Brain-derived neurotrophic factor signaling via its receptor tro pomyosin receptor kinase B regulates several crucial physiological processes.It has been shown to act in the brain,promoting neuronal survival,growth,an...Brain-derived neurotrophic factor signaling via its receptor tro pomyosin receptor kinase B regulates several crucial physiological processes.It has been shown to act in the brain,promoting neuronal survival,growth,and plasticity as well as in the rest of the body where it is involved in regulating for instance aspects of the metabolism.Due to its crucial and very pleiotro pic activity,reduction of brain-derived neurotrophic factor levels and alterations in the brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling have been found to be associated with a wide spectrum of neurological diseases.Howeve r,because of its poor bioavailability and pharmacological properties,brain-derived neurotrophic factor itself has a very low therapeutic value.Moreover,the concomitant binding of exogenous brain-derived neurotrophic factor to the p75 neurotrophin receptor has the potential to elicit several unwanted and deleterious side effects.Therefo re,developing tools and approaches to specifically promote tropomyosin receptor kinase B signaling has become an important goal of translational research.Among the newly developed tools are different categories of tropomyosin receptor kinase B receptor agonist molecules.In this review,we give a comprehensive description of the diffe rent tro pomyosin receptor kinase B receptor agonist drugs developed so far and of the res ults of their application in animal models of several neurological diseases.Moreover,we discuss the main benefits of tropomyosin receptor kinase B receptor agonists,concentrating especially on the new tropomyosin receptor kinase B agonist antibodies.The benefits observed both in vitro and in vivo upon application of tropomyosin receptor kinase B receptor agonist drugs seem to predominantly depend on their general neuroprotective activity and their ability to promote neuronal plasticity.Moreover,tro pomyosin receptor kinase B agonist antibodies have been shown to specifically bind the tropomyosin receptor kinase B receptor and not p75 neurotrophin receptor.Therefore,while,based on the current knowledge,the tropomyosin receptor kinase B receptor agonists do not seem to have the potential to reve rse the disease pathology per se,promoting brainderived neurotrophic factor/tro pomyosin receptor kinase B signaling still has a very high therapeutic relevance.展开更多
During the last decade,the rapid development of lithium-ion battery(LIB)energy storage systems has provided significant support for the efficient operation of renewable energy stations.In the coming years,the service ...During the last decade,the rapid development of lithium-ion battery(LIB)energy storage systems has provided significant support for the efficient operation of renewable energy stations.In the coming years,the service life demand of energy storage systems will be further increased to 30 years from the current 20 years on the basis of the equivalent service life of renewable energy stations.However,the life of the present LIB is far from meeting such high demand.Therefore,research on the next-generation LIB with ultra-long service life is imminent.Prelithiation technology has been widely studied as an important means to compensate for the initial coulombic efficiency loss and improve the service life of LIBs.This review systematically summarized the different prelithiation methods from anode and cathode electrodes.Moreover,the large-scale industrialization challenge and the possibility of the existing prelithiation technology are analyzed,based on three key parameters:industry compatibility,prelithiation efficiency,and energy density.Finally,the future trends of improvement in LIB performance by other overlithiated cathode materials are presented,which gives a reference for subsequent research.展开更多
Stroke is a leading cause of adult motor disability. Despite recent progress, recovery of motor function after stroke is usually incomplete. This double blind , Sham-controlled, crossover study was designed to test th...Stroke is a leading cause of adult motor disability. Despite recent progress, recovery of motor function after stroke is usually incomplete. This double blind , Sham-controlled, crossover study was designed to test the hypothesis that non -invasive stimulation of the motor cortex could improve motor function in the p aretic hand of patients with chronic stroke. Hand function was measured using th e Jebsen-Taylor Hand Function Test (JTT),a widely used, well validated test for functional motor assessment that reflects activities of daily living. JTT measu red in the paretic hand improved significantly with non-invasive transcranial direct current stimulat ion (tDCS), but not with Sham, an effect that outlasted the stimulation period, was present in every single patient tested and that correlated with an increment in motor cortical excitability within the affected hemisphe- re, expressed as increased recruitment curves(RC) and reduced short-interval intracortical inhibition. These results document a beneficial effect of non-inv asive cortical stimulation on a set of hand functions that mimic activities of d aily living in the paretic hand of patients with chronic stroke, and suggest tha t this interventional strategy in combination with customary rehabilitative trea tments may play an adjuvant role in neurorehabilitation.展开更多
Objective: To study the safety and efficacy of a cholinesterase inhibitor, do nepezil hydrochloride, for the treatment of dementia in Parkinson’ s disease (P D). Methods: This was a randomised double blind, placebo c...Objective: To study the safety and efficacy of a cholinesterase inhibitor, do nepezil hydrochloride, for the treatment of dementia in Parkinson’ s disease (P D). Methods: This was a randomised double blind, placebo controlled, crossover s tudy in 22 subjects with PD and dementia. Participants were randomised to receiv e either donepezil followed by identical placebo, or placebo followed by donepezil. Do nepezil was administered at 5- 10 mg/day. Treatment periods were 10 weeks with a washout period of 6 weeks between the two periods. The primary outcome measure was the Alzheimer’ s Disease Assessment Scale Cognitive Subscale (ADAScog). Re sults: Donepezil was well tolerated and most adverse events were mild. There was no worsening of PD symptoms as measured by the total or motor sections of the U nified Parkinson’ s Disease Rating Scale. There was a 1.9 point trend toward be tter scores on the ADAScog on treatment compared with placebo that was not stati stically significant. The secondary cognitive measures showed a statistically si gnificant 2 point benefit on the Mini Mental Status Examination and no change on the Mattis Dementia Rating Scale (MDRS). The Clinical Global Impression of Chan ge (CGI) showed a significant 0.37 point improvement on donepezil. No improvemen t was observed on the MDRS or the Brief Psychiatric Rating Scale. Carryover betw een treatment periods was observed but was not statistically significant. Conclu sions: Donepezil was well tolerated and did not worsen PD. There may be a modest benefit on aspects of cognitive function. The possible clinical benefit measure d by CGI was reflected in only one of the cognitive scales used in this study.展开更多
Bax, a pro-apoptotic member of the Bcl-2 family, changes intracellular location as it accelerates cell death. Bax consists of 9 α-helices where the assembly of helices α1-α8 resembles that of the anti-apoptotic pro...Bax, a pro-apoptotic member of the Bcl-2 family, changes intracellular location as it accelerates cell death. Bax consists of 9 α-helices where the assembly of helices α1-α8 resembles that of the anti-apoptotic protein, Bcl-xL. The opposite biological functions between Bcl-xL and Bax stem from relatively minor differences in their structures. The C-terminal α helix, that functions in mitochondrial membrane targeting, sits in the hydrophobic BH3 binding pocket proposed previously to mediate heterodimer formation among Bcl-2 family members. The structure of soluble Bax shows that the conformation of the C-terminal helix may simultaneously inhibit BH3 peptide binding associated with dimer formation and mitochondrial展开更多
As Dr.hsiang-Tung Chang approached his late 80s,he began the task of sorting and compiling all of his scientific writings into volumes.He later acknowledged that he was initially ambivalent about the idea when colleag...As Dr.hsiang-Tung Chang approached his late 80s,he began the task of sorting and compiling all of his scientific writings into volumes.He later acknowledged that he was initially ambivalent about the idea when colleagues first suggested it to him,but quickly came to believe that the effort should be seen as beyond his own personal interest and significance,and that the archives would be of good value from both the scientific and展开更多
We present results of real-time and sensitive MR Thermometry (MRT) using a paramagnetic lanthanide complex thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethyl-1,4,7,10-tetraa-cetate (Tm-DOTMA) to study radio f...We present results of real-time and sensitive MR Thermometry (MRT) using a paramagnetic lanthanide complex thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethyl-1,4,7,10-tetraa-cetate (Tm-DOTMA) to study radio frequency (RF) heating induced by a copper wire and a titanium bone screw in an agarose gel phantom. The temperature dependent chemical shift coefficient (TDCSC) of the methyl resonance was found to be 0.7 ± 0.03 ppm/°;C in agarose gel. The methyl protons of Tm-DOTMA were imaged using 2D chemical shift imaging (CSI) and 3D phase mapping methods (PMM), approximately 7 sec long, and compared with conventional water proton resonance frequency (PRF) method. Two RF-induced heating approaches were tested: 1) using a prescan before the MRT;or 2) using the heating caused by the imaging pulse during continuous imaging. Both approaches allowed detection of temperature changes which are less than 1°;C and continuously mapping temperature changes around the copper wire. Using a heating pre-scan, the Tm-DOTMA 2D-CSI allowed better qualitative visualization of the temperature changes around the titanium screw compared with water phase shift thermometry. Numerical electromagnetic field simulations were also conducted for the evaluation of orientation dependency using the copper wire in 4.7 T (200 MHz). Thermometry approach using Tm-DOTMA can detect smaller temperature changes with decreased scanning time resulting in real-time and sensitive temperature mapping.展开更多
Recently there have been exciting research advances in neuroprotective therapies for ischemic stroke. In the past, the search for neu- roprotective agents has been fraught with failure at the clinical trials stage due...Recently there have been exciting research advances in neuroprotective therapies for ischemic stroke. In the past, the search for neu- roprotective agents has been fraught with failure at the clinical trials stage due to numerous factors, including subject heterogeneity and improper therapeutic windows (Tymianski, 2017). Moreover, it is becoming clearer that the complex and evolving pathobiology of stroke requires multimodal therapeutic approaches capable of modulating the numerous axes that contribute to ischemia/reperfusion damage, rather than targeting a single axis (Bernstock et al., 2018a). With the success of recent endovascular thrombectomy (EVT) trials, it has been suggested that clinical trials of EVT with adjunct neuroprotection can overcome past difficulties and maximize the effect size by using imaging to reduce patient heterogeneity (i. e., selecting those with large vessel occlusions, small ischemic cores, and good collateral circulation), restoring perfusion using better EVT devices, and enrolling patients in the correct therapeutic window (i.e., when they still have salvageable brain tissue) (Tymianski, 2017). Considering the opportunity that this represents for new, better clinical trials of neuroprotective agents, the search is on for high-potential compounds that may be investigated in these future studies.展开更多
We report two siblings who presented with non- progressive marked sensory ataxia associated with arthrogryposis multiplex congenita (AMC). Deep tendon reflexes and H reflex were completely absent, but F waves were pre...We report two siblings who presented with non- progressive marked sensory ataxia associated with arthrogryposis multiplex congenita (AMC). Deep tendon reflexes and H reflex were completely absent, but F waves were preserved. The sensory nerve conduction studies indicated the presence of relatively mild sensory polyneuropathy. The conventional somatosensory evoked potentials (SEPs) showed mildly prolonged latency for both the peripheral and cortical responses, suggesting a slowed conduction through the peripheral as well as central pathway. However, the ‘ proprioceptive SEPs’ were absent, in conformity with complete loss of joint sense. Sural nerve biopsy revealed only mild thinning of myelin in the younger sister but was entirely normal in her brother. Taken together with the characteristic electrophysiological findings, the symptoms were considered to be due to predominant involvement of a selective population of somatosensory ganglions. The present cases showed no progression of the neurological deficit what- so- ever since birth, which strongly suggests a developmental anomaly or aplasia of a limited population of peripheral sensory neurons.展开更多
Background: Whereas recent data from imaging studies challenge the prevailing notion that multiple sclerosis (MS) is purely an inflammatory disease, pathologic studies suggest differences in the disease processes betw...Background: Whereas recent data from imaging studies challenge the prevailing notion that multiple sclerosis (MS) is purely an inflammatory disease, pathologic studies suggest differences in the disease processes between individual patients with MS. The ability to dissect the pathophysiologic disease heterogeneity, if it indeed exists, by methodologies that can be applied in vivo is important both for the development of new therapeutics and for the ability to identify the optimal therapy for an individual patient. Objective: To design a stratification algorithm for patients with MS based on accepted MRI measurements reflective of inflammation and axonal damage/tissue loss and to assess if such MS subgroups retain their intergroup differences long term. Methods: Mathematical modeling was used to select three discriminatory MRI measures for clinical outcome based on the cross-sectional analysis of 71 patients with untreated MS and tested general applicability of the stratification scheme on the independent longitudinal cohort of 71 MS patients. Results: By consecutive employment of MRI measures reflect ive of inflammation and tissue loss, the authors were able to separate MS patients into four clinically meaningful subgroups. The analysis of the longitudinal confirmatory cohort demonstrated persistence of the intergroup differences in sel ected MRI measures for 8 years. Conclusions: The inflammatory activity and destr uctiveness of the multiple sclerosis process are to some degree independent of each other, and the successive evaluation of both of these variables can strengthen prediction of clinical outcome in individual patients.展开更多
Background:The cardinal features of Parkinson’s disease(PD)are bradykinesia,rigidity and rest tremor.Abnormal activity in the basal ganglia is predicted to underlie the mechanism of motor symptoms.This study aims to ...Background:The cardinal features of Parkinson’s disease(PD)are bradykinesia,rigidity and rest tremor.Abnormal activity in the basal ganglia is predicted to underlie the mechanism of motor symptoms.This study aims to characterize properties of oscillatory activity in the basal ganglia and motor thalamus in patients with PD.Methods:Twenty-nine patients with PD who underwent bilateral or unilateral electrode implantation for subthalamic nucleus(STN)DBS(n=11),unilateral pallidotomy(n=9)and unilateral thalamotomy(n=9)were studied.Microelectrode recordings in the STN,globus pallidus internus(GPi)and ventral oral posterior/ventral intermediate of thalamus(Vop/Vim)were performed.Electromyography of the contralateral limbs was recorded.Single unit characteristics including interspike intervals were analyzed.Spectral and coherence analyses were assessed.Mean spontaneous firing rate(MSFR)of neurons was calculated.Analysis of variance and χ^(2) test were performed.Results:Of 76 STN neurons,39.5% were 4–6 Hz band oscillatory neurons and 28.9% were β frequency band(βFB)oscillatory neurons.The MSFR was 44.2±7.6 Hz.Of 62 GPi neurons,37.1% were 4–6 Hz band oscillatory neurons and 27.4% were βFB neurons.The MSFR was 80.9±9.6 Hz.Of 44 Vop neurons,65.9% were 4–6 Hz band oscillatory neurons and 9%were βFB neurons.The MSFR was 24.4±4.2 Hz.Of 30 Vim oscillatory neurons,70% were 4–6 Hz band oscillatory neurons and 13.3% were β FB neurons.The MSFR was 30.3±3.6 Hz.Further analysis indicated that proportion of βFB oscillatory neurons in STN and GPi was higher than that of similar neurons in the Vop and Vim(P<0.05).Conversely,the proportion of 4–6 Hz band oscillatory neurons and tremor related neurons in the Vim and Vop was higher than that of STN and GPi(P<0.05).The highest MSFR was for GPi oscillatory neurons whereas the lowest MSFR was for Vop oscillatory neurons(P<0.005).Conclusion:The alterations in neuronal activity in basal ganglia play a critical role in generation of parkinsonism.β oscillatory activity is more prominent in basal ganglia than in thalamus suggesting that the activity likely results from dopaminergic depletion.While both basal ganglia and thalamus have tremor activity,the thalamus appears to play a more important role in tremor production,and basal ganglia β oscillatory activity might be the trigger.展开更多
Te content of the rectifed motor evoked potential(MEP)induced by transcranial magnetic stimulation(TMS)has ambiguously been assessed without the precision that energy calculation deserves.Tis fact has misled data inte...Te content of the rectifed motor evoked potential(MEP)induced by transcranial magnetic stimulation(TMS)has ambiguously been assessed without the precision that energy calculation deserves.Tis fact has misled data interpretation and misguided biomedical interventions.To defnitively fll the gap that exits in the neurophysics processing of these signals,we computed,in Walls(̂�),the bioenergy within the rectifed MEP recorded from the human frst digitorum index(FDI)muscle at rest and under isometric contraction.We also gauged the biowork exerted by this muscle.Here we show that bioenergy and biowork can accurately and successfully be assessed,validated,and determined in̂�from MEP signals induced by TMS,regardless of knowing the mathematical expression of the function of the signal.Our novel neurophysics approach represents a dramatic paradigm shif in analysis and interpretation of the content of the MEP and will give a true meaning to the content of rectifed signals.Importantly,this innovative approach allowed unveiling that women exerted more bioenergy than men at the magnetic stimulations used in this study.Revisitation of conclusions drawn from studies published elsewhere assessing rectifed EMG signals that have used ambiguous units is strongly recommended.展开更多
背景和目的2015年10月5日至6日在美国华盛顿特区召开的第4届卒中治疗专业学术圆桌会议(Stroke Treatment Academy Industry Roundtable,STAIR)期间,卒中影像学研究(Stroke Imaging Research Group,STIR)组、卒中网络影像学工作组、美国...背景和目的2015年10月5日至6日在美国华盛顿特区召开的第4届卒中治疗专业学术圆桌会议(Stroke Treatment Academy Industry Roundtable,STAIR)期间,卒中影像学研究(Stroke Imaging Research Group,STIR)组、卒中网络影像学工作组、美国神经放射学学会和美国神经放射学学会基金会共同举办了一次影像学会议和研讨会。本路径图的目的是关注影像学在将来的研究和临床试验中的作用。方法此次会议将卒中神经病学专家、神经放射学专家、神经影像学研究人员、美国国立神经疾病与卒中研究所(National Institute of Neuro Wlgical Dworders and Stroke,NINDS)成员、企业代表以及美国食品药品管理局(Food and Drug Administramion,)成员汇聚一堂,根据前所未有的一系列急性卒中血管内治疗临床试验的阳性结果来探讨将来STIR的重点。结果此次影像学会议对影像学在近期阳性血管内治疗试验中的作用进行了总结和比较,并且提出了汇总分析的可能。此次影像学研讨会对多重影像学模式中采集和分析缺血核心、半暗带不匹配以及侧支循环的最佳成像方法制定出共识推荐,并且提出了在前瞻性临床试验中测量最终梗死灶体积的标准化方法。结论近期的阳性急性卒中血管内治疗临床试验证明了神经血管成像的额外价值。血管内治疗的最佳影像学特征包括大血管闭塞、梗死核心较小、侧支循环良好和半暗带较大。然而,可能需要利用来自近期阳性血管内治疗试验的汇总数据对这些影像学特征参数在不同成像模式之间进行等效定义以及做出标准化尝试。展开更多
Type 1 regulatory T cells(CD4^(+)Foxp3^(−)LAG3^(+)CD49b^(+)),or Tr1 cells,have a remarkable capacity to suppress autoimmune inflamma tion through IL-10.1 Although the signals that lead to Tr1-cell differentiation are ...Type 1 regulatory T cells(CD4^(+)Foxp3^(−)LAG3^(+)CD49b^(+)),or Tr1 cells,have a remarkable capacity to suppress autoimmune inflamma tion through IL-10.1 Although the signals that lead to Tr1-cell differentiation are not completely elucidated,it is known that IL 27 plays a major role in this phenomenon.展开更多
A study published in Nature Neuroscience indicates that autophagy dysfunction in neurons precedes the formation of amyloid plaques.1 These findings ask for a reconsideration of the conventionally accepted sequence of ...A study published in Nature Neuroscience indicates that autophagy dysfunction in neurons precedes the formation of amyloid plaques.1 These findings ask for a reconsideration of the conventionally accepted sequence of events in plaque formation in Alzheimer’s disease.展开更多
文摘Brain-derived neurotrophic factor signaling via its receptor tro pomyosin receptor kinase B regulates several crucial physiological processes.It has been shown to act in the brain,promoting neuronal survival,growth,and plasticity as well as in the rest of the body where it is involved in regulating for instance aspects of the metabolism.Due to its crucial and very pleiotro pic activity,reduction of brain-derived neurotrophic factor levels and alterations in the brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling have been found to be associated with a wide spectrum of neurological diseases.Howeve r,because of its poor bioavailability and pharmacological properties,brain-derived neurotrophic factor itself has a very low therapeutic value.Moreover,the concomitant binding of exogenous brain-derived neurotrophic factor to the p75 neurotrophin receptor has the potential to elicit several unwanted and deleterious side effects.Therefo re,developing tools and approaches to specifically promote tropomyosin receptor kinase B signaling has become an important goal of translational research.Among the newly developed tools are different categories of tropomyosin receptor kinase B receptor agonist molecules.In this review,we give a comprehensive description of the diffe rent tro pomyosin receptor kinase B receptor agonist drugs developed so far and of the res ults of their application in animal models of several neurological diseases.Moreover,we discuss the main benefits of tropomyosin receptor kinase B receptor agonists,concentrating especially on the new tropomyosin receptor kinase B agonist antibodies.The benefits observed both in vitro and in vivo upon application of tropomyosin receptor kinase B receptor agonist drugs seem to predominantly depend on their general neuroprotective activity and their ability to promote neuronal plasticity.Moreover,tro pomyosin receptor kinase B agonist antibodies have been shown to specifically bind the tropomyosin receptor kinase B receptor and not p75 neurotrophin receptor.Therefore,while,based on the current knowledge,the tropomyosin receptor kinase B receptor agonists do not seem to have the potential to reve rse the disease pathology per se,promoting brainderived neurotrophic factor/tro pomyosin receptor kinase B signaling still has a very high therapeutic relevance.
基金funded by the National Natural Science Foundation of China(No.U21A20170(X.He))the Ministry of Science and Technology of China(No.2019YFE0100200(X.He)and 2019YFA0705703(L.Wang))the Tsinghua University Initiative Scientific Research Program(No.2019Z02UTY06(X.He)and 2019THFS0132(L.Wang)).The authors also thank Joint Work Plan for Research Projects under the Clean Vehicles Consortium at U.S.and China-Clean Energy Research Center(CERC-CVC2.0,2016-2020)
文摘During the last decade,the rapid development of lithium-ion battery(LIB)energy storage systems has provided significant support for the efficient operation of renewable energy stations.In the coming years,the service life demand of energy storage systems will be further increased to 30 years from the current 20 years on the basis of the equivalent service life of renewable energy stations.However,the life of the present LIB is far from meeting such high demand.Therefore,research on the next-generation LIB with ultra-long service life is imminent.Prelithiation technology has been widely studied as an important means to compensate for the initial coulombic efficiency loss and improve the service life of LIBs.This review systematically summarized the different prelithiation methods from anode and cathode electrodes.Moreover,the large-scale industrialization challenge and the possibility of the existing prelithiation technology are analyzed,based on three key parameters:industry compatibility,prelithiation efficiency,and energy density.Finally,the future trends of improvement in LIB performance by other overlithiated cathode materials are presented,which gives a reference for subsequent research.
文摘Stroke is a leading cause of adult motor disability. Despite recent progress, recovery of motor function after stroke is usually incomplete. This double blind , Sham-controlled, crossover study was designed to test the hypothesis that non -invasive stimulation of the motor cortex could improve motor function in the p aretic hand of patients with chronic stroke. Hand function was measured using th e Jebsen-Taylor Hand Function Test (JTT),a widely used, well validated test for functional motor assessment that reflects activities of daily living. JTT measu red in the paretic hand improved significantly with non-invasive transcranial direct current stimulat ion (tDCS), but not with Sham, an effect that outlasted the stimulation period, was present in every single patient tested and that correlated with an increment in motor cortical excitability within the affected hemisphe- re, expressed as increased recruitment curves(RC) and reduced short-interval intracortical inhibition. These results document a beneficial effect of non-inv asive cortical stimulation on a set of hand functions that mimic activities of d aily living in the paretic hand of patients with chronic stroke, and suggest tha t this interventional strategy in combination with customary rehabilitative trea tments may play an adjuvant role in neurorehabilitation.
文摘Objective: To study the safety and efficacy of a cholinesterase inhibitor, do nepezil hydrochloride, for the treatment of dementia in Parkinson’ s disease (P D). Methods: This was a randomised double blind, placebo controlled, crossover s tudy in 22 subjects with PD and dementia. Participants were randomised to receiv e either donepezil followed by identical placebo, or placebo followed by donepezil. Do nepezil was administered at 5- 10 mg/day. Treatment periods were 10 weeks with a washout period of 6 weeks between the two periods. The primary outcome measure was the Alzheimer’ s Disease Assessment Scale Cognitive Subscale (ADAScog). Re sults: Donepezil was well tolerated and most adverse events were mild. There was no worsening of PD symptoms as measured by the total or motor sections of the U nified Parkinson’ s Disease Rating Scale. There was a 1.9 point trend toward be tter scores on the ADAScog on treatment compared with placebo that was not stati stically significant. The secondary cognitive measures showed a statistically si gnificant 2 point benefit on the Mini Mental Status Examination and no change on the Mattis Dementia Rating Scale (MDRS). The Clinical Global Impression of Chan ge (CGI) showed a significant 0.37 point improvement on donepezil. No improvemen t was observed on the MDRS or the Brief Psychiatric Rating Scale. Carryover betw een treatment periods was observed but was not statistically significant. Conclu sions: Donepezil was well tolerated and did not worsen PD. There may be a modest benefit on aspects of cognitive function. The possible clinical benefit measure d by CGI was reflected in only one of the cognitive scales used in this study.
文摘Bax, a pro-apoptotic member of the Bcl-2 family, changes intracellular location as it accelerates cell death. Bax consists of 9 α-helices where the assembly of helices α1-α8 resembles that of the anti-apoptotic protein, Bcl-xL. The opposite biological functions between Bcl-xL and Bax stem from relatively minor differences in their structures. The C-terminal α helix, that functions in mitochondrial membrane targeting, sits in the hydrophobic BH3 binding pocket proposed previously to mediate heterodimer formation among Bcl-2 family members. The structure of soluble Bax shows that the conformation of the C-terminal helix may simultaneously inhibit BH3 peptide binding associated with dimer formation and mitochondrial
文摘As Dr.hsiang-Tung Chang approached his late 80s,he began the task of sorting and compiling all of his scientific writings into volumes.He later acknowledged that he was initially ambivalent about the idea when colleagues first suggested it to him,but quickly came to believe that the effort should be seen as beyond his own personal interest and significance,and that the archives would be of good value from both the scientific and
文摘We present results of real-time and sensitive MR Thermometry (MRT) using a paramagnetic lanthanide complex thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethyl-1,4,7,10-tetraa-cetate (Tm-DOTMA) to study radio frequency (RF) heating induced by a copper wire and a titanium bone screw in an agarose gel phantom. The temperature dependent chemical shift coefficient (TDCSC) of the methyl resonance was found to be 0.7 ± 0.03 ppm/°;C in agarose gel. The methyl protons of Tm-DOTMA were imaged using 2D chemical shift imaging (CSI) and 3D phase mapping methods (PMM), approximately 7 sec long, and compared with conventional water proton resonance frequency (PRF) method. Two RF-induced heating approaches were tested: 1) using a prescan before the MRT;or 2) using the heating caused by the imaging pulse during continuous imaging. Both approaches allowed detection of temperature changes which are less than 1°;C and continuously mapping temperature changes around the copper wire. Using a heating pre-scan, the Tm-DOTMA 2D-CSI allowed better qualitative visualization of the temperature changes around the titanium screw compared with water phase shift thermometry. Numerical electromagnetic field simulations were also conducted for the evaluation of orientation dependency using the copper wire in 4.7 T (200 MHz). Thermometry approach using Tm-DOTMA can detect smaller temperature changes with decreased scanning time resulting in real-time and sensitive temperature mapping.
文摘Recently there have been exciting research advances in neuroprotective therapies for ischemic stroke. In the past, the search for neu- roprotective agents has been fraught with failure at the clinical trials stage due to numerous factors, including subject heterogeneity and improper therapeutic windows (Tymianski, 2017). Moreover, it is becoming clearer that the complex and evolving pathobiology of stroke requires multimodal therapeutic approaches capable of modulating the numerous axes that contribute to ischemia/reperfusion damage, rather than targeting a single axis (Bernstock et al., 2018a). With the success of recent endovascular thrombectomy (EVT) trials, it has been suggested that clinical trials of EVT with adjunct neuroprotection can overcome past difficulties and maximize the effect size by using imaging to reduce patient heterogeneity (i. e., selecting those with large vessel occlusions, small ischemic cores, and good collateral circulation), restoring perfusion using better EVT devices, and enrolling patients in the correct therapeutic window (i.e., when they still have salvageable brain tissue) (Tymianski, 2017). Considering the opportunity that this represents for new, better clinical trials of neuroprotective agents, the search is on for high-potential compounds that may be investigated in these future studies.
文摘We report two siblings who presented with non- progressive marked sensory ataxia associated with arthrogryposis multiplex congenita (AMC). Deep tendon reflexes and H reflex were completely absent, but F waves were preserved. The sensory nerve conduction studies indicated the presence of relatively mild sensory polyneuropathy. The conventional somatosensory evoked potentials (SEPs) showed mildly prolonged latency for both the peripheral and cortical responses, suggesting a slowed conduction through the peripheral as well as central pathway. However, the ‘ proprioceptive SEPs’ were absent, in conformity with complete loss of joint sense. Sural nerve biopsy revealed only mild thinning of myelin in the younger sister but was entirely normal in her brother. Taken together with the characteristic electrophysiological findings, the symptoms were considered to be due to predominant involvement of a selective population of somatosensory ganglions. The present cases showed no progression of the neurological deficit what- so- ever since birth, which strongly suggests a developmental anomaly or aplasia of a limited population of peripheral sensory neurons.
文摘Background: Whereas recent data from imaging studies challenge the prevailing notion that multiple sclerosis (MS) is purely an inflammatory disease, pathologic studies suggest differences in the disease processes between individual patients with MS. The ability to dissect the pathophysiologic disease heterogeneity, if it indeed exists, by methodologies that can be applied in vivo is important both for the development of new therapeutics and for the ability to identify the optimal therapy for an individual patient. Objective: To design a stratification algorithm for patients with MS based on accepted MRI measurements reflective of inflammation and axonal damage/tissue loss and to assess if such MS subgroups retain their intergroup differences long term. Methods: Mathematical modeling was used to select three discriminatory MRI measures for clinical outcome based on the cross-sectional analysis of 71 patients with untreated MS and tested general applicability of the stratification scheme on the independent longitudinal cohort of 71 MS patients. Results: By consecutive employment of MRI measures reflect ive of inflammation and tissue loss, the authors were able to separate MS patients into four clinically meaningful subgroups. The analysis of the longitudinal confirmatory cohort demonstrated persistence of the intergroup differences in sel ected MRI measures for 8 years. Conclusions: The inflammatory activity and destr uctiveness of the multiple sclerosis process are to some degree independent of each other, and the successive evaluation of both of these variables can strengthen prediction of clinical outcome in individual patients.
基金This work was supported by the National Natural Science Foundation of China(NSFC)(No.81371256,81171061,81361128012)Ministry of Education of Republic of China(BIBD-PXM2013-014226-07-000084)Seed Grant of International Alliance of Translational Neuroscience(PXM2014-014226-000015).
文摘Background:The cardinal features of Parkinson’s disease(PD)are bradykinesia,rigidity and rest tremor.Abnormal activity in the basal ganglia is predicted to underlie the mechanism of motor symptoms.This study aims to characterize properties of oscillatory activity in the basal ganglia and motor thalamus in patients with PD.Methods:Twenty-nine patients with PD who underwent bilateral or unilateral electrode implantation for subthalamic nucleus(STN)DBS(n=11),unilateral pallidotomy(n=9)and unilateral thalamotomy(n=9)were studied.Microelectrode recordings in the STN,globus pallidus internus(GPi)and ventral oral posterior/ventral intermediate of thalamus(Vop/Vim)were performed.Electromyography of the contralateral limbs was recorded.Single unit characteristics including interspike intervals were analyzed.Spectral and coherence analyses were assessed.Mean spontaneous firing rate(MSFR)of neurons was calculated.Analysis of variance and χ^(2) test were performed.Results:Of 76 STN neurons,39.5% were 4–6 Hz band oscillatory neurons and 28.9% were β frequency band(βFB)oscillatory neurons.The MSFR was 44.2±7.6 Hz.Of 62 GPi neurons,37.1% were 4–6 Hz band oscillatory neurons and 27.4% were βFB neurons.The MSFR was 80.9±9.6 Hz.Of 44 Vop neurons,65.9% were 4–6 Hz band oscillatory neurons and 9%were βFB neurons.The MSFR was 24.4±4.2 Hz.Of 30 Vim oscillatory neurons,70% were 4–6 Hz band oscillatory neurons and 13.3% were β FB neurons.The MSFR was 30.3±3.6 Hz.Further analysis indicated that proportion of βFB oscillatory neurons in STN and GPi was higher than that of similar neurons in the Vop and Vim(P<0.05).Conversely,the proportion of 4–6 Hz band oscillatory neurons and tremor related neurons in the Vim and Vop was higher than that of STN and GPi(P<0.05).The highest MSFR was for GPi oscillatory neurons whereas the lowest MSFR was for Vop oscillatory neurons(P<0.005).Conclusion:The alterations in neuronal activity in basal ganglia play a critical role in generation of parkinsonism.β oscillatory activity is more prominent in basal ganglia than in thalamus suggesting that the activity likely results from dopaminergic depletion.While both basal ganglia and thalamus have tremor activity,the thalamus appears to play a more important role in tremor production,and basal ganglia β oscillatory activity might be the trigger.
基金The authors would like to thank Robert Reed for reviewing the English grammar of this article and Mayra A.Gualdron for graphical design.Dr.Fidias E.Leon-Sarmiento was supported by the US National Institutes of Health(RO1DA019055-04)the Department of Defense(USAMRAA W81XWH-09-1-0467)+1 种基金the Michael J.Fox Foundation(Grant no.11805)Alexander Gonzalez-Castano,MSc.,was supported by the Corporacion Universitaria Minuto de Dios-UNIMINUTO.
文摘Te content of the rectifed motor evoked potential(MEP)induced by transcranial magnetic stimulation(TMS)has ambiguously been assessed without the precision that energy calculation deserves.Tis fact has misled data interpretation and misguided biomedical interventions.To defnitively fll the gap that exits in the neurophysics processing of these signals,we computed,in Walls(̂�),the bioenergy within the rectifed MEP recorded from the human frst digitorum index(FDI)muscle at rest and under isometric contraction.We also gauged the biowork exerted by this muscle.Here we show that bioenergy and biowork can accurately and successfully be assessed,validated,and determined in̂�from MEP signals induced by TMS,regardless of knowing the mathematical expression of the function of the signal.Our novel neurophysics approach represents a dramatic paradigm shif in analysis and interpretation of the content of the MEP and will give a true meaning to the content of rectifed signals.Importantly,this innovative approach allowed unveiling that women exerted more bioenergy than men at the magnetic stimulations used in this study.Revisitation of conclusions drawn from studies published elsewhere assessing rectifed EMG signals that have used ambiguous units is strongly recommended.
文摘背景和目的2015年10月5日至6日在美国华盛顿特区召开的第4届卒中治疗专业学术圆桌会议(Stroke Treatment Academy Industry Roundtable,STAIR)期间,卒中影像学研究(Stroke Imaging Research Group,STIR)组、卒中网络影像学工作组、美国神经放射学学会和美国神经放射学学会基金会共同举办了一次影像学会议和研讨会。本路径图的目的是关注影像学在将来的研究和临床试验中的作用。方法此次会议将卒中神经病学专家、神经放射学专家、神经影像学研究人员、美国国立神经疾病与卒中研究所(National Institute of Neuro Wlgical Dworders and Stroke,NINDS)成员、企业代表以及美国食品药品管理局(Food and Drug Administramion,)成员汇聚一堂,根据前所未有的一系列急性卒中血管内治疗临床试验的阳性结果来探讨将来STIR的重点。结果此次影像学会议对影像学在近期阳性血管内治疗试验中的作用进行了总结和比较,并且提出了汇总分析的可能。此次影像学研讨会对多重影像学模式中采集和分析缺血核心、半暗带不匹配以及侧支循环的最佳成像方法制定出共识推荐,并且提出了在前瞻性临床试验中测量最终梗死灶体积的标准化方法。结论近期的阳性急性卒中血管内治疗临床试验证明了神经血管成像的额外价值。血管内治疗的最佳影像学特征包括大血管闭塞、梗死核心较小、侧支循环良好和半暗带较大。然而,可能需要利用来自近期阳性血管内治疗试验的汇总数据对这些影像学特征参数在不同成像模式之间进行等效定义以及做出标准化尝试。
文摘Type 1 regulatory T cells(CD4^(+)Foxp3^(−)LAG3^(+)CD49b^(+)),or Tr1 cells,have a remarkable capacity to suppress autoimmune inflamma tion through IL-10.1 Although the signals that lead to Tr1-cell differentiation are not completely elucidated,it is known that IL 27 plays a major role in this phenomenon.
基金Open Access funding enabled and organized by Projekt DEAL.
文摘A study published in Nature Neuroscience indicates that autophagy dysfunction in neurons precedes the formation of amyloid plaques.1 These findings ask for a reconsideration of the conventionally accepted sequence of events in plaque formation in Alzheimer’s disease.
