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A sustainable CO2 polymerization using surface activated zinc glutarate catalysts produces industrially useful polymers with good catalytic activity.

Physical activity has been known to improve survival and quality of life of patients with breast cancer. To find factors associated with physical activity, we analyzed the dataset of the multicenter controlled trial of exercise intervention. Three hundred fifty-six participants were assigned to two groups: “Smart After-Care” (smartphone application and pedometer were provided) or exercise education only. Physical activity was measured by International Physical Activity Questionnaire–Short Form (IPAQ-SF) at baseline and after 12 weeks. The association between physical activity and other clinical characteristics was analyzed. At baseline, physical activity amount was 2315.5 ± 3513.2 MET min/week: 33.0% inactive, 49.6% minimally active, and 17.4% health-enhancing physical activity (HEPA) active. Factors associated with HEPA include cancer stage and grip strength. A significantly lower proportion was HEPA active among those with advanced stage than among those with stage 0. After intervention, physical activity was increased to 3466.2 ± 4712.5 MET min/week: 15.3% inactive, 50.4% minimally active, and 34.2% HEPA active. Physical activity was increased in 63.4% of the participants. Factors associated with physical activity increase include cancer stage, diarrhea, and type of exercise intervention. Participants with advanced stage have a 3.3 times higher chance of increasing physical activity. Participants who received “Smart After-Care” have a 64% higher chance of increasing physical activity. Before the intervention, participants with advanced stage are less likely to be HEPA active. Exercise intervention was more beneficial for those with advanced stage or physical symptoms. “Smart After-Care” was more effective than education only in increasing physical activity.

To investigate and compare the effects of mobile health (mHealth) and pedometer with conventional exercise program using a brochure on physical function and quality of life (QOL).The study was a prospective, quasi-randomized multicenter trial where 356 patients whose cancer treatment had been terminated were enrolled. All patients were instructed to perform a 12-week regimen of aerobic and resistance exercise. The mHealth group received a pedometer and a newly developed smartphone application to provide information and monitor the prescribed exercises. Those in the conventional group received an exercise brochure. Physical measurements were conducted at baseline, 6 weeks, and 12 weeks. Self-reported physical activity (international physical activity questionnaire-short form), general QOL (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30), and breast cancer-specific QOL (Quality of Life Questionnaire Breast Cancer Module 23) were assessed at baseline and 12 weeks. A user satisfaction survey was assessed in the mHealth group.Basic characteristics were not different between the two groups except for age and previous radiotherapy. Physical function, physical activity, and QOL scores were significantly improved regardless of the intervention method, and changes were not significantly different between the two groups. Additionally, the mean Likert scale response for overall satisfaction with the service was 4.27/5 in the mHealth group.Overall, both the mHealth coupled with pedometer and conventional exercise education using a brochure were effective in improving physical function, physical activity, and QOL. This study provides a basis of mHealth research in breast cancer patients for progressing further developing field, although superiority of the mHealth over the conventional program was not definitely evident.

// Hyun Gyu Lee 1 , Hyemi Kim 1, 2 , Taekwon Son 3 , Youngtae Jeong 4 , Seung Up Kim 5 , Seung Myung Dong 6 , Young Nyun Park 2, 7 , Jong Doo Lee 8 , Jae Myun Lee 1, 2 , Jeon Han Park 1 1 Department of Microbiology and Immunology, Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Republic of Korea 2 Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Republic of Korea 3 Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Republic of Korea 4 Stanford Cancer Institute and Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA 5 Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea 6 Research Institute, National Cancer Center, Goyang, Gyeonggi-do, Republic of Korea 7 Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea 8 Department of Nuclear Medicine, International St. Mary's Hospital, Catholic Kwandong University College of Medicine, Incheon, Republic of Korea Correspondence to: Jeon Han Park, email: jhpark5277@yuhs.ac Keywords: hexokinase 2, HumanMethylation450 BeadChip, HK2-CIMP, hypoxia response element, HIF-1α Received: March 22, 2016 Accepted: May 23, 2016 Published: May 30, 2016 ABSTRACT Hexokinase 2 (HK2) is a rate-determining enzyme in aerobic glycolysis, a process upregulated in tumor cells. HK2 expression is controlled by various transcription factors and epigenetic alterations and is heterogeneous in hepatocellular carcinomas (HCCs), though the cause of this heterogeneity is not known. DNA methylation in the HK2 promoter CpG island ( HK2 -CGI) and its surrounding regions (shore and shelf) has not previously been evaluated, but may provide clues about the regulation of HK2 expression. Here, we compared HK2 promoter methylation in HCCs and adjacent non-cancerous liver tissues using a HumanMethylation450 BeadChip array. We found that, while the HK2 -CGI N-shore was hypomethylated, thereby enhancing HK2 expression, the HK2 -CGI was itself hypermethylated in some HCCs. This hypermethylation suppressed HK2 expression by inhibiting interactions between HIF-1α and a hypoxia response element (HRE) located at –234/–230. HCCs that were HK2 negative and had distinct promoter CGI methylation were denoted as having a HK2 -CGI methylation phenotype ( HK2 -CIMP), which was associated with poor clinical outcome. These findings indicate that HK2 -CGI N-shore hypomethylation and HK2 -CGI hypermethylation affect HK2 expression by influencing the interaction between HIF 1α and HRE. HK2 -CGI hypermethylation induces HK2 -CIMP and could represent a prognostic biomarker for HCC.

Background Long-term cigarette smoking induces sensitization of incentive salience and conditioning of contextual cues which involves brain function alteration across multiple regions. Understanding how nicotine affects hub-based functional connectivities involved in affective and cognitive function can help us determine the treatment strategy for nicotine dependence. Method Functional MRI was conducted on 30 smokers and 30 non-smokers while mentally simulating neutral and smoking hand movements. Smoking cue and mental simulation processing-related changes in functional connectivity strengths of the subcallosal and posterior cingulate cortex (SCC and PCC) with major brain network nodes were examined. Results Compared to non-smokers, smokers showed cue-induced SCC functional connectivities which were enhanced with the intraparietal sulcus and reduced with the medial prefrontal cortex. The PCC activation and functional connectivity enhancements with the anterior insula cortex and rostro-lateral prefrontal cortex was found during smoking mental simulation. The PCC-lateral prefrontal cortex functional connectivity correlated with nicotine dependence severity. Conclusion The present results demonstrate that smokers can be identified by cue-induced SCC functional connectivity strength decline and increment in the default mode and dorsal attention network nodes. However, nicotine dependence was associated with smoking mental simulation-related PCC-lateral prefrontal cortex functional connectivity strength, suggesting that the development of nicotine dependence may depend on the strength of coupling between the default mode network and the central executive network at the cognitive level.

Objectives To evaluate the clinical implications of lymph node (LN) density on 18F-FDG PET/CT for mediastinal LN characterization in non-small cell lung cancer (NSCLC).

509 Objectives Left atrial fibrosis is a prominent feature in patients with atrial fibrillation (AF) and the degree of fibrosis as measured by delayed enhancement magnetic resonance imaging (MRI) has prognostic and therapeutic implications. However, MRI imaging of the thin-walled left atrium can be technically challenging and is prone to artifacts. FDG-PET has the potential to assess left atrial fibrosis as the absence of metabolism. In this study, we evaluated the feasibility of assessing left atrial fibrosis using FDG-PET and compare the degree of fibrosis in clinically-referred patients in sinus rhythm and AF. Methods 28 patients in sinus rhythm and 31 with paroxysmal AF were randomly selected from patients undergoing FDG-PET myocardial viability assessment from 2013 to 2015. Gated rest Rb-82 and F-18 FDG-PET imaging with CT attenuation correction were performed. Images were manually segmented to isolate the left atrium. Volumetric assessment was performed over all vertical long axis, horizontal long axis, and short axis images to visually score extent of FDG uptake on a semi-quantitative basis. The extent of FDG uptake defects was defined as small or normal ( 50%). Results Images for the classification of FDG uptake defects are shown in Figure 1. In patients in sinus rhythm, 8 (28.6%) patients were classified as having small or normal FDG uptake defects, 3 (10.7%) with medium, 6 (21.4%) with large, and 11 (39.4%) with extensive. In patients with paroxysmal AF, 5 (16.1%) had small or normal FDG uptake defects, 6 (19.4%) had medium, 3 (9.7%) had large, and 17 (54.8%) had extensive defects. Overall, patients with paroxysmal AF had more FDG uptake defects than those in sinus rhythm. (P Conclusions FDG-PET appears capable of assessing left atrial myopathy in patients with and without AF. Patients with AF have a higher burden of left atrial fibrosis compared to those in sinus rhythm. Further research is required to determine if FDG-PET can be used to identify those at risk for developing AF or predict therapeutic response to ablation.

Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide; however, the genetic mechanisms underlying its pathogenesis are incompletely understood. Genetically engineered mouse (GEM) models of HCC have been developed to elucidate the role of individual cancer-related genes in hepatocarcinogenesis. However, the expensive and time-consuming processes related to generating a GEM model discourage the development of diverse genotype models. Recently, a simple and inexpensive liver-specific transgenic approach was developed, in which a hydrodynamics-based transfection (HT) method was coupled with the Sleeping Beauty transposase system. Various HT models in which different oncogenic pathways are activated and/or tumor-suppressing pathways inactivated have been developed in recent years. The applicability of HT models in liver cancer research is expected to broaden and ultimately elucidate the cooperation between oncogenic signaling pathways and aid in designing molecular therapy to target altered pathways.

Purpose: As Parkinson’s disease (PD) can be considered a network abnormality, the effects of deep brain stimulation (DBS) need to be investigated in the aspect of networks. This study aimed to examine how DBS of the bilateral subthalamic nucleus (STN) affects the motor networks of patients with idiopathic PD during motor performance and to show the feasibility of the network analysis using crosssectional positron emission tomography (PET) images in DBS studies. Materials and Methods: We obtained [ 15 O]H2O PET images from ten patients with PD during a sequential finger-to-thumb opposition task and during the resting state, with DBS-On and DBS-Off at STN. To identify the alteration of motor networks in PD and their changes due to STN-DBS, we applied independent component analysis (ICA) to all the cross-sectional PET images. We analysed the strength of each component according to DBS effects, task effects and interaction effects. Results: ICA blindly decomposed components of functionally associated distributed clusters, which were comparable to the results of univariate statistical parametric mapping. ICA further revealed that STN-DBS modifies usage-strengths of components corresponding to the basal ganglia-thalamo-cortical circuits in PD patients by increasing the hypoactive basal ganglia and by suppressing the hyperactive cortical motor areas, ventrolateral thalamus and cerebellum. Conclusion: Our results suggest that STN-DBS may affect not only the abnormal local activity, but also alter brain networks in patients with PD. This study also demonstrated the usefulness of ICA for cross-sectional PET data to reveal network modifications due to DBS, which was not observable using the subtraction method.

The aim of this study was to evaluate the prognostic value of metabolic tumor volume (MTV) on pre-treatment F-18 fluorodeoxyglucose (FDG) PET/CT in patients with hepatocellular carcinoma (HCC). A total of 59 HCC patients who underwent FDG PET/CT before transarterial chemoembolization (TACE) or transarterial chemotherapy infusion (TACI) were retrospectively enrolled. The region of interest was drawn in the HCC and normal liver tissue. MTV2SD, defined as the sum of the voxels with higher standardized uptake values (SUV) than the SUV of the 97.5th percentile of voxels of the normal liver for each patient, was calculated using an intensity–volume histogram (IVH). The ratio of the maximum SUV of the tumor to the mean SUV of normal liver (T max/L mean) was also calculated. The prognostic significance of MTV2SD and Tmax/Lmean for progression-free survival (PFS) and overall survival (OS) was evaluated along with other clinical factors. The tumor number, Tmax/Lmean, and MTV2SD were significant prognostic factors affecting PFS (p

The purpose of this study was to investigate the prognostic value of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with ampullary adenocarcinoma (AAC) after curative surgical resection. Fifty-two patients with AAC who had undergone 18F-FDG PET/CT and subsequent curative resections were retrospectively enrolled. The maximum standardized uptake value (SUVmax) and tumor to background ratio (TBR) were measured on 18F-FDG PET/CT in all patients. The prognostic significances of PET/CT parameters and clinicopathologic factors for recurrence-free survival (RFS) and overall survival (OS) were evaluated by univariate and multivariate analyses. Of the 52 patients, 19 (36.5 %) experienced tumor recurrence during the follow-up period and 18 (35.8 %) died. The 3-year RFS and OS were 62.3 and 61.5 %, respectively. Preoperative CA19-9 level, tumor differentiation, presence of lymph node metastasis, SUVmax, and TBR were significant prognostic factors for both RFS and OS (p 4.80) or TBR (>1.75) had poor survival outcomes. The role of and indications for adjuvant therapy after curative resection of AAC are still unclear. 18F-FDG uptake in the primary tumor could provide additive prognostic information for the decision-making process regarding adjuvant therapy.

Purpose To assess the role of coregistered 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) in detecting radiographically occult distant metastasis (DM) at staging in patients with locally advanced pancreatic cancer (LAPC) and to study whether FDG-PET parameters can predict relatively long-term survival in patients who are more likely to benefit from chemoradiation therapy (CRT). Methods and Materials From our institutional database, we identified 388 LAPC patients with M0 on conventional computed tomography (CT) who were planned to undergo CRT. Coregistered FDG-PET staging was offered to all patients, and follow-up FDG-PET was used at the clinical discretion of the physician. Results FDG-PET detected unsuspected CT-occult DM in 33% of all 388 patients and allowed them to receive systemic therapy immediately. The remaining 260 patients (PET-M0) underwent CRT selectively as an initial treatment. Early DM arose in 13.1% of 260 patients, and the 1-year estimated locoregional recurrence rate was 5.4%. Median overall survival (OS) and progression-free survival (PFS) were 14.6 and 9.3 months, respectively, at a median follow-up time of 32.3 months (range, 10-99.1 months). Patients with a baseline standardized uptake value (SUV) P Conclusions FDG-PET can detect radiographically occult DM at staging in one-third of patients and spare them from the potentially toxic therapy. Additionally, FDG-PET parameters including baseline SUV and SUV changes may serve as useful clinical markers for predicting the prognosis in LAPC patients.

Purpose This study assessed the prognostic value of pre-operative 2-[18F] fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) volumetric parameters, including metabolic tumor volume (MTV) and total lesion glycolysis (TLG), in patients with epithelial ovarian cancer.

In this study, we aimed to assess the prognostic value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) measured on 18F-FDG PET/CT in pancreatic cancer patients who underwent resection with curative intent. Methods: Eighty-seven patients with pancreatic ductal adenocarcinoma who underwent 18F-FDG PET/CT and subsequent surgical resection with curative intent with (30 patients) or without (57 patients) neoadjuvant therapy were retrospectively enrolled. The maximum standardized uptake value (SUVmax), MTV, and TLG were measured on 18F-FDG PET/CT in all patients. The prognostic significances of PET/CT parameters and tumor factors for recurrence-free survival (RFS) and overall survival (OS) were evaluated by univariate and multivariate analyses. Results: Of the 87 patients, 57 (64%) experienced recurrence during the follow-up period. The tumor size, pathologic T (pT) stage, SUVmax, MTV, and TLG were significant prognostic factors for both RFS and OS (P

Dysregulation of cellular energy metabolism is closely linked to cancer development and progression. Calorie or glucose restriction (CR or GR) inhibits energy-dependent pathways, including IGF-1/PI3K/Akt/mTOR, in cancer cells. However, alterations in proton dynamics and reversal of the pH gradient across the cell membrane, which results in intracellular alkalinization and extracellular acidification in cancer tissues, have emerged as important etiopathogenic factors. We measured glucose, lactate, and ATP production after GR, plant-derived CR-mimetic curcumin treatment, and curcumin plus GR in human hepatoma cells. Intracellular pH regulatory effects, in particular, protein&ndash, protein interactions within mTOR complex-1 and its structural change, were investigated. Curcumin treatment or GR mildly inhibited Na+/H+ exchanger-1 (NHE1). vATPase, monocarboxylate transporter (MCT)-1, and MCT4 level. Combination treatment with curcumin and GR further enhanced the inhibitory effects on these transporters and proton-extruding enzymes, with intracellular pH reduction. ATP and lactate production decreased according to pH change. Modeling of mTOR protein revealed structural changes upon treatments, and curcumin plus GR decreased binding of Raptor and G&beta, L to mTOR, as well as of Rag A and Rag B to Raptor. Consequently, 4EBP1 phosphorylation was decreased and cell migration and proliferation were inhibited in a pH-dependent manner. Autophagy was increased by curcumin plus GR. In conclusion, curcumin treatment combined with GR may be a useful supportive approach for preventing intracellular alkalinization and cancer progression.

One of the major purposes of fiber is to protect the body from hazardous environments and keep the body temperature at its normal level. To enhance thermal insulation, specially processed fibers have been produced to form air pockets, or various types of heat storage materials are mixed with polymer fiber filament yarns. In addition to thermal insulation, heat-generating fibers have recently been developed. In terms of heat-generating mechanism, there are two methods: the chemical method in which heat is generated through reaction with sweat, and physical method, which converts kinetic energy into thermal energy through the continuous expansion and contraction of fibers. Unlike these heat-generating methods, a brand-new fiber that generates heat using microorganisms was developed. Heat-generating polyester yarn was successfully produced by combining heat-generating microorganisms and ceramic powder together. New fabrics made with this yarn showed superior thermal properties compared to other specially developed fabrics for good thermal insulation. In addition to this, since ceramic powder is embedded in yarns, the heat-generating function of fiber was found to operate normally despite tens of washing. This process may open up a new possibility for the development of functional textiles.

Purpose To determine whether persisting cervical fluorodeoxyglucose (FDG) uptake after concurrent chemoradiotherapy (CCRT) for cervical cancer can reflect residual malignancy. Methods F-FDG PET/CT was performed before and after CCRT in 136 patients with cervical cancer. The maximum and mean standardized uptake values (SUVmax and SUVmean) were recorded from PET/CT scans performed pre- and post-treatment. SUVs were correlated with treatment response after CCRT. Final treatment response was determined by MRI and further follow-up PET/CT. One hundred four of 136 patients underwent pelvic MRI, and 32 of 136 patients underwent further follow-up PET/CT. Patients were classified into two categories: patients with residual tumor or patients without residual tumor (complete responder). Pre- and post-treatment serum squamous cell carcinoma antigen (SCC) levels were also recorded for comparison. The optimal cutoff value of SUVmax for predicting residual cervical tumor was determined using receiver-operating characteristic (ROC) analysis. Results Of 136 patients, 124 showed complete response on further follow-up studies and 12 were confirmed to have residual tumor. The post-treatment SUVmax and pre-/post-treatment SUVmean of complete responders were significantly lower than those of patients with residual tumor: 2.5 ± 0.8 and 7.2 ± 4.2/1.9 ± 0.7 for complete responders and 5.7 ± 2.6 and 12.8 ± 6.9/3.7 ± 0.7 for patients with residual tumor (p

Pulmonary lesions from active tuberculosis patients are thought to contain persistent, nonreplicating bacilli that arise from hypoxic stress. Metronidazole, approved for anaerobic infections, has antituberculosis activity against anoxic bacilli in vitro and in some animal models and may target persistent, nonreplicating bacilli. In this double-blind, placebo-controlled trial, pulmonary multidrug-resistant tuberculosis subjects were randomly assigned to receive metronidazole (500 mg thrice daily) or placebo for 8 weeks in addition to an individualized background regimen. Outcomes were measured radiologically (change on high-resolution computed tomography [HRCT]), microbiologically (time to sputum smear and culture conversion), and clinically (status 6 months after stopping therapy). Enrollment was stopped early due to excessive peripheral neuropathies in the metronidazole arm. Among 35 randomized subjects, 31 (15 metronidazole, 16 placebo) were included in the modified intent-to-treat analysis. There were no significant differences by arm in improvement of HRCT lesions from baseline to 2 or 6 months. More subjects in the metronidazole arm converted their sputum smear ( P = 0.04) and liquid culture ( P = 0.04) to negative at 1 month, but these differences were lost by 2 months. Overall, 81% showed clinical success 6 months after stopping therapy, with no differences by arm. However, 8/16 (50%) of subjects in the metronidazole group and 2/17 (12%) of those in the placebo group developed peripheral neuropathy. Subjects who received metronidazole were 4.3-fold (95% confidence interval [CI], 1.1 to 17.1) more likely to develop peripheral neuropathies than subjects who received placebo. Metronidazole may have increased early sputum smear and culture conversion but was too neurotoxic to use over the longer term. Newer nitroimidazoles with both aerobic and anaerobic activity, now in clinical trials, may increase the sterilizing potency of future treatment regimens.

The aim of this study was to develop a highly reliable radiofluorination method for the preparation of N-{2-[4-(2-methoxyphenyl)piperazinyl]ethyl}-N-(2-pyridyl)-N-(4-(18) F-fluoromethylcyclohexane)carboxamide ([(18) F]Mefway) by using a fully automated system. The optimal condition is composed of two parts. The extraction system of the trapped F-18 in the anion exchange resin (i.e., quaternary methylamine cartridge) is a complex of Kryptofix 2.2.2. (K222, 4 mg/0.9 mL methanol) and K2 CO3 (1 mg/0.1 mL H2 O). After removing the solvents, the trans-tosylated Mefway precursor (1 mg/0.5 mL acetonitrile) was reacted with dried K222-K[(18) F] at 100°C for 5 min. After purification and formulation, [(18) F]Mefway was obtained with 38 ± 2.4% (decay corrected, n = 34) radiochemical yield, a total synthesis time of 52 ± 3.4 min, specific activity was 120.6 ± 8.7 GBq/µmol at the end of synthesis and a radiochemical purity of 99%. According to the quality control tests, formulated [(18) F]Mefway is suitable to apply parenteral clinical application.

γ-aminobutyric acid (GABA)-A receptor–mediated neural transmission is important to promote practice-dependent plasticity after brain injury. This study investigated alterations in GABA-A receptor binding and functional and anatomic connectivity within the motor cortex in children with cerebral palsy (CP). Methods: We conducted 18F-fluoroflumazenil PET on children with hemiplegic CP to investigate whether in vivo GABA-A receptor binding is altered in the ipsilateral or contralateral hemisphere of the lesion site. To evaluate changes in the GABA-A receptor subunit after prenatal brain injury, we performed GABA-A receptor immunohistochemistry using rat pups with a diffuse hypoxic ischemic insult. We also performed diffusion tensor MR imaging and resting-state functional MR imaging on the same children with hemiplegic CP to investigate alterations in anatomic and functional connectivity at the motor cortex with increased GABA-A receptor binding. Results: In children with hemiplegic CP, the 18F-fluoroflumazenil binding potential was increased within the ipsilateral motor cortex. GABA-A receptors with the α1 subunit were highly expressed exclusively within cortical layers III, IV, and VI of the motor cortex in rat pups. The motor cortex with increased GABA-A receptor binding in children with hemiplegic CP had reduced thalamocortical and corticocortical connectivity, which might be linked to increased GABA-A receptor distribution in cortical layers in rats. Conclusion: Increased expression of the GABA-A receptor α1 subunit within the ipsilateral motor cortex may be an important adaptive mechanism after prenatal brain injury in children with CP but may be associated with improper functional connectivity after birth and have adverse effects on the development of motor plasticity.

Altered transmission of gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter, may contribute to the development of schizophrenia. The purpose of the present study was to investigate the presence of GABA-A/benzodiazepine (BZ) receptor binding abnormalities in individuals at ultra-high risk (UHR) for psychosis in comparison with normal controls using [(18)F]-fluoroflumazenil (FFMZ) positron emission tomography (PET). In particular, we set regions of interest in the striatum (caudate, putamen, and nucleus accumbens) and medial temporal area (hippocampus and parahippocampal gyrus).Eleven BZ-naive people at UHR and 15 normal controls underwent PET scanning using [(18)F]-FFMZ to measure GABA-A/BZ receptor binding potential. The regional group differences between UHR individuals and normal controls were analyzed using Statistical Parametric Mapping 8 software. Participants were evaluated using the structured interview for prodromal syndromes and neurocognitive function tasks.People at UHR demonstrated significantly reduced binding potential of GABA-A/BZ receptors in the right caudate.Altered GABAergic transmission and/or the imbalance of inhibitory and excitatory systems in the striatum may be present at the putative prodromal stage and play a pivotal role in the pathophysiology of psychosis.

Manifestation of the functionalities from the structural brain network is becoming increasingly important to understand a brain disease. With the aim of investigating the differential structure-function couplings according to network systems, we investigated the structural and functional brain networks of patients with spastic diplegic cerebral palsy with periventricular leukomalacia compared to healthy controls. The structural and functional networks of the whole brain and motor system, constructed using deterministic and probabilistic tractography of diffusion tensor magnetic resonance images and Pearson and partial correlation analyses of resting-state functional magnetic resonance images, showed differential embedding of functional networks in the structural networks in patients. In the whole-brain network of patients, significantly reduced global network efficiency compared to healthy controls were found in the structural networks but not in the functional networks, resulting in reduced structural-functional coupling. On the contrary, the motor network of patients had a significantly lower functional network efficiency over the intact structural network and a lower structure-function coupling than the control group. This reduced coupling but reverse directionality in the whole-brain and motor networks of patients was prominent particularly between the probabilistic structural and partial correlation-based functional networks. Intact (or less deficient) functional network over impaired structural networks of the whole brain and highly impaired functional network topology over the intact structural motor network might subserve relatively preserved cognitions and impaired motor functions in cerebral palsy. This study suggests that the structure-function relationship, evaluated specifically using sparse functional connectivity, may reveal important clues to functional reorganization in cerebral palsy. Hum Brain Mapp 38:5292-5306, 2017. © 2017 Wiley Periodicals, Inc.

Purpose: To demonstrate the significance of simultaneous electroencephalography (EEG) recording during 2-deoxy-2-[ 18 F] fluoro-D-glucose (FDG)-positron emission tomography (PET) in childhood partial epilepsy. Materials and Methods: We included 46 children with partial epilepsy who underwent simultaneous EEG during PET. We compared the epileptogenic area of several EEG features including epileptiform discharges, focal polymorphic slow waves, and electrographic seizures, with the abnormal metabolic region on PET. We also compared the epileptogenic area of simultaneous EEG and PET with findings on magnetic resonance imaging (MRI) and video/EEG, as well as the histopathological diagnosis of the resected cortical area, in eight patients who underwent surgical resection of the epileptogenic area. Results: Hypometabolic regions on interictal PET were concordant with epileptogenic areas of epileptiform discharges and focal polymorphic slow waves, according to their frequency and/or severity, with odds ratios of 1.35 and 1.81, respectively (p

The surface of multi-walled carbon nanotube (MWCNT) was chemically oxidized using nitric acid and sulfuric–nitric acid mixtures. Thermogravimetric analysis, transmission electron microscopy and infrared spectroscopy revealed that the use of acid mixtures led to higher degree of oxidation. More quantitative identification of surface carboxylic acids was carried out using X-ray photoelectron spectroscopy (XPS) and acid–base titration. However, these techniques are costly and require very long analysis times to promptly respond to the extent of the reaction. We propose a much simpler method using pH measurements and pre-determined pKa value in order to estimate the concentration of carboxylic acids on the oxidized MWCNT surfaces. The results from this technique were consistent with those obtained from XPS and titration, and it is expected that this simple quantification method can provide a cheap and fast way to monitor and control the oxidation reaction of MWCNT.

Aim Attention deficit has been reported in both schizophrenia patients and patients with major depressive disorder (MDD). The aim of this study was to elucidate the deficits in sustained attention and associated neural network dysfunctions in schizophrenia patients and MDD patients, and to investigate the difference between the two patient groups. Methods Twelve schizophrenia patients, 12 patients with non-psychotic MDD, and 12 healthy control subjects participated in this study. A sustained attention to response task (SART) was used to measure attention capacity. Cerebral blood flow (CBF) during attention tasks was measured using H215O positron emission tomography. Statistical parametric mapping and analysis of covariance were performed to compare the behavioral performance and CBF changes during SART among three groups. Results Behavioral performances were not significantly different among the three groups except for an increased commission error rate in the schizophrenia group. Regional CBF during SART was significantly reduced in the left inferior frontal gyrus, the left cuneus, and the right superior parietal lobule and increased in the right superior frontal gyrus and the right cuneus in the schizophrenia group compared to the healthy control group. In the MDD group, neither significant regional CBF difference nor behavioral deficit was found compared to the healthy control group. Conclusion Behavioral performance deficit and perfusion changes in the prefrontal and parietal cortices during SART were observed only in the schizophrenia group. Prefrontal and parietal network dysfunction for sustained attention may be involved in the pathophysiology of schizophrenia.

PURPOSE Dendritic cell (DC) vaccination for melanoma was introduced because melanoma carries distinct tumor-associated antigens. The purpose of this study was to investigate the efficacy and safety of DC vaccination for melanoma in Korea. MATERIALS AND METHODS Five patients with stage IV and one with stage II were enrolled. Autologous monocyte-derived DCs (MoDCs) were cultured and pulsed with tumor-lysate, keyhole limpet hemocyanin, and cytokine cocktail for mature antigen-loaded DC. DC vaccination was repeated four times at 2-week intervals and 2-4×10⁷ DC were injected each time. RESULTS Reduced tumor volume was observed by PET-CT in three patients after DC vaccination. Delayed type hypersensitivity responses against tumor antigen were induced in five patients. Tumor antigen-specific IFN-γ-producing peripheral blood mononuclear cells were detected with enzyme-linked immunosorbent spot in two patients. However, the overall clinical outcome showed disease progression in all patients. CONCLUSION In this study, DC vaccination using tumor antigen-loaded, mature MoDCs led to tumor regression in individual melanoma patients. Further standardization of DC vaccination protocol is required to determine which parameters lead to better anti-tumor responses and clinical outcomes.

Aim: Liver transplantation (LT) is a curative treatment for localized hepatocellular carcinoma (HCC), but the recurrence rate after LT is about 10–20%, with a dismal prognosis. Little data exist as to the natural history, treatment outcome and optimal treatment of recurrent HCC after LT. We reviewed various treatment modalities given to patients with recurrent HCC after LT. Methods: Among 132 patients who underwent LT for localized HCC, we retrospectively reviewed medical records of 39 of the 132 patients who developed recurrent HCC after LT. We analyzed the clinical outcome of various treatment modalities and treatment-related adverse events. Results: A total of 39 (29%) of the original 132 patients had recurrent HCC, most recurrences (82%) having occurred within 1 year after LT and involved extrahepatic lesions. Only seven patients had recurrent disease limited to the liver. The median overall survival from the initial treatment of all relapsed patients was 6.9 months. There were various initial treatment modalities, namely palliative systemic chemotherapy, trans-catheter arterial chemo-embolization/infusion (TACE/I), radiation therapy (RT), surgical resection and no treatment. The median overall survival was 9.5 months for first-line chemotherapy, including those who had prior local therapy, 6.3 months TACE/I and 6.9 months for RT. Conclusion: Various clinical approaches have been used to treat patients with recurrent HCC after LT in a clinical setting. More effective strategies and clinical guidelines for recurrent HCC following LT must be established.

Oncogenic osteomalacia is a rare paraneoplastic syndrome characterized by renal phosphate excretion, hypophosphatemia, and osteomalacia. This syndrome is often caused by tumors of mesenchymal origin. Patients with oncogenic osteomalacia have abnormal bone mineralization, resulting in a high frequency of fractures. Tumor resection is the treatment of choice, as it will often correct the metabolic imbalance. Although oncogenic osteomalacia is a potentially curable disease, diagnosis is difficult and often delayed because of the small size and sporadic location of the tumor. Bone scintigraphy and radiography best characterize osteomalacia; magnetic resonance imaging findings are nonspecific. Here, we report a case of oncogenic osteomalacia secondary to a phosphaturic mesenchymal tumor that was successfully detected by (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT). This case illustrates the advantages of (18)F-FDG PET/CT in detecting the occult mesenchymal tumor that causes oncogenic osteomalacia.

Background: Sorafenib (Nexavar) is an orally active multikinase inhibitor that is approved for the treatment of hepatocellular carcinoma (HCC). In this study, we used 18F-2-fluoro-2-deoxyglucose (18F-FDG) with positron emission tomography (PET) to predict the treatment outcome of sorafenib in patients with advanced HCC. Materials and methods: A total of 29 patients with HCC were included. Baseline 18F-FDG PET scans were performed a median of 14 days before sorafenib treatment. Sorafenib was administered orally at a dose of 400 mg twice daily. For statistical analysis, the standardized uptake value (SUV) of the most hypermetabolic lesion was obtained and assigned as the SUVmax for each patient. Results: Among 29 patients, one patient achieved partial remission and 14 patients showed stable disease. The overall survival (OS) and progression free survival (PFS) were 5.1 months [95% confidence interval (CI): 0.0–12.0] and 3.8 months (95% CI: 1.4–6.2). The multivariate analysis of OS showed that four indices, Eastern Cooperative Oncology Group performance status, α-fetoprotein (AFP) concentration, portal vein thrombosis and SUVmax were significant prognostic factors (P=0.030, P=0.024, P=0.020 and P=0.015 respectively). AFP concentration and SUVmax were independent prognostic factors for PFS, too (P=0.003 and P=0.026 respectively). When the patients were divided into two groups: low SUVmax (n=10

BACKGROUND: Metabolic activity assessed by 18F-fluorodeoxyglocuse-positron emission tomography (18F-FDG-PET) reflects biological aggressiveness and prognoses in various tumors. The authors present a correlation between tumor metabolic activity and clinical outcomes in patients with hepatocellular carcinoma (HCC). METHODS: Over a 3-year period (2005-2008), 135 locally advanced HCC patients were treated with localized concurrent chemoradiotherapy (CCRT; external beam radiotherapy at 45 grays for 5 weeks plus concurrent hepatic arterial infusion of 5-fluorouracil during the first and fifth week) followed by repetitive hepatic arterial infusional chemotherapy with 5-fluorouracil and cisplatin. Among them, the authors studied 107 who received 18F-FDG-PET before CCRT. Maximal standardized uptake values (SUVs) of tumors were calculated. RESULTS: The median maximal tumor SUV was 6.1 (range, 2.4-∼19.2). Patients with low maximal tumor SUVs (

Periventricular leucomalacia has long been investigated as a leading cause of motor and cognitive dysfunction in patients with spastic diplegic cerebral palsy. However, patients with periventricular leucomalacia on conventional magnetic resonance imaging do not always have motor dysfunction and preterm children without neurological abnormalities may have periventricular leucomalacia. In addition, it is uncertain whether descending motor tract or overlying cortical injury is related to motor impairment. To investigate the relationship between motor pathway injury and motor impairment, we conducted voxelwise correlation analysis using tract-based spatial statistics of white matter diffusion anisotropy and voxel-based-morphometry of grey matter injury in patients with periventricular leucomalacia and spastic diplegia ( n = 43, mean 12.86 ± 4.79 years, median 12 years). We also evaluated motor cortical and thalamocortical connectivity at resting state in 11 patients using functional magnetic resonance imaging. The functional connectivity results of patients with spastic diplegic cerebral palsy were compared with those of age-matched normal controls. Since γ-aminobutyric acidA receptors play an important role in the remodelling process, we measured neuronal γ-aminobutyric acidA receptor binding potential with dynamic positron emission tomography scans ( n = 27) and compared the binding potential map of the patient group with controls ( n = 20). In the current study, white matter volume reduction did not show significant correlation with motor dysfunction. Although fractional anisotropy within most of the major white matter tracts were significantly lower than that of age-matched healthy controls ( P

OBJECTIVE In previous studies, some brain areas, including parahippocampal gyrus, were suggested to be associated with panic disorder. Both panic disorder and somatoform disorders are associated with anxiety. This study sought to determine if there are shared neural activity underlying panic disorder and undifferentiated somatoform disorder. METHOD Sixteen nonmedicated patients with panic disorder, 16 nonmedicated patients with undifferentiated somatoform disorder, and 10 healthy subjects were scanned between February 2005 and August 2006. Diagnoses were made according to the Korean version of the Structured Clinical Interview for DSM-IV Axis I Disorders, Research Version, Patient/Non-Patient Edition. Regional cerebral perfusion was measured by 99 m-Tc-ethyl cysteinate dimer single photon emission computed tomography (SPECT). Using statistical parametric mapping analysis, we compared the SPECT images between the groups. RESULTS Significant hyperperfusion was found at the left superior temporal gyrus and the left supramarginal gyrus in the panic disorder patients when compared to the controls (family-wise error [FWE], P < .001). The somatoform disorder patients showed hyperperfusion in the left hemisphere at the superior temporal gyrus, inferior parietal lobule, middle occipital gyrus, precentral gyrus, postcentral gyrus, and, in the right hemisphere, at the superior temporal gyrus when compared to the controls (false discovery rate [FDR], P < .001). In contrast, significant hypoperfusion was found at the right parahippocampal gyrus in each of panic disorder (FWE, P = .001) and somatoform disorder (FWE, P < .001) groups compared to healthy controls. However, no significant differences were found in regional cerebral perfusion between the 2 disorder groups. CONCLUSIONS Both panic disorder and undifferentiated somatoform disorder showed hyperperfusion in the left superior temporal gyrus and hypoperfusion in the right parahippocampal gyrus, which suggests that the 2 disorders are likely to share neural activity.

We observed bilateral pelvic foci of 18F-FDG uptake (BiPF) exclusively in females—a finding not previously reported—and assessed the frequency, anatomic localization, and clinical significance of the uptake. Methods: On 18F-FDG PET/CT and coregistered contrast-enhanced CT scans of 159 females (age, 16–81 y), the presence of BiPF and their location were evaluated. The findings were correlated with the age and menstrual history of the patient. Results: BiPF were seen in 14 (22%) of 63 patients up to 53 y old, predominantly at mid menstrual cycle, and were best coregistered to the fallopian tubes on contrast-enhanced CT. None of 96 patients older than 53 y showed BiPF. Conclusion: Fallopian 18F-FDG uptake was seen predominantly in premenopausal women at mid menstrual cycle. This finding is in accordance with known cyclic changes of fallopian tubes in response to ovarian hormones and may be the first, to our knowledge, imaging evidence revealing the influence of estrogen on the fallopian tubes.

The electrical, morphological and rheological properties of melt- and dry-mixed composites of polypropylene (PP)/nickel-coated carbon fiber (NCCF) with multi-walled carbon nanotubes (MWCNTs) was investigated. Melt mixed PP/NCCF/MWCNT composites were prepared by mixing the materials with a twin screw extruder. From the results of the electrical conductivity of the PP/NCCF/MWCNT composites, the MWCNTs increased the electric conductivity of the PP/NCCF composites appreciably. A higher aspect ratio of MWCNTs can increase the conductivity of PP/NCCF composites in a polymer matrix compared to the composites without the MWCNTs. The tensile and flexural strengths of the PP/NCCF/MWCNT composites were higher than the composites without MWCNTs. This is might be due to the reinforcing effect of the well dispersed MWCNT in the PP matrix. The results of electrical, morphological and mechanical studies indicate that the MWCNTs increased the electrical conductivity and mechanical strength of the PP/NCCF composites.

Despite clinical and neuropsychological similarities between Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB), recent studies have demonstrated that structural and pathological changes are more severe in DLB than in PDD.19 patients with probable PDD and 18 patients with probable DLB who had a similar overall severity of dementia and demographic characteristics were examined by a standardised neuropsychological test and voxel-based analysis of fractional anisotropy (FA) using diffusion tensor imaging (DTI).The patients with DLB performed significantly worse in visual recognition memory, semantic fluency and ideomotor praxis than those with PDD (p0.05). Compared with controls, the FA value in patients with PDD was significantly lower in bilateral frontal, left temporal and left parietal white matter. In patients with DLB, the pattern of FA reduction was similar to that of patients with PDD; however, white-matter abnormalities were more severe and extended into bilateral insular, bilateral posterior cingular and bilateral visual association regions. In a direct comparison between PDD and DLB, the FA value in patients with DLB was significantly decreased in bilateral posterior temporal, posterior cingular and bilateral visual association fibres extending into occipital areas.Despite global similarities in cognitive performance and white-matter pathology between DLB and PDD patients, those with DLB had more severely impaired frontal and temporal area-associated cognitive subsets, and more severe white-matter pathology in temporal and visual association fibres. These data suggest that differences in the underlying nature of PDD and DLB may exist with global similarities in their cognitive performance and white-matter pathology.

Background: We measured donor kidney weight (D-KW), functional renal volume (D-FRV), and single-kidney glomerular filtration rate (D-SKGFR), and then evaluated the impact of the indices to recipient body weight (R-BW) on graft function. Methods: This study included 44 recipients of live donor transplants without delayed graft function or acute rejection within 2 years of transplantation. Results: There was a statistically significant difference in serum creatinine between recipients with a D-KW/R-BW ratio of ≤4.25, D-FRV/R-BW ratio of ≤5.14, or D-SKGFR/R-BW ratio of ≤1.06 and recipients with a D-KW/R-BW ratio of >4.25, D-FRV/R-BW ratio of >5.14, or D-SKGFR/R-BW ratio of >1.06, respectively. D-KW/R-BW, D-FRV/R-BW, and D-SKGFR/R-BW strongly correlated with serum creatinine at 1 year and 2 years post-transplantation. In multivariate analysis, D-FRV and donor age were statistically significant risk factors which influenced serum creatinine at 1 year and 2 years post-transplantation. Conclusion: D-FRV/R-BW and donor age have significant impact on graft function. D-FRV/R-BW can be measured ahead of surgery. Therefore, measuring the D-FRV is useful to select a more optimal donor kidney among otherwise similar candidates during preoperative evaluation to improve posttransplant graft function.

We analyzed the pattern of (11)C-acetate and (18)F-FDG uptake on PET/CT in patients with hepatocellular carcinoma (HCC). We also assessed the expression of important regulatory enzymes related to glycolysis and lipid synthesis in relation to (18)F-FDG and (11)C-acetate uptake in human HCC cell lines. The significance of (11)C-acetate uptake regulation was further evaluated with regard to cell viability.(18)F-FDG and (11)C-acetate uptake patterns in HCC in 11 patients and in 5 HCC cell lines were assessed. We evaluated the gene expression of metabolic enzymes related to glycolysis and lipid synthesis in a cell line with the highest (18)F-FDG uptake and another cell line with the highest (11)C-acetate uptake. They included hexokinase II, adenosine triphosphate citrate lyase, acetyl coenzyme A (CoA) synthetase 1 (ACSS1), acetyl CoA synthetase 2 (ACSS2), acetyl CoA carboxylase, and fatty acid synthase. In a cell line with high (11)C-acetate uptake, the enzymatic activities of ACSS1 and ACSS2 were blocked using respective small, interfering RNAs (siRNAs), and the impact on (11)C-acetate uptake and cell viability was assessed.In all 11 patients and 4 of the 5 cell lines, the uptake patterns of the 2 radiotracers were complementary. ACSS1 and ACSS2 were highly expressed in a cell line with low (18)F-FDG uptake and high (11)C-acetate uptake, whereas only ACSS2 was expressed in a cell line with high (18)F-FDG uptake and low (11)C-acetate uptake. Fatty acid synthase expression was seen in cells with high (18)F-FDG or (11)C-acetate uptake. These findings indicate the possibility that both glucose and acetate can be a compensatory carbon source for lipid synthesis in cancer. Transient transfection with ACSS1 or ACSS2 siRNA in cells with high (11)C-acetate uptake decreased (11)C-acetate uptake and cell viability.The patterns of (18)F-FDG and (11)C-acetate uptake seemed to complement each other in both human HCC and HCC cell lines. Fatty acid synthase expression was seen in cells with high (18)F-FDG or (11)C-acetate uptake, suggesting glucose- or acetate-dependent lipid synthesis. Acetyl CoA synthetase appears to be important in (11)C-acetate uptake and acetate-dependent lipid synthesis for the growth of cancer cells with a low-glycolysis phenotype. Inhibition of acetyl CoA synthetase in these cells may be promising for anticancer treatment.

Objectives: To determine the effects of treatment with donepezil on cortical metabolism in patients with traumatic brain injury using 18 F-fluorodeoxyglucose positron emission tomography. Methods: Twenty-six patients with cognitive impairment after traumatic brain injury were enrolled and randomly assigned into the donepezil-treated group and the control group. There was no significant difference between 2 groups in age, sex, education, and postinjury duration. Donepezil 5 mg was administered daily for 3 weeks and then 10 mg/d for 3 weeks to patients in the experimental groups. For both groups, we evaluated cognitive function with Mini-Mental State Examination, Wechsler Memory Test, Boston Naming Test, Colored Progressive Matrices upon initial evaluation and at the 6-week follow-up. An 18 F-fluorodeoxyglucose positron emission tomography of the brain was performed before and after 6 weeks of the donepezil-treated group. Effects of donepezil treatment on cortical metabolism were analyzed using Statistical Parametric Mapping software (Institute of Neurology, University College London, UK). Results: There was no significance difference between the 2 groups in initial evaluation of cognitive functions. After 6 weeks, compared with the control group, donepezil-treated group showed enhanced cognitive functions (P < 0.05), and 18 F-fluorodeoxyglucose positron emission tomography showed a statistically significant increase in the cerebral cortical metabolism for both of the frontal, parietal, occipital, and temporal cortices (P < 0.01) which are the key role of attention and object naming. Conclusions: Cholinergic augmentation by donepezil therapy in traumatic brain injury shows a cortical metabolic effect on the both of the frontal, parietal, occipital, and temporal cortices associated with clinical response to treatment.