Understanding the spectrum of non-motor symptoms in multiple sclerosis:insights from animal models

Multiple sclerosis is a chronic autoimmune disease of the central nervous system and is generally considered to be a non-traumatic,physically debilitating neurological disorder.In addition to experiencing motor disability,patients with multiple sclerosis also experience a variety of nonmotor symptoms,including cognitive deficits,anxiety,depression,sensory impairments,and pain.However,the pathogenesis and treatment of such non-motor symptoms in multiple scle rosis are still under research.Preclinical studies for multiple sclerosis benefit from the use of disease-appropriate animal models,including experimental autoimmune encephalomyelitis.Prior to understanding the pathophysiology and developing treatments for non-motor symptoms,it is critical to chara cterize the animal model in terms of its ability to replicate certain non-motor features of multiple sclerosis.As such,no single animal model can mimic the entire spectrum of symptoms.This review focuses on the non-motor symptoms that have been investigated in animal models of multiple sclerosis as well as possible underlying mechanisms.Further,we highlighted gaps in the literature to explain the nonmotor aspects of multiple sclerosis in expe rimental animal models,which will serve as the basis for future studies.

An LED-Side-Pumped Intracavity Frequency-Doubled Nd,Ce:YAG Laser Producing a 2W Q-Switched Red Beam

We report a high-average-power acousto-optic(AO)Q-switched intracavity frequency-doubled red laser based on a high-efficiency light-emitting-diode(LED)pumped two-rod Nd,Ce:YAG laser module.Under quasi-continuous wave operation conditions,a maximum output power of 1319.08 nm wavelength was achieved at 11.26 W at a repetition rate of 100 Hz.

Origin of tradeoff between movement velocity and attachment duration of kinesin motor on a microtubule

Kinesin-1 motor protein is a homodimer containing two identical motor domains connected by a common long coiledcoil stalk via two flexible neck linkers. The motor can step on a microtubule with a velocity of about 1 μm·s-1and an attachment duration of about 1 s under physiological conditions. The available experimental data indicate a tradeoff between velocity and attachment duration under various experimental conditions, such as variation of the solution temperature,variation of the strain between the two motor domains, and so on. However, the underlying mechanism of the tradeoff is unknown. Here, the mechanism is explained by a theoretical study of the dynamics of the motor under various experimental conditions, reproducing quantitatively the available experimental data and providing additional predictions. How the various experimental conditions lead to different decreasing rates of attachment duration versus velocity is also explained.

Liquid Subcutaneous Levodopa-Carbidopa ND0612 Effects on Motor Symptoms in Individuals with Parkinson’s Disease: A Systematic Review and Meta-Analysis

Objective: In the manuscript titled “Liquid subcutaneous Levodopa-Carbidopa ND0612 effects on motor symptoms in individuals with Parkinson’s Disease: A systematic review and meta-analysis”, the objective was to conduct a systematic review with meta-analysis to investigate the effects ND0612 24-hour dosing regimen has on motor symptoms in individuals with Parkinson’s Disease (PD). Introduction: ND0612 is a novel minimally invasive continuous subcutaneous delivery system of liquid Levodopa-Carbidopa being investigated for the treatment of PD in individuals experiencing motor symptoms. Methods: A systematic literature search was conducted in PubMed, Cochrane, and EBSCO databases to identify randomized controlled trials investigating the effects of ND0612 on motor symptoms in individuals with PD. Outcomes included the Unified Parkinson’s Disease Rating Scale (UPDRS) Part II and Part III scores. Methodological quality was assessed using the Cochrane Grading of Recommendations Assessment, Development, and Evaluation approach. Meta-analysis was performed using a random effects model with the DerSimonian and Laird method to estimate the effects of the ND0612 24-hour dosing regimen on UPDRS Part II and Part III scores. Results: Three studies were included in our review. There were statistically significant reductions in UPDRS Part II scores (mean difference (MD) −3.299;95% confidence interval (CI) −3.438, −3.159) and in UPDRS Part III scores (MD −12.695;95% CI −24.428, −0.962) in the ND0612 24-hour dosing regimen. Results were based on very low certainty of evidence. Conclusion: Based on very low certainty evidence, the ND0612 24-hour dosing regimen is effective at improving motor symptoms in individuals with PD. Our findings suggest that ND0612 is more effective at improving UPDRS Part II and Part III scores in individuals with PD than other pharmacological and non-pharmacological treatments, warranting further study.

Elevated brain temperature under severe heat exposure impairs cortical motor activity and executive function

Background:Excessive heat exposure can lead to hyperthermia in humans,which impairs physical performance and disrupts cognitive function.While heat is a known physiological stressor,it is unclear how severe heat stress affects brain physiology and function.Methods:Eleven healthy participants were subjected to heat stress from prolonged exercise or warm water immersion until their rectal temperatures(T_(re))attained 39.5℃,inducing exertional or passive hyperthermia,respectively.In a separate trial,blended ice was ingested before and during exercise as a cooling strategy.Data were compared to a control condition with seated rest(normothermic).Brain temperature(T_(br)),cerebral perfusion,and task-based brain activity were assessed using magnetic resonance imaging techniques.Results:T_(br)in motor cortex was found to be tightly regulated at rest(37.3℃±0.4℃(mean±SD))despite fluctuations in T_(re).With the development of hyperthermia,T_(br)increases and dovetails with the rising T_(re).Bilateral motor cortical activity was suppressed during high-intensity plantarflexion tasks,implying a reduced central motor drive in hyperthermic participants(T_(re)=38.5℃±0.1℃).Global gray matter perfusion and regional perfusion in sensorimotor cortex were reduced with passive hyperthermia.Executive function was poorer under a passive hyperthermic state,and this could relate to compromised visual processing as indicated by the reduced activation of left lateral-occipital cortex.Conversely,ingestion of blended ice before and during exercise alleviated the rise in both T_(re)and T_(bc)and mitigated heat-related neural perturbations.Conclusion:Severe heat exposure elevates T_(br),disrupts motor cortical activity and executive function,and this can lead to impairment of physical and cognitive performance.

Dual-wavelength pumped latticed Fermi-Pasta-Ulam recurrences in nonlinear Schrödinger equation

We show that the nonlinear stage of the dual-wavelength pumped modulation instability(MI)in nonlinear Schrödinger equation(NLSE)can be effectively analyzed by mode truncation methods.The resulting complicated heteroclinic structure of instability unveils all possible dynamic trajectories of nonlinear waves.Significantly,the latticed-Fermi-Pasta-Ulam recurrences on the modulated-wave background in NLSE are also investigated and their dynamic trajectories run along the Hamiltonian contours of the heteroclinic structure.It is demonstrated that there has much richer dynamic behavior,in contrast to the nonlinear waves reported before.This novel nonlinear wave promises to inject new vitality into the study of MI.

Research on Cavitation Characteristics and Influencing Factors of Herringbone Gear Pump

Cavitation is a common issue in pumps,causing a decrease in pump head,a fall in volumetric efficiency,and an intensification of outlet flow pulsation.It is one of the main hazards that affect the regular operation of the pump.Research on pump cavitation mainly focuses on mixed flow pumps,jet pumps,external spur gear pumps,etc.However,there are few cavitation studies on external herringbone gear pumps.In addition,pumps with different working principles significantly differ in the flow and complexity of the internal flow field.Therefore,it is urgent to study the cavitation characteristics of external herringbone gear pumps.Compared with experimentalmethods,visual research and cavitation area identification are achieved through computation fluid dynamic(CFD),and changing the boundary conditions and shape of the gear rotor is easier.The simulation yields a head error of only 0.003%under different grid numbers,and the deviation between experimental and simulation results is less than 5%.The study revealed that cavitation causes flow pulsation at the outlet,and the cavitation serious area is mainly distributed in the meshing gap and meshing area.Cavitation can be inhibited by reducing the speed,increasing the inlet pressure,and changing the helix angle can be achieved.For example,when the inlet pressure is 5 bar,the maximumgas volume fraction in themeshing area is less than 50%.These results provide a reference for optimizing the design and finding the optimal design parameters to reduce or eliminate cavitation.

Overlapping approach Proton Pump Inhibitors/Nux vomica-Heel as new intervention for gastro-esophageal reflux management:Delphi consensus study

BACKGROUND Gastro-esophageal reflux disease(GERD)may affect the upper digestive tract;up to 20%of population in Western nations are affected by GERD.Antacids,histamine H2-receptor antagonists,and Proton Pump Inhibitors(PPIs)are considered the referring medications for GERD.Nevertheless,PPIs must be managed carefully because their use,especially chronic,could be linked with some adverse effects.An effective and safe alternative pharmacological tool for GERD is needed.After the identification of potentially new medications to flank PPIs,it is mandatory to revise and improve good clinical practices even through a consensus process.AIM To optimize diagnosis and treatment guidelines for GERD through a consensus based on Delphi method.METHODS The availability of clinical studies describing the action of the multicomponent/multitarget medication Nux vomica-Heel,subject of the consensus,is the basic prerequisite for the consensus itself.A modified Delphi process was used to reach a consensus among a panel of Italian GERD specialists on the overlapping approach PPIs/Nux vomica-Heel as a new intervention model for the management of GERD.The Voting Consensus group was composed of 49 Italian Medical Doctors with different specializations:Gastroenterology,otolaryngology,geriatrics,and general medicine.A scientific committee analyzed the literature,determined areas that required investigation(in agreement with the multiple-choice questionnaire results),and identified two topics of interest:(1)GERD disease;and(2)GERD treatment.Statements for each of these topics were then formulated and validated.The Delphi process involved two rounds of questioning submitted to the panel experts using an online platform.RESULTS According to their routinary GERD practice and current clinical evidence,the panel members provided feedback to each questionnaire statement.The experts evaluated 15 statements and reached consensus on all 15.The statements regarding the GERD disease showed high levels of agreement,with consensus ranging from 70%to 92%.The statements regarding the GERD treatment also showed very high levels of agreement,with consensus ranging from 90%to 100%.This Delphi process was able to reach consensus among physicians in relevant aspects of GERD management,such as the adoption of a new approach to treat patients with GERD based on the overlapping between PPIs and Nux vomica-Heel.The consensus was unanimous among the physicians with different specializations,underlying the uniqueness of the agreement reached to identify in the overlapping approach between PPIs and Nux vomica-Heel a new intervention model for GERD management.The results support that an effective approach to deprescribe PPIs through a progressive decalage timetable(reducing PPIs administration to as-needed use),should be considered.CONCLUSION Nux vomica-Heel appears to be a valid opportunity for GERD treatment to favor the deprescription of PPIs and to maintain low disease activity together with the symptomatology remission.

Symmetric Brownian motor subjected to Lévy noise

In the past few years,attention has mainly been focused on the symmetric Brownian motor(BM)with Gaussian noises,whose current and energy conversion efficiency are very low.Here,we investigate the operating performance of the symmetric BM subjected to Lévy noise.Through numerical simulations,it is found that the operating performance of the motor can be greatly improved in asymmetric Lévy noise.Without any load,the Lévy noises with smaller stable indexes can let the motor give rise to a much greater current.With a load,the energy conversion efficiency of the motor can be enhanced by adjusting the stable indexes of the Lévy noises with symmetry breaking.The results of this research are of great significance for opening up BM’s intrinsic physical mechanism and promoting the development of nanotechnology.

Experimental Analysis of Radial Centrifugal Pump Shutdown

Centrifugal pumps are widely used in the metallurgy,coal,and building sectors.In order to study the hydraulic characteristics of a closed impeller centrifugal pump during its shutdown in the so-called power frequency and frequency conversion modes,experiments were carried to determine the characteristic evolution of parameters such as speed,inlet and outlet pressure,head,flow rate and shaft power.A quasi-steady-state method was also used to further investigate these transient behaviors.The results show that,compared to the power frequency input,the performance parameter curves for the frequency conversion input are less volatile and smoother.The characteristic time is longer and the response to shutdown is slower.The quasi-steady-state theoretical head-flow curves match the experimental head-flow curves more closely at low flow rates when the frequency conversion input is considered.Moreover,in this case,the similarity law predicts the hydraulic performance more accurately.

Early Application Study of Intravenous Pain Pump Combined with Parecoxib Injection in Relieving Pain in Patients after Thoracoscopy

Objective: To explore the clinical effectiveness of combined use of intravenous pain pump with Parecoxib injection in alleviating pain in patients during the early postoperative period after thoracoscopic surgery. Methods: Eighty patients who underwent thoracoscopic surgery in a tertiary hospital were selected as the study subjects and randomly divided into two groups, with 40 patients in each group. The control group received routine postoperative treatment with intravenous pain pump, while the experimental group received Parecoxib in addition to the standard postoperative pain pump treatment. Visual Analog Scale (VAS) pain scores were used to evaluate postoperative pain relief in both groups, along with adverse reactions, postoperative complications, and patient satisfaction with pain relief. Results: Patients who received Parecoxib injection in addition to the routine use of intravenous pain pump had VAS pain scores lower than 3 points at 6 h, 12 h, 24 h, and 36 h postoperatively compared to those in the control group. The incidence of postoperative lung collapse, pleural effusion, and pulmonary infections was also significantly lower in the experimental group. The differences between the two groups were statistically significant (P Conclusion: Early combined use of Parecoxib injection in the early postoperative period after thoracoscopic surgery has shown good clinical efficacy. It can reduce the level of pain in patients, promote effective coughing and expectoration, facilitate early mobilization of patients, improve patient compliance, reduce complications, shorten hospital stay, and expedite patient recovery. Therefore, it is worth promoting the widespread clinical application of Parecoxib injection in this setting.

A Stable Fuzzy-Based Computational Model and Control for Inductions Motors

In this paper,a stable and adaptive sliding mode control(SMC)method for induction motors is introduced.Determining the parameters of this system has been one of the existing challenges.To solve this challenge,a new self-tuning type-2 fuzzy neural network calculates and updates the control system parameters with a fast mechanism.According to the dynamic changes of the system,in addition to the parameters of the SMC,the parameters of the type-2 fuzzy neural network are also updated online.The conditions for guaranteeing the convergence and stability of the control system are provided.In the simulation part,in order to test the proposed method,several uncertain models and load torque have been applied.Also,the results have been compared to the SMC based on the type-1 fuzzy system,the traditional SMC,and the PI controller.The average RMSE in different scenarios,for type-2 fuzzy SMC,is 0.0311,for type-1 fuzzy SMC is 0.0497,for traditional SMC is 0.0778,and finally for PI controller is 0.0997.

A Unique Modelling Strategy to Dynamically Simulate the Performance of a Lobe Pump for Industrial Applications

The performance of a newly designed tri-lobe industrial lobe pump of high capacity is simulated by using commercial CFD solver Ansys Fluent. A combination of user-defined-functions and meshing strategies is employed to capture the rotation of the lobes. The numerical model is validated by comparing the simulated results with the literature values. The processes of suction, displacement, compression and exhaust are accurately captured in the transient simulation. The fluid pressure value remains in the range of inlet pressure value till the processes of suction and displacement are over. The instantaneous process of compression is accurately captured in the simulation. The movement of a particular working chamber is traced along the gradual degree of lobe’s rotation. At five different degrees of lobe’s rotation, pressure contour plots are reported which clearly shows the pressure values inside the working chamber. Each pressure value inside the working chamber conforms to the particular process in which the working chamber is operating. Finally, the power requirement at the shaft of rotation is estimated from the simulated values. The estimated value of power requirement is 3.61 BHP FHP whereas the same calculated theoretically is 3 BHP FHP. The discrepancy is attributed to the assumption of symmetry of blower along the thickness.

Blade Wrap Angle Impact on Centrifugal Pump Performance:Entropy Generation and Fluid-Structure Interaction Analysis

The centrifugal pump is a prevalent power equipment widely used in different engineering patterns,and the impeller blade wrap angle significantly impacts its performance.A numerical investigation was conducted to analyze the influence of the blade wrap angle on flow characteristics and energy distribution of a centrifugal pump evaluated as a low specific speed with a value of 69.This study investigates six impellermodels that possess varying blade wrap angles(95°,105°,115°,125°,135°,and 145°)that were created while maintaining the same volute and other geometrical characteristics.The investigation of energy loss was conducted to evaluate the values of total and entropy generation rates(TEG,EGR).The fluid-structure interaction was considered numerically using the software tools ANSYS Fluent and ANSYSWorkbench.The elastic structural dynamic equation was used to estimate the structural response,while the shear stress transport k–ωturbulence model was utilized for the fluid domain modeling.The findings suggest that the blade wrap angle has a significant influence on the efficiency of the pump.The impeller featuring a blade wrap angle of 145°exhibits higher efficiency,with a notable increase of 3.76%relative to the original model.Variations in the blade wrap angle impact the energy loss,shaft power,and pump head.The model with a 145°angle exhibited a maximum equivalent stress of 14.8MPa and a total deformation of 0.084 mm.The results provide valuable insights into the intricate flow mechanism of the centrifugal pump,particularly when considering various blade wrap angles.

An NMOS output-capacitorless low-dropout regulator with dynamic-strength event-driven charge pump

In this paper,an NMOS output-capacitorless low-dropout regulator(OCL-LDO)featuring dual-loop regulation has been proposed,achieving fast transient response with low power consumption.An event-driven charge pump(CP)loop with the dynamic strength control(DSC),is proposed in this paper,which overcomes trade-offs inherent in conventional structures.The presented design addresses and resolves the large signal stability issue,which has been previously overlooked in the event-driven charge pump structure.This breakthrough allows for the full exploitation of the charge-pump structure's poten-tial,particularly in enhancing transient recovery.Moreover,a dynamic error amplifier is utilized to attain precise regulation of the steady-state output voltage,leading to favorable static characteristics.A prototype chip has been fabricated in 65 nm CMOS technology.The measurement results show that the proposed OCL-LDO achieves a 410 nA low quiescent current(IQ)and can recover within 30 ns under 200 mA/10 ns loading change.

Effect of VOJTA Therapy on Gross Motor Function in Children with Cerebral Palsy

Objective: To investigate the effect of VOJTA therapy on gross motor function in children with cerebral palsy. Methods: The 86 children with cerebral palsy were all from the First People’s Hospital of Jingzhou City from January 2023-December 2023, and were divided into the control group and the study group with 43 cases according to the principle of voluntariness. Results: In terms of total effective rate of treatment, the gross motor function scale-88 (GMFM-88) was used to evaluate the effective rate before and after treatment, and the effective rate of the study group was higher than that of the control group, and the difference was statistically significant, and the scores of gross motor items of GMFM-88 were better than those of the control group after treatment, and the difference was statistically significant (P 0.05). Conclusion: The application of VOJTA therapy in the treatment of children with cerebral palsy can not only promote the rehabilitation of gross motor function, but also help to improve the treatment effect, and the earlier the treatment, the better.

Working condition recognition of sucker rod pumping system based on 4-segment time-frequency signature matrix and deep learning

High-precision and real-time diagnosis of sucker rod pumping system(SRPS)is important for quickly mastering oil well operations.Deep learning-based method for classifying the dynamometer card(DC)of oil wells is an efficient diagnosis method.However,the input of the DC as a two-dimensional image into the deep learning framework suffers from low feature utilization and high computational effort.Additionally,different SRPSs in an oil field have various system parameters,and the same SRPS generates different DCs at different moments.Thus,there is heterogeneity in field data,which can dramatically impair the diagnostic accuracy.To solve the above problems,a working condition recognition method based on 4-segment time-frequency signature matrix(4S-TFSM)and deep learning is presented in this paper.First,the 4-segment time-frequency signature(4S-TFS)method that can reduce the computing power requirements is proposed for feature extraction of DC data.Subsequently,the 4S-TFSM is constructed by relative normalization and matrix calculation to synthesize the features of multiple data and solve the problem of data heterogeneity.Finally,a convolutional neural network(CNN),one of the deep learning frameworks,is used to determine the functioning conditions based on the 4S-TFSM.Experiments on field data verify that the proposed diagnostic method based on 4S-TFSM and CNN(4S-TFSM-CNN)can significantly improve the accuracy of working condition recognition with lower computational cost.To the best of our knowledge,this is the first work to discuss the effect of data heterogeneity on the working condition recognition performance of SRPS.

Simulation of Underground Reservoir Stability of Pumped Storage Power Station Based on Fluid-Structure Coupling

Based on global initiatives such as the clean energy transition and the development of renewable energy,the pumped storage power station has become a new and significant way of energy storage and regulation,and its construction environment is more complex than that of a traditional reservoir.In particular,the stability of the rock strata in the underground reservoirs is affected by the seepage pressure and rock stress,which presents some challenges in achieving engineering safety and stability.Using the advantages of the numerical simulation method in dealing deal with nonlinear problems in engineering stability,in this study,the stability of the underground reservoir of the Shidangshan(SDS)pumped storage power station was numerically calculated and quantitatively analyzed based on fluid-structure coupling theory,providing an important reference for the safe operation and management of the underground reservoir.First,using the COMSOL software,a suitablemechanicalmodel was created in accordance with the geological structure and project characteristics of the underground reservoir.Next,the characteristics of the stress field,displacement field,and seepage field after excavation of the underground reservoir were simulated in light of the seepage effect of groundwater on the nearby rock of the underground reservoir.Finally,based on the construction specifications and Molar-Coulomb criterion,a thorough evaluation of the stability of the underground reservoir was performed through simulation of the filling and discharge conditions and anti-seepage strengthening measures.The findings demonstrate that the numerical simulation results have a certain level of reliability and are in accordance with the stress measured in the project area.The underground reservoir excavation resulted in a maximum displacement value of the rock mass around the caverns of 3.56 mm in a typical section,and the safety coefficient of the parts,as determined using the Molar-Coulomb criterion,was higher than 1,indicating that the project as a whole is in a stable state.

Coupled Numerical Simulation of Electromagnetic and Flow Fields in a Magnetohydrodynamic Induction Pump

Magnetohydrodynamic(MHD)induction pumps are contactless pumps able to withstand harsh environments.The rate of fluid flow through the pump directly affects the efficiency and stability of the device.To explore the influence of induction pump settings on the related delivery speed,in this study,a numerical model for coupled electromagnetic and flow field effects is introduced and used to simulate liquid metal lithium flow in the induction pump.The effects of current intensity,frequency,coil turns and coil winding size on the velocity of the working fluid are analyzed.It is shown that the first three parameters have a significant impact,while changes in the coil turns have a negligible influence.The maximum increase in working fluid velocity within the pump for the parameter combination investigated in this paper is approximately 618%.As the frequency is increased from 20 to 60 Hz,the maximum increase in the mean flow rate of the working fluid is approximately 241%.These research findings are intended to support the design and optimization of these devices.

Harmonics in the Squirrel Cage Induction Motor Analytic Calculation Part III: Influence on the Torque-speed Characteristic

The harmonics that appear in the squirrel cage asynchronous machine have been discussed in great detail in the literature for a long time. However, the systematization of the phenomenon is still pending, so we made an attempt to fill this gap in the previous parts of our study by elaborating formulas for calculation of parasitic torques. It was a general demand among those who work in this field towards the author to verify his formulas with measurements. In the literature, it seems,only one detailed, purposeful series of measurements has been published so far, the purpose of which was to investigate the effect of the number of rotor slots on the torque-speed characteristic curve of the machine. The main goal of this study is to verify the correctness of the formulas by comparing them with the referred series of measurements. Relying on this, the expected synchronous parasitic torques were developed for the frequently used rotor slot numbers-as a design guide for the engineer.Thus, together with our complete table for radial magnetic pull published in our previous work, the designer has all the principles, data and formulas available for the right number of rotor slots for his given machine and for the drive system. This brings this series of papers to an end.