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1H nuclear magnetic resonance spectroscopy-basedmetabonomic study in patients with cirrhosis and hepaticencephalopathy

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World Journal of Hepatology 2015年第12期7卷 1701-1707页

作者： konstantinos john dabos john Andrew Parkinson Ian Howard Sadler john Nicholas Plevris Peter Clive Hayes Centre of Liver and Digestive Disorders Royal Infirmary of Edinburgh Department of Chemistry University of Strathclyde Department of Chemistry University of Edinburgh

AIM: To identify plasma metabolites used as biomarkers in order to distinguish cirrhotics from controls and ***: A clinical study involving stable cirrhotic patients with and without overt hepatic encephalopathy was designed. A control group of healthy volunteers was used. Plasma from those patients was analysed using 1H- nuclear magnetic resonance spectroscopy. We used the Carr Purcell Meiboom Gill sequence to process the sample spectra at ambient probe temperature. We used a gated secondary irradiation field for water signal suppression. Samples were calibrated and referenced using the sodium trimethyl silyl propionate peak at 0.00 ppm. For each sample 128 transients(FID's) were acquired into 32 K complex data points over a spectral width of 6 KHz. 30 degree pulses were applied with an acquisition time of 4.0 s in order to achieve better resolution, followed by a recovery delay of 12 s, to allow for complete relaxation and recovery of the magnetisation. A metabolic profile was created for stable cirrhotic patients without signs of overt hepatic encephalopathy and encephalopathic patients as well as healthy controls. Stepwise discriminant analysis was then used and discriminant factors were created to differentiate between the three ***: Eighteen stabled cirrhotic patients, eighteen patients with overt hepatic encephalopathy and seventeen healthy volunteers were recruited. Patients with cirrhosis had significantly impaired ketone body metabolism, urea synthesis and gluconeogenesis. This was demonstrated by higher concentrations of acetoacetate(0.23 ± 0.02 vs 0.05 ± 0.00, P < 0.01), and b-hydroxybutarate(0.58 ± 0.14 vs 0.08 ± 0.00, P < 0.01), lower concentrations of glutamine(0.44 ± 0.08 vs 0.63 ± 0.03, P < 0.05), histidine(0.16 ± 0.01 vs 0.36 ± 0.04, P < 0.01) and arginine(0.08 ± 0.01 vs 0.14 ± 0.02, P < 0.03) and higher concentrations of glutamate(1.36 ± 0.25 vs 0.58 ± 0.04, P < 0.01), lactate(1.53 ± 0.11 vs 0.42 ± 0.05, P < 0.01),

关键词： Ketone bodies Branch chain amino acids Glutamine Glycolysis

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New markers of fibrosis in hepatitis C:A step towards the Holy Grail?

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World Journal of Hepatology 2024年第2期16卷 112-114页

作者： konstantinos john dabos Department of Hepatology St Hohn's HospitalLivingston EH546PPWest LothianUnited Kingdom

In the present issue of the World Journal of Hepatology,Ferrassi et al examine the problem of liver fibrosis staging in chronic hepatitis *** identify novel biomarkers in an effort to predict accurate fibrosis staging with the aid of the metabolome of Hepatitis C *** I think Ferrassi et al took a different approach in identifying fibrosis biomarkers,by looking at the patients’*** biomarkers clearly separate patients from *** can also separate out,patients with minimal fibrosis(F0-F1 stage)and patients with cirrhosis(F4 stage).Obviously,if these biomarkers were to be widely used,tests for all the important metabolites would need to be readily available for use in hospitals or outpatient setting and that may prove difficult and above all,***,this step could eventually lead to a metabolomic approach for novel biomarkers of ***,it would need to be validated,but could represent a step towards the Holy Grail of Hepatology.

关键词： Hepatitis C metabolomics Fibrosis Non invasive markers Metavir

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Targeting TrkB–PSD-95 coupling to mitigate neurological disorders

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Neural Regeneration Research 2025年第3期20卷 715-724页

作者： Xin Yang Yu-Wen Alvin Huang john Marshall Department of Molecular Biology Cell Biology and BiochemistryBrown UniversityProvidenceRIUSA Department of Neurology Warren Alpert Medical School of Brown UniversityProvidenceRIUSA Center for Translational Neuroscience Robert J.and Nancy D.Carney Institute for Brain Science and Brown Institute for Translational ScienceBrown UniversityProvidenceRIUSA

Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and *** activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term ***,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term *** this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and *** with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 *** TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific *** TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

关键词： Angelman syndrome autism brain-derived neurotrophic factor depression neurodegenerative disorder neurodevelopmental disorder postsynaptic density protein-95 synaptic plasticity TrkB

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Impaired gluconeogenesis in a porcine model of paracetamol induced acute liver failure

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World Journal of Gastroenterology 2011年第11期17卷 1457-1461页

作者： konstantinos J dabos Henry R Whalen Philip N Newsome john A Parkinson Neil C Henderson Ian H Sadler Peter C Hayes john N Plevris Liver Cell Biology Laboratory Department of HepatologyUniversity of EdinburghEdinburghEH16 4SAUnited Kingdom Gastroenterology Unit Ioannina General Hospital Hatzikosta450-01 IoanninaGreece Gastroenterology Department Hatzikosta General HospitalLeoforos Makrygianni450-01 IoanninaGreece Department of Chemistry University of EdinburghEdinburghEH16 6AAUnited Kingdom

AIM:To investigate glucose homeostasis and in particular gluconeogenesis in a large animal model of acute liver failure(ALF).METHODS:Six pigs with paracetamol induced ALF under general anaesthesia were studied over 25 *** samples were withdrawn every five hours from a central *** animals were used as controls and were maintained under anaesthesia *** 1 H NMR spectroscopy we identified most gluconeogenic amino acids along with lactate and pyruvate in the animal plasma ***:No significant changes were observed in the concentrations of the amino acids studied in the animals maintained under anaesthesia *** we look at the ALF animals,we observed a statistically significant rise of lactate(P<0.003)and pyruvate(P<0.018) at the end of the *** also observed statistically significant rises in the concentrations of alanine(P<0.002),glycine(P<0.005),threonine(P< 0.048),tyrosine(P<0.000),phenylalanine(P<0.000) and isoleucine(P<0.01).Valine levels decreased significantly(P<0.05).CONCLUSION:Our pig model of ALF is characterized by an altered gluconeogenetic capacity,an impaired tricarboxylic acid(TCA)cycle and a glycolytic state.

关键词： Lactate Pyruvate Branch chain amino acids Aromatic amino acids

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A spotlight on dosage and subject selection for effective neuroprotection: exploring the central role of mitochondria

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Neural Regeneration Research 2025年第4期20卷 1081-1082页

作者： john Mitrofanis Jonathan Stone Michael R.Hamblin Pierre Magistretti Alim-Louis Benabid Glen Jeffery Fonds Clinatec UniversitéGrenoble AlpesGrenobleFrance School of Medical Science University of SydneySydneyAustralia Faculty of Health Sciences University of JohannesburgJohannesburgSouth Africa King Abdullah University of Science and Technology ThuwalSaudi Arabia Institute of Ophthalmology University College LondonLondonUK

Neurons are notoriously vulnerable cell *** the slightest change in their internal and/or external environments will cause much distress and dysfunction,leading often to their death.A range of pathological conditions,including stroke,head trauma,and neurodegenerative disease,can generate stress in neurons,affecting their survival and proper *** most neural pathologies,mitochondria become dysfunctional and this plays a pivotal role in the process of cell *** challenge over the last few decades has been to develop effective interventions that improve neuronal homeostasis under pathological *** interventions,often referred to as disease-modifying or neuroprotective,have,however,proved frustratingly elusive,at both preclinical and,in particular,clinical *** this perspective,we highlight two factors that we feel are key to the development of effective neuroprotective *** are:firstly,the choice of dose of intervention and method of application,and secondly,the selection of subjects,whether they be patients or the animal model.

关键词： protective dosage distress

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Subcutaneous extension of a large diaphragmatic hydatid cyst

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World Journal of Gastroenterology 2006年第44期12卷 7210-7212页

作者： Athanasios Marinis Georgios Fragulidis konstantinos Karapanos Christos Konstantinidis Paraskevas Brestas john Vassiliou Vassilios Smyrniotis 2nd Department of Surgery Areteion University Hospital 76 Vassilisis Sofias avenue 11528 Athens Medical School Athens Greece

A 53-year-old male patient with a large hydatid cyst of the left hemidiaphragm and smaller secondary cysts located in the left thoracic cavity and upper left abdominal quadrant presented with two progressively enlarging lipoma-like masses in the left hypochondrium and under the left scapulae respectively. Total excision of all the cysts was performed through a bilateral subcostal incision, with the left hemidiaphragm near totally excised and replaced by a synthetic bilayer mesh.

关键词： Hydatid cyst Diaphragm Mesh reconstruction Intrathoracic cavity Subcutaneous extension

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Early-onset gastrointestinal cancer:An epidemiological reality with great significance and implications

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 583-597页

作者： john K Triantafillidis konstantinos Georgiou Manousos M Konstadoulakis Apostolos E Papalois Department of IBD and GI Endoscopy Metropolitan General HospitalHolargos 15562AthensGreece.Hellenic Society for Gastrointestinal Oncology354 Iera OdosChaidari 12461AtticaGreece 2nd Department of Surgery University of Athens School of MedicineAretaieion HospitalAthens 11528Greece

During the last few years,epidemiological data from many countries suggest that the incidence and prevalence of many cancers of the digestive system are shifting from the older to the younger ages,the so-called“early-onset cancer”.This is particularly evident in colorectal cancer and secondarily in other malignant digestive neoplasms,mainly stomach and in a lesser degree pancreas,and biliary *** should be emphasized that data concerning digestive neoplasms,except for those referring to the colon and stomach,could be characterized as rather *** exact magnitude of the shift in younger ages is expected to become clearer shortly,as long as relevant epidemiological data from many parts of the world would be *** most important question concerns the etiology of this phenomenon,since its magnitude cannot be explained solely by the better diagnostic methodology and the preventive programs applied in many *** existing data support the assumption that a number of environ-mental factors may play a primary role in influencing carcinogenesis,sometimes from *** that have appeared in the last decades related mainly to eating habits,consistency of gut microbiome and an increase of obese people interacting with genetic factors,ultimately favor the process of *** these factors however,are not entirely sufficient to explain the age-related changes in the frequency of digestive *** of the individual effect of each of the already known factors or factors likely to be involved in the etiology of this phenomenon and studies using state-of-the-art technologies to accurately determine the degree of the population exposure to these factors are *** this article,we attempt to describe the epidemiological data supporting the age-shifting of digestive malignancies and their possible ***,we propose some measures regarding the attitude of the scientific community to this alarming phenomenon.

关键词： Gastrointestinal cancer Endoscopy Epidemiology Early-onset Environment

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Rectal carcmosarcoma: A case report and review of literature

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World Journal of Gastroenterology 2006年第9期12卷 1481-1484页

作者： Dimitrios konstantinos Tsekouras Stylianos Katsaragakis Dimitrios Theodorou Georgia Kafiri Fotis Archontovasilis Panagiotis Giannopoulos Panagiotis Drimousis john Bramis University De partment of General Surgery Athens School of Medicine Ippokration HospitalAthensGreece Department of Pathology Ippokration Hospital AthensGreece

A 60-years old male was admitted to our department for investigation of constipation and hypogastric discomfort intensified during defecation of a few weeks duration. The cause proved to be a rectal carcinosarcoma that was treated by abdominoperineal resection and postoperative chemo-radiotherapy. The patient died 6 months later due to hepatic failure, showing evidence of disseminated disease. In general colonic carcinosarcomas constitute a rare category of malignant neoplasms whose nature is still incompletely understood. No specific treatment guidelines exist. Surgery is the mainstay of treatment and regardless of the addition of adjuvant therapy the prognosis is very poor. Systematic genetic analysis may be the clue for understanding the pathogenesis of these mysterious tumors.

关键词： Carcinosarcoma Rectum

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Complex knee injuries treated in acute phase: Long-term results using Ligament Augmentation and Reconstruction System artificial ligament

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World Journal of Orthopedics 2018年第3期9卷 24-34页

作者： john Gliatis konstantinos Anagnostou Pantelis Tsoumpos Evdokia Billis Maria Papandreou Spyridon Plessas Department of Orthopaedic University Hospital of Patras Department of Physical Therapy Technological Educational Institute of Western Greece Department of Physiotherapy Technological Educational Institute of Athens Department of Orthopaedic General Hospital of Nikaia "Snt.Panteleimon"

AIM To present the long-term results of complex knee injuries, treated early using the Ligament Augmentation and Reconstruction System(LARS) artificial ligament to reconstruct posterior cruciate ligament(PCL).METHODS From September 1997 to June 2010, thirty-eight complex knee injuries were treated, where early arthroscopic PCL reconstructions were undergone, using the LARS(Surgical Implants and Devices, Arc-sur-Tille, France) artificial ligament. Exclusion criteria were: Late(> 4 wk) reconstruction, open technique, isolated PCL reconstruction, knee degenerative disease, combinedfracture or vascular injury and use of allograft or autograft for PCL reconstruction. Clinical and functional outcomes were assessed with IKDC Subjective Knee Form, KOS-ADLS questionnaire, Lysholm scale and SF-12 Health Survey. Posterior displacement(PD) was measured with the Telos Stress Device. RESULTS Seven patients were excluded; two because of coexisting knee osteoarthritis and the remaining five because of failure to attend the final follow-up. The sample consisted of 31 patients with mean age at the time of reconstruction 33.2 ± 12.5 years(range 17-61). The postoperative follow-up was on average 9.27 ± 4.27 years(range 5-18). The mean average IKDC and KOS scores were 79.32 ± 17.1 and 88.1 ± 12.47% respectively. Average PD was 3.61 ± 2.15 mm compared to 0.91 ± 1.17 mm in the uninjured knees(one with grade 1+ and two with grade 2 +). Dial test was found positive in one patient, whereas the quadriceps active drawer test was positive in three patients. None was tested positive on the reverse-pivot shift test. The range of motion(ROM) was normal in thirty knees, in comparison with the contralateral one. There was no extension deficit. Osteoarthritic changes were found in three knees(9.6%).CONCLUSION Early treatment of complex knee injuries, using LARS artificial ligament for PCL reconstruction sufficiently reduces posterior tibia displacement and provides satisfactory long-term functional o

关键词： Complex knee injuries Posterior cruciate ligament Acute reconstruction Ligament Augmentation and Reconstruction System

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AWARE@HOME:A CASE STUDY IN TECHNOLOGICAL DESIGN TO PROMOTE ENVIRONMENTAL CONSERVATION IN THE AMERICAN HOME

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Journal of Green Building 2006年第4期1卷 112-128页

作者： Andres Clarens Antonio Vittorini Brad Lamiman konstantinos Boukouris john Pariseau Prashanth Pandian Steven Skerlos 不详 Department of Mechanical Engineering The University of Michigan at Ann Arbor

This paper describes an inexpensive technology called AWARE@home that was designed for households to receive information regarding their utility consumption patterns through at-home wireless *** information devices have been proposed or developed in the past but to the authors’knowledge this is the first to be:1)designed specifically for homeowners to facilitate choices regarding consumption 2)built on existing home wireless“WiFi”networks and 3)developed with retrofit sensors that do not require meter *** that AWARE@home is designed to empower consumers to save money and conserve resources,the technology was selected as a winner of the inaugural EPA P3 competition in *** system is designed for minimal effort by consumers:first,a service professional installs the AWARE@home retrofit device onto the existing meters in a process that takes approximately 30 *** the consumer receives a startup kit that includes a CD and,if needed,a USB wireless antenna for the *** loading software from the CD onto the computer,the homeowner is asked basic questions about utility rates,billing cycles and how much he or she wants to spend on utilities each *** any point in the month that the desired expenditure on utilities set by the consumer is likely to be exceeded,AWARE@home will send an e-mail message or pop-up window message providing a warning about this predicted over-spending on *** paper describes the prototype AWARE@home system that was produced for the EPA P3 competition and later installed in the home of an author for further *** AWARE@home prototype meets a number of design specifications related to simplicity,reliability,and *** includes both hardware and software components for“Wi-Fi”monitoring and alerting of home water,gas,and electricity *** prototype for electricity monitoring has been operating continuously for over eight months at a home in Ann Arbor,Michigan,it has consistentl

关键词： energy efficiency household consumption environmental footprint

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