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Objectives: National health insurance herbal prescription of Korean medicine has been serving important role in public healthcare in spite of continuous demand on revision of system. However, the categories of insurance herbal prescriptions are not equally distributed throughout the KCD-based major disease categories. We analyzed statistical database of claimed national health insurance classified as major disease categories by years. We classified all 56 herbal prescriptions as per their total medical indications into 22 major disease categories to analyze their distribution. Significant increase of M and S-T code claims were found, whereas decrease of U code claims by years. We figured out that the 56 prescriptions were unequally distributed along with enrichment of certain codes such as K and J. Meanwhile, the insurance claim of each prescription was positively correlated with number of code types of their indications. As a result, we believe that the reform of national health insurance herbal prescription list is necessary to promote use of it in clinic.

The network pharmacology (NP) approach is a valuable novel methodology for understanding the complex pharmacological mechanisms of medicinal herbs. In addition, various in silico analysis techniques combined with the NP can improve the understanding of various issues used in natural product research. This study assessed the therapeutic effects of Arum ternata (AT), Poria cocos (PC), and Zingiber officinale (ZO) on hyperlipidemia after network pharmacologic analysis. A protein–protein interaction (PPI) network of forty-one key targets was analyzed to discover core functional clusters of the herbal compounds. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene ontology (GO) term enrichment analysis identified significant categories of hypolipidemic mechanisms. The STITCH database indicated a high connection with several statin drugs, deduced by the similarity in targets. AT, PC, and ZO regulated the genes related to the energy metabolism and lipogenesis in HepG2 cells loaded with free fatty acids (FFAs). Furthermore, the mixture of three herbs had a combinational effect. The herbal combination exerted superior efficacy compared to a single herb, particularly in regulating acetyl-CoA carboxylase (ACC) and carnitine palmitoyltransferase 1 (CPT-1). In conclusion, the network pharmacologic approach was used to assess potential targets of the herbal combination for treatment. Experimental data from FFA-induced HepG2 cells suggested that the combination of AT, PC, and ZO might attenuate hyperlipidemia and its associated hepatic steatosis.

Background: Although the beneficial effects of cardiac resynchronization therapy (CRT) in heart failure (HF) are fully established in HF with left ventricular ejection fraction (LVEF) ≤ 35%, CRT strategy for HF with mildly reduced ejection fraction (HFmrEF) is controversial. Left bundle branch area pacing (LBBAP) is an emerging pacing modality and an alternative option to CRT, and the efficacy and safety are promising so far. The aim of this analysis was to perform a systematic review of the literature and meta‐analysis on impact of LBBAP strategy in HFmrEF, with LVEF between 35 % and 50%. Methods: PubMed, Embase, and Cochrane Library were searched for full-text articles on LBBAP from inception to July 17, 2022. The outcomes of interest were QRS duration, and LVEF at baseline and at follow-up in mid-range HF. Data were extracted and summarized. A random-effect model incorporating the potential heterogeneity was used to synthesize the results. Results: Out of 1065 articles, 8 met the inclusion criteria for 211 mid-range HF patients with an implant LBBAP across the 16 centers. The average implant success rate with lumenless pacing lead use was 91.3%, and 19 complications were reported among all 211 enrolled patients. During the average follow-up of 9.1 months, average LVEF were 39.8% at baseline and 50.5% at follow-up (MD: 10.90%, 95% CI: 6.56 - 15.23 PConclusion: LBBAP could significantly reduce QRS duration and improve systolic function in patient with LVEF between 35 and 50%. Application of LBBAP as a CRT strategy for heart failure with mildly reduced ejection fraction may be a viable option.

Introduction: His bundle pacing (HBP) was developed as a physiological conduction system pacing to complement the problem of conventional right ventricular pacing (RVP) related to dyssynchrony. Recently, left bundle branch area pacing (LBBAP), which overcomes the shortcomings of HBP, has been implemented. Most researches on initial experiences with LBBAP have reported that it was achieved through a lumen-less pacing lead (LLL) with a fixed helix design; however, there are situations in which LLL cannot be used. The purpose of present research is to evaluate the initial experience and learning curve of LBBAP using a standard stylet-driven lead with an extendable helix design. Methods: 265 patients who underwent LBBAP or conventional RVP performed by operators without previous LBBAP experience at Yonsei University Severance Hospital in Korea between December 2020 and October 2021 were enrolled. LBBAP was performed using a stylet‐driven pacing lead with an extendable helix. The learning curve was evaluated by analyzing fluoroscopy and procedure times. Results: LBBAP was successful in 65 of 69 (94.2%) patients during the observation period. In 65 patients who underwent LBBAP, mean fluoroscopy and procedural times were 17.1 ± 17.2 minutes and 64.2 ± 33.5 minutes, respectively. The learning curve for achieving LBBAP plateaued after the 24th case, with a gradually shortened in procedure time. Conclusion: During the initial experience with LBBAP, fluoroscopy and procedural times improved with increasing operator experience. For operators who were experienced in cardiac pacemaker implantation, the steepest part of the learning curve was over the first 20-25 cases.

Targeting Toll-like receptor 4/myeloid differentiation factor 2 (TLR4/MD2) signaling is regarded as a potential strategy for treating inflammatory diseases. Saponaria officinalis L. is rich in saponin, which include quillaic acid, gypsogenin, saponarin, and hederagenin. We evaluated the pharmacological activity of a Saponaria officinalis extract in THP-1 derived macrophages and RAW264.7 macrophages. TLR4/MyD88 complex formation and downstream signals were investigated by co-immunoprecipitation (Co-IP). In silico docking simulation was conducted to predict binding scores and perform 3D modeling of saponarin-TLR4/MD2 complex. A hexane fraction of Saponaria officinalis (SH) and fr.1 (a sub-fraction 1 of SH) inhibited mitogen-activated protein kinase (MAPK) signaling, nuclear factor kappa b (NF-κB) activity, cytokine production, and the expressions of marker genes specific for M1 polarization. The inhibitory effects of fr.1 and saponarin on TLR4/MyD88 complex formation were observed by western blotting TLR4 co-immunoprecipitated proteins. Saponarin and fr.1 markedly attenuated LPS-induced inflammatory cytokines, thus reducing mortality and morphological abnormality in zebrafish larvae. Finally, docking simulation revealed that saponarin can directly interact with TLR4/MD2 complex to inhibit downstream signalings. Our findings suggest that saponarin reduces downstream inflammatory response by disrupting TLR4/MD2 complex and blocking MyD88-dependent inflammatory signaling.

Despite its deleterious effects on living cells, oxidative stress plays essential roles in normal physiological processes and provides signaling molecules for cell growth, differentiation, and inflammation. Macrophages are equipped with antioxidant mechanisms to cope with intracellular ROS produced during immune response, and Nrf2 (NF-E2-related factor 2)/HO-1 (heme oxygenase-1) pathway is an attractive target due to its protective effect against ROS-induced cell damage in inflamed macrophages. We investigated the effects of ethanol extract ofA. villosum(AVEE) on lipopolysaccharide- (LPS-) stimulated inflammatory responses generated via the Nrf2/HO-1 signaling pathway in murine peritoneal macrophages and RAW 264.7 cells. AVEE was found to suppress the NF-κB signaling pathway, thus, to reduce proinflammatory cytokine, nitric oxide, and prostaglandin levels in peritoneal macrophages and Raw 264.7 cells treated with LPS, and to enhance HO-1 expression by activating Nrf2 signaling. Furthermore, these anti-inflammatory effects of AVEE were diminished when cells were pretreated with SnPP (a HO-1 inhibitor). HPLC analysis revealed AVEE contained quercetin, a possible activator of the Nrf2/HO-1 pathway. These results showA. villosumethanol extract exerts anti-inflammatory effects by activating the Nrf2/HO-1 pathway in LPS-stimulated macrophages.

Matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9, are very important gelatinases that are overexpressed during tumor metastasis. Up to date, several MMP inhibitors have been developed from natural sources as well as organic synthesis. In the present study, the MMP-2 and MMP-9 inhibitory effects of 3,5-dicaffeoyl-epi-quinic acid (DCEQA), a caffeoylquinic acid derivative isolated from Atriplex gmelinii, were investigated in phorbol 12-myristate 13-acetate (PMA)-treated human HT1080 fibrosarcoma cells. Gelatin zymography and immunoblotting showed that DCEQA significantly inhibited the PMA-induced activation and expression of MMP-9 but was not able to show any effect against MMP-2. DCEQA treatment was also shown to upregulate the protein expression of tissue inhibitor of MMP-1 along with decreased MMP-9 protein levels. Moreover, the effect of DCEQA on phosphorylation of mitogen activated protein kinases (MAPKs), analyzed by immunoblotting, indicated the DCEQA inhibited the MMP-9 by downregulation of MAPK pathway. Collectively, current results suggested that DCEQA is a potent MMP-9 inhibitor and can be utilized as lead compound for treatment of pathological complications involving enhanced MMP activity such as cancer metastasis.

Background Herbal combinations are regarded as basic strategy in oriental medicine with various purposes. Ephedrae herba (EH) and Coicis semen (CS) are two herbal medicines used to treat obesity in many herbal prescriptions, yet the effect and significance of this herbal pair have not been evaluated. Purpose This study is to elucidate the effect of a novel herbal pair, EH-CS, on obesity and identify the key synergistic mechanism underlying it. Methods We investigated the network of herbs comprising the anti-obesity herbal prescriptions. Using the tools of network pharmacology, we investigated the compound-target interactions of EH and CS in combination to predict their effects in combination. Five EH-CS samples with different EH to CS ratios were prepared to investigate their efficacies in adipocytes. Results 1-mode network analysis of herbs in prescriptions based on literature review revealed the importance of EH-CS in anti-obesity prescriptions. The herbal combination comprised of equivalent weights (1:1) of EH and CS most potently reduced mature adipocyte adiposity, although several markers of adipogenesis and lipid synthesis were more suppressed by pure EH. PTGS2 (COX-2 gene) expression, a common target of EH and CS as deduced by compound-target network analysis, was affected by EH-CS extract treatments. However, EH at high concentration (25 μg/ml) notably increased PTGS2 expression without adversely affecting cell viability. However, EH-CS combination of the same concentration markedly decreased PTGS2 gene expression. Conclusion These results show that the compounds in CS and EH act in concert to enhance the pharmacological effect of EH, but control unexpected effects of EH treatment.

Sochehwan (SCH) is an herbal prescription from traditional oriental medicine and is currently used to treat digestive ailments. In a previous study, SCH was found to have the potential to attenuate metabolic syndrome (MetS) by activating AMPK and downstream signaling. From the view of drug repurposing, the efficacy of SCH on alcoholic liver injury is implied in classic medical texts but is yet to be proven. C57BL/6J mice were pre-treated with SCH orally for 5 days and challenged by providing a pair-fed Lieber DeCarli diet containing alcohol for 20 days. Hepatic enzyme and triglyceride levels and endoplasmic reticulum (ER) stress-related markers were analyzed. Moreover, mitogen-activated protein kinases (MAPKs) and cytochrome P450 2E1 (CYP2E1) levels were determined. CYP2E1-transfected HepG2 cells were used to test the cytoprotective efficacy of SCH against the adverse effects of alcohol in vitro. In mice, SCH administration notably reduced hepatic enzyme activity and neural lipid levels. Furthermore, ER-stress markers and MAPK phosphorylation were reduced due to ROS suppression, which was attributed to decreased CYP2E1 expression in liver tissue. In addition, SCH successfully protected CYP2E1-transfected HepG2 cells against ethanol. Our findings suggest SCH attenuated alcohol-induced liver injury by inhibiting CYP2E1 expression and indicate drug repurposing should be considered as a valuable option for drug development in traditional herbal medicines.

Objective: To investigate matrix metalloproteinases (MMP)-2 and MMP-9 inhibitory effect of Salsola komarovii Iljin, an edible halophyte with health beneficial effects. Methods: Salsola komarovii crude extracts (SKI), and solvent (n-hexane, 85% aq. MeOH, n-BuOH, and H2O) fractionated extracts of SKI were prepared. Gelatin zymography was carried out to observe MMP enzymatic activity. The release of the MMP enzymes was measured by enzyme-linked immunosorbent assay. Expression of MMPs in mRNA and protein level were investigated by polymerase chain reaction analysis and immunoblotting, respectively. Results: SKI and SKI fractions inhibited active MMP-2 and MMP-9 amount in the treated cell culture medium. Also, SKI suppressed the release of MMP-2 and MMP-9 from stimulated HT1080 human fibrosarcoma cells. Furthermore, SKI suppressed the mRNA and protein expression of MMP-2 and MMP-9. SKI fractions showed parallel effects except for H2O fraction which did not yield any significant MMP inhibitory effect. Among fractions, 85% aq. MeOH was the most active fraction to inhibit both the enzymatic effect and expression of MMP-2 and MMP-9. Conclusions: SKI may contain potential MMP release inhibitory compounds. Salsola komarovii is a promising source of compounds against MMP and could be utilized in the development of antitumor agents.

Network pharmacology (NP) is a useful, emerging means of understanding the complex pharmacological mechanisms of traditional herbal medicines. Sochehwan (SCH) is a candidate herbal prescription for drug repurposing as it has been suggested to have beneficial effects on metabolic syndrome. In this study, NP was adopted to complement the shortcomings of literature-based drug repurposing strategies in traditional herbal medicine. We conducted in vitro studies to confirm the effects of SCH on potential pharmacological targets identified by NP analysis. Herbal compounds and molecular targets of SCH were explored and screened from a traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) and an oriental medicine advanced searching integrated system (OASIS). Forty-seven key targets selected from a protein-protein interaction (PPI) network were analyzed with gene ontology (GO) term enrichment and KEGG pathway enrichment analysis to identify relevant categories. The tumor necrosis factor (TNF) and mitogen-activated protein kinase (MAPK) signaling pathways were presented as significant signaling pathways with lowest p-values by NP analysis, which were downregulated by SCH treatment. The signal transducer and activator of transcription 3 (STAT3) was identified as a core key target by NP analysis, and its phosphorylation ratio was confirmed to be significantly suppressed by SCH. In conclusion, the NP-based approach used for target prediction and experimental data obtained from Raw 264.7 cells strongly suggested that SCH can attenuate inflammatory status by modulating the phosphorylation status of STAT3.

Matrix metalloproteinases (MMPs) are endopeptidases that take significant roles in extracellular matrix degradation and therefore linked with several complications such as metastasis of cancer progression, oxidative stress, and hepatic fibrosis. Ishige okamurae, a brown alga, has been reported to possess various bioactivities including but not limited to antiviral, antimicrobial, and anti-inflammatory. In this study, the potential of I. okamurae against cancer cell invasion was evaluated through MMP inhibitory effect in HT1080 fibrosarcoma cells in vitro. I. okamurae crude extract was fractionated with organic solvents, namely water (H2O), n-butanol (n-BuOH), 85% aqueous methanol (85% aq. MeOH), and n-hexane (n-Hex). The non-toxicity of fractions was confirmed by MTT assay. All fractions inhibited the enzymatic activities of MMP-2 and MMP-9 according to gelatin zymography assay. Cell migration was also inhibited by 85% aq. MeOH fraction, significantly. In addition, both gene and protein expressions of MMP-2 and MMP-9, and tissue inhibitor of MMPs (TIMPs) were evaluated by RT-PCR and Western blotting, respectively. Fractions suppressed the mRNA and protein levels of MMP-2 and MMP-9 while elevating the TIMP-1 and TIMP-2, H2O fraction being the least effective while 85% aq. MeOH fraction the most. Collectively, 85% aq. MeOH fraction from brown algae could be a potential inhibitor of MMPs, suggestively considering presence of poly-unsaturated fatty acids in high amounts.

BACKGROUND Rhythm and timing training is stimulation that substitutes for a damaged function controls muscular movement or temporal element, which has positive impacts on the neurological aspect and movement of the brain. OBJECTIVE This study is to assess the changes caused by rhythm and timing training using an interactive metronome (IM) on upper extremity function, ADL and QOL in stroke patients. METHODS In order to assess the effects of IM training, a group experiment was conducted on 30 stroke patients. Twelve sessions of IM training were provided for the experimental group three times a week for four weeks, while the control group was trained with a Bilateral arm Self-Exercise (BSE) for the same period. Both groups were evaluated by pre- and post-tests through MFT, MAL, K-MBI and SS-QOL. RESULT There were more statistically significant differences (

Relatively high proportions of proinflammatory M1-like macrophages in tissues may lead to vascular impairment and trigger numerous diseases including atherosclerosis-related cardiovascular disease (CVD). Jisil Haebaek Gyeji-tang (JHGT), a polyherbal decoction, is traditionally used to treat various human ailments including chest pain, angina, and myocardial infarction. In the present study, we investigated the anti-inflammatory effects of JHGT on lipopolysaccharide- (LPS-) stimulated M1 macrophage polarization generated via the mitogen-activated protein kinases (MAPKs) pathway in RAW 264.7 mouse macrophages. The reducing power of JHGT was also investigated using DAF-FA DA in a zebrafish model. JHGT significantly reduced inflammatory mediator levels, including iNOS, COX2, TNF-α, IL-6, and IL-1β, as compared with LPS-stimulated controls in vitro and ex vivo. Furthermore, JHGT suppressed the ERK1/2, JNK, and p38 MAPK pathways and reduced p-IκBα levels and the nuclear translocation of NF-κB in RAW 264.7 cells. In addition, treatment with JHGT significantly reduced the NO levels in LPS-treated zebrafish larva ex vivo. Our findings show the potent anti-inflammatory properties of JHGT are due to its suppression of MAPK signaling, NF-κB translocation, and M1 macrophage polarization.

As the battery energy storage system (BESS) has been considered to be a solution to the diminished performance of frequency response in the Korean power system, in which renewable energy resources (RESs) are expected to increase rapidly, this paper proposes a control strategy for providing both the virtual inertia and primary frequency response considering the MW-scale BESS installed by the Korea Electricity Power Corporation (KEPCO). The benefit of such a fast and flexible BESS can be maximized by the proposed control strategy for making it provide both the inertia and primary frequency response, which would be deficit with the increased RES. In the proposed control strategy, the state of charge (SOC) is maintained in the specific range in which the life cycle is maximized, the interference of SOC recovery by frequency control is minimized, the responding capacity for providing the virtual inertia response is maximized during the transient period, and the performance requirements for frequency response are satisfied. The effectiveness of the proposed strategy is verified by both Korean power system model-based simulation and on-site operations.

BACKGROUND In this study, we aimed to investigate the relationship between echocardiographic epicardial fat thickness (EFT), neutrophil to lymphocyte ratio (NLR; an important inflammatory marker), and diurnal blood pressure (BP) changes in patients with recently diagnosed essential hypertension. METHODS A total of 647 patients underwent echocardiography and 24 hours of ambulatory BP monitoring. EFT was measured by echocardiography, while NLR was measured by dividing the neutrophil count by the lymphocyte count. Patients were categorized into three groups according to BP pattern: the normotensive group, the dipper group, and the non-dipper group. RESULTS The mean EFT was highest in the non-dipper group (non-dipper group, 7.3 ± 3.0 mm; dipper group, 6.1 ± 2.0 mm; control group, 5.6 ± 2.0 mm; p < 0.001). NLR was also highest in the non-dipper group (non-dipper, 2.75 ± 2.81; dipper, 2.01 ± 1.32; control, 1.92 ± 1.11; p < 0.001). EFT was significantly correlated with age (r = 0.160, p < 0.001) and NLR (r = 0.353, p < 0.001). Furthermore, an EFT ≥ 7.0 mm was associated with the non-dipper BP pattern with 51.3% sensitivity and 71.6% specificity [95% confidence interval (CI) = 0.56-0.65, p < 0.001]. In a multivariate analysis, EFT [adjusted odds ratio (OR) = 3.99, 95% CI = 1.22-13.10, p = 0.022] and NLR (OR = 1.34, 95% CI = 1.05-1.71, p = 0.018) were independent parameters that distinguished a non-dipper pattern after adjustment for cardiovascular risk factors. CONCLUSION EFT and NLR are independently associated with impaired diurnal BP profiles in hypertensive individuals. EFT (as measured by echocardiography) and NLR appear to be helpful in stratifying cardiometabolic risk.

Over the last decade, the link between nonalcoholic fatty liver disease (NAFLD) and insulin resistance has attracted considerable attention. Caused by chronic hyperglycemic stress, insulin resistance (IR) impairs insulin signal transduction and leads to the development of NAFLD. Jwa Kum Whan (JKW), a herbal formula in Traditional Korean Medicine, consists of two medicinal herbs that possess notable effects against hyperglycemia and IR. In this study, we sought to determine the pharmacological effects of JKW, and the mechanisms responsible, on hepatic steatosis in free fatty acids (FFAs)-stimulated HepG2 cells and in high-fat diet (HFD)-fed obese mice. Treatment with JKW significantly decreased intracellular lipid accumulation in vitro. Furthermore, JKW significantly triggered the phosphorylation of insulin receptor substrate-1 (IRS-1) and phosphoinositide 3-kinase (PI3K) and modulated glucose and lipid metabolism via an AMP-activated protein kinase (AMPK) signaling pathway. Analysis of serum parameters in HFD-fed mice showed that JKW improved glucose levels and insulin resistance index (HOMA-IR). In addition, JKW successfully reduced hepatic triglyceride (TG) and cholesterol accumulation. Our results suggest that JKW alleviates NAFLD by modulating the insulin signaling pathway and glucose metabolism. These findings provide a scientific rationale for the potential use of JKW for the treatment and prevention of NAFLD.

Background and Objectives: The incidence of atrial fibrillation (AF) is increased in heart failure (HF). Two major mechanisms of ventricular arrhythmia in HF are reentry mechanism due to tissue fibrosis and triggered activity due to an altered calcium-handling process. Unlike studies on ventricular arrhythmogenesis, only few studies investigated the relationship between changes in the calcium-handling process in atrial tissue and their relationship with atrial arrhythmogenesis in HF. Materials and Methods: HF was induced by myocardial infarction, and the rats were fed a normal sodium diet for 10 weeks and administered isoproterenol (30 μg/[kg∙h]) for the last 2 weeks of the experiment. Echocardiography and AF induction studies were conducted. In addition, mRNA and protein expressions of sarcoplasmic reticulum Ca 2+ -ATPase (SERCA), phospholamban (PLB), ryanodine receptor 2 (RyR2), and sodium calcium exchanger (NCX) were studied. Results: In the HF group, the ejection fractions were significantly decreased. AF duration (12.4±7.9 sec sham and 441.7±12.4 sec HF) and inducibility (8.0%±3.3% sham and 48.5%±10.6% HF) were significantly increased relative to the sham group. Atrial fibrosis tissue amounts were significantly increased in HF (0.20%±0.02% sham and 3.41%±0.45% HF). Atrial SERCA, PLB, RyR2 protein, and mRNA expressions were significantly decreased in HF, while the NCX protein expression was significantly increased in the HF group. The protein PLB/SERCA ratio was significantly increased by about 33% in the HF group. Conclusion: Changes in the protein and mRNA levels of calciumhandling proteins and increase in the degree of atrial fibrosis are important contributing factors of AF in severe HF.

Limonium tetragonum has been well-known for its antioxidative properties as a halophyte. This study investigated the antimetastasis effect of solvent-partitioned L. tetragonum extracts (LTEs) and isolated compounds on HT1080 mouse melanoma cell model with a focus on matrix metalloproteinase (MMP) activity and TIMP and MAPK pathways. Upregulation and stimulation of MMPs result in elevated degradation of extracellular matrix which is part of several complications such as metastasis, cirrhosis, and arthritis. The anti-MMP capacity of LTEs was confirmed by their MMP-inhibitory effects, regulation of MMP and TIMP expression, and suppression of MAPK pathway. Among all tested LTEs, 85% aq. MeOH and n-BuOH were found to be most active fractions which later yielded two known flavonoid glycosides, myricetin 3-galactoside and quercetin 3-o-beta-galactopyranoside. Anti-MMP potential of the compounds was confirmed by their ability to regulate MMP expression through inhibited MAPK pathway activation. These results suggested that L. tetragonum might serve as a potential source of bioactive substances with effective anti-MMP properties.

Background The sitting position has potential for serious complications such as cerebral ischemia and venous air embolism. This study investigated the effects of intermittent sequential compression device (SCD) on the changes in regional cerebral oxygen saturation (rSO2) during the sitting position. Methods Sixty-six healthy patients undergoing shoulder arthroscopy in sitting position were randomly assigned to either control (N = 33) or SCD (N = 33) groups. Hemodynamic variables and the rSO2 were measured 5 minutes after the induction of anesthesia (Tsupine, baseline values), and 1, 3, and 5 minutes after raising the patient to a 70-degree sitting position (T1, T3, and T5). The incidence of hypotension was recorded. Results The incidence of hypotension was significantly higher in the control group (8/33) than that in the SCD group (1/33) (P = 0.027, odds ratio 0.170, 95% CI 0.042-0.684). The rSO2 was significantly higher in the SCD group compared with those in the control group at T3 and T5. Within the group, rSO2 decreased significantly only in the control group compared with baseline value at T1, T3, and T5. The % change in rSO2 from T0 to T1, T3, and T5 were significantly lower in the SCD group compared to those in the control group. Conclusions The application of SCD to the lower extremities during sitting position under sevoflurane anesthesia was a simple and effective method to attenuate the decrease in cerebral oxygen saturation.

This review describes the characterization and application of poly(hydroxyalkanoates), PHAs, a remarkable family of natural polyesters with a wide array of useful properties and potential applications. It places specific emphasis on the work of Robert H. Marchessault and his many colleagues outlining how Marchessault’s body of work both shaped the field and complemented the work of his contemporaries. Particular attention will focus on the “rediscovery” of poly(β-hydroxybutyrate), PHB, the first PHA to be discovered, from the late 1950s onward, highlighting some of the historical aspects of PHA’s path toward commercial applications. It will also cover why this class of materials is so unique, including PHA structure–properties relationships, its unique crystalline behaviour, in vivo – in vitro synthesis and degradation, and PHA-graft-copolymers.Key words: poly(hydroxyalkanoate), PHA, poly(β-hydroxybutyrate), PHB, biopolymers, bacterial polyester, random copolymers, polymer single crystals, graft copolymers.

Poly(ethylene oxide)-block-poly(styrene oxide) (PEO-b-PSO) and PEO-b-poly(butylene oxide) (PEO-b-PBO) of different chain lengths were synthesized and characterized for their self-assembling properties in water by dynamic/static light scattering, spectrofluorimetry, and transmission electron microscopy. The resulting polymeric micelles were evaluated for their ability to solubilize and protect the anticancer drug docetaxel (DCTX) from degradation. The drug release kinetics as well as the cytotoxicity of the loaded micelles were assessed in vitro. All polymers formed micelles with a highly viscous core at low critical association concentrations (10 mg/L). Micelle morphology depended on the nature of the hydrophobic block, with PBO- and PSO-based micelles yielding monodisperse spherical and cylindrical nanosized aggregates, respectively. The maximum solubilization capacity for DCTX ranged from 0.7 to 4.2% and was the highest for PSO micelles exhibiting the longest hydrophobic segment. Despite their high affinity for DCTX, PEO-b-PSO micelles were not able to efficiently protect DCTX against hydrolysis under accelerated stability testing conditions. Only PEO-b-PBO bearing 24 BO units afforded significant protection against degradation. In vitro, DCTX was released slower from the latter micelles, but all formulations possessed a similar cytotoxic effect against PC-3 prostate cancer cells. These data suggest that PEO-b-P(SO/BO) micelles could be used as alternatives to conventional surfactants for the solubilization of taxanes.

Atrial fibrillation (AF) is the most common sustained arrhythmia. AF is caused by inflammation, oxidative stress, and various structural heart diseases. An important key factor in AF promotion is that atrial cardiomyocytes have constitutively active acetylcholine-activated K+ (IKACh) current that is enhanced by the tachycardia. Furthermore, it is known that heat shock proteins (HSPs) are involved in the protection against different forms of cellular stress and recent investigators reported that the HSP inducing compound geranylgeranylacetone (GGA, also known as teprenone) prevents atrial remodeling and attenuates the promotion of AF. Whether GGA and GGA-derivatives prevent the acetylcholine-activated K+ current is unknown. Methods: We examined the effect of HSP inducer GGA and 5 derivatives on IKACh current in mouse atrial cardiomyocytes. In the present study, the IKACh current was recorded using a nystatin-perforated whole cell patch-clamp technique following activation by acetylcholine (10 μM for 2 min). After the measurement of the baseline IKACh current, atrial cardiomyocytes were treated with GGA 10μM or a derivative of GGA (NYK9274, NYK9308, NYK9354, NYK9356 or NYK9376) for 10min and the IKACh current was re-measured. Results: IKACh current in mouse atrial cardiomyocyte treated with acetylcholine (10 μM) was significantly increased, which was markedly attenuated by GGA 10μM treatment (n=5, peak; 54±11.2%, quasi-steady-state; 58±11.4%, p Conclusion: This study provides important evidences that the HSP inducer GGA facilitates its potent antiarrhythmic effect by inhibiting IKAch, which underlies electrical remodeling in mammalian atrial cardiomyocytes. Furthermore, two GGA derivatives, NYK9308 and NYK9356, with improved pharma-chemical properties compared to GGA, reveal similar protective effects compared to GGA, and provide important background information for the use of GGA and GGA-like compounds in patients with AF.

Introduction: Recently, several studies have shown that high-intensity interval training (HIT) is superior to continuous moderate-intensity exercise (CME) for improvement on endothelial in patients with cardiovascular disease. However, little is known about its effects on changes in blood pressure, especially in hypertensive patients. Hypothesis: To compare the effects of HIT and CME on changes in blood pressure reduction and endothelial function in pre- and hypertensive patients.. Methods: Seventeen pre- and hypertensive patients, aged 52.1±7.6, participated in this study, tapered off their medications, if necessary, and were randomized to either HIT (n=9) or CME (n=8) group. HIT was composed of 5 sets of 3 min exercise at 80% HRR, and each interval was separated by 3 min recovery at 40% HRR. CME was composed of 35 min exercise at 60% HRR. Both groups were designed to use same energy expenditure, and performed exercise 5 days per week for 4 weeks. Endothelial function was determined by assessing endothelial progenitor cells (EPCs) using flow cytometry and flow mediated dilation (FMD) using ultrasonography. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured at rest and during exercise at 60% HRR by using automatic blood pressure monitor Results: : SBP at rest were significantly decreased in both groups, but these changes were not different between groups. DBP at rest and during exercise was significantly decreased in HIT, but not in CME. However, SBP during exercise was significantly decreased in CME, but not in HIT. EPCs and FMD were significantly increased in HIT, but not in CME. Conclusions: The results of this study suggest that HIT and CME equally have beneficial effects on blood pressure reduction in pre- and hypertensive patients. However, HIT may improve endothelial function better than CME. Therefore, HIT can be an effective rehabilitation programs for hypertensive patients.

We aimed to investigate the role of brain natriuretic peptide (BNP) levels and left ventricular (LV) filling pressures in thromboembolic risk in patients with non-valvular atrial fibrillation (AF).Among 327 patients with non-valvular AF, the ratio of peak early filling velocity to mitral annulus velocity (E/Ea) and N-terminal proBNP (NT-proBNP) was compared according to the presence of left atrial appendage (LAA) dysfunction [presence of spontaneous echo contrast (SEC)≥grade 3 and/or reduced LAA emptying flow velocity20cm/s].Compared to patients without LAA dysfunction, patients with LAA dysfunction presented with significantly higher CHADS2 scores (1.24±1.14 vs. 1.68±1.31, p=0.005), high-sensitivity C-reactive protein (0.36±1.18mg/dl vs. 0.66±1.32mg/dl, p=0.043), and NT-proBNP (765.3±2534.8pg/ml vs. 2266.9±6117.4pg/ml, p=0.002). Furthermore, patients with LAA dysfunction showed significantly higher left atrial volume index (LAVI, 25.1±10.9 vs. 43.1±22.1, p0.001) and E/Ea (10.8±7.27 vs. 7.97±2.50mg/dl, p0.001). Plasma logNT-proBNP levels were significantly correlated with the presence of SEC (r=0.276, p0.001), LAA emptying flow velocity (r=-0.492, p0.001), LAVI (r=0.405, p0.001), and E/Ea (r=0.353, p0.001). Binary logistic regression analysis showed that high NT-proBNP level249.7pg/ml (odds ratio, OR 6.79, 95% confidence interval, CI 3.16-15.55, p0.001) and E/Ea10 (OR 4.41, 95% CI 2.39-8.15, p0.001) were independent predictors of LAA dysfunction after adjustment of known thromboembolic risk factors.Elevated plasma NT-proBNP concentrations and LV filling pressures represented by LAA dysfunction may be reliable surrogate markers for predicting thromboembolic risk in patients with AF.

The direct impact of sevoflurane on intraoperative left ventricular (LV) systolic performance during cardiac surgery has not been fully elucidated. Peak systolic tissue Doppler velocities of the lateral mitral annulus (S′) have been used to evaluate LV systolic long-axis performance. We hypothesized that incremental sevoflurane concentration (1.0–3.0 inspired-vol%) would dose-dependently reduce S′ in patients undergoing cardiac surgery due to mitral or aortic insufficiency. In 20 patients undergoing cardiac surgery in sevoflurane–remifentanil anesthesia, we analyzed intraoperative S′ values which were determined after 10 min exposure to sevoflurane at 1.0, 2.0, and 3.0 inspired-vol% (T1, T2, and T3, respectively) with a fixed remifentanil dose (1.0 μg/kg/min) using transesophageal echocardiography. Linear mixed-effect modeling demonstrated dose-dependent declines in S′ according to the end-tidal sevoflurane concentration increments (CET-sevoflurane, p

Solutions of copolymers E 2 1 B 1 0 E 2 1 and E 3 5 B 1 0 E 3 5 were studied by rheometry, polarized light microscopy, small-angle X-ray scattering, and small-angle neutron scattering. With increase in concentration, both copolymers first form a body-centered cubic hard gel. Comparison is made with published results (Langmuir 1998, 14, 5782) for the related copolymer E 1 6 B 1 0 E 1 6 , which first forms a hexagonal hard gel. Published values of the association numbers of the micelles were used to characterize the stretching of the B blocks in the micelle cores, hence the tendency to form cylindrical micelles and so hexagonal hard gels. Soft gels were detected at concentrations below and at temperatures below and above the boundaries for hard gel formation.

In the present paper, low molecular weight poly(β-hydroxybutyrates) (PHBs), which were obtained by acidic and basic hydrolysis of bacterially produced PHB, were characterized by gel permeation chromotography (GPC), 1H, 13C and 31P NMR. The assignments of the resonances of 13C NMR spectra from unsaturated end and hydroxy end groups were made using heteronuclear multiple quantum coherence (HMQC) NMR technique. Unsaturation contents and number average molecular weights of the PHBs were determined mainly by 1H and 31P NMR. Direct measurement of the molecular weights of PHB has also been carried out by matrix assisted laser desorption ionization (MALDI). Based on the characterization of these low molecular weight PHBs, the heterogeneous hydrolysis mechanism is discussed and the scission of PHB chains is proposed to occur at the surfaces and interfaces of lamellar crystals. The unsaturated end group is formed by dehydration of the chain ends by β-elimination after ester hydrolysis, which is different from the mechanistic steps of the formation of unsaturated ends in thermal decomposition of PHB. The correlation of thickness of crystal lamellae and the melting points has also been discussed. The plot of the melting point against reciprocal lamellar thickness for low molecular weight PHB indicates the pronounced effect of the surface energy of these crystals, which is caused by the large proportion of end groups.

The first observation of ordered microphase structures in poly(oxyethylene)–poly(oxypropylene) diblock copolymers melts is reported. Two diblock copolymers were synthesised by anionic polymerisation, i.e. E130P58 and E107P69 where E represents an oxyethylene unit, OCH2CH2, and P an oxypropylene unit, OCH2CH(CH3). The volume fractions of the two components were in the range 0.5–0.6. Order in the melt phase was confirmed by small angle X-ray scattering, and order-to-disorder transitions (ODT) were located at 106°C (E130P58) and 114°C (E107P69). In a related experiment, a triblock copolymer with perdeuterated P blocks, E33dP42E33, was synthesised and studied in the melt phase by small-angle neutron scattering. This allowed determination of the temperature dependence of the Flory–Huggins interaction parameter for the poly(oxyethylene)–poly(oxypropylene) system, i.e. χ=20.2/T+0.0221.

Small-angle neutron scattering (SANS) has been used to investigate structural changes during the de-swelling of poly(N-isopropylacrylamide) [poly(NIPAM)] microgel particles induced by temperature variation and the addition of free polymer [poly(ethylene oxide)]. The extent of particle de-swelling was characterized by photon correlation spectroscopy (PCS). Thermally-induced de-swelling of poly(NIPAM)/deuterated water dispersions occurred on increasing the temperature in the region of the lower critical solution temperature (LCST). The latter was found to be 34°C, which is 2°C higher than the value reported for poly(NIPAM) particles dispersed in water. The SANS data exhibit a Porod form (Q−4) of scattering in regard to the size of the colloidal particles. However, in the swollen state, the scattering measured at temperatures less than the LCST, also has a contribution from poly(NIPAM) chains in a solution-like environment (Ornstein–Zernike scattering). The trends observed in the SANS data as a function of temperature were simulated using a model comprised of Porod and Ornstein–Zernike scattering terms. The SANS data confirm earlier PCS measurements showing that addition of free polymer induces particle de-swelling. The SANS data obtained using added free polymer are the first examples of their type to be reported.

The structure of (deuterated ethylene oxide)23−(propylene oxide)34−(deuterated ethylene oxide)23 block copolymer micelles was studied in the unimer-to-micelle transition region using small angle neutron scattering (SANS). A three-parameter core−corona model fit to the set of scattering curves obtained with various mixtures of D2O and H2O as the solvent yielded the aggregation number, the core and corona radii, and the water contents of the core and the corona. The results showed that the micellar core cannot consist of PPO only but must contain significant quantities of water. The micelle aggregation number increased with temperature while the core and corona radii were constant over a 10 °C temperature region above the critical micellization temperature. The values of the corona radius obtained from the model fit (56−57 ± 3 A) are in a good agreement with the hydrodynamic radius of the micelle (56−61 ± 2 A) measured by dynamic light scattering.

Gels of a poly(oxyethylene)−poly(oxybutylene) diblock copolymer in an aqueous solution forming a bcc phase have been examined using small-angle neutron scattering (SANS) with simultaneous rheology. Application of large amplitude oscillatory shear was observed to induce macroscopic alignment of twinned bcc crystals. The structure of these crystals was probed in three dimensions using SANS with a shear-oriented sample that was fixed in situ in the shear cell and mounted on a goniometer. This corresponds to a kind of “mesoscopic crystallography” which enabled the eludication of the twinned bcc structure, in which the [111] direction was oriented along the shear direction, this being a 6-fold rotation axis. Flow was found to occur in (110) planes oriented normal to the shear gradient direction. A comparison is made between this twinned structure, probed comprehensively in three dimensions, and those previously reported for block copolymer solutions and melts.