Locally Self-Adjustive Smoothing for Measurement Noise Reduction with Application to Automated Peak Detection.

Smoothing is a widely used approach for measurement noise reduction in spectral analysis. However, it suffers from signal distortion caused by peak suppression. A locally self-adjustive smoothing method is developed that retains sharp peaks and less distorted signals. The proposed method uses only one parameter that determines the global smoothness of data, while balancing the local smoothness using the data itself. Simulation and real experiments in comparison with existing convolution-based smoothing methods indicate both qualitatively and quantitatively improved noise reduction performance in practical scenarios. We also discuss parameter selection and demonstrate an application for the automated smoothing and detection of a given number of peaks from noisy measurement data.

Fast computational approach with prior dimension reduction for three-dimensional chemical component analysis using CT data of spectral imaging.

Spectral image (SI) measurement techniques, such as X-ray absorption fine structure (XAFS) imaging and scanning transmission electron microscopy (STEM) with energy-dispersive X-ray spectroscopy (EDS) or electron energy loss spectroscopy (EELS), are useful for identifying chemical structures in composite materials. Machine-learning techniques have been developed for automatic analysis of SI data, and their usefulness has been proven. Recently, an extended measurement technique combining SI with a computed tomography (CT) technique (CT-SI), such as CT-XAFS and STEM-EDS/EELS tomography, was developed to identify the three-dimensional (3D) structures of chemical components. CT-SI analysis can be conducted by combining CT reconstruction algorithms and chemical component analysis based on machine learning techniques. However, this analysis incurs high computational costs owing to the size of the CT-SI datasets. To address this problem, this study proposed a fast computational approach for 3D chemical component analysis in an unsupervised learning setting. The primary idea for reducing the computational cost involved compressing the CT-SI data prior to CT computation and performing 3D reconstruction and chemical component analysis on the compressed data. The proposed approach significantly reduced the computational cost without losing information about the 3D structure and chemical components. We experimentally evaluated the proposed approach using synthetic and real CT-XAFS data, which demonstrated that our approach achieved a significantly faster computational speed than the conventional approach while maintaining analysis performance. As the proposed procedure can be implemented with any CT algorithm, it is expected to accelerate 3D analyses with sparse regularized CT algorithms in noisy and sparse CT-SI datasets.

Procalcitonin, brain natriuretic peptide and albumin as markers to predict prognosis in hospitalized older Japanese patients with a risk of infection.

AIM: Whether serum concentration of procalcitonin (PCT), brain natriuretic peptide (BNP) and albumin (Alb) have an association with the outcome of hospitalized older patients is unclear. We investigated clinical outcomes and any predictive factors in hospitalized Japanese older patients with a risk of infection. METHODS: In the retrospective study, 820 Japanese patients were followed up for 30 days or until death. During the observation period, 656 patients survived and 164 patients died. The predictive factors of death were analyzed according to demographic and clinical variables. RESULTS: The survival rate was decreased as the serum PCT increased from <0.5 to ≥10 ng/mL, as was also the case with BNP from <300 to ≥300 pg./mL, whereas low Alb (<2.5 g/dL) showed a lower survival rate than high Alb (≥2.5 g/dL; P < 0.01). Using the Cox regression model, the multivariable-adjusted hazard ratios (95% confidence interval) were as follows: PCT 0.5-2 versus <0.5 ng/mL: 1.61(1.04-2.49), PCT 2-10 versus <0.5 ng/mL: 1.91(1.15-3.16), PCT ≥10 versus <0.5 ng/mL: 2.90(1.84-4.59), high BNP 1.26 (0.89-1.76) and low Alb 0.68 (0.52-0.87). The mortality rate increased as the number of scores (PCT + BNP + Alb) increased. CONCLUSIONS: Concentration-dependent high PCT, high BNP and low Alb were positive risk factors associated with poor prognosis in hospitalized older patients with a risk of infection. Geriatr Gerontol Int 2024; 24: 571-576.

Eurycoma longifolia (Tongkat Ali) enhances wakefulness during active periods but facilitates sleep during resting periods in C57BL/6 mice.

The effects of the Eurycoma longifolia (also known as Tongkat Ali [TA]) on sleep and wakefulness was evaluated in C57BL/6 mice. While TA has been used as an aphrodisiac in males, it exhibits various pharmacological effects. The most notable effect observed with TA was wake-enhancement during the second half of the active period, accompanied by significant elevations in core body temperature (CBT). In contrast, sleep was enhanced during the resting period (i.e., increase in rapid eye movement [REM] sleep and delta electroencephalography [EEG] power in non-REM sleep) with significant declines in CBT. The transition of TA's effects between resting and active periods was rapid. The results of the experiments in constant darkness indicate that TA prolongs the circadian tau and that this transition is governed by circadian clock mechanisms rather than light exposure. TA did not demonstrate efficacy in aiding sleep in an acute stress-induced insomnia model; thus, TA may be more suitable as a wake-enhancing agent for daytime sleepiness, as sleep propensity tends to accumulate towards the end of active period. Since TA amplifies the rest-activity pattern, prolongs circadian tau and increases REM sleep, thereby reversing some common symptoms seen in elderly subjects, it may also hold promise as a rejuvenating medicine.

Characteristics of hypersomnia due to inflammatory demyelinating diseases of the central nervous system.

Background: Neuromyelitis optica spectrum disorder (NMOSD) diagnostic criteria for inflammatory demyelinating central nervous system diseases included symptomatic narcolepsy; however, no relevant case-control studies exist. We aimed to examine the relationship among cerebrospinal fluid orexin-A (CSF-OX) levels, cataplexy and diencephalic syndrome; determine risk factors for low-and-intermediate CSF-OX levels (≤200 pg/mL) and quantify hypothalamic intensity using MRI. Methods: This ancillary retrospective case-control study included 50 patients with hypersomnia and 68 controls (among 3000 patients) from Akita University, the University of Tsukuba and community hospitals (200 facilities). Outcomes were CSF-OX level and MRI hypothalamus-to-caudate-nucleus-intensity ratio. Risk factors were age, sex, hypersomnolence and MRI hypothalamus-to-caudate-nucleus-intensity ratio >130%. Logistic regression was performed for the association between the risk factors and CSF-OX levels ≤200 pg/mL. Results: The hypersomnia group (n=50) had significantly more cases of NMOSD (p<0.001), diencephalic syndrome (p=0.006), corticosteroid use (p=0.011), hypothalamic lesions (p<0.023) and early treatment (p<0.001). No cataplexy occurred. In the hypersomnia group, the median CSF-OX level was 160.5 (IQR 108.4-236.5) pg/mL and median MRI hypothalamus-to-caudate-nucleus-intensity ratio was 127.6% (IQR 115.3-149.1). Significant risk factors were hypersomnolence (adjusted OR (AOR) 6.95; 95% CI 2.64 to 18.29; p<0.001) and MRI hypothalamus-to-caudate-nucleus-intensity ratio >130% (AOR 6.33; 95% CI 1.18 to 34.09; p=0.032). The latter was less sensitive in predicting CSF-OX levels ≤200 pg/mL. Cases with MRI hypothalamus-to-caudate-nucleus-intensity ratio >130% had a higher rate of diencephalic syndrome (p<0.001, V=0.59). Conclusions: Considering orexin as reflected by CSF-OX levels and MRI hypothalamus-to-caudate-nucleus-intensity ratio may help diagnose hypersomnia with diencephalic syndrome.

Pharmacologic Management of Excessive Daytime Sleepiness.

Excessive daytime sleepiness (EDS) is defined as "irresistible sleepiness in a situation when an individual would be expected to be awake, and alert." EDS has been a big concern not only from a medical but also from a public health point of view. Patients with EDS have the possibility of falling asleep even when they should wake up and concentrate, for example, when they drive, play sports, or walk outside. In this article, clinical characteristics of common hypersomnia and pharmacologic treatments of each hypersomnia are described.

Brain Mast Cells in Sleep and Behavioral Regulation.

The function of mast cells in the brain for the mediation of neurobehavior is largely unknown. Mast cells are a heterogeneous population of granulocytic cells in the immune system. Mast cells contain numerous mediators, such as histamine, serotonin, cytokines, chemokines, and lipid-derived factors. Mast cells localize not only in the periphery but are also resident in the brain of mammalians. Mast cells in the brain are constitutively active, releasing their contents gradually or rapidly by anaphylactic degranulation. Their activity is also increased by a wide range of stimuli including both immune and non-immune signals. Brain mast cell neuromodulation may thus be involved in various neurobehavior in health and diseases.Using Kit mutant mast cell deficient mice (KitW/KitW-v), we obtained results indicating that brain mast cells regulate sleep/wake and other behavioral phenotypes and that histamine from brain mast cells promotes wakefulness. These findings were also confirmed using a newer inducible and Kit-independent mast cell deficient Mas-TRECK (toxin receptor knockout) mouse. Injections of diphtheria toxin (DT) selectively deplete mast cells and reduce wakefulness during the periods of mast cell depletion.We recently introduced a mouse model for chronic sleep loss associated with diabetes. The mice reared on the wire net for 3 weeks (i.e., mild stress [MS]) showed decreased amount of non-rapid eye movement (NREM) sleep, increased sleep fragmentation, and abnormal glucose tolerance test [GTT] and insulin tolerance test [ITT], phenotypes which mirror human chronic insomnia. Interestingly, these mice with insomnia showed an increased number of mast cells in both the brain and adipose tissue. Mast cell deficient mice (KitW/KitW-v) and inhibition of mast cell functions with cromolyn or a histamine H1 receptor antagonist administration ameliorated both insomnia and abnormal glycometabolism. Mast cells may therefore represent an important pathophysiological mediator in sleep impairments and abnormal glycometabolism associated with chronic insomnia.

Diagnostic performance of nutritional indicators in patients with heart failure.

AIMS: The aim of this study was to compare the diagnostic performance of the nutritional indicators, the mini nutritional assessment-short form (MNA-SF), the geriatric nutritional risk index (GNRI), and the controlling nutritional status (CONUT), in heart failure (HF) patients. METHODS AND RESULTS: Nutritional status was prospectively assessed by the aforementioned three nutritional indicators in 150 outpatients with HF who were then followed for 1 year. The prevalence of patients with the nutritional risk as assessed by the MNA-SF, GNRI, and CONUT scores was 50.0%, 13.3%, and 54.0%, respectively. There was slight agreement of nutritional risk assessment between the MNA-SF and GNRI scores (κ coefficient = 0.16), as well as the GNRI and CONUT scores (κ = 0.11), but poor agreement between the MNA-SF and CONUT scores (κ = -0.09). The CONUT score had the lowest area under the curve (AUC) for the identification of low body weight, low muscle mass, and low physical function among the three indicators (all P < 0.05). Compared with the MNA-SF score, both the GNRI and CONUT scores had lower AUCs for the identification of reduced dietary intake and weight loss (all P < 0.05). There was no significant difference in predicting all-cause mortality or HF rehospitalization among the three indicators. The prescription of statins reduced the diagnostic performance of the CONUT score, as the CONUT score includes cholesterol level assessment. CONCLUSIONS: Of the three indicators, the diagnostic ability of the MNA-SF score was the highest, and that of the CONUT score was the lowest, for the assessment of HF patient nutritional status. The CONUT score may misrepresent nutritional status, particularly in patients receiving statins.

Impact of citrus fruit intake on the mental health of patients with chronic heart failure.

BACKGROUND: The full impact of the intake of citrus fruits on the risk of depression in individuals with chronic heart failure (HF) is unknown. Here, we examined the associations between the estimated habitual intakes of citrus fruits and depressive symptoms in patients with chronic HF. METHODS: We enrolled 150 stable outpatients with chronic HF who had a history of worsening HF. To assess the patients' daily dietary patterns, we used a brief self-administered diet-history questionnaire to calculate the daily consumption of foods and nutrients. To assess the patients' mental state, we used a nine-item Patient Health Questionnaire (PHQ-9). RESULTS: Twelve patients (8%) were identified as having moderate-to-severe depression (PHQ-9 score ≥10). The patients with PHQ-9 ≥10 had lower daily intakes of citrus fruits compared to those with no or mild depressive symptoms (PHQ-9 <10). The daily intakes of various antioxidants, including vitamin C, ß-carotene, and ß-cryptoxanthin, all of which are abundant in citrus fruits, were reduced in the patients with PHQ-9 ≥10, accompanied by higher serum levels of 8-isoprostane (an oxidative stress marker). A multivariate logistic regression analysis using forward selection showed that a lowered daily intake of citrus fruits was an independent predictor of the comorbidity of moderate-to-severe depression in patients with chronic HF, after adjustment for age, gender, and the hemoglobin value. CONCLUSIONS: A lower daily consumption of citrus fruits was associated with higher prevalence of depression in patients with chronic HF. Our findings support the hypothesis that a daily consumption of citrus fruits has a beneficial effect on the prevention and treatment of depression in chronic HF patients.

Impact of Inadequate Calorie Intake on Mortality and Hospitalization in Stable Patients with Chronic Heart Failure.

Malnutrition is highly prevalent in patients with heart failure (HF), but the precise impact of dietary energy deficiency on HF patients' clinical outcomes is not known. We investigated the associations between inadequate calorie intake and adverse clinical events in 145 stable outpatients with chronic HF who had a history of hospitalization due to worsening HF. To assess the patients' dietary pattern, we used a brief self-administered diet-history questionnaire (BDHQ). Inadequate calorie intake was defined as <60% of the estimated energy requirement. In the total chronic HF cohort, the median calorie intake was 1628 kcal/day. Forty-four patients (30%) were identified as having an inadequate calorie intake. A Kaplan-Meier analysis revealed that the patients with inadequate calorie intake had significantly worse clinical outcomes including all-cause death and HF-related hospitalization during the 1-year follow-up period versus those with adequate calorie intake (20% vs. 5%, p < 0.01). A multivariate logistic regression analysis showed that inadequate calorie intake was an independent predictor of adverse clinical events after adjustment for various factors that may influence patients' calorie intake. Among patients with chronic HF, inadequate calorie intake was associated with an increased risk of all-cause mortality and rehospitalization due to worsening HF. However, our results are preliminary and larger studies with direct measurements of dietary calorie intake and total energy expenditure are needed to clarify the intrinsic nature of this relationship.

False-positive cases in multiple sleep latency test by accumulated sleep debt.

PURPOSE: Multiple sleep latency test (MSLT) is performed as objective assessment of sleepiness, on the following day after polysomnography (PSG). In most clinics, patients are required to stay for 2 days. However, if patients have chronic sleep debt before the examination, even if they get adequate nocturnal sleep during the initial PSG, their sleep debt would not be fully resolved, affecting MSLT results. This may lead to improper administration of psycho-stimulant medication. To clarify the sleep debt for the patients who showed short sleep latencies, we compared the mean sleep latencies of MSLTs. METHODS: Twelve hypersomnolent males, who underwent MSLTs (1st MSLT with 1 night and 2nd MSLT with more than 3 nights), were enrolled. We selected these cases based on the longer total sleep time on PSG night compared to the mean total sleep time on pre-examination sleep logs and shortened sleep latencies on PSG. To evaluate the effect of the sleep debt for the patients who showed short sleep latencies, we extended their hospitalization or re-hospitalized them. RESULTS: The mean sleep latency of 1st MSLT was 5.8 minutes and that of 2nd was 13.9 minutes (P < .001). Among these 12 cases, 5 cases altered from short to normal sleep latencies at the 2nd MSLT. These 5 cases were prevented from over-diagnoses by the extension of evaluations. CONCLUSIONS: The sleep debt may produce false-positive results when patients are examined by standard PSG and MSLT. Accumulation of sleep debt will cause shortened sleep latencies in the following nights. Patients should be advised to extend their hospitalization before PSG and MSLT to reduce the chronic sleep debt for accurate diagnosis of hypersomnia.

Evaluations of effects of sleep surfaces on athletic performance in youth.

We recently demonstrated that sleeping on high rebound [HR] mattress toppers induced a continuous and more rapid decline in core body temperature compared to low rebound [LR] mattress toppers during the initial phase of nocturnal sleep in young healthy volunteers. HR toppers are characterized by their supportive feel and high breathability whereas LR toppers are pressure-absorbing. In the current study, we evaluated effects of HR mattress toppers on objectively-(actigraphy) and subjectively-(questionnaires) evaluated sleep, vigilance (psychomotor vigilance test), and athletic performance (40-m sprint time, long jump distance, and star drill time) in youth male athletes age 10-19, in two sessions: fifty-one subjects in 2013 (study I) and 23 subjects in 2014 (study II). Sleeping on HR mattress toppers for four to six weeks improved some athletic performance measures compared to sleeping on LR or sleeping directly on spring mattresses without a topper. Statistically significant improvements in 40-m sprint time in study I (compared to LR) and in star drill time in study II (no topper) were observed. No changes in sleep and psychomotor vigilance were observed. These results suggest selecting optimal sleep surfaces may contribute to the maximization of athletic performances, and further studies are warranted.

Curcumin ameliorates skeletal muscle atrophy in type 1 diabetic mice by inhibiting protein ubiquitination.

NEW FINDINGS: What is the central question of this study? We sought to examine whether curcumin could ameliorate skeletal muscle atrophy in diabetic mice by inhibiting protein ubiquitination, inflammatory cytokines and oxidative stress. What is the main finding and its importance? We found that curcumin ameliorated skeletal muscle atrophy in streptozotocin-induced diabetic mice by inhibiting protein ubiquitination without affecting protein synthesis. This favourable effect of curcumin was possibly due to the inhibition of inflammatory cytokines and oxidative stress. Curcumin may be beneficial for the treatment of muscle atrophy in type 1 diabetes mellitus. Skeletal muscle atrophy develops in patients with diabetes mellitus (DM), especially in type 1 DM, which is associated with chronic inflammation. Curcumin, the active ingredient of turmeric, has various biological actions, including anti-inflammatory and antioxidant properties. We hypothesized that curcumin could ameliorate skeletal muscle atrophy in mice with streptozotocin-induced type 1 DM. C57BL/6 J mice were injected with streptozotocin (200 mg kg(-1) i.p.; DM group) or vehicle (control group). Each group of mice was randomly subdivided into two groups of 10 mice each and fed a diet with or without curcumin (1500 mg kg(-1) day(-1)) for 2 weeks. There were significant decreases in body weight, skeletal muscle weight and cellular cross-sectional area of the skeletal muscle in DM mice compared with control mice, and these changes were significantly attenuated in DM+Curcumin mice without affecting plasma glucose and insulin concentrations. Ubiquitination of protein was increased in skeletal muscle from DM mice and decreased in DM+Curcumin mice. Gene expressions of muscle-specific ubiquitin E3 ligase atrogin-1/MAFbx and MuRF1 were increased in DM and inhibited in DM+Curcumin mice. Moreover, nuclear factor-κB activation, concentrations of the inflammatory cytokines tumour necrosis factor-α and interleukin-1ß and oxidative stress were increased in the skeletal muscle from DM mice and inhibited in DM+Curcumin mice. Curcumin ameliorated skeletal muscle atrophy in DM mice by inhibiting protein ubiquitination, inflammatory cytokines and oxidative stress. Curcumin may be beneficial for the treatment of muscle atrophy in type 1 DM.

(Pro)renin receptor in skeletal muscle is involved in the development of insulin resistance associated with postinfarct heart failure in mice.

We previously reported that insulin resistance was induced by the impairment of insulin signaling in the skeletal muscle from heart failure (HF) via NAD(P)H oxidase-dependent oxidative stress. (Pro)renin receptor [(P)RR] is involved in the activation of local renin-angiotensin system and subsequent oxidative stress. We thus examined whether (P)RR inhibitor, handle region peptide (HRP), could ameliorate insulin resistance in HF after myocardial infarction (MI) by improving oxidative stress and insulin signaling in the skeletal muscle. C57BL6J mice were divided into four groups: sham operated (Sham, n = 10), Sham treated with HRP (Sham+HRP, 0.1 mg·kg(-1)·day(-1), n = 10), MI operated (MI, n = 10), and MI treated with HRP (MI+HRP, 0.1 mg/kg/day, n = 10). After 4 wk, MI mice showed left ventricular dysfunction, which was not affected by HRP. (P)RR was upregulated in the skeletal muscle after MI (149% of sham, P < 0.05). The decrease in plasma glucose after insulin load was smaller in MI than in Sham (21 ± 2 vs. 44 ± 3%, P < 0.05), and was greater in MI+HRP (38 ± 2%, P < 0.05) than in MI. Insulin-stimulated serine phosphorylation of Akt and glucose transporter 4 translocation were decreased in the skeletal muscle from MI by 48 and 49% of Sham, both of which were ameliorated in MI+HRP. Superoxide production and NAD(P)H oxidase activities were increased in MI, which was inhibited in MI+HRP. HRP ameliorated insulin resistance associated with HF by improving insulin signaling via the inhibition of NAD(P)H oxidase-induced superoxide production in the skeletal muscle. The (P)RR pathway is involved in the development of insulin resistance, at least in part, via the impairment of insulin signaling in the skeletal muscle from HF.

Combination of exercise training and diet restriction normalizes limited exercise capacity and impaired skeletal muscle function in diet-induced diabetic mice.

Exercise training (EX) and diet restriction (DR) are essential for effective management of obesity and insulin resistance in diabetes mellitus. However, whether these interventions ameliorate the limited exercise capacity and impaired skeletal muscle function in diabetes patients remains unexplored. Therefore, we investigated the effects of EX and/or DR on exercise capacity and skeletal muscle function in diet-induced diabetic mice. Male C57BL/6J mice that were fed a high-fat diet (HFD) for 8 weeks were randomly assigned for an additional 4 weeks to 4 groups: control, EX, DR, and EX+DR. A lean group fed with a normal diet was also studied. Obesity and insulin resistance induced by a HFD were significantly but partially improved by EX or DR and completely reversed by EX+DR. Although exercise capacity decreased significantly with HFD compared with normal diet, it partially improved with EX and DR and completely reversed with EX+DR. In parallel, the impaired mitochondrial function and enhanced oxidative stress in the skeletal muscle caused by the HFD were normalized only by EX+DR. Although obesity and insulin resistance were completely reversed by DR with an insulin-sensitizing drug or a long-term intervention, the exercise capacity and skeletal muscle function could not be normalized. Therefore, improvement in impaired skeletal muscle function, rather than obesity and insulin resistance, may be an important therapeutic target for normalization of the limited exercise capacity in diabetes. In conclusion, a comprehensive lifestyle therapy of exercise and diet normalizes the limited exercise capacity and impaired muscle function in diabetes mellitus.

Angiotensin II receptor blocker improves the lowered exercise capacity and impaired mitochondrial function of the skeletal muscle in type 2 diabetic mice.

NAD(P)H oxidase-induced oxidative stress is at least in part involved with lowered exercise capacity and impaired mitochondrial function in high-fat diet (HFD)-induced diabetic mice. NAD(P)H oxidase can be activated by activation of the renin-angiotensin system. We investigated whether ANG II receptor blocker can improve exercise capacity in diabetic mice. C57BL/6J mice were fed a normal diet (ND) or HFD, and each group of mice was divided into two groups: treatment with or without olmesartan (OLM; 3 mg·kg(-1)·day(-1) in the drinking water). The following groups of mice were studied: ND, ND+OLM, HFD, and HFD+OLM (n = 10 for each group). After 8 wk, HFD significantly increased body weight, plasma glucose, and insulin compared with ND, and OLM did not affect these parameters in either group. Exercise capacity, as determined by treadmill tests, was significantly reduced in HFD, and this reduction was ameliorated in HFD+OLM. ADP-dependent mitochondrial respiration was significantly decreased, and NAD(P)H oxidase activity and superoxide production by lucigenin chemiluminescence were significantly increased in skeletal muscle from HFD, which were attenuated by OLM. There were no such effects by OLM in ND. We concluded that OLM ameliorated the decrease in exercise capacity in diabetic mice via improvement in mitochondrial function and attenuation of oxidative stress in skeletal muscle. These data may have a clinical impact on exercise capacity in the medical treatment of diabetes mellitus.

Activation of natural killer T cells ameliorates postinfarct cardiac remodeling and failure in mice.

RATIONALE: Chronic inflammation in the myocardium is involved in the development of left ventricular (LV) remodeling and failure after myocardial infarction (MI). Invariant natural killer T (iNKT) cells have been shown to produce inflammatory cytokines and orchestrate tissue inflammation. However, no previous studies have determined the pathophysiological role of iNKT cells in post-MI LV remodeling. OBJECTIVE: The purpose of this study was to examine whether the activation of iNKT cells might affect the development of LV remodeling and failure. METHODS AND RESULTS: After creation of MI, mice received the injection of either α-galactosylceramide (αGC; n=27), the activator of iNKT cells, or phosphate-buffered saline (n=31) 1 and 4 days after surgery, and were followed during 28 days. Survival rate was significantly higher in MI+αGC than MI+PBS (59% versus 32%, P<0.05). LV cavity dilatation and dysfunction were significantly attenuated in MI+αGC, despite comparable infarct size, accompanied by a decrease in myocyte hypertrophy, interstitial fibrosis, and apoptosis. The infiltration of iNKT cells were increased during early phase in noninfarcted LV from MI and αGC further enhanced them. It also enhanced LV interleukin (IL)-10 gene expression at 7 days, which persisted until 28 days. AntienIL-10 receptor antibody abrogated these protective effects of αGC on MI remodeling. The administration of αGC into iNKT cell-deficient Jα18(-/-) mice had no such effects, suggesting that αGC was a specific activator of iNKT cells. CONCLUSIONS: iNKT cells play a protective role against post-MI LV remodeling and failure through the enhanced expression of cardioprotective cytokines such as IL-10.

Conduction and refractory disorders in the diabetic atrium.

Diabetes mellitus (DM) is an independent risk of atrial fibrillation. However, its arrhythmogenic substrates remain unclear. This study sought to examine the precise propagation and the spatiotemporal dispersion of the action potential (AP) in the diabetic atrium. DM was induced by streptozotocin (65 mg/kg) in 8-wk-old male Wister rats. Optical mapping and histological analysis were performed in the right atrium (RA) from control (n = 26) and DM (n = 27) rats after 16 wk. Rate-dependent alterations of conduction velocity (CV) and its heterogeneity and the spatial distribution of AP were measured in RA using optical mapping. The duration of atrial tachyarrhythmia (AT) induced by rapid atrial stimulation was longer in DM (2.4 ± 0.6 vs. 0.9 ± 0.3 s, P < 0.05). CV was decreased, and its heterogeneity was greater in DM than control. Average action potential duration of 80% repolarization (APD(80)) at pacing cycle length (PCL) of 200 ms from four areas within the RA was prolonged (53 ± 2 vs. 40 ± 3 ms, P < 0.01), and the coefficient of variation of APD(80) was greater in DM than control (0.20 ± 0.02 vs. 0.15 ± 0.01%, P < 0.05). The ratio of APD(80) at PCL shorter than 200 ms to that at 200 ms was smaller (P < 0.001), and the incidence of APD alternans was higher in DM than control (100 vs. 0%, P < 0.001). Interstitial fibrosis was greater and connexin 40 expression was lower in DM than control. The remodeling of the diabetic atrium was characterized as follows: greater vulnerability to AT, increased conduction slowing and its heterogeneity, the prolongation of APD, the increase in spatial dispersion and frequency-dependent shortening of APD, and increased incidence of APD alternans.