Prolonged Relaxation Time Research Articles

Patellofemoral Cartilage Lesions Treated With Particulated Juvenile Allograft Cartilage: A Prospective Study With Minimum 2-Year Clinical and Magnetic Resonance Imaging Outcomes

To analyze the functional outcomes of patients treated with particulated juvenile articular cartilage (PJAC) for symptomatic articular cartilage lesions in the patellofemoral joint, correlates clinical outcomes with magnetic resonance imaging (MRI) appearance of the repair tissue using cartilage-sensitive quantitative T2-mapping. All patients treated with PJAC for patellofemoral lesions were identified and prospectively followed with clinical outcome scores (International Knee Documentation Committee [IKDC], Knee Outcome Survey-Activities of Daily Living [KOS-ADL], and Marx Activity Scale [MAS]). Postoperative MRI scans using quantitative T2 mapping were obtained and interpreted by an independent musculoskeletal radiologist. Twenty-seven patients treated with PJAC for 30 full-thickness patellofemoral cartilage lesions were identified; mean postoperative follow-up was 3.84years. Improvements from pre- to postoperative mean IKDC (45.9 vs 71.2, P < .001) and KOS-ADL (60.7 vs 78.8, P < .001) scores were observed; no significant change in MAS was seen (7.04 vs 7.17, P= .97). Advanced age, history of previous surgery, lesion location (patella vs trochlea), or concomitant tibial tubercle osteotomy did not affect outcome scores. Greater body mass index was associated with less improvement in KOS-ADL score. No patients required reoperation for graft-related issues. Lesion fill exceeding 67% by MRI assessment was noted in 69.2% of lesions; depth of lesion fill did not correlate with clinical outcomes. Quantitative T2-mapping revealed prolonged relaxation time at the graft site compared with adjacent normal cartilage at both deep and superficial zones. This study found significantly improved pain and function in patients treated with PJAC for symptomatic patellofemoral articular cartilage defects. No patients required reoperation for graft-related issues. Postoperative MRI revealed majority lesion fill in more than 69% of patients, but persistent morphologic differences between graft site and normal adjacent cartilage remain. Though we support PJAC use in this setting to improve patient subjective outcomes, improved appearance on postoperative imaging was not found to provide additional clinical benefit. Level IV, case series.

Characterization of brain tumours with spin-spin relaxation: pilot case study reveals unique T 2 distribution profiles of glioblastoma, oligodendroglioma and meningioma.

Prolonged spin-spin relaxation times in tumour tissue have been observed since some of the earliest nuclear magnetic resonance investigations of the brain. Over the last three decades, numerous studies have sought to characterize tumour morphology and malignancy using quantitative assessment of T 2 relaxation times, although attempts to categorize and differentiate tumours have had limited success. However, previous work must be interpreted with caution as relaxation data were typically acquired using a variety of multiple echo sequences with a range of echoes and T 2 decay curves and were frequently fit with monoexponential analysis. We defined the distribution of T 2 components in three different human brain tumours (glioblastoma, oligodendroglioma, meningioma) using a multi-echo sequence with a greater number of echoes and a longer acquisition window than previously used (48 echoes, data collection out to 1120ms) with no a priori assumptions about the number of exponential components contributing to the T 2 decay. T 2 relaxation times were increased in tumour tissue and each tumour showed a distinct T 2 distribution profile. Tumours have complex and unique compartmentalization characteristics. Quantitative assessment of T 2 relaxation in brain cancer may be useful in evaluating different grades of brain tumours on the basis of their T 2 distribution profile, and has the potential to be a non-invasive diagnostic tool which may also be useful in monitoring therapy. Further study with a larger sample size and varying grades of tumours is warranted.

Prolonged spin relaxation time in Zn-doped GaAs/GaAsP strain-compensated superlattice

A GaAs/GaAsP strain-compensated superlattice (SL) is a highly promising spin-polarized electron source. To realize higher quantum efficiency, it is necessary to consider spin relaxation mechanisms. We have investigated the electron spin relaxation time in a Zn-doped GaAs/GaAsP strain-compensated SL by time-resolved spin-dependent pump and probe reflection measurements. The long spin relaxation time of 104 ps was observed at room temperature (RT), which is about three times longer than that of conventional undoped GaAs multiple quantum wells. Even when the excitation power increases from 30 to 110 mW, the change in the spin relaxation time at RT was small. This relationship implies that the intensity of the electron beam can be increased without affecting the spin relaxation time. These results indicate that a Zn-doped GaAs/GaAsP strain-compensated SL has the great advantage for use as a spin-polarized electron source.

Assessment of Cardiac Function in Fetuses of Gestational Diabetic Mothers During the Second Trimester.

Fetuses of diabetic mothers may have structural or functional cardiac abnormalities which increase morbidity and mortality. Isolated functional abnormalities have been identified in the third trimester. The aim of the present study was to assess fetal cardiac function (systolic, diastolic, and global myocardial performance) in the second trimester in mothers with gestational diabetes, and also to relate cardiac function with glycemic control. Mothers with gestational diabetes mellitus referred for fetal cardiac evaluation in the second trimester (between 19 and 24 weeks) from March 2015 to February 2016 were enrolled as case subjects in this study. Non-diabetic mothers who had a fetal echocardiogram done between 19 and 24 weeks for other indications were enrolled as controls. Functional cardiac variables showed a statistically significant difference in isovolumetric relaxation and contraction times and the myocardial performance index and mitral E/A ratios in the gestational diabetic group (p = 0.003). Mitral annular plane systolic excursion was significantly less in the diabetic group (p = 0.01). The only functional cardiac variable found abnormal in mothers with poor glycemic control was the prolonged isovolumetric relaxation time. Functional cardiac abnormalities can be detected in the second trimester in fetuses of gestational diabetic mothers and timely intervention can improve postnatal outcomes.

Effects of Surgical Factors on Cartilage Can Be Detected Using Quantitative Magnetic Resonance Imaging After Anterior Cruciate Ligament Reconstruction

Background: Quantitative magnetic resonance (qMR) can be used to measure macromolecules in tissues and is a potential method of observing early cartilage changes in the development of posttraumatic osteoarthritis. Hypothesis/Purpose: We hypothesized that specific patient and surgical factors affecting cartilage matrix composition after anterior cruciate ligament (ACL) reconstruction (ACLR) can be detected using T1ρ and T2 relaxation times. Our purpose was to demonstrate this ability in a multicenter feasibility study. Study Design: Case series; Level of evidence, 4. Methods: A total of 54 patients who underwent ACLR underwent bilateral MRI at baseline before surgery and 6 months postoperatively. Operative findings were recorded. T1ρ and T2 relaxation times were calculated for 6 cartilage regions: the medial femur, lateral femur, medial tibia, lateral tibia, patella, and trochlea. A paired t test compared relaxation times at baseline and 6 months, univariate regression identified regions that influenced patient-reported outcome measures, and analysis of covariance was used to determine the surgical factors that resulted in elevated relaxation times at 6 months. Results: The injured knee had significantly prolonged T1ρ and T2 relaxation times in the tibiofemoral compartment at baseline and 6 months but had shorter values in the patellofemoral compartment compared with the uninjured knee. Prolonged T1ρ and T2 times at 6 months were noted for both the injured and uninjured knees. At 6 months, prolongation of T1ρ and T2 times in the tibial region was associated with lower patient-reported outcome measures. ACLR performed within 30 days of injury had significantly shorter T1ρ times in the tibial regions, and lateral meniscal tears treated with repair had significantly shorter T1ρ times than those treated with excision. Conclusion: Prolonged relaxation times in multiple regions demonstrate how the injury affects the entire joint after an ACL tear. Changes observed in the uninjured knee may be caused by increased loading during rehabilitation, especially in the patellofemoral articular cartilage and distal femur. Relaxation times in the tibial regions may be predictive of patient symptoms at 6 months. These same regions are affected by surgical timing as early as 30 days after injury, but this may partially be reflective of the severity of the preoperative injury and the choice of treatment of meniscal tears.

The effect of strain and age on the mechanical properties of rat Achilles tendons.

Achilles tendon (AT) ruptures are common in the middle age population; however, the pathophysiology and influence of age on AT ruptures is not fully understood. This study evaluates the effect and interactions between, strain and age on the in vitro biomechanical properties of ATs. Bilateral ATs were harvested from 17 young (8 months) and 14 middle-aged (24 months) rats and underwent stress-relaxation using Fung's quasilinear viscoelastic (QLV) modeling and load-to-failure testing. The initial viscoelastic response (parameter B) in middle-age animals was dependent on the amount of strain applied to the tendon and was significantly increased in middle-aged animals at higher strain. Higher strain in older animals led to a prolonged relaxation time (parameter tau 2). There was a trend toward an increased magnitude of the relaxation response (parameter C) at higher strain in the middle-aged animals. Middle-aged animals had a significantly lower mean stress at ultimate failure (p=0.01), while Young's modulus was similar in both groups (p=0.46). The passive biomechanical properties of the rat AT change with age and the influence stress-relaxation response of the AT, thereby possibly predisposing the AT of older animals to fail at lower loads compared to younger animals. Not applicable, this is a basic science study.

Prevention of the development of heart failure with preserved ejection fraction by the phosphodiesterase-5A inhibitor vardenafil in rats with type 2 diabetes.

AimsHeart failure with preserved ejection fraction (HFpEF) has a great epidemiological burden. The pathophysiological role of cyclic guanosine monophosphate (cGMP) signalling has been intensively investigated in HFpEF. Elevated levels of cGMP have been shown to exert cardioprotective effects in various cardiovascular diseases, including diabetic cardiomyopathy. We investigated the effect of long‐term preventive application of the phosphodiesterase‐5A (PDE5A) inhibitor vardenafil in diabetic cardiomyopathy‐associated HFpEF.Methods and resultsZucker diabetic fatty (ZDF) rats were used as a model of HFpEF and ZDF lean rats served as controls. Animals received vehicle or 10 mg/kg body weight vardenafil per os from weeks 7 to 32 of age. Cardiac function, morphology was assessed by left ventricular (LV) pressure–volume analysis and echocardiography at week 32. Cardiomyocyte force measurements were performed. The key markers of cGMP signalling, nitro‐oxidative stress, apoptosis, myocardial hypertrophy and fibrosis were examined. The ZDF animals showed diastolic dysfunction (increased LV/cardiomyocyte stiffness, prolonged LV relaxation time), preserved systolic performance, decreased myocardial cGMP level coupled with impaired protein kinase G (PKG) activity, increased nitro‐oxidative stress, enhanced cardiomyocyte apoptosis, and hypertrophic and fibrotic remodelling of the myocardium. Vardenafil effectively prevented the development of HFpEF by maintaining diastolic function (decreased LV/cardiomyocyte stiffness and LV relaxation time), by restoring cGMP levels and PKG activation, by lowering apoptosis and by alleviating nitro‐oxidative stress, myocardial hypertrophy and fibrotic remodelling.ConclusionsWe report that vardenafil successfully prevented the development of diabetes mellitus‐associated HFpEF. Thus, PDE5A inhibition as a preventive approach might be a promising option in the management of HFpEF patients with diabetes mellitus.

Prolongation of Relaxation Time in Extraocular Muscles With Brain Derived Neurotrophic Factor in Adult Rabbit.

PurposeWe tested the hypothesis that short-term treatment with brain derived neurotrophic factor (BDNF) would alter the contractile characteristics of rabbit extraocular muscle (EOM).MethodsOne week after injections of BDNF in adult rabbit superior rectus muscles, twitch properties were determined in treated and control muscles in vitro. Muscles were also examined for changes in mean cross-sectional areas, neuromuscular junction size, and percent of myofibers expressing specific myosin heavy chain isoforms, and sarcoendoplasmic reticulum calcium ATPases (SERCA) 1 and 2.ResultsBrain derived neurotrophic factor–treated muscles had prolonged relaxation times compared with control muscles. Time to 50% relaxation, time to 100% relaxation, and maximum rate of relaxation were increased by 24%, 27%, and 25%, respectively. No significant differences were seen in time to peak force, twitch force, or maximum rate of contraction. Brain derived neurotrophic factor treatment significantly increased mean cross-sectional areas of slow twitch and tonic myofibers, with increased areas ranging from 54% to 146%. Brain derived neurotrophic factor also resulted in an increased percentage of slow twitch myofibers in the orbital layers, ranging from 54% to 77%, and slow-tonic myofibers, ranging from 44% to 62%. No significant changes were seen SERCA1 or 2 expression or in neuromuscular junction size.ConclusionsShort-term treatment with BDNF significantly prolonged the duration and rate of relaxation time and increased expression of both slow-twitch and slow-tonic myosin-expressing myofibers without changes in neuromuscular junctions or SERCA expression. The changes induced by BDNF treatment might have potential therapeutic value in dampening/reducing uncontrolled eye oscillations in nystagmus.

Feasibility of fat fraction quantification by measuring J-coupling related signal modulation in multi echo fast spin echo sequences

Introduction Echo spacing in Fast Spin Echo techniques can affect signal intensity mainly of fatty tissue and is presented as effectively prolonged T2 relaxation time (magnetic fat liquefaction). Purpose The aim of this study is to measure signal intensity in multi echo Fast Spin Echo techniques with variable echo spacing in order to examine the feasibility of fat quantification from J-coupling related signal modulation. T2 maps were calculated from all different acquisition schemes. Materials and methods A phantom containing porcine fat, vegetable oils, gadolinium doped agarose gels that mimic fat magnetic relaxation properties, double distilled water at controlled temperature of 36–38 °C was scanned at 1.5 T utilizing a single slice multi echo SE technique with equidistant echoes of variable TE intervals (6.7–40 ms). Results Fat signal modulation as a function of echo spacing varied significantly between short and long echo spacing acquisitions (28.97–56.26%) and this dependence could be approximated by a linear sequence ( Δ S fat = S short ESP - S long ESP = 3.38*n*TE + 27.18, residual 7,88 for n ranging from 1 to 12) for a wide range of routinely used TEs in clinical practice (13.4–160.8 ms) while effect on water was minimal ( Δ S water = 22.11%, SD for same TE range: 0.53). Difference of calculated T2 relaxation times between sequences with different echo spacing ranged from 9.5 to 35%. Conclusion Echo spacing in MESE sequences may serve as a metric of signal manipulation and fat quantification. Bright fat sequences should be avoided for T2 relaxation parametric maps.

Abstract 266: Is the Col4a3 -/- Alport Mouse a Novel Model for Heart Failure With Preserved Ejection Fraction?

Heart failure with preserved ejection fraction (HFpEF) accounts for more than 50% of all HF cases. HFpEF patients manifest normal or mildly reduced left ventricle (LV) ejection fraction (LVEF), LV hypertrophy, diastolic dysfunction, myocardial stiffness, cardiac fibrosis, hypertension, nephropathy and sudden death. There is no appropriate animal model for HFpEF. The Alport Col4a3 -/- mouse, a model of nephropathy, hypertension and early death, develops a cardiovascular pathology that is yet to be well characterized. We elected to analyze the cardiovascular pathology of the Alport mouse and investigate any commonalities with HFpEF. Male Alport and wild type (WT) littermates of mixed background at 2 months of age were subjected to echocardiographic and 2D speckle tracking analyses and heart tissues were used for histopathological examinations (N=6 mice per group). Circulating Galectin-3, a marker of HFpEF, was measured by Elisa in plasma samples. Data are shown as mean±SEM. Normalized heart weight increased in Alport relative to WT mice - p&lt;0.01, indicative of cardiac hypertrophy. Consistently, echocardiography showed interventricular septum (IVS) thickening -p&lt;0.05. Reduced stroke volume p&lt;0.01, and impaired global longitudinal and circumferential strain (GLS and GCS) indicated systolic dysfunction in Alport mice. No significant reduction in LVEF was observed. Alport mice developed diastolic dysfunction evidenced by a prolonged Isovolumetric relaxation time -P&lt;0.05, and a reduced E/A, a marker of LV relaxation and stiffness -p&lt;0.01. Elevated LV filling pressure and pulmonary artery wedge pressure were demonstrated by an increase in E/E’ - p&lt;0.01. Galectin-3 increased in Alport relative to WT plasma (P&lt;0.01). Alport hearts had more Fibronectin protein - P&lt;0.05 and increased number of fibroblasts with “activated” phenotype as demonstrated by increased mass of rough endoplasmic reticulum in EM cross sections. Our study suggests that the cardiovascular pathologies of the Alport mouse are similar to HFpEF, specifically preserved ejection fraction, diastolic dysfunction, hypertension, early death and cardiac stiffness and fibrosis. Further study of this multi-factorial pathology may render the Alport mouse as a useful novel model for HFpEF.

Abstract 85: Interactions Between Cardiac Myosin Binding Protein C and Actin Contribute to the Regulation of Cardiac Contraction

Cardiac myosin binding protein C (cMyBP-C) is a regulatory muscle protein that is essential for proper cardiac contraction, and mutations in cMyBP-C are commonly associated with hypertrophic cardiomyopathy. cMyBP-C not only interacts with myosin, but with actin as well. In vitro studies have demonstrated that multiple functions of cMyBP-C could readily be explained by an interaction between cMyBP-C and actin, but the in vivo significance of cMyBP-C binding to either myosin or actin is not well understood. Here we created transgenic mice with a single point mutation (L348P) in a key binding domain of cMyBP-C that enhances the binding affinity of cMyBP-C for actin in vitro (Bezold et al , JBC 2013) to gain insights into the relevance of cMyBP-C binding to actin in working hearts. Echocardiograms from 3 month old male L348P-Tg mice (N=23) and non-transgenic (nTg, N=17) controls were used to assess systolic and diastolic function. Results showed significantly prolonged isovolumetric relaxation time (L348P-Tg: 18.5±0.6 vs nTg: 10.2±0.3 ms) and slower movement of the mitral valve annulus (E’: -17.2±1.5 vs -32.2±1.6 and A’: -9.1±1.7 vs -17.6±1.0 mm/s, p&lt;0.05), accompanied by slower inflow of blood into the left ventricle (reduced E and A, prolonged mitral valve deceleration time). Pressure-volume measurements showed significantly reduced rates of pressure decay in L348P-Tg mice (Tau Glantz: 39.1±2.6 vs 12.7±0.9 ms) and an increased end-diastolic pressure volume relationship (0.13±0.02 vs 0.07±0.01). We challenged mice with acute beta-adrenergic stimulation (isoprenaline injection) to determine whether the L348P mutation affected contractile reserve. Isoprenaline had little effect on diastolic parameters, but revealed systolic dysfunction in L348P-Tg mice as evident from a blunted increase in contraction (e.g. fractional shortening after isoprenaline: 38.5±1.3 vs 44.2±1.7%). Taken together our results show for the first time that interactions between cMyBP-C and actin are relevant for functioning of the whole heart. Increasing the cMyBP-C-actin interaction by the L348P mutation caused increased stiffness of the left ventricle, slowed relaxation and diastolic dysfunction. Results also suggested that the L348P mutation reduces contractile reserve.

T2 relaxometry improves detection of non-sclerotic epileptogenic hippocampus

ObjectThe use of T2 relaxometry was investigated to detect non-sclerotic epileptogenic abnormality of the hippocampus in presurgical evaluation of temporal lobe epilepsy (TLE). MethodsThis prospective study included 30 patients who underwent hippocampectomy as part of surgical treatment of refractory TLE. Ten patients had structural epileptogenic lesions in the extra-hippocampal temporal lobe. Twelve patients underwent intracranial electroencephalography (iEEG) study before surgery. Visual assessment of atrophy and increased T2 signal intensity, volumetry, and T2 relaxometry of hippocampus were performed pre-operatively using 3T magnetic resonance imaging, and compared with the neuropathological findings and iEEG findings. Magnetic resonance imaging of 30 age- and sex-matched healthy controls was used to establish normal values, which were defined as z score within 2. ResultsVisual assessment, volumetry, and T2 relaxometry detected hippocampal abnormalities on the surgical side in 16 (53%), 16 (53%), and 26 (87%) patients, respectively. Hippocampal volume loss was always associated with prolonged T2 relaxation time, and supported by histopathological diagnosis of HS in all cases except one. Hippocampal abnormality was detected only by T2 relaxometry in nine patients (30%). Pathological diagnosis of these cases included mild HS in one, microdysgenesis in one, and granule cell pathology in three. Four patients with normal hippocampal volume and T2 relaxation time had no HS or granule cell pathology. Prolonged T2 relaxation time was associated with medial temporal seizure onset in iEEG (p<0.05). ConclusionsT2 relaxometry improves the detection of non-sclerotic epileptogenic abnormality of the hippocampus.

Circulating Histone Concentrations Differentially Affect the Predominance of Left or Right Ventricular Dysfunction in Critical Illness.

Cardiac complications are common in critical illness and associated with grave consequences. In this setting, elevated circulating histone levels have been linked to cardiac injury and dysfunction in experimental models and patients with sepsis. The mechanisms underlying histone-induced cardiotoxicity and the functional consequences on left ventricle and right ventricle remain unclear. This study aims to examine dose-dependent effects of circulating histones on left ventricle and right ventricle function at clinically relevant concentrations. Prospective laboratory study with in vitro and in vivo investigations. University research laboratory. Twelve-week old male C57BL/6N mice. Cultured cardiomyocytes were incubated with clinically relevant histone concentrations, and a histone infusion mouse model was also used with hemodynamic changes characterized by echocardiography and left ventricle/right ventricle catheter-derived variables. Circulating histones and cardiac troponin levels were obtained from serial blood samples. IV histone infusion caused time-dependent cardiac troponin elevation to indicate cardiac injury. At moderate sublethal histone doses (30 mg/kg), left ventricular contractile dysfunction was the prominent abnormality with reduced ejection fraction and prolonged relaxation time. At high doses (≥ 60 mg/kg), pulmonary vascular obstruction induced right ventricular pressure increase and dilatation, but left ventricular end-diastolic volume improved because of reduced blood return from the lungs. Mechanistically, histones induced profound calcium influx and overload in cultured cardiomyocytes with dose-dependent detrimental effects on intracellular calcium transient amplitude, contractility, and rhythm, suggesting that histones directly affect cardiomyocyte function adversely. However, increasing histone-induced neutrophil congestion, neutrophil extracellular trap formation, and thrombosis in the pulmonary microvasculature culminated in right ventricular dysfunction. Antihistone antibody treatment abrogated histone cardiotoxicity. Circulating histones significantly compromise left ventricular and right ventricular function through different mechanisms that are dependent on histone concentrations. This provides a translational basis to explain and target the spectral manifestations of cardiac dysfunction in critical illness.

Early Cartilage Changes After Anterior Cruciate Ligament Injury: Evaluation With Imaging and Serum Biomarkers—A Pilot Study

To determine if magnetic resonance imaging markers of cartilage matrix and morphology and circulating serum biomarkers of inflammation and matrix degradation differ over time in patients with anterior cruciate ligament (ACL) injury and bone marrow edema lesions (BMELs) when compared with matched control subjects. We performed a case-control study, in which 11 ACL-injured subjects scheduled to undergo reconstruction and 11 matched control subjects were scheduled for testing. Participants were selected for the ACL reconstruction (ACLR) group if they injured their ACL while participating in sports, were aged 14 to 30 years, had 1 or more BMELs, and were scheduled to undergo bone-patellar tendon-bone ACLR. Testing required patients to undergo magnetic resonance imaging for measurement of T2 relaxation times in standardized regions of interest over the medial and lateral tibial plateaus and femoral condyles and have blood drawn for measurement of cartilage oligomeric matrix protein (COMP) and C-reactive protein levels before ligament reconstruction and 1 year after surgery. ACL patients had prolonged T2 relaxation times, indicative of cartilage matrix degradation, in the superficial central lateral tibial plateau (P= .02) and deep medial tibial plateau when compared with control subjects (P= .0001). Prolonged T2 relaxation times were also noted over the lateral femoral condyle at baseline for ACL patients compared with control subjects (P= .001), but the differences resolved by 1 year (P= .98). Circulating serum COMP levels were greater in ACL patients (233.23 ± 88.26 ng/mL) compared with control subjects (169.05 ± 64.53 ng/mL, P= .05). T2 mapping showed prolonged relaxation times in the lateral compartment of the knee in ACLR patients with lateral BMELs. Furthermore, prolonged T2 relaxation times were apparent in the medial compartment of the knee in ACL-injured patients where bone marrow lesions were not present. Higher serum COMP levels were present in ACL-injured subjects when compared with control subjects. Level II, prospective case-control study.

Delayed grip relaxation and altered modulation of intracortical inhibition with aging.

Grip relaxation is a voluntary action that requires an increase in short-interval intracortical inhibition (SICI) in healthy young adults, rather than a simple termination of excitatory drive. The way aging affects this voluntary inhibitory action and timing of grip relaxation is currently unknown. The objective of this study was to examine aging-related delays in grip relaxation and SICI modulation for the flexor digitorum superficialis muscle during grip relaxation. The main finding was that young adults increased SICI to relax their grips, whereas older adults did not increase SICI with a prolonged grip relaxation time (p < 0.05 for both SICI modulation and grip relaxation time). A secondary experiment showed that both young and older adults did not change H reflex excitability during grip relaxation. Our data suggest that grip relaxation is mediated by increased cortical inhibitory output in young adults, and aging-related impairment in increasing cortical inhibitory output may hamper timely cessation of muscle activity. Our data also suggest a lesser role of the spinal circuits in grip muscle relaxation. This knowledge may contribute to understanding of aging-related movement deterioration and development of interventions for improving modulation of SICI to improve muscle relaxation and movement coordination.

In Vivo Longitudinal Monitoring of Changes in the Corpus Callosum Integrity During Disease Progression in a Mouse Model of Alzheimer's Disease.

The corpus callosum is the largest commissural fiber connecting left and right hemisphere of the brain. Emerging evidence suggests that a variety of abnormalities detected in the microstructure of this white matter fiber can be an early event in Alzheimer's disease (AD) pathology. However, little is known about tissue characteristics of these abnormalities and how these abnormalities evolve during AD progression. In this study, we measured in vivo magnetic resonance transverse relaxation times (T2) to longitudinally monitor changes in tissue integrity and abnormalities related to myelination and demyelination processes in corpus callosum of AD mouse models. The most striking finding of our study was a significant elongation of T2 values in the corpus callosum at 10, 14, 16 and 18 months of age compared to age-matched wild-type mice. In contrast, the gray matter regions surrounding the corpus callosum, such as the cortex and hippocampus, showed a significant T2 decrease compared to wild-type mice. Histological analyses clearly revealed demyelination, gliosis and amyloid-plaque deposition in the corpus callosum. Our results suggest that demyelinating and inflammatory pathology may result in prolonged relaxation time during AD progression. To our knowledge, this is the first in vivo T2 study assessing the microstructural changes with age in the corpus callosum of the Tg2576 mouse model and it demonstrates the application of T2 measurement to noninvasively detect tissue integrity of the corpus callosum, which can be an early event in disease progression.

Endothelial Mineralocorticoid Receptor Deletion Prevents Diet-Induced Cardiac Diastolic Dysfunction in Females.

Overnutrition and insulin resistance are especially prominent risk factors for the development of cardiac diastolic dysfunction in females. We recently reported that consumption of a Western diet (WD) containing excess fat (46%), sucrose (17.5%), and high fructose corn syrup (17.5%) for 16 weeks resulted in cardiac diastolic dysfunction and aortic stiffening in young female mice and that these abnormalities were prevented by mineralocorticoid receptor blockade. Herein, we extend those studies by testing whether WD-induced diastolic dysfunction and factors contributing to diastolic impairment, such as cardiac fibrosis, hypertrophy, inflammation, and impaired insulin signaling, are modulated by excess endothelial cell mineralocorticoid receptor signaling. Four-week-old female endothelial cell mineralocorticoid receptor knockout and wild-type mice were fed mouse chow or WD for 4 months. WD feeding resulted in prolonged relaxation time, impaired diastolic septal wall motion, and increased left ventricular filling pressure indicative of diastolic dysfunction. This occurred in concert with myocardial interstitial fibrosis and cardiomyocyte hypertrophy that were associated with enhanced profibrotic (transforming growth factor β1/Smad) and progrowth (S6 kinase-1) signaling, as well as myocardial oxidative stress and a proinflammatory immune response. WD also induced cardiomyocyte stiffening, assessed ex vivo using atomic force microscopy. Conversely, endothelial cell mineralocorticoid receptor deficiency prevented WD-induced diastolic dysfunction, profibrotic, and progrowth signaling, in conjunction with reductions in macrophage proinflammatory polarization and improvements in insulin metabolic signaling. Therefore, our findings indicate that increased endothelial cell mineralocorticoid receptor signaling associated with consumption of a WD plays a key role in the activation of cardiac profibrotic, inflammatory, and growth pathways that lead to diastolic dysfunction in female mice.

Effect of Charge Transfer in Magnetic-Plasmonic Au@MOx (M = Mn, Fe) Heterodimers on the Kinetics of Nanocrystal Formation

Heteronanoparticles represent a new class of nanomaterials exhibiting multifunctional and collective properties, which could find applications in medical imaging and therapy, catalysis, photovoltaics, and electronics. This present work demonstrates the intrinsic heteroepitaxial linkage in heterodimer nanoparticles to enable interaction of the individual components across their interface. It revealed distinct differences between Au@MnO and Au@Fe3O4 regarding the synthetic procedure and growth kinetics, as well as the properties to be altered by the variation of the electronic structure of the metal oxides. The chemically related metal oxides differ concerning their band gap; while MnO is a Mott-Hubbard insulator with a large band gap, Fe3O4 is a semimetal with thermally activated conductivity. The fluorescence dynamics indicate a prolonged relaxation time (>2 ns) for electrons of the conduction band of the Au nanoparticles after interfacing to Fe3O4. Here, the semiconductor is not depleted and forms an ohm...

Assessment of Myocardial Function in Children before and after Autologous Peripheral Blood Stem Cell Transplantation.

Increased interest is focused on the long-term adverse effects of bone marrow transplantation. Subclinical cardiac involvement appears common in adults, but only a few reports have examined pediatric patients. A prospective case-control study of 19 children with normal cardiac function undergoing autologous hematopoietic stem cell transplantation (HSCT) was performed. Tissue Doppler imaging (TDI) and echocardiographic measurements were obtained according to the guidelines of the American Society of Echocardiography before and 3 months after HSCT. Lateral mitral annulus before HSCT showed significant reduced mitral systolic annular velocity (P < 0.0001), early diastolic annular velocity (P < 0.0001), late diastolic annular velocity (P = 0.02) and prolonged isovolumetric relaxation time (IRT) (P < 0.0001) compared with control. Significant reduced mitral systolic annular velocity (P < 0.0001), early diastolic annular velocity (P = 0.0005) and Em/Am ratio (P = 0.004), with higher late diastolic annular velocity (P = 0.02) and prolonged isovolumetric contraction time (ICT) (P = 0.003) and IRT (P = 0.002) after HSCT, were observed. Investigation of lateral tricuspid annulus showed nearly similar results as the lateral mitral annulus. LV and RV Tei indices were higher before HSCT compared with control and remained high after HSCT. TDI detected subtle abnormalities in systolic and diastolic functions before and after HSCT, which suggests that a conditioning regimen may affect cardiac function.

Incomplete RV Remodeling After Transcatheter ASD Closure in Pediatric Age.

Published data showing the intermediate effect of transcatheter device closure of atrial septal defect (ASD) in the pediatric age-group are scarce. The objective of the study was to assess the effects of transcatheter ASD closure on right and left ventricular functions by tissue Doppler imaging (TDI). The study included 37 consecutive patients diagnosed as ASD secundum by transthoracic echocardiography and TEE and referred for transcatheter closure at Cairo University Specialized Pediatric Hospital, Egypt, from October 2010 to July 2013. Thirty-seven age- and sex-matched controls were selected. TDI was obtained using the pulsed Doppler mode, interrogating the right cardiac border (the tricuspid annulus) and lateral mitral annulus, and myocardial performance index (MPI) was calculated at 1-, 3-, 6- and 12-month post-device closure. Transcatheter closure of ASD and echocardiographic examinations were successfully performed in all patients. There were no significant differences between two groups as regards the age, gender, weight or BSA. TDI showed that patients with ASD had significantly prolonged isovolumetric contraction, relaxation time and MPI compared with control group. Decreased tissue Doppler velocities of RV and LV began at one-month post-closure compared with the controls. Improvement in RVMPI and LVMPI began at 1-month post-closure, but they are still prolonged till 1 year. Reverse remodeling of right and left ventricles began 1 month after transcatheter ASD closure, but did not completely normalize even after 1 year of follow-up by tissue Doppler imaging.