Brain endothelial cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway in aging and neurodegeneration

The cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway has emerged as a key mediator of neuroinflammation.While current studies primarily attribute its effects to neurons and glial cells,emerging research suggests that cGAS-STING signaling may play a critical role in cerebral vasculature,particularly in brain endothelial cells.Therefore,studying the role 7of inflammation caused by the cGAS-STING pathway in brain endothelial cells could provide a more comprehensive understanding of neuroinflammatory disease and new avenues for therapeutic interventions.Here,we review the multifaceted role of global cGAS-STING signaling in various neurological and neuroinflammatory diseases and the potential contribution of cGAS-STING in brain endothelial cells.

Outcomes and efficacy of magnetic resonance imaging-compatible sacral nerve stimulator for management of fecal incontinence: A multi-institutional study

BACKGROUND Fecal incontinence(FI)is an involuntary passage of fecal matter which can have a significant impact on a patient’s quality of life.Many modalities of treatment exist for FI.Sacral nerve stimulation is a well-established treatment for FI.Given the increased need of magnetic resonance imaging(MRI)for diagnostics,the In-terStim which was previously used in sacral nerve stimulation was limited by MRI incompatibility.Medtronic MRI-compatible InterStim was approved by the United States Food and Drug Administration in August 2020 and has been widely used.AIM To evaluate the efficacy,outcomes and complications of the MRI-compatible InterStim.METHODS Data of patients who underwent MRI-compatible Medtronic InterStim placement at UPMC Williamsport,University of Minnesota,Advocate Lutheran General Hospital,and University of Wisconsin-Madison was pooled and analyzed.Patient demographics,clinical features,surgical techniques,complications,and outcomes were analyzed.Strengthening the Reporting of Observational studies in Epidemiology(STROBE)cross-sectional reporting guidelines were used.RESULTS Seventy-three patients had the InterStim implanted.The mean age was 63.29±12.2 years.Fifty-seven(78.1%)patients were females and forty-two(57.5%)patients had diabetes.In addition to incontinence,overlapping symptoms included diarrhea(23.3%),fecal urgency(58.9%),and urinary incontinence(28.8%).Fifteen(20.5%)patients underwent Peripheral Nerve Evaluation before proceeding to definite implant placement.Thirty-two(43.8%)patients underwent rechargeable InterStim placement.Three(4.1%)patients needed removal of the implant.Migration of the external lead connection was observed in 7(9.6%)patients after the stage I procedure.The explanation for one patient was due to infection.Seven(9.6%)patients had other complications like nerve pain,hematoma,infection,lead fracture,and bleeding.The mean follow-up was 6.62±3.5 mo.Sixty-eight(93.2%)patients reported significant improvement of symptoms on follow-up evaluation.CONCLUSION This study shows promising results with significant symptom improvement,good efficacy and good patient outcomes with low complication rates while using MRI compatible InterStim for FI.Further long-term follow-up and future studies with a larger patient population is recommended.

Treadmill exercise in combination with acousto-optic and olfactory stimulation improves cognitive function in APP/PS1 mice through the brain-derived neurotrophic factor-and Cygb-associated signaling pathways

A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.

Pain Efficacy of a Home-Based Low-Intensity Continuous Ultrasound Stimulator for Knee Arthritis: A Single-Arm, Open-Label, Prospective Clinical Trial

1) Background: Osteoarthritis (OA) is defined as a degenerative joint disease that mainly affects the bone. This study aims to evaluate the effect of low-intensity continuous ultrasound (LICUS) treatment on the knee of osteoarthritis patients through home-based intervention using the LICUS medical device. 2) Methods: The clinical trials were designed in a single-arm, open-label, and intervention study. Thirty-five participants, including those who dropped out (12%), were screened and enrolled. The patients received LICUS (1.1 MHz, 1.5 W/cm2, collimated beams) on the knee by the instructions of the investigator at home (5 min/session, 3 times/day, for four-weeks). Outcome measures were assessed using the Visual Analog Scale (VAS) as a primary endpoint and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) as a secondary endpoint to evaluate pain relief and functional recovery of the knee between pre-treatment (baseline) and post-treatment (four-weeks). 3) Results: Knee pain scores measured using the VAS and WOMAC indices were significantly reduced after a four-week treatment with LICUS compared to baseline. Knee stiffness and functional capacity were significantly reduced after the LICUS application. In addition, there were no reports of adverse effects during the study period. 4) Conclusion: Long-term and home-based application of LICUS can be recommended as an alternative option for the treatment of OA patients, as evidenced by the effect of pain relief and knee function recovery.

Vagus nerve stimulation in intracerebral hemorrhage:the need for further research

Vagus nerve stimulation(VNS)and stroke:Stroke is the second leading cause of death and the third leading cause of disability worldwide(Baig et al.,2023).There have been significant paradigm shifts in the management of acute ischemic stroke through mechanical thrombectomy.In chronic ischemic stroke,invasive VNS paired with rehabilitation is associated with a significant increase in upper limb motor recovery and is FDA-approved(Baig et al.,2023).There are no treatments of similar efficacy in acute intracerebral hemorrhage(ICH)where several promising trials,e.g.,TICH-2,STOP-AUST,and TRAIGE did not show improvements in functional outcomes(Puy et al.,2023).

Prolonged intermittent theta burst stimulation restores the balance between A_(2A)R-and A_(1)R-mediated adenosine signaling in the 6-hydroxidopamine model of Parkinson's disease

An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control.

Repetitive transcranial magnetic stimulation in Alzheimer’s disease:effects on neural and synaptic rehabilitation

Alzheimer’s disease is a neurodegenerative disease resulting from deficits in synaptic transmission and homeostasis.The Alzheimer’s disease brain tends to be hyperexcitable and hypersynchronized,thereby causing neurodegeneration and ultimately disrupting the operational abilities in daily life,leaving patients incapacitated.Repetitive transcranial magnetic stimulation is a cost-effective,neuro-modulatory technique used for multiple neurological conditions.Over the past two decades,it has been widely used to predict cognitive decline;identify pathophysiological markers;promote neuroplasticity;and assess brain excitability,plasticity,and connectivity.It has also been applied to patients with dementia,because it can yield facilitatory effects on cognition and promote brain recovery after a neurological insult.However,its therapeutic effectiveness at the molecular and synaptic levels has not been elucidated because of a limited number of studies.This study aimed to characterize the neurobiological changes following repetitive transcranial magnetic stimulation treatment,evaluate its effects on synaptic plasticity,and identify the associated mechanisms.This review essentially focuses on changes in the pathology,amyloidogenesis,and clearance pathways,given that amyloid deposition is a major hypothesis in the pathogenesis of Alzheimer’s disease.Apoptotic mechanisms associated with repetitive transcranial magnetic stimulation procedures and different pathways mediating gene transcription,which are closely related to the neural regeneration process,are also highlighted.Finally,we discuss the outcomes of animal studies in which neuroplasticity is modulated and assessed at the structural and functional levels by using repetitive transcranial magnetic stimulation,with the aim to highlight future directions for better clinical translations.

Enhanced mechanical squeezing in an optomechanical system via backward stimulated Brillouin scattering

We investigate theoretically the enhancement of mechanical squeezing in a multimode optomechanical system by introducing a coherent phonon–photon interaction via the backward stimulated Brillouin scattering(BSBS)process.The coherent photon–phonon interaction where two optical modes couple to a Brillouin acoustic mode with a large decay rate provides an extra channel for the cooling of a Duffing mechanical oscillator.The squeezing degree and the robustness to the thermal noises of the Duffing mechanical mode can be enhanced greatly.When the Duffing nonlinearity is weak,the squeezing degree of the mechanical mode in the presence of BSBS can be improved by more than one order of magnitude compared with that in the absence of BSBS.Our scheme may be extended to other quantum systems to study novel quantum effects.

Purification and Characterization of Hepatocyte Regeneration Stimulatory Factor from Shark Liver

Aim To purify hepatocyte regeneration stimulatory factor from shark liver and research its molecular feature and activity. Methods and Results Hepatocyte regeneration stimulatory factor (sHRSF) was isolated from healthy shark livers and separated by homogenization, freezing melting, heat treating, centrifugation, and ultrafiltration. HRSF activity was found mainly in the subfraction of molecular weight less than 30 000 daltons. This crude ultrafiltrate was further purified successively by DEAE Sepharose fast flow chromatography, FPLC Resource 30Q, Resource Q and Mono Q chromatography. A single band was displayed on sodium dodecyl sulfate polyacrylamide gel electrophoresis, which corresponds to molecular weight of 14 600 daltons. The characteristic absorption was obtained at the wavelength 276 nm. The isoelectric point was about 5 1. It contained 18 amino acids and the 15 N terminal amino acid residues were LVGPIGAVGPAGKDG. It had a significant activity in stimulating liver to regenerate. Conclusion We obtained an unknown new active protein, that is hepatocyte regeneration stimulatory factor from shark liver (sHRSF).

Growth induction of hepatic stimulator substance in hepatocytes through its regulation on EGF receptors

The cytosolic liver-specific growth factor-hepatic stimulator substance (HSS) has been shown to be able to amplify the rat hepatocyte proliferation responded to EGF. In order to get more insight into the mechanism, the regulatory effect of HSS on EGF-receptor(EGF-R) and the receptor phosphorylation at molecular level was studied. HSS partially purified from weanling rat liver was given to cultured hepatocytes and its influence on EGF-R specific binding and internalization as well as mRNA expression were investigated. The results showed that preincubation of hepatocytes with HSS could lead to an increase in [125I]-EGF binding to its receptors and inhibit EGFinduced receptor down-regulation. Furthermore, the overexpression of EGF-R mRNA stimulated by HSS was seen during 2-12 h after the incubation. Additionally, it was demonstrated with human hepatoma sMMC-7721 cells in Western blot that the EGF-R expression and the receptor autophosphorylation were increased with dose/timedependency after HSS treatment. These results strongly suggest that the mechanism of HSS action on hepatocyte growth might be related to its modulation on EGF-R and receptor-mediated signaling transduction.

Partial isolation and identification of hepatic stimulator substance mRNA extracted from human fetal liver

IM To partially isolate and identify hepatic stimulator substance mRNA from human fetal liver tissues.METHODS The poly (A)mRNA was extracted from human fetal liver tissues of 4-5 month gestation, fractionated by size on sucrose gradient centrifugation, translated into protein from each fraction in vitro and then its products were tested for HSS activity.RESULTS Twentytwo 500μg total RNA was obtained from human fetal liver tissues and pooled. mRNA of 420μg was yielded, processed by oligo(dT)cellulose column chromatography, then was sizefractionated by ultracentrifution on a continuous sucrose density gradient (5%-25%), and separated into 18 fractions. Translated products of mRNA in fraction 8 and 9 could produce a twofold increase in the incorporation of 3HTdR into DNA of SMMC7721 hepatoma cells and in a heatresistant and organspecific way.CONCLUSION The partially purified HSS mRNA was obtained and this would facilitate the cloning of HSS using expression vectors.

Safety and efficacy of soluble guanylate cyclase stimulators in patients with heart failure: A systematic review and meta-analysis

BACKGROUND The utility of novel oral soluble guanylate cyclase(sGC)stimulators(vericiguat and riociguat),in patients with reduced or preserved ejection fraction heart failure(HFrEF/HFpEF)is currently unclear.AIM To determine the efficacy and safety of sGC stimulators in HF patients.METHODS Multiple databases were searched to identify relevant randomized controlled trials(RCTs).Data on the safety and efficacy of sGC stimulators were compared using relative risk ratio(RR)on a random effect model.RESULTS Six RCTs,comprising 5604 patients(2801 in sGC stimulator group and 2803 placebo group)were included.The primary endpoint(a composite of cardiovascular mortality and first HF-related hospitalization)was significantly reduced in patients receiving sGC stimulators compared to placebo[RR 0.92,95%confidence interval(CI):0.85-0.99,P=0.02].The incidence of total HF-related hospitalizations were also lower in sGC group(RR 0.91,95%CI:0.86-0.96,P=0.0009),however,sGC stimulators had no impact on all-cause mortality(RR 0.96,95%CI:0.86-1.07,P=0.45)or cardiovascular mortality(RR 0.94,95%CI:0.83-1.06,P=0.29).The overall safety endpoint(a composite of hypotension and syncope)was also similar between the two groups(RR 1.50,95%CI:0.93-2.42,P=0.10).By contrast,a stratified subgroup analysis adjusted by type of sGC stimulator and HF(vericiguat vs riociguat and HFrEF vs HFpEF)showed near identical rates for all safety and efficacy endpoints between the two groups at a mean follow-up of 19 wk.For the primary composite endpoint,the number needed to treat was 35,the number needed to harm was 44.CONCLUSION The use of vericiguat and riociguat in conjunction with standard HF therapy,shows no benefit in terms of decreasing HF-related hospitalizations or mortality.

Novel T-cell co-stimulators in cancer gene therapy and immunotherapy

Optimal activation of T cells requires at least 2signals. Signal one is generated by interactionsbetween T cell receptor and antigenic peptide-majorhistocompatibility complex on antigen-presentingcells. Signal two is delivered by co-stimulatory ligandson antigen-presenting cells to their receptors on

Vagus nerve stimulation in cerebral stroke:biological mechanisms,therapeutic modalities,clinical applications,and future directions

Stroke is a major disorder of the central nervous system that poses a serious threat to human life and quality of life.Many stro ke victims are left with long-term neurological dysfunction,which adversely affects the well-being of the individual and the broader socioeconomic impact.Currently,poststroke brain dysfunction is a major and difficult area of treatment.Vagus nerve stimulation is a Food and Drug Administration-approved exploratory treatment option for autis m,refractory depression,epilepsy,and Alzheimer’s disease.It is expected to be a novel therapeutic technique for the treatment of stroke owing to its association with multiple mechanisms such as alte ring neurotransmitters and the plasticity of central neuro ns.In animal models of acute ischemic stroke,vagus nerve stimulation has been shown to reduce infarct size,reduce post-stroke neurological damage,and improve learning and memory capacity in rats with stroke by reducing the inflammatory response,regulating bloodbrain barrier permeability,and promoting angiogenesis and neurogenesis.At present,vagus nerve stimulation includes both invasive and non-invasive vagus nerve stimulation.Clinical studies have found that invasive vagus nerve stimulation combined with rehabilitation therapy is effective in im proving upper limb motor and cognitive abilities in stroke patients.Further clinical studies have shown that non-invasive vagus nerve stimulation,including ear/ce rvical vagus nerve stimulation,can stimulate vagal projections to the central nervous system similarly to invasive vagus nerve stimulation and can have the same effect.In this paper,we first describe the multiple effects of vagus nerve stimulation in stroke,and then discuss in depth its neuroprotective mechanisms in ischemic stroke.We go on to outline the res ults of the current major clinical applications of invasive and non-invasive vagus nerve stimulation.Finally,we provide a more comprehensive evaluation of the advantages and disadvantages of different types of vagus nerve stimulation in the treatment of cerebral ischemia and provide an outlook on the developmental trends.We believe that vagus nerve stimulation,as an effective treatment for stroke,will be widely used in clinical practice to promote the recovery of stroke patients and reduce the incidence of disability.

High-frequency repetitive transcranial magnetic stimulation promotes neural stem cell proliferation after ischemic stroke

Prolife ration of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage.Transcranial magnetic stimulation(TMS)has recently emerged as a tool for inducing endogenous neural stem cell regeneration,but its underlying mechanisms remain unclea r In this study,we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem cells.Additionally,repetitive TMS reduced the volume of cerebral infa rction in a rat model of ischemic stro ke caused by middle cerebral artery occlusion,im p roved rat cognitive function,and promoted the proliferation of neural stem cells in the ischemic penumbra.RNA-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ischemia.Furthermore,PCR analysis revealed that repetitive TMS promoted AKT phosphorylation,leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and Cdk4.This effect was also associated with activation of the glycogen synthase kinase 3β/β-catenin signaling pathway,which ultimately promotes the prolife ration of neural stem cells.Subsequently,we validated the effect of repetitive TMS on AKT phosphorylation.We found that repetitive TMS promoted Ca2+influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway,thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3β/β-catenin pathway.These findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+influx-dependent phosphorylated AKT/glycogen synthase kinase 3β/β-catenin signaling pathway.This study has produced pioneering res ults on the intrinsic mechanism of repetitive TMS to promote neural function recove ry after ischemic stro ke.These results provide a stro ng scientific foundation for the clinical application of repetitive TMS.Moreover,repetitive TMS treatment may not only be an efficient and potential approach to support neurogenesis for further therapeutic applications,but also provide an effective platform for the expansion of neural stem cells.

Contribution of glial cells to the neuroprotective effects triggered by repetitive magnetic stimulation:a systematic review

Repetitive transcranial magnetic stimulation has been increasingly studied in different neurological diseases,and although most studies focus on its effects on neuronal cells,the contribution of nonneuronal cells to the improvement trigge red by repetitive transcranial magnetic stimulation in these diseases has been increasingly suggested.To systematically review the effects of repetitive magnetic stimulation on non-neuronal cells two online databases.Web of Science and PubMed were searched fo r the effects of high-frequency-repetitive transcranial magnetic stimulation,low-frequencyrepetitive transcranial magnetic stimulation,intermittent theta-bu rst stimulation,continuous thetaburst stimulation,or repetitive magnetic stimulation on non-neuronal cells in models of disease and in unlesioned animals or cells.A total of 52 studies were included.The protocol more frequently used was high-frequency-repetitive magnetic stimulation,and in models of disease,most studies report that high-frequency-repetitive magnetic stimulation led to a decrease in astrocyte and mic roglial reactivity,a decrease in the release of pro-inflammatory cyto kines,and an increase of oligodendrocyte proliferation.The trend towards decreased microglial and astrocyte reactivity as well as increased oligodendrocyte proliferation occurred with intermittent theta-burst stimulation and continuous theta-burst stimulation.Few papers analyzed the low-frequency-repetitive transcranial magnetic stimulation protocol,and the parameters evaluated were restricted to the study of astrocyte reactivity and release of pro-inflammatory cytokines,repo rting the absence of effects on these paramete rs.In what concerns the use of magnetic stimulation in unlesioned animals or cells,most articles on all four types of stimulation reported a lack of effects.It is also important to point out that the studies were developed mostly in male rodents,not evaluating possible diffe rential effects of repetitive transcranial magnetic stimulation between sexes.This systematic review supports that thro ugh modulation of glial cells repetitive magnetic stimulation contributes to the neuroprotection or repair in various neurological disease models.Howeve r,it should be noted that there are still few articles focusing on the impact of repetitive magnetic stimulation on non-neuronal cells and most studies did not perform in-depth analyses of the effects,emphasizing the need for more studies in this field.

Pulse electrical arc stimulator based on single-electrode for active exercise in tail-suspension rat

To make rat do active exercise to counteract bone loss in the rat tail-suspension model, a pulse electrical stimulator based on single-electrode with a low-current and a high-voltage was designed. The stimulator was controlled by SCM (single chip micyoco) that could accurately control the stimulation duration and the interval between stimulations, and cease the operation after the recorded number of stimulation had reached the value set by the program. With the help of posture estimation part, the device would operate intelligently by determining whether to stimulate or not, depending on the posture of rat's limb. Software was developed to make operator control the stimulator using computer, save the experiment data and print the report. In practical experiment, the voltaic arc is generated by the stimulator, and impacted on the rat's thenar. This induced pain to the rat and the rat would actively contract its hindlimb to evade the pain, so active exercise was carried out. The tail-suspension rats were trained twice every day for 14 d. At the 0 and 14th day, bone mineral density of rat femurs was determined by dual energy X-ray absorptiometry (DXA). The results show that the active exercise stimulated by the pulse electrical arc stimulator can attenuate weightlessness-induced bone loss, and this device is a convenient steady performance electrical stimulator that can surely induce rat's hindlimb to do active exercise.

Working toward an integrated plasticity/network framework for repetitive transcranial magnetic stimulation to inform tailored treatments

Non-invasive brain stimulation techniques(NIBS),including repetitive transcranial magnetic stimulation(rTMS) and transcranial electric stim ulation(tES),are increasingly being adopted clinically for treatment of neuropsychiatric and neurological disorders,albeit with varying success.The rationale behind the use of NIBS has historically been that stim ulation techniques modulate neuronal activity in the targeted region and consequently induce plasticity which can lead to therapeutic outcomes.

Pain management using Han’s acupoint nerve stimulator combined with patient-controlled analgesia following neurosurgery A randomized case control study

BACKGROUND： Han＇s acupoint nerve stimulator （HANS） has been frequently used to relieve pain by promoting the central nerve system＇s release of endogenous opioid peptides through electric stimulation to the body surface. OBJECTIVE： To investigate the pain-relieving effects of HANS, combined with patient-controlled analgesia, following neurosurgery, and to observe adverse reactions and effects. DESIGN, TIME AND SETTING： A randomized control observation was performed at the Department of Neurology in the First Affiliated Hospital of Gannan Medical College （Ganzhou, Jiangxi Province, China） from January 2005 to February 2006. PARTICIPANTS： Forty patients, who were selected for craniotomy and required pain relief following surgery at the Department of Neurology in the First Affiliated Hospital of Gannan Medical College （China）, were included in this study. METHODS： Forty patients underwent neurosurgery and were randomly divided into two groups： patient-controlled analgesia plus HANS （＋HANS, n = 20） and patient-controlled analgesia （-HANS, n = 20）. Both groups were well matched in baseline data. Automatic syringe infusion pump ZZB-150 was the product of Nantong Aipeng Medical Instruments Co., Ltd. （China）. Patient-controlled analgesia consisted of 100 mL 0.02% lappaconitine/0.02% metoclopramide. LH-402 HANS instrument was produced in Beijing （China）, with a serial number of 402183. The HANS instrumentation was used to stimulate the Hegu-Laogong acupoint on one side and Jiaogan, Shenmen penetrating Shen, Waifei, Naogan penetrating Pizhixia ear acupoints on the affected side for one hour, with 2-hour intervals. The disperse-dense wave was alternating, with a 2/100 Hz frequency of electrical stimulation. MAIN OUTCOME MEASURE： The scores of visual analogue scale and incidence of adverse reaction were observed in two groups following surgery. RESULTS： Compared with the HANS group, the visual analogue scale scores were remarkably lower in the ＋HANS group six hours after surgery （P 〈 0.01）, and the incidence rate of adverse reactions, such as nausea and vomiting, was also decreased （P 〈 0.05）.CONCLUSION： The application of HANS to induce body surface stimulation can enhance the effect of pain relief and reduce adverse reactions when used in combination with patient-controlled analgesia following neurosurgery. The effect of combined therapy is superior to patient-controlled analgesia alone.

Allelochemicals as Growth Stimulators for Drought Stressed Maize

Sorgaab, an aqueous extract of sorghum leaves was applied to probe the modulation in growth and physiological attributes of maize under drought in lab and greenhouse studies. Sorgaab soaked seeds (10 dilutions) were germinated to assess drought tolerance at germination and seedling growth stages. More concentrated Sorgaab solutions (2 mL·L-1) were damaging, while lower concentration in the range of 0.75 to 1.5 mL·L-1 improved the root and shoot growth of maize under drought. Applied drought stress decreased chlorophyll b greater than chlorophyll a that improved the chl a/b ratio. Application of Sorgaab also improved the internal CO2 assimilation, which increased the net photosynthesis and A/E ratio of drought affected plants. Soluble phenolics and anthocyanins were also more increased in plant receiving Sorgaab under drought than control. Although greater concentrations of phenolic acids inhibit the uptake of ions, but its lower concentrations stimulate the uptake of K+, Ca2+, NO3, PO4. In conclusion, although high concentrations of Sorgaab reduced the growth of plants, it might alleviate the adverse effects of drought, if applied at the low concentration. Dilute concentrations of Sorgaab can be utilized as a natural source for improving drought resistance in maize both at germination and later growth stages.