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.

Elevated serum growth differentiation factor 15 in multiple system atrophy patients:A case control study

BACKGROUND Multiple system atrophy(MSA) is a serious progressive neurodegenerative disease. Early diagnosis of MSA is very difficult, and diagnostic biomarkers are limited. Growth differentiation factor 15(GDF15) is involved in the differentiation and progression of the central nervous system, and is widely distributed in peripheral blood, which may be a novel biomarker for MSA.AIM To determine serum GDF15 levels, related factors and their potential diagnostic value in MSA patients, compared with Parkinson’s disease(PD) patients and healthy controls.METHODS A case-control study was conducted, including 49 MSA patients, 50 PD patients and 50 healthy controls. Serum GDF15 levels were measured by human enzymelinked immunosorbent assay, and the differences between the MSA, PD and control groups were analyzed. Further investigations were performed in different MSA subgroups according to age of onset, sex, clinical subtypes, diagnostic criteria, and disease duration. Receiver-operating characteristic curve analysiswas used to evaluate the diagnostic value of GDF15, especially for the differential diagnosis between MSA and PD.RESULTS Serum GDF15 levels were significantly higher in MSA patients than in PD patients and healthy controls(P = 0.000). Males and those with a disease duration of more than three years showed higher serum GDF15 levels(P = 0.043 and 0.000;respectively). Serum GDF15 levels may be a potential diagnostic biomarker for MSA patients compared with healthy controls and PD patients(cutoff: 470.42 pg/m L, sensitivity: 85.7%, specificity: 88.0%;cutoff: 1075.91 pg/m L, sensitivity:51.0%, specificity: 96.0%;respectively).CONCLUSION Serum GDF15 levels are significantly higher in MSA patients and provide suggestions on the etiology of MSA.

Post-post-Newtonian deflection of light ray in multiple systems with PPN parameters

The post-Newtonian scheme in multiple systems with post-Newtonian parameters presented by Klioner and Soffel is extended to the post-post-Newtonian （PPN） order for light propagation problem in the solar system. Under considering the solar system experiment requirement, a new parameter ε is introduced. This extension does not change the virtue of the scheme on the linear partial differential equations of the potential and vector potential mentioned in previous work. Furthermore, this extension is based on the former work done by Richter and Matzner in one global system theory. As an application, we also consider the deflection of light ray in the global coordinates. And the deflection angle of light ray is obtained with post-Newtonian parameters.

Pulmonary Langerhans cell histiocytosis and multiple system involvement:A case report

BACKGROUND Pulmonary Langerhans cell histiocytosis(PLCH)is a relatively rare type of lung disease,common in middle-aged smoking men.It is characterized by proliferation and infiltration of Langerhans cells,and the formation of multiple parabronchial mesenchymal nodules in lung tissue,and may lead to organ dysfunction.There are no typical symptoms and signs,and it is easily misdiagnosed or missed,and therefore deserves clinical attention and further discussion.CASE SUMMARY We describe the case of a nonsmoking 46-year-old man with PLCH diagnosed based on clinical manifestations of fever and dry cough,with a history of hypothyroidism and diabetes insipidus for 9 years.Computed tomography(CT)-and CT-guided puncture examinations revealed no abnormalities,and he ultimately underwent thoracoscopic biopsy to confirm the diagnosis.The pathological diagnosis was PLCH.Thyroid function was maintained by medication.Pituitary magnetic resonance imaging showed that the pituitary stalk had become thinner.CONCLUSION LCH often involves multiple systems.Moreover,the pathogenesis is not clear,clinical manifestations lack specificity,and diagnosis requires special attention.Diagnosis of PLCH can significantly benefit from comprehensive multidisciplinary analysis.

Coenzyme Q10 in neurodegenerative disorders: Potential benefit of Co Q10 supplementation for multiple system atrophy

Coenzyme Q10(Co Q10) is an essential cofactor in the mitochondrial respiratory pathway and also functions as a lipid-soluble antioxidant. Co Q10 deficiency has been implicated in many clinical disorders and aging. Primary Co Q10 deficiency is a group of recessively inherited diseases caused by mutations in any gene involved in the Co Q10 biosynthesis pathway. Although primary Co Q10 deficiency is rare, its diagnosis is important because it is potentially treatable with exogenous Co Q10. Multiple system atrophy(MSA) was recently shown to be linked to mutations in the COQ2 gene, one of the genes involved in the Co Q10 biosynthesis pathway. MSA is relatively common in adult-onset neurodegenerative diseases characterized by Parkinsonism, cerebellar ataxia and autonomic failures. Because COQ2 mutations are associated with an increased risk of MSA, oral Co Q10 supplementation may be beneficial for MSA, as for other primary Co Q10 deficiencies. Statins are 3-hydroxy-3-methylglutaryl coenzyme A inhibitors that inhibit the biosynthesis of cholesterol, as well as the synthesis of mevalonate, a critical intermediate in cholesterol synthesis. Statin therapy has been associ-ated with a variety of muscle complaints from myalgia to rhabdomyolysis. Statin treatment carries a potential risk of Co Q10 deficiency, although no definite evidence has implicated CQ10 deficiency as the cause of statinrelated myopathy.

New advances in multiple system atrophy

Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder characterized by a variable combination of autonomic failure, parkinsonism with poor response to levodopa, cerebellar ataxia and pyramidal symptoms. The pathological hallmark of MSA is the oligodendrocytic glial cytoplasmic inclusions (GCIs) consisting of α-synuclein, and so MSA, together with Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), is an α-synucleinopathy. Currently few effective biomarkers have been identified for the diagnosis or prognosis of MSA, and there is no established therapy to delay its progression. In this review, we discuss the epidemiology, neuropathology, genetics, clinical presentation and diagnostic biomarkers of MSA, as well as recent advances in its treatment.

Pathogenic roles of alpha-synuclein in Parkinson’s disease and multiple system atrophy

Alpha-synucleinopathies(α-synucleinopathies)are a diverse group of neurodegenerative diseases comprising Parkinson’s disease(PD),dementia with Lewy bodies(DLB),and multiple system atrophy(MSA).Although in all these diseases there exist abnormal accumulation of alpha-synuclein(α-syn)aggregates in nerve tissues,the pathological lesions formed byα-syn aggregates and their cellular locations are quite different.In PD and DLB,the hallmark pathological lesions are Lewy bodies(LBs)and Lewy neurites(LNs),which are localized in the neuronal somata and processes.In MSA,the characteristic pathologic structures are glial cytoplasmic inclusions,which are deposited in the cytoplasm of oligodendrocytes.The fact that PD and MSA have distinct pathologicalα-syn lesions suggest that different mechanisms play a role in the pathogenesis of the two diseases.In this review article,we compare the clinical manifestations and pathological features of PD and MSA,the two common synucleinopathies,and discuss the potential mechanisms for the formation ofα-syn aggregates and their pathologic roles in PD and MSA.

Infiltration by monocytes of the central nervous system and its role in multiple sclerosis: reflections on therapeutic strategies

Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple roles of mononuclear macrophages in the neuroinflammatory process. Monocytes play a significant role in neuroinflammation, and managing neuroinflammation by manipulating peripheral monocytes stands out as an effective strategy for the treatment of multiple sclerosis, leading to improved patient outcomes. This review outlines the steps involved in the entry of myeloid monocytes into the central nervous system that are targets for effective intervention: the activation of bone marrow hematopoiesis, migration of monocytes in the blood, and penetration of the blood–brain barrier by monocytes. Finally, we summarize the different monocyte subpopulations and their effects on the central nervous system based on phenotypic differences. As activated microglia resemble monocyte-derived macrophages, it is important to accurately identify the role of monocyte-derived macrophages in disease. Depending on the roles played by monocyte-derived macrophages at different stages of the disease, several of these processes can be interrupted to limit neuroinflammation and improve patient prognosis. Here, we discuss possible strategies to target monocytes in neurological diseases, focusing on three key aspects of monocyte infiltration into the central nervous system, to provide new ideas for the treatment of neurodegenerative diseases.

Changes of China’s Status in the Global System and Its Influencing Factors:A Multiple Contact Networks Perspective

Clarifying China’s position in the global system is an important logical basis for developing national diplomacy.Although much research has been done on China’s development status,most studies have been based on country comparisons or institutional en-vironment.In today’s networked era in which the global economy,trade,personnel,and information are closely connected,studies on China’s global position and its status changes and influencing factors in multiple contact networks are still insufficient.In this study,from the perspective of diverse global contact networks,we constructed economic,cultural,and political influence indices to explore the changes and influencing factors on China’s status in the global system from 2005 to 2018.The results show that during the study period,China’s global influence in the fields of economic ties,cultural exchanges,and political contacts increased significantly,but its influ-ence in the fields of cultural exchanges and political contacts lagged far economic ties.The pattern of China’s economic influence on various economies around the world has shown a transformation from an‘upright pyramid’to an‘inverted pyramid’structure.The proportion of these economies in low-influence zones has decreased from more than 60%in 2005 to less than 20%in 2018.China’s cultural and political influence on various economies around the world has increased significantly;however,for the former,the percentage of high-influence areas is still less than 20%,whereas for the latter the percentage of these economies in medium-and high-influence areas is still less than 50%.Analyses such as a scatter plot matrix show that geographical proximity,economic globalization,close cooperation with developing countries,and a proactive and peaceful foreign policy are important factors in improving China’s status in the diverse global network system.

A new method for evaluating the firing precision of multiple launch rocket system based on Bayesian theory

How to effectively evaluate the firing precision of weapon equipment at low cost is one of the core contents of improving the test level of weapon system.A new method to evaluate the firing precision of the MLRS considering the credibility of simulation system based on Bayesian theory is proposed in this paper.First of all,a comprehensive index system for the credibility of the simulation system of the firing precision of the MLRS is constructed combined with the group analytic hierarchy process.A modified method for determining the comprehensive weight of the index is established to improve the rationality of the index weight coefficients.The Bayesian posterior estimation formula of firing precision considering prior information is derived in the form of mixed prior distribution,and the rationality of prior information used in estimation model is discussed quantitatively.With the simulation tests,the different evaluation methods are compared to validate the effectiveness of the proposed method.Finally,the experimental results show that the effectiveness of estimation method for firing precision is improved by more than 25%.

Characteristic analysis of 5D symmetric Hamiltonian conservative hyperchaotic system with hidden multiple stability

Conservative chaotic systems have unique advantages over dissipative chaotic systems in the fields of secure communication and pseudo-random number generator because they do not have attractors but possess good traversal and pseudorandomness. In this work, a novel five-dimensional(5D) Hamiltonian conservative hyperchaotic system is proposed based on the 5D Euler equation. The proposed system can have different types of coordinate transformations and time reversal symmetries. In this work, Hamilton energy and Casimir energy are analyzed firstly, and it is proved that the new system satisfies Hamilton energy conservation and can generate chaos. Then, the complex dynamic characteristics of the system are demonstrated and the conservatism and chaos characteristics of the system are verified through the correlation analysis methods such as phase diagram, equilibrium point, Lyapunov exponent, bifurcation diagram, and SE complexity. In addition, a detailed analysis of the multistable characteristics of the system reveals that many energy-related coexisting orbits exist. Based on the infinite number of center-type and saddle-type equilibrium points, the dynamic characteristics of the hidden multistability of the system are revealed. Then, the National Institute of Standards and Technology(NIST)test of the new system shows that the chaotic sequence generated by the system has strong pseudo-random. Finally, the circuit simulation and hardware circuit experiment of the system are carried out with Multisim simulation software and digital signal processor(DSP) respectively. The experimental results confirm that the new system has good ergodicity and realizability.

Linear paired electrolysis of furfural to furoic acid at both anode and cathode in a multiple redox mediated system

Implementing a new energy-saving electrochemical synthesis system with high commercial value is a strategy of the sustainable development for upgrading the bulk chemicals preparation technology in the future.Here,we report a multiple redox-mediated linear paired electrolysis system,combining the hydrogen peroxide mediated cathode process with the I2 mediated anode process,and realize the conversion of furfural to furoic acid in both side of the dividedflow cell simultaneously.By reasonably controlling the cathode potential,the undesired water splitting reaction and furfural reduction side reactions are avoided.Under the galvanostatic electrolysis,the two-mediated electrode processes have good compatibility,which reduce the energy consumption by about 22%while improving the electronic efficiency by about 125%.This system provides a green electrochemical synthesis route with commercial prospects.

Three-dimensional magnetic reconnection in complex multiple X-point configurations in an ancient solar-lunar terrestrial system

Magnetic reconnection processes in three-dimensional(3D)complex field configurations have been investigated in different magneto-plasma systems in space,laboratory,and astrophysical systems.Two-dimensional(2D)features of magnetic reconnection have been well developed and applied successfully to systems with symmetrical property,such as toroidal fusion plasmas and laboratory experiments with an axial symmetry.But in asymmetric systems,the 3D features are inevitably different from those in the 2D case.Magnetic reconnection structures in multiple celestial body systems,particularly star-planet-Moon systems,bring fresh insights to the understanding of the 3D geometry of reconnection.Thus,we take magnetic reconnection in an ancient solar-lunar terrestrial magneto-plasma system as an example by using its crucial parameters approximately estimated already and also some specific applications in pathways for energy and matter transports among Earth,ancient Moon,and the interplanetary magnetic field(IMF).Then,magnetic reconnection of the ancient lunar-terrestrial magnetospheres with the IMF is investigated numerically in this work.In a 3D simulation for the Earth-Moon-IMF system,topological features of complex magnetic reconnection configurations and dynamical characteristics of magnetic reconnection processes are studied.It is found that a coupled lunar-terrestrial magnetosphere is formed,and under various IMF orientations,multiple X-points emerge at distinct locations,showing three typical magnetic reconnection structures in such a geometry,i.e.,the X-line,the triple current sheets,and the A-B null pairs.The results can conduce to further understanding of reconnection physics in 3D for plasmas in complex magnetic configurations,and also a possible mechanism for energy and matters transport in evolutions of similar astrophysical systems.

Carbon efficiency evaluation method for urban energy system with multiple energy complementary

Urban energy systems(UESs)play a pivotal role in the consumption of clean energy and the promotion of energy cascade utilization.In the context of the construction and operation strategy of UESs with multiple complementary energy resources,a comprehensive assessment of the energy efficiency is of paramount importance.First,a multi-dimensional evaluation system with four primary indexes of energy utilization,environmental protection,system operation,and economic efficiency and 21 secondary indexes is constructed to comprehensively portray the UES.Considering that the evaluation system may contain a large number of indexes and that there is overlapping information among them,an energy efficiency evaluation method based on data processing,dimensionality reduction,integration of combined weights,and gray correlation analysis is proposed.This method can effectively reduce the number of calculations and improve the accuracy of energy efficiency assessments.Third,a demonstration project for a UES in China is presented.The energy efficiency of each scenario is assessed using six operational scenarios.The results show that Scenario 5,in which parks operate independently and investors build shared energy-storage equipment,has the best results and is best suited for green and low-carbon development.The results of the comparative assessment methods show that the proposed method provides a good energy efficiency assessment.This study provides a reference for the optimal planning,construction,and operation of UESs with multiple energy sources.

Systemic lupus erythematosus in a 15-year-old female with multiple splenic nodules:A case report

BACKGROUND Systemic lupus erythematosus(SLE)is a chronic inflammatory disease primarily affecting young females.SLE can invade any organ,and various forms of splenic invasion have been reported.Manifestations include splenomegaly and splenic infarction,rupture,and calcification.The study encountered a rare case of splenic involvement,with nodules of various sizes without calcifications or ruptures.CASE SUMMARY A 15-year-old girl presented with arthralgia,weight loss,fever,increased levels of inflammatory markers,and positive antinuclear antibody test results.The patient was diagnosed with SLE.She was asymptomatic while taking steroids and hydroxychloroquine.Ten months after discharge,the patient developed a fever and abdominal pain.Lupus enteritis was suspected,and abdominopelvic computed tomography(AP-CT)was performed.There were no specific findings in the gastrointestinal tract,but multiple splenic nodules were observed.Infection or hemangioma was considered;however,no specific radiological findings were observed.A biopsy of the spleen was performed to determine the possibility of malignancy.The histological findings of the spleen included extensive periarteriolar necrosis with hematoxylin bodies and numerous karyorrhectic debris.Based on the biopsy results,the patient was diagnosed with an SLE flare-up and was maintained on high-dose steroids and immunosuppressants.CONCLUSION As disease activity increased,multiple nodules in the spleen that were previously unseen were observed using AP-CT and histologically confirmed.Spleen invasion by SLE can appear in multiple nodular forms and patterns.Therefore,physicians should consider these findings when differentiating these nodules from infections and malignancies.

Designing a Protection Scheme in Micro-Grid Systems with DG Using Central Protection Unite and Multiple Setting Group Protection Relays

Distributed generators now is widely used in electrical power networks, in some cases it works seasonally, and some types works at special weather conditions like photo voltaic systems and wind energy, and due to this continuous changes in generation condition, the fault current level in network will be affected, this changes in fault current level will affect in the coordination between protection relays and to keep the coordination at right way, an adaptive protection system is required that can adaptive its setting according to generation changes, the fault current level in each case is evaluated using ETAP software, and the required relay setting in each case is also evaluated using Grey Wolf Optimizer (GWO) algorithm, and to select suitable setting which required in each condition, to select the active setting group of protection relay according to generation capacity, central protection unite can be used, and to improve protection stability and minimizing relays tripping time, a proposed method for selecting suitable backup relay is used, which leads to decrease relays tripping time and increase system stability, output settings for relays in all cases achieved our constrains.

Multiple Solutions for a Class of Singular Boundary Value Problems of Hadamard Fractional Differential Systems with p-Laplacian Operator

This paper discusses the existence and multiplicity of positive solutions for a class of singular boundary value problems of Hadamard fractional differential systems involving the p-Laplacian operator. First, for the sake of overcoming the singularity, sequences of approximate solutions to the boundary value problem are obtained by applying the fixed point index theory on the cone. Next, it is demonstrated that these sequences of approximate solutions are uniformly bounded and equicontinuous. The main results are then established through the Ascoli-Arzelà theorem. Ultimately, an instance is worked out to test and verify the validity of the main results.

Multidimensional biomarkers for multiple system atrophy:an update and future directions

Multiple system atrophy(MSA)is a fatal progressive neurodegenerative disease.Biomarkers are urgently required for MSA to improve the diagnostic and prognostic accuracy in clinic and facilitate the development and monitoring of disease-modifying therapies.In recent years,significant research efforts have been made in exploring multidimensional biomarkers for MSA.However,currently few biomarkers are available in clinic.In this review,we systematically summarize the latest advances in multidimensional biomarkers for MSA,including biomarkers in fluids,tissues and gut microbiota as well as imaging biomarkers.Future directions for exploration of novel biomarkers and promotion of implementation in clinic are also discussed.

Gut flora in multiple sclerosis:implications for pathogenesis and treatment

Multiple sclerosis is an inflammatory disorder chara cterized by inflammation,demyelination,and neurodegeneration in the central nervous system.Although current first-line therapies can help manage symptoms and slow down disease progression,there is no cure for multiple sclerosis.The gut-brain axis refers to complex communications between the gut flo ra and the immune,nervous,and endocrine systems,which bridges the functions of the gut and the brain.Disruptions in the gut flora,termed dys biosis,can lead to systemic inflammation,leaky gut syndrome,and increased susceptibility to infections.The pathogenesis of multiple sclerosis involves a combination of genetic and environmental factors,and gut flora may play a pivotal role in regulating immune responses related to multiple scle rosis.To develop more effective therapies for multiple scle rosis,we should further uncover the disease processes involved in multiple sclerosis and gain a better understanding of the gut-brain axis.This review provides an overview of the role of the gut flora in multiple scle rosis.

Two-dimensional Parameter Relationships for W UMa-type Systems Revisited

Reviewing the empirical and theoretical parameter relationships between various parameters is a good way to understand more about contact binary systems.In this investigation,two-dimensional(2D)relationships for P–MV(system),P–L1,2,M1,2–L1,2,and q–Lratiowere revisited.The sample used is related to 118 contact binary systems with an orbital period shorter than 0.6 days whose absolute parameters were estimated based on the Gaia Data Release 3 parallax.We reviewed previous studies on 2D relationships and updated six parameter relationships.Therefore,Markov chain Monte Carlo and Machine Learning methods were used,and the outcomes were compared.We selected 22 contact binary systems from eight previous studies for comparison,which had light curve solutions using spectroscopic data.The results show that the systems are in good agreement with the results of this study.