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The Schlager mouse as a model of altered retinal phenotype

Neural Regeneration Research 2020年第3期15卷 512-518页

作者： Lakshini Y.Herat Aaron L.Magno Márcio G.Kiuchi Kristy L.Jackson Revathy Carnagarin Geoffrey A.Head Markus P.Schlaich Vance B.Matthews Dobney Hypertension Centre School of Biomedical Science-Royal Perth Hospital UnitUniversity of Western AustraliaPerthAustralia Research Centre Royal Perth HospitalPerthAustralia Dobney Hypertension Centre School of Medicine-Royal Perth Hospital UnitUniversity of Western AustraliaPerthAustralia Neuropharmacology Laboratory Baker Heart and Diabetes InstituteMelbourneAustralia Department of Cardiology and Department of Nephrology Royal Perth HospitalPerthAustralia

Hypertension is a risk factor for a large number of vision-threatening eye *** this study,we investigated for the first time the retinal neural structure of the hypertensive BPH/2J mouse(Schlager mouse)and compared it to its control counterpart,the normotensive BPN/3J *** BPH/2J mouse is a selectively inbred mouse strain that develops chronic hypertension due to elevated sympathetic nervous system *** compared to the BPN/3J strain,the hypertensive BPH/2J mice showed a complete loss of outer layers of the neural retina at 21 weeks of age,which was indicative of a severe vision-threatening disease potentially caused by *** elucidate whether the retinal neural phenotype in the BPH/2J strain was attributed to increased BP,we investigated the neural retina of both BPN/3J and BPH/2J mice at 4 weeks of *** preliminary results showed for the first time that the BPH/2J strain develops severe retinal neural damage at a young *** findings suggest that the retinal phenotype in the BPH/2J mouse is possibly due to elevated blood pressure and may be contributed by an early onset spontaneous mutation which is yet to be identified or a congenital defect occurring in this *** characterization of the BPH/2J mouse strain is likely to i)elucidate gene defects underlying retinal disease;ii)understand mechanisms leading to neural retinal disease and iii)permit testing of molecules for translational research to interfere with the progression of retinal *** animal experiments were performed with the approval of the royal Perth hospital Animal Ethics Committee(R535/17-18)on June 1,2017.

关键词： blood pressure eye hypertension mice neural regeneration retina Schlager mouse sympathetic nervous system

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Volatile organic compounds for the detection of hepatocellular carcinoma—A scoping review

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iLIVER 2024年第1期3卷 45-51页

作者： Sayed Metwaly Alicja Psica Opeyemi Sogaolu Irfan Ahmed Ashis Mukhopadhya Mirela Delibegovic Mohamed Bekheit Division of Internal Medicine Aberdeen Royal InfirmaryNHS GrampianScotlandAberdeenAB252ZDUnited Kingdom Aberdeen Cardiovascular and Diabetes Centre School of MedicineMedical Sciences and NutritionUniversity of AberdeenForesterhill Health CampusAberdeenAB252ZDUnited Kingdom Department of Critical Care Medicine University of CalgaryAlberta T2N 2T9Canada Department of General Surgery Aberdeen Royal InfirmaryNHS GrampianScotlandAberdeen AB252ZDUnited Kingdom Pakistan Kidney and Liver Institute and Research Centre Lahore 54000Pakistan Hépatica Centre of Integrated HPB CareElite HospitalAlexandria 21325Egypt

Hepatocellular carcinoma(HCC)is an increasingly common and the second leading cause of cancer mortality worldwide with a 5-year survival rate about 12%.Less than 20%of HCC patients are eligible to curative treatment owing to the late ***,there is a need for a readily accessible,early screening *** scoping review critically appraises and synthesizes the current published knowledge about the use of exhaled volatile organic compounds(VOCs)as a potential noninvasive means for HCC detection aiming to advance this nascent field.A systematic electronic search was *** search strategy included all studies published until the 24th of March 2023 using a combination of relevant *** search yielded 9 publications using the Preferred Reporting Items for Systematic Reviews and Meta-analyses *** of the studies described in vitro experiments,and seven clinical studies were conducted on small groups of ***,42 headspace gases were analyzed in the in vitro ***,the clinical studies included 420 HCC patients and 630 *** studies reported potential role for a combination of VOCs in the diagnosis of ***,there is lack of *** there appears to be promise in VOCs research associated with HCC,there is no single volatile biomarker in exhaled breath attributed to HCC and data from extracted studies indicates a lack of *** multicentre population studies are required to verify the existence of VOCs linked to HCC.

关键词： Hepatocellular carcinoma Volatile organic compounds Metabolomics

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Management of necrotizing pancreatitis

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World Journal of Gastroenterology 2001年第4期7卷 476-481页

作者： John Slavin Paula Ghaneh Robert Sutton Mark Hartley Peter Rowlands Conall Garvey Mark Hughes John Neoptolemos Departments of Surgery royal Liverpool University hospital Departments of Radiology royal Liverpool University hospital

Infection complicating pancreatic necrosis leads to persisting sepsis, multiple organ dysfunction syndrome and accounts for about half the deaths that occur following acute pancreatitis. Severe cases due to gallstones require urgent endoscopic sphincterotomy. Patients with pancreatic necrosis should be followed with serial contrast enhanced computed tomography (CE-CT) and if infection is suspected fine needle aspiration of the necrotic area for bacteriology (FNAB) should be undertaken. Treatment of sterile necrosis should initially be non-operative. In the presence of infection necrosectomy is indicated. Although traditionally this has been by open surgery, minimally invasive procedures are a promising new alternative. There are many unresolved issues in the management of pancreatic necrosis. These include, the use of antibiotic prophylaxis, the precise indications for and frequency of repeat CE-CT and FNAB,and the role of enteral feeding.

关键词： Humans Pancreatitis, Acute Necrotizing Surgical Procedures, Minimally Invasive

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The thymic stromal cell line MTSC4 induced thymocyte apoptosis in a non-MHC-restricted manner

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Cell Research 2004年第2期14卷 125-133页

作者： Xue Ying HE~1, Juan LI~1, Xiao Ping QIAN~1, Wen Xian FU~1, Yan LI~1, Li WU~2, Wei Feng CHEN~1 ~1Department of Immunology, Peking University Health Science Center,38 Xueyuan Road, Beijing 100083, China. ~2The Walter and Eliza Hall Institute, PO royal melbourne hospital, Victoria 3050, Australia. Department of Immunology Peking University Health Science Center Beijing China The Walter and Eliza Hall Institute PO Royal Melbourne Hospital Victoria Australia

Mouse thymic stromal cell line 4 （MTSC4） is one of the stromal cell lines established in our laboratory. While losing the characteristics of epithelial cells, they express some surface markers shared with thymic dendritic cells （TDCs）. To further study the biological functions of these cells, we compared the capability of MTSC4 with TDCs in the induction of thymocyte apoptosis, using thymic reaggregation culture system. Apoptosis of thymocytes induced by MTSC4 and TDCs was measured by Annexin V and PI staining and analyzed by flow cytometry. We found that MTSC4 selectively augmented the apoptosis of CD4+8+ （DP） thymocytes. This effect was Fas/FasL independent and could not be blocked by antibodies to MHC class Ⅰ and class Ⅱ molecules. In addition, MTSC4 enhanced the apoptosis of DP thymocytes from different strains of mice, which implies that MTSC4-induced thymocyte apoptosis is not mediated by the TCR recognition of self peptide/MHC molecules. In contrast to MTSC4, thymocyte apoptosis induced by TD

关键词： MHC thymic dendritic cells thymic stromal cell line thymocyte apoptosis.

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Neurological heterotopic ossification:novel mechanisms,prognostic biomarkers and prophylactic therapies

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Bone Research 2020年第4期8卷 379-392页

作者： Ker Rui Wong Richelle Mychasiuk Terence J.O’Brien Sandy R.Shultz Stuart J.McDonald Rhys D.Brady Department of Neuroscience Central Clinical SchoolMonash UniversityMelbourneVICAustralia Department of Medicine Royal Melbourne HospitalThe University of MelbourneParkvilleVICAustralia Department of Physiology Anatomy and MicrobiologySchool of Life SciencesLa Trobe UniversityBundooraVICAustralia

Neurological heterotopic ossification(NHO)is a debilitating condition where bone forms in soft tissue,such as muscle surrounding the hip and knee,following an injury to the brain or spinal *** abnormal formation of bone can result in nerve impingement,pain,contractures and impaired *** are often diagnosed with NHO after the bone tissue has completely mineralised,leaving invasive surgical resection the only remaining treatment *** resection of NHO creates potential for added complications,particularly in patients with concomitant injury to the central nervous system(CNS).Although recent work has begun to shed light on the physiological mechanisms involved in NHO,there remains a significant knowledge gap related to the prognostic biomarkers and prophylactic treatments which are necessary to prevent NHO and optimise patient *** article reviews the current understanding pertaining to NHO epidemiology,pathobiology,biomarkers and treatment *** particular,we focus on how concomitant CNS injury may drive ectopic bone formation and discuss considerations for treating polytrauma patients with *** conclude that understanding of the pathogenesis of NHO is rapidly advancing,and as such,there is the strong potential for future research to unearth methods capable of identifying patients likely to develop NHO,and targeted treatments to prevent its manifestation.

关键词： such has likely

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Ventricular Arrhythmia in the Fontan Circulation:Prevalence,Risk Factors and Clinical Implications

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Congenital Heart Disease 2023年第5期18卷 507-523页

作者： Charis Tan Diana Zannino Carley Clendenning Sophie Offen Thomas LGentles Julian Ayer David Tanous Vishva Wijesekera Leeanne Grigg David Celermajer Mark McGuire Yves d’Udekem Rachael Cordina Department of Cardiothoracic Surgery Royal Prince Alfred HospitalCamperdownAustralia Sydney Medical School University of SydneyCamperdownAustralia Clinical Epidemiology and Biostatistics Unit Murdoch Children’s Research InstituteParkvilleAustralia Department of Cardiology Royal Prince Alfred HospitalCamperdownAustralia Department of Paediatric Cardiology Starship HospitalAucklandNew Zealand Department of Paediatric Cardiology The Children’s Hospital at WestmeadWestmeadAustralia Department of Cardiology Westmead HospitalWestmeadAustralia Adult Congenital Heart Disease Unit The Prince Charles HospitalBrisbaneAustralia Department of Cardiology The Royal Melbourne HospitalMelbourneAustralia Heart Research Institute CamperdownAustralia Department of Cardiac Surgery The Royal Children’s Hospital MelbourneParkvilleAustralia Department of Paediatrics The University of MelbourneParkvilleAustralia

Objective:Sudden cardiac death(SCD)and malignant ventricular arrhythmia(VA)are increasingly recognized as important issues for people living with a Fontan circulation,but data are *** sought to characterize the cohort who had sudden cardiac death,most likely related to VA and/or documented VA in the Australia and New Zealand Fontan Registry including risk factors and clinical ***:A retrospective cohort study was *** criteria were documented non-sustained ventricular tachycardia,sustained ventricular tachycardia,ventricular fibrillation,resuscitated cardiac arrest or SCD>30 days post-Fontan ***:Of 1611 patients,20(1.2%)had VA;14(1.0%)had VA without SCD and 6(<1%)had SCD(6%of all deaths recorded in Registry;5 of those had documented VA at the time of arrest and 1 was presumed to be VA-associated).The median age at first VA was 20.5(14–32)years,10(50%)were females,and the median age at Fontan operation was 8(4–17)*** univariable analysis,hypoplastic left heart syndrome(p=0.03)and older age Fontan operation(p<0.001)were associated with *** Fontan era(p<0.003),atriopulmonary Fontan(p<0.001),pre-Fontan atrioventricular valve repair(p=0.013)pre-or post-Fontan atrial arrhythmia(p=0.010)were associated with *** with VA had a 3 times higher risk of death or heart transplant(HR 3.27(1.19,8.98),p=0.02).Conclusions:A proportion of people living with a Fontan circulation have malignant *** VA screening in this cohort is *** data are needed to aid risk stratification.

关键词： Fontan congenital cardiac arrhythmia sudden cardiac death ventricular tachyarrhythmia

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Intrahepatic cholestasis of pregnancy:When should you look further?

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World Journal of Gastroenterology 2009年第9期15卷 1126-1129页

作者： Winita Hardikar Shivani Kansal Ronald P J Oude Elferink Peter Angus Victorian Liver Transplant Unit Austin HospitalMelbourne 3084Australia Department of Gastro-enterology&Clinical Nutrition Royal Children's HospitalMelbourne 3052Australia Department of Paediatrics University of MelbourneMelbourne 3052Australia Murdoch Children's Research Institute Melbourne 3052Australia AMC Liver Centre Academic Medical CentreAmsterdam 1105AZThe Netherlands

Pruritis with abnormal liver function tests is the classical presentation of intrahepatic cholestasis of pregnancy(ICP),a condition associated with significant fetal *** the etiology of ICP is unclear in many cases,certain features of the clinical presentation should alert the practitioner to the possibility of an underlying metabolic defect, which may not only affect subsequent pregnancies, but may be an indicator of more serious subsequent liver *** report a kindred of Anglo-Celtic descent,among whom many members present with ICP,gallstones or cholestasis related to use of oral *** studies revealed a novel mutation in the ABCB4 gene,which codes for a phospholipid transport *** clinical significance of this mutation and the importance of identifying such patients are discussed.

关键词： ABCB4 gene ABCB4 transporter Phospholipids Cholestasis of pregnancy Gallstones

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Outcomes after robot-assisted laparoscopic radical prostatectomy

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Asian Journal of Andrology 2009年第1期11卷 94-99页

作者： Declan G. Murphy Benjamin J. Challacombe Anthony J. Costello The Urology Centre Guy＇s ＆ St. Thomas ＇NHS Foundation Trust London SE1 9RT UK Department of Urology Royal Melbourne Hospital Melbourne VIC 3054 Australia

Robot-assisted laparoscopic radical prostatectomy （RALRP） using the da Vinci surgical system is now in widespread use in many countries where economic conditions allow the installation of this expensive technology. Controversy has surrounded the procedure since it was first performed in 2000, with many critics highlighting the lack of evidence to support its use. However, despite the lack of level I evidence, many large studies of patients have confirmed that the procedure is feasible and safe, with low morbidity. Available longer-term oncological data seem to show that outcomes from the robotic approach at least match those of traditional open radical prostatectomy. Functional outcomes also seem satisfactory, although randomized controlled trials are lacking. This paper reviews the current status of RALRP with respect to perioperative data and complications and oncologic and functional outcomes.

关键词： da Vinci laparoscopic outcomes prostate cancer radical prostatectomy robotic

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Confocal laser endomicroscopy for gastric neoplasm

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World Journal of Gastrointestinal Endoscopy 2024年第9期16卷 540-544页

作者： Arkadeep Dhali Rick Maity Roger B Rathna Jyotirmoy Biswas Department of Gastroenterology Sheffield Teaching Hospitals NHS Foundation TrustRoyal Hallamshire HospitalSheffield S102JFUnited Kingdom School of Medicine and Population Health University of SheffieldSheffield S102HQUnited Kingdom General Medicine Institute of Post Graduate Medical Education and ResearchKolkata 700020India Department of Internal Medicine University Hospitals Leicester NHS TrustLeicester Royal InfirmaryLeicester LE15WWUnited Kingdom General Medicine College of Medicine and Sagore Dutta HospitalKolkata 700058India

Confocal laser endomicroscopy(CLE)is a novel endoscopic modality that provides real-time histological information via high-resolution magnified view of the *** has a higher sensitivity,specificity,and diagnostic accuracy in detecting atrophic gastritis as compared to chromoendoscopy and narrow-band *** can even predict low-grade and high-grade intraepithelial neoplasia by analyzing gastric pit *** may have some advantages over the standard biopsy protocol,such as higher diagnostic yield and fewer biopsy *** diagnostic accuracy in detecting superficial gastric cancer is higher than that of white-light *** limitations,such as a narrow field of vision,can be surpassed by technological advancements and integration with other detection *** intelligence holds promise in automated analysis of histopathological ***,CLE can be helpful in screening for early gastric cancer and may help reduce the risk of complications from repeated biopsies,such as mucosal damage,bleeding,and infection.

关键词： Confocal laser endomicroscopy Gastric cancer Narrow band imaging Diagnostic yield

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Impaired glymphatic function in the early stages of disease in a TDP-43 mouse model of amyotrophic lateral sclerosis

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Translational Neurodegeneration 2022年第1期11卷 707-717页

作者： Akram Zamani Adam K.Walker Ben Rollo Katie L.Ayers Raysha Farah Terence J.O’Brien David K.Wright Department of Neuroscience Central Clinical SchoolMonash UniversityMelbourneVIC 3004Australia Queensland Brain Institute The University of QueenslandSt LuciaQLD 4072Australia The Murdoch Children’s Research Institute The Royal Children’s HospitalParkvilleVIC 3052Australia Department of Pediatrics The University of MelbourneParkvilleVIC 3052Australia Department of Medicine The Royal Melbourne HospitalThe University of MelbourneParkvilleVIC 3052Australia

Background: Multiple lines of evidence suggest possible impairment of the glymphatic system in amyotrophic lateral sclerosis (ALS). To investigate this, we used in vivo magnetic resonance imaging (MRI) to assess glymphatic func-tion early in the course of disease in a transgenic mouse with doxycycline (Dox)-controlled expression of cytoplasmic human TDP-43 (hTDP-43ΔNLS), mimicking the key pathology implicated in ALS. Methods: Adult TDP-43 transgenic and littermate monogenic control mice underwent longitudinal multimodal MRI one and three weeks after the cessation of Dox feed, together with weekly rotarod assessments of motor per-formance. Glymphatic function was assessed using dynamic contrast-enhanced MRI to track the clearance of an MR contrast agent injected into the cisterna magna. Results: Compared to their littermate controls, TDP-43 mice exhibited progressive neurodegeneration including that within the primary motor cortex, primary somatosensory cortex and corticospinal tract, significant weight loss includ-ing gastrocnemius atrophy, and shortened telomere length. Furthermore, in the presence of this ALS-like phenotype, these mice have significantly disrupted glymphatic function. Conclusions: Although the relationship between glymphatic clearance and ALS disease progression remains to be elucidated, these changes occurred very early in the disease course. This provides initial evidence to suggest that the glymphatic system might be a potential therapeutic target in the treatment of ALS.

关键词： Magnetic resonance imaging Diffusion-weighted imaging Neurodegeneration Cerebrospinal fluid Telomere

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