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Associations of accelerometry-measured and self-reported physical activity and sedentary behavior with skeletal muscle energetics:The Study of Muscle,Mobility and Aging(SOMMA)

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Journal of Sport and Health Science 2024年第5期13卷 621-630页

作者： Yujia(Susanna)Qiao Terri L.Blackwell Peggy M.Cawthon Paul M.Coen Steven R.Cummings Giovanna Distefano Samaneh Farsijani Daniel E.Forman Bret H.Goodpaster Stephen B.Kritchevsky Theresa Mau Frederico G.S.Toledo Anne B.Newman Nancy W.Glynn Department of Epidemiology School of Public HealthUniversity of PittsburghPittsburghPA 15261USA San Francisco Coordinating Center California Pacific Medical Center Research InstituteSan FranciscoCA 94143USA Department of Epidemiology and Biostatistics University of CaliforniaSan FranciscoCA 94143USA Translational Research Institute AdventHealthOrlandoFL 32804USA Department of Medicine(Geriatrics and Cardiology) University of Pittsburghand GeriatricsResearchEducationand Clinical Center(GRECC)VA Pittsburgh Healthcare SystemPittsburghPA 15261USA Department of Internal Medicine Section on Gerontology and Geriatric MedicineWake Forest School of MedicineWinston-SalemNC 27109USA Division of Endocrinology and Metabolism Department of MedicineUniversity of PittsburghPittsburghPA 15261USA

Background:Skeletal muscle energetics decline with age,and physical activity(PA)has been shown to offset these declines in older adults.Yet,many studies reporting these effects were based on self-reported PA or structured exercise interventions.Therefore,we examined the associations of accelerometry-measured and self-reported PA and sedentary behavior(SB)with skeletal muscle energetics and explored the extent to which PA and sedentary behavior would attenuate the associations of age with muscle energetics.Methods:As part of the Study of Muscle,Mobility and Aging,enrolled older adults(n=879),810(age=76.4±5.0 years old,mean±SD;58%women)had maximal muscle oxidative capacity measured ex vivo via high-resolution re spirometry of permeabilized myofibers(maximal oxidative phosphorylation(maxOXPHOS))and in vivo by ^(31)phosphorus magnetic resonance spectroscopy(maximal adenosine triphosphate(ATP_(max))).Accelerometry-measured sedentary behavior,light activity,and moderate-to-vigorous PA(MVPA)were assessed using a wrist-worn ActiGraph GT9X over 7 days.Self-reported sedentary behavior,MVPA,and all PA were assessed with the Community Healthy Activities Model Program for Seniors(CHAMPS)questionnaire.Linear regression models with progressive covariate adjustments evaluated the associations of sedentary behavior and PA with muscle energetics,as well as the attenuation of the age/muscle energetics association by MVP A and sedentary behavior.As a sensitivity analysis,we also examined activPAL-measured daily step count and time spent in sedentary behavior and their associations with muscle energetics.Results:Every 30 min/day more of ActiGraph-measured MVPA was associated with 0.65 pmol/(s×mg)higher maxOXPHOS and 0.012 mM/s higher ATP_(max)after adjusting for age,site/technician,and sex(p<0.05).Light activity was not associated with maxOXPHOS or ATP_(max).Meanwhile,every 30 min/day spent in ActiGraph-measured sedentary behavior was associated with 0.39 pmol/s×mg lower maxOXPHOS and0.006 mM/s lower ATP_(max)(p<0.05).Only associatio

关键词： Aging Exercise Mitochondria

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Multisensory mechanisms of gait and balance in Parkinson’s disease:an integrative review

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Neural Regeneration Research 2025年第1期20卷 82-92页

作者： Stiven Roytman Rebecca Paalanen Giulia Carli Uros Marusic Prabesh Kanel Teus van Laar Nico I.Bohnen Department of Radiology University of MichiganAnn ArborMIUSA Department of Neurology University of MichiganAnn ArborMIUSA Morris K.Udall Center of Excellence for Parkinson’s Disease Research University of MichiganAnn ArborMIUSA Institute for Kinesiology Research Science and Research Centre KoperKoperSlovenia Department of Health Sciences Alma Mater Europaea–ECMMariborSlovenia Parkinson’s Foundation Research Center of Excellence University of MichiganAnn ArborMIUSA Department of Neurology University of GroningenUniversity Medical Center GroningenGroningenThe Netherlands Neurology Service and grecc VA Ann Arbor Healthcare SystemAnn ArborMIUSA

Understanding the neural underpinning of human gait and balance is one of the most pertinent challenges for 21st-century translational neuroscience due to the profound impact that falls and mobility disturbances have on our aging population.Posture and gait control does not happen automatically,as previously believed,but rather requires continuous involvement of central nervous mechanisms.To effectively exert control over the body,the brain must integrate multiple streams of sensory information,including visual,vestibular,and somatosensory signals.The mechanisms which underpin the integration of these multisensory signals are the principal topic of the present work.Existing multisensory integration theories focus on how failure of cognitive processes thought to be involved in multisensory integration leads to falls in older adults.Insufficient emphasis,however,has been placed on specific contributions of individual sensory modalities to multisensory integration processes and cross-modal interactions that occur between the sensory modalities in relation to gait and balance.In the present work,we review the contributions of somatosensory,visual,and vestibular modalities,along with their multisensory intersections to gait and balance in older adults and patients with Parkinson’s disease.We also review evidence of vestibular contributions to multisensory temporal binding windows,previously shown to be highly pertinent to fall risk in older adults.Lastly,we relate multisensory vestibular mechanisms to potential neural substrates,both at the level of neurobiology(concerning positron emission tomography imaging)and at the level of electrophysiology(concerning electroencephalography).We hope that this integrative review,drawing influence across multiple subdisciplines of neuroscience,paves the way for novel research directions and therapeutic neuromodulatory approaches,to improve the lives of older adults and patients with neurodegenerative diseases.

关键词： aging balance encephalography functional magnetic resonance imaging gait multisensory integration Parkinson’s disease positron emission tomography somatosensory vestibular visual

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SARS-CoV-2 infection of monocytes:balancing acts of antibodies and inflammasomes

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Signal Transduction and Targeted Therapy 2022年第8期7卷 2668-2669页

作者： R.Camille Brewer William H.Robinson Tobias V.Lanz Division of Immunology and Rheumatology Department of MedicineStanford University School of Medicine269 Campus DriveStanfordCA 94305USA Geriatric Research Educationand Clinical Centers(GRECC)VA Palo Alto Health Care System3801 Miranda AvePalo AltoCA 94304USA

In a recent study in Nature,Junqueira et al.provided evidence that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infects human monocytes and lung macrophages.1 The infection is antibody-mediated via Fc-receptors(FcγRs),and activates NLRP3 and AIM2 inflammasomes,which in turn induce pyroptosis and halt viral replication.Infected monocytes secrete the proinflammatory cytokines interleukin-1β(IL-1β)and IL-18,which contribute to systemic inflammation and severe coronavirus disease 19(COVID-19)(Fig.1).

关键词： NLRP3 monocytes infection

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Effects of meditation and mind-body exercise on brain-derived neurotrophic factor:A literature review of human experimental studies

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Sports Medicine and Health Science 2020年第1期2卷 7-9页

作者： Tongjian You Elisa F.Ogawa Department of Exercise and Health Sciences College of Nursing and Health SciencesUniversity of Massachusetts BostonBostonMAUSA New England grecc VA Boston Healthcare SystemBostonMAUSA

This paper provides a literature review of current studies investigating the effects of meditation and mind-body exercise on peripheral concentrations of brain-derived neurotrophic factor(BDNF),an important mediator of the neuroplasticity of the central nervous system and cognitive function.A literature search was conducted to collect currently published randomized controlled,non-randomized controlled and uncontrolled intervention studies.Fifteen studies were identified;and among these studies,seven were randomized controlled studies,three were non-randomized studies,and five were uncontrolled studies.Current limited evidence tends to support that mindfulness meditation and mind-body exercise(e.***.yoga and tai chi)increase circulating BDNF concentrations in healthy and diseased individuals.It is noteworthy that these findings are based on current studies with a relatively small sample size,or without a randomized controlled design.Further studies are needed to identify a definite effect of meditation or mind-body exercise on BDNF and its role in improving/maintaining brain functions in various populations.

关键词： Meditation Mind-body exercise BDNF

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老年心血管疾病医护照料

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英国医学杂志中文版 2022年第2期25卷 87-100页

作者： Deirdre E O′Neill Daniel E Forman 唐施祺(译) 周红霞(校) University of Alberta Hospital EdmontonABCanada University of Pittsburgh University of Pittsburgh Medical Center and VA Pittsburgh GeriatricResearchEducation and Clinical Center(GRECC)PittsburghPAUSA 广西医科大学外国语学院广西医科大学公共卫生学院

年龄是心血管疾病的独立危险因素。随着老年人口的加速增长,老年医学与心脏病照护越来越息息相关。尽管年轻的心血管疾病患者一般不伴有其他疾病,但老年患者常伴随与年龄相关的多种疾病。因此,对心血管疾病的管理方案也会因其他共病、... 详细信息

年龄是心血管疾病的独立危险因素。随着老年人口的加速增长,老年医学与心脏病照护越来越息息相关。尽管年轻的心血管疾病患者一般不伴有其他疾病,但老年患者常伴随与年龄相关的多种疾病。因此,对心血管疾病的管理方案也会因其他共病、衰弱、多重用药、认知功能障碍、机体功能减退和年龄相关的复杂问题而变化。这意味着在管理老年心血管疾病患者时,需要更多的洞察力和技能来应对普遍存在的相关问题。本综述涵盖了治疗老年心血管疾病时可能存在的其他老年问题,特别是在心血管疾病管理方面应考虑的问题。传统的实践指南通常比较适合健康的老年人,用于应对多变的医疗状况、实现特殊照护目标的个体化治疗方案才会使更多人受益。这需要根据患者的总体状况权衡风险和效益,同时具备在决策时与患者沟通,并在适宜情况下与其他照护者进行交流的能力。这种个性化方案的效果尤为显著,为老年患者提供了改善机体功能和提升生活质量的机会,而这往往是治疗老年患者的首要目标。

关键词：老年心血管疾病老年问题医疗状况实践指南老年患者照护者多重用药老年医学

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Intracrine androgen biosynthesis and drug resistance

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Cancer Drug Resistance 2020年第4期3卷 912-929页

作者： Trevor M.Penning Irfan A.Asangani Cynthia Sprenger Stephen Plymate Department of Systems Pharmacology&Translational Therapeutics Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA Department Cancer Biology Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA Division of Gerontology&Geriatric Medicine Department of MedicineUniversity of WashingtonSeattleWA 98109USA Geriatric Research Education and Clinical Center(grecc) VA Puget Sound Health Care SystemSeattleWA 98108USA

Castration-resistant prostate cancer is the lethal form of prostate cancer and most commonly remains dependent on androgen receptor(AR)signaling.Current therapies use AR signaling inhibitors(ARSI)exemplified by abiraterone acetate,a P450c17 inhibitor,and enzalutamide,a potent AR antagonist.However,drug resistance to these agents occurs within 12-18 months and they only prolong overall survival by 3-4 months.Multiple mechanisms can contribute to ARSI drug resistance.These mechanisms can include but are not limited to germline mutations in the AR,post-transcriptional alterations in AR structure,and adaptive expression of genes involved in the intracrine biosynthesis and metabolism of androgens within the tumor.This review focuses on intracrine androgen biosynthesis,how this can contribute to ARSI drug resistance,and therapeutic strategies that can be used to surmount these resistance mechanisms.

关键词： Prostate cancer abiraterone acetate enzalutamide aldo-keto reductase 1C3 androgen biosynthesis

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CRISPR-mediated genome editing and human diseases

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Genes & Diseases 2016年第4期3卷 244-251页

作者： Liquan Cai Alfred L.Fisher Haochu Huang Zijian Xie Marshal l Institute for Interdisciplinary Research(MIIR) Marshall UniversityWeisberg Engineering ComplexMarshall University1628 Third AvenueHuntingtonWV 25703USA University of Texas Health Science Center at San Antonio Department of MedicineDivision of GeriatricsGerontologyand Palliative MedicineSan AntonioTX 78229USA grecc South Texas VA Healthcare SystemSan AntonioTX 78229USA Committee on Immunology Section of RheumatologyDepartment of MedicineKnapp Center for Lupus and Immunology ResearchUniversity of ChicagoChicagoIL 60637USA

CRISPR(Clustered Regularly Interspaced Short Palindromic Repeats)technology has emerged as a powerful technology for genome editing and is now widely used in basic biomedical research to explore gene function.More recently,this technology has been increasingly applied to the study or treatment of human diseases,including Barth syndrome effects on the heart,Duchenne muscular dystrophy,hemophilia,b-Thalassemia,and cystic fibrosis.CRISPR/Cas9(CRISPR-associated protein 9)genome editing has been used to correct diseasecausing DNA mutations ranging from a single base pair to large deletions in model systems ranging from cells in vitro to animals in vivo.In addition to genetic diseases,CRISPR/Cas9 gene editing has also been applied in immunology-focused applications such as the targeting of C-C chemokine receptor type 5,the programmed death 1 gene,or the creation of chimeric antigen receptors in T cells for purposes such as the treatment of the acquired immune deficiency syndrome(AIDS)or promoting anti-tumor immunotherapy.Furthermore,this technology has been applied to the genetic manipulation of domesticated animals with the goal of producing biologic medical materials,including molecules,cells or organs,on a large scale.Finally,CRISPR/Cas9 has been teamed with induced pluripotent stem(iPS)cells to perform multiple tissue engineering tasks including the creation of disease models or the preparation of donor-specific tissues for transplantation.This review will explore the ways in which the use of CRISPR/Cas9 is opening new doors to the treatment of human diseases.

关键词： CRISPR DNA double-stranded break Genome editing Human diseases iPS cells

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遗传性神经病变的双重干扰:PMP-22基因和另一基因共突变产生新表型

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世界核心医学期刊文摘(神经病学分册) 2006年第4期 20-21页

作者： Hodapp J.A. Carter G.T. Lipe H.P. T.D. Bird 方伯言 S- 182- grecc 1660 S Columbian Way Seattle WA 98108 United States.Dr

Background: Mutations in the peripheral myelin protein 22 (PMP- 22) gene are the most common cause of Charcot-Marie-Tooth neuropathy and may rarely occur in combination with other neurogenetic diseases. Objective: To characterize 3 families having a mutation in PMP-22 in addition to another neurogenetic disease mutation. Design: Clinical, electrophysiologic, and genetic evaluations were made of 3 families with more than 1 genetic neuromuscular disease. Setting and Patients: Family members were evaluated in neurogenetic and muscular dystrophy clinics in a university medical center setting. Results: Three unusual families were found: (1) 2 young brothers each having a PMP- 22 duplication and a missense mutation in the GJB1 (Connexin- 32) gene; (2) a 32- year- old woman having a PMP- 22 duplication and a 1000- fold CTG repeat expansion in the DMPK gene (DM1 myotonic dystrophy); and (3) a 39- year- old man with a PMP- 22 deletion and a missense mutation in the ABCD1 gene (adrenomyeloneuro-pathy). The mutations were “ additive," causing a more severe phenotype than expected with each individual disease and coinciding with the important impact of each gene on peripheral nerve function. Conclusions: Individuals having 2 separate mutations in neuromuscular disease-related genes may develop unusually severe phenotypes. Neurologists should be alert to this possibility.

关键词：神经病变 PMP-22 遗传性基因突变点突变表型

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胰岛素对阿尔茨海默病患者血浆β-淀粉样蛋白的差异调节

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世界核心医学期刊文摘(神经病学分册) 2006年第11期 57-58页

作者： Kulstad J.J Green P.S Cook D.G S. Craft 郭俊 VAPSHCS S-182-GRECC 1660 S. Columbian Way Seattle WA 98108 United States Dr.

BACKGROUND: Hyperinsulinemia and insulin resistance are risk factors for memory impairment and Alzheimer disease (AD). Insulin regulates levels of the amyloid β-peptide (Aβ)in vitro in neuronal cultures and in vivo in the CSF of normal older adults. OBJECTIVE: To determine whether insulin affected plasma Aβlevels and whether such effects differed for patients with AD compared with normal older adults. METHODS: Fifty-nine patients with AD and 50 healthy older adults each received infusions of saline and of insulin (1.0 mU·kg·min)with accompanying dextrose to maintain euglycemia. A subset of participants (19 AD, 12 normal) received two additional conditions, in which insulin was infused at a lower (0.33 mU·kg·min) and higher (1.67 mU·kg·min) rate. Plasma insulin and Aβ.were measured after 120 minutes of infusion. RESULTS: Adults with AD had higher plasma insulin vs normal adults at the two higher infusion rates, despite receiving comparable amounts of insulin. For normal adults, insulin reduced plasma Aβlevels at the middle (1.0 mU·kg·min) dose, with attenuated effects at lower and higher doses. In contrast, for patients with AD, insulin raised plasma Aβ.levels at the two higher doses (1.0 and 1.67 mU·kg·min). CONCLUSIONS: These results suggest that patients with Alzheimer disease (AD) have reduced insulin clearance and insulin-provoked plasma amyloid β-peptide (Aβ) elevation. Abnormal regulation of peripheral Aβby insulin may contribute to AD risk.

关键词：胰岛素 AD 多肽 β-淀粉样蛋白阿尔茨海默病患者血浆

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Risk Factors for Failure of OPAT （Outpatient Parenteral Antimicrobial Therapy） in Veterans with Staphylococcus aureus Bacteremia

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Journal of Pharmacy and Pharmacology 2016年第6期4卷 241-247页

作者： John J. Veillette Leslie Bittner Marion J. Skalweit Usha Stiefel Christopher J. Burant Amy A.Hirsch Sharanie Sims Pharmacy Service Louis Stokes Cleveland Department of Veterans Affairs Medical Center (LSCDVAMC) Cleveland OH USA Medicine Service LSCDV.4MC Cleveland OH USA Case Western Reserve University School of Medicine Cleveland OH USA Cleveland Geriatric Research Education and Clinical Center (grecc) LSCDVAMC Cleveland OH USA Case Western Reserve University Frances Payne Bolton School of Nursing Cleveland OH USA

To identify risk factors for failure of OPAT (outpatient parenteral antimicrobial therapy) among veterans with SAB (Staphylococcus aureus bacteremia), a retrospective review was conducted of all patients receiving OPAT for SAB between 01/2011-09/2013 at a large, tertiary-care VA (Veterans" Affairs) medical center. Treatment failure was defined as incomplete therapy, therapy extension, infection relapse, or hospital admission or surgical intervention within 60 days of therapy completion. Of 118 SAB patients treated with OPAT, 101 met inclusion criteria. Treatment failure occurred in 36 (35.6%) patients. In multivariate analysis, heart failure (OR 3.67; CI 1.13-12.0), previous OPAT (OR 14.1; CI 2.02-97.8), immunosuppression (OR 10.5; CI 1.74-63.3), and treatment with daptomycin (OR 9.56; CI 1.89-48.4) were independently associated with failure. A trend toward lower failure rates was seen in the community living center, a VA long-term care facility possessing its own infectious diseases consultation service. In veterans with SAB, specific health factors were associated with higher rates of OPAT failure. Given the morbidity and cost of SAB treatment failures, similar analyses may benefit other large OPAT programs to optimize the selection of patients and settings in which successful treatment will most likely occur.

关键词：抗菌药物治疗金黄色葡萄球菌退伍军人危险因素血症胃肠门诊社区生活

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