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From nonalcoholic fatty liver disease to metabolic dysfunction-associated fatty liver disease: is it time for a change of terminology?

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Hepatoma Research 2020年第9期6卷 107-115页

作者： Giovanni Targher christopher d.Byrne department of Medicine Section of EndocrinologyDiabetes and MetabolismUniversity of VeronaVerona 37126Italy Southampton National Institute for Health Research Biomedical Research Centre University Hospital SouthamptonSouthampton General HospitalSouthampton SO166YDUnited Kingdom.

Nonalcoholic fatty liver disease(NAFLd)has become the most common cause of liver disease in many parts of the world,causing considerable liver-related(steatohepatitis,cirrhosis,liver failure and hepatocellular carcinoma)and extra-hepatic morbidity and mortality(mainly cardiovascular disease,chronic kidney disease or certain types of extra-hepatic cancers).Recently,based on insights gained from the past two decades,an international panel of experts from 22 countries has taken the initiative to propose a new name and definition for NAFLd in adult individuals-that is,metabolic dysfunction-associated fatty liver *** proposed change in nomenclature is not simply a semantic revision,but may facilitate improved diagnosis of this common liver disease for health promotion,case identification,patient awareness,ongoing clinical trials and health services *** aim of this commentary is to discuss the proposal for a change in nomenclature of this common and burdensome liver disease and to address the“pros and cons”for changing the name according to the perspective of different stakeholders.

关键词： Nonalcoholic fatty liver disease metabolic dysfunction-associated fatty liver disease liver fat commentary

Post electrical or lightning injury syndrome: a proposal for an American Psychiatric Association's diagnostic and Statistical Manual formulation with implications for treatment

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Neural Regeneration Research 2017年第9期12卷 1405-1412页

作者： christopher J.Andrews Andrew d.Reisner Mary Ann Cooper Medicine The University of Queensland Lightning and Electrical Injuries Mt Ommaney Family Practice Forensic diagnostic Center of district Nine Lightning Injury Research Program University of Illinois at Chicago African Centres for Lightning and Electromagnetics Network

In the past, victims of electrical and lightning injuries have been assessed in a manner lacking a system- atic formulation, and against ad hoc criteria, particularly in the area of neuropsychological disability. In this manner patients have, for example, only been partially treated, been poorly or incorrectly diagnosed, and have been denied the full benefit of compensation for their injuries. This paper contains a proposal for diagnostic criteria particularly for the neuropsychological aspects of the post injury syndrome. It pays attention to widely published consistent descriptions of the syndrome, and a new cluster analysis of post electrical injury patients. It formulates a proposal which could be incorporated into future editions of the American Psychiatric Association＇s diagnostic and Statistical Manual （dSM）. The major neuropsycholog- ical consequences include neurocognitive dysfunction, and memory subgroup dysfunction, with ongoing consequences, and sometimes including progressive or delayed psychiatric, cognitive, and/or neurological symptoms. The proposed diagnostic criteria insist on a demonstrated context for the injury, both specifying the shock circumstance, and also physical consequences. It allows for a certain delay in onset of symptoms. It recognizes exclusory conditions. The outcome is a proposal for a dSM classification for the post electrical or lightning injury syndrome. This proposal is considered important for grounding patient treatment, and for further treatment trials. Options for treatment in electrical or lightning injury are summarised, and future trials are foreshadowed.

关键词： electrical injury lightning injury neuropsychology neuropsychiatry injury American Psychiatric Association's diagnostic and Statistical Manual

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 ***,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 *** primary outcome was a shift in scores on the modified Rankin scale(mRS)at day *** 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’*** were reported as n(%),mean(Sd),median[IQR],adjusted common OR(acOR),mean difference or Mann-Whitney difference(MWd)with 95%*** 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]***‘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 *** 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 *** IS ALREAdY KNOWN ON THIS TOPIC⇒Transdermal glyceryl trinitrate(GTN)was associat-ed with less death and dependency in those w

关键词： Glasgow nitrate random

3-dimensional Kinematic Comparison of Arm Movements between an Individual with NGLY1 deficiency and a Neurotypical Individual

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Case Reports in Clinical Medicine 2024年第4期13卷 122-146页

作者： Charles S. Layne christopher A. Malaya Brock Futrell dacia Martinez diaz Christian Alfaro Hannah E. Gustafson Subhalakshmi Chandrasekaran Rhea M. Phatak Bernhard Suter department of Health and Human Performance University of Houston Houston TX USA Center for Neuromotor and Biomechanics Research University of Houston Houston TX USA Center for Neuro Engineering and Cognitive Science University of Houston Houston TX USA department of Computer Science and Engineering Texas A&M University College Station TX USA Blue Bird Circle Rett Center Texas Children&#8217s Hospital Houston TX USA Baylor College of Medicine Houston TX USA

NGLY1 deficiency is an ultra-rare autosomal recessively inherited disorder. Characteristic symptoms include among others, developmental delays, movement disorders, liver function abnormalities, seizures, and problems with tear formation. Movements are hyperkinetic and may include dysmetric, choreo-athetoid, myoclonic and dystonic movement elements. To date, there have been no quantitative reports describing arm movements of individuals with NGLY1 deficiency. This report provides quantitative information about a series of arm movements performed by an individual with NGLY1 deficiency and an aged-matched neurotypical participant. Three categories of arm movements were tested: 1) open ended reaches without specific end point targets;2) goal-directed reaches that included grasping an object;3) picking up small objects from a table placed in front of the participants. Arm movement kinematics were obtained with a camera-based motion analysis system and “initiation” and “maintenance” phases were identified for each movement. The combination of the two phases was labeled as a “complete” movement. Three-dimensional analysis techniques were used to quantify the movements and included hand trajectory pathlength, joint motion area, as well as hand trajectory and joint jerk cost. These techniques were required to fully characterize the movements because the NGLY1 individual was unable to perform movements only in the primary plane of progression instead producing motion across all three planes of movement. The individual with NGLY1 deficiency was unable to pick up objects from a table or effectively complete movements requiring crossing the midline. The successfully completed movements were analyzed using the above techniques and the results of the two participants were compared statistically. Almost all comparisons revealed significant differences between the two participants, with a notable exception of the 3d initiation area as a percentage of the complete movement. The stati

关键词： NGLY1 deficiency developmental disorders Kinematics 3 dimensional Analyses

Cardiac remodeling as a consequence of atrial fibrillation： An anatomical study of perfusion-fixed human heart specimens

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Journal of Geriatric Cardiology 2011年第3期8卷 141-146页

作者： christopher d Rolfes Stephen A Howard Ryan P Golf Paul A Iaizzo department of Biomedical Engineering University of Minnesota Minneapolis MAr 55455 USA department of Surgery University of Minnesota Minneapolis MN55455 USA department of Integrative Biology and Physiology University of Minnesota Minneapolis MN 55455 USA

Background Atrial fibrillation （AF） causes a continuum of atrial anatomical remodeling. Methods Using a library of perfusion-fixed human hearts, specimens with AF were compared to controls. during this preliminary assessment study, direct measurements were taken of atrial volume, pulmonary vein （PV） circumference, and left atrial （LA） wall thicknesses. Results Hearts with AF typically had larger atrial volumes, as well as a much larger variation in volume compared to controls （range of 59.6-227.1 mL in AF hearts compared to 65.1-115.9 mL in controls）. For all hearts, right PVs were larger than left PVs （mean： 171.4 ± 84.6 mm^2 for right and 1182 ± 50.1 mm^2 for left, P 〈 0.005）. LA wall thicknesses ranged from 0.7 mm to 3.1 mm for both AF and control hearts. Conclusions Hearts with AF had a large range of sizes which is consistent with the progression of atrial remodeling during AF. The large range of thicknesses will influence the amount of energy needed to create transmural lesions during ablation procedures.

关键词： left atrial dimensions volumes pulmonary vein ostia atrial fibrillation

The gut microbiome and nicotine metabolism in NAFLd

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Science Bulletin 2023年第3期68卷 233-235页

作者： Lei Miao Giovanni Targher christopher d.Byrne Ming-Hua Zheng department of Gastroenterology The Second Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325000China Section of Endocrinology Diabetes and MetabolismDepartment of MedicineUniversity of VeronaVerona 37129Italy Southampton National Institute for Health and Care Research Biomedical Research Centre University Hospital SouthamptonSouthampton General HospitalSouthampton SO166YDUK MAFLd Research Center Department of HepatologyThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325000China Key Laboratory of diagnosis and Treatment for The development of Chronic Liver disease in Zhejiang Province Wenzhou 325000China

A history of cigarette smoking is present in approximately 40%of patients with chronic liver diseases and there is considerable interest in better understanding if and how cigarette smoking may affect chronic liver diseases[1].Non-alcoholic fatty liver disease(NAFLd)is currently the most common cause of chronic liver disease,affecting up to 30%of the world’s adults[2].Genetic and environmental factors contribute to the development and progression of NAFLd,and increasing evidence shows that smoking is associated with more severe liver disease in NAFLd[3,4].despite convincing evidence of this association between smoking and liver disease,the underlying mechanism(s)linking smoking with NAFLd is still poorly understood.

关键词： NAFLd metabolism diseases

Thoracotomy in the emergency department for resuscitation of the mortally injured

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Chinese Journal of Traumatology 2017年第3期20卷 141-146页

作者： J. christopher diGiacomo L.d. George Angus Long Island Comprehensive Trauma Center Department of Surgery Nassau University Medical Center. East Meadow NY 11554 USA

Purpose： Emergency department resuscitative thoracotomy is an intervention of last resort for the acutely dying victim of trauma. In light of improvements in pre-hospital emergency systems, improved operative strategies for survival such as damage control and improvements in critical care medicine, the most extreme of resuscitation efforts should be re-evaluated for the potential survivor, with success properly defined as the return of vital signs which allow transport of the patient to the operating room. Methods： A retrospective review of all patients at a suburban level I trauma center who underwent emergency department resuscitative thoracotomy as an adjunct to the resuscitation efforts normally delivered in the trauma receiving area over a 22 year period was performed. Survival of emergency department resuscitative thoracotomy was defined as restoration of vital signs and transport out of the trauma resuscitation area to the operating room. Results： Sixty-eight patients were identified, of whom 27 survived the emergency department resusci- tative thoracotomy and were transported to the operating room. Review of pre-hospital and initial hospital data between these potential long term survivors and those who died in the emergency department failed to demonstrate trends which were predictive of survival of emergency department resuscitative thoracotomy. The only subgroup which failed to respond to emergency department resuscitative thoracotomy was patients without signs of life at the scene who arrived to the treatment facility without signs of life. Conclusion： The patient population of the ＂potential survivor＂ has been expanded due to advances in critical care practices, technology, and surgical technique and every opportunity for survival should be provided at the outset. Emergency department resuscitative thoracotomy is warranted for any patient with thoracic or subdiaphragmatic trauma who presents in extremis with a history of signs of life at the scene or or

关键词： Emergencies Thoracotomy InJuries Resuscitation

Structure and activity of thermophilic methanogenic microbial communities exposed to quaternary ammonium sanitizer

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Journal of Environmental Sciences 2017年第6期29卷 164-168页

作者： Jesus d.Fernandez-Bayo Juliano Toniato Blake A.Simmons christopher W.Simmons department of Food Science and Technology University of CaliforniaDauisCA 95616USA department of Biological and Agricultural Engineering Uniuersity of CaliforniaDauisCA 95616USA Joint BioEnergy Institute EmeryvilleCA 94608USA Biological and Engineering Sciences Center Sandia National LaboratoriesLiuermoreCA 94551USA Energy Efficiency Center University of CaliforniaDauisCA 95616USA

Food processing facilities often use antimicrobial quaternary ammonium compound （QAC） sanitizers to maintain cleanliness. These QACs can end up in wastewaters used as feedstock for anaerobic digestion. The aim of this study was to measure the effect of QAC contamination on biogas production and structure of microbial communities in thermo- philic digester sludge. Methane production and biogas quality data were analyzed in batch anaerobic digesters containing QAC at 0, 15, 50, 100 and 150 mg/L. Increasing sanitizer concentration in the bioreactors negatively impacted methane production rate and biogas quality. Microbial community composition data was obtained through 16S rRNA gene sequencing from the QAG-contaminated sludges. Sequencing data showed no significant restructuring of the bacterial communities. However, significant restructuring was observed within the archaeal communities as QAC concentration increased. Further studies to confirm these effects on a larger scale and with a longer retention time are necessary.

关键词： Anaerobic digestionAntimicrobialsBiofuelsMicrobial ecologyWaste management

Heterozygous carriers of galactocerebrosidase mutations that cause Krabbe disease have impaired microglial function and defective repair of myelin damage

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Neural Regeneration Research 2018年第3期13卷 393-401页

作者： Nicole J.Scott-Hewitt christopher J.Folts Mark d.Noble department of Biomedical Genetics University of Rochester School of Medicine and Dentistry

This review addresses two puzzling findings related to mutations in galactocerebrosidase （GALC） that cause Krabbe disease （Kd）, a severe lysosomal storage disorder characterized by extensive myelin damage in children with mutations in both GALC alleles. First, heterozygous carriers of Kd-causing mutations, which include the biological parents of children with Kd, exhibit increased risk for developing other diseases. Second, variants in the GALC locus increase the risk of developing multiple sclerosis （MS）, another disease characterized by extensive myelin damage. What explains these correlations？ In studies on cuprizone-induced myelin damage in heterozygous （GALC＋/–） mice carrying one copy of a mutation that causes Kd-like disease, the extent of damage was similar in GALC＋/– and wild-type （WT） mice. In contrast, GALC＋/- mice had striking defects in repair of cuprizone-induced damage. We further found unexpected microglial defects in myelin debris clearance and in the ability to up-regulate the Trem2 microglial protein critical for debris uptake. These defects were rescued by exposure to a lysosomal re-acidifying drug discovered in our studies on Kd, and which provides multiple clinically relevant benefits in the twitcher （GALC＋/–） mouse model of Kd. Thus, heterozygous GALC mutations cause effects on biological function that may help to understand the increased disease risk in heterozygous carriers of such mutations and to understand why GALC variations increase the risk of MS. Our findings indicate that while some genetic risk factors may contribute to complex diseases by increasing the risk of tissue damage, others may do so by compromising tissue repair.

关键词： vulnerability locus multiple sclerosis Krabbe disease galactocerebrosidase microglia myelin repair lysosomal storage disorders heterozygous carriers Trem2 demyelination