Spontaneous Discharge Research Articles

A Pilot Study to Evaluate the Feasibility of Anti-Fibrinolytic Agents in Reducing Hemorrhagic Complications in Pediatric Patients with Thrombocytopenia

Background: The risk of bleeding remains high in thrombocytopenic pediatric hematology-oncology patients despite the use of prophylactic platelet transfusions. In one study, WHO grade 2 or higher bleeding occurred in >80% of pediatric subjects receiving hematopoietic stem cell transplantation or chemotherapy despite a platelet transfusion threshold of 10,000/µl. The risk of bleeding is not decreased with higher transfusion thresholds or increased platelet doses. Bleeding episodes are associated with increased mortality rates, greater utilization of resources and increased transfusion requirements. We examined the use of anti-fibrinolytic agents in decreasing bleeding events and platelet transfusions. Methods: We conducted a randomized double-blinded Phase 2 trial of tranexamic acid versus placebo in inpatient pediatric patients undergoing chemotherapy or HSCT expected to have prolonged thrombocytopenia. All patients admitted to the Oncology or HSCT services were screened for eligibility. Patients consenting for enrollment received either tranexamic acid 10m/kg/dose or normal saline every 8 hours while the platelet count as <30,000/ul until discharge or spontaneous platelet recovery (maximum 30 days). We conducted daily hemostatic assessments using the WHO bleeding scale and monitored adverse events and platelet transfusion requirements. Follow-up assessments took place at 7 and 30 days following completion of study medication. Primary aims were to assess safety and feasibility of tranexamic acid in children with hypoproliferative thrombocytopenia. Results: We screened 697 admissions over 11 months, 31 patients were eligible for enrollment. Enrollment was suspended in March 2020 for COVID reasons though screening continued through July 2020. An additional 10 eligible patients were identified in this period. The most common reasons for ineligibility included recent asparaginase administration, predicted inpatient stay <5 days and age ≤ 2 or ≥ 18 years. Eleven patients enrolled and completed all study procedures. There were no missed doses of medication, 88.4% of doses were administered within one hour of prescribed time. Patients remained on study for a mean of 11.1 days. Five patients each met criteria for spontaneous platelet count recovery or discharge, 1 patient received the study medication for 30 days. Bleeding (all grades) occurred on 29.5% of days. Grade 2 or higher bleeding occurred on 4.9% of days and was experienced by 27.3% of patients. The most common sites of bleeding were oral/nasal and cutaneous. Subjects received a median of 2 platelet transfusions per patient. There were no thromboembolic events or serious adverse events. Conclusion: Tranexamic acid is well tolerated can be safely administered to pediatric oncology patients as an adjunct to therapy. We are planning a multi-center randomized controlled trial to assess the efficacy of tranexamic acid in reducing bleeding complications in this population. Disclosures Triulzi: Fresenius Kabi: Consultancy; Cerus Corp: Research Funding. OffLabel Disclosure: Tranexamic Acid - This medication is being studied as an adjuvant to therapy to prevent bleeding complications and reduce platelet transfusions in pediatric patients with hypoproliferative thrombocytopenia.

Effect of acute mitochondrial dysfunction on hyperexcitable network activity in rat hippocampus in vitro

Metabolic stress imposed by epileptic seizures can result in mitochondrial dysfunction, believed to act as positive feedback on epileptogenesis and seizure susceptibility. As the mechanism behind this positive feedback is unclear, the aim of the present study was to investigate the causal link between acute mitochondrial dysfunction and increased seizure susceptibility in hyperexcitable hippocampal networks. Following the induction of spontaneous interictal-like discharges, acute selective pharmacological blockade of either of the mitochondrial respiratory complexes (MRC) I-IV induced seizure-like events (SLE) in 78–100% of experiments. A similar result was obtained by uncoupling the oxidative phosphorylation (OXPHOS) but not by selective blockade of MRCV (ATP synthase) which did not induce SLE. The reactive oxygen species (ROS) scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (tempol, 2 mM) significantly reduced the proconvulsant effect of blocking MRCI but did not reduce the proconvulsant effect of OXPHOS uncoupling. These findings indicate that acute mitochondrial dysfunction can lead to a convulsive state within a short timeframe, and that increased ROS production makes substantial contribution to such induction in addition to other mitochondrial related factors, which appears to be independent of changes in ROS and ATP production.

The Specific Effects of OD-1, a Peptide Activator, on Voltage-Gated Sodium Current and Seizure Susceptibility.

OD-1, a scorpion toxin, has been previously recognized as an activator of voltage-gated Na+ currents. To what extent this agent can alter hippocampal neuronal Na+ currents and network excitability and how it can be applied to neuronal hyperexcitability research remains unclear. With the aid of patch-clamp technology, it was revealed that, in mHippoE-14 hippocampal neurons, OD-1 produced a concentration-, time-, and state-dependent rise in the peak amplitude of INa. It shifted the INa inactivation curve to a less negative potential and increased the frequency of spontaneous action currents. Further characterization of neuronal excitability revealed higher excitability in the hippocampal slices treated with OD-1 as compared with the control slices. A stereotaxic intrahippocampal injection of OD-1 generated a significantly higher frequency of spontaneous seizures and epileptiform discharges compared with intraperitoneal injection of lithium-pilocarpine- or kainic acid-induced epilepsy, with comparable pathological changes. Carbamazepine significantly attenuated OD-1 induced seizures and epileptiform discharges. The OD-1-mediated modifications of INa altered the electrical activity of neurons in vivo and OD-1 could potentially serve as a novel seizure and excitotoxicity model.

A Nomogram to Predict the Probability of Breast Intraductal Tumors in Patients with Nipple Discharge: A Real-World Study Based on Our 13-Year Clinical Experience.

IntroductionNipple discharge is a common symptom of breast disease. We aimed to perform a descriptive statistical analysis of the cases we evaluated and establish a model to predict intraductal tumors.Materials and MethodsWe conducted a retrospective study of patients from 2007 to 2019. In total, 1333 patients who completed the fiberoptic ductoscopy (FDS) were evaluated. The variables were analyzed by χ2 test. Logistic regression was used to analyze the relationship between the patient’s clinical characteristics and intraductal tumors and establish a predictive model. Receiver operating characteristic (ROC) curve analysis was used to assess the sensitivity and specificity of the predictive ability of the model. Calibration curves and decision curve analysis (DCA) were used to evaluate the model.ResultsPatients with spontaneous, single-duct, bloody discharge and a smooth ductal wall were more likely to be diagnosed with tumors by ductoscopy. A model was established based on five variables: age, side of discharge, spontaneous discharge status, duration of discharge, and color of discharge. The model was subsequently validated in 183 patients with complete data on the variables in the validation cohort. The area under the ROC curve (AUC) was calculated to be 0.716, indicating good predictive ability.ConclusionPatients with the clinical characteristics of unilateral, bloody, single-duct, spontaneous discharge and a smooth ductal wall were more likely to have intraductal tumors by ductoscopy. Our nomogram can effectively predict intraductal tumors in patients with nipple discharge.

Recycling electrochemical processing of Ag(I) species dispersed in polypyrrole towards Ag0 nanoparticles

Silver(I) hexafluorophosphate was dispersed in electrosynthezed polypyrrole hexafluorophosphate by precipitation, using an aqueous Ag(I) nitrate solution. The electrochemistry of the resulting composite was studied in aqueous hexafluorophosphate. The examined potential window encompassed the reversible redox process of the polymer and the redox transformations of the inorganic components, i.e. silver species, taking place within this window. The electrocrystallization of silver nanoparticles was controlled by dc potential. The Ag nanoparticles entrapped in polypyrrole, generated at reduction potentials of the composite, were 101 nm in diameter. The slightly larger AgNP of a mixed chemical nature was formed by a spontaneous discharge of the oxidized polypyrrole - salt composite towards the open circuit potential. Electrochemical processing and characterization of the composite were done using the dc and ac methods. Several other methods of chemical and structural identification were employed. The influence of oxygen for the processing of the composite towards metallic nanoparticles was shown. Electrochemical chemically irreversible oxidation of Ag2O to AgO in the polypyrrole matrix was found.

Repetitive transcranial photobiomodulation but not long-term omega-3 intake reduces epileptiform discharges in rats with stroke-induced epilepsy.

Epilepsy is a yet under-recognized consequence after a stroke and nearly 30% of cases are pharmacoresistant. There is an unmet need for therapeutic interventions during epileptogenesis for better long-term disease outcomes. Transcranial photobiomodulation (PBM) and omega-3 (Ω-3) dietary supplementation are two approaches that have been shown promising neuroprotective effects after brain injuries. Here, we studied the PBM treatment or Ω-3 diet during epileptogenesis in long-term recurrent spontaneous abnormal electrical discharges after stroke. Wistar rats received repetitive 780 nm-laser in the scalp or oral diet with Ω-3 for 2-months after photothrombotic stroke. EEG recordings were performed 60 days after treatment end. PBM but not Ω-3 reduced both electrographic seizure duration and spikes number in the ipsilateral and contralateral cortices and ventral posteromedial thalamic nucleus. Conclusively, PBM reduced epileptiform discharges in stroke-induced epilepsy. Our results suggest the PBM as a therapeutic approach for stroke-induced epileptogenesis to minimize long-term disease outcomes.

LncRNA MEG3 Reduces Hippocampal Neuron Apoptosis via the PI3K/AKT/mTOR Pathway in a Rat Model of Temporal Lobe Epilepsy.

PurposeTemporal lobe epilepsy (TLE) is a common neurological disorder, which is characterized by recurrent spontaneous seizures. Exploring the mechanisms of epileptogenesis has been considered as a priority. The aim of this study is to investigate the effects of LncRNA MEG3 in spontaneous recurrent epileptiform discharges (SREDs) and rats with TLE.MethodsRat model of TLE was produced by intraperitoneal injection of lithium chloride and pilocarpine. Rat hippocampal neuronal model of SREDs was established by Mg2+-free treatment. MEG3 was overexpressed by transfection of AAV-MEG3 in TLE and SREDs model. The expression of MEG3, interleukin-1β (IL-1β), interleukin-6 (IL-6) and recombinant human tumor necrosis factor-alpha (TNF-α) was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were detected by corresponding kit. The apoptosis of hippocampal neurons was detected by terminal deoxynucleotidyl transferase transfer‑mediated dUTP nick end‑labeling (TUNEL) assay and flow cytometry. The expression of proteins related to apoptosis (Caspase-3, Bax, and Bcl-2) and the PI3K/AKT/mTOR pathway was detected by Western blot.ResultsMEG3 expression was downregulated in SREDs and rats with TLE. Overexpression of MEG3 reduced the expression of IL-1β, IL-6, and TNF-α, MDA content, apoptosis rate of hippocampal neuron, increased SOD activity, and inhibited the PI3K/AKT/mTOR pathway in rats with TLE. In addition, overexpression of MEG3 enhanced cell viability and inhibited apoptosis through the activation of the PI3K/AKT/mTOR pathway in SREDs.ConclusionMEG3 reduced proinflammatory cytokines, oxidative stress, and apoptosis rate of hippocampal neuron and enhanced cell viability through the activation of the PI3K/AKT/mTOR pathway in SREDs and rats with TLE. Our findings may contribute to find a new therapeutic target for the treatment of epilepsy.

Neuropathic pain increases spontaneous and noxious-evoked activity of locus coeruleus neurons

The noradrenergic locus coeruleus nucleus is an important station in both the ascending and descending pain regulatory pathways. These neurons discharge in tonic and phasic modes in response to sensory stimuli. However, few studies have set out to characterize the electrophysiological response of the locus coeruleus to noxious stimuli in conditions of neuropathic pain. Thus, the effects of mechanical nociceptive stimulation of the sciatic nerve area on spontaneous (tonic) and sensory-evoked (phasic) locus coeruleus discharge were studied by extracellular recording in anesthetized rats seven, fourteen and twenty-eight days after chronic constriction injury. Minor significant electrophysiological changes were found seven and fourteen days after nerve injury. However, alterations to the spontaneous activity in both the ipsilateral and contralateral locus coeruleus were found twenty-eight days after nerve constriction, as witnessed by an increase of burst firing incidence and irregular firing patterns. Furthermore, noxious-evoked responses were exacerbated in the contralateral and ipsilateral nucleus at twenty-eight days after injury, as were the responses evoked when stimulating the uninjured paw. In addition, mechanical stimulation of the hindpaw produced a significant sensitization of neuronal tonic activity after 28 days of neuropathy. In summary, long-term nerve injury led to higher spontaneous activity and exacerbated noxious-evoked responses in the locus coeruleus to stimulation of nerve-injured and even uninjured hindpaws, coinciding temporally with the development of depressive and anxiogenic-like behavior.

Detection of neurophysiological features in female R255X MeCP2 mutation mice

Rett syndrome (RTT) is a severe neurodevelopmental disorder (NDD) that is nearly always caused by loss of function mutations in Methyl-CpG-binding Protein 2 (MECP2) and shares many clinical features with other NDD. Genetic restoration of Mecp2 in symptomatic mice lacking MeCP2 expression can reverse symptoms, providing hope that disease modifying therapies can be identified for RTT. Effective and rapid clinical trial completion relies on well-defined clinical outcome measures and robust biomarkers of treatment responses. Studies on other NDD have found evidence of differences in neurophysiological measures that correlate with disease severity. However, currently there are no well-validated biomarkers in RTT to predict disease prognosis or treatment responses. To address this, we characterized neurophysiological features in a mouse model of RTT containing a knock-in nonsense mutation (p.R255X) in the Mecp2 locus. We found a variety of changes in heterozygous female Mecp2R255X/X mice including age-related changes in sleep/wake architecture, alterations in baseline EEG power, increased incidence of spontaneous epileptiform discharges, and changes in auditory evoked potentials. Furthermore, we identified association of some neurophysiological features with disease severity. These findings provide a set of potential non-invasive and translatable biomarkers that can be utilized in preclinical therapy trials in animal models of RTT and eventually within the context of clinical trials.

Glial Modulation of Electrical Rhythms in a Neuroglial Network Model of Epilepsy.

An important EEG-based biomarker for epilepsy is the phase-amplitude cross-frequency coupling (PAC) of electrical rhythms; however, the underlying pathways of these pathologic markers are not always clear. Since glial cells have been shown to play an active role in neuroglial networks, it is likely that some of these PAC markers are modulated via glial effects. We developed a 4-unit hybrid model of a neuroglial network, consisting of 16 sub-units, that combines a mechanistic representation of neurons with an oscillator-based Cognitive Rhythm Generator (CRG) representation of glial cells-astrocytes and microglia. The model output was compared with recorded generalized tonic-clonic patient data, both in terms of PAC features, and state classification using an unsupervised hidden Markov model (HMM). The neuroglial model output showed PAC features similar to those observed in epileptic seizures. These generated PAC features were able to accurately identify spontaneous epileptiform discharges (SEDs) as seizure-like states, as well as a postictal-like state following the long-duration SED, when applied to the HMM machine learning algorithm trained on patient data. The evolution profile of the maximal PAC during the SED compared well with patient data, showing similar association with the duration of the postictal state. The hybrid neuroglial network model was able to generate PAC features similar to those observed in ictal and postictal epileptic states, which has been used for state classification and postictal state duration prediction. Since PAC biomarkers are important for epilepsy research and postictal state duration has been linked with risk of sudden unexplained death in epilepsy, this model suggests glial synaptic effects as potential targets for further analysis and treatment.

What is the true discharge rate and pattern of the striatal projection neurons in Parkinson's disease and Dystonia?

Dopamine and striatal dysfunctions play a key role in the pathophysiology of Parkinson's disease (PD) and Dystonia, but our understanding of the changes in the discharge rate and pattern of striatal projection neurons (SPNs) remains limited. Here, we recorded and examined multi-unit signals from the striatum of PD and dystonic patients undergoing deep brain stimulation surgeries. Contrary to earlier human findings, we found no drastic changes in the spontaneous discharge of the well-isolated and stationary SPNs of the PD patients compared to the dystonic patients or to the normal levels of striatal activity reported in healthy animals. Moreover, cluster analysis using SPN discharge properties did not characterize two well-separated SPN subpopulations, indicating no SPN subpopulation-specific (D1 or D2 SPNs) discharge alterations in the pathological state. Our results imply that small to moderate changes in spontaneous SPN discharge related to PD and Dystonia are likely amplified by basal ganglia downstream structures.

Anaesthesia and orphan disease: A patient with neuromyotonia undergoing single lung ventilation.

Anaesthesia and orphan disease: A patient with neuromyotonia undergoing single lung ventilation.

Relationship between oxygen consumption and neuronal activity in a defined neural circuit

BackgroundNeuronal computations related to sensory and motor activity along with the maintenance of spike discharge, synaptic transmission, and associated housekeeping are energetically demanding. The most efficient metabolic process to provide large amounts of energy equivalents is oxidative phosphorylation and thus dependent on O2 consumption. Therefore, O2 levels in the brain are a critical parameter that influences neuronal function. Measurements of O2 consumption have been used to estimate the cost of neuronal activity; however, exploring these metabolic relationships in vivo and under defined experimental conditions has been limited by technical challenges.ResultsWe used isolated preparations of Xenopus laevis tadpoles to perform a quantitative analysis of O2 levels in the brain under in vivo-like conditions. We measured O2 concentrations in the hindbrain in relation to the spike discharge of the superior oblique eye muscle-innervating trochlear nerve as proxy for central nervous activity. In air-saturated bath Ringer solution, O2 levels in the fourth ventricle and adjacent, functionally intact hindbrain were close to zero. Inhibition of mitochondrial activity with potassium cyanide or fixation of the tissue with ethanol raised the ventricular O2 concentration to bath levels, indicating that the brain tissue consumed the available O2. Gradually increasing oxygenation of the Ringer solution caused a concurrent increase of ventricular O2 concentrations. Blocking spike discharge with the local anesthetics tricaine methanesulfonate diminished the O2 consumption by ~ 50%, illustrating the substantial O2 amount related to neuronal activity. In contrast, episodes of spontaneous trochlear nerve spike bursts were accompanied by transient increases of the O2 consumption with parameters that correlated with burst magnitude and duration.ConclusionsControlled experimental manipulations of both the O2 level as well as the neuronal activity under in vivo-like conditions allowed to quantitatively relate spike discharge magnitudes in a particular neuronal circuitry with the O2 consumption in this area. Moreover, the possibility to distinctly manipulate various functional parameters will yield more insight in the coupling between metabolic and neuronal activity. Thus, apart from providing quantitative empiric evidence for the link between physiologically relevant spontaneous spike discharge in the brain and O2-dependent metabolism, isolated amphibian preparations are promising model systems to further dissociate the O2 dynamics in relation to neuronal computations.

The intrinsic plasticity of medial vestibular nucleus neurons during vestibular compensation\u2014a systematic review and meta-analysis

BackgroundVestibular compensation is a homeostatic process that occurs in the central nervous system in response to peripheral vestibular dysfunction. Experimental studies in rodent models have suggested that unilateral peripheral vestibular lesions are correlated with an increase in the intrinsic excitability of central vestibular neurons. This process may be dependent on the intrinsic properties of the neurons themselves. We aimed to conduct a systematic review of the literature to survey the evidence for changes in intrinsic plasticity observed during the acute phase of vestibular compensation.MethodsWe systematically reviewed the literature regarding the electrophysiological effect of experimentally induced unilateral vestibular deafferentation (UVD) on the intrinsic membrane properties of medial vestibular nucleus neurons in animal models. We developed tools to assess the methodological quality (precision, validity and bias) of studies that met pre-determined inclusion and exclusion criteria. We extracted numerical data and performed a meta-analysis of specific quantitative data pooled from these studies.ResultsWe identified 17 studies that satisfied the inclusion criteria. There is moderate quality evidence to suggest a statistically significant increase in the intrinsic excitability of medial vestibular nucleus neurons following unilateral vestibular deafferentation. Specifically, the spontaneous discharge rate increases by 4 spikes/s on average and the sensitivity to current stimuli increases.ConclusionUsing this novel approach, we demonstrate that the methodology of systematic review and meta-analysis is a useful tool in the summation of data across experimental animal studies with similar aims.

Reproductive potential and early spore settlement on different substrates in Gigartina skottsbergii (Gigartinaceae, Rhodophyta) from the South American Atlantic coast

The aims of this study were to estimate seasonal spore availability in the carrageenophyte Gigartina skottsbergii from the Patagonian Atlantic coast, evaluate the effect of induction methods and culture conditions on spore release, and assess spore settlement on different substrates. Fertile fronds were collected in southern Argentina. The density and size of reproductive structures and spore output were registered seasonally. Spore release was evaluated using different induction methods and conditions. Finally, different natural substrates were assessed for spore settlement. Spore availability is restricted to winter and spring. Cystocarps and tetrasporangial sori reached maturity towards winter, and spores were released in large amounts during winter and spring, with higher tetraspore than carpospore release. Spontaneous discharge would appear to be a more advisable induction method than desiccation and high salinity. Temperature and photoperiod did not have a significant effect on total spore output. After 2 weeks of incubation, no differences were found among spore densities on glass, pebbles, clams, or mussels. Despite the low survival rate registered on all substrates, spores germinated and developed healthily. This is the first study to evaluate carpospore and tetraspore availability throughout the year and the viability of in vitro spore culture of G. skottsbergii from the South American Atlantic coast.

Crocin Reverses Depression-Like Behavior in Parkinson Disease Mice via VTA-mPFC Pathway.

Depression is a common non-motor symptom in patients with Parkinson's disease (PD) and difficult to treat. Crocin is a natural multipotential neuroprotective compound that has been shown to elicit antidepressant activity and is promising for the therapy of neuropsychological diseases. Here, we investigated the therapeutic effect of crocin in a mouse model of Parkinson's disease depression (PDD) and clarified the underlying mechanism. We prepared 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced subacute mouse model of PD, and found that around 60% of the model mice showed depression-like behavior, using the forced swimming test (FST). A regime of 10-day treatment of crocin alleviated the PDD symptoms. The crocin reduced the structural damage in soma volume and axon length of neurons and inhibited their spontaneous discharge in dopaminergic (DA) neurons in the ventral tegmental area (VTA). Notably, the MPTP-treated mice showed the decrease in the critical signaling for synaptic plasticity, including the proteins of PSD-95, synapsin-1, and GluR-1, in the medial prefrontal cortex (mPFC) where it receives efferent from VTA and regulates depression-like behavior. However, crocin treatment rescued the defect of the mammalian target of rapamycin (mTOR) signaling in PDD mice. Furthermore, the antidepressant action of crocin was blunted after blockade of mTOR signaling with the antagonist rapamycin. In conclusion, our study demonstrated that crocin protected the DA projection neurons in the VTA through activating mTOR, which subsequently improved the neural synaptic plasticity of mPFC, and ameliorated depression-like behavior in PD mice.

Etomidate reduces excitability of the neurons and suppresses the function of nAChR ventral horn in the spinal cord of neonatal rats

To investigate the effects of etomidate on electrophysiological properties and nicotinic acetylcholine receptors (nAChRs) of ventral horn neurons in the spinal cord. The spinal cord containing lumbosacral enlargement was isolated from 19 neonatal SD rats aged 7-12 days. The spinal cord were sliced and digested with papain (0.18 g/30 mL artificial cerebrospinal fluid) and incubated for 40 min. At the ventral horn, acute mechanical separation of neurons was performed with fire-polished Pasteur pipettes, and perforated patch-clamp recordings combined with pharmacological methods were employed on the adherent healthy neurons. In current-clamp mode, the spontaneous action potential (AP) of the ventral horn neurons in the spinal cord was recorded. The effects of pretreatment with different concentrations of etomidate on AP recorded in the ventral horn neurons were examined. In the voltage-clamp mode, nicotine was applied to induce inward currents in the ventral horn neurons, and the effect of pretreatment with etomidate on the inward currents induced by nicotine were examined with different etomidate concentrations, different holding potentials and different use time. The isolated ventral horn neurons were in good condition with large diverse somata and intact processes. The isolated spinal ventral horn neurons (n=21) had spontaneous action potentials, and were continuously perfused for 2 min with 0.3, 3.0 and 30.0 μmol/L etomidate. Compared with those before administration, the AP amplitude, spike potential amplitude and overshoot were concentration-dependently suppressed (P < 0.01), and spontaneous discharge frequency was obviously reduced (P < 0.01, n=12). The APs of the other 9 neurons were completely abolished by etomidate at 3.0 or 30 μmol/L. At the same holding potential (VH=-70 mV), pretreatment with 0.3, 3.0 or 30.0 μmol/L etomidate for 2 min concentration-dependently suppressed the current amplitude induced by 0.4 mmol/L nicotine (P < 0.01, n=7). At the holding potentials of - 30, - 50, and - 70 mV, pretreatment with 30.0 μmol/L etomidate for 2 min voltage-dependently suppressed the current amplitude induced by 0.4 mmol/L nicotine (P < 0.01, n=6 for each holding potential). During the 6 min of 30.0 μmol/L etomidate pretreatment, the clamped cells were exposed to 0.4 mmol/L nicotine for 4 times at 0, 2, 4, and 6 min (each exposure time was 2 s), and the nicotinic current amplitude decreased gradually as the number of exposures increased. But at the same concentration, two nicotine exposures (one at the beginning and the other at the end of the 6 min pretreatment) resulted in a significantly lower inhibition rate compared with 4 nicotine exposures (P < 0.01, n=6). etomidate reduces the excitability of the spinal ventral neurons in a concentration-dependent manner and suppresses the function of nAChR in a concentration-, voltage-, and use-dependent manner.

A nomogram to predict the probability of breast intraductal tumors in patients with nipple discharge: A report based on our 13-year clinical experience.

e13582 Background: Nipple discharge is a common symptom of breast disease. Our aim was to perform a descriptive statistical analysis of the cases we collected and to establish a model to predict intraductal tumors. Methods: We conducted a retrospective study of patients from 2007 to 2019. The variables were analyzed by the c2 test. Univariate binary logistic regression was used to analyze the relationship between clinical features of patients. Receiver operating characteristics (ROC) were used to assess the sensitivity and specificity of the predictive ability of the model. Results: Patients with spontaneous, single duct, bloody discharge and smooth ductal wall were more likely to diagnose with tumor by ductoscopy. A model was established based on seven variables: age, side of discharge, spontaneous or not, duration of discharge, ductal wall and characteristics of discharge. It was subsequently validated in 178 patients with complete data on variables in the validation cohort. The area under ROC curve (AUC) were calculated to be 0.7024 indicating a good predictive ability. Conclusions: Patients with clinical characteristics of unilateral, bloody, single duct, spontaneous discharge and smooth ductal wall were more likely to have intraductal tumors by ductoscopy. Our nomogram can effectively predict intraductal tumors in patients with nipple discharge.

Microbial load of the urine in patients with recurrent urolithiasis and its correction

Among the causes of stone formation in the urinary system, an important role belongs to the microbiome, which affects the stability of the colloidal system of urine. Understanding the level of microbial tension in the urine allows to use pathogenetic approaches both for prevention and for the relapses of stone formation. The study included 162 patients with recurrent urolithiasis, 12 patients underwent complex anti-relapse therapy after surgical treatment (or spontaneous discharge of concretions after litokinetic therapy). It was determined that along with the known factors, there is a violation of quantitative indicators of urine microbiota. An increase of the microbial load of urine leads to a violation of the structure of uromodulin (Tamm Horsfall protein), which in turn determines the high frequency of recurrence of urinary lithogenesis. Thus, a comprehensive assessment of the urine microbiota and its impact on the state of uromodulin, lead to an improvement in the quality of urolithiasis metaphylaxis. In the complex of metaphylaxis and prevention of urolithiasis, it is advisable to use antimicrobial agents (uroseptics) not only to reduce the risk of infectious and inflammatory complications, but also to increase the stability of the colloidal properties of urine.

Ionic channel blockage in stochastic Hodgkin-Huxley neuronal model driven by multiple oscillatory signals.

Ionic channel blockage and multiple oscillatory signals play an important role in the dynamical response of pulse sequences. The effects of ionic channel blockage and ionic channel noise on the discharge behaviors are studied in Hodgkin-Huxley neuronal model with multiple oscillatory signals. It is found that bifurcation points of spontaneous discharge are altered through tuning the amplitude of multiple oscillatory signals, and the discharge cycle is changed by increasing the frequency of multiple oscillatory signals. The effects of ionic channel blockage on neural discharge behaviors indicate that the neural excitability can be suppressed by the sodium channel blockage, however, the neural excitability can be reversed by the potassium channel blockage. There is an optimal blockage ratio of potassium channel at which the electrical activity is the most regular, while the order of neural spike is disrupted by the sodium channel blockage. In addition, the frequency of spike discharge is accelerated by increasing the ionic channel noise, the firing of neuron becomes more stable if the ionic channel noise is appropriately reduced. Our results might provide new insights into the effects of ionic channel blockages, multiple oscillatory signals, and ionic channel noises on neural discharge behaviors.