaging and clinical assessments. In SCA3 patients, an innovative approach utilizing gradients in resting-state functional connectivity (FC) was employed to examine atypical patterns of hierarchical processing topology from sensorimotor to supramodal regions in the cerebellum and cerebrum. Coupling analyses of abnormal FC and structural connectivity among regions of interest (ROIs) in the brain were also performed to characterize connectivity alterations. Additionally, relationships between quantitative ROI values and clinical variables were explored.
RESULTS: Patients with SCA3 exhibited either compression or expansion within the primary sensorimotor-to-supramodal gradient through four distinct calculation methods, along with disruptions in FC and structural connectivity coupling. A comprehensive correlation was identified between the altered gradients and the clinical manifestations observed in patients. Notably, altered fractional anisotropy values were not significantly correlated with clinical variables.
CONCLUSIONS: Abnormal gradients and connectivity in the cerebellar and cerebral cortices in SCA3 patients may contribute to disrupted motor-to-supramodal functions. Moreover, these findings support the potential utility of FCG analysis as a biomarker for diagnosing SCA3 and assessing treatment efficacy.

The aim of the present study was to compare the coordination patterns and levels of coordination variability of healthy and injured runners with iliotibial band syndrome (ITBS). Sixty runners divided into four groups (15 healthy males, 15 healthy females, 15 males with ITBS and 15 females with ITBS) ran at a steady and freely chosen pace on an over-ground track, and their coordination patterns of the lower limbs were calculated during 10 running stances using the vector coding technique. Both male and female runners with ITBS showed a greater dominance of the pelvis segment and the anti-phase patterns in the frontal plane thigh-pelvis coupling (p = 0.001, η2 = 0.36). In addition, injured female runners showed a greater hip adduction dominance, whereas injured males presented a greater anti-phase pattern in the transverse plane-frontal plane hip coupling (p = 0.003, η2 = 0.08). The levels of coordination variability during running stance did not change between ITBS injured and healthy runners in any of the couplings. Currently injured runners with ITBS appeared to present altered coordination patterns on the hip couplings that were partly dependent on gender but did not lead to changes in the coordination variability levels.

Coupling, the mechanism that controls the sequence of events in bone remodelling, is a fundamental theory for understanding the way the skeleton changes throughout life. This review is an adapted version of the Louis V Avioli lecture, delivered at the Annual Scientific Meeting of the American Society of Bone and Mineral Research. It outlines the history of the coupling concept and details how coupling occurs within trabecular and cortical bone and describes its multiple contexts and the many mechanisms suggested to couple bone forming osteoblasts to the prior action of osteoclasts on the same bone surface. These mechanisms include signals produced at each stage of the remodelling sequence (resorption, reversal, and formation), such as factors released by osteoclasts through their resorptive action and through protein synthesis, molecules deposited in the cement line during the reversal phase, and potentially signals from osteocytes within the local bone environment. The review highlights two examples of coupling factors (Cardiotrophin 1 and EphrinB2:EphB4) to illustrate the limited data available, and the need to integrate both the many functions of these factors within the basic multicellular unit (BMU), and the multiple origins of these factors, including other cell types present during the remodelling sequence (such as osteocytes, macrophages, endothelial cells, and T-cells).
Coupling is a fundamental process by which bone resorbing cells (osteoclasts) are followed by bone forming cells (osteoblasts) on the same surface during the process of bone remodelling. This review outlines the history, basic concepts, and mechanisms proposed, and suggests directions for further research into the way this sequence of events in controlled in bone maintenance, development, and healing.

Within-individual coupling between measures of brain structure and function evolves in development and may underlie differential risk for neuropsychiatric disorders. Despite increasing interest in the development of structure-function relationships, rigorous methods to quantify and test individual differences in coupling remain nascent. In this article, we explore and address gaps in approaches for testing and spatially localizing individual differences in intermodal coupling. We propose a new method, called CIDeR, which is designed to simultaneously perform hypothesis testing in a way that limits false positive results and improve detection of true positive results. Through a comparison across different approaches to testing individual differences in intermodal coupling, we delineate subtle differences in the hypotheses they test, which may ultimately lead researchers to arrive at different results. Finally, we illustrate the utility of CIDeR in two applications to brain development using data from the Philadelphia Neurodevelopmental Cohort.

BACKGROUND: Coupling between left ventricle (LV) and left atrium (LA) plays a central role in the process of cardiac remodeling during aging and development of cardiac disease. The hydraulic force (HyF) is related to variation in size between LV and LA. The objectives of this study were to: (1) derive an estimate of left atrioventricular HyF using cine- Magnetic Resonance Imaging (MRI) in healthy subjects with a wide age range, and (2) study its relationship with age and conventional diastolic function parameters, as estimated by reference echocardiography.
METHODS: We studied 119 healthy volunteers (mean age 44 ± 17 years, 58 women) who underwent Doppler echocardiography and MRI on the same day. Conventional transmitral flow early (E) and late (A) LV filling peak velocities as well as mitral annulus diastolic longitudinal peak velocity (E\') were derived from echocardiography. MRI cine SSFP images in longitudinal two and four chamber views were acquired, and analyzed using feature tracking (FT) software. In addition to conventional LV and LA strain measurements, FT-derived LV and LA contours were further used to calculate chamber cross-sectional areas. HyF was approximated as the difference between the LV and LA maximal cross-sectional areas in the diastasis phase corresponding to the lowest LV-LA pressure gradient. Univariate and multivariate analyses while adjusting for appropriate variables were used to study the associations between HyF and age as well as diastolic function and strain indices.
RESULTS: HyF decreased significantly with age (R²=0.34, p < 0.0001). In addition, HyF was significantly associated with conventional indices of diastolic function and LA strain: E/A: R²=0.24, p < 0.0001; E\': R²=0.24, p < 0.0001; E/E\': R²=0.12, p = 0.0004; LA conduit longitudinal strain: R²=0.27, p < 0.0001. In multivariate analysis, associations with E/A (R2 = 0.39, p = 0.03) and LA conduit strain (R2 = 0.37, p = 0.02) remained significant after adjustment for age, sex, and body mass index.
CONCLUSIONS: HyF, estimated using FT contours, which are primarily used to quantify LV/LA strain on standard cardiac cine MRI, varied significantly with age in association with subclinical changes in ventricular filling. Its usefulness in cohorts of patients with left heart disease to detect LV-LA uncoupling remains to be evaluated.

Balance control is an important indicator of mobility and independence in activities of daily living. How the functional coupling between the cortex and the muscle for balance control is affected following stroke remains to be known. We investigated the changes in coupling between the cortex and leg muscles during a challenging balance task over multiple frequency bands in chronic stroke survivors. Fourteen participants with stroke and ten healthy controls performed a challenging balance task. They stood on a computerized support surface that was either fixed (low difficulty condition) or sway-referenced with varying gain (medium and high difficulty conditions). We computed corticomuscular coherence between electrodes placed over the sensorimotor area (electroencephalography) and leg muscles (electromyography) and assessed balance performance using clinical and laboratory-based tests. We found significantly lower delta frequency band coherence in stroke participants when compared with healthy controls under medium difficulty condition, but not during low and high difficulty conditions. These differences were found for most of the distal but not for proximal leg muscle groups. No differences were found at other frequency bands. Participants with stroke showed poor balance clinical scores when compared with healthy controls, but no differences were found for laboratory-based tests. The observation of effects at distal but not at proximal muscle groups suggests differences in the (re)organization of the descending connections across two muscle groups for balance control. We argue that the observed group difference in delta band coherence indicates balance context-dependent alteration in mechanisms for the detection of somatosensory modulation resulting from sway-referencing of the support surface for balance maintenance following stroke.

1,2-Dihydroisoquinolines are important compounds due to their biological and medicinal activities, and numerous approaches to their synthesis have been reported. Recently, we reported a facile synthesis of trisubstituted allenamides via N-acetylation followed by DBU-promoted isomerization, where various substituted allenamides were conveniently synthesized from readily available propargylamines with high efficiency. In light of this research background, we focused on the utility of this methodology for the synthesis of substituted 1,2-dihydroisoquinolines. In this study, a palladium-catalyzed cascade cyclization-coupling of trisubstituted allenamides containing a bromoaryl moiety with arylboronic acids is described. When N-acetyl diphenyl-substituted trisubstituted allenamide and phenylboronic acid were treated with 10 mol% of Pd(OAc)2, 20 mol% of P(o-tolyl)3, and 5 equivalents of NaOH in dioxane/H2O (4/1) at 80 °C, the reaction proceeded to afford a substituted 1,2-dihydroisoquinoline. The reaction proceeded via intramolecular cyclization, followed by transmetallation with the arylboronic acid of the resulting allylpalladium intermediate. A variety of highly substituted 1,2-dihydroisoquinolines were concisely obtained using this methodology because the allenamides, as reaction substrates, were prepared from readily available propargylamines in one step.