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How do neurons age?A focused review on the aging of the microtubular cytoskeleton

Neural Regeneration Research 2024年第9期19卷 1899-1907页

作者： brad Richardson Thomas Goedert Shmma Quraishe Katrin Deinhardt Amritpal Mudher School of Biological Sciences University of SouthamptonSouthamptonUK Institute of Developmental and Regenerative Medicine University of OxfordOxfordUK

Aging is the leading risk factor for Alzheimer’s disease and other neurodegenerative diseases. We now understand that a breakdown in the neuronal cytoskeleton, mainly underpinned by protein modifications leading to the destabilization of microtubules, is central to the pathogenesis of Alzheimer’s disease. This is accompanied by morphological defects across the somatodendritic compartment, axon, and synapse. However, knowledge of what occurs to the microtubule cytoskeleton and morphology of the neuron during physiological aging is comparatively poor. Several recent studies have suggested that there is an age-related increase in the phosphorylation of the key microtubule stabilizing protein tau, a modification, which is known to destabilize the cytoskeleton in Alzheimer’s disease. This indicates that the cytoskeleton and potentially other neuronal structures reliant on the cytoskeleton become functionally compromised during normal physiological aging. The current literature shows age-related reductions in synaptic spine density and shifts in synaptic spine conformation which might explain age-related synaptic functional deficits. However, knowledge of what occurs to the microtubular and actin cytoskeleton, with increasing age is extremely limited. When considering the somatodendritic compartment, a regression in dendrites and loss of dendritic length and volume is reported whilst a reduction in soma volume/size is often seen. However, research into cytoskeletal change is limited to a handful of studies demonstrating reductions in and mislocalizations of microtubule-associated proteins with just one study directly exploring the integrity of the microtubules. In the axon, an increase in axonal diameter and age-related appearance of swellings is reported but like the dendrites, just one study investigates the microtubules directly with others reporting loss or mislocalization of microtubule-associated proteins. Though these are the general trends reported, there are clea

关键词： age-related changes aging cytoskeleton microtubules neuronal morphology

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Effects of exosomes from mesenchymal stem cells on functional recovery of a patient with total radial nerve injury: A pilot study

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World Journal of Stem Cells 2024年第1期16卷 19-32页

作者： ErdinçCivelek Serdar Kabatas eyüp Can Savrunlu Furkan Diren Necati Kaplan Demet Ofluoğlu Erdal Karaöz Department of Neurosurgery University of Health SciencesGaziosmanpaşa Training and Research HospitalGaziosmanpaşa 34255IstanbulTurkey Department of Neurosurgery University of Health Sciences TurkeyGaziosmanpaşa Training and Research HospitalGaziosmanpaşa 34255IstanbulTurkey Center for Stem Cell&Gene Therapy Research and Practice University of Health Sciences TurkeyGaziosmanpaşa 34255IstanbulTurkey Department of Neurosurgery Nevşehir State HospitalNevşehir 50300Turkey Department of Neurosurgery Istanbul Rumeli UniversityÇorlu Reyap HospitalÇorlu 59860TekirdağTurkey Department of Physical Medicine and Rehabilitation Ofluoğlu KlinikGöztepe 34728IstanbulTurkey Liv Hospital Center for Regenerative Medicine and Stem Cell Research&Manufacturing(LivMedCell)Beşiktaş34340IstanbulTurkey Department of Histology and Embryology Istinye UniversityFaculty of MedicineZeytinburnu 34010IstanbulTurkey Istinye University Center for Stem Cell and Tissue Engineering Research and PracticeBeşiktaş34340IstanbulTurkey

BACKGROUND Peripheral nerve injury can result in significant clinical complications that have uncertain ***,there is a lack of effective pharmacological interventions for nerve damage,despite the existence of several small compounds,Despite the objective of achieving full functional restoration by surgical intervention,the persistent challenge of inadequate functional recovery remains a significant concern in the context of peripheral nerve *** To examine the impact of exosomes on the process of functional recovery following a complete radial nerve *** A male individual,aged 24,who is right-hand dominant and an immigrant,arrived with an injury caused by a knife *** cut is located on the left arm,specifically below the *** neurological examination and electrodiagnostic testing reveal evidence of left radial nerve *** sural autograft was utilized for repair,followed by the application of 1 mL of mesenchymal stem cell-derived exosome,comprising 5 billion *** exosome was split into four equal volumes of 0.25 mL each and delivered microsurgically to both the proximal and distal stumps using the subepineural *** patient was subjected to a period of 180 d during which they had neurological examination and electrodiagnostic *** The duration of the patient’s follow-up period was 180 *** increasing Tinel’s sign and sensory-motor recovery were detected even at the 10th wk following nerve *** the conclusion of the 6-mo post-treatment period,an evaluation was conducted to measure the extent of improvement in motor and sensory functions of the *** assessment was based on the British Medical Research Council scale and the Mackinnon-Dellon *** results indicated that the level of improvement in motor function was classified as M5,denoting an excellent ***,the level of improvement in sensory function was classified as S3+,indicating a good *** is

关键词： Mesenchymal stem cell Exosomes Radial nerve Sural nerve

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The influence of resistance exercise training prescription variables on skeletal muscle mass,strength,and physical function in healthy adults:An umbrella review

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Journal of Sport and Health Science 2024年第1期13卷 47-60页

作者： Jonathan C.Mcleod brad S.Currier Caroline V.Lowisz Stuart M.Phillips Department of Kinesiology Faculty of ScienceMcMaster UniversityHamilton L8S4L8Canada

Purpose:The aim of this umbrella review was to determine the impact of resistance training(RT)and individual RT prescription variables on muscle mass,strength,and physical function in healthy ***:Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines,we systematically searched and screened eligible systematic reviews reporting the effects of differing RT prescription variables on muscle mass(or its proxies),strength,and/or physical function in healthy adults aged>18 ***:We identified 44 systematic reviews that met our inclusion *** methodological quality of these reviews was assessed using A Measurement Tool to Assess Systematic Reviews;standardized effectiveness statements were *** found that RT was consistently a potent stimulus for increasing skeletal muscle mass(4/4 reviews provide some or sufficient evidence),strength(4/6 reviews provided some or sufficient evidence),and physical function(1/1 review provided some evidence).RT load(6/8 reviews provided some or sufficient evidence),weekly frequency(2/4 reviews provided some or sufficient evidence),volume(3/7 reviews provided some or sufficient evidence),and exercise order(1/1 review provided some evidence)impacted RT-induced increases in muscular *** discovered that 2/3 reviews provided some or sufficient evidence that RT volume and contraction velocity influenced skeletal muscle mass,while 4/7 reviews provided insufficient evidence in favor of RT load impacting skeletal muscle *** was insufficient evidence to conclude that time of day,periodization,inter-set rest,set configuration,set end point,contraction velocity/time under tension,or exercise order(only pertaining to hypertrophy)influenced skeletal muscle adaptations.A paucity of data limited insights into the impact of RT prescription variables on physical ***:Overall,RT increased muscle mass,strength,and physical function compared to no ***

关键词： Hypertrophy Resistance training Resistance training prescription variables Strength Umbrella review

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Safety and efficiency of Wharton’s Jelly-derived mesenchymal stem cell administration in patients with traumatic brain injury:First results of a phase I study

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World Journal of Stem Cells 2024年第6期16卷 641-655页

作者： Serdar Kabatas ErdinçCivelek Osman Boyalı Gülseli Berivan Sezen Omer Ozdemir Yeliz Bahar-Ozdemir Necati Kaplan eyüp Can Savrunlu Erdal Karaöz Department of Neurosurgery University of Health Sciences TurkeyGaziosmanpaşa Training and Research HospitalIstanbul 34360Türkiye Center for Stem Cell&Gene Therapy Research and Practice University of Health Sciences TurkeyIstanbul 34255Türkiye Department of Neurosurgery University of Health SciencesGaziosmanpaşa Training and Research HospitalIstanbul 34255Türkiye Department of Physical Medicine and Rehabilitation Health Sciences University Sultan Abdulhamid Han Training and Research HospitalIstanbul 34668Türkiye Department of Neurosurgery Istanbul Rumeli UniversityÇorlu Reyap HospitalTekirdağ59860Türkiye Department of Neurosurgery Nevşehir State HospitalNevşehir 50300Türkiye Center for Regenerative Medicine and Stem Cell Research&Manufacturing(LivMedCell) Liv HospitalIstanbul 34340Türkiye Department of Histology and Embryology Istinye UniversityFaculty of MedicineIstanbul 34010Türkiye Center for Stem Cell and Tissue Engineering Research and Practice Istinye UniversityIstanbul 34340Türkiye

BACKGROUND Traumatic brain injury(TBI)is characterized by a disruption in the normal function of the brain due to an injury following a trauma,which can potentially cause severe physical,cognitive,and emotional *** cell transplantation has evolved as a novel treatment modality in the management of TBI,as it has the potential to arrest the degeneration and promote regeneration of new cells in the ***’s Jelly-derived mesenchymal stem cells(WJ-MSCs)have recently shown beneficial effects in the functional recovery of neurological *** To evaluate the safety and efficiency of MSC therapy in *** We present 6 patients,4 male and 2 female aged between 21 and 27 years who suffered a *** 6 patients underwent 6 doses of intrathecal,intramuscular(i.m.)and intravenous transplantation of WJ-MSCs at a target dose of 1×106/kg for each application *** was assessed using the Modified Ashworth scale(MAS),motor function according to the Medical Research Council Muscle Strength Scale,quality of life was assessed by the Functional Independence Measure(FIM)scale and Karnofsky Performance Status *** Our patients showed only early,transient complications,such as subfebrile fever,mild headache,and muscle pain due to ***,which resolved within 24 *** the one year follow-up,no other safety issues or adverse events were *** 6 patients showed improvements in their cognitive abilities,muscle spasticity,muscle strength,performance scores and fine motor skills when compared before and after the *** values,which we used to assess spasticity,were observed to statistically significantly decrease for both left and right sides(P<0.001).The FIM scale includes both motor scores(P<0.05)and cognitive scores(P<0.001)and showed a significant increase in pretest posttest *** difference observed in the participants’Karnofsky Performance Scale values pre and post the intervention was statistically si

关键词： Traumatic brain injury Wharton Jelly Stem cell therapy Transplantation Mesenchymal stem cell

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Telomeric DNA breaks in human induced pluripotent stem cells trigger ATR-mediated arrest and telomerase-independent telomere damage repair

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Journal of Molecular Cell Biology 2024年第3期16卷 46-60页

作者： Katrina N.Estep John W.Tobias Rafael J.Fernandez Brinley M.Beveridge F.brad Johnson Department of Pathology and Laboratory Medicine University of PennsylvaniaPhiladelphiaPA 19104USA Quantiative Biosciences Merck&Co.Inc.West PointPA 19486USA Penn Genomic Analysis Core University of PennsylvaniaPhiladelphiaPA 19104USA

Although mechanisms of telomere protection are well-defined in differentiated cells,how stem cells sense and respond to telomere dysfunction,in particular telomeric double-strand breaks(DSBs),is poorly ***,we report the DNA damage signaling,cell cycle,and transcriptome changes in human induced pluripotent stem cells(iPSCs)in response to telomere-internal *** engineer human iPSCs with an inducible TRF1-FokI fusion protein to acutely induce DSBs at *** this model,we demonstrate that TRF1-FokI DSBs activate an ATR-dependent DNA damage response,which leads to p53-independent cell cycle arrest in *** CRISPR–Cas9 to cripple the catalytic domain of telomerase reverse transcriptase,we show that telomerase is largely dispensable for survival and lengthening of TRF1-FokI-cleaved telomeres,which instead are effectively repaired by robust homologous recombination(HR).In contrast to HR-based telomere maintenance in mouse embryonic stem cells,where HR causes ZSCAN4-dependent extension of telomeres beyond their initial lengths,HR-based repair of telomeric breaks is sufficient to maintain iPSC telomeres at a normal length,which is compatible with sustained survival of the cells over several days of TRF1-FokI *** findings suggest a previously unappreciated role for HR in telomere maintenance in telomerase-positive iPSCs and reveal distinct iPSC-specific responses to targeted telomeric DNA damage.

关键词： telomeres telomerase alternative lengthening of telomeres pluripotent stem cells DNA damage double-strand breaks

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Allogeneic mesenchymal stem cells may be a viable treatment modality in cerebral palsy

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World Journal of Clinical Cases 2024年第9期12卷 1585-1596页

作者： Osman Boyalı Serdar Kabatas ErdinçCivelek Omer Ozdemir Yeliz Bahar-Ozdemir Necati Kaplan eyüp Can Savrunlu Erdal Karaöz Department of Neurosurgery University of Health Sciences TurkeyGaziosmanpaşa Training and Research HospitalIstanbul 34360Turkey Center for Stem Cell&Gene Therapy Research and Practice University of Health Sciences TurkeyIstanbul 34360Turkey Department of Physical Medicine and Rehabilitation Health Sciences University Sultan Abdulhamid Han Training and Research HospitalIstanbul 34668Turkey Department of Neurosurgery Istanbul Rumeli UniversityÇorlu Reyap HospitalTekirdağ59860Turkey Department of Neurosurgery Nevşehir State HospitalNevşehir 50300Turkey Center for Regenerative Medicine and Stem Cell Research&Manufacturing(LivMedCell) Liv HospitalIstanbul 34340Turkey Department of Histology and Embryology Istinye UniversityFaculty of Medicineİstanbul 34010Turkey Center for Stem Cell and Tissue Engineering Research and Practice Istinye UniversityIstanbul 34340Turkey

BACKGROUND Cerebral palsy(CP)describes a group of disorders affecting movement,balance,and *** in motor functions constitute the main body of CP *** symptoms surface in early childhood and patients are affected for the rest of their ***,treatment involves various pharmacotherapies for different types of CP,including antiepileptics for epilepsy and Botox A for focal ***,none of these methods can provide full symptom *** has prompted researchers to look for new treatment modalities,one of which is mesenchymal stem cell therapy(MSCT).Despite being a promising tool and offering a wide array of possibilities,mesenchymal stem cells(MSCs)still need to be investigated for their efficacy and *** To analyze the efficacy and safety of MSCT in CP *** Our sample consists of four CP patients who cannot stand or walk without external *** of these cases received allogeneic MSCT six times as 1×106/kg intrathecally,intravenously,and intramuscularly using umbilical cord-derived MSCs(UC-MSC).We monitored and assessed the patients pre-and post-treatment using the Wee Functional Independence Measure(WeeFIM),Gross Motor Function Classification System(GMFCS),and Manual Ability Classification Scale(MACS)*** utilized the Modified Ashworth Scale(MAS)to measure *** We found significant improvements in MAS scores after the intervention on both *** months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=0.046;four months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=0.046;12 months:Rightχ^(2)=4000,P=0.046,leftχ^(2)=4000,P=***,there was no significant difference in motor functions based on WeeFIM results(P>0.05).GMFCS and MACS scores differed significantly at 12 months after the intervention(P=0.046,P=0.046).Finally,there was no significant change in cognitive functions(P>0.05).CONCLUSION In light of our findings,we believe that UC-MSC therapy has a positive effect on spasticity

关键词： Cerebral palsy Mesenchymal stem cell Transplantation Wharton’s jelly Muscle spasticity

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Multi-aspect analysis of ureteral access sheath usage in retrograde intrarenal surgery: A RIRSearch group study

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Asian Journal of Urology 2024年第1期11卷 80-85页

作者： Oktay Özman Hacı M.Akgül Cem Başataç Önder Çınar eyüp B.Sancak Cenk M.Yazıcı Bülent Önal Haluk Akpınar Gaziosmanpasa Training and Research Hospital Urology ClinicİstanbulTurkey TekirdağNamık Kemal University School of MedicineDepartment of UrologyTekirdağTurkey Group Florence Nightingale Hospitals Department of UrologyİstanbulTurkey Zonguldak Bulent Ecevit University School of MedicineDepartment of UrologyZonguldakTurkey Çanakkale Onsekiz Mart University School of MedicineDepartment of UrologyÇanakkaleTurkey İstanbul University-Cerrahpaşa Cerrahpaşa Medical FacultyDepartment of UrologyİstanbulTurkey

Objective:To evaluate the effect of ureteral access sheath(UAS)use and calibration change on stone-free rate and complications of retrograde intrarenal surgery(RIRS).Methods:Data from 568 patients undergoing RIRS for kidney or upper ureteral stones were retrospectively ***,patients were compared after 1:1 propensity score matching,according to UAS usage during RIRS(UAS used[+]87 and UAS non-used[−]87 patients).Then all UAS+patients(n=481)were subdivided according to UAS calibration:9.5-11.5 Fr,10-12 Fr,11-13 Fr,and 13-15 *** outcomes of the study were the success and complications of ***:Stone-free rate of UAS+patients(86.2%)was significantly higher than UAS−patients(70.1%)after propensity score matching(p=0.01).Stone-free rate increased with higher caliber UAS(9.5-11.5 Fr:66.7%;10-12 Fr:87.0%;11-13 Fr:90.6%;13-15 Fr:100%;p<0.001).Postoperative complications of UAS+patients(11.5%)were significantly lower than UAS−patients(27.6%)(p=0.01).Complications(8.7%)with 9.5-11.5 Fr UAS was lower than thicker UAS(17.2%)but was not statistically significant(p=0.09).UAS usage was an independent factor predicting stone-free status or peri-and post-operative complications(odds ratio[OR]3.654,95%confidence interval[CI]1.314-10.162;OR 4.443,95%CI 1.350-14.552;OR 4.107,95%CI 1.366-12.344,respectively).Conclusion:Use of UAS in RIRS may increase stone-free rates,which also increase with higher caliber *** usage may reduce complications;however,complications seemingly increase with higher UAS calibration.

关键词： Stone Retrograde intrarenal surgery Ureteral access sheath Urolithiasis Kidney

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Item-Level Analysis of the Revised Occupational Therapy Fieldwork Performance Evaluation Applied in Practice

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Open Journal of Therapy and Rehabilitation 2024年第2期12卷 145-159页

作者： Cynthia L. Sears brad E. Egan Patricia F. Tomsic Craig A. Velozo Graduate College of Health Professions Occupational Therapy Program Hawai&#8217i Pacific University Honolulu HI USA College of Science and Health Occupational Therapy Program DePaul University Chicago IL USA Department of Occupational Therapy Wingate University Wingate NC USA College of Health Professions Department of Rehabilitation Sciences Division of Occupational Therapy Medical University of South Carolina Charleston SC USA

Competency-based assessments for healthcare professionals are critical for safe and effective client outcomes. Rehabilitation clinical skill competency assessments must be validated and revised to produce safe and skilled practitioners. The revised American Occupational Therapy Association (AOTA) Fieldwork Performance Evaluation (FWPE) instrument measures occupational therapy student performance to determine readiness for practice. The assessment includes thirty-seven competencies that address both profession specific clinical skills and general professional behavior skills. The objective of this study was to use Rasch methods to explore the use of the revised FWPE in actual fieldwork practice and to determine the instrument’s psychometric properties when separating the item components into two distinct subdomains: General Health Professions Competences and Occupational Therapy-Specific Competencies. Internal construct validity and test reliability were analyzed using data from 149 occupational therapy students after completing their initial Level II A fieldwork clinical internship. This study examined the item difficulty hierarchy, item fit, person-fit to model, person separation index, person separation reliability coefficient, strata, ceiling and floor effect, and unidimensionality of the FWPE instrument as a whole and as two separate domains. With the exception of not meeting the criteria for unidimensionality, the full FWPE instrument and the Occupational Therapy-Specific Competencies subdomain showed acceptable item-level psychometrics for reliability and precision. While the General Health Professions Competencies subdomain showed good item-level psychometrics, it was below the criterion for reliability and only separated the sample into two strata. Results support the validity, reliability, and clinical use of the revised FWPE full instrument and the Occupational Therapy-Specific Competencies subdomain to measure entry-level clinical skill competencies in pr

关键词： Rehabilitation Competency-Based Assessments Occupational Therapy Measurement Rasch Analysis

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美国富豪对特朗普热情高涨

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商业周刊（中文版） 2024年第6期 4-5页

作者： brad Stone 易语(译) 不详

乔·拜登(Joe Biden)与唐纳德·特朗普(Donald Trump)在2024年美国总统大选中的再度对决,给人的感觉或许是早该退休的两个老家伙之间以自由世界未来为赌注的一场令人乏味的复赛。不过这一次,有些东西感觉有点不一样,而且很难解释。特朗... 详细信息

乔·拜登(Joe Biden)与唐纳德·特朗普(Donald Trump)在2024年美国总统大选中的再度对决,给人的感觉或许是早该退休的两个老家伙之间以自由世界未来为赌注的一场令人乏味的复赛。不过这一次,有些东西感觉有点不一样,而且很难解释。特朗普最明显的支持者不再是来自红州那些戴着印有MAGA标识的帽子、在集会上挥舞着“抽干沼泽”标语的愤怒蓝领工人,反倒变成了国内一些最成功的商界精英,他们不断在网上发帖表达心中的不满,大力秤击移民问题和乌克兰战争,并不断对拜登的表现和老迈提出质疑。

关键词：美国总统大选特朗普商界精英乌克兰提出质疑

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成功传承之路

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商业周刊（中文版） 2024年第12期 4-5页

作者： brad Stone 易语(译) 不详

最近的研究显示,家族控股不但在上市公司中司空见惯,也具有一定的优势雅各布·萨皮尔斯坦(Jacob Sapirstein)是波兰瓦索什(Wasosz)一位拉比的儿子,他于1905年移民到美国,辗转芝加哥最终在克利夫兰落下了脚。他投奔亲戚找到了一份工作,... 详细信息

最近的研究显示,家族控股不但在上市公司中司空见惯,也具有一定的优势雅各布·萨皮尔斯坦(Jacob Sapirstein)是波兰瓦索什(Wasosz)一位拉比的儿子,他于1905年移民到美国,辗转芝加哥最终在克利夫兰落下了脚。他投奔亲戚找到了一份工作,在市中心一家酒店的大堂里卖明信片,后来靠着50美元银行贷款开始自己创业,驾着一辆马车向糖果店、新奇物品商店和药店兜售从德国进口的精美明信片。

关键词：银行贷款拉比上市公司克利夫兰德国进口明信片雅各布萨皮尔

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