Impact of pandemic-related movement restriction on public access defibrillation in Japan: a retrospective cohort study.

OBJECTIVES: To analyse monthly changes in public access defibrillation (PAD) incidence and outcomes of out-of-hospital cardiac arrest (OHCA) during the 2020-2021 COVID-19 pandemic compared with those during the 2016-2019 prepandemic period with consideration of pandemic-related movement restriction. DESIGN: Retrospective cohort study. SETTING: An extended database was created by combining and reconciling the nationwide Utstein-style OHCA and the emergency medical service (EMS) transportation databases in Japan. PARTICIPANTS: We analysed 226 182 EMS-witnessed, non-newborn and out-of-home OHCA cases in Japan. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes were the PAD incidence and neurologically favourable 1-month survival rate. The secondary outcomes were bystander cardiopulmonary resuscitation (CPR) provision and dispatcher-assisted CPR attempts. RESULTS: The proportion of out-of-home OHCA cases slightly decreased during the pandemic (from 33.7% to 31.9%). Although the pandemic was associated with a decreased PAD incidence, 2-year trend analyses by an interaction test showed that the PAD incidence was lower during the first nationwide declaration of a state of emergency (p<0.001) and in the pandemic's second year (p<0.01). Regardless of location, delays in basic life support (BLS) actions and EMS contact with patients were more common and the rate of PAD-induced return of spontaneous circulation was lower during the pandemic. PAD incidence reduction was significant only in locations with a recommendation of automated external defibrillator placement (p<0.001). In other locations, a pronounced delay in BLS was found during the pandemic. The neurologically favourable survival rate was reduced in parallel with the reduced PAD incidence during the pandemic (r=0.612, p=0.002). CONCLUSIONS: Prolonged and repeated movement restrictions during the COVID-19 pandemic worsened the OHCA outcomes concurrently with disturbed BLS actions, including the reduced PAD incidence in out-of-home settings. Maintaining BLS training, re-arranging automated external defibrillator placement and establishing a local alert system for recruiting well-trained citizens to the scene are essential.

Deficiency of mastl, a mitotic regulator, results in cell detachment from developing tissues of zebrafish embryos.

To form tissues with unique functions and structures, it is important that the cells that comprise them maintain physical contact. On the other hand, with each mitosis, drastic changes in cell shapes, cell adhesion, and cytoskeletal architecture may cause such contacts to be temporarily weakened, risking improper development and maintenance of tissues. Despite such risks, tissues form properly during normal development. However, it is not well understood whether mitotic abnormalities affect tissue formation. Here, analysis of zebrafish embryos with aberrant mitosis shows that proper progression of mitosis is important to maintain cell contact in developing tissues. By screening mutants with abnormal trunk and tail development, we obtained a mutant with perturbed expression of some tissue-specific genes in embryonic caudal regions. The responsible gene is mastl/gwl, which is involved in progression of mitosis. Analysis focusing on the chordo-neural hinge (CNH), the primordium of axial tissues, shows that cell detachment from the CNH is increased in mastl mutant embryos. Time-lapse imaging reveals that this cell detachment occurs during mitosis. These results suggest that cells are unable to maintain contact due to abnormalities in progression of mitosis in mastl mutants.

Structure-based engineering of Tor complexes reveals that two types of yeast TORC1 produce distinct phenotypes.

Certain proteins assemble into diverse complex states, each having a distinct and unique function in the cell. Target of rapamycin (Tor) complex 1 (TORC1) plays a central role in signalling pathways that allow cells to respond to the environment, including nutritional status signalling. TORC1 is widely recognised for its association with various diseases. The budding yeast Saccharomyces cerevisiae has two types of TORC1, Tor1-containing TORC1 and Tor2-containing TORC1, which comprise different constituent proteins but are considered to have the same function. Here, we computationally modelled the relevant complex structures and then, based on the structures, rationally engineered a Tor2 mutant that could form Tor complex 2 (TORC2) but not TORC1, resulting in a redesign of the complex states. Functional analysis of the Tor2 mutant revealed that the two types of TORC1 induce different phenotypes, with changes observed in rapamycin, caffeine and pH dependencies of cell growth, as well as in replicative and chronological lifespan. These findings uncovered by a general approach with huge potential - model structure-based engineering - are expected to provide further insights into various fields such as molecular evolution and lifespan.

Cellular responses to compound stress induced by atmospheric-pressure plasma in fission yeast.

The stress response is one of the most fundamental cellular processes. Although the molecular mechanisms underlying responses to a single stressor have been extensively studied, cellular responses to multiple stresses remain largely unknown. Here, we characterized fission yeast cellular responses to a novel stress inducer, non-thermal atmospheric-pressure plasma. Plasma irradiation generates ultraviolet radiation, electromagnetic fields and a variety of chemically reactive species simultaneously, and thus can impose multiple stresses on cells. We applied direct plasma irradiation to fission yeast and showed that strong plasma irradiation inhibited fission yeast growth. We demonstrated that mutants lacking sep1 and ace2, both of which encode transcription factors required for proper cell separation, were resistant to plasma irradiation. Sep1-target transcripts were downregulated by mild plasma irradiation. We also demonstrated that plasma irradiation inhibited the target of rapamycin kinase complex 1 (TORC1). These observations indicate that two pathways, namely the Sep1-Ace2 cell separation pathway and TORC1 pathway, operate when fission yeast cope with multiple stresses induced by plasma irradiation.

Metarhizium robertsii COH1 functionally complements Schizosaccharomyces pombe Ecl family proteins.

The fission yeast Schizosaccharomyces pombe ecl family genes respond to various starvation signals and induce appropriate intracellular responses, including the extension of chronological lifespan and induction of sexual differentiation. Herein, we propose that the colonization of hemocoel 1 (COH1) protein of Metarhizium robertsii, an insect-pathogenic fungus, is a functional homolog of S. pombe Ecl1 family proteins.

The physiological response during optogenetic-based cardiac pacing in awake freely moving mice.

There are several methods to control a heart rate, such as electrical stimulation and drug administration. However, these methods may be invasive or affect other organs. Recently, an optogenetic-based cardiac pacing method has enabled us to stimulate the cardiac muscle in non-contact. In many previous studies, the pacing was applied ex vivo or in anesthetized animals. Therefore, the physiologic response of animals during optogenetic pacing remains unclear. Here, we established a method of optogenetic-based cardiac pacing in awake, freely moving mice and simultaneously measured electrocardiogram, blood pressure, and respiration. As a result, light-induced myocardial contraction produces blood flow and indirectly affects the respiration rhythm. Additionally, light illumination enabled heart rate recovery in bradycardic mice. These findings may be employed for further research that relates a heartbeat state to animal behavior. Together, this method may drive the development of less invasive pacemakers without pacing leads.

ecl family genes: Factors linking starvation and lifespan extension in Schizosaccharomyces pombe.

In the fission yeast Schizosaccharomyces pombe, the duration of survival in the stationary phase, termed the chronological lifespan (CLS), is affected by various environmental factors and the corresponding gene activities. The ecl family genes were identified in the genomic region encoding non-coding RNA as positive regulators of CLS in S. pombe, and subsequently shown to encode relatively short proteins. Several studies revealed that ecl family genes respond to various nutritional starvation conditions via different mechanisms, and they are additionally involved in stress resistance, autophagy, sexual differentiation, and cell cycle control. Recent studies reported that Ecl family proteins strongly suppress target of rapamycin complex 1, which is a conserved eukaryotic nutrient-sensing kinase complex that also regulates longevity in a variety of organisms. In this review, we introduce the regulatory mechanisms of Ecl family proteins and discuss their emerging findings.

ILF3 prion-like domain regulates gene expression and fear memory under chronic stress.

The prion-like domain (PrLD) is a class of intrinsically disordered regions. Although its propensity to form condensates has been studied in the context of neurodegenerative diseases, the physiological role of PrLD remains unclear. Here, we investigated the role of PrLD in the RNA-binding protein NFAR2, generated by a splicing variant of the Ilf3 gene. Removal of the PrLD in mice did not impair the function of NFAR2 required for survival, but did affect the responses to chronic water immersion and restraint stress (WIRS). The PrLD was required for WIRS-sensitive nuclear localization of NFAR2 and WIRS-induced changes in mRNA expression and translation in the amygdala, a fear-related brain region. Consistently, the PrLD conferred resistance to WIRS in fear-associated memory formation. Our study provides insights into the PrLD-dependent role of NFAR2 for chronic stress adaptation in the brain.

Peripheral vs. core body temperature as hypocretin/orexin neurons degenerate: Exercise mitigates increased heat loss.

Hypocretins/Orexins (Hcrt/Ox) are hypothalamic neuropeptides implicated in diverse functions, including body temperature regulation through modulation of sympathetic vasoconstrictor tone. In the current study, we measured subcutaneous (Tsc) and core (Tb) body temperature as well as activity in a conditional transgenic mouse strain that allows the inducible ablation of Hcrt/Ox-containing neurons by removal of doxycycline (DOX) from their diet (orexin-DTA mice). Measurements were made during a baseline, when mice were being maintained on food containing DOX, and over 42 days while the mice were fed normal chow which resulted in Hcrt/Ox neuron degeneration. The home cages of the orexin-DTA mice were equipped with running wheels that were either locked or unlocked. In the presence of a locked running wheel, Tsc progressively decreased on days 28 and 42 in the DOX(-) condition, primarily during the dark phase (the major active period for rodents). This nocturnal reduction in Tsc was mitigated when mice had access to unlocked running wheels. In contrast to Tsc, Tb was largely maintained until day 42 in the DOX(-) condition even when the running wheel was locked. Acute changes in both Tsc and Tb were observed preceding, during, and following cataplexy. Our results suggest that ablation of Hcrt/Ox-containing neurons results in elevated heat loss, likely through reduced sympathetic vasoconstrictor tone, and that exercise may have some therapeutic benefit to patients with narcolepsy, a disorder caused by Hcrt/Ox deficiency. Acute changes in body temperature may facilitate prediction of cataplexy onset and lead to interventions to mitigate its occurrence.

The ecl family gene ecl3+ is induced by phosphate starvation and contributes to sexual differentiation in fission yeast.

In Schizosaccharomyces pombe, ecl family genes are induced by several signals, such as starvation of various nutrients, including sulfur, amino acids and Mg2+, and environmental stress, including heat or oxidative stress. These genes mediate appropriate cellular responses and contribute to the maintenance of cell viability and induction of sexual differentiation. Although this yeast has three ecl family genes with overlapping functions, any environmental conditions that induce ecl3+ remain unidentified. We demonstrate that ecl3+ is induced by phosphate starvation, similar to its chromosomally neighboring genes, pho1+ and pho84+, which respectively encode an extracellular acid phosphatase and an inorganic phosphate transporter. ecl3+ expression was induced by the transcription factor Pho7 and affected by the cyclin-dependent kinase (CDK)-activating kinase Csk1. Phosphate starvation induced G1 arrest and sexual differentiation via ecl family genes. Biochemical analyses suggested that this G1 arrest was mediated by the stabilization of the CDK inhibitor Rum1, which was dependent on ecl family genes. This study shows that ecl family genes are required for appropriate responses to phosphate starvation and provides novel insights into the diversity and similarity of starvation responses.

A force balance model for a cell size-dependent meiotic nuclear oscillation in fission yeast.

Fission yeast undergoes premeiotic nuclear oscillation, which is dependent on microtubules and is driven by cytoplasmic dynein. Although the molecular mechanisms have been analyzed, how a robust oscillation is generated despite the dynamic behaviors of microtubules has yet to be elucidated. Here, we show that the oscillation exhibits cell length-dependent frequency and requires a balance between microtubule and viscous drag forces, as well as proper microtubule dynamics. Comparison of the oscillations observed in living cells with a simulation model based on microtubule dynamic instability reveals that the period of oscillation correlates with cell length. Genetic alterations that reduce cargo size suggest that the nuclear movement depends on viscous drag forces. Deletion of a gene encoding Kinesin-8 inhibits microtubule catastrophe at the cell cortex and results in perturbation of oscillation, indicating that nuclear movement also depends on microtubule dynamic instability. Our findings link numerical parameters from the simulation model with cellular functions required for generating the oscillation and provide a basis for understanding the physical properties of microtubule-dependent nuclear movements.

[Patient Radiation Dose for Percutaneous Coronary Intervention by Treatment Area: Dosimetry Using DRLs 2020].

PURPOSE: Skin injury in patients due to radiation exposure has been a complication in percutaneous coronary intervention (PCI) for a long time. To the best of our knowledge, there have been no reports comparing radiation dose by treatment area with diagnostic reference levels (DRLs) 2020, although the radiation dose varies by treatment area in PCI. METHODS: In this study, the treatment areas were classified into four segments (i.e., AHA #1-3, AHA #4, AHA #5-10, and AHA #11-15), and each segment was compared with DRLs 2020. This retrospective study included 984 consecutive patients with single-vessel disease and non-chronic total occlusion. PCI was performed on a single device. RESULTS: The median radiation dose was 1640.8 mGy, and the radiation dose for AHA #4 was 2732.0 mGy, which was significantly higher than the other treatment areas (p<0.001). In AHA #4, the radiation dose increased due to the heavy use of the left cranial view, and the patient background contributed to the increased lesion complexity. Therefore, it was challenging to evaluate AHA #4 and the other treatment areas with a uniform DRL value. CONCLUSION: Establishing a subdivided index for each treatment area is crucial if DRLs are used as a reference during procedures and as a guide for dose optimization.

Epidemiology of out-of-hospital cardiac arrests caused by anaphylaxis and factors associated with outcomes: an observational study.

OBJECTIVES: Describe the epidemiologic features of out-of-hospital cardiac arrest (OHCA) caused by anaphylaxis and identify outcome-associated factors. DESIGN: Observational study. SETTING: Data from the Japanese Fire and Disaster Management Agency database. PARTICIPANTS: A total of 292 patients from 879 057 OHCA events between 2013 and 2019 with OHCA caused by anaphylaxis and for whom prehospital resuscitation was attempted were included in the analysis. OUTCOME MEASURES: The incidence of anaphylaxis-induced OHCA, neurologically favourable 1-month survival, defined as cerebral performance category 1 or 2, and 1-month survival. RESULTS: The proportion of OHCAs caused by anaphylaxis was high in non-elderly and male patients from July to September and during business hours. Bystander-witnessed (adjusted OR=4.43; 95% CI 1.84 to 10.7) and emergency medical service-witnessed events (adjusted OR=3.28; 95% CI 1.21 to 8.87) were associated with higher rates of neurologically favourable 1-month survival as well as better 1-month survival. Shockable initial ECG rhythms were recorded in only 19 patients (6.5%), and prehospital defibrillation was attempted in 16 such patients (84.2%). Neither shockable initial rhythms nor prehospital defibrillation was associated with better outcomes. Patients requiring advanced airway management had poor neurological outcomes (adjusted OR=0.17; 95% CI 0.07 to 0.42) and worse 1-month survival (adjusted OR=0.28; 95% CI 0.14 to 0.58). CONCLUSIONS: Few cases of OHCA were attributable to anaphylaxis. Witnessed OHCAs, particularly those witnessed by bystanders, were associated with better neurological outcomes. Airway complications requiring advanced airway management were likely associated with poor outcomes.

Activity of putative orexin neurons during cataplexy.

It is unclear why orexin-deficient animals, but not wild-type mice, show cataplexy. The current hypothesis predicts simultaneous excitation of cataplexy-inhibiting orexin neurons and cataplexy-inducing amygdala neurons. To test this hypothesis, we measured the activity of putative orexin neurons in orexin-knockout mice during cataplexy episodes using fiber photometry. We created two animal models of orexin-knockout mice with a GCaMP6 fluorescent indicator expressed in putative orexin neurons. We first prepared orexin-knockout mice crossed with transgenic mice carrying a tetracycline-controlled transactivator transgene under the control of the orexin promoter. TetO-GCaMP6 was then introduced into mice via an adeno-associated virus injection or natural crossing. The resulting two models showed restricted expression of GCaMP6 in the hypothalamus, where orexin neurons should be located, and showed excitation to an intruder stress that was similar to that observed in orexin-intact mice in our previous study. The activity of these putative orexin neurons increased immediately before the onset of cataplexy-like behavior but decreased (approximately - 20% of the baseline) during the cataplexy-like episode. We propose that the activity of orexin neurons during cataplexy is moderately inhibited by an unknown mechanism. The absence of cataplexy in wild-type mice may be explained by basal or residual activity-induced orexin release, and emotional stimulus-induced counter activation of orexin neurons may not be necessary. This study will serve as a basis for better treatment of cataplexy in narcolepsy patients.

Effect of large-scale disasters on bystander-initiated cardiopulmonary resuscitation in family-witnessed, friend-witnessed and colleague-witnessed out-of-hospital cardiac arrest: a retrospective analysis of prospectively collected, nationwide, population-based data.

IMPORTANCE: The effect of large-scale disasters on bystander cardiopulmonary resuscitation (BCPR) performance is unknown. OBJECTIVE: To investigate whether and how large-scale earthquake and tsunami as well as subsequent nuclear pollution influenced BCPR performance for out-of-hospital cardiac arrest (OHCA) witnessed by family and friends/colleagues. DESIGN AND SETTING: Retrospective analysis of prospectively collected, nationwide, population-based data for OHCA cases. PARTICIPANTS: From the nationwide OHCA registry recorded between 11 March 2010 and 1 March 2013, we extracted 74 684 family-witnessed and friend/colleague-witnessed OHCA cases without prehospital physician involvement. EXPOSURE: Earthquake and tsunamis that were followed by nuclear pollution and largely affected the social life of citizens for at least 24 weeks. MAIN OUTCOME AND MEASURE: Neurologically favourable outcome after 1 month, 1-month survival and BCPR. METHODS: We analysed the 4-week average trend of BCPR rates in the years affected and before and after the disaster. We used univariate and multivariate logistic regression analyses to investigate whether these disasters affected BCPR and OHCA results. RESULTS: Multivariable logistic regression for tsunami-affected prefectures revealed that the BCPR rate during the impact phase in 2011 was significantly lower than that in 2010/2012 (42.5% vs 48.2%; adjusted OR; 95% CI 0.82; 0.68 to 0.99). A lower level of bystander compliance with dispatcher-assisted CPR instructions (62.1% vs 69.5%, 0.72; 95% CI 0.57 to 0.92) in the presence of a preserved level of voluntary BCPR performance (23.6% vs 23.8%) was also observed. Both 1-month survival and neurologically favourable outcome rates during the impact phase in 2011 were significantly poorer than those in 2010/2012 (8.5% vs 10.7%, 0.72; 95% CI 0.52 to 0.99, 4.0% vs 5.2%, 0.62; 95% CI 0.38 to 0.98, respectively). CONCLUSION AND RELEVANCE: A large-scale disaster with nuclear pollution influences BCPR performance and clinical outcomes of OHCA witnessed by family and friends/colleagues. Basic life-support training leading to voluntary-initiated BCPR might serve as preparedness for disaster and major accidents.

Association between the types of bystander cardiopulmonary resuscitation and the survival with good neurologic outcome of preschool pediatric out-of-hospital cardiac arrest cases in Japan: A propensity score matching analysis using an extended nationwide database.

Background: Pediatric out-of-hospital cardiac arrests (OHCAs) are frequently associated with a respiratory etiology. Despite the high proportion of preschool children with OHCAs, very few studies on this special population exist. This study characterizes the epidemiologic features of preschool pediatric OHCAs and analyzes the advantage of conventional (ventilations with chest compressions) bystander cardiopulmonary resuscitation (CPR) over compression-only bystander CPR (BCPR) on the one-month post-event neurological status of the patient. Methods: Japanese nationwide databases for all ambulance transport events and OHCAs occurring during a 4-year period between 2016 and 2019 were combined, totalling 3,608 patient events. Children ≤6-years-old were included; physician- and EMS-witnessed events, no prehospital resuscitation effort events, and neonatal patient events were excluded. Neurologically favorable 1-month survival rates were compared among groups using univariate and multivariate analyses before and after propensity score matching. Results: From the combined database, 2,882 pediatric OHCAs meeting selection criteria were categorized as no BCPR (984), compression-only BCPR (1,428), and conventional BCPR (470). The proportion of bystander-witnessed cases was low (22.3%). Most OHCA witnesses were family members (88.5%), and most OHCAs occurred at home (88.0%). The neurologically favorable 1-month survival rates were: no BCPR 2.4%, compression only, 3.2%, and conventional 6.6% (P < 0.01). Multivariate logistic regression analysis before and after matching showed that conventional BCPR was associated with higher neurologically favorable 1-month survival than compression-only BCPR. Subgroup analyses after matching demonstrated that conventional BCPR was associated with better outcomes in nonmedical (adjusted odds ratio; 95% confidence interval, 2.83; 1.09-7.32) and unwitnessed OHCA cases (3.42; 1.09-10.8). Conclusions: Conventional CPR is rarely performed by bystanders in preschool pediatric OHCA. However, conventional BCPR results in neurologically favorable outcomes in nonmedical and unwitnessed cases.

Involvement of A5/A7 noradrenergic neurons and B2 serotonergic neurons in nociceptive processing: a fiber photometry study.

In the central nervous system, the A6 noradrenaline (NA) and the B3 serotonin (5-HT) cell groups are well-recognized players in the descending antinociceptive system, while other NA/5-HT cell groups are not well characterized. A5/A7 NA and B2 5-HT cells project to the spinal horn and form descending pathways. We recorded G-CaMP6 green fluorescence signal intensities in the A5/A7 NA and the B2 5-HT cell groups of awake mice in response to acute tail pinch stimuli, acute heat stimuli, and in the context of a non-noxious control test, using fiber photometry with a calcium imaging system. We first introduced G-CaMP6 in the A5/A7 NA or B2 5-HT neuronal soma, using transgenic mice carrying the tetracycline-controlled transactivator transgene under the control of either a dopamine ß-hydroxylase or a tryptophan hydroxylase-2 promoters and by the site-specific injection of adeno-associated virus (AAV-TetO(3G)-G-CaMP6). After confirming the specific expression patterns of G-CaMP6, we recorded G-CaMP6 green fluorescence signals in these sites in awake mice in response to acute nociceptive stimuli. G-CaMP6 fluorescence intensity in the A5, A7, and B2 cell groups was rapidly increased in response to acute nociceptive stimuli and soon after, it returned to baseline fluorescence intensity. This was not observed in the non-noxious control test. The results indicate that acute nociceptive stimuli rapidly increase the activities of A5/A7 NA or B2 5-HT neurons but the non-noxious stimuli do not. The present study suggests that A5/A7 NA or B2 5-HT neurons play important roles in nociceptive processing in the central nervous system. We suggest that A5/A7/B2 neurons may be new therapeutic targets. All performed procedures were approved by the Institutional Animal Use Committee of Kagoshima University (MD17105) on February 22, 2018.

The dorsal hippocampal protein targeting to glycogen maintains ionotropic glutamate receptor subunits expression and contributes to working and short-term memories in mice.

Brain glycogen metabolism is known to be involved in the learning and memory processes. Protein targeting to glycogen (PTG) is a crucial molecule for glycogenesis, and its expression level is shown to be increased in the dorsal hippocampus during fear memory acquisition and recall, suggesting that PTG may contribute to the memory process. However, its detailed role in the dorsal hippocampus remains unclear. Therefore, we knocked down the expression of PTG in the dorsal hippocampus and attempted to analyze its function behaviorally. PTG expression was found to be enriched in astrocytes. Furthermore, short hairpin RNA against PTG suppressed the expression of PTG in astrocytes. Mice with knockdown of PTG in the dorsal hippocampus showed suppressed alternation behavior in the Y-maze test and reduced memory recall at the first hour after acquisition in the passive avoidance test. Knockdown of mouse dorsal hippocampal astrocyte-specific PTG also impaired working memory in the Y-maze test. GluR1, GluR2, and NR2a subunits expressions were significantly down-regulated in the dorsal hippocampus of mice in which PTG was knocked down. These results indicate that PTG in the dorsal hippocampal astrocytes may contribute to working and short-term memories by maintaining the expression of glutamate receptor subunits.

Intensity dependency of peripheral nerve stimulation in spinal LTP induced by paired associative corticospinal-motoneuronal stimulation (PCMS).

Paired associative corticospinal-motoneuronal stimulation (PCMS) induces plasticity at synapses between corticospinal tracts (CSTs) and spinal motoneurons (SMs). We investigated the effects of peripheral nerve electrical stimulation (PNS) intensity on PCMS-induced plasticity. PCMS consisted of 180 paired stimuli of transcranial magnetic stimulation (TMS) over the left primary motor cortex with PNS on the right ulnar nerve at the wrist. We compared effects induced by different PNS intensities: supramaximal, twice and three times sensory threshold intensities. For evaluating efficacy of the synapse between CSTs and SMs, single-pulse TMS was delivered at cervicomedullary junction level, and cervicomedullary motor-evoked potentials (CMEPs) were recorded from the right first-dorsal interosseous muscle before and after PCMS. PCMS with the supramaximal PNS intensity increased CMEP amplitude. The facilitatory effect of PCMS with the supramaximal PNS was larger than those of PCMS with weaker PNS intensities. Sham TMS with the supramaximal PNS showed no CMEP changes after the intervention. PNS intensity of PCMS influences the magnitude of synaptic plasticity induction between the CSTs and SMs at the spinal level, and the supramaximal intensity is the best for induction of long-term potentiation-like effects. The PNS intensity may influence the number of activated SMs by axonal backpropagating pulses with PNS which must overlap with descending volleys induced by TMS.

Seizure-like activity at the onset of emergency medical service-witnessed out-of-hospital cardiac arrest: An observational study.

AIMS: Emergency medical service (EMS) may detect seizure-like activity in addition to agonal breathing in out-of-hospital cardiac arrest (OHCA). This study investigates the incidence and predictors of seizure-like activity in nontraumatic, EMS-witnessed OHCA and their association with clinical outcomes. METHODS: This prospective study explored EMS-recorded concomitant signs/symptoms that lead to the requirement of advanced life support in patients with nontraumatic, EMS-witnessed OHCA. Seizure-like activity includes abnormal/tonic movements and eyeball deviation. Sudden OHCA was defined by the absence of signs/symptoms of impending cardiac arrest at EMS contact or progressive circulatory/respiratory depressions after the EMS contact. Neurologically favorable outcomes were defined as the cerebral performance category score of 1 or 2 at discharge. RESULTS: From April 2012 to March 2020, 465 patients were studied. The incidence of seizure-like activity at cardiac arrest onset was 12.7% (59/465) in all patients with nontraumatic, EMS-witnessed OHCA. Seizure-like activity was common during shockable initial rhythm; in patients with "sudden" OHCA; and in patients who were younger, male, or had a presumed cardiac etiology. In a boosting tree, shockable initial rhythm, "sudden" OHCA, and presumed cardiac etiology were major factors that predicted the incidence of seizure-like activity. Multivariate logistic regression models including and excluding OHCA characteristics revealed that both seizure-like activity and agonal breathing recorded during EMS-witnessed OHCA were associated with favorable outcomes. CONCLUSIONS: Seizure-like activity is a major sign/symptom of the onset of "sudden" cardiac arrest of presumed cardiac etiology, particularly in patients with shockable initial rhythms. Such activity were significantly associated with neurologically favorable outcomes.