Prolonged Relaxation Research Articles

An end-to-end LSTM-Attention based framework for quasi-steady-state CEST prediction.

Chemical exchange saturation transfer (CEST)-magnetic resonance imaging (MRI) often takes prolonged saturation duration (Ts) and relaxation delay (Td) to reach the steady state, and yet the insufficiently long Ts and Td in actual experiments may underestimate the CEST measurement. In this study, we aimed to develop a deep learning-based model for quasi-steady-state (QUASS) prediction from non-steady-state CEST acquired in experiments, therefore overcoming the limitation of the CEST effect which needs prolonged saturation time to reach a steady state. To support network training, a multi-pool Bloch-McConnell equation was designed to derive wide-ranging simulated Z-spectra, so as to solve the problem of time and labor consumption in manual annotation work. Following this, we formulated a hybrid architecture of long short-term memory (LSTM)-Attention to improve the predictive ability. The multilayer perceptron, recurrent neural network, LSTM, gated recurrent unit, BiLSTM, and LSTM-Attention were included in comparative experiments of QUASS CEST prediction, and the best performance was obtained by the proposed LSTM-Attention model. In terms of the linear regression analysis, structural similarity index (SSIM), peak signal-to-noise ratio (PSNR), and mean-square error (MSE), the results of LSTM-Attention demonstrate that the coefficient of determination in the linear regression analysis was at least R2 = 0.9748 for six different representative frequency offsets, the mean values of prediction accuracies in terms of SSIM, PSNR and MSE were 0.9991, 49.6714, and 1.68 × 10-4 for all frequency offsets. It was concluded that the LSTM-Attention model enabled high-quality QUASS CEST prediction.

Study on interface engineering and chemical bonding of the ReS2@ZnO heterointerface for efficient charge transfer and nonlinear optical conversion efficiency.

Rhenium sulfide (ReS2) has emerged as a promising two-dimensional material, demonstrating broad-spectrum visible absorption properties that make it highly relevant for diverse optoelectronic applications. Manipulating and optimizing the pathway of photogenerated carriers play a pivotal role in enhancing the efficiency of charge separation and transfer in novel semiconductor composites. This study focuses on the strategic construction of a semiconductor heterostructure by synthesizing ZnO on vacancy-containing ReS2 (VRe-ReS2) through chemical bonding processes. The ingeniously engineered built-in electric field within the heterostructure effectively suppresses the recombination of photogenerated electron-hole pairs. A direct and well-established interfacial connection between VRe-ReS2 and ZnO is achieved through a robust Zn-S bond. This distinctive bond configuration leads to enhanced nonlinear optical conversion efficiency, attributed to shortened carrier migration distances and accelerated charge transfer rates. Furthermore, theoretical calculations unveil the superior chemical interactions between Re vacancies and sulfide moieties, facilitating the formation of Zn-S bonds. The photoluminescence (PL) intensity is increased by the formation of VRe-ReS2 and ZnO heterostructure and the PL quantum yield of VRe-ReS2 is improved. The intricate impact of the Zn-S bond on the nonlinear absorption behavior of the VRe-ReS2@ZnO heterostructure is systematically investigated using femtosecond Z-scan techniques. The charge transfer from ZnO to ReS2 defect levels induces a transition from saturable absorption to reverse saturable absorption in the VRe-ReS2@ZnO heterostructure. Transient absorption measurements further confirm the presence of the Zn-S bond between the interfaces, as evidenced by the prolonged relaxation time (τ3) in the VRe-ReS2@ZnO heterostructure. This study offers valuable insights into the rational construction of heterojunctions through tailored interfacial bonding and surface/interface charge transfer pathways. These endeavors facilitate the modulation of electron transfer dynamics, ultimately yielding superior nonlinear optical conversion efficiency and effective charge regulation in optoelectronic functional materials.

Constructing battery impedance spectroscopy using partial current in constant-voltage charging or partial relaxation voltage

Electrochemical impedance spectroscopy (EIS) is an important technique to measure the impedance of lithium-ion batteries. However, practical applications of this technique are hindered by various factors such as expensive equipment costs, prolonged battery relaxation time, and lengthy measurement time, posing significant challenges and limitations. Without the need of an impedance analyzer, this study presents a machine learning (ML) approach by utilizing the current signals in constant voltage (CV) charging or the relaxation voltage (RV) data after charging as the input to construct the complete impedance spectrum of a battery at its full capacity. To validate the robustness and reliability of this approach, various scenarios, including the changes in the data length, the sampling interval, and the ML model, are discussed. We demonstrate that with 600 s of input data, using the CV current yields a root mean square error (RMSE) of 0.84 mΩ, while the RV achieves an even lower RMSE of 0.69 mΩ. With an input data of as short as 30 s, the two respective RMSEs simply increase to 1.94 and 0.82 mΩ. Incorporating the voltage curve in constant current (CC) charging into estimation analysis shows that, with the same data length, both CC and RV inputs yield even more accurate predictions than CV data.

Multiparametric MRI of Knees in Collegiate Basketball Players: Associations With Morphological Abnormalities and Functional Deficits.

Rates of cartilage degeneration in asymptomatic elite basketball players are significantly higher compared with the general population due to excessive loads on the knee. Compositional quantitative magnetic resonance imaging (qMRI) techniques can identify local biochemical changes of macromolecules observed in cartilage degeneration. The purpose of this study was to utilize multiparametric qMRI to (1) quantify how T1ρ and T2 relaxation times differ based on the presence of anatomic abnormalities and (2) correlate T1ρ and T2 with self-reported functional deficits. It was hypothesized that prolonged relaxation times will be associated with knees with MRI-graded abnormalities and knees belonging to basketball players with greater self-reported functional deficits. Cross-sectional study; Level of evidence, 3. A total of 75 knees from National Collegiate Athletic Association Division I basketball players (40 female, 35 male) were included in this multicenter study. All players completed the Knee injury and Osteoarthritis Outcome Score (KOOS) and had bilateral knee MRI scans taken. T1ρ and T2 were calculated on a voxel-by-voxel basis. The cartilage surfaces were segmented into 6 compartments: lateral femoral condyle, lateral tibia, medial femoral condyle, medial tibia (MT), patella (PAT), and trochlea (TRO). Lesions from the MRI scans were graded for imaging abnormalities, and statistical parametric mapping was performed to study cross-sectional differences based on MRI scan grading of anatomic knee abnormalities. Pearson partial correlations between relaxation times and KOOS subscore values were computed, obtaining r value statistical parametric mappings and P value clusters. Knees without patellar tendinosis displayed significantly higher T1ρ in the PAT compared with those with patellar tendinosis (average percentage difference, 10.4%; P = .02). Significant prolongation of T1ρ was observed in the MT, TRO, and PAT of knees without compared with those with quadriceps tendinosis (average percentage difference, 12.7%, 13.3%, and 13.4%, respectively; P ≤ .05). A weak correlation was found between the KOOS-Symptoms subscale values and T1ρ/T2. Certain tissues that bear the brunt of impact developed tendinosis but spared cartilage degeneration. Whereas participants reported minimal functional deficits, their high-impact activities resulted in structural damage that may lead to osteoarthritis after their collegiate careers.

Longitudinal assessment of skeletal muscle functional mechanics in the DE50-MD dog model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD), caused by mutations in the dystrophin (DMD) gene, is associated with fatal muscle degeneration and atrophy. Patients with DMD have progressive reductions in skeletal muscle strength and resistance to eccentric muscle stretch. Using the DE50-MD dog model of DMD, we assessed tibiotarsal joint (TTJ) flexor and extensor force dynamics, and the resistance of dystrophic muscle to eccentric stretch. Male DE50-MD and wild-type (WT) dogs were analysed every 3 months until 18 months of age. There was an age-associated decline in eccentric contraction resistance in DE50-MD TTJ flexors that discriminated, with high statistical power, WT from DE50-MD individuals. For isometric contraction, at the majority of timepoints, DE50-MD dogs had lower maximum absolute and relative TTJ flexor force, reduced TTJ muscle contraction times and prolonged relaxation compared to those in WT dogs. Cranial tibial muscles, the primary TTJ flexor, of 18-month-old DE50-MD dogs had significant numbers of regenerating fibres as expected, but also fewer type I fibres and more hybrid fibres than those in WT dogs. We conclude that these parameters, in particular, the eccentric contraction decrement, could be used as objective outcome measures for pre-clinical assessment in DE50-MD dogs.

THE EFFECTIVENESS OF INTERPERSONAL PSYCHOTHERAPY FOR POSTTRAUMATIC STRESS DISORDER (PTSD)

Background:Interventions are required that give a lecture depression and post-traumatic stress disorder (PTSD) indications and social wellbeing.The Psychotherapies aimed at Chronic PTSD randomizedexperimentalestablish that three fourteen -week psychotherapies severelyfurthered patients with chronic posttraumatic stress disorder (PTSD). Earlierinvestigation has describedconstant follow-up assistances for prolonged exposure (PE) and relaxation therapy (RT), but few comparable data exist for interpersonal psychotherapy (IPT). Mode:Theassociated Interpersonal Psychotherapy-Trauma (IPT-T), an IPT adaptation for this residents and background, to Clinic Psychotherapy (CP). CP clinicians were free to implement the psychotherapy of choice. Women with a major depressive episode (MDE) and history of sexual abuse before eighteen were randomly assigned to IPT-T or CP. Outcomes were MDE remission, improved depression (Beck Depression Inventory, Hamilton Depression Rating Scale) and PTSD symptoms (Modified PTSD Symptom Scale), and developed social health (e.g., UCLA Loneliness Scale). Weighted generalized estimating equations were used to examine outcomes at eight (primary) and twenty (secondary) months post-randomization.Acute responders, defined a priori as _30% improved from baseline, were reconsidered after three-month no-treatment follow-up by independent evaluators using the Clinician-Administered PTSD Scale (CAPS). Conclusion:Evidence-based psychotherapies like IPT-T are desired in CMHCs, where several of the maximumexposed patients obtain treatment. By means ofas good asconclusions for depression, IPT-Ts superior developments in social wellbeing and PTSD symptoms are source for hopefulness. IPT-T should be appraised in dissemination trials.These are the first methodicalstatistics on follow-up responder position and perseverance of acute treatment assistances in patientsacceptanceseparate IPT for prolonged PTSD. Patients usually maintained gains across treatments, mutablemaximum in RT. Study boundariesembraceminor sample size and momentary follow-up interval. PTSD examination should service response and decreasestandards.

Synthesis of dynamic polymers by amino-yne click reaction using multifunctional amine

Covalent adaptable networks (CANs) have become sustainable alternatives to traditional thermosetting materials due to their powerful reprocessing and rearrangement capabilities. Therefore, developing and investigating reversible reactions that can be used in the construction of CANs is a popular research topic. Amino-yne click chemistry is known for its green characteristics—it is a catalyst-free and efficient reaction—and is widely applied in the synthesis of bio-organic molecules, but there have been few reports on CANs, especially multifunctional amine-based amino-yne click reactions. In this study, various CANs were synthesized via the amino-yne click reaction using multifunctional amines (diethylenetriamine (DETA), triethylenetetramine (TETA), tetraethylenepentamine (TEPA)), and they were compared with CANs that were prepared from a primary amine (tris(2-aminoethyl) amine (TREN) and a secondary amine (tris[2-(methylamino)ethyl]amine (TMEN)) under the same conditions. The results showed that H-DETA CANs exhibited the smallest glass transition temperature Tg (15 °C) and Young's modulus (105 MPa) because the crosslinker (DETA) contained a low content of primary amine and secondary amine, but its crosslinking density followed the trend of H-TMEN < H-DETA < H-TREN. In addition, the relaxation time, activation energy, and creep rate results for the CANs followed the same trend as the crosslinking density. With the increase in the secondary amine content of the multifunctional amines, the Tg of the CANs increased from 15 °C to 57 °C, the Young's modulus increased from 105 to 666 MPa, and the crosslinking density increased from 955 to 2690 mol/m3. Notably, the increase in the secondary amine content led to the weaker dynamics of the material, namely, prolonged relaxation time, increased activation energy, and decreased creep rate. This work also verified the dynamic exchange mechanism of the materials by the molecular model reaction and the amine solvent dissolution tests. Finally, hot-pressing experiments demonstrated the good plasticity and recovery ability of prepared CANs. This work provides an elegant path for preparing materials in energy and chemical fields such as coatings and rubber.

Polyimide films with ultralow dielectric loss for 5G applications: Influence and mechanism of ester groups in molecular chains

Polyimides are ideal candidates for 5G high-frequency communications due to their good thermal stability, mechanical properties and processability. However, the exploration of how to reduce their high-frequency dissipation factor (Df) remains an urgent and alluring challenge. Inspired by the molecular structure of liquid crystal polyester, which is insensitive to high-frequency electric fields, here we design two series of polyimides derived from diamines with multiple ester groups (AXEB, X = 1, 2 or 3) and 4,4′-(hexafluoroisopropylidene)diphthalic anhydride (6FDA) or p-phenylene bis (trimellitate anhydride) (TA2EB). We investigated the effects of ester number on the aggregation structure, water absorption, dielectric properties, heat resistance and mechanical properties of the polyimides and find that the Df of the multiple ester-containing polyimides decreases rapidly with increasing frequency and number of ester groups. Wide-angle X-ray diffraction analysis, polarized optical microscopy observations and molecular dynamics simulations show that the unique properties of these polyimides benefit from the tight packing of the molecular chain and the strong intermolecular interaction force caused by the ester group, as well as the resulting prolonged dipole relaxation time and the greatly reduced water absorption. Therefore, the polyimide films show extremely low Df values of 0.0030 for AXEB-6FDA and 0.0013 for AXEB-TA2EB. Furthermore, AXEB-TA2EB also shows excellent thermal stability, mechanical properties, electrical properties and permittivity. More importantly, their ultralow moisture rate (<0.83 %) ensures that the high-frequency Df remains stable in different humid environments, even after soaking in water. This method can also be extended to other polymers, thus providing a new strategy for the design of low dielectric loss materials.

The evaluation of fetal interventricular septum with M-mode and spectral tissue Doppler imaging in gestational diabetes mellitus: a case-control study.

To demonstrate possible functional changes in the frequently affected fetal interventricular septum (IVS) with spectral tissue Doppler imaging (TDI) and M-mode imaging to compare gestational diabetes mellitus (GDM) and control groups. A total of 63 pregnant women with GDM, 30 on diet (A1 GDM) and 33 on treated with insulin (A2 GDM), and 63 healthy pregnant women randomly selected and matched to the case group in the control group were included. The GDM fetuses had significantly thickened IVS, increased early diastole (E'), atrial contraction (A'), systole (S'), higher myocardial performance index (MPI'), prolonged isovolumetric relaxation time (IVRT'), shortened ejection time (ET'), and decreased septal annular plane systolic excursion (SAPSE) than the controls. The A2 GDM group fetuses had significantly thickened IVS, increased S' and shortened ET' than the A1 GDM group. In the GDM group, we found a significantly positive low correlation between glycated hemoglobin levels and maternal serum fasting glucose and one-hour postprandial glucose with fetal IVS thickness. We demonstrated a significantly negative low correlation between maternal serum one-hour postprandial glucose, glycated hemoglobin levels, and gestational weight gain with fetal IVS ET'. Fetal IVS diastolic and systolic functions were altered in the GDM group compared to controls, and systolic functions were altered in A2 GDM compared to A1 GDM. This may alert clinicians to possible cardiovascular diseases in the postnatal life, and early preventive strategies and long-term lifestyle changes may provide protection in fetuses with GDM.

Determinants of myocardial work indices in women.

By incorporating myocardial deformation and afterload, novel echocardiographic myocardial work indices appear to be advantageous compared to load-dependent left ventricular (LV) deformation analyses. As such, these indices may provide a more accurate and, above all, load-independent estimation of LV function in patients with chronically increased afterload. To date however, data on the relation of these indices to clinical and conventional echocardiographic parameters are scarce. Our aim was to evaluate the relationship between myocardial work indices and age, body mass index (BMI), NTproBNP, the clinical history of arterial hypertension and diastolic dysfunction as well as selected conventional echocardiographic parameters in women. We analyzed echocardiographic data of women included in the Berlin Female Risk Evaluation (BEFRI) trial. Global Work Index (GWI), Global Constructive Work (GCW), Global Wasted Work (GWW) and Global Work Efficiency (GWE) were calculated using commercially available software based on noninvasive pressure-strain loops. The impact of selected clinical and echocardiographic characteristics on myocardial work parameters was investigated by uni- and multivariate regression analyses. A total of 224 women were included in the final analysis. 155 of them were normotensive and 69 had a history of arterial hypertension. Diastolic dysfunction was more prevalent in subjects with arterial hypertension. Study participants with arterial hypertension showed higher GWI and GCW whereas GWW and GWE did not significantly differ between groups. GCW and GWW were lower and GWE higher in the presence of normal diastolic function. In multivariate regression analyses, arterial hypertension, LV GLS, and interventricular septal thickness were significantly associated with GWI. GCW showed significant associations with the clinical history of arterial hypertension, LV GLS, age and IVRT. Similarly, LV GLS, IVRT and mitral inflow E wave deceleration time were identified to be significant determinants of GWW and GWE. Our data confirm that, in a randomly selected sample of the general urban female population, myocardial work parameters are predominantly determined by LV GLS. In addition, the presence of arterial hypertension was identified to be a significant determinant of GWI and GCW, but not for GWW and GWE. Finally, a prolonged LV relaxation time was significantly associated with GWW and GWE, suggesting more wasted myocardial work and lower GWE values with increasing LV relaxation time.

Myocardial T1 mapping by cardiac magnetic resonance imaging shows early myocardial changes in treatment-naive patients with active rheumatoid arthritis and positive autoantibodies.

We aimed to study whether myocardial changes are already detectable by cardiac magnetic resonance (CMR) imaging at the time of rheumatoid arthritis (RA) diagnosis. This single-centre prospective study included 39 treatment-naive patients with early rheumatoid arthritis (ERA, symptom duration <1 year) without any history of heart disease, and 38 age- and sex-matched healthy volunteers. The disease severity was assessed with clinical evaluation (Disease Activity Score-28 for Rheumatoid Arthritis with CRP (DAS28-CRP) score) and serological testing (rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA)). The ERA patients were classified into group A (DAS28-CRP score ≥3.2, positive RF and ACPA; n=17) and group B (not fulfilling the group A criteria). The ERA patients and healthy controls underwent 1.5T CMR. Group A patients had significantly higher myocardial global T1 relaxation times than the healthy controls, 987 [965, 1003] ms vs. 979 [960, 991] ms (median [IQR]; p=0.041). A significant difference in T1 was found in the basal, mid inferior and mid anterolateral segments. In a multivariate analysis, prolonged global T1 relaxation time was independently associated with female sex (95% CI [5.62, 51.31] ms, p=0.016), and group A status (95% CI [4.65, 39.01] ms p=0.014). At the time of diagnosis, ERA patients with a higher disease activity (DAS28-CRP score ≥3.2) and both positive RF and ACPA showed prolonged T1 relaxation times in basal myocardial segments. These segments could be most susceptible to the development of myocardial fibrosis, and a segmental reporting style could be useful when estimating the first signs of myocardial fibrosis.

Polymer architecture effect on rheology and segmental dynamics in poly (methyl methacrylate)-silica nanocomposite melts.

Architecturally different polymer chains lead to fundamentally different rheological responses and internal dynamics, which can be utilized to rationalize advanced thermoplastic nanocomposites with tunable mechanical behavior. In this work, three model poly (methyl methacrylate) (PMMA) polymers with linear, bottlebrush, and star architectures with the same total molar mass were investigated in their neat form, and nanocomposites with well-dispersed silica nanoparticles using rheology and broadband dielectric spectroscopy (BDS). The master curves of the dynamic moduli obtained by time-temperature superposition (TTS) over the entire range from the Rouse regime to the terminal flow and a sequence of significantly different relaxation modes were observed for the samples with linear and branch chains. While linear chains form an entangled polymer network, the branched bottlebrush, and star chains show a viscoelastic response with no sign of rubbery entanglement plateau and a weak arm relaxation regime between Rouse and terminal flow, akin to other branched polymers. Moreover, branched chains showed a higher fragility index (m = 3.46 for the bottlebrush and 5.36 for the star) compared to linear chains (m = 3.29) due to dynamical heterogeneities induced by arm relaxation. The addition of nanoparticles affects only the terminal relaxation regime, where the whole chain motion is hindered by the attractive nanoparticles. The dynamics of the polymer segment were investigated by performing broadband dielectric spectroscopy (BDS) at a frequency range from 10-2 Hz to 107 Hz. The results revealed more than 10 times slower segmental relaxation for the star homopolymers and a slowdown in the α-relaxation process for all three architectures in their composite form. The dynamical slowdown in the composites is temperature dependent and more pronounced at low temperatures (leading to approximately equal to 80 times slower dynamics for nanocomposite with bottlebrush PMMA at 150 °C) due to prolonged relaxation of the interfacial polymer compared to the matrix chains. The results from this study have practical applications in fields such as gas separation and polymeric electrolyte membranes, where simultaneous improvement of segmental mobility and mechanical moduli is highly desired.

Abstract P3185: ATP Citrate Lyase Regulates Cardiomyocyte Function By Controlling Mitochondrial Reductive Stress

ATP citrate lyase (ACLY) is a cytosolic enzyme that converts citrate transported from the mitochondria into oxaloacetate and acetyl-CoA. It was recently reported to support a non-canonical TCA cycle, which is particularly important in immature and proliferating cells. Cardiomyocytes are both mature and non-proliferating and the role of ACLY in such cells is unknown. Using uniformly labeled C 13 glucose, we found that inhibiting ACLY using highly specific BMS-303141 (ACLY-I) significantly elevated M2 malate/M2 citrate ratio in adult cardiomyocytes in 1 hour, indicating their engagement in a non-canonical TCA cycle. In isolated hearts (Langendorff), we found both dP/dt max and dP/dt min markedly depressed after 40 minutes of ACLY-I. Isolated adult myocytes exposed to 1 hour of ACLY-I had depressed sarcomere shortening and prolonged relaxation. Reactive oxygen species was unchanged. BMS303141 at &gt;10 μM was cardiotoxic while concentrations up to 50μM are not toxic in cardiac fibroblasts or hepatocytes. Untargeted metabolomics from ACLY-I treated hearts found significant decreases in TCA cycle intermediates citrate and α-ketoglutarate, accompanied by reduction in ATP production despite accumulation of NADH. The NAD/NADH ratio was reduced after 1-hr ACLY-I in cardiomyocytes, supporting its induction of reductive stress. Consistent with this, lactate was increased perhaps as a mechanism to oxidize NADH and alleviate reductive stress. These results have translational importance, as we find in human heart failure biopsies that ACLY is significantly downregulated at both transcript and protein levels. This finding is inversely related to body mass index, raising the hypothesis that exposure to high fat diet may reduce ACLY levels. This was tested in adult cardiomyocytes isolated from hearts 4 weeks after transaortic constriction and then treated with palmitate and oleate. ACLY mRNA declined post fatty acid treatment and paralleled a decline in ACLY promoter activity. These results identify a critical role of ACLY in normal myocyte NAD/NADH balance and mitochondrial function. ACLY reduction in heart failure particularly with obesity (e.g. heart failure with preserved ejection fraction) suggests a potentially new metabolic therapeutic target.

Dielectric Matching by the Unique Dynamic Dipoles in Hybrid Organic/Inorganic Superlattices toward Ultrathin Microwave Absorber.

There is an urgent demand of ultrathin high-performance microwave absorbing materials (MAMs) in the electromagnetic protection field. However, minimizing thickness is challenging mainly due to dielectric mismatch at high permittivity from excessive dielectric loss, leading to strong reflection at 2-18GHz. Here, a hybrid TaS2 /Co(Cp)2 superlattice is fabricated with alternating [TaS2 ] inorganic layers and [Co(Cp)2 ] organic layers. Dynamic Ta─Co dipoles offer a unique interfacial polarization relaxation mechanism involving the inversion and rotation of dynamic Ta─Co dipoles. The prolonged relaxation time of limited dynamic Ta─Co dipoles contributes to enhanced dielectric matching at high permittivity, which is essential for ultrathin high-performance MAMs. Furthermore, the confinement of paramagnetic Co(Cp)2 molecules in the interlayer space of the diamagnetic TaS2 sublattice triggers unexpected ferromagnetism via interfacial magnetic coupling conducive to the improved microwave-absorbing performance at reduced thickness. Therefore, it presents a 1.271-mm thick ultrathin absorber that can attenuate up to 99.99% of electromagnetic wave energy with a broad effective absorption bandwidth of 4.05GHz, thus pushing the limits of thickness of 2D-based high-performance MAMs. This paper demonstrates a new strategy toward ultrathin MAMs with tunable and decent electromagnetic loss derived from electrical and magnetic coupling at the atomic scale.

Cardiac Magnetic Resonance Relaxometry Parameters, Late Gadolinium Enhancement, and Feature-Tracking Myocardial Longitudinal Strain in Patients Recovered from COVID-19.

COVID-19 infection is associated with myocarditis, and cardiovascular magnetic resonance (CMR) is the reference non-invasive imaging modality for myocardial tissue characterization. Quantitative CMR techniques, such as feature tracking (FT) and left ventricular global longitudinal strain (GLS) analysis, have been introduced as promising diagnostic tools to improve the diagnostic accuracy of suspected myocarditis. The aim of this study was to analyze the left ventricular global longitudinal strain (GLS) and the influence of T1 and T2 relaxation times, ECV, and LGE appearance on GLS parameters in a multiparametric imaging protocol in patients who recovered from COVID-19. The 86 consecutive patients enrolled in the study had all recovered from mild or moderate COVID-19 infections; none required hospitalization. Their persistent symptoms and suspected myocarditis led to cardiac magnetic resonance imaging within 3 months of the diagnosis of the SARS-CoV-2 infection. Results: Patients with GLS less negative than -15% had significantly lower LVEF (53.6% ± 8.9 vs. 61.6% ± 4.8; <0.001) and were significantly more likely to have prolonged T1 (28.6% vs. 7.5%; p = 0.019). Left ventricular GLS correlated significantly with T1 (r = 0.303; p = 0.006) and LVEF (r = -0.732; p < 0.001). Left ventricular GLS less negative than -15% was 7.5 times more likely in patients with prolonged T1 (HR 7.62; 95% CI 1.25-46.64). The reduced basal inferolateral longitudinal strain had a significant impact on the global left ventricular longitudinal strain. ROC results suggested that a GLS of 14.5% predicted prolonged T1 relaxation time with the best sensitivity and specificity. Conclusions: CMR abnormalities, including a myocarditis pattern, are common in patients who have recovered from COVID-19. The CMR feature-tracking left ventricular GLS is related to T1 relaxation time and may serve as a novel parameter to detect global and regional myocardial injury and dysfunction in patients with suspected myocardial involvement after recovery from COVID-19.

Cardiovascular characterisation of a novel mouse model that combines hypertension and diabetes co-morbidities

Epidemiologic data suggest that the prevalence of hypertension in patients with diabetes mellitus is ∼1.5–2.0 times greater than in matched non-diabetic patients. This co-existent disease burden exacerbates cardiac and vascular injury, leading to structural and functional changes to the myocardium, impaired cardiac function and heart failure. Oxidative stress and persistent low-grade inflammation underlie both conditions, and are identified as major contributors to pathological cardiac remodelling. There is an urgent need for effective therapies that specifically target oxidative stress and inflammation to protect against cardiac remodelling. Animal models are a valuable tool for testing emerging therapeutics, however, there is a notable lack of appropriate animal models of co-morbid diabetes and hypertension. In this study, we describe a novel preclinical mouse model combining diabetes and hypertension to investigate cardiac and vascular pathology of co-morbid disease. Type 1 diabetes was induced in spontaneously hypertensive, 8-week old, male Schlager (BPH/2) mice via 5 consecutive, daily injections of streptozotocin (55 mg/kg in citrate buffer; i.p.). Non-diabetic mice received citrate buffer only. After 10 weeks of diabetes induction, cardiac function was assessed by echocardiography prior to post-mortem evaluation of cardiomyocyte hypertrophy, interstitial fibrosis and inflammation by histology, RT-PCR and flow cytometry. We focussed on the oxidative and inflammatory stress pathways that contribute to cardiovascular remodelling. In particular, we demonstrate that markers of inflammation (monocyte chemoattractant protein; MCP-1), oxidative stress (urinary 8-isoprostanes) and fibrosis (connective tissue growth factor; CTGF) are significantly increased, whilst diastolic dysfunction, as indicated by prolonged isovolumic relaxation time (IVRT), is elevated in this diabetic and hypertensive mouse model. In summary, this pre-clinical mouse model provides researchers with a tool to test therapeutic strategies unique to co-morbid diabetes and hypertension, thereby facilitating the emergence of novel therapeutics to combat the cardiovascular consequences of these debilitating co-morbidities.

(086) Phase II Study of AbobotulinumtoxinA in Patients with Provoked Vestibulodynia: Outcomes From Dose-finding Stage

Abstract Introduction Vulvodynia is associated with significant burden and impaired quality of life and affects up to 28% of women of reproductive age. The most common subtype is provoked vestibulodynia (PVD), in which pain is localized and triggered by vestibular contact. Treatment options are limited; no therapy is approved for PVD. Hypertonicity of the pelvic floor muscles is a common factor associated with PVD; therefore, patients may benefit from treatments that relax the pelvic floor. BotulinumtoxinA is used for prolonged muscle relaxation across multiple conditions. Current clinical data in patients with PVD are inconclusive, but off-label anecdotal use suggests benefit. Objective To assess the safety, efficacy, and optimal dosing of abobotulinumtoxinA (aboBoNT-A) for the treatment of PVD and explore the utility of a novel endpoint for pain assessment in PVD. Methods This phase II, randomized, placebo-controlled study (NCT03598777) comprised two steps: dose escalation (stage 1) and dose expansion (stage 2). Stage 1 included up to four treatment cycles; cycle 1 was double-blind, while cycles 2–4 were open-label. Patients were assessed for retreatment every 6 weeks. Enrolled premenopausal, adult women with PVD associated with pelvic-floor hypertonia were randomized 4:1 to receive aboBoNT-A (100 units [U] [n=8], 300 U [n=8], 400 U [n=14], and 500 U [n=17]) or placebo (n=13). A new efficacy endpoint was introduced, combining the use of eight vaginal dilators of increasing diameter and patient-reported pain in response to dilator insertion on an 11-point numeric rating scale (NRS) to derive a composite pain score. Based on the subjective pain threshold, the largest-sized dilator that the patient accepted was defined as the dilator maximum tested size (DMTS). Results Patients (aged 19–45 years; mean, 29.4 years) received aboBoNT-A or placebo. Baseline demographics and disease characteristics were well-balanced across treatment groups. All treatment-emergent adverse events (TEAEs) were mild or moderate. Among aboBoNT-A-treated patients, urinary incontinence occurred in one patient in cycle 1, one patient in cycle 2, and two patients in cycle 3. During cycle 1, treatment-related TEAEs occurred in patients receiving aboBoNT-A 500 U or placebo (3/17 patients and 1/13 patients, respectively), with none reported for doses &amp;lt;500 U. In terms of composite score for dilator test, there was a numerical trend for benefit with aboBoNT-A 300 U and a trend for increasing benefit with increasing number of injections. All women who received at least three active treatment cycles with aboBoNT-A had a decrease in dilator-induced pain from baseline of ≥30% and ≥2 points at week 6, as reported on the 11-point NRS. Efficacy and validity of the DMTS were not statistically analyzed owing to the sponsor’s decision to discontinue the trial (for reasons unrelated to efficacy or safety). Conclusions AboBoNT-A showed an acceptable safety profile in patients with PVD. Patients treated with multiple sequential cycles showed continued reductions in dilator-induced pain and NRS scores with repeated injections, suggesting a potential benefit of repeated aboBoNT-A treatment; trials assessing efficacy and validating DMTS are warranted to explore these findings. Disclosure Yes, this is sponsored by industry/sponsor: Ipsen Clarification: Industry initiated, executed and funded study Any of the authors act as a consultant, employee or shareholder of an industry for: Ipsen.

Hemodynamic Assessment in Takotsubo Syndrome

BackgroundTakotsubo syndrome (TTS) is a reversible form of heart failure with incompletely understood pathophysiology. ObjectivesThis study analyzed altered cardiac hemodynamics during TTS to elucidate underlying disease mechanisms. MethodsLeft ventricular (LV) pressure–volume loops were recorded in 24 consecutive patients with TTS and a control population of 20 participants without cardiovascular diseases. ResultsTTS was associated with impaired LV contractility (end-systolic elastance 1.74 mm Hg/mL vs 2.35 mm Hg/mL [P = 0.024]; maximal rate of change in systolic pressure over time 1,533 mm Hg/s vs 1,763 mm Hg/s [P = 0.031]; end-systolic volume at a pressure of 150 mm Hg, 77.3 mL vs 46.4 mL [P = 0.002]); and a shortened systolic period (286 ms vs 343 ms [P < 0.001]). In response, the pressure–volume diagram was shifted rightward with significantly increased LV end-diastolic (P = 0.031) and end-systolic (P < 0.001) volumes, which preserved LV stroke volume (P = 0.370) despite a lower LV ejection fraction (P < 0.001). Diastolic function was characterized by prolonged active relaxation (relaxation constant 69.5 ms vs 45.9 ms [P < 0.001]; minimal rate of change in diastolic pressure –1,457 mm Hg/s vs –2,192 mm Hg/s [P < 0.001]), whereas diastolic stiffness (1/compliance) was not affected during TTS (end-diastolic volume at a pressure of 15 mm Hg, 96.7 mL vs 109.0 mL [P = 0.942]). Mechanical efficiency was significantly reduced in TTS (P < 0.001) considering reduced stroke work (P = 0.001), increased potential energy (P = 0.036), and a similar total pressure–volume area compared with that of control subjects (P = 0.357). ConclusionsTTS is characterized by reduced cardiac contractility, a shortened systolic period, inefficient energetics, and prolonged active relaxation but unaltered diastolic passive stiffness. These findings may suggest decreased phosphorylation of myofilament proteins, which represents a potential therapeutic target in TTS. (Optimized Characterization of Takotsubo Syndrome by Obtaining Pressure Volume Loops [OCTOPUS]; NCT03726528)

Monodomain liquid crystal elastomer bionic muscle fibers with excellent mechanical and actuation properties

Monodomain liquid crystal elastomers (m-LCEs) exhibit large reversible deformations when subjected to light and heat stimuli. Herein, we developed a new method for the large-scale continuous preparation of m-LCE fibers. These m-LCE fibers exhibit a reversible contraction ratio of 55.6%, breaking strength of 162MPa (withstanding a load of 1 million times its weight), and maximum output power density of 1250J/kg, surpassing those of previously reported m-LCEs. These excellent mechanical properties are mainly attributed to the formation of a homogeneous molecular network. Furthermore, the fabrication of m-LCEs with permanent plasticity using m-LCEs with impermanent instability without external intervention was realized by the synergistic effects of the self-restraint of mesogens and the prolonged relaxation process of LCEs. The designed LCE fibers, which are similar to biological muscle fibers and can be easily integrated, exhibit broad application prospects in artificial muscles, soft robots, and micromechanical systems.

Surface and subsurface alterations in freshly fractured and corroded soda‐lime float glass

AbstractWe have investigated the corrosion behavior of the soda‐lime silicate float glass on freshly created active surfaces. The process of ion diffusion and ion exchange during surface corrosion is explained at the initial stages. We have reported a unique subsurface activity in the glass, which achieves equilibrium. This varies at the subsurface depth level of ≈ 10–30 nm and is visible as a broad peak in the elemental depth profile. The prolonged corrosion and heating process assists surface relaxation of the glass samples. We have observed the formation of active nucleation sites for the corrosion process on the surface. In this study, we report that the sodium ions and its corrosion compounds are decoupled from other metal ions present in the glass during diffusion relaxation and ion exchange. A combination of time of flight secondary ion mass spectrometry (TOF‐SIMS) and energy dispersive X‐ray (EDX) microanalysis help to explain the evolution and quantify the changes at the initial stages in the freshly formed glass surface.