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Byung Chull An,1 Yeo-Sang Yoon,1 Ho Jin Park,1 Sangkyun Park,1 Tai Yeub Kim,1 Jun Young Ahn,1 Daebeom Kwon,1 Oksik Choi,1 Jin Young Heo,1 Yongku Ryu,1 Joong-Hyun Kim,2 Heejong Eom,2 Myung Jun Chung1 1R&D Center, Cell Biotech, Co., Ltd., Gimpo-si, Gyeonggi-do, Korea; 2Laboratory Animal Center, Osong Medical Innovation Foundation, Chungbuk, Cheongju, 28160, KoreaCorrespondence: Myung Jun Chung Tel +82-31-987-6205Fax +82-31-987-6216Email ceo@cellbiotech.comPurpose: This study aimed to toxicological evaluate a probiotics-based delivery system for p8 protein as an anti-colorectal cancer drug.Introduction: Lactic acid bacteria (LAB) have been widely ingested for many years and are regarded as very safe. Recently, a Pediococcus pentosaceus SL4 (PP) strain that secretes the probiotic-derived anti-cancer protein P8 (PP-P8) has been developed as an anti-colorectal cancer (CRC) biologic by Cell Biotech. We initially identified a Lactobacillus rhamnosus (LR)-derived anti-cancer protein, P8, that suppresses CRC growth. We also showed that P8 penetrates specifically into CRC cells (DLD-1 cells) through endocytosis. We then confirmed the efficacy of PP-P8, showing that oral administration of this agent significantly decreased tumor mass (∼ 42%) relative to controls in a mouse CRC xenograft model. In terms of molecular mechanism, PP-P8 induces cell-cycle arrest in G2 phase through down-regulation of Cyclin B1 and Cdk1. In this study, we performed in vivo toxicology profiling to obtain evidence that PP-P8 is safe, with the goal of receiving approval for an investigational new drug application (IND).Methods: Based on gene therapy guidelines of the Ministry of Food and Drug Safety (MFDS) of Korea, the potential undesirable effects of PP-P8 had to be investigated in intact small rodent or marmoset models prior to first-in-human (FIH) administration. The estimated doses of PP-P8 for FIH are 1.0× 1010 – 1.0× 1011 CFU/person (60 kg). Therefore, to perform toxicological investigations in non-clinical animal models, we orally administered PP-P8 at doses of 3.375 × 1011, 6.75 × 1011, and 13.5× 1011 CFU/kg/day; thus the maximum dose was 800– 8000-fold higher than the estimated dose for FIH.Results: In our animal models, we observed no adverse effects of PP-P8 on clinicopathologic findings, relative organ weight, or tissue pathology. In addition, we observed no inflammation or ulceration during pathological necropsy.Conclusion: These non-clinical toxicology studies could be used to furnish valuable data for the safety certification of PP-P8.Keywords: biologics, therapeutic protein, probiotics derived anti-cancer protein P8, Pediococcus pentosaceus SL4, Lactobacillus rhamnosus, colorectal cancer, drug delivery system, protein secretion system, oral administration, non-clinical trial, toxicology finding

Shin-Woo Ha,1,2,* Kihwan Hwang,3,* Jun Jin,3 Ae-Sin Cho,1 Tae Yoon Kim,1,2 Sung Il Hwang,1 Hak Jong Lee,1–2,4–5 Chae-Yong Kim3,61Department of Radiology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 13605, South Korea; 2Research Institute, IMGT Co., Ltd, Seongnam, 13605, South Korea; 3Department of Neurosurgery, Seoul National University Bundang Hospital, Seongnam-si, South Korea; 4Department of Nanoconvergence, Seoul National University Graduate School of Convergence Science and Technology, Seoul, South Korea; 5Research Strategy and Management Division and Medical Device R&D Center, Seoul National University Bundang Hospital, Seongnam 13605, South Korea; 6Department of Neurosurgery, Seoul National University College of Medicine, Seoul National University, Seoul, South Korea*These authors contributed equally to this workBackground: Crossing the blood–brain barrier (BBB) is crucial for drug delivery to the brain and for treatment of brain tumors, such as glioblastoma, the most common of all primary malignant brain tumors. Microbubble (MB) is oscillated and destroyed by controlling ultrasound (US) parameters. This oscillation and destruction of MB can open the BBB transiently, and a drug can be delivered to the brain.Materials and methods: For testing the efficiency of delivery to the brain, we synthesized a US-sensitizing nanoparticle (NP) complex via chemically binding MBs and NPs for the BBB opening, including near-infrared dye-incorporated albumin nanoparticles (NIR-Alb NPs) for fluorescence detection.Results: The human-derived, biocompatible NIR-Alb NPs did not show significant cytotoxicity to 500 μg/mL for 3 days in four human glioma cell lines. In an in vivo animal study, some US parameters were investigated to determine optimal conditions. The optimized US conditions were applied in a U87MG orthotopic mouse model. We found that the fluorescence intensity in the brain was 1.5 times higher than in the control group.Conclusion: Our US-sensitizing NP complex and US technique could become one of the critical technologies for drug delivery to the brain.Keywords: blood–brain barrier, ultrasound, nanoparticle, microbubble, complex, drug delivery

Yi-Hwa Choi,1 Dae-Hwan Kim,2 Tae-Young Kim,2 Tae-Wan Lim,1 Seok-Woo Kim,2 Je-Hyun Yoo2 1Department of Anesthesiology and Pain Medicine, Hallym Sacred Heart Hospital, Hallym University College of Medicine, 2Department of Orthopaedic Surgery, Hallym Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea Purpose: Postoperative delirium is a risk factor for worse outcome after hip fracture surgery in elderly patients. Postoperative delirium is associated with anesthesia, postoperative pain, and patient factors. We investigated the incidence, predictors, and prognostic implications of postoperative delirium after hemiarthroplasty (HA) in elderly patients with femoral neck fracture.Patients and methods: A total of 356 consecutive patients aged >70 years who underwent HA for femoral neck fracture were enrolled. Diagnosis of delirium was made by a psychiatrist based on patient status and an objective scoring system. The patients were divided into 2 categories according to the HA onset time (immediate [≤24 h after surgery] vs delayed delirium [>24 h after surgery]) and its incidence, predictors and mortality were evaluated.Results: Postoperative delirium was diagnosed in 110 patients (30.9%) during hospitalization. Immediate and delayed delirium occurred in 59 (53.6%), and 51 (46.4%) patients, respectively. The independent predictors of immediate delirium included age (odds ratio [OR] 1.47, 95% CI 0.98–2.23, p=0.066), and general anesthesia (OR 2.25, 95% CI 1.17–4.43, p=0.015). The independent predictors of delayed delirium were parkinsonism (OR 5.75, 95% CI 1.66–19.96, p=0.006), intensive care unit stay (OR 1.85, 95% CI 0.97–3.56, p=0.064), and higher American Society of Anesthesiologists grade (OR 2.33, 95% CI 0.90–6.07, p=0.083). On Kaplan–Meier survival analysis, the 2-year survival rate was significantly lower in the immediate delirium group than those in the delayed and control groups (71.0% vs 83.6% vs 87.8%, respectively; p=0.031).Conclusion: Immediate and delayed delirium after HA for femoral neck fracture had different predictors and immediate delirium was associated with worse prognosis. Keywords: delirium, elderly patients, femoral neck fracture, hemiarthroplasty

Seung Won Ahn,1 Tong Yoon Kim,1 Sangmin Lee,1 Jeong Yeon Jeong,1 Hojoon Shim,1 Yu min Han,1 Kyu Eun Choi,1 Seok Joon Shin,1,2 Hye Eun Yoon,1,2 1Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, 2Division of Nephrology, Department of Internal medicine, Incheon St. Mary’s Hospital, Incheon, Republic of Korea Abstract: Adrenal insufficiency is an uncommon cause of hypercalcemia and not easily considered as an etiology of adrenal insufficiency in clinical practice, as not all cases of adrenal insufficiency manifest as hypercalcemia. We report a case of secondary adrenal insufficiency presenting as hypercalcemia and acute kidney injury in a 66-year-old female. The patient was admitted to the emergency department with general weakness and poor oral intake. Hypercalcemia (11.5 mg/dL) and moderate renal dysfunction (serum creatinine 4.9 mg/dL) were shown in her initial laboratory findings. Studies for malignancy and hyperparathyroidism showed negative results. Basal cortisol and adrenocorticotropic hormone levels and adrenocorticotropic hormone stimulation test confirmed the diagnosis of adrenal insufficiency. With the administration of oral hydrocortisone, hypercalcemia was dramatically resolved within 3 days. This case shows that adrenal insufficiency may manifest as hypercalcemia and acute kidney injury, which implicates that adrenal insufficiency should be considered a cause of hypercalcemia in clinical practice. Keywords: hypercalcemia, adrenal insufficiency, acute kidney injury

Sangwha Lee,1,* Jongsung Kim,1,* Chung Wung Bark,2 Bonghee Lee,3 Heongkyu Ju,4 Se Chan Kang,5 TaeYoung Kim,6 Moon Il Kim,6 Young Tag Ko,3 Jeong-Seok Nam,3 Hyon Hee Yoon,1 Kyu-Sik Yun,1,6 Young Soo Yoon,1 Seong Soo A An,1,6 John Hulme6 1BioNano Sensor Research Center, 2Department of Electrical Engineering, Gachon University, Seongnam-si, 3Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, 4Department of Nano-Physics, 5Department of Life Science, Gachon University, 6Department of BioNano Technology, Gachon BioNano Research Institute, Seongnam-si, South Korea *These authors contributed equally to this work Abstract: From the synergistic integration and the multidisciplinary strengths of the BioNano Sensor Research Center, Gachon Bionano Research Institute, and Lee GilYa Cancer and Diabetes Institute, researchers, students, and faculties at Gachon University in collaboration with other institutions in Korea, Australia, France, America, and Japan have come together to produce a special issue on the diverse applications of nano-theranostics in nanomedicine. This special issue will showcase new research conducted by various scientific groups in Gyonggi-do and Songdo/Incheon, South Korea. The objectives of this special issue are as follows: 1) to bring together and demonstrate some of the latest research results in the field, 2) to introduce new multifunctional nanomaterials and their applications in imaging and detection methods, and 3) to stimulate collaborative interdisciplinary research at both national and international levels in nanomedicine. Keywords: cancer, imaging and therapeutics, antibacterial, disease, neurodegenerative

Tran Thanh Tung,1,2 Dusan Losic,1 Seung Jun Park,3 Jean-Francois Feller,2 TaeYoung Kim3 1School of Chemical Engineering, The University of Adelaide, North Terrace, Adelaide, SA, Australia; 2Smart Plastics Group, European University of Brittany (UEB), LIMATB-UBS, Lorient, France; 3Department of Bionanotechnology, Gachon University, Sujeong-gu, Seongnam-si, Gyeonggi-do South Korea Abstract: We report a high-performance chemiresistive sensor for detection of volatile organic compound (VOC) vapors based on core-shell hybridized nanostructures of Fe3O4 magnetic nanoparticles (MNPs) and poly(3,4-ethylenedioxythiophene) (PEDOT)-conducting polymers. The MNPs were prepared using microwave-assisted synthesis in the presence of polymerized ionic liquids (PILs), which were used as a linker to couple the MNP and PEDOT. The resulting PEDOT–PIL-modified Fe3O4 hybrids were then explored as a sensing channel material for a chemiresistive sensor to detect VOC vapors. The PEDOT–PIL-modified Fe3O4 sensor exhibited a tunable response, with high sensitivity (down to a concentration of 1 ppm) and low noise level, to VOCs; these VOCs include acetone vapor, which is present in the exhaled breath of potential lung cancer patients. The present sensor, based on the hybrid nanostructured sensing materials, exhibited a 38.8% higher sensitivity and an 11% lower noise level than its PEDOT–PIL-only counterpart. This approach of embedding MNPs in conducting polymers could lead to the development of new electronic noses, which have significant potential for the use in the early diagnosis of lung cancer via the detection of VOC biomarkers. Keywords: hybrid nanomaterials, nanoparticle, conducting polymer, electronic nose, lung cancer detection

Two experiments were conducted in a 14,400 head nursery using 3,087 (experiment 1) and 988 (experiment 2) pigs to determine the effect of gruel feeding (experiment 1) and supplemental oral dextrose (experiment 2) on nursery pig survivability after weaning. Upon arrival to the nursery, for experiment 1, the smallest 10% of pigs were selected and randomly placed in pens with 61 to 108 pigs per pen. Pens of small pigs were assigned to one of two treatments in a completely randomized design. Treatments consisted of gruel feeding two or four times per day for 14 d postplacement. At each gruel feeding, approximately 1.13 kg of solid feed was added to a round bowl (Rotecna S.A. Agramunt, Spain) located at the front of each pen and water added at a decreasing rate over time. In experiment 2, every other pig removed for welfare considerations (lameness, sick, or unthrifty) from the general population or pens of small pigs received a single 10 mL oral dose of a 50% dextrose solution (Vet One, MWI Animal Health, Boise, ID), as a source of glucose, before being placed in a removal pen. All removed pigs were tagged and weighed, body temperature recorded, and blood glucose concentration measured prior to and 30 min after entering removal pens. Overall, gruel feeding small pigs two or four times per day for 14 d postplacement did not influence (P  > 0.10) mortality from weaning to the end of gruel feeding (3.78% vs. 4.25%, respectively). Likewise, dextrose administration did not influence (P  > 0.10) pig mortality after removal to approximately 38 d postweaning (21.4% vs. 23.4% respectively), even though blood glucose concentration increased (P  < 0.001) 30 min after removal for pigs administered dextrose. An interaction was observed for blood glucose concentration and body temperature (P  < 0.001) where pigs with blood glucose concentrations less than 70 mg/dL had increased mortality as body temperature increased. In contrast, pigs with a blood glucose concentration of 70 mg/dL or greater had decreased mortality as body temperature increased. Pigs weighing less than 4.5 kg also had increased mortality (P  < 0.001) compared with pigs weighing greater than or equal to 4.5 kg at removal. In summary, gruel feeding four times per day vs. two times per day or providing a dextrose supplement to pigs removed from the general population did not improve the survivability of pigs after weaning. Additionally, pigs removed with decreased body weight or with body temperature or blood glucose concentrations below or above the normal range had decreased survivability. [ABSTRACT FROM AUTHOR]

Aims: Recent evidence has demonstrated that ketone bodies, particularly β‐hydroxybutyrate (BHB), are beneficial to the failing heart due to their potential as an alternative energy substrate as well as their anti‐inflammatory and anti‐oxidative properties. Exogenous supplementation of ketones also helps prevent heart failure (HF) development in rodent models, but whether ketones can be used to treat HF remains unexplored. Herein, we investigated whether chronic supplementation of ketones is beneficial for the heart in a mouse model of established HF. Methods and results: To elevate circulating ketone levels, we utilized (R)‐3‐hydroxybutyl‐(R)‐3‐hydroxybutyrate [ketone ester (KE)]. C57Bl/6N male mice were subjected to transverse aortic constriction (TAC) surgery. After developing HF, mice were treated with either 20% KE or vehicle via drinking water for 2 weeks. In another cohort, mice 3–4 weeks post‐TAC received acute intravenous infusions of BHB or saline for 1 h and their cardiac function was measured. 20% KE significantly elevated blood BHB in mice (P < 0.01) without inducing ketoacidosis or altering other metabolic parameters. Mice with overt HF (30–45% ejection fraction) treated with 20% KE displayed significantly elevated circulating ketone levels compared with vehicle‐treated mice (P < 0.05). The significant cardiac dysfunction in mice with HF continued to worsen after 2 weeks of vehicle treatment, whereas this decline was absent in KE‐treated mice (mean difference 4.7% ejection fraction; P < 0.01). KE treatment also alleviated TAC‐induced cardiomyocyte hypertrophy (P < 0.05) and reduced the TAC‐induced elevated cardiac periostin (P < 0.05), a marker of activated fibroblasts. Cardiac fibrosis was also significantly reduced with KE treatment in TAC mice (P < 0.01). In another cohort, acute BHB infusion significantly increased the cardiac output of mice with HF (P < 0.05), providing further support that ketone therapy can be used to treat HF. Conclusions: We show that chronic treatment of exogenous ketones is of benefit to the failing heart and that chronic ketone elevation may be a therapeutic option for HF. Further investigations to elucidate the underlying mechanism(s) are warranted. [ABSTRACT FROM AUTHOR]

The recent development in the technologies of supercritical carbon dioxide (S-CO2) has caused a remarkable change in the dyeing process in the textile industry. The conventional wet-dyeing process using water is being replaced with the dry-dyeing process using S-CO2. The uniform addition of coloring material is necessary for any dyeing process. In the case of the beam dyeing process, an equal distribution of the dye fluid through the porous beam has to be ensured in order to achieve an evenly distributed dyeing. The present study focuses on the fluid dynamics aspects of the S-CO2 beam dyeing process in order to study the flow characteristics and thereby obtain performance improvement. Computational fluid dynamics analyses were carried out and the methodology is validated with experimental results from a previous study. The flow distribution of S-CO2 through a porous beam is analyzed at different conditions, such as varying the operating pressure, mass flow rate and inlet temperature. The comparison of compressible and incompressible flow through beam dyeing is also discussed. The current study revealed that the increase in mass flow rate through the system leads to higher non-uniformity in distribution. The operating pressure and inlet temperature were found to significantly affect the flow distribution. The flow reversal condition showed a mass flow distribution opposite to that of the normal flow condition. The cyclic flow condition with periodic normal and the reversed flow condition provide better uniformity in distribution of the flow than the normal flow condition. The present results provide guidelines to improve the levelness of the dye distribution in the fabric material. [ABSTRACT FROM AUTHOR]

Oral administration of resveratrol attenuates several symptoms associated with the metabolic syndrome, such as impaired glucose homeostasis and hypertension. Recent work has shown that resveratrol can improve glucose homeostasis in obesity via changes in the gut microbiota. Studies involving fecal microbiome transplants (FMTs) suggest that either live gut microbiota or bacterial-derived metabolites from resveratrol ingestion are responsible for producing the observed benefits in recipients. Herein, we show that obese mice receiving FMTs from healthy resveratrol-fed mice have improved glucose homeostasis within 11 days of the first transplant, and that resveratrol-FMTs is more efficacious than oral supplementation of resveratrol for the same duration. The effects of FMTs from resveratrol-fed mice are also associated with decreased inflammation in the colon of obese recipient mice. Furthermore, we show that sterile fecal filtrates from resveratrol-fed mice are sufficient to improve glucose homeostasis in obese mice, demonstrating that nonliving bacterial, metabolites, or other components within the feces of resveratrol-fed mice are sufficient to reduce intestinal inflammation. These postbiotics may be an integral mechanism by which resveratrol improves hyperglycemia in obesity. Resveratrol-FMTs also reduced the systolic blood pressure of hypertensive mice within 2 wk of the first transplant, indicating that the beneficial effects of resveratrol-FMTs may also assist with improving cardiovascular conditions associated with the metabolic syndrome. [ABSTRACT FROM AUTHOR]

Despite advancements in therapies for cardiovascular disease and heart failure (HF), the incidence and prevalence of HF are increasing. Previous work has suggested that inhibiting adipose triglyceride lipase (ATGL) in adipose tissue during HF development may assist in the treatment of HF. The ability to specifically target the adipocyte as a potential treatment for HF is a novel approach that could significantly influence the management of HF in the future. Our objectives were to assess the cardiac structural and functional effects of pharmacological inhibition of ATGL in mice with HF, to assess whether ATGL inhibition works in an adipocyte-autonomous manner, and to determine the role that adiposity and glucose homeostasis play in this HF treatment approach. Using a known ATGL inhibitor, atglistatin, as well as mice with germline deletion of adipocyte-specific ATGL, we tested the effectiveness of ATGL inhibition in mice with pressure overloadinduced HF. Here, we show that atglistatin can prevent the functional decline in HF and provide evidence that specifically targeting ATGL in the adipocyte is sufficient to prevent worsening of HF. We further demonstrate that the benefit resulting from atglistatin in HF is not dependent on previously suggested improvements in glucose homeostasis, nor are the benefits derived from increased adiposity. Overall, the results of this study suggest that adipocyte-specific pharmacological inhibition of ATGL may represent a novel therapeutic option for HF. [ABSTRACT FROM AUTHOR]

We investigated whether treatment of mice with established pressure overload-induced heart failure (HF) with the naturally occurring polyphenol resveratrol could improve functional symptoms of clinical HF such as fatigue and exercise intolerance. C57Bl/6N mice were subjected to either sham or transverse aortic constriction surgery to induce HF. Three weeks postsurgery, a cohort of mice with established HF (%ejection fraction <45) was administered resveratrol (~450 mg·kg-1·day-1) or vehicle for 2 wk. Although the percent ejection fraction was similar between both groups of HF mice, those mice treated with resveratrol had increased total physical activity levels and exercise capacity. Resveratrol treatment was associated with altered gut microbiota composition, increased skeletal muscle insulin sensitivity, a switch toward greater whole body glucose utilization, and increased basal metabolic rates. Although muscle mass and strength were not different between groups, mice with HF had significant declines in basal and ADP-stimulated O2 consumption in isolated skeletal muscle fibers compared with sham mice, which was completely normalized by resveratrol treatment. Overall, resveratrol treatment of mice with established HF enhances exercise performance, which is associated with alterations in whole body and skeletal muscle energy metabolism. Thus, our preclinical data suggest that resveratrol supplementation may effectively improve fatigue and exercise intolerance in HF patients. [ABSTRACT FROM AUTHOR]

Previous studies have shown that loss of CD36 protects the heart from dysfunction induced by pressure overload in the presence of dietinduced insulin resistance and/or obesity. The beneficial effects of CD36 ablation in this context are mediated by preventing excessive cardiac fatty acid (FA) entry and reducing lipotoxic injury. However, whether or not the loss of CD36 can prevent pressure overloadinduced cardiac dysfunction in the absence of chronic exposure to high circulating FAs is presently unknown. To address this, we utilized a tamoxifen-inducible cardiomyocyte-specific CD36 knockout (icCD36KO) mouse and genetically deleted CD36 in adulthood. Control mice (CD36 floxed/floxed mice) and icCD36KO mice were treated with tamoxifen and subsequently subjected to transverse aortic constriction (TAC) surgery to generate pressure overload-induced cardiac hypertrophy. Consistent with CD36 mediating a significant proportion of FA entry into the cardiomyocyte and subsequent FA utilization for ATP production, hearts from icCD36KO mice were metabolically inefficient and displayed signs of energetic stress, including activation of the energetic stress kinase, AMPK. In addition, impaired energetics in icCD36KO mice contributed to a rapid progression from compensated hypertrophy to heart failure. However, icCD36KO mice fed a medium-chain FA diet, whereby medium-chain FAs can enter into the cardiomyocyte independent from CD36, were protected from TAC-induced heart failure. Together these data suggest that limiting FA uptake and partial inhibition of FA oxidation in the heart via CD36 ablation may be detrimental for the compensated hypertrophic heart in the absence of sufficiently elevated circulating FAs to provide an adequate energy source. [ABSTRACT FROM AUTHOR]

Oral administration of resveratrol is able to improve glucose homeostasis in obese individuals. Herein we show that resveratrol ingestion produces taxonomic and predicted functional changes in the gut microbiome of obese mice. In particular, changes in the gut microbiome were characterized by a decreased relative abundance of Turicibacteraceae, Moryella, Lachnospiraceae, and Akkermansia and an increased relative abundance of Bacteroides and Parabacteroides Moreover, fecal transplantation from healthy resveratrol-fed donor mice is sufficient to improve glucose homeostasis in obese mice, suggesting that the resveratrol-mediated changes in the gut microbiome may play an important role in the mechanism of action of resveratrol. [ABSTRACT FROM AUTHOR]

Since the heart has one of the highest energy requirements of all organs in the body, it requires a constant and plentiful supply of fuel to function properly. Mitochondrial oxidation of lipids provides a major source of ATP for the heart, and the cellular processes that regulate lipid uptake and utilization are important contributors to maintaining proper myocardial energetic status. Although numerous proteins are coordinately regulated in order to ensure proper fatty acid utilization in the cardiomyocyte, a key first step in this process is the entry of fatty acids into the cell. An important protein involved in the transport of fatty acids into the cardiomyocyte is the plasma membrane-associated protein known as fatty acid translocase (FAT; also known as CD36). While multiple proteins are involved in facilitating fatty acid uptake in the heart, CD36 accounts for approximately 50–70% of the total fatty acid taken up in cardiomyocytes. As such, myocardial metabolism of fatty acids may depend upon proper CD36 function. Consistent with this, changes in CD36 levels/function have been implicated in the alteration of myocardial metabolism in the pathophysiology of certain cardiovascular diseases. As such, a better understanding of the role and function of CD36 in the heart may provide important insights for the development of new treatments for specific cardiovascular diseases. Herein, we review the role of CD36 in myocardial lipid metabolism in the healthy heart and describe how CD36-mediated alterations in lipid metabolism may contribute to cardiovascular disease. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. [ABSTRACT FROM AUTHOR]

STUDY DESIGN: A finite element analysis. OBJECTIVE: To evaluate the differences between surgical techniques in terms of the effects of arthrodesis on adjacent segments. SUMMARY OF BACKGROUND DATA: Augmentation with posterior rigid fixation combined with transpedicular screw insertion, which is one of the most popular techniques for lumbar arthrodesis, shows benefits in immediate stabilization and a higher fusion rate but is reportedly correlated with greater stress on adjacent segments. However, the increased stress on adjacent segments needs further evaluation because the differences of the effects on adjacent segments between surgical techniques, including anterior lumbar interbody fusion, posterior lumbar interbody fusion, and semirigid fixation, have not yet been determined. METHODS: A finite element model of the human lumbar spine was developed. Three spinal segments (L2-L5) were used to investigate. The intact spinal model was validated by comparing it with previously reported models. Then, 4 arthrodesis models were analyzed and compared: (1) anterior lumbar interbody fusion model; (2) posterior lumbar interbody fusion model; (3) semirigid fixation model combined with posterior lumbar interbody fusion; and (4) rigid fixation model combined with posterior lumbar interbody fusion. RESULTS: Among these 4 models, the rigid fixation model showed the greatest amount of stress, with increased intervertebral disc pressure and contact force of the facet joints of both upper and lower adjacent segments. The second highest stress levels were seen in the semirigid fixation model and the lowest stress levels were seen in the anterior lumbar interbody fusion model. CONCLUSION: Although bony fusion had been completed, the effects of lumbar arthrodesis on adjacent segments could vary according to the surgical technique used for arthrodesis. Semirigid fixation combined with arthrodesis deserves careful consideration and further detailed study because it may cause less stress on adjacent segments than rigid fixation while maintaining the benefits of the latter procedure. [ABSTRACT FROM AUTHOR]

Purpose: The role of (18)F FDG-PET in hepatocellular carcinoma (HCC) has not been firmly established. We conducted this study to investigate the clinical implication of SUVmax on (18)F FDG-PET as a prognostic factor in patients with HCC, especially in the metastatic setting. Methods: HCC patients with extrahepatic metastatic lesions were enrolled that were evaluated by (18)F FDG-PET before palliative systemic therapy, between January 2002 and December 2009 at the Seoul National University Hospital. We retrospectively analyzed the clinical outcome and the value of the SUVmax. Results: A total of 25 patients (men, 88.0%) were enrolled. The response rate and disease control rate was 18.2% (95% CI: 2.1-34.3) and 32.0% (95% CI: 16.3-56.5), respectively. The progression-free survival (PFS) and overall survival (OS) were 2.3 months (95% CI: 1.1-3.4) and 14.2 months (95% CI: 9.1-19.2), respectively. The univariate analysis of OS showed that SUVmax and alphafetoprotein (AFP) were significant prognostic factors (P = 0.023 and P = 0.006, respectively). The multivariate analysis of OS showed that SUVmax and AFP were significant prognostic factors (P = 0.008 and P = 0.006, respectively). SUVmax and AFP were independent prognostic factors for PFS, too (P = 0.010 and P = 0.016, respectively). When the patients were divided according to the SUVmax and AFP, the patients with an SUVmax < 4.9 and an AFP ≤ 400 ng/ml showed longer OS and PFS than the patients with SUVmax ≥ 4.9 or AFP > 400 ng/ml (26.7 months vs. 9.3 months, P < 0.001 and 5.6 months vs. 1.7 months, P = 0.012, respectively). Conclusions: The SUVmax of the (18)F FDG-PET has a prognostic value for OS and PFS in patients with metastatic HCC undergoing systemic therapy. The combined analysis of the SUVmax with AFP might provide more detailed prognostic information. [ABSTRACT FROM AUTHOR]

This randomised controlled trial compared the effect of equipotent anaesthetic doses of sevoflurane (S group) versus propofol (P group), during remifentanil-based anaesthesia for off-pump coronary artery bypass surgery, on myocardial injury. Either sevoflurane or propofol was titrated to maintain bispectral index values between 40 and 50. In both groups, a targeted concentration of remifentanil 20 ng x ml(-1) was maintained during anaesthesia. The concentrations of creatine kinase MB and troponin I were measured before the start of surgery, on admission to the intensive care unit, and at 12 and 24 hours after intensive care unit admission. The postoperative values of creatine kinase MB (S group: 15.08 +/- 18.97, 20.78 +/- 20.92, 12.76 +/- 12.82 vs 2.09 +/- 1.54 ng x ml(-1); P group: 10.99 +/- 13.15 27.16 +/- 56.55 11.88 +/- 18.80 vs 1.84 +/- 1.67 ng x ml(-1)) and troponin I (S group: 3.56 +/- 5.19, 566 +/- 7.89, 3.35 +/- 4.55 vs 0.52 +/- 1.90 ng x ml(-1); P group: 2.42 +/- 3.33, 4.11 +/- 6.01, 3.04 +/- 5.31 vs 0.43 +/- 1.28 ng x ml(-1)) were significantly higher than preoperative values in both groups but there were no significant differences between the two groups. There were no significant differences in time to extubation (S group, 476 +/- 284 minutes; P group, 450 +/- 268 minutes) and intensive care unit length of stay (S group, 2775 +/- 1449 minutes; P group, 2797 +/- 1534 minutes) between the two groups. In conclusion, sevoflurane and propofol at equipotent doses guided by bispectral index with remifentanil 20 ng x ml(-1) had similar creatine kinase MB and troponin I values. [ABSTRACT FROM AUTHOR]

Objective: Endoscopic vein harvest (EVH) for coronary artery bypass grafting surgery is performed with carbon dioxide (CO2) insufflation for visualization and dissection. The insufflated CO2 is rapidly absorbed into the body and may influence haemodynamics. However, the haemodynamic changes during EVH have not been clearly defined. This study evaluated the haemodynamic effects during EVH of the saphenous vein for off-pump coronary artery bypass grafting surgery (OPCAB).Methods: After fixing the position for harvesting of the left internal mammary artery, EVH of the saphenous vein was performed at a maximum CO2 pressure of 12 mmHg and a flow of 3 l/min. The haemodynamic parameters were measured before and just after the end of endoscopic vein harvest.Results: One hundred patients were studied. The end-tidal CO2 pressure (P(ET)CO2, 35.0 +/- 2.7 vs. 52.0 +/- 6.2 mmHg), partial pressure of arterial CO2 (PaCO2, 35.1 +/- 3.1 vs. 52.5 +/- 4.3 mmHg), mixed venous oxygen saturation (SvO2, 75.6 +/- 4.1 vs. 82.0 +/- 1.6%), cardiac index (2.7 +/- 0.6 vs. 3.3 +/- 0.6 l/min/m2), and cerebral oxygen saturation (ScO2, left: 63.5 +/- 7.9 vs. 73.3 +/- 8.4; right: 62.2 +/- 8.0 vs. 72.3 +/- 6.3%) differed significantly between before and after CO2 insufflation, whereas mean systemic blood pressure, mean pulmonary artery blood pressure, central venous pressure, heart rate, partial pressure of arterial oxygen, and peak inspiratory pressure did not differ significantly between before and after CO2 insufflation.Conclusions: EVH, at a maximum CO2 pressure of 12 mmHg and a flow of 3 l/min, of the saphenous vein for OPCAB was associated with hypercarbia and a tolerable range of hypercarbia (PaCO2 < 60 mmHg) increased the cardiac index and ScO2 without any complications. [ABSTRACT FROM AUTHOR]

Treating young patients with femoral head osteonecrosis (ON) remains challenging. Anatomic stems were introduced in the 1980s and 1990s to improve the proximal canal fit in an attempt to enhance long-term implant survival, an important aspect of treating young patients. We began using one design in 1993 and asked three questions to confirm whether the design criteria improved outcomes in patients with ON: (1) What is the long term survivorship of these implants?; (2) What is the amount and rate of wear?; and (3) What is the incidence of osteolysis? We retrospectively reviewed 56 patients (69 hips) who underwent THA for femoral head ON with a cementless anatomic stem proximally coated with hydroxyapatite. Four patients (four hips) were lost to followup and 16 patients (19 hips) died. In the remaining 36 patients (46 hips) the minimum followup was 10 years (mean, 11.2 years; range, 10-13 years). The mean age at operation was 48.6 years. The average Harris hip score at last followup was 87 points. Worst-case survivorship was 58.1% at 13 years and best-case was 93.3%. The average linear wear of the polyethylene liner was 2.02 mm and the average annual wear was 0.18 mm per year. Thirty-seven hips (80%) had femoral osteolysis and 14 (30%) had acetabular osteolysis. One patient who had extensive femoral osteolysis and stem loosening was revised at 11.2 years postoperatively. The high rates of polyethylene wear and osteolysis are of concern. [ABSTRACT FROM AUTHOR]

The aim of this phase II study was to evaluate the response rate to gemcitabine combined with cisplatin in patients with locally advanced, metastatic or recurrent biliary tract cancer who had received no prior chemotherapy. The treatment consisted of cisplatin 70 mg/m2 in intravenous infusion followed by gemcitabine 1,250 mg/m2 in 30-min intravenous infusion on days 1 and 8, repeated every 3 weeks until disease progression, unacceptable toxicity, patient’s refusal or up to 8 cycles. Thirty-nine patients with advanced biliary cancer were enrolled between March 2003 and August 2003. Fourteen patients (40%) had gall bladder cancer and 20 patients (57%) had cholangiocarcinoma. Thirty-two patients (91%) had metastatic disease at study entry with liver being the most commonly involved site of metastasis. About 84.5 and 94.2% of the initially planned dose were administered for gemcitabine and cisplatin, respectively. In the ITT population ( n = 35), six partial responses were observed for an objective response rate of 17.1% (95% CI; 4.7–29.6%). Ten patients (28.6%) had stable disease, 16 (45.7%) progressed, and three (8.6%) were not evaluable. For the 35 patients in the ITT population, the median overall survival time was 8.6 months (95% CI; 6.1–10.4 months). The median time to disease progression was 3.2 months (95% CI; 2.3–4.9 months) and the median time to treatment failure was 3.1 months (95% CI; 1.9–4.1 months). Among the six tumor responders, the median duration of tumor response was 7.3 months (95% CI; 5.6–11.0 months). The most common grade 3/4 maximum toxicities were nausea (3.4%) and vomiting (2.7%). The combination chemotherapy with gemcitabine and cisplatin in this trial demonstrated moderate antitumor activity with favorable toxicity profile. [ABSTRACT FROM AUTHOR]

Objective: There are few reports in the medical literature describing removal of a coin from the upper esophageal tract of a child by an emergency physician. However, given the nature of their training and practice, emergency physicians are well suited to perform this common procedure. We describe our experience with this procedure.Methods: This was a retrospective review of a continuous quality improvement data set from a university-based tertiary care pediatric emergency department between Nov. 1, 2003, and Mar. 31, 2004.Results: Thirteen children, with a median age of 20 months, underwent rapid sequence intubation and had coins successfully removed from their upper esophageal tract by emergency physicians. In 10 cases, the coin was visible at laryngoscopy and removed with Magill forceps. In 3 cases this approach failed and a Foley catheter was used to remove the coin. One child suffered a tonsillar abrasion and two sustained minor lip trauma, but all were extubated and discharged home from the emergency department with no significant complications. Eleven of the 13 patients were successfully followed up, and the parents reported no problems.Conclusions: This pilot study suggests that the removal of a coin from the upper esophageal tract by an emergency physician can be both safe and effective. A larger study is needed before this procedure can be generally recommended. [ABSTRACT FROM AUTHOR]