Baseline Recordings Research Articles

Comparison Of Dynamic Calcium Signaling Profiles On Activation Of TRPV4 Channel And T‐Type Calcium Channel In Pulmonary Microvasculature

BackgroundAcute Lung Injury (ALI) is characterized by inflammation, barrier disruption and edema within lung microvasculature. A dysregulation in intercellular signaling of calcium (Ca2+) within pulmonary microvascular endothelium potentially damages lung endothelial barrier integrity. Recently, two plasma membrane ion channels, the vanilloid transient receptor potential IV (TRPV4) and the T‐type voltage gated calcium channels (TTCC) have been implicated as potential conduits for spatially and temporally targeted Ca2+ signals within lung endothelium. Ca2+ entry via TRPV4 causes barrier disruption and Ca2+ entry via TTCC regulates P‐selectin expression, but their underlying patterns of specific Ca2+ signaling events are unknown. Therefore, in this study we aim to determine whether these channels elicit distinct Ca2+ signaling events that might contribute to their different functions in lung endothelium.MethodPulmonary microvascular endothelial cells (PMVECs) grown in 35mm glass‐bottomed dishes were loaded with fluorescent Ca2+ indicator Cal‐520 AM and recorded for signals via spinning disk confocal microscopy. After baseline recording, cells were subjected to GSK1016790 (TRPV4 activator) and then to GSK2798754 (TRPV4 inhibitor). Another set of cells were treated with high K+ solution (TTCC activator) and then with mibefradil (TTCC inhibitor). Lung slices were mounted on Sylgard inserts, and loaded with Cal‐520 AM. Two different slices were recorded for baseline activities and were respectively subjected to same drug treatments as PMVECs. Time‐lapse image sequences recorded after each addition were analyzed for amplitude and frequency of events using ImageJ and customized signal detection software LC_Pro.ResultsIn PMVECs with TRPV4 channel activation, the amplitude and frequency of events increased 1.5‐fold when compared to baseline, whereas the TTCC activation showed an increase by 1.3‐fold. In lung slices, the TRPV4 channel activation exhibited an increase by 1.4‐fold compared to baseline, as opposed to an increase of only 1.1‐fold with TTCC activation. The addition of respective inhibitors brought the signals back to near baseline levels.ConclusionOur findings suggest both TRPV4 channel and TTCC activation caused an increase in Ca2+ dynamics, with the TRPV4 channel activation showing a greater increase in event amplitude and frequency than TTCCs, thereby indicating they both contribute to distinct signaling events in PMVECs and lung slices. Further studies will focus on how these different signatures contribute to the differential functional roles of the channels.

Prolonged diaphragm activation using closed loop optogenetic stimulation

Diaphragm dysfunction in individuals with late stage neuromuscular disease and cervical spinal cord injury is a substantial problem, often resulting in respiratory insufficiencies and ultimately respiratory failure. Therefore, there is a need to develop new methods that can improve diaphragm function in these clinical populations. Here we used an optogenetic method of activating diaphragm myofibers to assess the feasibility of prolonged photostimulation of the diaphragm. Our hypothesis was that closed loop photostimulation can pace the diaphragm over a prolonged period (1 hour) without a decrease in evoked response magnitude. Wild type mice (C57/bl6, n= 5) received an injection of AAV9‐CAG‐ChR2‐mVenus (34 µl, titer: 1.8x1013 vg/ml) to the intrapleural space between the lung and chest wall to target the diaphragm. After an 8‐18 week incubation period, diaphragm EMG and respiratory airflow were measured under isoflurane anesthesia. A light stimulus was delivered to the inferior diaphragm surface using a high‐power, 472 nm, micro‐LED. Photostimulation was delivered in a closed loop fashion using the onset of the inspiratory EMG burst recorded in intact hemi‐diaphragm to trigger the stimulus. The photostimulation paradigm consisted of a 250 ms, ramping/decrementing train of light pulses (pulse duration = 0.1 ms, interpulse interval = 0.1 ms). After a 10‐minute baseline recording, a unilateral right phrenicotomy was performed to paralyze the right diaphragm. The photostimulation paradigm immediately restored EMG activity to the paralyzed hemi‐diaphragm. Further, the magnitude of the evoked diaphragm EMG bursts stayed consistent over the sixty‐minute period of closed loop photostimulation, and there was no evidence of a decrement in EMG activation. Post‐mortem histology confirmed mVenus expression in diaphragm myofibers. We conclude that stimulation of the diaphragm using optogenetics is effective for up to one hour. This is a first demonstration of prolonged photostimulation of the diaphragm and provides evidence to support the feasibility of this method for the treatment of chronic diaphragm paralysis.

Application of Physiological Autonomic Activity Tracking GUI and Computational Algorithms for Measuring Persistent Vagal Nerve Dysfunction After Recovery from SARS‐CoV‐2 Infection

Post‐Acute Sequelae of SARS‐CoV‐2 infection (PASC) is now recognized as a constellation of symptoms such as postural hypotension, anxiety, and “brain fog” in addition to autonomic nervous system dysfunction such as tachycardia and labile hypertension. Better quantification of these conditions, specifically, autonomic nervous system dysfunction, is desired for future diagnostics, treatment modalities, and gaining a further understanding of PASC. This research has led to application of a novel autonomic activity tracking algorithm and GUI suite from previous work, see Figure 1, to study the physiological autonomic activity in six patients who had recovered from acute SARS‐CoV‐2 infection a mean of six months prior but were still experiencing symptoms. By measuring skin sympathetic nervous activity (SKNA), heart rate variability, and the cutaneous electrogastrogram (EGG), all before and after a water meal challenge, the data was fed into a custom analysis pipeline, shown in Figure 1. Each of the PASC patients were compared to a mean response of 34 healthy controls, each undergoing a 20‐minute baseline recording and another 20‐minute recording after ingestion of an 8 oz water test meal. All six patients showed significantly abnormal heart rate variability on frequency domain analysis in predominantly the low frequency (LF) and very low frequency (VLF) bands, and less so in the high frequency (HF) band, suggesting sympathetic nerve dysfunction. Three patients showed a significant decrease in SKNA while two showed a significant increase. All patients showed an abnormal cutaneous EGG. As shown in Figure 2, the temporal responses of aSKNA, VLF, LF, HF, and EGG for the PASC patients revealed that on average they were statistically different (p<0.05) from the healthy controls’ responses respectively during 98.4%, 78.4%, 86.76%, 47.9%, and 86.1% of the 40‐minute time period in testing, 20 minutes of baseline and 20 minutes after ingestion. In conclusion, we are looking at the sympathetic, parasympathetic, and enteric nervous systems synced temporally for applications with classification and further stratification of PASC based on the temporal dynamics of their autonomic nervous system mediated coordination from digestion. This shows that SARS‐CoV02 infection appears to have a significant effect on sympathetic and parasympathetic autonomic nervous system function and may be responsible for the disturbances noted in PASC. This work provides the framework and example of use for further applications in autonomic disorder physiological response exploration and furthermore can be expanded to other areas of neuromodulation.

The implementation of transcranial Doppler ultrasonography for preclinical study of migraine.

Transcranial Doppler ultrasonography is used to study intracranial blood flow changes associated with migraine in humans, but whether this method is helpful in preclinical settings is yet unknown. To identify changes in rat intracranial blood flow specific to trigeminovascular activation-a key process in migraine pathophysiology-we measured Doppler indices in the middle cerebral artery and basilar artery before, during, and after dural or somatosensory electrical stimulation. Hemodynamic changes specific to dural stimulation were tested further in separate experiments. After baseline recordings, the animals received cumulative infusions of valproate (100 mg/kg, trice), sumatriptan (0.3, 1, and 3mg/kg), or saline, and dural stimulation with measurement of Doppler indices was repeated every 10 min for 1 h. Several parameters of blood flow in the rat middle cerebral artery underwent alterations specific to trigeminovascular activation. These changes, however, were insensitive to valproate and sumatriptan and diminished over time. These findings question the reliability of blood flow velocity variations in large intracranial vessels as biological markers of migraine-related processes and do not support the idea of using transcranial Doppler ultrasonography for preclinical screening of antimigraine treatments, at least in the model of acute trigeminovascular activation in rats.

A feasibility pilot study of the effects of neurostimulation on swallowing function in Parkinson's Disease [version 2; peer review: 1 approved, 3 approved with reservations, 1 not approved

IntroductionDysphagia often occurs during Parkinson’s disease (PD) and can have severe consequences. Recently, neuromodulatory techniques have been used to treat neurogenic dysphagia. Here we aimed to compare the neurophysiological and swallowing effects of three different types of neurostimulation, 5 Hertz (Hz) repetitive transcranial magnetic stimulation (rTMS), 1 Hz rTMS and pharyngeal electrical stimulation (PES) in patients with PD.Method12 PD patients with dysphagia were randomised to receive either 5 Hz rTMS, 1 Hz rTMS, or PES. In a cross-over design, patients were assigned to one intervention and received both real and sham stimulation. Patients received a baseline videofluoroscopic (VFS) assessment of their swallowing, enabling penetration aspiration scores (PAS) to be calculated for: thin fluids, paste, solids and cup drinking. Swallowing timing measurements were also performed on thin fluid swallows only. They then had baseline recordings of motor evoked potentials (MEPs) from both pharyngeal and (as a control) abductor pollicis brevis (APB) cortical areas using single-pulse TMS. Subsequently, the intervention was administered and post interventional TMS recordings were taken at 0 and 30 minutes followed by a repeat VFS within 60 minutes of intervention.ResultsAll interventions were well tolerated. Due to lower than expected recruitment, statistical analysis of the data was not undertaken. However, with respect to PAS swallowing timings and MEP amplitudes, there was small but visible difference in the outcomes between active and sham.ConclusionPES, 5 Hz rTMS and 1 Hz rTMS are tolerable interventions in PD related dysphagia. Due to small patient numbers no definitive conclusions could be drawn from the data with respect to individual interventions improving swallowing function and comparative effectiveness between interventions. Larger future studies are needed to further explore the efficacy of these neuromodulatory treatments in Parkinson’s Disease associated dysphagia.

A randomised cross-over trial of QT response to hyperventilation-induced anxiety and diaphragmatic breathing in patients with stress cardiomyopathy and in control patients.

ObjectivesThe most perfect example of the mind-body interaction in all of medicine is provided by stress cardiomyopathy. In stress cardiomyopathy, what is initially a purely emotional event may become rapidly fatal. Prolongation of the QT interval is a cardinal feature of the condition, but the mechanism of the prolongation is unknown. We undertook a randomised controlled trial of stress with a cross-over design, comparing the cardiac response of women with a history of stress cardiomyopathy to age-matched controls to explore the mind-body interaction. Our hypothesis is that the hearts of women with a history of stress cardiomyopathy will respond differently to emotional stress than those of the controls.MethodThis is a randomised cross-over study. Each patient underwent two separate 24-hour Holter monitors performed at least 5 days apart. Baseline recording was followed by either the stress intervention (hyperventilation) or control (diaphragmatic breathing). Our primary endpoint is change in QTc interval over the first hour. Secondary endpoints were change in QTc over 24 hours, and change in SDNN, a measure of heart rate variability. As a secondary stressor, each participant was telephoned four times during their stressed recording and asked to complete a questionnaire.ResultsTwelve stress cardiomyopathy patients and twelve control patients were recruited. Baseline characteristics did not differ between cases and controls. With hyperventilation, there was a significant initial difference in anxiety (p<0.001), heart rate response (p<0.0001), and QTc (p<0.0002) compared to diaphragmatic breathing, but no differences between the cases and controls. Only first phone call caused an increase in QTc in cases and controls (p = 0.0098). SDNN increased with hyperventilation (p<0.0001) but did not differ between cases and controls.ConclusionsQTc response in women with a history of stress cardiomyopathy does not differ from controls. The relevance of QT prolongation and sensitivity in the autonomic response to the pathogenesis of stress cardiomyopathy remains uncertain.

Quantitative evaluation of aerosol generation from upper airway suctioning assessed during tracheal intubation and extubation sequences in anaesthetized patients

SummaryBackgroundOpen respiratory suctioning is defined as an aerosol generating procedure (AGP). Laryngopharyngeal suctioning, used to clear secretions during anaesthesia, is widely managed as an AGP. However, it is uncertain whether upper airway suctioning should be designated as an AGP due to the lack of both aerosol and epidemiological evidence.AimTo assess the relative risk of aerosol generation by upper airway suctioning during tracheal intubation and extubation in anaesthetized patients.MethodsThis prospective environmental monitoring study was undertaken in an ultraclean operating theatre setting to assay aerosol concentrations during intubation and extubation sequences, including upper airway suctioning, for patients undergoing surgery (N=19). An optical particle sizer (particle size 0.3–10 μm) sampled aerosol 20 cm above the patient's mouth. Baseline recordings (background, tidal breathing and volitional coughs) were followed by intravenous induction of anaesthesia with neuromuscular blockade. Four periods of laryngopharyngeal suctioning were performed with a Yankauer sucker: pre-laryngoscopy, post-intubation, pre-extubation and post-extubation.FindingsAerosol was reliably detected {median 65 [interquartile range (IQR) 39–259] particles/L} above background [median 4.8 (IQR 1–7) particles/L, P<0.0001] when sampling in close proximity to the patient's mouth during tidal breathing. Upper airway suctioning was associated with a much lower average aerosol concentration than breathing [median 6.0 (IQR 0–12) particles/L, P=0.0007], and was indistinguishable from background (P>0.99). Peak aerosol concentrations recorded during suctioning [median 45 (IQR 30–75) particles/L] were much lower than during volitional coughs [median 1520 (IQR 600–4363) particles/L, P<0.0001] and tidal breathing [median 540 (IQR 300–1826) particles/L, P<0.0001].ConclusionUpper airway suctioning during airway management was not associated with a higher aerosol concentration compared with background, and was associated with a much lower aerosol concentration compared with breathing and coughing. Upper airway suctioning should not be designated as a high-risk AGP.

Effect of a tadalafil 5-mg single daily dose on lifelong premature ejaculation: A single-blinded placebo-controlled study

ABSTRACT Objective To investigate the effectiveness and safety of a tadalafil 5-mg single daily dose in the treatment of lifelong premature ejaculation (PE). Patients and Methods A total of 55 men with lifelong PE were enrolled in this study. The intravaginal ejaculatory latency time (IELT) and Premature Ejaculation Diagnostic Tool (PEDT) were used to assess the efficacy of tadalafil. Baseline recording of the IELT (using a stopwatch) and PEDT was done. Patients were randomised to take a single daily dose of tadalafil 5 mg or placebo. Re-assessment was done by IELT and PEDT after 1 and 3 months. Results As regard, age, number of children, frequency of intercourse and duration of PE there are no statically significant differences between both groups. In both the tadalafil 5-mg and placebo groups the IELT statically significantly increased after 1 month by a mean (SD) of 4.8 (4.7) and 5 (4.9) s, and after 3 months by a mean (SD) of 6.6 (7) and 4.5 (9) s; and the PEDT scores significantly improved after 1 month by a mean (SD) of 2.1 (1.9) and 2 (1.5), and after 3 months by a mean (SD) of 3.5 (2.5) and 3.3 (2.2). However, there is was no statically significant difference between the tadalafil 5-mg and placebo groups for the IELT and PEDT at baseline or after 1 and 3 months of treatment. Conclusions Despite 5-mg tadalafil once daily being safe and it showed only a slight improvement in IELT and PEDT in the treatment of lifelong PE, failing to show any statistically significant difference from the placebo drug. Abbreviations: ED: erectile dysfunction; 5-HT: 5-hydroxytryptamine (serotonin); IELT: the intravaginal ejaculation latency time; ISSM: International Society of Sexual Medicine; PE: premature ejaculation; PEDT: Premature Ejaculation Diagnostic Tool; PDE5i: phosphodiesterase-5 inhibitor; SSRI: selective serotonin reuptake inhibitor

Pathological Human Tau Induces Alterations in the Brain Insulin Signaling Cascade.

The process of neurodegeneration in Alzheimer’s disease has been associated with a disruption of insulin signaling cascade in neurons, and to insulin resistance. T2DM correlates with Alzheimer’s disease, but mechanisms of interaction are unknown. We have developed a mouse model of tau induced neurodegeneration expressing pseudo-phosphorylated tau [Pathological Human Tau (PH-Tau)] in neurons. This model (PH-Tau-Tg) recapitulated cognitive decline and neurodegeneration observed in AD. In this study we examined if expression of PH-Tau could affect neuronal excitability and insulin receptor signaling. Neuronal excitability was investigated using intracerebral recordings of extracellular field potentials from prefrontal cortex after insulin and kainic acid (KA) injection. Analysis of baseline recordings indicated an increased excitability of PH-Tau-Tg as evidenced by higher spectrum densities (PSDs) of high frequencies brain waves. Injection of insulin (1IU, s.c) led to a decrease of fast ripples PSDs, more pronounced in PH-Tau-Tg mice than controls. Subsequent injection of kainic acid (KA, 5 mg/kg, s.c) led to significant increase in firing rate, amplitude of extracellular field potentials and PSDs of high frequency brain waves in control mice only. To further investigate the role of insulin in PH-Tau-Tg mice, we subjected mice to a glucose tolerance test. We found that PH-Tau-Tg mice were significantly hyperglycemic prior to glucose injection. Interestingly, the PH-Tau-Tg mice showed a moderate increase at 30 min due to the higher baseline, indicating a low sensitivity of insulin receptor in these mice. This is consistent with increased levels of activated insulin receptors in the brain and the inhibitory effect of insulin on ictal activity post KA injection in PH-Tau-Tg mice. We suggest that these mice have reduced insulin sensitivity (hyperglycemia) and as a compensatory mechanism there is overactivation/expression of insulin receptor in the brain rendering neuronal circuits resistant to seizure induction after injection of insulin. These data indicate that insulin signal transduction pathway is altered in PH-Tau-Tg mice, and that injection of exogenous insulin reduces hypersynchronous bursting activity of field potentials recorded from cortical neuronal circuits. We propose that the appearance of abnormal tau might potentiate the toxic environment by interfering with the insulin signaling cascade in the brain of patients with Alzheimer’s disease.

Effect of Resonance Breathing on Heart Rate Variability and Cognitive Functions in Young Adults: A Randomised Controlled Study.

Introduction: Heart rate variability (HRV) is an important physiological biomarker of wellbeing, mood, and adaptation, and hence improvements in HRV signify improved health, mood, and adaptation to stress. Resonance breathing has consistently been shown to increase HRV, mood, and adaptability. The study investigated the effects of four-week training of resonance breathing in young adults on HRV, stress, and cognition functions.Methods: The randomized controlled study was conducted on young men (18-30 years) after obtaining Institutional Ethics Committee approval and written informed consent from the participants. Participants were randomly divided into two groups: the control group and the resonance breathing (RB) group. Baseline parameters, along with heart rate variability, trail tests for cognition, and perceived stress level, were assessed in both groups. After undergoing four weeks of training, the intervention group practiced deep breathing at the resonance frequency for 20 minutes per day for four weeks, whereas the control group did not. All parameters were recorded again after four weeks of resonance breathing.Results: No difference was observed in the HRV parameters in the control group at baseline and four weeks after the baseline recording (p>0.05). In the intervention group, there was a significant improvement in the HRV parameters, the standard deviation of the normal-to-normal interval (SDNN), the proportion derived by dividing NN50 by the total number of NN intervals (pNN50), and total power, after practicing four weeks of resonance breathing (p<0.05). A significant difference in these parameters was also observed in the control and intervention groups after four weeks (p<0.05). There was a significant improvement in the Trails A and B test performance in the intervention group after practicing for four weeks of RB. Similarly, the perceived stress score decreased significantly in the RB group in comparison to its baseline value as well as the control group value. Conclusion: Increased parasympathetic and decreased sympathetic activity were observed after practicing 20 minutes of resonance frequency breathing every day for four weeks. It also improved cognition and reduced perceived stress levels among young adults. It is recommended that young adults should practice deep breathing at the resonance frequency for a few minutes every day. This would allay anxiety and stress, improve their cognitive performance, and also reduce their cardiovascular morbidity.

Bilateral electrodermal activity and asymmetric responses in normal healthy individuals

Background: Electrodermal activity (EDA) or galvanic skin response (GSR) is the change in the electrical properties of the skin which is used to measure the sympathetic activity and response. When a painful stimulus is applied, it elicits a sympathetic response by increasing sweat gland activity that, in turn, increases the skin conductance. Central nervous system plays important role in regulating sympathetic activity. Aims and Objectives: The objectives of this study were as follows: (1) To evaluate the electrodermal responses (EDR) in dominant and non-dominant hand; (2) to compare the EDRs in dominant and non-dominant hand. Materials and Methods: The study was done among MBBS students of age 18–23 years in physiology research laboratory and EDA values were analyzed using BIOCHART software (version1.0) through physiography. EDA was recorded using skin surface electrodes. Pulse and blood pressure were monitored before and after immersion in cold water. Baseline recording, recording after immersion of hand in cold water, and recovery recording of GSR were noted in dominant and non-dominant hands. Results: The mean GSR, baseline value, and the GSR after cold stimulation were significantly more in non-dominant hand compared to dominant hand. Conclusion: Our findings show an increased sympathetic activity in non-dominant hand in response to cold stimulation compared to dominant hand.

Successful continuous positive airway pressure treatment reduces skin sympathetic nerve activity in patients with obstructive sleep apnea.

Obstructive sleep apnea (OSA) is associated with cardiovascular diseases and increased sympathetic tone. We previously demonstrated that patients with OSA have increased skin sympathetic nerve activity (SKNA). The purpose of this study was to test the hypothesis that continuous positive airway pressure (CPAP) treatment reduces SKNA. The electrocardiogram, SKNA, and polysomnographic recording were recorded simultaneously in 9 patients with OSA. After baseline recording, CPAP titration was performed and the pressure was adjusted gradually for the optimal treatment, defined by reducing the apnea-hypopnea index (AHI) to ≤5/h. Otherwise the treatment was considered suboptimal (AHI > 5/h). Fast Fourier transform analyses were performed to investigate the frequency spectrum of SKNA. There were very low frequency (VLF), low frequency (LF), and high frequency (HF) oscillations in SKNA. The HF oscillation matched the frequency of respiration. OSA episodes were more frequently associated with the VLF and LF than with the HF oscillations of SKNA. Compared with baseline, CPAP significantly decreased the arousal index and AHI and increased the minimal and mean oxyhemoglobin levels. Optimal treatment significantly increased the dominant frequency and reduced the heart rate, average SKNA (aSKNA), SKNA burst duration, and total burst area. The dominant frequency negatively correlated with aSKNA. VLF, LF, and HF oscillations are observed in human SKNA recordings. Among them, VLF and LF oscillations are associated with OSA while HF oscillations are associated with normal breathing. CPAP therapy reduces aSKNA and shifts the frequency of SKNA oscillation from VLF or LF to HF.

The Effects of Meditation and Music on Stress in College Individuals

Background: Stress is a universal experience, now more than ever due to an ongoing worldwide pandemic. Modern college students are not only faced with the external pressures of succeeding academically, but they’re also affected by a multitude of other variables that are causing their mental health to suffer. This social trend highlights the need for a simple, efficient, and immediate remedy for individuals suffering from these stressors. Objective: In this controlled study, we assessed the effects of two methods proven by existing research to have stress-relieving effects. Participating college students underwent music (Weightless by Marconi Union) and mindfulness meditation (Daily Calm) treatments. Methods: Ten college students were screened via a self-reporting questionnaire to identify any pre-existing conditions that may present as extraneous variables. Quantitative variables related to stress, such as alpha frequency waves and heart rate, were obtained during baseline and post-treatment stress-induced environments using an iWire EEG recorder and oximeter pulse monitor. Each individual underwent treatments for a duration of five minutes, each with noise-canceling headphones. Students were placed in an experimental stressor state induced by the Stroop test, which provided baseline stressor data. Subsequently, participants underwent each treatment, recording their heart rate before and after each. Upon each treatment’s conclusion, the Stroop test was administered again while alpha wave data was recorded. The final data set was analyzed using a repeated-measures Analysis of Variance (ANOVA) test and paired T-tests. Results: Participants’ data showed a decrease in both max-min and mean frequencies for both treatment methods, though the only statistically significant difference between baseline recordings was found in mean frequencies for meditation treatment. No significance or trend was found in changes in heart rate. Conclusions: We concluded that our hypothesis was not supported as the statistical tests showed a significant decrease in mean alpha wave frequencies between the baseline stressor and meditation data rather than that for music therapy. This is indicative of meditation’s greater effectiveness in increasing stress tolerance in participants, which lessened the effects of the controlled stressor event, generating lower alpha frequency waves. Upon experiment conclusion, possible sources of error were identified and varied between potential compounding effects of consecutively administered treatments and an inability of the Stroop Test (SCWT) to induce an adequate level of stress in all patients. In order to circumvent the aforementioned errors, we suggest a change in methodology in which treatments would be conducted on separate days and further research into the efficacy of the SCWT as an all-inclusive stress inducer.

Efficacy of topical tulsi (Ocimum sanctum) paste for the management of oral submucous fibrosis - A clinical study.

Oral submucous fibrosis (OSMF) is a chronic insidious oral potentially malignant disorder characterized by increased collagen deposition and reduced collagen degradation causing burning sensation and difficulty in mouth opening. To assess the efficacy of topical Tulsi (Ocimum sanctum) paste for the management of OSMF. Institution-based clinical trial. The study included a total of 60 OSMF patients categorized into three Groups A, B and C (20 in each) depending on the severity according to Lai DR et al. classification. The patients were advised for topical Tulsi paste application and were evaluated for the reduction in the burning sensation and improvement in mouth opening every month for 3 subsequent months using the numeric pain rating scale (NRS) and a Vernier calliper, respectively. The baseline and 3-month recordings were subjected to inter- and intra-group statistical analysis using Kruskal-Wallis analysis of variance (ANOVA), Mann-Whitney U, one-way ANOVA, Tukey's multiple post-hoc and Wilcoxon matched-pairs tests. There was a reduction in the burning sensation and improvement in the mouth opening in all three groups. The reduction in the burning sensation was statistically significant among all the groups (P < 0.05) and the NRS scores after 3 months among the three groups were not statistically significant (P > 0.05). There was a statistically significant difference (P < 0.05) in the improvement of mouth opening between Group A and B; A and C; but not between B and C. Tulsi paste showed a significant reduction in the burning sensation and improvement of the mouth opening thereby proving to be a safe and promising medicament for OSMF.

How Do Case Mangers Determine the Types of Services Provided to Users in the Intensive Case Management? A Longitudinal Study

Introduction Intensive case management is an essential component of community mental health care system for people with severe mental illness. We examined the association of service types with previous and future functioning and hospital admissions using a longitudinal data, to clarify the case managers’ activity. Methods The study included baseline assessment, recording and analysis of services, and follow-up assessment. At the baseline and follow-up assessments, we examined functioning (ie, Personal and Social Performance Scale: PSP) and hospital admission of users for past periods. For recording and analysis of services, we recorded services provided by case managers over 2 months, and five core services were used for the analyses: regular face-to-face contact, outreach services, hospital-based (outpatient) services, and easy contacts and coordination. Results Outreach services were significantly associated with hospital admissions at baseline and follow-up assessments. Hospital-based services were significantly associated with lower PSP scores and hospital admission at follow-up assessment. Easy contacts and coordination were associated with lower PSP scores at follow-up assessment. Conclusion In Japan, most services are provided in the outpatient department of hospital, and outreach services are relatively time consuming for case managers; thus, the indications for providing outreach services need to be carefully considered. Therefore, we suggest that case managers provide flexible services to users according to the circumstances in Japan.

Human resting-state EEG and radiofrequency GSM mobile phone exposure: the impact of the individual alpha frequency

Purpose With the extensive use of mobile phone (MP), several studies have been realized to investigate the effects of radiofrequency electromagnetic fields (RF-EMF) exposure on brain activity at rest via electroencephalography (EEG), and the most consistent effect has been seen on the alpha band power spectral density (PSD). However, some studies reported an increase or a decrease of the PSD, while others showed no effect. It has been suggested that these differences might partly be due to a variability of the physiological state of the brain between subjects. So, the aim of this study was to investigate the alpha band modulation, exploring the impact of the alpha band frequency ranges applied in the PSD analysis. Materials and Methods Twenty-one healthy volunteers took part to the study with a double-blind, randomized and counterbalanced crossover design, during which eyes-open (EO) and eyes-closed (EC) resting-state EEG was recorded. The exposure system was a sham or a real GSM (global system for mobile) 900 MHz MP (pulse modulated at 217 Hz, mean power of 250 mW and 2 W peak, with a maximum specific absorption rate of 0.70 W/kg on 1 g tissue). The experimental protocol presented a baseline recording phase without MP exposure, an exposure phase during which the exposure system was placed against the left ear, and the post-exposure phase without MP. EEG data from baseline and exposure phases were analyzed and PSD was computed for the alpha band in the fixed range of 8–12 Hz and for the individual alpha band frequency range (IAF). Results Results showed a trend in decrease or increase of EEG power of both alpha oscillations during exposure in relation to EC and EO recording conditions, respectively, but not reaching statistical significance. Findings did not provide evidence for a different sensitivity to RF-EMF MP related to individual variability in the frequency of the alpha band. Conclusion In conclusion, these results did not show alpha band activity modulation during resting-state under RF-EMF. It might be argued the need of a delay after the exposure in order to appreciate an EEG spectral power modulation related to RF-EMF exposure.

Ampakines Stimulate Diaphragm Activity after Spinal Cord Injury.

Respiratory compromise after cervical spinal cord injury (SCI) is a leading cause of mortality and morbidity. Most SCIs are incomplete, and spinal respiratory motoneurons as well as proprio- and bulbospinal synaptic pathways provide a neurological substrate to enhance respiratory output. Ampakines are allosteric modulators of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, which are prevalent on respiratory neurons. We hypothesized that low dose ampakine treatment could safely and effectively increase diaphragm electromyography (EMG) activity that has been impaired as a result of acute- or sub-acute cervical SCI. Diaphragm EMG was recorded using chronic indwelling electrodes in unanesthetized, freely moving rats. A spinal hemi-lesion was induced at C2 (C2Hx), and rats were studied at 4 and 14 days post-injury during room air breathing and acute respiratory challenge accomplished by inspiring a 10% O2, 7% CO2 gas mixture. Once a stable baseline recording was established, one of two different ampakines (CX717 or CX1739, 5 mg/kg, intravenous) or a vehicle (2-hydroxypropyl-beta-cyclodextrin [HPCD]) was delivered. At 4 days post-injury, both ampakines increased diaphragm EMG output ipsilateral to C2Hx during both baseline breathing and acute respiratory challenge. Only CX1739 treatment also led to a sustained (15 min) increase in ipsilateral EMG output. At 14 days post-injury, both ampakines produced sustained increases in ipsilateral diaphragm EMG output and enabled increased output during the respiratory challenge. We conclude that low dose ampakine treatment can increase diaphragm EMG activity after cervical SCI, and therefore may provide a pharmacological strategy that could be useful in the context of respiratory rehabilitation.

Abstract 12259: Early Mechanical Signs of Myocardial Injury in a Model of Systemic Inflammation

Introduction: Early detection of myocardial dysfunction in severe inflammations, as myocarditis COVID-19 and sepsis, is of great merit. We hypothesized that metalloproteinases (MMPs) discharge from activated macrophages and leukocytes dismantles the extracellular matrix (ECM), leading to diastolic and systolic dysfunctions. Methods: The right and left ventricle functions were studies in a unique Langendorff setup, with computer controlled preloads and afterloads, utilizing rat hearts (n=7). Collagenase (MMP8) was added to the Krebs-Henseleit solution after the baseline recording. Pressure-Area loops and changes in the cardiac geometry were continuously recorded by short-axis ultrasound cines (15MHz, 20 fps) of both ventricles. Results: ECM dismantling caused immediate systolic and diastolic dysfunctions, especially in the LV. Significant decreases in the LV systolic pressure and EDV developed with overt shift of the end-diastolic pressure-volume relationship toward lower volumes. The decrease in the EDV was associated with myocardial wall thickening. After collagenase perfusion yielded 10% drop in systolic pressure, LV EDV at EDP of 12 mmHg dropped by 20.0±17.2 % (p=0.04) and LV wall volume increased by 3.39±3.68 % (p=0.04), without significant changes in the epicardial diameter. Consequently, both diastolic stiffness to volume ratio (S2V) of the diastolic elastance to EDV, and myocardial wall thickness to cavity area ratio (W2C) significantly increased. S2V and W2C increased by 1.48±0.51 and 1.32±0.34 folds relative to baseline, respectively (p=0.03, p =0.03). S2V and W2C increased by 1.82±0.71 and 1.52±0.46 folds, respectively, after 20% drop in systolic pressure (p= 0.02, p=0.02). An intact ECM is essential for the diastolic recoil. Dismantling the ECM diminishes the diastolic recoil and increases diastolic stiffness. Interestingly, the right ventricle presented similar trends, but the changes were insignificant, and the RV was less vulnerable to damage. Conclusion: ECM degradation causes severe systolic and diastolic dysfunctions. Novel indices (S2V and W2C) for early detection of myocardial involvement in severe inflammatory diseases were developed.

Effects of rocuronium dosage on intraoperative neurophysiological monitoring in patients undergoing spinal surgery.

What is known and objectiveIntraoperative neurophysiological monitoring (IONM) has been widely used in clinical practice. Therefore, the influence of neuromuscular blockers essential for spinal anaesthesia on IONM is worthy of our attention, but no randomized study has evaluated the dose‐response effect. This study investigated the effects of different doses of rocuronium bromide on the intraoperative monitoring of motor evoked potentials (MEPs).MethodsWe conducted a randomized, double‐blind trial to assess the effects of three rocuronium bromide doses (6.0, 9.0, 12 μg·kg−1·min−1) combined with intravenous infusion of propofol 6–8 mg·kg−1·h−1 and remifentanil 10 μg·kg−1·h−1 on the amplitudes of somatosensory evoked potentials (SEPs) and MEPs at the time of the baseline recording (T1), before pedicle screw placement (T2) and before spinal canal decompression (T3). Secondary outcomes included measurement of neuromuscular function, the occurrence of unexpected intraoperative body movement and recovery of spontaneous breathing.Results and discussionA total of 123 patients were enrolled, and 120 patients were ultimately analysed. No differences were observed in the amplitude of SEPs among the three groups (p > 0.05). The MEP amplitude differences at T1, T2 and T3 in all limbs did not differ in patients receiving rocuronium at 6.0 μg·kg−1·min−1 and 9.0 μg·kg−1·min−1 (p > 0.05). However, when rocuronium was administered at 12.0 μg·kg−1·min−1, MEP amplitudes at the time point T3 were significantly attenuated compared with the time points T1 and T2 in both right upper limb and left lower limb (p = 0.002, p = 0.025, respectively). In patients treated with rocuronium 6.0 μg·kg−1·min−1, the incidence of unexpected body movement was significantly higher (p = 0.026), and the train‐of‐four count (TOF count) showed a significant increase at T2 and T3 (p < 0.001) compared to other doses.What is new and conclusionRocuronium bromide at a rate of 9.0 μg·kg−1·min−1 provided suitable and adequate muscle relaxation without inhibiting IONM; thus, this dose is recommended for spinal surgery.

Hippocampal-ANT connectivity and ANT DBS: Circadian trends and response to stimulation

Abstract Although hippocampal (HC)-anterior nucleus of the thalamus (ANT) interactions are implicated in limbic epilepsy, their dynamics over the circadian cycle and following ANT deep brain stimulation (DBS) remain unclear. We used ultra-long, ambulatory, HC and ANT intracranial electroencephalographic recordings to describe HC-ANT connectivity in a patient with bilateral temporal lobe epilepsy. The patient was implanted with the investigational Medtronic Summit RC+S ™ sensing and stimulating DBS device. Electrodes were implanted into the long axis of the hippocampus and ANT bilaterally. Therapeutic stimulation was delivered to the ANT. HC-ANT coherence was calculated in the Berger bands (4-125 Hz) in 10 second segments from one month of baseline recordings and from a three week period of night-off stimulation that followed a month of continuous low frequency ANT stimulation (2Hz). Only coherence measurements wherein both contacts had spectral peaks in the relevant band, without seizures, spikes, or stimulation, were analyzed. Coherence values over the circadian cycle were compared across hemispheres and between baseline and post-stimulation periods. At baseline, concurrent spectral peaks in HC and ANT occurred across the circadian cycle, primarily in the high beta and low gamma frequency bands bilaterally, with the less epileptogenic, right hemisphere showing significantly greater high beta coherence (Wilcoxon Rank-Sum, n1 = 2638, n2 = 2515, p < 0.0001). Post-stimulation, nighttime left HC-ANT high beta coherence did not change, but the central frequency of coherent high beta peaks did increase significantly (Wilcoxon Rank-Sum, n1 = 368, n2 = 492, p < 0.0001). Our finding that HC-ANT high beta coherence was decreased in the more epileptogenic hemisphere is consistent with reports of functional isolation of epileptogenic zone. The stimulation-associated change in central frequency at which beta peaks occurred, but not in overall magnitude of HC-ANT coherence, suggests that low frequency ANT-DBS influences the spectral composition of HC-ANT connectivity. Keywords: Deep brain stimulation, Connectivity, Epilepsy, Anterior nucleus of the thalamus