Strain-dependent alpha-synuclein spreading in Parkinson's disease and multiple system atrophy

Parkinson's disease(PD) and atypical Parkinsonian syndromes,such as multiple system atrophy(MSA) and Dementia with Lewy bodies,are neurodegenerative movement disorders characterized by the accumulation of alphasynuclein(a-syn) aggregates.These a-syn aggregates propagate throughout the brain in a prion-like manner,where pathological a-syn recruits endogenous a-syn to form insoluble aggregates.Oligomeric forms representing intermediates on the way to insoluble aggregates result in the most pronounced neurotoxic effects.

Mitochondria replacement from transplanted amniotic fluid stem cells:a promising therapy for non-neuronal defects in spinal muscular atrophy

Spinal muscular atrophy(SMA)is a genetic disorder that primarily affects infants and leads to muscle weakness,atrophy,and paralysis.The main cause is the homozygous mutation or deletion of the SMN1 gene,resulting in inadequate levels of the survival motor neuron(SMN)protein.Approved treatments focus on restoring SMN levels through various approaches,but there is a need for“SMN-independent”therapies that target other pathological processes.Skeletal muscle is closely involved in SMA pathology,with impaired muscle function observed before motor neuron degeneration.Studies have revealed that SMN loss leads to skeletal muscle mitochondrial structural abnormalities,impaired respiration,and accumulation of reactive oxygen species.

Gene therapy for spinal muscular atrophy:perspectives on the possibility of optimizing SMN1 delivery to correct all neurological and systemic perturbations

Spinal muscular atrophy(SMA)is a genetic condition that results in selective lower motor neuron loss with concomitant muscle weakness and atrophy.The genetic cause of SMA was understood in 1995 when loss or impairment of the survival motor neuron 1(SMN1)gene was identified as the main contributing factor(Lefebvre et al.,1995).This,in combination with the discovery that humans have a“back-up”gene,SMN2,which can produce low levels(approximately 10%)of the full-length functional SMN protein,has led to the generation of SMA-specific gene therapies.SMA was traditionally classified according to age of symptom onset and developmental milestones achieved,with life expectancy and severity varying between individuals.Now,SMN2 copy number is used as a proxy for the prediction of disease severity,with higher SMN2 copy number typically being associated with reduced severity of SMA,although this relationship is not absolute:some individuals with low SMN2 copy number have less severe SMA phenotypes and vice versa.Additionally,the etiology of SMA is further complicated by other factors,such as non-typical nucleotide variants and SMN2-independent modifiers of disease severity.

Infantile Spinal Muscular Atrophy at the Albert Royer National Children’s Hospital Center in Dakar

Introduction: Infantile spinal muscular atrophy (ISA) is an autosomal recessive disease caused by primary degeneration of cells in the anterior horn of the spinal cord, leading to muscle weakness and hypotonia. Its incidence is estimated at 1 in 6000 births worldwide. In Africa, particularly in Senegal, there are few studies interested on this pathology. We therefore deemed this study necessary, which set itself the objective of describing the diagnostic, therapeutic and progressive aspects of infantile spinal muscular atrophy at the Albert Royer National Children’s Hospital Center in Dakar (CHNEAR). Methodology: We conducted a retrospective descriptive study over a period of two (2) years from December 2020 to December 2022. Included were all hospitalized patients in whom the diagnosis of spinal muscular atrophy was made with or without genetic confirmation. The data were collected on a pre-established form then entered and analyzed with the following software: Excel 2013 and R version 4.1.3. Results: During our study period, 2100 children were hospitalized, the annual incidence was 0.76%. The average age of our patients was 9 ± 9 months with a range of 3 months to 32 months and the median was 6.5 months. The sex ratio was 7. The notion of family consanguinity was found in 62.5% of cases and the notion of ISA in the family in 25% of cases. Hypotonia and respiratory distress were found at the forefront in equal proportions (50% of cases). Electromyogram (EMG) was performed in 3 patients (37.5%). Symptomatic medical treatment was administered in 100% of patients, 04 patients had benefited from respiratory physiotherapy, i.e. 50% of cases, and genetic counseling was carried out in one patient (12.5%). The evolution was immediately favorable in 2 patients or 25% of cases, unfavorable in 75% of cases with a death rate of 50% and the average age of death was 5.5 months ± 1 with extremes ranging from 3 to 7 months. Conclusion: The number of Infantile spinal muscular atrophy cases remains low in hospitals in Dakar. Diagnostic means are still difficult to access. The course is difficult to predict and is often marked in the long term by respiratory difficulties which can be fatal.

Anesthetic Management of a Patient with Spinal Muscular Atrophy Type III Undergoing Emergent Caesarean Section: A Case Report

In this case report, we describe the anesthetic management for a 36-year-old G2P0010 at 36 weeks gestation with Spinal Muscular Atrophy Type III who underwent an emergent caesarean section due to fetal footling breech position. The patient is a wheelchair-bound quadriplegic with kyphoscoliosis and a lack of cough reflex who required nasal continuous noninvasive ventilatory support (CNVS) for chronic hypercapnic respiratory failure. Surgery was done under general anesthesia due to its emergent nature, and the patient was successfully extubated and transitioned to nasal CNVS in the operating room at the end of the case. Postoperative care was provided in the medical intensive care unit for three days without complication and the patient was discharged home uneventfully.

Inverse relationship between platelet Akt activity and hippocampal atrophy:A pilot case-control study in patients with diabetes mellitus

BACKGROUND Akt plays diverse roles in humans.It is involved in the pathogenesis of type 2 diabetes mellitus(T2DM),which is caused by insulin resistance.Akt also plays a vital role in human platelet activation.Furthermore,the hippocampus is closely associated with memory and learning,and a decrease in hippocampal volume is reportedly associated with an insulin-resistant phenotype in T2DM patients without dementia.AIM To investigate the relationship between Akt phosphorylation in unstimulated platelets and the hippocampal volume in T2DM patients.METHODS Platelet-rich plasma(PRP)was prepared from the venous blood of patients with T2DM or age-matched controls.The pellet lysate of the centrifuged PRP was subjected to western blotting to analyse the phosphorylation of Akt,p38 mitogen-activated protein(MAP)kinase and glyceraldehyde 3-phosphate dehydrogenase(GAPDH).Phosphorylation levels were quantified by densitometric analysis.Hippocampal volume was analysed using a voxel-based specific regional analysis system for Alzheimer’s disease on magnetic resonance imaging,which proposes the Z-score as a parameter that reflects hippocampal volume.RESULTS The levels of phosphorylated Akt corrected with phosphorylated p38 MAP kinase were inversely correlated with the Z-scores in the T2DM subjects,whereas the levels of phosphorylated Akt corrected with GAPDH were not.However,this relationship was not observed in the control patients.CONCLUSION These results suggest that an inverse relationship may exist between platelet Akt activation and hippocampal atrophy in T2DM patients.Our findings provide insight into the molecular mechanisms underlying T2DM hippocampal atrophy.

Refractory lipoatrophy treated with autologous whole blood injection:A case report

BACKGROUND Intramuscular corticosteroid injection may cause adverse effects such as dermal and/or subcutaneous atrophy,alopecia,hypopigmentation,and hyperpigmentation.Although cutaneous atrophy can spontaneously resolve,several treatment options have been suggested for this condition.CASE SUMMARY In this paper,we report a case of corticosteroid injection induced lipoatrophy treated with autologous whole blood(AWB)injection,as the condition had been unresponsive to fractional laser therapy.A 29-year-old female patient visited the dermatology clinic complaining of skin depression on her right buttock area,which had appeared six months earlier.There had been only subtle improvement at the margins after fractional CO2 laser treatment;therefore,after obtaining informed consent from the patient,AWB treatment was initiated.One month after the first AWB injection,the size and depth of the lesion had noticeably improved,and a slight improvement was also observed in discoloration.CONCLUSION Close observation is the initial treatment of choice for steroid induced skin atrophy;however,for patients in need of immediate cosmetic improvement,AWB injection may be a safe and cost-effective alternative.

Mitochondrial dysfunction in type 2 diabetes:A neglected path to skeletal muscle atrophy

Over the course of several decades,robust research has firmly established the significance of mitochondrial pathology as a central contributor to the onset of skeletal muscle atrophy in individuals with diabetes.However,the specific intricacies governing this process remain elusive.Extensive evidence highlights that individuals with diabetes regularly confront the severe consequences of skeletal muscle degradation.Deciphering the sophisticated mechanisms at the core of this pathology requires a thorough and meticulous exploration into the nuanced factors intricately associated with mitochondrial dysfunction.

Insights into spinal muscular atrophy from molecular biomarkers

Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness.It is one of the most common genetic causes of mortality among infants aged less than 2 years.Biomarker research is currently receiving more attention,and new candidate biomarkers are constantly being discovered.This review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and cons.We also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy,which are classified as either specific or non-specific biomarkers.This review provides new insights into the pathogenesis of spinal muscular atrophy,the mechanism of biomarkers in response to drug-modified therapies,the selection of biomarker candidates,and would promote the development of future research.Furthermore,the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.

MSA方法在功能测试平台稳定性分析中的应用

功能测试平台是公司自主开发用来测试电路板功能输出参数的一种半自动化测试系统,测试平台的稳定性决定了电路板测试结果的信赖度。本文利用MSA理论方法对功能测试平台每个输出参数的检具能力和检具能力指数进行分析,并根据分析结果针对性地改进功能测试平台,为复杂功能测试系统稳定性评估提供了一定参考。

Reduced mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor contributes to neurodegeneration in a model of spinal and bulbar muscular atrophy pathology

Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen receptor protein,characterized by polyglutamine expansion,is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in spinal and bulbar muscular atrophy patients.These aggregates alter protein-protein interactions and compromise transcriptional activity.In this study,we reported that in both cultured N2a cells and mouse brain,mutant androgen receptor with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-de rived neurotrophic factor.Overexpressio n of mesencephalic astrocyte-derived neurotrophic factor amelio rated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor aggregation.Conversely.knocking down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor aggregation.Our findings suggest that inhibition of mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor is a potential mechanism underlying neurodegeneration in spinal and bulbar muscular atrophy.

基于MSA的无线网络安全系统设计和实现

随着无线通信技术发展,基于MSA的无线网络安全系统在提升网络覆盖与安全性,降低建设和维护成本方面起到相当的作用。本文深入探讨了无线网络安全系统的设计与实现,特别关注主服务协议(MSA)的优化。面对日益严重的安全挑战,提出以MSA为核心的解决方案,整合密钥分配与身份认证机制,提升安全性。同时,指出MAC地址等风险点,强调双重外部认证的重要性。还介绍了安全系统流程与功能模块设计,包括Mesh节点发现、连接管理及认证模块等。通过模拟实验验证,系统展现出优秀的非法节点拦截效能和认证精确度。未来,将继续深入研究无线网络安全技术,以应对不断变化的安全威胁,提升无线通信的安全性和可靠性。

基于MSA协议的无线网络安全系统设计和实现

近年来,无线技术不断发展和普及,承担着各行业多领域的通信任务,其安全问题愈加突出,研究设计并实现基于MSA协议的无线网络安全系统具有巨大的实用价值和现实意义。文章介绍了无线网络安全系统的相关概述,对基于MSA协议的无线网络安全系统进行了系统和功能模块设计。

基于MSA无线网络安全系统设计和实现

为解决互联网终端接入安全问题,保证无线网状网络部署规模,应用主服务协议(master service agreement,MSA)设计一款功能完善、实用性强的无线网络安全系统。首先,设计和搭建系统架构和运行环境;其次,分别完成对网状节点发现、网状连接管理、美国机动工程师协会(Society of Automotive Engineers,SAE)认证、网状钥匙分配器(management of key distribution,MKD)与密钥管理、四次握手过程等模块的设计,保证系统功能实现效果;最后,对系统安全性进行验证。结果表明:在MSA的应用背景下,所设计的无线网络安全系统可以在确保认证准确度的基础上,有效地缩小认证时延,完全符合预期设计标准和要求。

测量系统分析(MSA)在航天产品检测过程中的应用

文章主要介绍了测量系统分析(MSA)方法,并运用该方法针对有一定批量的航天典型产品,开展了MSA分析应用研究,明确了操作流程和步骤,通过改进测量系统,提升了测量系统的一致性和准确性,同时,明确了测量系统分析在航天产品的应用场景,为首件鉴定、九新分析提供了新思路新方法。

External anal sphincter electromyography in multiple system atrophy:implications for diagnosis,clinical correlations,and novel insights into prognosis

Multiple system atrophy is a sporadic,progressive,adult-onset,neurodegenerative disorder characte rized by autonomic dysfunction symptoms,parkinsonian features,and cerebellar signs in va rious combinations.An early diagnosis of multiple system atrophy is of utmost impo rtance for the proper prevention and management of its potentially fatal complications leading to the poor prognosis of these patients.The current diagnostic criteria incorporate several clinical red flags and magnetic resonance imaging marke rs supporting diagnosis of multiple system atrophy.Nonetheless,especially in the early disease stage,it can be challenging to differentiate multiple system atrophy from mimic disorders,in particular Parkinson’s disease.Electromyography of the external anal sphincter represents a useful neurophysiological tool for diffe rential diagnosis since it can provide indirect evidence of Onuf’s nucleus degeneration,which is a pathological hallmark of multiple system atrophy.However,the diagnostic value of external anal sphincter electromyography has been a matter of debate for three decades due to controve rsial reports in the literature.In this review,after a brief ove rview of the electrophysiological methodology,we first aimed to critically analyze the available knowledge on the diagnostic role of external anal sphincter electromyography.We discussed the conflicting evidence on the clinical correlations of neurogenic abnormalities found at external anal sphincter electro myography.Finally,we repo rted recent prognostic findings of a novel classification of electromyography patterns of the external anal sphincter that could pave the way toward the implementation of this neurophysiological technique for survival prediction in patients with multiple system atrophy.

郝风玲教授杞菊六味汤治疗MSA-C型多系统萎缩1例

多系统萎缩是一种神经系统变性疾病,临床表现为自主神经功能障碍、帕金森综合征、小脑性共济失调等症状,并分为MSA-P型和MSA-C型2个亚型。当前此病西医病因及发病机制尚不明确,现代医学尚无针对性治疗方法;中医学对此病的辨证论治不完全相同,但都能有效缓解其发病症状。此文报道郝风玲教授以杞菊六味汤加减治疗MSA-C型多系统萎缩1例。

基于MSA的OA系统平台框架设计研究

OA系统作为提高企业及高校科研院所办公效率和行政管理的重要工具,是实现办公自动化和办公新生态的重要内容。文章阐述OA系统的概念及发展历程;分析OA系统中不同架构的优缺点;从流程设计、用户体验、系统性能方面总结目前OA系统框架中存在的问题;并基于MSA技术设计以PaaS平台为核心的OA系统功能框架,可为OA系统设计在用户体验、操作、性能提升方面提供参考。

Three siblings with gyrate atrophy of the choroid and retina:a case report

Dear Editor,We report the cases of three siblings with gyrate atrophy(GA)of the choroid and retina with foveoschisis,anterior subcapsular cataracts,and capsular bag contraction.GA is a rare autosomal recessive degenerative disorder of the choroid and retina.About one-third of all reported cases are from Finland where the incidence is estimated to be around 1:50000 whereas the theoretical global incidence is only 1:1500000[1].

Pharmacological effects of denervated muscle atrophy due to metabolic imbalance in different periods

Denervation-induced skeletal muscle atrophy can potentially cause the decline in the quality of life of patients and an increased risk of mortality.Complex pathophysiological mechanisms with dynamic alterations have been documented in skeletal muscle atrophy resulting from innervation loss.Hence,an in-depth comprehension of the key mechanisms and molecules governing skeletal muscle atrophy at varying stages,along with targeted treatment and protection,becomes essential for effective atrophy management.Our preliminary research categorizes the skeletal muscle atrophy process into four stages using microarray analysis.This review extensively discusses the pathways and molecules potentially implicated in regulating the four stages of denervation and muscle atrophy.Notably,drugs targeting the reactivare oxygen species stage and the inflammation stage assume critical roles.Timely intervention during the initial atrophy stages can expedite protection against skeletal muscle atrophy.Additionally,pharmaceutical intervention in the ubiquitin-proteasome pathway associated with atrophy and autophagy lysosomes can effectively slow down skeletal muscle atrophy.Key molecules within this stage encompass MuRF1,MAFbx,LC3II,p62/SQSTM1,etc.This review also compiles a profile of drugs with protective effects against skeletal muscle atrophy at distinct postdenervation stages,thereby augmenting the evidence base for denervation-induced skeletal muscle atrophy treatment.