Exploration of a Novel Electric-Fuse Device with a Simple Structure of Ni Metal on a SiO2 Dielectric for Electrostatic Discharge Protection under a Human Body Model.

On-chip electrostatic discharge (ESD) protection poses a challenge in the chip fabrication process. In this study, a novel electric fuse (E-fuse) device featuring a simple structure of Ni metal on a SiO2 dielectric for ESD protection was proposed, and the physical mechanism of its operation was investigated in detail. Experimental evaluations, utilizing transmission line pulse (TLP) testing and fusing performance analyses, reveal that the E-fuse, constructed with a Ni metal layer measuring 5 µm in width, 100 µm in length, and 5 nm in thickness, achieved a significant ESD protection voltage of 251 V (VHBM) and demonstrates low-voltage fusing at a bias voltage of 7 V. Compared to traditional ESD protection devices, the E-fuse boasts a smaller size and removability. To assess fusing performance, devices of varying sizes were tested using a fusing lifetime model. This study supports both theoretical and empirical evidence, enabling the adoption of cost-effective, straightforward E-fuse devices for ESD protection.

3D printing chronicles in medical devices and pharmaceuticals: tracing the evolution and historical milestones.

The objective of this study is to collect the significant advancements of 3D printed medical devices in the biomedical area in recent years. Especially related to a range of diseases and the polymers employed in drug administration. To address the existing limitations and constraints associated with the method used for producing 3D printed medical devices, in order to optimize their suitability for degradation. The compilation and use of research papers, reports, and patents that are relevant to the key keywords are employed to improve comprehension. According to this thorough investigation, it can be inferred that the 3D Printing method, specifically Fuse Deposition Modeling (FDM), is the most suitable and convenient approach for preparing medical devices. This study provides an analysis and summary of the development trend of 3D printed implantable medical devices, focusing on the production process, materials specially the polymers, and typical items associated with 3D printing technology. This study offers a comprehensive examination of nanocarrier research and its corresponding discoveries. The FDM method, which is already facing significant challenges in terms of achieving optimal performance and cost reduction, will experience remarkable advantages from this highly valuable technology. The objective of this analysis is to showcase the efficacy and limitations of 3D-printing applications in medical devices through thorough research, highlighting the significant technological advancements it offers. This article provides a comprehensive overview of the most recent research and discoveries on 3D-printed medical devices, offering significant insights into their study.

Enhanced low-light image fusion through multi-stage processing with Bayesian analysis and quadratic contrast function.

This manuscript introduces an innovative multi-stage image fusion framework that adeptly integrates infrared (IR) and visible (VIS) spectrum images to surmount the difficulties posed by low-light settings. The approach commences with an initial preprocessing stage, utilizing an Efficient Guided Image Filter for the infrared (IR) images to amplify edge boundaries and a function for the visible (VIS) images to boost local contrast and brightness. Utilizing a two-scale decomposition technique that incorporates Lipschitz constraints-based smoothing, the images are effectively divided into distinct base and detail layers, thereby guaranteeing the preservation of essential structural information. The process of fusion is carried out in two distinct stages: firstly, a method grounded in Bayesian theory is employed to effectively combine the base layers, so effectively addressing any inherent uncertainty. Secondly, a Surface from Shade (SfS) method is utilized to ensure the preservation of the scene's geometry by enforcing integrability on the detail layers. Ultimately a Choose Max principle is employed to determine the most prominent textural characteristics, resulting in the amalgamation of the base and detail layers to generate an image that exhibits a substantial enhancement in both clarity and detail. The efficacy of our strategy is substantiated by rigorous testing, showcasing notable progressions in edge preservation, detail enhancement, and noise reduction. Consequently, our method presents significant advantages for real-world applications in image analysis.

From FUSE to a hands-on electrosurgery course using a cadaveric model.

INTRODUCTION: Surgical procedures in contemporary practice frequently employ energy-based devices, yet comprehensive education surrounding their safety and effectiveness remains deficient. We propose an innovative course for residents that aims to provide basic electrosurgery knowledge and promote the safe use of these devices. METHODS: We developed a simulated training course for first-year general surgery and orthopedic residents. First, a survey was conducted regarding their knowledge perception about energy devices. The course consisted of two online theoretical sessions, followed by three in-person practical sessions. First-year residents performed three video-recorded attempts using a cadaveric model and were assessed through a digital platform using the Objective Structured Assessment of Technical Skill (OSATS), a Specific Rating Scale (SRS), and a surgical energy-based devices scale (SEBS). Third-year residents were recruited as a control group. RESULTS: The study included 20 first-year residents and 5 third-year residents. First-year residents perceived a knowledge gap regarding energy devices. Regarding practical performance, both OSATS and checklist scores were statistically different between novices at their first attempt and the control group. When we analyzed the novice's performance, we found a significant increase in OSATS (13 vs 21), SRS (13 vs 17.5), and SEBS (5 vs 7) pre- and post-training scores. The amount of feedback referred to skin burns with the electro-scalpel reduced from 18 feedbacks in the first attempt to 2 in the third attempt (p-value = 0.0002). When comparing the final session of novices with the control group, no differences were found in the SRS (p = 0.22) or SEBS (p = 0.97), but differences remained in OSATS (p = 0.017). CONCLUSION: This study supports the implementation of structured education in electrosurgery among surgical trainees. By teaching first-year residents about electrosurgery, they can acquire a skill set equivalent to that of third-year residents. The integration of such courses can mitigate complications associated with energy device misuse, ultimately enhancing patient safety.

Exploring the role of the Kölliker-Fuse nucleus in breathing variability by mathematical modelling.

The Kölliker-Fuse nucleus (KF), which is part of the parabrachial complex, participates in the generation of eupnoea under resting conditions and the control of active abdominal expiration when increased ventilation is required. Moreover, dysfunctions in KF neuronal activity are believed to play a role in the emergence of respiratory abnormalities seen in Rett syndrome (RTT), a progressive neurodevelopmental disorder associated with an irregular breathing pattern and frequent apnoeas. Relatively little is known, however, about the intrinsic dynamics of neurons within the KF and how their synaptic connections affect breathing pattern control and contribute to breathing irregularities. In this study, we use a reduced computational model to consider several dynamical regimes of KF activity paired with different input sources to determine which combinations are compatible with known experimental observations. We further build on these findings to identify possible interactions between the KF and other components of the respiratory neural circuitry. Specifically, we present two models that both simulate eupnoeic as well as RTT-like breathing phenotypes. Using nullcline analysis, we identify the types of inhibitory inputs to the KF leading to RTT-like respiratory patterns and suggest possible KF local circuit organizations. When the identified properties are present, the two models also exhibit quantal acceleration of late-expiratory activity, a hallmark of active expiration featuring forced exhalation, with increasing inhibition to KF, as reported experimentally. Hence, these models instantiate plausible hypotheses about possible KF dynamics and forms of local network interactions, thus providing a general framework as well as specific predictions for future experimental testing. KEY POINTS: The Kölliker-Fuse nucleus (KF), a part of the parabrachial complex, is involved in regulating normal breathing and controlling active abdominal expiration during increased ventilation. Dysfunction in KF neuronal activity is thought to contribute to respiratory abnormalities seen in Rett syndrome (RTT). This study utilizes computational modelling to explore different dynamical regimes of KF activity and their compatibility with experimental observations. By analysing different model configurations, the study identifies inhibitory inputs to the KF that lead to RTT-like respiratory patterns and proposes potential KF local circuit organizations. Two models are presented that simulate both normal breathing and RTT-like breathing patterns. These models provide testable hypotheses and specific predictions for future experimental investigations, offering a general framework for understanding KF dynamics and potential network interactions.

Incorporating Modern Fault Ride-Through Standards into the Short-Circuit Calculation of Distribution Networks.

Modern fault ride-through (FRT) standards in many countries require distributed generators to remain connected for a specified period during the fault by providing reactive current, to support voltage and prevent a massive renewable outage. As a result, short-circuit current is not constant, but it varies depending on the current and disconnection order of distributed generators (DGs). This time-varying short-circuit current complicates the estimation of the time it will take for an overcurrent relay or fuse to trip. The existing short-circuit calculation algorithms usually assume that the fault current is constant throughout the whole period of fault. This assumption may result in incorrect conclusions regarding the tripping time of protective devices in networks with high renewable penetration. This paper incorporates modern FRT standards into the fault analysis by considering the influence of fault current variations on the protective devices (relays, fuses), significantly increasing the accuracy of the estimated tripping time. Simulations carried out in a 13-bus and the IEEE 8500-node network indicate that the traditional short-circuit calculation approaches may miscalculate the tripping time of protective devices, with deviations up to 80 s, when applied to networks complying with modern FRT standards.

Achieving High Expression of Cry in Green Tissues and Negligible Expression in Endosperm Simultaneously via rbcS Gene Fusion Strategy in Rice.

To allay excessive public concern about the safety of transgenic foods, and to optimize insect-resistant genes expression to delay the evolution of resistance in pests, we developed a promising strategy to fuse the GOI (gene of interest) with OsrbcS (rice small subunit of ribulose bisphosphate carboxylase/oxygenase) in transgenic rice, which acted as a carrier, driven by the OsrbcS native promoter to sequester its expression in green tissues. Using eYFP as a trial, we reported a high-level accumulation of eYFP in green tissue and almost none in the seed and root of the fused construct compared to the non-fused construct. After applying this fusion strategy in insect-resistant rice breeding, recombinant OsrbcS-Cry1Ab/Cry1Ac expressed rice plants conferred high resistance to leaffolders and striped stem borers, among which two single-copy lines possessed normal agronomic performance in the field. Specifically, Cry1Ab/Cry1Ac protein levels in single-copy construct transgenic lines ranged from 1.8 to 11.5 µg g-1 in the leaf, higher than the Actin I promoter-driven control, T51-1, about 1.78 µg g-1 in the leaf, but negligible (only 0.00012-0.00117 µg g-1) in endosperm by ELISA analysis. Our study provided a novel approach to creating Cry1Ab/Cry1Ac-free endosperm rice with a high level of insect-resistant protein in green tissues through the simultaneous usage of the OsrbcS promoter and OsrbcS as a fusion partner.

Research on MEMS Solid-State Fuse Logic Control Chip Based on Electrical Explosion Effect.

A microelectromechanical systems (MEMS) solid-state logic control chip with three layers-diversion layer, control layer, and substrate layer-is designed to satisfy fuse miniaturization and integration requirements. A mathematical model is established according to the heat conduction equation, and the limit conditions of different structures are presented. The finite element multi-physical field simulation method is used to simulate the size and the action voltage of the diversion layer of the control chip. Based on the surface silicon process, fuse processing, and testing with the MEMS solid-state fuse-logic control chip, a diversion layer constant current, maximum current resistance test, and a control layer of different bridge area sizes, the bridge area size is 200 × 30 µm, and the minimum electrical explosion voltage is 23.6 V. The theoretical calculation results at 20 V and 100 µF demonstrate that the capacitor energy is insufficient to support the complete vaporization of the bridge area, but can be partially vaporized, consistent with the experimental results.

3D Printing Technologies in Personalized Medicine, Nanomedicines, and Biopharmaceuticals.

3D printing technologies enable medicine customization adapted to patients' needs. There are several 3D printing techniques available, but majority of dosage forms and medical devices are printed using nozzle-based extrusion, laser-writing systems, and powder binder jetting. 3D printing has been demonstrated for a broad range of applications in development and targeting solid, semi-solid, and locally applied or implanted medicines. 3D-printed solid dosage forms allow the combination of one or more drugs within the same solid dosage form to improve patient compliance, facilitate deglutition, tailor the release profile, or fabricate new medicines for which no dosage form is available. Sustained-release 3D-printed implants, stents, and medical devices have been used mainly for joint replacement therapies, medical prostheses, and cardiovascular applications. Locally applied medicines, such as wound dressing, microneedles, and medicated contact lenses, have also been manufactured using 3D printing techniques. The challenge is to select the 3D printing technique most suitable for each application and the type of pharmaceutical ink that should be developed that possesses the required physicochemical and biological performance. The integration of biopharmaceuticals and nanotechnology-based drugs along with 3D printing ("nanoprinting") brings printed personalized nanomedicines within the most innovative perspectives for the coming years. Continuous manufacturing through the use of 3D-printed microfluidic chips facilitates their translation into clinical practice.

Understanding the safe application of electrosurgery: A cross sectional study of surgeons in KSA.

Objectives: To determine whether surgeons at different levels and in different specialties are aware of the safe and acceptable use of electrosurgery. In addition, we aimed to provide a fundamental understanding of electrosurgery and surgical diathermy. Materials and Methods: A total of 83 doctors from different specialties were randomly selected from several hospitals across KSA. The participants answered a questionnaire featuring 16 questions that addressed 10 domain questions regarding the safe use of electrosurgery. Results: Analysis revealed that the respondents either lacked knowledge or were unfamiliar with the use and safety of monopolar and bipolar electrosurgery in terms of application. Some respondents were unable to distinguish between the two protocols; this may have resulted in injuries being incurred by patients under their supervision. Conclusions: Electrosurgery should be formally included in specialty surgical Saudi hospital training programs to increase electrosurgery expertise and surgeons should be re-tested periodically. Our findings may be used to drive future learning. Surgeons may improve their electrosurgery skills by progressing along their learning curve to reach their peak. In addition, surgeons can use virtual reality surgical simulators to practice fundamental and sophisticated electrosurgery skills.

Impact of the fundamental use of surgical energy certification on surgeons' behavior and awareness of safe use of energy devices: a cross-sectional survey research.

BACKGROUND: The Fundamental Use of Surgical Energy (FUSE) program was established to educate surgeons and trainees to promote awareness and behaviors for the safe use of surgical energy devices. Despite its implementation, the impact of FUSE certification on surgeons' behavior and safety awareness regarding practice of energy devices remains unclear. This study aimed to identify the perceived impact of FUSE certification on surgeons' behavior and awareness regarding the safe use of surgical energy devices. METHODS: We performed a descriptive cross-sectional survey study, using non probabilistic purposive sampling, and distributed 22-item web-based questionnaires among all 59 FUSE-certified surgeons in Japan, excluding operating room nurses and medical students. The questionnaire items covered demographics, surgical techniques using various energy devices, changes in behavior and safety awareness, communication with colleagues about surgical energy devices, and educational activities related to energy devices. RESULTS: Fifty-seven participants completed the questionnaire (response rate 96.6%). Most surgeons (91.3%) could apply material learned from the FUSE program in practice, especially material related to monopolar electrosurgery. Fifty-six surgeons (98.3%) reported increased awareness of surgical safety, and 35 (61.5%) reported increased communication with operating room personnel about the safe use of energy devices. Moreover, 56 participants (98.3%) indicated a need for systematic education in surgical energy, with participants recommending fellows (94.7% of participants specified that fellows should participate in further education), residents (75.4%), and attending surgeons (63.2%) as the target recipients of this training. Conclusions After FUSE certification, not only did surgeons' knowledge increase, but their energy-related surgical techniques in practice also improved. Furthermore, FUSE-certified surgeons felt that they were more aware of surgical-energy safety and were dedicated to its promotion.

Fault Current Limitation in Electrical Power Networks Containing HTS Cable and HTS Fuse.

Numerical calculations of parameters of an electrical power network where an HTS fuse is used as a fault current limiting device have been done. The calculations were performed for networks containing different types of HTS cables as well. The design of HTS fuse was developed based on the numerical calculation for the network-rated parameters considering the special types 2G HTS tape characteristics. The distinctive feature of these tapes is the minimal thickness (about 30 µm) of the substrate at the critical current 450-600 A. The tests were performed at a voltage of 1 kV and demonstrated the ability of circuit breaking at fault currents about 3-4 kA. A comparison of experimental results with the calculations allows us to conclude that the HTS fuse of this design can operate as a fault current limiting device in electrical power networks at various rated voltage levels.

Activation of orexin-2 receptors in the KÓ§lliker-Fuse nucleus of anesthetized mice leads to transient slowing of respiratory rate.

Orexins are neuropeptides originating from the hypothalamus that serve broad physiological roles, including the regulation of autonomic function, sleep-wake states, arousal and breathing. Lack of orexins may lead to narcolepsy and sleep disordered breathing. Orexinergic hypothalamic neurons send fibers to KÓ§lliker-Fuse (KF) neurons that directly project to the rostroventral respiratory group, and phrenic and hypoglossal motor neurons. These connections indicate a potential role of orexin-modulated KF neurons in functionally linking the control of wakefulness/arousal and respiration. In a reduced preparation of juvenile rats Orexin B microinjected into the KF led to a transient increase in respiratory rate and hypoglossal output, however Orexin B modulation of the KF in intact preparations has not been explored. Here, we performed microinjections of the Orexin B mouse peptide and the synthetic Orexin 2 receptor agonist, MDK 5220, in the KF of spontaneously breathing, isoflurane anesthetized wild type mice. Microinjection of Orexin-2 receptor agonists into the KF led to transient slowing of respiratory rate, which was more exaggerated in response to Orexin-B than MDK 5220 injections. Our data suggest that Orexin B signaling in the KF may contribute to arousal-mediated respiratory responses.

Effect of pharmacological inhibition of the pontine respiratory group on swallowing interneurons in the dorsal medulla oblongata.

OBJECTIVES: To examine the role of neurons of the pontine respiratory group (PRG) overlapping with the Kölliker-Fuse nucleus in the regulation of swallowing, we compared the activity of swallowing motor activities and interneuron discharge in the dorsal swallowing group in the medulla before and after pharmacological inhibition of the PRG. METHODS: In 23 in situ perfused brainstem preparation of rats, we recorded the activities of the vagus (VNA), hypoglossal (HNA), and phrenic nerves (PNA), and swallowing interneurons of the dorsal medulla during fictive swallowing elicited by electrical stimulation of the superior laryngeal nerve or oral water injection. Subsequently, respiratory- and swallow-related motor activities and single unit cell discharge were assessed before and after local microinjection of the GABA-receptor agonist muscimol into the area of PRG ipsilateral to the recording sites of swallowing interneurons. RESULTS: After muscimol injection, the amplitude and duration of swallow-related VNA bursts decreased to 71.3 ± 2.84 and 68.1 ± 2.76 % during electrically induced swallowing and VNA interburst intervals during repetitive swallowing decreased. Similar effects were observed for swallowing-related HNA. The swallowing motor activity was similarly qualitatively altered during physiologically induced swallowing. All 23 neurons were changed in either discharge duration or frequency after PRG inhibition, however, the general discharge patterns in relation to the motor output remained unchanged. CONCLUSION: Descending synaptic inputs from PRG provide control of the primary laryngeal sensory gate and synaptic activity of the PRG partially determine medullary cell and cranial motor nerve activities that govern the pharyngeal stage of swallowing.

Fentanyl effects on respiratory neuron activity in the dorsolateral pons.

Opioids suppress breathing through actions in the brainstem, including respiratory-related areas of the dorsolateral pons, which contain multiple phenotypes of respiratory patterned neurons. The discharge identity of dorsolateral pontine neurons that are impacted by opioids is unknown. To address this, single neuronal units were recorded in the dorsolateral pons of arterially perfused in situ rat preparations that were perfused with an apneic concentration of the opioid agonist fentanyl, followed by the opioid antagonist naloxone (NLX). Dorsolateral pontine neurons were categorized based on respiratory-associated discharge patterns, which were differentially affected by fentanyl. Inspiratory neurons and a subset of inspiratory/expiratory phase-spanning neurons were either silenced or had reduced firing frequency during fentanyl-induced apnea, which was reversed upon administration of naloxone. In contrast, the majority of expiratory neurons continued to fire tonically during fentanyl-induced apnea, albeit with reduced firing frequency. In addition, pontine late-inspiratory and postinspiratory neuronal activity were absent from apneustic-like breaths during the transition to fentanyl-induced apnea and the naloxone-mediated transition to recovery. Thus, opioid-induced deficits in respiratory patterning may occur due to reduced activity of pontine inspiratory neurons, whereas apnea occurs with loss of all phasic pontine activity and sustained tonic expiratory neuron activity.NEW & NOTEWORTHY Opioids can suppress breathing via actions throughout the brainstem, including the dorsolateral pons. The respiratory phenotype of dorsolateral pontine neurons inhibited by opioids is unknown. Here, we describe the effect of the highly potent opioid fentanyl on the firing activity of these dorsolateral pontine neurons. Inspiratory neurons were largely silenced by fentanyl, whereas expiratory neurons were not. We provide a framework whereby this differential sensitivity to fentanyl can contribute to respiratory pattern deficits and apnea.

A fused biometrics information graph convolutional neural network for effective classification of patellofemoral pain syndrome.

Patellofemoral pain syndrome (PFPS) is a common, yet misunderstood, knee pathology. Early accurate diagnosis can help avoid the deterioration of the disease. However, the existing intelligent auxiliary diagnosis methods of PFPS mainly focused on the biosignal of individuals but neglected the common biometrics of patients. In this paper, we propose a PFPS classification method based on the fused biometrics information Graph Convolution Neural Networks (FBI-GCN) which focuses on both the biosignal information of individuals and the common characteristics of patients. The method first constructs a graph which uses each subject as a node and fuses the biometrics information (demographics and gait biosignal) of different subjects as edges. Then, the graph and node information [biosignal information, including the joint kinematics and surface electromyography (sEMG)] are used as the inputs to the GCN for diagnosis and classification of PFPS. The method is tested on a public dataset which contain walking and running data from 26 PFPS patients and 15 pain-free controls. The results suggest that our method can classify PFPS and pain-free with higher accuracy (mean accuracy = 0.8531 ± 0.047) than other methods with the biosignal information of individuals as input (mean accuracy = 0.813 ± 0.048). After optimal selection of input variables, the highest classification accuracy (mean accuracy = 0.9245 ± 0.034) can be obtained, and a high accuracy can still be obtained with a 40% reduction in test variables (mean accuracy = 0.8802 ± 0.035). Accordingly, the method effectively reflects the association between subjects, provides a simple and effective aid for physicians to diagnose PFPS, and gives new ideas for studying and validating risk factors related to PFPS.

Risk factors in distal interphalangeal joint arthrodesis in the hand: a retrospective study of 173 cases.

In this retrospective study we aimed to analyse the risk factors for complications after different methods of distal interphalangeal arthrodesis in the hand. Forty-four per cent were treated with K-wire/cerclage fixation, 46% with X-fuse® implants (Stryker GmbH, Selzach, Switzerland) and 10% with headless compression screws (HBS®-screw, KLS Martin Group, Tuttlingen, Germany). The median follow-up was 16 weeks (range 6-224). The overall complication incidence was 44% (minor complications 29% and major 15%). The logistic regression showed that osteoarthritis, revisional arthrodesis and smoking had a negative impact on the total complication incidence. A Cox-regression analysis showed that HBS®-screw arthrodesis was associated with a significantly lower incidence of major complications compared with K-wire/cerclage and X-Fuse®-arthrodesis. Revisional arthrodesis was five times more frequently connected with major complications than primary surgery. Smokers were three times more likely to experience major complications than non-smokers. We conclude that arthrodesis of the distal interphalangeal joint often leads to complications. Risk factors must be kept in mind.Level of evidence: III.

Virtual Simulation of the Effect of FMCW Laser Fuse Detector's Component Performance Variability on Target Echo Characteristics under Smoke Interference.

The laser transmitter and photoelectric receiver are the core modules of the detector in a laser proximity fuse, whose performance variability can affect the accuracy of target detection and identification. In particular, there is no study on the effect of detector's component performance variability on frequency-modulated continuous-wave (FMCW) laser fuse under smoke interference. Therefore, based on the principles of particle dynamic collision, ray tracing, and laser detection, this paper builds a virtual simulation model of FMCW laser transmission with the professional particle system of Unity3D, and studies the effect of performance variability of laser fuse detector components on the target characteristics under smoke interference. Simulation results show that the difference in the performance of the fuse detector components causes the amplitude variation and peak migration of the beat signal spectrum, and the change in the visibility of the smoke can also affect the results, which indicates that the factors affecting the signal-to-noise ratio (SNR) of the echo signal are related to the smoke interference and performance variability of the detector. The proposed simulation model is supported by experimental results, which reflect the reliability of the proposed findings. Therefore, this study can be used for the optimization of the parameters in the laser fuse antismoke interference to avoid false alarms.

Current research in pathophysiology of opioid-induced respiratory depression, neonatal opioid withdrawal syndrome, and neonatal antidepressant exposure syndrome.

Respiratory depression (RD) is the primary cause of death due to opioids. Opioids bind to mu (µ)-opioid receptors (MORs) encoded by the MOR gene Oprm1, widely expressed in the central and peripheral nervous systems including centers that modulate breathing. Respiratory centers are located throughout the brainstem. Experiments with Oprm1-deleted knockout (KO) mice undertaken to determine which sites are necessary for the induction of opioid-induced respiratory depression (OIRD) showed that the pre-Bötzinger complex (preBötC) and the pontine Kölliker-Fuse nucleus (KF) contribute equally to OIRD but RD was not totally eliminated. Morphine showed a differential influence on preBötC and KF neurons - low doses attenuated RD following deletion of MORs from preBötC neurons and an increase in apneas after high doses whereas deletion of MORs from KF neurons but not the preBötC attenuated RD at both high and low doses. In other KO mice studies, morphine administration after deletion of Oprm1 from both the preBötC and the KF/PBN neurons, led to the conclusion that both respiratory centres contribute to OIRD but the preBötC predominates. MOR-mediated post-synaptic activation of GIRK potassium channels has been implicated as a cause of OIRD. A complementary mechanism in the preBötC involving KCNQ potassium channels independent of MOR signaling has been described. Recent experiments in rats showing that morphine depresses normal, but not gasping breathing, cast doubt on the belief that eupnea, sighs, and gasps, are under the control of preBötC neurons. Methadone, administered to alleviate symptoms of neonatal opioid withdrawal syndrome (NOWES), desensitized rats to OIRD. Protection lost between postnatal days 1 and 2 coincides with the preBötC becoming the dominant generator of respiratory rhythm. Neonatal antidepressant exposure syndrome (NADES) and serotonin toxicity (ST) show similarities including RD. Enzyme CYP2D6 involved in opioid detoxification is polymorphic. Individuals of different CYP2D6 genotype may show increased, decreased, or no enzyme activity, contributing to the variability of patient responses to different opioids and OIRD.

Peripheral chemoreflex activation induces expiratory but not inspiratory excitation of C1 pre-sympathetic neurones of rats.

AIMS: Stimulation of peripheral chemoreceptors, as during hypoxia, increases breathing and respiratory-related sympathetic bursting. Activation of catecholaminergic C1 neurones induces sympathoexcitation, while its ablation reduces the chemoreflex sympathoexcitatory response. However, no study has determined the respiratory phase(s) in which the pre-sympathetic C1 neurones are recruited by peripheral chemoreceptor and whether C1 neurone activation affects all phases of respiratory modulation of sympathetic activity. We addressed these unknowns by testing the hypothesis that peripheral chemoreceptor activation excites pre-sympathetic C1 neurones during inspiration and expiration. METHODS: Using the in situ preparation of rat, we made intracellular recordings from baroreceptive pre-sympathetic C1 neurones during peripheral chemoreflex stimulation. We optogenetically activated C1 neurones selectively and compared any respiratory-phase-related increases in sympathetic activity with that which occurs following stimulation of the peripheral chemoreflex. RESULTS: Activation of peripheral chemoreceptors using cytotoxic hypoxia (potassium cyanide) increased the firing frequency of C1 neurones and both the frequency and amplitude of their excitatory post-synaptic currents during the phase of expiration only. In contrast, optogenetic stimulation of C1 neurones activates inspiratory neurones, which secondarily inhibit expiratory neurones, but produced comparable increases in sympathetic activity across all phases of respiration. CONCLUSION: Our data reveal that the peripheral chemoreceptor-mediated expiratory-related sympathoexcitation is mediated through excitation of expiratory neurones antecedent to C1 pre-sympathetic neurones; these may be found in the Kölliker-Fuse nucleus. Despite peripheral chemoreceptor excitation of inspiratory neurones, these do not trigger C1 neurone-mediated increases in sympathetic activity. These studies provide compelling novel insights into the functional organization of respiratory-sympathetic neural networks.