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1.  Usefulness of Ventricular Endocardial Electric Reconstruction from Body Surface Potential Maps to Noninvasively Localize Ventricular Ectopic Activity in Patients 
Physics in medicine and biology  2013;58(11):3897-3909.
As radio frequency (RF) catheter ablation becomes increasingly prevalent in the management of ventricular arrhythmia in patients, an accurate and rapid determination of the arrhythmogenic site is of important clinical interest. The aim of this study was to test the hypothesis that the inversely reconstructed ventricular endocardial current density distribution from body surface potential maps (BSPMs) can localize the regions critical for maintenance of a ventricular ectopic activity. Patients with isolated and monomorphic premature ventricular contractions (PVCs) were investigated by noninvasive BSPMs and subsequent invasive catheter mapping and ablation. Equivalent current density (CD) reconstruction (CDR) during symptomatic PVCs was obtained on the endocardial ventricular surface in 6 patients (4 men, 2 women, years 23–77), and the origin of the spontaneous ectopic activity was localized at the location of the maximum CD value. Compared with the last (successful) ablation site (LAS), the mean and standard deviation of localization error of the CDR approach were 13.8 mm and 1.3 mm, respectively. In comparison, the distance between the LASs and the estimated locations of an equivalent single moving dipole (SMD) in the heart was 25.5 ± 5.5 mm. The obtained CD distribution of activated sources extending from the catheter ablation site also showed a high consistency with the invasively recorded electroanatomical maps. The noninvasively reconstructed endocardial CD distribution is suitable to predict a region of interest containing or close to arrhythmia source, which may have the potential to guide RF catheter ablation.
doi:10.1088/0031-9155/58/11/3897
PMCID: PMC3776132  PMID: 23681281
electrocardiographic inverse problem; current density reconstruction; radio frequency catheter ablation; premature ventricular contraction; body surface potential mapping
2.  Androgen receptor agonism promotes an osteogenic gene program in preadipocytes 
Androgens regulate body composition by interacting with the androgen receptor (AR) to control gene expression in a tissue-specific manner. To identify novel regulatory roles for AR in preadipocytes, we created a 3T3-L1 cell line stably expressing human AR. We found AR expression is required for androgen-mediated inhibition of 3T3-L1 adipogenesis. This inhibition is characterized by decreased lipid accumulation, reduced expression of adipogenic genes, and induction of genes associated with osteoblast differentiation. Collectively, our results suggest androgens promote an osteogenic gene program at the expense of adipocyte differentiation.
doi:10.1016/j.bbrc.2013.03.078
PMCID: PMC3763992  PMID: 23567971
Adipocyte; Osteoblast; Androgen receptor; Gene regulation
3.  Complex B1 Mapping and Electrical Properties Imaging of the Human Brain using a 16-channel Transceiver Coil at 7T 
The electric properties (EPs) of biological tissue provide important diagnostic information within radio and microwave frequencies, and also play an important role in specific absorption rate (SAR) calculation which is a major safety concern at ultrahigh field (UHF). The recently proposed electrical properties tomography (EPT) technique aims to reconstruct EPs in biological tissues based on B1 measurement. However, for individual coil element in multi-channel transceiver coil which is increasingly utilized at UHF, current B1-mapping techniques could not provide adequate information (magnitude and absolute phase) of complex transmit and receive B1 which are essential for EPT, electric field, and quantitative SAR assessment. In this study, using a 16-channel transceiver coil at 7T, based on hybrid B1-mapping techniques within the human brain, a complex B1-mapping method has been developed, and in-vivo EPs imaging of the human brain has been demonstrated by applying a logarithm-based inverse algorithm. Computer simulation studies as well as phantom and human experiments have been conducted at 7T. The average bias and standard deviation for reconstructed conductivity in vivo were 28% and 67%, and 10% and 43% for relative permittivity, respectively. The present results suggest the feasibility and reliability of proposed complex B1-mapping technique and EPs reconstruction method.
doi:10.1002/mrm.24358
PMCID: PMC3549472  PMID: 22692921
electric properties; B1-mapping; B1 phase; ultrahigh field MRI; multi-channel transceiver array
4.  Investigation into the Toxicity of Traditional Uyghur Medicine Quercus Infectoria Galls Water Extract 
PLoS ONE  2014;9(3):e90756.
Objective
Quercus infectoria galls (QIG) is being widely used in Traditional Uyghur Medicine. To gather preclinical safety information for the aqueous extract of QIG, a toxicity study was performed.
Methods
Subject animals were randomized, and devided into exposure and control groups. In the acute toxicity phase, three different doses—5, 7.5, and 10 g/kg, respectively—were administered via enema to imprinting control region (ICR) mice. An experiment using the maximum tolerance dose (MTD) i.e.10 g/kg was also performed. Data were gathered for 14 days, and study parameters were clinical signs, body weight, general behavior, adverse effects and mortality. At the day 14, major organs of the subjects were examined histologically. Chronic toxicity was also evaluated in Wistar rats for over 180 consecutive days. The rats were divided into three groups with different doses of 0.2 g/kg, 0.8 g/kg, and 2 g/kg, QIG. Furthermore, observations were carried out in rabbits to investigate if there were signs of irritation.
Results
In comparison to control group, acute, chronic toxicity and mortality were not significantly increased in exposure group.
Conclusion
Study result suggests that the aqueous extract of QIG is unlikely to have significant toxicity and that clinical trials may proceed safely.
doi:10.1371/journal.pone.0090756
PMCID: PMC3946586  PMID: 24608135
5.  Promoting Female Condoms in the Sex Industry in Four Towns of Southern China: Context Matters 
Sexually transmitted diseases  2013;40(3):264-270.
Background
The female condom (FC) is an effective tool for dual protection, but it remains underused. Individual as well as contextual reasons need to be explored.
Objective
To compare individual and contextual characteristics of FC multi-time users, one-time users and non-users among women in the sex industry of four study sites in China.
Methods
A standardized one-year FC intervention along with male condoms was implemented through outreach to sex establishments. Three serial cross-sectional surveys were conducted at baseline and after each of two six-month intervention phases.
Results
A total of 445, 437 and 290 eligible women were interviewed at three cross-sectional surveys, respectively. At the first and second post-intervention surveys, 83.3% and 81.7% of women reported knowing about FC, and 28.8% and 36.6% had used FC at least once. Women who used FC multiple times reported less unprotected sex than non-users in the last 30 days (3.0% vs. 17.2% at first and 3.2% vs. 16.8% at second post-intervention survey, p<0.01). Polytomous logistic regression showed that both one-time and multi-time users were more likely to come from one particular site (about 3 times more than the reference site). Higher intervention scores (adjusted OR 1.8–4.0) and working in boarding houses (adjusted OR 3.4) were associated with FC use.
Conclusions
Adding FC into male-condom-only intervention may reduce unprotected sex among women in sex establishments in rural and small urban areas of China. Adoption of FC may be related not only to intervention exposure, but also to contextual factors associated with study site and type of sex establishments.
doi:10.1097/OLQ.0b013e31827c58c9
PMCID: PMC3572509  PMID: 23403607
female condom; sex workers; China; HIV/STI prevention; community intervention
6.  Neuromodulation for Brain Disorders: Challenges and Opportunities 
The field of neuromodulation encompasses a wide spectrum of interventional technologies that modify pathological activity within the nervous system to achieve a therapeutic effect. Therapies including deep brain stimulation (DBS), intracranial cortical stimulation (ICS), transcranial direct current stimulation (tDCS), and transcranial magnetic stimulation (TMS) have all shown promising results across a range of neurological and neuropsychiatric disorders. While the mechanisms of therapeutic action are invariably different amongst these approaches, there are several fundamental neuroengineering challenges that are commonly applicable to improving neuromodulation efficacy. This article reviews the state-of-the-art of neuromodulation for brain disorders and discusses the challenges and opportunities available for clinicians and researchers interested in advancing neuromodulation therapies.
doi:10.1109/TBME.2013.2244890
PMCID: PMC3724171  PMID: 23380851
neuromodulation; neuroengineering; deep brain stimulation; intracranial cortical stimulation; transcranial magnetic stimulation; transcranial direct current stimulation
7.  Magnetoacoustic Tomography with Magnetic Induction: Bioimepedance reconstruction through vector source imaging 
IEEE transactions on medical imaging  2013;32(3):10.1109/TMI.2013.2239656.
Magneto acoustic tomography with magnetic induction (MAT-MI) is a technique proposed to reconstruct the conductivity distribution in biological tissue at ultrasound imaging resolution. A magnetic pulse is used to generate eddy currents in the object, which in the presence of a static magnetic field induces Lorentz force based acoustic waves in the medium. This time resolved acoustic waves are collected with ultrasound transducers and, in the present work, these are used to reconstruct the current source which gives rise to the MAT-MI acoustic signal using vector imaging point spread functions. The reconstructed source is then used to estimate the conductivity distribution of the object. Computer simulations and phantom experiments are performed to demonstrate conductivity reconstruction through vector source imaging in a circular scanning geometry with a limited bandwidth finite size piston transducer. The results demonstrate that the MAT-MI approach is capable of conductivity reconstruction in a physical setting.
doi:10.1109/TMI.2013.2239656
PMCID: PMC3808985  PMID: 23322761
Electrical impedance imaging; Helmholtz decomposition; Magneto acoustic tomography (MAT-MI); reconstruction
8.  Combined thoracoscopic and laparoscopic minimally invasive esophagectomy 
Journal of Thoracic Disease  2014;6(2):152-155.
With the improvement in thoracoscopic and laparoscopic surgery, thoracoscopic and laparoscopic esophagectomy (TLE), a minimally invasive approach, has attracted increasing attention as an alternative to open three-field esophagectomy. From June 2012 to October 2013, 90 patients underwent laparoscopic and thoracoscopic resection of esophageal carcinoma in our department. The VATS esophagectomy technique described here is the approach currently employed in the department of thoracic surgery at Sichuan Provincial People’s Hospital of China.
doi:10.3978/j.issn.2072-1439.2014.02.04
PMCID: PMC3944189  PMID: 24605230
Thoracoscopic and laparoscopic; minimally invasive; esophagectomy
9.  Human herpes virus 8-unrelated primary effusion lymphoma-like lymphoma in a patient with hepatitis B virus-related liver cirrhosis: A case report 
This study describes a rare case of Human Immunodeficiency Virus and Human Herpes Virus 8 (HHV-8) negative primary effusion lymphoma (PEL)-like lymphoma in a patient with hepatitis B virus-related liver cirrhosis, diagnosed in a 66-year-old male who rapidly progressed to a sense of abdominal fullness. Cytological analysis of the pleural effusion demonstrated large atypical lymphoid cells with rounded nuclei, prominent nucleoli, and abundant cytoplasm. Immunocytochemistry of the pleural effusion detected atypical CD20+ lymphoid cells. The patient was hospitalized, and died following sepsis and multi-organ failure. Our case highlights that HHV-8-unrelated PEL-like lymphoma patients have different pathogenetic mechanisms of causality at the biological level, immunophenotype, clinical behavior, and prognosis.
PMCID: PMC3999608  PMID: 24778676
Hepatitis B virus; human herpes virus 8; liver cirrhosis; primary effusion lymphoma
10.  Magnetoacoustic Tomography with Magnetic Induction: A Rigorous Theory 
IEEE transactions on bio-medical engineering  2008;55(2 0 2):10.1109/TBME.2007.912674.
We have proposed a new theory on mechanism of the magnetoacoustic signal generation with magnetic induction for an object with an arbitrary shape. An object under a static magnetic field emits acoustic signals when excited by a time-varying magnetic field, and that the acoustic waveform is mainly generated at the conductivity boundaries within the object. The proposed theory on the magnetoacoustic tomography with magnetic induction produced highly consistent results among computational and experimental paradigms in a two-layer sample phantom and suggests the potential applications for bioimpedance imaging.
doi:10.1109/TBME.2007.912674
PMCID: PMC3878613  PMID: 18270025
Electrical impedance imaging; magnetic induction; magnetoacoustic generation; tomography
11.  A Linear/Nonlinear Characterization of Resting State Brain Networks in fMRI Time Series 
Brain topography  2012;26(1):39-49.
Resting state functional connectivity studies in fMRI have been used to demonstrate that the human brain is organized into inherent functional networks in the absence of stimuli. The basis for this activity is based on the spontaneous fluctuations observed during rest. In the present study, the time series generated from these fluctuations were characterized as either being linear or nonlinear based on the Delay Vector Variance method, applied through an examination of the local predictability of the signal. It was found that the default mode resting state network is composed of relatively more linear signals compared to the visual, task positive visuospatial, motor, and auditory resting state network time series. Also, it was shown that the visual cortex resting state network is more nonlinear relative to these aforementioned networks. Furthermore, using a histogram map of the nonlinearly characterized voxels for all the subjects, the histogram map was able to retrieve the peak intensity in four out of six resting state networks. Thus, the findings may provide the basis for a novel way to explore spontaneous fluctuations in the resting state brain.
doi:10.1007/s10548-012-0249-7
PMCID: PMC3537854  PMID: 22941499
Functional connectivity; Resting state network; Nonlinear; fMRI; Default mode; Visual cortex
12.  Noninvasive Mapping of Transmural Potentials During Activation in Swine Hearts from Body Surface Electrocardiograms 
IEEE transactions on medical imaging  2012;31(9):10.1109/TMI.2012.2202914.
The three-dimensional cardiac electrical imaging (3DCEI) technique was previously developed to estimate the initiation site(s) of cardiac activation and activation sequence from the noninvasively measured body surface potential maps (BSPMs). The aim of the present study was to develop and evaluate the capability of 3DCEI in mapping the transmural distribution of extracellular potentials and localizing initiation sites of ventricular activation in an in vivo animal model. A control swine model (n=10) was employed in this study. The heart-torso volume conductor model and the excitable heart model were constructed based on each animal's pre-operative MR images and a priori known physiological knowledge. Body surface potential mapping and intracavitary noncontact mapping (NCM) were simultaneously conducted during acute ventricular pacing. The 3DCEI analysis was then applied on the recorded BSPMs. The estimated initiation sites were compared to the precise pacing sites; as a subset of the mapped transmural potentials by 3DCEI, the electrograms on the left ventricular endocardium were compared to the corresponding output of the NCM system. Over the 16 LV and 48 RV pacing studies, the averaged localization error was 6.1±2.3 mm, and the averaged correlation coefficient between the estimated endocardial electrograms by 3DCEI and from the NCM system was 0.62±0.09. The present results demonstrate that the 3DCEI approach can well localize the sites of initiation of ectopic beats and can obtain physiologically reasonable transmural potentials in an in vivo setting during focal ectopic beats. This study suggests the feasibility of tomographic mapping of 3D ventricular electrograms from the body surface recordings.
doi:10.1109/TMI.2012.2202914
PMCID: PMC3874123  PMID: 22692900
3D Cardiac electrical imaging; Transmural potential; Electrocardiophysiology; Body surface potential mapping; Noncontact mapping
13.  Distinct patterns of dysregulated expression of enzymes involved in androgen synthesis and metabolism in metastatic prostate cancer tumors 
Cancer research  2012;72(23):6142-6152.
Androgen receptor (AR) signaling persists in castration-resistant prostate carcinomas (CRPCs), due to several mechanisms that include increased AR expression and intratumoral androgen metabolism. We investigated the mechanisms underlying aberrant expression of transcripts involved in androgen metabolism in CRPC. We compared gene expression profiles and DNA copy number alteration (CNA) data from 29 normal prostate tissue samples, 127 primary prostate carcinomas (PCas) and 19 metastatic PCas. Steroidogenic enzyme transcripts were evaluated by qRT-PCR in PCa cell lines and circulating tumor cells (CTCs) from CRPC patients. Metastatic PCas expressed higher transcript levels for AR and several steroidogenic enzymes, including SRD5A1, SRD5A3, and AKR1C3, while expression of SRD5A2, CYP3A4, CYP3A5 and CYP3A7 was decreased. This aberrant expression was rarely associated with CNAs. Instead, our data suggest distinct patterns of coordinated aberrant enzyme expression. Inhibition of AR activity by itself stimulated AKR1C3 expression. The aberrant expression of the steroidogenic enzyme transcripts were detected in CTCs from CRPC patients. In conclusion, our findings identify substantial interpatient heterogeneity and distinct patterns of dysregulated expression of enzymes involved in intratumoral androgen metabolism in PCa. These steroidogenic enzymes represent targets for complete suppression of systemic and intratumoral androgen levels, an objective that is supported by the clinical efficacy of the CYP17 inhibitor abiraterone. A comprehensive AR axis targeting approach via simultaneous, frontline enzymatic blockade and/or transcriptional repression of several steroidogenic enzymes, in combination with GnRH analogs and potent anti-androgens, would represent a powerful future strategy for PCa management.
doi:10.1158/0008-5472.CAN-12-1335
PMCID: PMC3685485  PMID: 22971343
Prostate cancer; androgen synthesis; testosterone; dihydrotestosterone; CYP17; AKR1C3; abiraterone; MDV3100 (enzalutamide)
14.  Genetic Complexity in a Drosophila Model of Diabetes-Associated Misfolded Human Proinsulin 
Genetics  2013;196(2):539-555.
Drosophila melanogaster has been widely used as a model of human Mendelian disease, but its value in modeling complex disease has received little attention. Fly models of complex disease would enable high-resolution mapping of disease-modifying loci and the identification of novel targets for therapeutic intervention. Here, we describe a fly model of permanent neonatal diabetes mellitus and explore the complexity of this model. The approach involves the transgenic expression of a misfolded mutant of human preproinsulin, hINSC96Y, which is a cause of permanent neonatal diabetes. When expressed in fly imaginal discs, hINSC96Y causes a reduction of adult structures, including the eye, wing, and notum. Eye imaginal discs exhibit defects in both the structure and the arrangement of ommatidia. In the wing, expression of hINSC96Y leads to ectopic expression of veins and mechano-sensory organs, indicating disruption of wild-type signaling processes regulating cell fates. These readily measurable “disease” phenotypes are sensitive to temperature, gene dose, and sex. Mutant (but not wild-type) proinsulin expression in the eye imaginal disc induces IRE1-mediated XBP1 alternative splicing, a signal for endoplasmic reticulum stress response activation, and produces global change in gene expression. Mutant hINS transgene tester strains, when crossed to stocks from the Drosophila Genetic Reference Panel, produce F1 adults with a continuous range of disease phenotypes and large broad-sense heritability. Surprisingly, the severity of mutant hINS-induced disease in the eye is not correlated with that in the notum in these crosses, nor with eye reduction phenotypes caused by the expression of two dominant eye mutants acting in two different eye development pathways, Drop (Dr) or Lobe (L), when crossed into the same genetic backgrounds. The tissue specificity of genetic variability for mutant hINS-induced disease has, therefore, its own distinct signature. The genetic dominance of disease-specific phenotypic variability in our model of misfolded human proinsulin makes this approach amenable to genome-wide association study in a simple F1 screen of natural variation.
doi:10.1534/genetics.113.157602
PMCID: PMC3914625  PMID: 24281154
mutant insulin; diabetes; misfolded protein; Drosophila; complex disease
15.  Effect of Genetic Variation in a Drosophila Model of Diabetes-Associated Misfolded Human Proinsulin 
Genetics  2013;196(2):557-567.
The identification and validation of gene–gene interactions is a major challenge in human studies. Here, we explore an approach for studying epistasis in humans using a Drosophila melanogaster model of neonatal diabetes mellitus. Expression of the mutant preproinsulin (hINSC96Y) in the eye imaginal disc mimics the human disease: it activates conserved stress-response pathways and leads to cell death (reduction in eye area). Dominant-acting variants in wild-derived inbred lines from the Drosophila Genetics Reference Panel produce a continuous, highly heritable distribution of eye-degeneration phenotypes in a hINSC96Y background. A genome-wide association study (GWAS) in 154 sequenced lines identified a sharp peak on chromosome 3L, which mapped to a 400-bp linkage block within an intron of the gene sulfateless (sfl). RNAi knockdown of sfl enhanced the eye-degeneration phenotype in a mutant-hINS-dependent manner. RNAi against two additional genes in the heparan sulfate (HS) biosynthetic pathway (ttv and botv), in which sfl acts, also modified the eye phenotype in a hINSC96Y-dependent manner, strongly suggesting a novel link between HS-modified proteins and cellular responses to misfolded proteins. Finally, we evaluated allele-specific expression difference between the two major sfl-intronic haplotypes in heterozygtes. The results showed significant heterogeneity in marker-associated gene expression, thereby leaving the causal mutation(s) and its mechanism unidentified. In conclusion, the ability to create a model of human genetic disease, map a QTL by GWAS to a specific gene, and validate its contribution to disease with available genetic resources and the potential to experimentally link the variant to a molecular mechanism demonstrate the many advantages Drosophila holds in determining the genetic underpinnings of human disease.
doi:10.1534/genetics.113.157800
PMCID: PMC3914626  PMID: 24281155
mutant insulin; Drosophila; genome-wide association study; heparan sulfate proteoglycan; sulfateless
16.  3D noninvasive ultrasound Joule heat tomography based on acousto-electric effect using unipolar pulses: a simulation study 
Physics in medicine and biology  2012;57(22):7689-7708.
Electrical properties of biological tissues are highly sensitive to their physiological and pathological status. Thus it is of importance to image electrical properties of biological tissues. However, spatial resolution of conventional electrical impedance tomography (EIT) is generally poor. Recently, hybrid imaging modalities combining electric conductivity contrast and ultrasonic resolution based on acouto-electric effect has attracted considerable attention. In this study, we propose a novel three-dimensional (3D) noninvasive ultrasound Joule heat tomography (UJHT) approach based on acouto-electric effect using unipolar ultrasound pulses. As the Joule heat density distribution is highly dependent on the conductivity distribution, an accurate and high resolution mapping of the Joule heat density distribution is expected to give important information that is closely related to the conductivity contrast. The advantages of the proposed ultrasound Joule heat tomography using unipolar pulses include its simple inverse solution, better performance than UJHT using common bipolar pulses and its independence of any priori knowledge of the conductivity distribution of the imaging object. Computer simulation results show that using the proposed method, it is feasible to perform a high spatial resolution Joule heat imaging in an inhomogeneous conductive media. Application of this technique on tumor scanning is also investigated by a series of computer simulations.
doi:10.1088/0031-9155/57/22/7689
PMCID: PMC3537837  PMID: 23123757
Ultrasound Joule heat tomography; acousto-electric effect; biomedical imaging; ultrasound
17.  Dynamic bonds and polar ejection force distribution explain kinetochore oscillations in PtK1 cells 
The Journal of Cell Biology  2013;201(4):577-593.
A computational model of kinetochore dynamics suggests that differences in the distribution of polar ejection forces at the periphery and in the middle of PtK1 cell spindles underlie the observed position-dependence of metaphase chromosome behavior.
Duplicated mitotic chromosomes aligned at the metaphase plate maintain dynamic attachments to spindle microtubules via their kinetochores, and multiple motor and nonmotor proteins cooperate to regulate their behavior. Depending on the system, sister chromatids may display either of two distinct behaviors, namely (1) the presence or (2) the absence of oscillations about the metaphase plate. Significantly, in PtK1 cells, in which chromosome behavior appears to be dependent on the position along the metaphase plate, both types of behavior are observed within the same spindle, but how and why these distinct behaviors are manifested is unclear. Here, we developed a new quantitative model to describe metaphase chromosome dynamics via kinetochore–microtubule interactions mediated by nonmotor viscoelastic linkages. Our model reproduces all the key features of metaphase sister kinetochore dynamics in PtK1 cells and suggests that differences in the distribution of polar ejection forces at the periphery and in the middle of PtK1 cell spindles underlie the observed dichotomy of chromosome behavior.
doi:10.1083/jcb.201301022
PMCID: PMC3653364  PMID: 23671311
18.  Dynamic imaging of seizure activity in pediatric epilepsy patients 
Objective
To investigate the feasibility of using noninvasive EEG source imaging approach to image continuous seizure activity in pediatric epilepsy patients.
Methods
Nine pediatric patients with medically intractable epilepsy were included in this study. Eight of the patients had extratemporal lobe epilepsy and one had temporal lobe epilepsy. All of the patients underwent resective surgery and seven of them underwent intracranial EEG (iEEG) monitoring. The ictal EEG was analyzed using a noninvasive dynamic seizure imaging (DSI) approach. The DSI approach separates scalp EEGs into independent components and extracts the spatio-temporal ictal features to achieve dynamic imaging of seizure sources. Surgical resection and intracranial recordings were used to validate the noninvasive imaging results.
Results
The DSI determined seizure onset zones (SOZs) in these patients were localized within or in close vicinity to the surgically resected region. In the seven patients with intracranial monitoring, the estimated seizure onset sources were concordant with the seizure onset zones of iEEG. The DSI also localized the multiple foci involved in the later seizure propagation, which were confirmed by the iEEG recordings.
Conclusions
Dynamic seizure imaging can noninvasively image the seizure activations in pediatric patients with both temporal and extratemporal lobe epilepsy.
Significance
EEG seizure imaging can potentially be used to noninvasively image the SOZs and aid the pre-surgical planning in pediatric epilepsy patients.
doi:10.1016/j.clinph.2012.04.021
PMCID: PMC3438337  PMID: 22608485
Pediatric patients; Epilepsy; EEG; Dynamic seizure imaging; Intracranial recording; Surgical resection
19.  Hippocampal ProNGF Signaling Pathways and β-Amyloid Levels in Mild Cognitive Impairment and Alzheimer Disease 
Hippocampal precursor of nerve growth factor (proNGF)/NGF signaling occurs in conjunction with β-amyloid (Aβ) accumulations in Alzheimer disease (AD). To assess the involvement of this pathway in AD progression, we quantified these proteins and their downstream pathway activators in postmortem tissues from the brains of subjects with no cognitive impairment (NCI), mild cognitive impairment (MCI), and AD using immunoblotting and enzyme-linked immunosorbent assay (ELISA). Hippocampal proNGF was significantly greater in AD compared to NCI and MCI cases. TrkA was significantly reduced in MCI compared to NCI and AD, whereas p75NTR, sortilin, and neurotrophin receptor homolog-2 remained stable. Akt decreased from NCI to MCI to AD, whereas phospho-Akt and phosphor-Akt to Akt ratio were elevated in AD compared to MCI and NCI. No differences were found in phospho-Erk, Erk or their ratio across groups. c-jun kinase (JNK) remained stable across groups, while phospho-JNK and the phospho-JNK to JNK ratio increased significantly in AD compared to NCI and MCI. Expression levels of Aβ1-40, Aβ1-42 and Aβ40/42 ratio were stable. Statistical analysis revealed a strong positive correlation between proNGF and phospho-JNK, though only proNGF was negatively correlated with cognitive function and only TrkA was negatively associated with pathologic criteria. These findings suggest that alterations in the hippocampal NGF signaling pathway in MCI and AD favor proNGF-mediated pro-apoptotic pathways, and that this is independent of Aβ accumulation during AD progression.
doi:10.1097/NEN.0b013e318272caab
PMCID: PMC3481187  PMID: 23095849
Alzheimer disease; Amyloid; Mild cognitive impairment; Nerve growth factor; proNGF; Protein kinases, TrkA
20.  Celecoxib effectively inhibits the formation of joint adhesions 
The present study investigated the effectiveness of celecoxib in preventing the formation of joint adhesions. Rabbit models of joint adhesion were created and the rabbits in two treatment groups were orally administered celecoxib or ibuprofen (as a positive control) for 30 days. Rabbits in the control group did not receive any treatment. Following the 30-day experimental period, the inhibitory effects of celecoxib and ibuprofen on the formation of joint adhesion were assessed using a number of methods, including the study of macroscopic appearance, histology and contracture angle. Thick fibrous adhesions developed in the knees of the rabbits in the control group. By contrast, few adhesions were observed in the two treatment groups, and those observed were soft, weak and easily stretched. Fewer adhesions were observed in the rabbits treated with celecoxib than in the rabbits in the other groups. The adhesion scores and contracture angles in the celecoxib (P<0.001) and ibuprofen (0.001
doi:10.3892/etm.2013.1336
PMCID: PMC3829728  PMID: 24255682
celecoxib; ibuprofen; nonselective cyclooxygenase-2 enzyme inhibitor; selective cyclooxygenase-2 enzyme inhibitor; joint adhesion
Nature  2013;496(7443):110-113.
The Sir2 family of enzymes or sirtuins are known as nicotinamide adenine dinucleotide (NAD)-dependent deacetylases1 and have been implicated in the regulation of transcription, genome stability, metabolism, and lifespan2, 3. However, four of the seven mammalian sirtuins have very weak deacetylase activity in vitro. Here we show that human Sirt6 efficiently removes long chain fatty acyl groups, such as myristoyl, from lysine residues. The crystal structure of Sirt6 reveals a large hydrophobic pocket that can accommodate long chain fatty acyl groups. We demonstrate further that Sirt6 promotes the secretion of tumor necrosis factor α (TNFα) by removing the fatty acyl modification on K19 and K20 of TNFα. Protein lysine fatty acylation has been known to occur in mammalian cells, but the function and regulatory mechanisms of this modification were unknown. Our data suggest that protein lysine fatty acylation is a novel mechanism that regulates protein secretion. The discovery of Sirt6 as an enzyme that controls protein lysine fatty acylation provides new opportunities to investigate the physiological function of the previously ignored protein posttranslational modification.
doi:10.1038/nature12038
PMCID: PMC3635073  PMID: 23552949
Brain  2012;135(10):3134-3143.
Temporal lobe seizures have a significant chance to induce impairment of normal brain functions. Even after the termination of ictal discharges, during the post-ictal period, loss of consciousness, decreased responsiveness or other cognitive dysfunctions can persist. Previous studies have found various anatomical and functional abnormalities accompanying temporal lobe seizures, including an abnormal elevation of cortical slow waves. Intracranial electroencephalography studies have shown a prominent increase of lower frequency components during and following seizures that impair (complex partial seizures) but not those that preserve (simple partial seizures) normal consciousness and responsiveness. However, due to the limited spatial coverage of intracranial electroencephalography, the investigation of cortical slow waves cannot be easily extended to the whole brain. In this study, we used scalp electroencephalography to study the spectral features and spatial distribution of post-ictal slow waves with comprehensive spatial coverage. We studied simple partial, complex partial and secondarily generalized seizures in 28 patients with temporal lobe seizures. We used dense-array electroencephalography and source imaging to reconstruct the post-ictal slow-wave distribution. In the studied cohort, we found that a ‘global’ spectral power shift to lower frequencies accompanied the increased severity of seizures. The delta spectral power relative to higher frequency bands was highest for secondarily generalized seizures, followed by complex partial seizures and lastly simple partial seizures. In addition to this ‘global’ spectral shift, we found a ‘regional’ spatial shift in slow-wave activity. Secondarily generalized seizures and complex partial seizures exhibited increased slow waves distributed to frontal areas with spread to contralateral temporal and parietal regions than in simple partial seizures. These results revealed that a widespread cortical network including temporal and fronto-parietal cortex is involved in abnormal slow-wave activity following temporal lobe seizures. The differential spectral and spatial shifts of post-ictal electroencephalography activity in simple partial, complex partial and secondarily generalized seizures suggest a possible connection between cortical slow waves and behavioural and cognitive changes in a human epilepsy model.
doi:10.1093/brain/aws221
PMCID: PMC3470709  PMID: 22923634
cortical slowing; temporal lobe seizure; post-ictal state; consciousness; responsiveness
Objective
Ascites in patients with hepatic cirrhosis is caused by cirrhosis in most cases. For most malignant ascites, the primary malignancy could be readily identified using conventional imaging methods, e.g., computed tomography (CT) and magnetic resonance imaging (MRI). However, in a small fraction of the patients, the primary malignancy remains occult even with these examinations. In this retrospective study, we assessed the usefulness of 18F-FDG PET/CT in patients with hepatic cirrhosis and malignant ascites of otherwise unknown origin.
Methods
Twenty-eight patients with malignant ascites of unknown primary sites after CT, MRI and ultrasound during the period of five years between January 2008 and December 2012 had received 18F-FDG PET/CT. Medical records of these patients were reviewed and analyzed.
Results
Elevated 18F-FDG absorption was found in 23 of 28 cases in the following sites: gastrointestinal tract (n=10, 43.5%), prostate (n=5, 21.7%), peritoneum (n=4, 13.3%), and ovary (n=4, 13.3%). Cancer was confirmed by pathology in 20 cases after open or laparoscopic surgeries. Five patients were found to have benign ascites, among which, 3 were found to be false positive due to tuberculosis. SUV values were significantly higher for tumors than for benign lesions (mean values, 6.95 vs. 2.94; P=0.005).
Conclusions
The 18F-FDG PET/CT can be as a powerful imaging tool in identifying tissue origin in liver cirrhosis patients suspected of cancers or with cancers of unknown primary sites.
doi:10.3978/j.issn.1000-9604.2013.09.01
PMCID: PMC3828429  PMID: 24255572
PET/CT; liver cirrhosis; cancer, ascites
Scientific Reports  2013;3:2806.
Sirt5, localized in the mitochondria, is a member of sirtuin family of NAD+-dependent deacetylases. Sirt5 was shown to deacetylate and activate carbamoyl phosphate synthase 1. Most recently, Sirt5 was reported to be the predominant protein desuccinylase and demalonylase in the mitochondria because the ablation of Sirt5 enhanced the global succinylation and malonylation of mitochondrial proteins, including many metabolic enzymes. In order to determine the physiological role of Sirt5 in metabolic homeostasis, we generated a germline Sirt5 deficient (Sirt5−/−) mouse model and performed a thorough metabolic characterization of this mouse line. Although a global protein hypersuccinylation and elevated serum ammonia during fasting were observed in our Sirt5−/− mouse model, Sirt5 deficiency did not lead to any overt metabolic abnormalities under either chow or high fat diet conditions. These observations suggest that Sirt5 is likely to be dispensable for the metabolic homeostasis under the basal conditions.
doi:10.1038/srep02806
PMCID: PMC3786297  PMID: 24076663
Different control strategies exist for use in a brain-computer interface (BCI). Although process control is the prevailing control strategy for most sensorimotor rhythm based BCIs, the goal selection strategy more closely resembles normal motor control and may be more accurate, faster to use, and easier to learn. We describe here a sensorimotor rhythm based goal selection BCI and a pilot study to compare it with process control strategy in terms of accuracy and speed of use. In both trained and naïve subjects studied, goal selection outperformed process control.
doi:10.1109/IEMBS.2009.5332384
PMCID: PMC3774529  PMID: 19963467

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