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Androgen effects on skeletal muscle： implications for the development and management of frailty

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Asian Journal of Andrology 2014年第2期16卷 203-212,I0007,I0008页

作者： Matthew DL O'Connell Frederick CW Wu The Irish Longitudinal Study on Ageing Department of Medical Gerontology Trinity College Dublin Ireland Andmlogy research Unit Institute of Human Development Centre for Endocrinology and Diabetes University of Manchester Manchester UK.

Androgens have potent anabolic effects on skeletal muscle and decline with age in parallel to losses in muscle mass and strength. This loss of muscle mass and function, known as sarcopenia, is the central event in development of frailty, the vulnerable health status that presages adverse outcomes and rapid functional decline in older adults. The potential role of falling androgen levels in the development of frailty and their utility as function promoting therapies in older men has therefore attracted considerable attention. This review summarizes current concepts and definitions in muscle ageing, sarcopenia and frailty, and evaluates recent developments in the study of androgens and frailty. Current evidence from observational and interventional studies strongly supports an effect of androgens on muscle mass in ageing men, but effects on muscle strength and particularly physical function have been less clear. Androgen treatment has been generally well-tolerated in studies of older men, but concerns remain over higher dose treatments and use in populations with high cardiovascular risk. The first trials of selective androgen receptor modulators （SARMs） suggest similar effects on muscle mass and function to traditional androgen therapies in older adults. Important future directions include the use of these agents in combination with exercise training to promote functional ability across different populations of older adults, as well as more focus on the relationships between concurrent changes in hormone levels, body composition and physical function in observational studies.

关键词： ageing androgens body composition frailty muscle physical function sarcopenia selective androgen receptor modulators sex hormones testosterone

Using statistics and mathematical modelling to understand infectious disease outbreaks:COVID-19 as an example

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Infectious Disease Modelling 2020年第1期5卷 409-441页

作者： Christopher E.Overton Helena B.Stage Shazaad Ahmad Jacob Curran-Sebastian Paul Dark Rajenki Das Elizabeth Fearon Timothy Felton Martyn Fyles Nick Gent Ian Hall Thomas House Hugo Lewkowicz Xiaoxi Pang Lorenzo Pellis Robert Sawko Andrew Ustianowski Bindu Vekaria Luke Webb Department of Mathematics University of ManchesterUK IBM research Hartree CentreSciTech DaresburyUK Department of Global Health and Development London School of Hygiene and Tropical MedicineUK Emergency Response Department Public Health EnglandUK Division of Infection Immunity and Respiratory MedicineNIHR Biomedical Research CentreUniversity of ManchesterUK Department of Virology Manchester Medical Microbiology PartnershipManchester Foundation TrustUK Regional Infectious Diseases Unit North Manchester General HospitalUK School of Medical Sciences University of ManchesterUK Intensive Care Unit Wythenshawe HospitalManchester University NHS Foundation TrustUK Department of Health Sciences University of ManchesterUK Department of Mathematical Sciences University of LiverpoolUK The Alan Turing Institute UK manchester Academic Health Sciences centre UK Critical Care Unit Salford Royal HospitalNorthern Care Alliance NHS GroupUK

During an infectious disease outbreak,biases in the data and complexities of the underlying dynamics pose significant challenges in mathematically modelling the outbreak and designing *** by the ongoing response to COVID-19,we provide a toolkit of statistical and mathematical models beyond the simple SIR-type differential equation models for analysing the early stages of an outbreak and assessing *** particular,we focus on parameter estimation in the presence of known biases in the data,and the effect of non-pharmaceutical interventions in enclosed subpopulations,such as households and care *** illustrate these methods by applying them to the COVID-19 pandemic.

关键词： COVID-19 Epidemic modelling Parameter estimation Outbreak Bias Intervention

Machine perfusion of the liver: Which is the best technique to mitigate ischaemia-reperfusion injury?

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World Journal of Transplantation 2019年第1期9卷 14-20页

作者： Yuri L Boteon Simon C Afford Liver Unit Queen Elizabeth HospitalUniversity Hospitals Birmingham NHS Foundation Trust centre for Liver and Gastrointestinal research Institute of Immunology and ImmunotherapyCollege of Medical and Dental SciencesUniversity of Birmingham National Institute for Health research (nihr) Birmingham biomedical research centre University of Birmingham and University Hospitals Birmingham NHS Foundation Trust

Longstanding research describes the mechanisms whereby the restoration of blood flow and reoxygenation(reperfusion) aggravates the ischaemic injury caused by a period of anoxia to a donor liver. This phenomenon, called ischaemia-reperfusion injury(IRI), leads to parenchymal cell death,microcirculatory failure, and inflammatory immune response. Clinically, IRI is the main factor responsible for the occurrence of posttransplant graft dysfunction and ischaemic-type biliary lesions. While extended criteria donor livers are more vulnerable to IRI, their utilisation is required to address the shortfall in donor organs. Thus, the mitigation of IRI should drive the setting of a new benchmark for marginal organ preservation. Herein, strategies incorporating different modalities of machine perfusion of the liver to alleviate IRI are discussed in conjunction with advantages and disadvantages of individual *** leading to reperfusion of the liver during machine perfusion(in situ normothermic regional perfusion and ex situ normothermic machine perfusion)may mitigate IRI by shortening the ischaemic period of the organs. This benefit potentially escalates from the minimum level, obtained following just partial alleviation of the ischaemic period, to the maximum level, which can be potentially achieved with ischaemia-free organ transplantation. Techniques that do not lead to reperfusion of the liver during machine perfusion(hypothermic,subnormothermic, and controlled-oxygenated rewarming) optimise mitochondrial oxidative function and replenish cellular energy stores, thereby lowering reactive oxygen species production as well as the activation ofdownstream inflammatory pathways during reperfusion. Further mechanistic insights into IRI may guide the development of donor-specific protocols of machine perfusion on the basis of the limitations of individual categories of extended criteria donor organs.

关键词： Machine perfusion of the liver Ischaemia-reperfusion injury Liver transplantation Organ preservation Organ reconditioning

Label-free super-resolution imaging of adenoviruses by submerged microsphere optical nanoscopy

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Light(Science & Applications) 2013年第1期2卷 64-72页

作者： Lin Li Wei Guo Yinzhou Yan Seoungjun Lee Tao Wang Laser Processing research centre School of MechanicalAerospace and Civil Engineeringand Photon Science InstituteThe University of ManchesterManchester M139PLUK Faculty of Medical and Human Sciences The University of ManchesterManchester M139PLUK

Because of the small sizes of most viruses(typically 5–150 nm),standard optical microscopes,which have an optical diffraction limit of 200 nm,are not generally suitable for their direct *** microscopes usually require specimens to be placed under vacuum conditions,thus making them unsuitable for imaging live biological specimens in liquid *** optical imaging of viruses has been made possible by the use of fluorescence optical microscopy that relies on the stimulated emission of light from the fluorescing specimens when they are excited with light of a specific wavelength,a process known as labeling or self-fluorescent emissions from certain organic *** this paper,we describe direct white-light optical imaging of 75-nm adenoviruses by submerged microsphere optical nanoscopy(SMON)without the use of fluorescent labeling or *** mechanism involved in the imaging is *** calculations of the imaging planes and the magnification factors have been verified by experimental results,with good agreement between theory and experiment.

关键词： imaging microscope optical super-resolution virus

Molecular Oxygen Abundance in Galactic Massive Star Formation Regions Based on SWAS Observations

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research in Astronomy and Astrophysics 2024年第9期24卷 83-98页

作者： Bing-Ru Wang Di Li Paul F.Goldsmith Jingwen Wu Chao-Wei Tsai Donghui Quan Xia Zhang Junzhi Wang Gary J.Melnick Jin-Zeng Li Gary A.Fuller Jinjin Xie National Astronomical Observatories Chinese Academy of SciencesBeijing 100101China Tsinghua University Beijing 100084China University of Chinese Academy of Sciences Beijing 100049China research Center for Astronomical Computing Zhejiang LaboratoryHangzhou 311100China Jet Propulsion Laboratory California Institute of TechnologyPasadenaCA 91109USA Institute for Frontiers in Astronomy and Astrophysics Beijing Normal UniversityBeijing 102206China Xinjiang Astronomical Observatory Chinese Academy of SciencesUrumqi 830011China Guangxi Key Laboratory for Relativistic Astrophysics School of Physical Science and TechnologyGuangxi UniversityNanning 530004China Center for Astrophysics Harvard&Smithsonian60 Garden StreetMS 66CambridgeMA 02138USA Jodrell Bank Center for Astrophysics Department of Physics&AstronomyUniversity of ManchesterOxford RoadManchesterM139PLUK I.Physikalisches Institut University of CologneZülpicher Str.7750937 KölnGermany

Molecular oxygen abundance is a key parameter in understanding the chemical network of the interstellar *** estimate the molecular oxygen column density and abundance for a sample of Galactic massive star formation regions based on observations from the Submillimiter Wave Astronomy Satellite(SWAS)*** obtained an averaged O_(2)spectrum based on this sample using the(SWAS)survey data(O_(2),487.249 GHz,N=3-1,J=3-2).No emission or absorption feature is seen around the supposed central velocity with a total integration time of t_(total)=8.67×10^(3)hr and an rms noise per channel of 1.45 m *** a kinetic temperature T_(kin)=30 K,we derive the 3σupper limit of the O_(2)column density to be 3.3×10^(15)cm^(-2),close to the lowest values reported in Galactic massive star formation regions in previous *** corresponding O_(2)abundance upper limit is6.7×10^(-8),lower than all previous results based on SWAS observations and is close to the lowest reported value in massive star formation *** a galactic scale,our statistical results confirm a generally low O_(2)abundance for Galactic massive star formation *** abundance is also lower than results reported in extragalactic sources.

关键词： ISM:molecules galaxies:abundances ISM:lines and bands Galaxy:abundances

Schwann-like adipose-derived stem cells as a promising therapeutic tool for peripheral nerve regeneration:effects of cholinergic stimulation

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Neural Regeneration research 2021年第6期16卷 1218-1220页

作者： Roberta Piovesana Alessandro Faroni Ada Maria Tata Adam J.Reid Department of Biology and Biotechnologies“Charles Darwin” SapienzaUniversity of RomeRomeItaly Blond McIndoe Laboratories Division of Cell Matrix Biology and Regenerative MedicineSchool of Biological SciencesFaculty of BiologyMedicine and HealthThe University of ManchesterManchester Academic Health Science CentreManchesterUK research centre of Neurobiology“Daniel Bovet” SapienzaUniversity of RomeRomeItaly Department of Plastic Surgery&Burns Wythenshawe HospitalManchester University NHS Foundation TrustManchester Academic Health Science CentreManchesterUK

Schwann-like adipose-derived stem cells and nerve injury:Peripheral nerve injuries(PNIs)are a common clinical problem usually as a consequence of *** optimal surgical management,PNI has a lifelong impact on function and wellbeing of the *** peripheral nervous system(PNS)has regenerative capability,in contrast to the central nervous system(CNS),and is dependent on the plasticity of the peripheral glia,Schwann cells(SCs).Despite this regenerative capability,PNI recovery of sensorial and motor function is always incomplete causing pain,cold intolerance,paralysis and impairment of activities of daily living.

关键词： stimulation injuries paralysis

In vivo study of corneal responses to increased intraocular pressure loading

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Eye and Vision 2015年第1期2卷 177-186页

作者： Ahmed Elsheikh Charles W.McMonnies Charles Whitford Gavin C.Boneham School of Engineering University of LiverpoolBrownlow HillLiverpool L693GHUK National Institute for Health research(nihr)biomedical research centre Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of OphthalmologyLondonUK School of Optometry and Vision Science University of New South WalesSydneyAustralia

Background:The cornea is responsible for two-thirds of the eye's refractive power which is a function of the shape and refractive *** aim of this present study is to examine human eyes in vivo for corneal shape changes in response to short-term elevation in intraocular ***:Videokeratographic and tonometric assessments at baseline were compared with the same assessments when intraocular pressure was elevated to approximately double(199±22%)the baseline levels using ophthalmodynamometer applanation of the *** maps of the cornea and limbus were created by combining topographical assessments for central,nasal,temporal,inferior and superior *** finiteelement simulations were custom built for each subject and the stiffness distribution across corneal surface modified to achieve matches between simulated and experimental ***:The stiffness distributions required to achieve simulation-experimental matches showed a consistent trend with the 2.5 mm annulus bounded by the limbus showing a mean stiffness reduction of 47.3±10.8%compared with the central cornea(P=0.001).Conclusions:Corneal structure appears to provide the central cornea with a greater stiffness compared with the peripheral cornea and associated greater tolerance to elevation in intraocular pressure,consistent with the need for stable corneal refraction and *** method adopted to examine corneal biomechanical performance in vivo may have applications in additional studies.

关键词： Corneal biomechanics Topography Numerical simulation

Can training extend current guidelines for cochlear implant candidacy?

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Neural Regeneration research 2015年第5期10卷 718-720页

作者： Amal Isaiah Douglas E.H.Hartley Department of Otorhinolaryngology-Head and Neck Surgery University of Maryland School of Medicine National Institute for Health research (nihr) Nottingham Hearing Biomedical Research Unit Otology and Hearing Group Division of Clinical NeuroscienceSchool of MedicineUniversity of Nottingham Medical research Council (MRC) Institute of Hearing research

Since their introduction in the 1960s, cochlear implants （CIS） have undergone several transformations, ulti- mately positioning themselves as the best-performing neural prosthesis available today. They have also been recognized as a unique tool for studying the potential protective effects of patterned electrical stimulation on the developing auditory system, with results from animal models often changing the manner in which CIs are used clinically to deliver auditory information to the brain （Moore and Shannon, 2009）. From the development of the first successful commercial single-channel device, they have evolved into multi-channel devices that are part of the national health programmes of several coun- tries. From the limited speech information provided by the early, rudimentary cochlear implants, these devices are now in a position to deliver intelligible speech infor- mation to the auditory system, largely due to advances in signal processing. Concerted efforts from several dis- ciplines, including engineering, acoustics, neurobiology and otolaryngology have ensured that the continued development of CI technology has resulted in signifi- cant benefits to individuals with profound sensorineural hearing loss.

关键词： Can training extend current guidelines for cochlear implant candidacy CI

Nutrition in alcohol-related liver disease:Physiopathology and management

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World Journal of Gastroenterology 2020年第22期26卷 2916-2930页

作者： Umair Kamran Jennifer Towey Amardeep Khanna Abhishek Chauhan Neil Rajoriya Andrew Holt The Liver Unit Queen Elizabeth Hospital BirminghamBirmingham B152GWUnited Kingdom Department of Dietetics Queen Elizabeth Hospital BirminghamBirmingham B152GWUnited Kingdom centre for Liver research Institute of Immunology and Inflammationand National Institute for Health Research(NIHR)Birmingham Biomedical Research CentreThe Medical SchoolUniversity of BirminghamBirmingham B152TTUnited Kingdom

Malnutrition encompassing both macro-and micro-nutrient deficiency,remains one of the most frequent complications of alcohol-related liver disease(ArLD).Protein-energy malnutrition can cause significant complications including sarcopenia,frailty and immunodepression in cirrhotic *** reduces patient’s survival and negatively affects the quality of life of individuals with ***,nutritional deficit increases the likelihood of hepatic decompensation in *** recognition of at-risk individuals,early diagnosis and treatment of malnutrition remains a key component of ArLD *** this review,we describe the pathophysiology of malnutrition in ArLD,review the screening tools available for nutritional assessment and discuss nutritional management strategies relevant to the different stages of ArLD,ranging from acute alcoholic hepatitis through to decompensated end stage liver disease.

关键词： Malnutrition Sarcopenia Alcohol-related liver disease Nutritional assessment Nutrition support Micronutrients