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Background: Erythropoietin (EPO), which is associated with anemia, exerts neuroprotective effects in ischemic stroke. In cases of stenosis or narrowing of the main cerebral blood vessel, the prognosis is favorable if collateral blood circulation is well developed in acute stroke. Several studies have investigated the relationship between EPO administration and stroke outcomes. The present study investigated the correlation between serum EPO level and cerebral collateral circulation, which could result in favorable clinical outcomes.Methods: The study subjects were patients diagnosed with acute ischemic stroke who underwent initial brain magnetic resonance imaging between January 2020 and March 2022. Following brain computed tomography perfusion for collateral flow, serum EPO levels were measured. Collaterals were assessed according to the Mass system and divided into good collateral (GC) or poor collateral (PC) groups. Serum EPO levels were determined using a chemiluminescence immunoassay method. A correlation coefficient analysis was conducted to determine the correlation between serum EPO levels and GC. A receiver operating characteristic curve analysis determined the cutoff value of EPO for GC.Results: Serum EPO levels were significantly higher in the GC than that in the PC group (P9.1 mIU/mL) could be a marker of GC in patients with acute ischemic stroke that predicts good clinical outcomes.

ObjectiveTo describe neurophysiological abnormalities in Long COVID and correlate quantitative electromyography (qEMG) and single fiber EMG (sfEMG) results to clinical scores and histopathology.Methods84 patients with non-improving musculoskeletal Long COVID symptoms were examined with qEMG and sfEMG. Muscle biopsies were taken in a subgroup.ResultsMean motor unit potential (MUP) duration was decreased in ≥ 1 muscles in 52 % of the patients. Mean jitter was increased in 17 % of the patients in tibialis anterior and 25 % in extensor digitorum communis. Increased jitter was seen with or without myopathic qEMG. Low quality of life score correlated with higher jitter values but not with qEMG measures. In addition to our previously published mitochondrial changes, inflammation, and capillary injury, we show now in muscle biopsies damage of terminal nerves and motor endplate with abundant basal lamina material. At the endplate, axons were present but no vesicle containing terminals. The post-synaptic cleft in areas appeared atrophic with short clefts and coarse crests.ConclusionsMyopathic changes are common in Long COVID. sfEMG abnormality is less common but may correlate with clinical scores. sfEMG changes may be due to motor endplate pathology. OBJECTIVE: To describe neurophysiological abnormalities in Long COVID and correlate quantitative electromyography (qEMG) and single fiber EMG (sfEMG) results to clinical scores and histopathology.METHODS: 84 patients with non-improving musculoskeletal Long COVID symptoms were examined with qEMG and sfEMG. Muscle biopsies were taken in a subgroup.RESULTS: Mean motor unit potential (MUP) duration was decreased in ≥ 1 muscles in 52 % of the patients. Mean jitter was increased in 17 % of the patients in tibialis anterior and 25 % in extensor digitorum communis. Increased jitter was seen with or without myopathic qEMG. Low quality of life score correlated with higher jitter values but not with qEMG measures. In addition to our previously published mitochondrial changes, inflammation, and capillary injury, we show now in muscle biopsies damage of terminal nerves and motor endplate with abundant basal lamina material. At the endplate, axons were present but no vesicle containing terminals. The post-synaptic cleft in areas appeared atrophic with short clefts and coarse crests.CONCLUSIONS: Myopathic changes are common in Long COVID. sfEMG abnormality is less common but may correlate with clinical scores. sfEMG changes may be due to motor endplate pathology.SIGNIFICANCE: These findings may indicate a muscle pathophysiology behind fatigue in Long COVID.

Contemporary biometric technologies have been gaining traction in both public and private security sectors. Facial recognition is the most commonly used biometric technology for this purpose. We aimed to evaluate the ability of a publicly available facial recognition application program interface to calculate similarity scores of presurgical and postsurgical photographs of patients who had orthognathic surgery.Presurgical and postsurgical photographs of 75 patients who had orthognathic surgery between January 2018 and November 2020 in our department were used. Frontal photographs of patients in relaxed and smiling states were taken. The patients were classified into three groups: Group 2 had one-jaw surgery, Group 3 had two-jaw surgery to correct mandibular prognathism, and Group 4 had two-jaw surgery to correct facial asymmetry. For comparison, photographs of 10 participants were used as controls (Group 1). Two facial recognition application programs (Face X and Azure) were used to assess similarity scores.The similarity scores in the two programs showed significant results. The similarity score of the control group, which did not undergo orthognathic surgery, was the highest. The results for Group 2, Group 3, and Group 4 were higher in the order of Group 2, Group 3, and Group 4.In this study, all orthodontic patients were recognized as the same person using the face recognition program before and after surgery. A significant difference in similarity results was obtained between the groups with both Face X and Azure and in both relaxed and smiling states.

Purpose: Hyperpolarized [1- 13C]pyruvate MRS can measure cardiac metabolism in vivo. We investigated whether [1- 13C]pyruvate MRS could predict left ventricular remodeling following myocardial infarction (MI), long-term left ventricular effects of heart failure medication, and could identify responders to treatment. Methods: Thirty-five rats were scanned with hyperpolarized [1- 13C]pyruvate MRS 3 days after MI or sham surgery. The animals were re-examined after 30 days of therapy with β-blockers and ACE-inhibitors (active group, n = 12), placebo treatment (placebo group, n = 13) or no treatment (sham group, n = 10). Furthermore, heart tissue mitochondrial respiratory capacity was assessed by high-resolution respirometry. Metabolic results were compared between groups, over time and correlated to functional MR data at each time point. Results: At 30 ± 0.5 days post MI, left ventricular ejection fraction (LVEF) differed between groups (sham, 77% ± 1%; placebo, 52% ± 3%; active, 63% ± 2%, P 13C]pyruvate MRS and respirometry, neither differed between groups nor between baseline and follow-up. Three days post MI, low bicarbonate + CO 2/pyruvate ratio was associated with low LVEF. At follow-up, in the active group, a poor recovery of LVEF was associated with high bicarbonate + CO 2/pyruvate ratio, as measured by hyperpolarized MRS. Conclusion: In a rat model of moderate heart failure, medical treatment improved function, but did not on average influence [1- 13C]pyruvate flux as measured by MRS; however, responders to heart failure medication had reduced capacity for carbohydrate metabolism.

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is characterized by clinical evidence of myocardial infarction with normal or near-normal coronary arteries on angiography (less-than 50% stenosis). MINOCA is a group of heterogeneous diseases with different pathophysiologic mechanism which all can cause ischaemia. MINOCA is considered a "working diagnosis" after angiography until further evaluation regarding its underlying cause is made. The aim of this review is to assess the literature on clinical features, aetiology, diagnosis, treatment and prognosis of patients with MINOCA.

The effect of limb remote ischaemic conditioning (RIC) on myocardial infarct (MI) size and left ventricular ejection fraction (LVEF) was investigated in a pre-planned cardiovascular magnetic resonance (CMR) substudy of the CONDI-2/ERIC-PPCI trial. This single-blind multi-centre trial (7 sites in UK and Denmark) included 169 ST-segment elevation myocardial infarction (STEMI) patients who were already randomised to either control (n = 89) or limb RIC (n = 80) (4 × 5 min cycles of arm cuff inflations/deflations) prior to primary percutaneous coronary intervention. CMR was performed acutely and at 6 months. The primary endpoint was MI size on the 6 month CMR scan, expressed as median and interquartile range. In 110 patients with 6-month CMR data, limb RIC did not reduce MI size [RIC: 13.0 (5.1–17.1)% of LV mass; control: 11.1 (7.0–17.8)% of LV mass, P = 0.39], or LVEF, when compared to control. In 162 patients with acute CMR data, limb RIC had no effect on acute MI size, microvascular obstruction and LVEF when compared to control. In a subgroup of anterior STEMI patients, RIC was associated with lower incidence of microvascular obstruction and higher LVEF on the acute scan when compared with control, but this was not associated with an improvement in LVEF at 6 months. In summary, in this pre-planned CMR substudy of the CONDI-2/ERIC-PPCI trial, there was no evidence that limb RIC reduced MI size or improved LVEF at 6 months by CMR, findings which are consistent with the neutral effects of limb RIC on clinical outcomes reported in the main CONDI-2/ERIC-PPCI trial.

A Gram-negative, aerobic, non-motile, and rod-shaped bacterial strain, designated BSSL-BM10T, was isolated from a sand dune that was collected from the Yellow Sea, Republic of Korea. It was subjected to a polyphasic taxonomic study. 16S rRNA gene sequence analysis showed that strain BSSL-BM10T fell phylogenetically within the radiation comprising type strains of Devosia species. The 16S rRNA gene sequence of strain BSSL-BM10T shared sequence similarities of 98.2% with the type strain of D. naphthalenivorans and 93.5-97.7% with type strains of other Devosia species. ANI and dDDH values between strain BSSL-BM10T and type strains of 18 Devosia species were 71.0-78.4% and 18.8-21.5%, respectively. The DNA G+C content of strain BSSL-BM10T was 60.9% based on its genomic sequence data. Strain BSSL-BM10T contained Q-10 as the predominant ubiquinone and 11-methyl C18:1 ω7c, C18:1 ω7c, summed feature 3 (C16:1 ω7c and/or C16:1 ω6c), and C16:0 as its major fatty acids. Major polar lipids of strain BSSL-BM10T were phosphatidylglycerol and two unidentified glycolipids. Strain BSSL-BM10T showed distinguished phenotypic properties with its phylogenetic and genetic distinctiveness separated from recognized Devosia species. Based on data presented in this study, strain BSSL-BM10T should be placed in the genus Devosia. The name Devosia litorisediminis sp. nov. is proposed for strain BSSL-BM10T (= KACC 21633T = NBRC 115152T).

Background Cadmium is a toxic element in cigarette smoke associated with ischemic vascular disease. Its association with cerebral aneurysm is unknown. Methods We retrospectively analyzed the medical records of patients with headache who underwent imaging studies between March 2014 and August 2016. An unruptured intracranial aneurysm (UIA) was confirmed by brain magnetic resonance angiography or computed tomography angiography. A control group included age- and sex-matched patients without an UIA. Whole blood and random urine tests were used for detection of cadmium and arsenic levels, respectively. Student t-test was used to compare subject characteristics, mean cadmium and arsenic levels between groups, and differences between groups with small (2.0 mcg/L (OR, 1.39; 95% CI, 1.15–1.84; P=0.043) were associated with aneurysm incidence. Conclusion UIA incidence was associated with pack-years of smoking and serum cadmium level, but aneurysm size was not associated with serum cadmium level.

In dry reforming of methane (DRM), coke deposition on the Ni-based catalyst is the main cause of instability of the process. Perovskite LaNiO3 is a well-known highly active catalyst precursor for DRM, but the La-Ni catalyst derived from it is susceptible to severe coke deposition and thus difficult for practical applications. To improve its stability and activity, Co and Mn are introduced to develop a tri-metallic LaNi0.34Co0.33Mn0.33O3 catalyst precursor. The role of Mn is to improve the stability of the catalyst, whereas Co is an additional active component to increase the reaction rates. A strong metal and support interaction mediated by MnO is noted in the tri-metallic catalyst, which contributes to a synergistic effect of the tri-metals to sustain the high activity and stability under the harsh conditions of DRM.

The purpose of the study was to validate by histopathology, contrast enhanced cine steady-state free precession and T2-weighted CMR for the assessment of ischemic myocardial area-at-risk (AAR) in the presence of microvascular obstruction (MVO). Eleven anesthetized pigs underwent CMR 7 to 10 days post infarction. The area-at-risk was measured from T2-weighted fast spin echo (T2-STIR) and contrast-enhanced steady-state free precession magnetic resonance imaging (CE-SSFP) images using semi-automated algorithms based on a priori knowledge of perfusion territory. Also, late gadolinium enhancement (LGE) was performed to measure final infarct size (FIS). Histopathological comparison with Evans blue dye to define AAR and triphenyltetrazolium chloride to define FIS served as the reference. All infarcts demonstrated MVO on LGE images. Bland-Altman analysis showed no significant bias in AAR or myocardial salvage between T2-STIR and CE-SSFP or between CMR and histopathology. The mean differences ± 2SD from Bland-Altman analysis were: AAR: Evans Blue vs. T2-STIR [0.7%; + 13.5%; - 12.1%]; AAR: Evans Blue vs. CE-SSFP [0.1%; + 13.8%; - 13.7%]; AAR: T2-STIR vs. CE-SSFP [0.7%; + 6.2%; - 4.9%]; Salvage: Evans Blue - TTC vs. T2-STIR-LGE [0.8%; + 11.1%; - 9.6%]; Salvage: Evans Blue - TTC vs. CE-SSFP-LGE [0.1%; + 9.9%; - 9.6%]; Salvage: CE-SSFP-LGE vs. T2-STIR-LGE [0.7%; + 6.2%; - 4.9%]. Both T2-STIR and CE-SSFP sequences allow for unbiased quantification of AAR in the presence of ischemia/reperfusion injury when analysed by semi-automated algorithms. These experimental data, which was validated by histopathology, supports the use of CMR for the assessment of myocardial salvage during the subacute phase.

Hyperpolarized [1-Thirty-five rats were scanned with hyperpolarized [1-At 30 ± 0.5 days post MI, left ventricular ejection fraction (LVEF) differed between groups (sham, 77% ± 1%; placebo, 52% ± 3%; active, 63% ± 2%, P.001). Cardiac metabolism, measured by both hyperpolarized [1-In a rat model of moderate heart failure, medical treatment improved function, but did not on average influence [1

A Gram stain-negative, aerobic, motile by gliding, rod-shaped bacterial strain CAU 1569T was isolated from marine sediment on Shido Island in Incheon. It grew at 20-37°C (optimum, 30°C), pH 6.0–9.0 (optimum, 7.0), 2–6% NaCl (w/v) (optimum, 2%). Phylogenetic analysis based on 16S rRNA gene sequence indicated that strain CAU 1569T formed a distinct lineage within the type strain of Snuella. Strain CAU 1569T showed high similarity to S. lapsa JC2132T (95.8%), Mariniflexile gromovii KMM 60388T (95.5%), Aestuariibaculum marinum IP7T (95.4%), A. suncheonense SC17T (94.6%) and Yeosuana aromativorans GW1-1T (94.4%). The genome contained 57 contigs, 3,437 protein-coding gene, 3 rRNAs (5, 16, and 23S), 43 tRNAs, and with a 35.7 mol% G + C content. The isoprenoid quinone was only menaquinone 6 (MK-6). The major fatty acids were iso-C15:0, C15:1−iso G, and C17:0 iso 3-OH. Strain CAU 1569T contained diphosphatidylglycerol, aminoglycolipid, unidentified aminolipid, and three unidentified lipids. Based on phylogenetic, genomic, physiologic, and chemotaxonomic characterizations, strain CAU 1569T represents a novel Snuella species, which the name Snuella sedimenti sp. nov. is proposed. The type of strain is CAU 1569T (= KCTC 82409T = MCCC 1K05670T).

Background Stroke is a serious complication in patients with type 2 diabetes (T2DM). Arterial stiffness may improve stroke prediction. We investigated the association between carotid-femoral pulse wave velocity [PWV] and the progression of cerebral white matter hyperintensities (WMH), a marker of stroke risk, in patients with T2DM and controls. Methods In a 5-year cohort study, data from 45 patients and 59 non-diabetic controls were available for analysis. At baseline, participants had a mean (± SD) age of 59 ± 10 years and patients had a median (range) diabetes duration of 1.8 (0.8–3.2) years. PWV was obtained by tonometry and WMH volume by an automated segmentation algorithm based on cerebral T2-FLAIR and T1 MRI (corrected by intracranial volume, cWMH). High PWV was defined above 8.94 m/s (corresponding to the reference of high PWV above 10 m/s using the standardized path length method). Results Patients with T2DM had a higher PWV than controls (8.8 ± 2.2 vs. 7.9 ± 1.4 m/s, p Conclusions PWV is associated with cWMH progression in patients with type 2 diabetes and non-diabetic controls. Our results indicate that arterial stiffness may be involved early in the pathophysiology leading to cerebrovascular diseases.

Renal ischemia-reperfusion injury (IRI) is one of the most common types of acute kidney injury. Spironolactone has shown promising kidney protective effects in renal IRI in rats. We investigated the hemodynamic and metabolic effects of spironolactone (100 mg/kg) administered immediately after 40 min unilateral kidney ischemia in rats. Hyperpolarized MRI using co-polarized [1-13 C]pyruvate and [13 C,15 N2 ]urea as well as 1 H dynamic contrast-enhanced (DCE) MRI was performed 24 h after induction of ischemia. We found a significant decrease in renal blood flow (RBF) in the ischemic kidney compared with the contralateral one measured using DCE and [13 C,15 N2 ]urea. The RBF measured using [1-13 C]pyruvate and [13 C,15 N2 ]urea was significantly altered by spironolactone. The RBFs in the ischemic kidney compared with the contralateral kidney were decreased similarly as measured using both [13 C,15 N2 ]urea and [1-13 C]pyruvate in the spironolactone-treated group. Spironolactone treatment increased the perfusion-corrected pyruvate metabolism by 54% in both the ischemic and contralateral kidney. Furthermore, we showed a correlation between vascular permeability using a histological Evans blue analysis and the ratio of the volumes of distribution (VoDs), ie VoD-[13 C,15 N2 ]urea/VoD-[1-13 C]pyruvate. This suggests that [13 C,15 N2 ]urea/[1-13 C]pyruvate VoD ratio may be a novel indicator of renal vascular permeability associated with renal damage in rodents.

Purpose: Owing to its noninvasive nature, hyperpolarized MRI may improve delineation of myocardial metabolic derangement in heart disease. However, consistency may depend on the changeable nature of cardiac metabolism in relation to whole-body metabolic state. This study investigates the impact of feeding status on cardiac hyperpolarized MRI in a large animal model resembling human physiology. Methods: Thirteen 30-kg pigs were subjected to an overnight fast, and 5 pigs were fed a carbohydrate-rich meal on the morning of the experiments. Vital parameters and blood samples were registered. All pigs were then scanned by hyperpolarized [1- 13 C]pyruvate cardiac MRI, and results were compared between the 2 groups and correlated with circulating substrates and hormones. Results: The fed group had higher blood glucose concentration and mean arterial pressure than the fasted group. Plasma concentrations of free fatty acids (FFAs) were decreased in the fed group, whereas plasma insulin concentrations were similar between groups. Hyperpolarized MRI showed that fed animals had increased lactate/pyruvate, alanine/pyruvate, and bicarbonate/pyruvate ratios. Metabolic ratios correlated negatively with FFA levels. Conclusion: Hyperpolarized MR can identify the effects of different metabolic states on cardiac metabolism in a large animal model. Unlike previous rodent studies, all metabolic derivatives of pyruvate increased in the myocardium of fed pigs. Carbohydrate-rich feeding seems to be a feasible model for standardized, large animal hyperpolarized MRI studies of myocardial carbohydrate metabolism.

Purpose We aimed to identify and assess cardiac abnormalities by cardiovascular magnetic resonance (CMR) in a non-ischaemic aborted sudden cardiac death (SCD) population and to establish possible predictors of SCD. Methods Thirty-six consecutive SCD survivors [median age 37.6 years (IQR 24.1-43.2), 31% female] with no previous cardiac history or evidence of ischaemic heart disease underwent CMR on day 6 (IQR 4-10) after admission. Data on ventricular volumes and the extent of late gadolinium enhancement (LGE) were collected. Systolic strain analysis was performed using feature tracking software. Results Left ventricular (LV) and right ventricular (RV) indexed diastolic volumes were 92.9 ± 28.4 ml/m2 and 94.1 ± 29 ml/m2, respectively. LV ejection fraction (EF) and RV EF were 56.8 ± 10.7% and 53.7 ± 10.7%, respectively. Global peak endocardial longitudinal, circumferential, and radial strain were −17.9 ± 4.28%, −23.2 ± 5.8%, and 32.8 ± 10.6%, respectively. Compared to normal range, global longitudinal endocardial strain, longitudinal epicardial strain, circumferential endocardial strain, radial strain, and circumferential endocardial strain rate were impaired. Median volume of LGE was 0.25% (IQR 0.12-1.12) of the LV myocardium with highest prevalence in the inferolateral wall. Patients with cardiomyopathy diagnosis (n = 16) had lower LV strain rate compared to patients without cardiomyopathy (n = 20). Conclusions CMR findings in young patients with aborted SCD due to non-ischaemic heart disease seem to be minor. Although only present in small amounts, LGE appears to have a predilection towards the inferolateral wall in this population.

Stock options are one of the most widely used equity-based compensation mechanisms to mitigate misalignment between managers’ and shareholders’ interests. And yet, it is sometimes suspiciously used as a method of extracting shareholders’ wealth to managers (Bebchuk et al., 2009). The typical ways to do so is using opportunistic timing such as backdating, spring-loading, etc. As shown in Bebchuk et al. (2010), opportunistic timing of option grants increases the incidence of lucky grants, or stock option grants that CEOs receive when the price is abnormally low. We investigate whether lucky grants to CEOs impact firm innovations and, by extension, long-term growth. Using patent citations as a proxy variable for innovation (Kogan et al., 2017), we find that innovation decreases if CEOs received lucky grant in the previous year. The results imply that lucky grants may reduce the incentive for CEOs to invest in risky, long-term projects and negatively affect fir innovation.

Myocardial efficiency measured by 11C-acetate positron emission tomography (PET) has successfully been used in clinical research to quantify mechanoenergetic coupling. The objective of this study was to establish the repeatability of myocardial external efficiency (MEE) and work metabolic index (WMI) by non-invasive concepts. Ten healthy volunteers (63 ± 4 years) were examined twice, one week apart, using 11C-acetate PET, cardiovascular magnetic resonance (CMR), and echocardiography. Myocardial oxygen consumption from PET was combined with stroke work data from CMR, echocardiography, or PET to obtain MEE and WMI for each modality. Repeatability was estimated as the coefficient of variation (CV) between test and retest. MEECMR, MEEEcho, and MEEPET values were 21.9 ± 2.7%, 16.4 ± 3.7%, and 23.8 ± 4.9%, respectively, P

Purpose Deranged metabolism is now recognized as a key causal factor in a variety of heart diseases, and is being studied extensively. However, invasive methods may alter metabolism, and conventional imaging techniques measure tracer uptake but not downstream metabolism. These challenges may be overcome by hyperpolarized MR, a noninvasive technique currently crossing the threshold into human trials. The aim of this study was to image metabolic changes in the heart in response to endogastric glucose bolus and to acute hypertension. Methods Five postprandial pigs were scanned with hyperpolarized [1-13 C]pyruvate cardiac MR at baseline, after oral glucose bolus, and after infusion of angiotensin-II. Results No effect of glucose bolus was seen using hyperpolarized [1-13 C]pyruvate MR despite changes in circulating substrates. During angiotensin-II infusion, blood pressure increased 179% (P = 0.008) and ejection fraction decreased from 54 ± 2% to 47 ± 6% (P = 0.03) The hemodynamic changes were accompanied by increases in the hyperpolarized [1-13 C]pyruvate MR derived ratios of lactate/alanine (from 0.58 ± 0.13 to 0.78 ± 0.06, P = 0.03) and bicarbonate/alanine (from 0.55 ± 0.12 to 0.91 ± 0.14, P = 0.007). Conclusion Glucose loading did not alter cardiac metabolism, but during acute hypertensive stress, cardiac aerobic, carbohydrate metabolism, and pyruvate-lactate exchange was altered. Hyperpolarized MR allows noninvasive evaluation of acute changes in cardiac metabolism. However, hemodynamics must be taken into account when interpreting the results.

Purpose The purpose of this paper is to present a literature review of research on board size, structure, and independence. The paper also reviews research on director voting, and discusses recent work on “busy” directors and board diversity. Design/methodology/approach The authors limited the review to a focused set of research areas. Findings The authors summarize the research on boards of directors and note that research on this important topic should continue. Originality/value This review is intended to summarize the literature on boards of directors.

Background Chronic stress contributes to the development of brain disorders, such as neurodegenerative and psychiatric diseases. Oxidative damage is well known as a causative factor for pathogenic process in brain tissues. The aim of this study is to evaluate the neuroprotective effect of a 30% ethanol extract of Aquilariae Lignum (ALE) in repeated stress-induced hippocampal oxidative injury. Methods Fifty BALB/c male mice (12 weeks old) were randomly divided into five groups (n = 10). For 11 consecutive days, each group was orally administered with distilled water, ALE (20 or 80 mg/kg) or N-acetylcysteine (NAC; 100 mg/kg), and then all mice (except unstressed group) were subjected to restraint stress for 6 h. On the final day, brain tissues and sera were isolated, and stress hormones and hippocampal oxidative alterations were examined. We also treated lipopolysaccharide (LPS, 1 μg/mL)-stimulated BV2 microglial cells with ALE (1 and 5 μg/mL) or NAC (10 μM) to investigate the pharmacological mechanism. Results Restraint stress considerably increased the serum levels of corticosterone and adrenaline and the hippocampal levels of reactive oxygen species (ROS), nitric oxide (NO), and malondialdehyde (MDA). ALE administration significantly attenuated the above abnormalities. ALE also significantly normalized the stress-induced activation of astrocytes and microglial cells in the hippocampus as well as the elevation of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β). The in vitro assay outcome supplemented ALE could dramatically block NF-κB activation in microglia. The anti-oxidative stress effects of ALE were supported by the results of antioxidant components, 4-hydroxynonenal (4-HNE), NADPH oxidase 2 (NOX2), inducible nitric oxide synthase (iNOS) and NFE2L2 (Nrf2) in the hippocampal tissues. Conclusions We firstly demonstrated the neuroprotective potentials of A. Lignum against hippocampal oxidative injury in repeated restraint stress. The corresponding mechanisms might involve modulations in the release of ROS, pro-inflammatory cytokines and stress hormones.

Objective Perturbations in the insulin-like growth factor (IGF) system may contribute to the accelerated cardiovascular disease (CVD) that occurs in patients with type 2 diabetes (T2D). However, it remains unknown whether the IGF system is also involved in the development of early, subclinical CVD. We characterised the IGF system in T2D patients and matched controls and examined the associations with markers of subclinical target organ damage. Methods The study included 99 patients with recently diagnosed T2D and 99 age- and sex-matched controls. IGF-1 and IGFBP-1 to -4 were measured by immunoassays, as were pregnancy-associated plasma protein-A (PAPP-A) and the PAPP-A-generated N-terminal (NT) and C-terminal (CT) IGFBP-4 fragments, which are novel CVD risk markers. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (PWV). Cerebral white matter lesions (WMLs) and carotid artery remodelling were determined by MRI. Results After multivariate adjustments, patients with T2D had lower concentrations of IGFBP-2, IGFBP-4, NT- and CT-IGFBP-4, when compared with controls. IGFBP-2 was inversely correlated to PWV in all subjects in multivariate analysis (P P P = 0.011). Levels of NT- and CT-IGFBP-4 were reduced in T2D patients receiving metformin compared to those in controls and patients not receiving metformin. Conclusions Even in recently diagnosed and well-controlled T2D patients, IGF protein levels are altered and associated with CVD risk factors.

Introduction Uwhangchungsimwon (UCW) is one of the most representative standardized herbal drugs for the treatment of central nervous system diseases, including mood disorders, and has been used for over 600 years in Korea and China. In spite of the long clinical application of UCW, no experimental evidence for its use against depressive disorders exists. Here, we performed an animal study to investigate the anti-depressive effect of UCW and the underlying mechanisms. Methods A social isolation-induced depressive-like model was produced using C57BL/6J male mice by housing the mice individually for 31 days, and the mice underwent daily oral administration of distilled water, UCW (100, 200, 400 mg/kg) or fluoxetine (20 mg/kg) during the final 17 days. A tail suspension test (TST), forced swimming test (FST), and open field test (OFT) were used to explore the effects of UCW on depressive-like behaviors. 5-Hydroxytryptamine (5-HT) was measured in the dorsal raphe nuclei (DRN) using immunofluorescence. The serum corticosterone level was measured with its receptor and catecholamine, along with cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in the hippocampus. Results Social isolation stress effectively induced depressive-like behaviors, and UCW treatment significantly improved the symptoms of depressive-like behavior in the FST, TST, and OFT. The isolation stress-induced depletion of 5-HT was significantly ameliorated by UCW treatment. UCW also attenuated the activation of the glucocorticoid receptor (GR) and the elevated serum corticosterone level, as well as the hippocampal levels of dopamine and norepinephrine. Dexametasone-derived translocation of GR was inhibited by UCW treatment in PC12 cells and HT22 cells. In addition, alterations of tryptophan hydroxylase 2 (TPH2), BDNF, and CREB in the protein analyses were notably regulated by UCW treatment. Conclusions These results provide animal-based evidence for the anti-depressive effect of UCW, and its underlying mechanisms may involve regulating the serotonergic system, the hypothalamic-pituitary-adrenal (HPA) axis, and neurotrophin.

Nonalcoholic fatty liver disease (NAFLD) is very prevalent worldwide and is associated with insulin resistance and metabolic syndrome. Stress is a physiological and biological response to maintain homeostasis of the body against stressors while severe stress response is an important contributor to various illnesses, including metabolic syndrome and brain disorders. We have evaluated the effects of intermittent restraint stress on NAFLD in a high-fat diet (HFD)-fed mouse model. C57/BL6 mice had free access to a 60% HFD for 8 wk, with or without intermittent restraint stress (3 h) conducted three times a week. HFD administration increased fat accumulation in liver tissues. Unlike the stressed standard diet group, the levels of hepatic total cholesterol and triglycerides were significantly ameliorated in the HFD with stress group compared with the HFD alone group. These beneficial results were in accordance with serum levels of liver enzymes (aspartate transaminase, alanine transaminase) and hepatic levels of TNF-α and oxidative stress parameters (reactive oxygen species, nitric oxide, and malondialdehyde). The intermittent restraint stress significantly attenuated the HFD-derived alterations in serum insulin levels, hepatic protein kinase B activity, and gene expression, especially related to lipogenesis. This intermittent restraint stress also elevated the serum epinephrine concentration and activated the adrenergic receptor β2 or β3 in livers or white adipose tissue (WAT). Activation of energy expenditure markers (uncoupling protein 1, peroxisome proliferator-activated receptor-γ coactivator-1α) in brown adipose tissue and the browning of WAT were also observed in the HFD with stress group. Taken together, our findings showed the beneficial effects of sympathetic activation by intermittent restraint stress on HFD-induced hepatic steatosis and partial inflammation.NEW & NOTEWORTHY In modern society, stress is a part of daily life, and a certain level of stress is inevitable to most of the general population. Uncontrolled severe stress is obviously harmful; however, certain kind/level of stress could be beneficial on lipid metabolism via sympathetic activation. Our data suggest that a sympathetic activation by intermittent restraint stress could play a positive role in maintaining the balance of hepatic lipid metabolism, especially under high-fat diet conditions.

In the isopropylation of naphthalene for the production of 2,6-naphthalenedicarboxylate, the monomer of polyethylene naphthalate plastic, a shape-selective mordenite (MOR) zeolite catalyst provides the best selectivity for the desired 2,6-diisopropylnaphthalene. However, the small pore size of the zeolite limits the naphthalene conversion and lowers the stability because of pore-mouth blocking by coke. We discovered that these problems could be mitigated by synthesizing a micro-meso hierarchical pore structure in the MOR zeolite by the recrystallization of MOR with cetyltrimethylammonium bromide as a mesopore-forming surfactant. The recrystallized catalysts allow the facile diffusion of bulky molecules through connected meso- and micropores to and from active catalytic sites located in the small MOR pores. Relative to microporous MOR, the hierarchical MOR catalyst demonstrated a greatly enhanced activity, stability, and coke tolerance, and the intrinsic high shape selectivity of MOR for 2,6-diisopropylnaphthalene was maintained. Mild desilication enlarged the pore volume and formed additional acid sites to increase the activity further.

Objectives: We evaluated the anti-fatigue effects of Rh2-enriched Korean ginseng (Ginseng Rh2+) using a forced exercise-induced chronic fatigue mouse model. Methods: ICR male mice were subjected to running wheel for 1 h, 5 days/week during 4 weeks, and running velocity was gradually increased. Each running session was followed by oral administration of distilled water, Ginseng Rh2+ (150 or 300 mg/kg), or N-acetyl-L-cysteine (NAC, 100 mg/kg) 1 h later. The exercise tolerance and forced swimming test were performed to evaluate the fatigue condition. Results: Chronic forced exercise reduced the physical activity, as evidenced by the behavioral tests, which were notably ameliorated by Ginseng Rh2+ treatment. Ginseng Rh2+ treatment also attenuated the alterations of energy metabolism and oxidative stress in skeletal muscle tissues and/or sera, including malondialdehyde (MDA), lactate concentration and its related factors (lactate dehydrogenase, blood urea nitrogen, and glucose levels). Conclusion: These findings strongly suggest that Ginseng Rh2+ exerts a potent anti-fatigue effect through modulation of energy metabolism and oxidative response.

This paper examines the effect of board characteristics, especially board independence, on firm performance from a dynamic perspective through copula-based quantile regression approaches, which allow us to focus on changes at different points in the distribution of board characteristics. We find that the effect of board independence on Tobin&rsquo, s Q, a proxy of firm value, is negatively associated with firm value, using ordinary least squares (OLS) regression. This negative effect using the conditional mean of the firm value does not hold across the conditional quantiles of the distribution of Tobin&rsquo, s Q, and this finding is still held under both the linear and the nonlinear quantile regressions. We even lessen the assumption of distributions of multivariate board variables by employing parametric copula-based quantile regressions as well as nonparametric ones. The results support our findings. Our results suggest that estimating the quantile effect of board variables on firm value can provide more meaningful insight than just examining the conditional mean effect.

Background Myocardial external efficiency (MEE) is defined as the ratio of kinetic energy associated with cardiac work [forward cardiac output (FCO)*mean systemic pressure] and the chemical energy from oxygen consumed (MVO2) by the left ventricular mass (LVM). We developed a fully automated method for estimating MEE based on a single 11C-acetate PET scan without ECG-gating. Methods and Results Ten healthy controls, 34 patients with aortic valve stenosis (AVS), and 20 patients with mitral valve regurgitation (MVR) were recruited in a dual-center study. MVO2 was calculated using washout of 11C -acetate activity. FCO and LVM were calculated automatically using dynamic PET and parametric image formation. FCO and LVM were also obtained using cardiac magnetic resonance (CMR) in all subjects. The correlation between MEEPET-CMR and MEEPET was high (r = 0.85, P

Owing to its noninvasive nature, hyperpolarized MRI may improve delineation of myocardial metabolic derangement in heart disease. However, consistency may depend on the changeable nature of cardiac metabolism in relation to whole-body metabolic state. This study investigates the impact of feeding status on cardiac hyperpolarized MRI in a large animal model resembling human physiology.Thirteen 30-kg pigs were subjected to an overnight fast, and 5 pigs were fed a carbohydrate-rich meal on the morning of the experiments. Vital parameters and blood samples were registered. All pigs were then scanned by hyperpolarized [1-The fed group had higher blood glucose concentration and mean arterial pressure than the fasted group. Plasma concentrations of free fatty acids (FFAs) were decreased in the fed group, whereas plasma insulin concentrations were similar between groups. Hyperpolarized MRI showed that fed animals had increased lactate/pyruvate, alanine/pyruvate, and bicarbonate/pyruvate ratios. Metabolic ratios correlated negatively with FFA levels.Hyperpolarized MR can identify the effects of different metabolic states on cardiac metabolism in a large animal model. Unlike previous rodent studies, all metabolic derivatives of pyruvate increased in the myocardium of fed pigs. Carbohydrate-rich feeding seems to be a feasible model for standardized, large animal hyperpolarized MRI studies of myocardial carbohydrate metabolism.

An imbalance between excitatory and inhibitory neurotransmitters is known to induce neuronal excitotoxicity which is a major cause of neurodegenerative disorders. Excessive glutamate concentration leads to the neuronal death by increasing oxidative stress and affecting the apoptotic signaling pathway. We investigated the anti-excitotoxic effects and associated working mechanisms of 30% ethanol extract of Aquilariae Lignum (ALE) against hippocampal neuronal death by glutamate. HT22 cells were treated with glutamate (20 mM) for 24 h following pretreatment with ALE (5, 10, 25 μg/mL). Cell viability, biochemical analysis, flow chemistry, and Western blotting assays were performed. Glutamate treatment substantially increased the intracellular level of reactive oxygen species (ROS) and Ca2+ influx into the cell, which were followed by apoptosis. ALE pretreatment, however, significantly attenuated these excitotoxicity-related features according to the results of Annexin V analysis and the lactate dehydrogenase assay, in which the calpain pathway (in a caspase 3-independent manner) may be involved. ALE pretreatment also significantly attenuated the glutamate-induced activation of both inflammation-associated molecules (extracellular signal–regulated kinase, c-Jun N-terminal kinases and p38) and death-related molecules (p53, apoptosis-inducing factor). The inactivation of brain-derived neurotrophic factor (BDNF) was restored by ALE pretreatment. Our results verified that A. Lignum has potential neuroprotective effects on glutamate-induced excitotoxicity in hippocampal neuron cells, and its underlying mechanism may involve the regulation of ROS-mediated cell death pathways.

Background: As one of forces extrinsic to the myocardium, we hypothesized that epicardial fat may contribute to diastolic dysfunction. The objective of this study was to evaluate epicardial fat as a contributing factor to diastolic function. Methods: Two hundred and twenty-one patients without significant arrhythmia, left ventricular hypertrophy, significant valvular disease, decreased left ventricular systolic function, or coronary artery disease were studied. Epicardial fat thickness on the free wall of the right ventricle was measured at end-diastole from the parasternal long-axis views of 3 cardiac cycles. Diastolic function was evaluated using the left atrium volume index, mitral inflow parameters (E, A, E/A, DT [deceleration time]) and mitral annular tissue-Doppler imaging parameters (E’, A’, E/E’). Results: Two hundred and twenty-one patients were divided into 2 groups according to diastolic pattern (normal versus abnormal mitral inflow pattern). There were significant differences in epicardial fat thickness (0.31±0.11 mm vs. 0.48±0.2 mm; P