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Efficacy and safety of tenofovir in chronic hepatitis B: Australian real world experience

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World journal of Hepatology 2017年第1期9卷 48-56页

作者： Grace C Lovett Tin Nguyen David M Iser jacinta A Holmes Robert Chen Barbara Demediuk Gideon Shaw Sally j Bell Paul V Desmond alexander j thompson Department of Gastroenterology St Vincent’s Hospital Melbourne Faculty of Medicine University of Melbourne

AIM To evaluate the long-term treatment outcomes of tenofovir therapy in patients in a real world Australian tertiary care setting.METHODS We performed a retrospective analysis of treatment outcomes among treatment-na?ve and treatment-experienced patients receiving a minimum 3 mo tenofovir therapy through St Vincent's Hospital Melbourne, Australia. We included patients receiving tenofovir [tenofovir disoproxil fumarate(TDF)] monotherapy, as well as patients treated with TDF in combination with a second antiviral agent. Patients were excluded if they demonstrated human immune-deficiency virus/hepatitis C virus/hepatitis delta virus coinfection or were less than 18 years of age. We considered virological and biochemicalresponse, as well as safety outcomes. Virological response was determined by measurement of hepatitis B virus(HBV) DNA using sensitive assays; biochemical response was determined via serum liver function tests; histological response was determined from liver biopsy and fibroscan; safety analysis focused on glomerular renal function and bone mineral density. The primary efficacy endpoint was complete virological suppression over time, defined by HBV DNA < 20 IU/m L. Secondary efficacy endpoints included rates of biochemical response, and HB e antigen(HBe Ag)/HB surface antigen loss and seroconversion over time.RESULTS Ninety-two patients were identified who fulfilled the enrolment criteria. Median follow-up was 26 mo(range 3-114). Mean age was 46(24-78) years, 64(70%) were male and 77(84%) were of Asian origin. 55(60%) patients were treatment-na?ve and 62 patients(67%) were HBe Ag-negative. Complete virological suppression was achieved by 45/65(71%) patients at 12 mo, 37/46(80%) at 24 mo and 25/28(89%) at 36 mo. Partial virological response(HBV DNA 20-2000 IU/m L) was achieved by 89/92(96.7%) of patients. Multivariate analysis showed a significant relationship between virological suppression at end of follow-up and baseline HBV DNA level(OR = 0.897, 95%CI: 0.833-0.967, P = 0.0046) and HBe Ag positive

关键词： Tenofovir 肝炎 B 病毒澳大利亚真实 Virological 抑制长期的肝炎 B

A proton birdcage coil integrated with interchangeable single loops for multi-nuclear MRI/MRS

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journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第2期25卷 168-180页

作者： Yi ZHANG Zhiyan QUAN Feiyang LOU Yujiao FANG Garth j.thompson Gao CHEN Xiaotong ZHANG Department of Neurosurgery the Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou310009China Key Laboratory of Precise Treatment and Clinical Translational Research of Neurological Diseases Hangzhou310009China MOE Frontier Science Center for Brain Science and Brain-machine Integration Zhejiang UniversityHangzhou310058China Interdisciplinary Institute of Neuroscience and Technology College of Biomedical Engineering&Instrument ScienceZhejiang UniversityHangzhou310027China School of Medicine Zhejiang UniversityHangzhou310020China iHuman Institute School of Life Science and TechnologyShanghaiTech UniversityShanghai201210China College of Electrical Engineering Zhejiang UniversityHangzhou310027China

Energy metabolism is fundamental for life.It encompasses the utilization of carbohydrates,lipids,and proteins for internal processes,while aberrant energy metabolism is implicated in many diseases.In the present study,using three-dimensional(3D)printing from polycarbonate via fused deposition modeling,we propose a multi-nuclear radiofrequency(RF)coil design with integrated 1H birdcage and interchangeable X-nuclei(^(2)H,^(13)C,^(23)Na,and^(31)P)single-loop coils for magnetic resonance imaging(MRI)/magnetic resonance spectroscopy(MRS).The single-loop coil for each nucleus attaches to an arc bracket that slides unrestrictedly along the birdcage coil inner surface,enabling convenient switching among various nuclei and animal handling.Compared to a commercial 1H birdcage coil,the proposed 1H birdcage coil exhibited superior signal-excitation homogeneity and imaging signal-to-noise ratio(SNR).For X-nuclei study,prominent peaks in spectroscopy for phantom solutions showed excellent SNR,and the static and dynamic peaks of in vivo spectroscopy validated the efficacy of the coil design in structural imaging and energy metabolism detection simultaneously.

关键词： Energy metabolism Magnetic resonance imaging(MRI) Magnetic resonance spectroscopy(MRS) Multi-nuclear Radiofrequency coil Three-dimensional(3D)printing

Reduction of epinephrine in the lumbar spinal cord following repetitive blast-induced traumatic brain injury in rats

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Neural Regeneration Research 2024年第7期19卷 1548-1552页

作者： Shigeharu Tsuda Mustafa Golam jiamei Hou Kevin K.W.Wang Floyd j.thompson Prodip Bose Brain Rehabilitation Research Center Malcom Randall VA Medical CenterNorth Florida/South Georgia Veterans Health SystemGainesvilleFLUSA Department of Anesthesiology College of MedicineUniversity of FloridaGainesvilleFLUSA Department of Emergency Medicine University of FloridaGainesvilleFLUSA Department of Neuroscience University of FloridaGainesvilleFLUSA Department of Neurology University of FloridaGainesvilleFLUSA

Traumatic brain inju ry-induced unfavorable outcomes in human patients have independently been associated with dysregulated levels of monoamines,especially epinephrine,although few preclinical studies have examined the epinephrine level in the central nervous system after traumatic brain injury.Epinephrine has been shown to regulate the activities of spinal motoneurons as well as increase the heart rate,blood pressure,and blood flow to the hindlimb muscles.Therefore,the purpose of the present study was to determine the impact of repeated blast-induced traumatic brain injury on the epinephrine levels in seve ral function-s pecific central nervous system regions in rats.Following three repeated blast injuries at 3-day intervals,the hippocampus,motor cortex,locus coeruleus,vestibular nuclei,and lumbar spinal cord were harvested at post-injury day eight and processed for epinephrine assays using a high-sensitive electrochemical detector cou pled with high-performance liquid chromatography.Our results showed that the epinephrine levels were significantly decreased in the lumbar spinal cord tissues of blast-induced traumatic brain injury animals compared to the levels detected in age-and sex-matched sham controls.In other function-specific central nervous system regions,although the epinephrine levels were slightly altered following blast-induced tra u matic brain injury,they were not statistically significant.These results suggest that blast injury-induced significant downregulation of epinephrine in the lumbar spinal cord could negatively impact the motor and cardiovascular function.This is the first repo rt to show altered epinephrine levels in the spinal cord following repetitive mild blast-induced traumatic brain injury.

关键词： balance blood flow cardiovascular system central nervous system epinephrine ischemic damage lumbar spinal cord muscle tone repeated blast spasticity traumatic brain injury

A new perspective on intervertebral disc calcification—from bench to bedside

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Bone Research 2024年第1期12卷 50-61页

作者： Emanuel j.Novais Rajkishen Narayanan jose A.Canseco Koen van de Wetering Christopher K.Kepler Alan S.Hilibrand alexander R.Vaccaro Makarand V.Risbud Department of Orthopaedic Surgery Sidney Kimmel Medical CollegeThomas Jefferson UniversityPhiladelphiaPAUSA Unidade Local de Saúde do Litoral Alentejano Orthopedic DepartmentSantiago do CacémPortugal Rothman Orthopedic Institute at Thomas jefferson University PhiladelphiaPAUSA

Disc degeneration primarily contributes to chronic low back and neck pain.Consequently,there is an urgent need to understand the spectrum of disc degeneration phenotypes such as fibrosis,ectopic calcification,herniation,or mixed phenotypes.Amongst these phenotypes,disc calcification is the least studied.Ectopic calcification,by definition,is the pathological mineralization of soft tissues,widely studied in the context of conditions that afflict vasculature,skin,and cartilage.Clinically,disc calcification is associated with poor surgical outcomes and back pain refractory to conservative treatment.It is frequently seen as a consequence of disc aging and progressive degeneration but exhibits unique molecular and morphological characteristics:hypertrophic chondrocyte-like cell differentiation;TNAP,ENPP1,and ANK upregulation;cell death;altered Pi and PPi homeostasis;and local inflammation.Recent studies in mouse models have provided a better understanding of the mechanisms underlying this phenotype.It is essential to recognize that the presentation and nature of mineralization differ between AF,NP,and EP compartments.Moreover,the combination of anatomic location,genetics,and environmental stressors,such as aging or trauma,govern the predisposition to calcification.Lastly,the systemic regulation of calcium and Pi metabolism is less important than the local activity of PPi modulated by the ANK-ENPP1 axis,along with disc cell death and differentiation status.While there is limited understanding of this phenotype,understanding the molecular pathways governing local intervertebral disc calcification may lead to developing disease-modifying drugs and better clinical management of degeneration-related pathologies.

关键词： degeneration metabolism intervertebral

Enhancing 3D Reconstruction Accuracy of FIB Tomography Data Using Multi‑voltage Images and Multimodal Machine Learning

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Nanomanufacturing and Metrology 2024年第1期7卷 48-60页

作者： Trushal Sardhara alexander Shkurmanov Yong Li Lukas Riedel Shan Shi Christian j.Cyron Roland C.Aydin Martin Ritter Institute for Continuum and Material Mechanics Hamburg University of TechnologyHamburgGermany Electron Microscopy Unit Hamburg University of TechnologyHamburgGermany Institute of Materials Physics and Technology Hamburg University of TechnologyHamburgGermany Institute of Materials Mechanics Helmholtz-Zentrum HereonGeesthachtGermany Research Group of Integrated Metallic Nanomaterials Systems Hamburg University of TechnologyHamburgGermany Institute of Material Systems Modeling Helmholtz-Zentrum HereonGeesthachtGermany

FIB-SEM tomography is a powerful technique that integrates a focused ion beam(FIB)and a scanning electron microscope(SEM)to capture high-resolution imaging data of nanostructures.This approach involves collecting in-plane SEM imagesand using FIB to remove material layers for imaging subsequent planes,thereby producing image stacks.However,theseimage stacks in FIB-SEM tomography are subject to the shine-through effect,which makes structures visible from theposterior regions of the current plane.This artifact introduces an ambiguity between image intensity and structures in thecurrent plane,making conventional segmentation methods such as thresholding or the k-means algorithm insufficient.Inthis study,we propose a multimodal machine learning approach that combines intensity information obtained at differentelectron beam accelerating voltages to improve the three-dimensional(3D)reconstruction of nanostructures.By treatingthe increased shine-through effect at higher accelerating voltages as a form of additional information,the proposed methodsignificantly improves segmentation accuracy and leads to more precise 3D reconstructions for real FIB tomography data.

关键词： Multimodal machine learning Multi-voltage images FIB-SEM Overdeterministic systems 3D reconstruction FIB tomography

Prehospital transdermal glyceryl trinitrate for ultra- acute ischaemic stroke: data from the RIGHT- 2 randomised sham- controlled ambulance trial

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Stroke & Vascular Neurology 2024年第1期9卷 38-49,I0035-I0046页

作者： jason Philip Appleton Lisa j Woodhouse Craig S Anderson Sandeep Ankolekar Lesley Cala Mark Dixon Timothy j England Kailash Krishnan Grant Mair Keith W Muir john Potter Christopher I Price Marc Randall thompson G Robinson Christine Roffe Else C Sandset jeffrey L Saver Angela Shone Aloysius Niroshan Siriwardena joanna M Wardlaw Nikola Sprigg Philip M Bath Stroke University Hospitals Birmingham NHS Foundation TrustBirminghamUK Institute of Applied HealthResearch University of Birmingham College of Medical and Dental SciencesBirminghamUK Stroke Trials Unit Mental Health and Clinical NeurosciencesUniversity of NottinghamNottinghamUK Faculty of Medicine The George Institute for Global HealthSydneyNew South WalesAustralia The George Institute China at Peking University Health Science Center BeijingChina Neurology Royal Prince Alfred HospitalSydney Health PartnersSydneyNew South WalesAustralia Department of Neurology King's College Hospital NHS Foundation TrustLondonUK Faculty of Health and Medical Sciences University of Western AustraliaCrawleyWestern AustraliaAustralia East Midlands Ambulance Service NHS Trust NottinghamUK Stroke Queen's Medical CentreNottingham University Hospitals NHS TrustNottinghamUK Centre for Clinical Brain Sciences Dementia Research InstituteUniveristy of EdinburghEdinburghUK Institute of Neurology and Psychology University of GlasgowGlasgowUK Bob Champion Research and Education Building University of East AngliaNorwichUK Institute of Neuroscience Newcastle UniversityNewcastle upon TyneUK Department of Neurology Leeds Teaching Hospitals NHS TrustLeedsUK Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre University of LeicesterLeicesterUK Stroke Research in Stoke Institute for Science and Technology in MedicineKeele UniversityStoke-on TrentUK Department of Neurology Oslo University HospitalOsloNorway Research and Development Norwegian Air Ambulance FoundationOsloNorway Department of Neurology and Comprehensive Stroke Center David Geffen School of MedicineUCLALos AngelesCaliforniaUSA Research and Graduate Services University of NottinghamNottinghamUK Community and Health Research Unit University of LincolnLincolnUK

Background The effect of transdermal glyceryl trinitrate(GTN,a nitrovasodilator)on clinical outcome when administered before hospital admission in suspected stroke patients is unclear.Here,we assess the safety and efficacy of GTN in the prespecified subgroup of patients who had an ischaemic stroke within the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2(RIGHT-2).Methods RIGHT-2 was an ambulance-based multicentre sham-controlled blinded-endpoint study with patients randomised within 4hours of onset.The primary outcome was a shift in scores on the modified Rankin scale(mRS)at day 90.Secondary outcomes included death;a global analysis(Wei-Lachin test)containing Barthel Index,EuroQol-5D,mRS,telephone interview for cognitive status-modified and Zung depression scale;and neuroimaging-determined‘brain frailty’markers.Data were reported as n(%),mean(SD),median[IQR],adjusted common OR(acOR),mean difference or Mann-Whitney difference(MWD)with 95%CI.Results 597 of 1149(52%)patients had a final diagnosis of ischaemic stroke;age 75(12)years,premorbid mRS>2107(18%),Glasgow Coma Scale 14(2)and time from onset to randomisation 67[45,108]min.Neuroimaging‘brain frailty’was common:median score 2[2,3](range 0–3).At day 90,GTN did not influence the primary outcome(acOR for increased disability 1.15,95%CI 0.85 to 1.54),death or global analysis(MWD 0.00,95%CI-0.10 to 0.09).In subgroup analyses,there were non-significant interactions suggesting GTN may be associated with more death and dependency in participants randomised within 1hour of symptom onset and in those with more severe stroke.Conclusions In patients who had an ischaemic stroke,ultra-acute administration of transdermal GTN in the ambulance did not improve clinical outcomes in a population with more clinical and radiological frailty than seen in previous in-hospital trials.WHAT IS ALREADY KNOWN ON THIS TOPIC⇒Transdermal glyceryl trinitrate(GTN)was associat-ed with less death and dependency in those with acute stroke treated within 6hours of stroke

关键词： Glasgow nitrate random

The influence of reflections from the train body and the ground on the sound radiation from a railway rail

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Railway Sciences 2024年第1期3卷 1-17页

作者： David j.thompson Dong Zhao Evangelos Ntotsios Giacomo Squicciarini Ester Cierco Erwin jansen Institute of Sound and Vibration Research University of SouthamptonSouthamptonUK Ingenierıa para el Control del Ruido SL BarcelonaSpain TNO Acoustics and Sonar Den HaagThe Netherlands

Purpose – The vibration of the rails is a significant source of railway rolling noise, often forming the dominantcomponent of noise in the important frequency region between 400 and 2000 Hz. The purpose of the paper is toinvestigate the influence of the ground profile and the presence of the train body on the sound radiation fromthe rail.Design/methodology/approach – Two-dimensional boundary element calculations are used, in which therail vibration is the source. The ground profile and various different shapes of train body are introduced in themodel, and results are observed in terms of sound power and sound pressure. Comparisons are also made withvibro-acoustic measurements performed with and without a train present.Findings – The sound radiated by the rail in the absence of the train body is strongly attenuated by shieldingdue to the ballast shoulder. When the train body is present, the sound from the vertical rail motion is reflectedback down toward the track where it is partly absorbed by the ballast. Nevertheless, the sound pressure at thetrackside is increased by typically 0–5 dB. For the lateral vibration of the rail, the effects are much smaller. Oncethe sound power is known, the sound pressure with the train present can be approximated reasonably well withsimple line source directivities.Originality/value – Numerical models used to predict the sound radiation from railway rails have generallyneglected the influence of the ground profile and reflections from the underside of the train body on the soundpower and directivity of the rail. These effects are studied in a systematic way including comparisons with measurements.

关键词： Rolling noise Sound radiation Railway track Boundary elements Ground reflections Directivity

Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

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Neural Regeneration Research 2025年第4期20卷 1207-1216页

作者： Pascal j.Goldschmidt-Clermont Aisha Khan George jimsheleishvili Patricia Graham Adriana Brooks Risset Silvera alexander j.P.Goldschmidt Damien D.Pearse W.Dalton Dietrich Allan D.Levi james D.Guest Miller School of Medicine University of MiamiMiamiFLUSA Stem Cell Institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The Miami Project to Cure Paralysis Miller School of MedicineUniversity of MiamiMiamiFLUSA Alzady International LLC MiamiFLUSA Neurological Surgery Miller School of MedicineUniversity of MiamiMiamiFLUSA

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular junction.In amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be impaired.Recently,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been reported.This case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such treatment.An 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral sclerosis.After initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and taurursodiol.The patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron function.We confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in vitro.After a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered saline.None of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or changes in vital signs.Clinical lab serum neuro

关键词： allogeneic amyotrophic lateral sclerosis exosomes infusion neuromuscular junction Schwann cell

The Oral Health Status of Person with Special Needs in Kumasi

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Open journal of Stomatology 2024年第1期14卷 14-31页

作者： Ama Agyeibea Amuasi alexander Oti-Acheampong Victoria N. A. Boadu Lord j. j. Gowans The Department Child Oral Health & Orthodontics School of Medicine and Dentistry College of Health Sciences Kwame Nkrumah University of Science and Technology Kumasi Ghana The Department of Oral & Maxillofacial Sciences School of Medicine and Dentistry College of Health Sciences Kwame Nkrumah University of Science and Technology Kumasi Ghana The Department of Community Dentistry School of Medicine and Dentistry College of Health Sciences Kwame Nkrumah University of Science and Technology Kumasi Ghana

Background: The most prevalent non-communicable disease worldwide is oral health-related disease, with dental caries and periodontal conditions being common. Oral health status significantly impacts overall health and quality of life. Barriers to dental care affect children with special needs. This study evaluates the oral health status and treatment requirements of people with special needs. Methodology: This descriptive cross-sectional study in Kumasi, Ghana examined oral health status among people, 121 children with special needs over two months, in june-july 2022. Dental caries, periodontal changes, malocclusion, and trauma were assessed. The data was analyzed using SPSS 20.0. Results: The oral health status among people with special needs in this study was generally moderate, with a range from very good to very poor. The prevalence of dental caries was 37%, with a mean DMFT score of 2.82. Periodontal health showed unsatisfactory indicators such as mobile teeth, poor gingival health, high plaque scores, and the presence of halitosis. Conclusion: This descriptive study aimed to provide baseline data on the oral health status of special needs students in Kumasi, addressing the lack of knowledge in this area. It highlighted the importance of dental care in maintaining good oral health and overall well-being in individuals with special needs. Coordinated efforts by dental professionals are needed to provide dental health education and preventive interventions for these children.

关键词： Special Needs Oral Health Dental Caries Periodontal Diseases Malocclusion