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Airway neuroendocrine (NE) cells have been proposed to serve as specialized sensory epithelial cells that modulate respiratory behavior by communicating with nearby nerve endings. However, their functional properties and physiological roles in the healthy lung, trachea, and larynx remain largely unknown. In this work, we show that murine NE cells in these compartments have distinct biophysical properties but share sensitivity to two commonly aspirated noxious stimuli, water and acid. Moreover, we found that tracheal and laryngeal NE cells protect the airways by releasing adenosine 5'-triphosphate (ATP) to activate purinoreceptive sensory neurons that initiate swallowing and expiratory reflexes. Our work uncovers the broad molecular and biophysical diversity of NE cells across the airways and reveals mechanisms by which these specialized excitable cells serve as sentinels for activating protective responses.

Humans experience unanticipated external postural perturbations and recover their posture faster via involuntary responses than voluntary responses. Previous cross-sectional comparisons between athletes and untrained populations have suggested that daily motor experiences can lead to adaptations in the reftex system, but the temporal aspect of this adaptation has been unclear. Here we show that judokas have an earlier muscle activation response to even non-judo-specific external perturbations compared with an untrained population. The response latency to a backward push-and-release type postural perturbation was compared between male judokas (n = 7. career >13 years. ranging from world champions to prefectural competitors) and untrained nonjudokas (n = 7). Latency was defined as the instant of tibialis anterior muscle activity onset. Judokas exhibited shorter latency (20.6 ± 7.1 ms) than nonjudokas (28.3 ± 8.9 ms). The rank order of latency in judokas did not correlate with their competition performance. We suggest that daily training in responding to perturbations might improve some parts of the sensorimotor pathway relating to postural response latency, and that this excellence in involuntary response is independent of athletic performance. The findings provide a novel perspective for understanding postural control ability in humans. [ABSTRACT FROM AUTHOR]

The aberrant expression of specific long noncoding RNAs (lncRNAs) has been associated with cognitive and psychiatric disorders. Although a growing number of lncRNAs are now known to regulate neural cell development and function, relatively few lncRNAs have been shown to underlie animal behavior. Pnky is an evolutionarily conserved, neural lncRNA that regulates brain development. Using mouse genetic strategies, we show that Pnky has sex-specific roles in mouse behavior and that this lncRNA can underlie specific behavior by functioning in trans. Male Pnky-knockout mice have decreased context generalization in a paradigm of associative fear learning and memory. In female Pnky-knockout mice, there is an increase in the acoustic startle response, a behavior that is altered in affective disorders. Remarkably, expression of Pnky from a bacterial artificial chromosome transgene decreases the acoustic startle response in female Pnky-knockout mice, demonstrating that Pnky can modulate specific animal behavior by functioning in trans. More broadly, these studies illustrate how specific lncRNAs can underlie cognitive and mood disorders.

No preclinical experimental approach enables the study of voluntary oral consumption of high-concentration Δ9-tetrahydrocannabinol (THC) and its intoxicating effects, mainly owing to the aversive response of rodents to THC that limits intake. Here, we developed a palatable THC formulation and an optimized access paradigm in mice to drive voluntary consumption. THC was formulated in chocolate gelatin (THC-E-gel). Adult male and female mice were allowed ad libitum access for 1 and 2 hr. Cannabimimetic responses (hypolocomotion, analgesia, and hypothermia) were measured following access. Levels of THC and its metabolites were measured in blood and brain tissue. Acute acoustic startle responses were measured to investigate THC-induced psychotomimetic behavior. When allowed access for 2 hr to THC-E-gel on the second day of a 3-day exposure paradigm, adult mice consumed up to ≈30 mg/kg over 2 hr, which resulted in robust cannabimimetic behavioral responses (hypolocomotion, analgesia, and hypothermia). Consumption of the same gelatin decreased on the following third day of exposure. Pharmacokinetic analysis shows that THC-E-gel consumption led to parallel accumulation of THC and its psychoactive metabolite, 11-OH-THC, in the brain, a profile that contrasts with the known rapid decline in brain 11-OH-THC levels following THC intraperitoneal (i.p.) injections. THC-E-gel consumption increased the acoustic startle response in males but not in females, demonstrating a sex-dependent effect of consumption. Thus, while voluntary consumption of THC-E-gel triggered equivalent cannabimimetic responses in male and female mice, it potentiated acoustic startle responses preferentially in males. We built a dose-prediction model that included cannabimimetic behavioral responses elicited by i.p. versus THC-E-gel to test the accuracy and generalizability of this experimental approach and found that it closely predicted the measured acoustic startle results in males and females. In summary, THC-E-gel offers a robust preclinical experimental approach to study cannabimimetic responses triggered by voluntary consumption in mice, including sex-dependent psychotomimetic responses.

ABSTRACT Aims/Introduction Materials and Methods Results Conclusions We investigated the association between the ankle reflex and the estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes.This was a single‐center, retrospective, observational cohort study. A total of 1,387 patients who underwent an ankle reflex examination between January 2005 and December 2015 were included in the analysis for the primary outcome. The findings of the ankle reflex examination were classified into three groups: normal, decreased, or absent. The primary outcome was defined as the incidence of a 40% loss of eGFR from baseline. A survival time analysis using the Kaplan–Meier method and a regression analysis using a Cox proportional hazards model were conducted to evaluate the association between the ankle reflex test results and loss of eGFR.The ankle reflex test results were as follows: normal, n = 678 (48.9%); decreased, n = 270 (19.5%); and absent, n = 439 (31.6%) patients. The median follow‐up period was 5.6 years in the observational period. In the univariate regression analysis, decreased and absent ankle reflexes were significantly associated with loss of eGFR. Moreover, decreased ankle reflex (hazard ratio: 1.83, 95% confidence interval: 1.16–2.87) and absent ankle reflex (hazard ratio: 2.57, 95% confidence interval: 1.76–3.76) were independently associated with loss of eGFR after adjusting for prognostic risk factors.Decreased and absent ankle reflexes are closely and independently associated with loss of eGFR in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Purpose: Percutaneous lesioning-techniques for treating refractory Trigeminal Neuralgias not amenable to Micro-Vascular Decompression remain useful in neurosurgical practice. Success, avoidance of complications and reduction of side-effects depend on the accurate location of the lesion-maker especially for Radio-Frequency-Thermo-Rhizotomy (RF-Th-Rh). Added to X-ray-guidance, Intra-Operative Neurophysiology can be of significant help to achieve optimal accuracy of the surgery. Based on previous research, this article aims to describe the simplest way to use direct electrical stimulation of the trigeminal root to evoke clinically observable muscle responses allowing to precisely position the tip of the needle for accurate lesioning. Technique to evoke specific localizing muscle responses: Masticatory twitches can be easily produced by stimulating the motor root, through orthodromic conduction to the masticatory muscles. Evoked Muscle Responses (EMRs) can be elicited in the facial nerve territory by stimulating the sensory rootlets, through Trigemino-Facial Reflexes' pathways (TFRs). Responses in the Orbicularis Oculi is the well-known and readily used "Blink reflex". On the contrary, TFRs in the lower territory of the facial nerve escaped clinical investigations not having been explored under direct stimulation of the trigeminal root. For both, stimulation at 5 c/s produces better observable twitches (because saccadic) than at 50 c/s which elicits tetanic contractions. Conclusion: The localizing-value of these facial EMRs (associated to evocation of paresthesias) and of the masticatory responses, justifies mapping the trigeminal root before lesioning. Their use could be extended to the other lesioning-techniques: not only Glycerol Neurolysis but also to Balloon Compression (to ascertain location of the trocar at the contact of the TGN inside the Meckel cave) and Open partial Rhizotomies (before deciding to cut the rootlets corresponding to the trigger-zone). This is of importance since lesioning-techniques are needed because not all trigeminal neuralgias are responsive to or even indications of Micro-Vascular Decompression. [ABSTRACT FROM AUTHOR]

A given dose of hypoxia causes a greater increase in pulmonary ventilation during physical exercise than during rest, representing an exercise‐induced potentiation of the acute hypoxic ventilatory response (HVR). This phenomenon occurs independently from hypoxic blood entering the contracting skeletal muscle circulation or metabolic byproducts leaving skeletal muscles, supporting the contention that neural mechanisms per se can mediate the HVR when humoral mechanisms are not at play. However, multiple neural mechanisms might be interacting intricately. First, we discuss the neural mechanisms involved in the ventilatory response to hypoxic exercise and their potential interactions. Current evidence does not support an interaction between the carotid chemoreflex and central command. In contrast, findings from some studies support synergistic interactions between the carotid chemoreflex and the muscle mechano‐ and metaboreflexes. Second, we propose hypotheses about potential mechanisms underlying neural interactions, including spatial and temporal summation of afferent signals into the medulla, short‐term potentiation and sympathetically induced activation of the carotid chemoreceptors. Lastly, we ponder how exercise‐induced potentiation of the HVR results in hyperventilation‐induced hypocapnia, which influences cerebral blood flow regulation, with multifaceted potential consequences, including deleterious (increased central fatigue and impaired cognitive performance), inert (unchanged exercise) and beneficial effects (protection against excessive cerebral perfusion). What is the topic of this review?What neural mechanisms are involved in the ventilatory response to hypoxic exercise and do they interact? What are the mechanisms underlying neural interactions during hypoxic exercise?What advances does it highlight?Current evidence does not support an interaction between the carotid chemoreflex and central command. In contrast, findings from some studies support synergistic interactions between the carotid chemoreflex and the muscle mechano‐ and metaboreflexes. Medullary signal summation, short‐term potentiation and sympathetic carotid chemoreceptor activation probably contribute to potentiation of the hypoxic ventilatory response during exercise, impacting cerebral blood flow and oxygenation via hyperventilation‐induced hypocapnia. [ABSTRACT FROM AUTHOR]

It remains unclear whether feedback from group III/IV muscle afferents is of continuous significance for regulating the pulmonary response during prolonged (>5 min), steady‐state exercise. To elucidate the influence of these sensory neurons on hyperpnoea, gas exchange efficiency, arterial oxygenation and acid–base balance during prolonged locomotor exercise, 13 healthy participants (4 females; 21 (3) years, V̇O2max${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{max}}}}$: 46 (8) ml/kg/min) performed consecutive constant‐load cycling bouts at ∼50% (20 min), ∼75% (20 min) and ∼100% (5 min) of V̇O2max${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{max}}}}$ with intact (CTRL) and pharmacologically attenuated (lumbar intrathecal fentanyl; FENT) group III/IV muscle afferent feedback from the legs. Pulmonary responses were continuously recorded and arterial blood (radial catheter) periodically collected throughout the exercise. Pulmonary gas exchange efficiency was evaluated using the alveolar‐arterial PO2${{P}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ difference (A−aDO2${\mathrm{A - a}}{{D}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$). There were no differences in any of the variables of interest between conditions before the start of the exercise. Pulmonary ventilation was up to 20% lower across all intensities during FENT compared to CTRL exercise (P < 0.001) and this hypoventilation was accompanied by an up to 10% lower arterial PO2${{P}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ and a 2–4 mmHg higher PCO2${{P}_{{\mathrm{C}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$ (both P < 0.001). The exercise‐induced widening of A−aDO2${\mathrm{A - a}}{{D}_{{{{\mathrm{O}}}_{\mathrm{2}}}}}$ was up to 25% larger during FENT compared to CTRL (P < 0.001). Importantly, the differences developed within the first minute of each stage and persisted, or further increased, throughout the remainder of each bout. These findings reflect a critical and time‐independent significance of feedback from group III/IV leg muscle afferents for continuously regulating the ventilatory response, gas exchange efficiency, arterial oxygenation and acid–base balance during human locomotion. Key points: Feedback from group III/IV leg muscle afferents reflexly contributes to hyperpnoea during short duration (i.e. <5 min) locomotor exercise.Whether continuous feedback from these sensory neurons is obligatory to ensure adequate pulmonary responses during steady‐state exercise of longer duration remains unknown.Lumbar intrathecal fentanyl was used to attenuate the central projection of group III/IV leg muscle afferents during prolonged locomotor exercise (i.e. 45 min) at intensities ranging from 50% to 100% of V̇O2max${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{max}}}}$.Without affecting the metabolic rate, afferent blockade compromised pulmonary ventilation and gas exchange efficiency, consistently impairing arterial oxygenation and facilitating respiratory acidosis throughout exercise.These findings reflect the time‐independent significance of feedback from group III/IV muscle afferents for regulating exercise hyperpnoea and gas exchange efficiency, and thus for optimizing arterial oxygenation and acid–base balance, during prolonged human locomotion. [ABSTRACT FROM AUTHOR]

The majority of tumor comprehensive genomic profiling (CGP) currently does not include a matched normal control. The use of a tumor-only CGP approach needs the development of a strategy to refine germline pathogenic/likely pathogenic variants (gP/LPVs) calls, so as to limit the performance of unnecessary germline reflex tests and instead successfully identify patients who are carriers of likely gP/LPVs. Guidelines have been developed for the identification of gP/LPVs in BRCA1/2 genes on the basis of tumor-only CGP results and for the evaluation of the appropriateness of performing germline reflex BRCA1/2 testing. In this study, an algorithm to assist decision-making for germline reflex testing of BRCA1/2 variants following tumor-only CGP is proposed. [ABSTRACT FROM AUTHOR]

Introduction Approximately 89% of all service members with amputations do not return to duty. Restoring intuitive neural control with somatosensory sensation is a key to improving the safety and efficacy of prosthetic locomotion. However, natural somatosensory feedback from lower-limb prostheses has not yet been incorporated into any commercial prostheses Materials and Methods We developed a neuroprosthesis with intuitive bidirectional control and somatosensation and evoking phase-dependent locomotor reflexes, we aspire to significantly improve the prosthetic rehabilitation and long-term functional outcomes of U.S. amputees. We implanted the skin and bone integrated pylon with peripheral neural interface pylon into the cat distal tibia, electromyographic electrodes into the residual gastrocnemius muscle, and nerve cuff electrodes on the distal tibial and sciatic nerves. Results. The bidirectional neural interface that was developed was integrated into the existing passive Free-Flow Foot and Ankle prosthesis, WillowWood, Mount Sterling, OH. The Free-Flow Foot was chosen because it had the highest Index of Anthropomorphicity among lower-limb prostheses and was the first anthropomorphic prosthesis brought to market. Conclusion. The cats walked on a treadmill with no cutaneous feedback from the foot in the control condition and with their residual distal tibial nerve stimulated during the stance phase of walking [ABSTRACT FROM AUTHOR]

Introduction The initial management of penetrating ocular injuries is a major sight-threatening problem for both civilian and military medicine. A novel device (Eye-Aid) temporarily tamponades leakage from such injuries while being easy to remove upon arrival to specialized ophthalmologic care. Eye-Aid consists of a protective eye shield with an adhesive backing that connects to a portable canister containing rapidly deployable thermoresponsive foam. The aim of this study was to compare the use of the novel Eye-Aid device to control in a new live swine ocular injury model. Materials and Methods Bilateral penetrating ocular injuries were created on 14 male Yorkshire swine in a standardized manner using a 16-gauge needle device to puncture the central cornea and cause a full-thickness wound. Researchers randomized eye intervention side, with the contralateral eye used as paired control. Two minutes after the injury, the eye shield components of the Eye-Aid system, which has a sticky pad for attachment to the skin and a luer-lock for foam deployment, were placed bilaterally. Eight minutes after the injury, foam was deployed for the intervention eye according to the device instructions for use. For the control eye, no additional procedures were performed. Six hours post-injury, end A-scan and intraocular pressure (IOP) were measured. Primary study outcome was change in axial length of the globe. Secondary outcomes were as follows: (1) Presence of full anterior chamber collapse, defined as a lack of measurable anterior lens capsule-reflex (ALC-reflex) on A-scan and (2) change in IOP. Outcomes were analyzed as paired intra-animal data, with intervention and control data for each animal. A paired t -test was used to analyze the difference in axial length change and IOP change between treatment groups, whereas a conditional logistic regression was used to analyze dichotomous ALC-reflex outcome and estimate the odds ratio associated with the Eye-Aid device. Results A significant difference (P  < .0001) in mean change in axial length between intervention (−210 μm) and control (−1,202 μm) groups was found. There was a significant difference in ALC-reflex presence, with 79% of eyes having an ALC-reflex in the intervention group, compared to 14% in the control (P  = .008). IOP remained higher in the intervention group, with a mean change of −1.5 mmHg for the intervention group compared to −4.0 mmHg in the control (P  = .0001). Conclusions This study describes the first development of an in vivo large animal ocular injury model that realistically approximates the emergent time course and pathophysiology of patients with full-thickness corneal open globe injuries. It also gives the first description of using thermoreversible hydrogel foam for such injuries. Eye-Aid was found to be significantly better than control for treatment of such injuries, based on measurements of both structure and pressure. Assuming that the absence of an ALC-reflex demonstrates complete anterior chamber collapse, the Eye-Aid group demonstrated a 79% eye "save" rate compared to only 14% in the control group, as described earlier. This results in a Number Needed to Treat of 3 for this finding. Eye-Aid additionally demonstrated several characteristics that would be beneficial in a device targeted for emergent deployment by non-ophthalmologists. [ABSTRACT FROM AUTHOR]

Abstract A given dose of hypoxia causes a greater increase in pulmonary ventilation during physical exercise than during rest, representing an exercise‐induced potentiation of the acute hypoxic ventilatory response (HVR). This phenomenon occurs independently from hypoxic blood entering the contracting skeletal muscle circulation or metabolic byproducts leaving skeletal muscles, supporting the contention that neural mechanisms per se can mediate the HVR when humoral mechanisms are not at play. However, multiple neural mechanisms might be interacting intricately. First, we discuss the neural mechanisms involved in the ventilatory response to hypoxic exercise and their potential interactions. Current evidence does not support an interaction between the carotid chemoreflex and central command. In contrast, findings from some studies support synergistic interactions between the carotid chemoreflex and the muscle mechano‐ and metaboreflexes. Second, we propose hypotheses about potential mechanisms underlying neural interactions, including spatial and temporal summation of afferent signals into the medulla, short‐term potentiation and sympathetically induced activation of the carotid chemoreceptors. Lastly, we ponder how exercise‐induced potentiation of the HVR results in hyperventilation‐induced hypocapnia, which influences cerebral blood flow regulation, with multifaceted potential consequences, including deleterious (increased central fatigue and impaired cognitive performance), inert (unchanged exercise) and beneficial effects (protection against excessive cerebral perfusion).

Statement of the Problem: Gag reflex is among the most common problems during dental and endoscopic procedures. Benzydamine hydrochloride is a non-steroidal anti-inflammatory medica-tion and a local anesthetic that might be useful in reducing the gag reflex. Purpose: This study aimed to evaluate the effects of benzydamine hydrochloride mouthwash on the intensity of the gag reflex.Materials and Method: In this randomized clinical trial study, 30 participants aged 21-26 with a gag trigger point index (GTPI) higher than 2 were divided into 2 groups. In the case group, 15 ml of 0.15% benzydamine hydrochloride mouthwash was gargled for 1 minute, and after 10 minutes GTPI test was conducted. In the control group, 4 puffs of 10% lidocaine spray were applied to the mucosa of the targeted area, and after 5 minutes, GTPI was measured. Participants were asked about the taste and smell of the medications. Results: GTPI was significantly reduced in both groups. In the lidocaine group, the GTPI score changed from 4.47 to 2.00 (P

Heteronymous inhibition between lower limb muscles is primarily attributed to recurrent inhibitory circuits in humans but could also arise from Golgi tendon organs (GTOs). Distinguishing between recurrent inhibition and mechanical activation of GTOs is challenging because their heteronymous effects are both elicited by stimulation of nerves or a muscle above motor threshold. Here, the unique influence of mechanically activated GTOs was examined by comparing the magnitude of heteronymous inhibition from quadriceps (Q) muscle stimulation onto ongoing soleus electromyographic at five Q stimulation intensities (1.5–2.5× motor threshold) before and after an acute bout of stimulation‐induced Q fatigue. Fatigue was used to decrease Q stimulation evoked force (i.e., decreased GTO activation) despite using the same pre‐fatigue stimulation currents (i.e., same antidromic recurrent inhibition input). Thus, a decrease in heteronymous inhibition after Q fatigue and a linear relation between stimulation‐evoked torque and inhibition both before and after fatigue would support mechanical activation of GTOs as a source of inhibition. A reduction in evoked torque but no change in inhibition would support recurrent inhibition. After fatigue, Q stimulation‐evoked knee torque, heteronymous inhibition magnitude and inhibition duration were significantly decreased for all stimulation intensities. In addition, heteronymous inhibition magnitude was linearly related to twitch‐evoked knee torque before and after fatigue. These findings support mechanical activation of GTOs as a source of heteronymous inhibition along with recurrent inhibition. The unique patterns of heteronymous inhibition before and after fatigue across participants suggest the relative contribution of GTOs, and recurrent inhibition may vary across persons. [ABSTRACT FROM AUTHOR]

BACKGROUND: Since the physiological background of motion sickness is not entirely clear, it was aimed to examine the physiological differences in groups consisting of individuals susceptible and non-susceptible to motion sickness. METHODS: Sixty subjects [motion sickness (MS) group: 33 female, 3 male; 28.8 ± 8.1 years; control group: 19 female, 5 male; 24.5 ± 4.3 years] were included in the study. Near visual acuity test on the treadmill in the presence of visual stimulation, pattern visual-evoked potentials, oculomotor tests, and computerized dynamic posturography were applied. Receiver operating characteristic analysis was performed to determine the parameter that provides the excellent discrimination between the groups. RESULTS: The most effective parameter in differentiating the study groups was determined as dynamic visual acuity with 77.8% sensitivity and 95.8% specificity. Significant differences were found in the vestibular (mean ± standard deviation: 0.63 ± 0.17), visual (0.77 ± 0.18), and composite scores (73.11 ± 11.89) of the patients (P = .000) in posturographic evaluation. In the visual-evoked potential examination, a significant decrease was found in the amplitude values between the P100-N145 waves in the binocular (5.0 ± 2.8, P = .002), right eye (7.6 ± 3.2, P = .009) and left eye (7.9 ± 2.9, P = .016) in the symptomatic patients. In binocular oculomotor evaluation, directional asymmetric findings were obtained. CONCLUSION: It has been shown that the most effective test parameter that distinguishes the MS susceptible and non-susceptible individuals is the dynamic visual acuity value. Based on the results of neuro-physiological tests, it was suggested that a possible visual-vestibular integration disorder in individuals susceptible to motion sickness may affect visual and vestibular performance. [ABSTRACT FROM AUTHOR]

Background: Jaw clenching improves dynamic reactive balance on an oscillating platform during forward acceleration and is associated with decreased mean sway speed of different body regions. Objective: It is suggested that jaw clenching as a concurrent muscle activity facilitates human motor excitability, increasing the neural drive to distal muscles. The underlying mechanism behind this phenomenon was studied based on leg and trunk muscle activity (iEMG) and co‐contraction ratio (CCR). Methods: Forty‐eight physically active and healthy adults were assigned to three groups, performing three oral motor tasks (jaw clenching, tongue pressing against the palate or habitual lower jaw position) during a dynamic one‐legged stance reactive balance task on an oscillating platform. The iEMG and CCR of posture‐relevant muscles and muscle pairs were analysed during platform forward acceleration. Results: Tongue pressing caused an adjustment of co‐contraction patterns of distal muscle groups based on changes in biomechanical coupling between the head and trunk during static balancing at the beginning of the experiment. Neither iEMG nor CCR measurement helped detect a general neuromuscular effect of jaw clenching on the dynamic reactive balance. Conclusion: The findings might indicate the existence of robust fixed patterns of rapid postural responses during the important initial phases of balance recovery. [ABSTRACT FROM AUTHOR]

Statement of the Problem: Gag reflex is among the most common problems during dental and endoscopic procedures. Benzydamine hydrochloride is a non-steroidal anti-nflammatory medication and a local anesthetic that might be useful in reducing the gag reflex. Purpose: This study aimed to evaluate the effects of benzydamine hydrochloride mouth-wash on the intensity of the gag reflex. Materials and Method: In this randomized clinical trial study, 30 participants aged 21-26 with a gag trigger point index (GTPI) higher than 2 were divided into 2 groups. In the case group, 15 ml of 0.15% benzydamine hydrochloride mouthwash was gargled for 1 minute, and after 10 minutes GTPI test was conducted. In the control group, 4 puffs of 10% lidocaine spray were applied to the mucosa of the targeted area, and after 5 minutes, GTPI was measured. Participants were asked about the taste and smell of the medications. Results: GTPI was significantly reduced in both groups. In the lidocaine group, the GTPI score changed from 4.47 to 2.00 (p< 0.001), and that for the benzydamine group was 4.20 to 1.47 (p< 0.001). The variance rate of the gag reflex was -2.73 and -2.47 in the benzydamine group and lidocaine group, respectively. However, this reduction was not statistically significant between the two groups. Moreover, benzydamine mouthwash has a significantly better taste and smell than lidocaine (p= 0.001). Conclusion: The results of this study showed that benzydamine mouthwash could be used quite effectively in reducing the gag reflex. [ABSTRACT FROM AUTHOR]

Recent studies involving transplantation of feces from schizophrenia (SCZ) patients and their healthy controls into germ-free mice have demonstrated that the gut microbiome plays a critical role in mediating SCZ-linked physiology and behavior. To date, only one animal model (a metabotropic glutamate receptor 5 knockout) of SCZ has been reported to recapitulate SCZ-linked gut dysbiosis. Since human 22q11.2 microdeletion syndrome is associated with increased risk of SCZ, we investigated whether the 22q11.2 microdeletion (Q22) mouse model of SCZ exhibits both SCZ-linked behaviors and intestinal dysbiosis. We demonstrated that Q22 mice display increased acoustic startle response and ileal (but not colonic) dysbiosis, which may be due to the role of the ileum as an intestinal region with high immune and neuroimmune activity. We additionally identified a negative correlation between the abundance of a Streptococcus species in the ilea of Q22 mice and their acoustic startle response, providing early evidence of a gut-brain relationship in these mice. Given the translational relevance of this mouse model, our work suggests that Q22 mice could have considerable utility in preclinical research probing the relationship between gut dysbiosis and the gut-brain axis in the pathogenesis of SCZ.

PurposeNon-human primates (NHPs) are useful models for human retinal disease. Chromatic pupillometry has been proposed as a noninvasive method of identifying inherited retinal diseases (IRDs) in humans; however, standard protocols employ time-consuming dark adaptation. We utilized shortened and standard dark-adaptation protocols to compare pupillary light reflex characteristics following chromatic stimulation in rhesus macaques with achromatopsia to wild-type (WT) controls with normal retinal function.MethodsNine rhesus macaques homozygous for the p.R656Q mutation (PDE6C HOMs) and nine WT controls were evaluated using chromatic pupillometry following 1-minute versus standard 20-minute dark adaptations. The following outcomes were measured and compared between groups: pupil constriction latency, peak constriction, pupil constriction time, and constriction velocity.ResultsPupil constriction latency was significantly longer in PDE6C HOMs with red-light (P = 0.0002) and blue-light (P = 0.04) stimulation versus WT controls. Peak constriction was significantly less in PDE6C HOMs with all light stimulation compared to WT controls (P < 0.0001). Pupil constriction time was significantly shorter in PDE6C HOMs versus WT controls with red-light (P = 0.04) and white-light (P = 0.003) stimulation. Pupil constriction velocity was significantly slower in PDE6C HOMs versus WT controls with red-light (P < 0.0001), blue-light (P < 0.0001), and white-light (P = 0.0002) stimulation. Dark adaptation time only significantly affected peak (P = 0.008) and time of pupil constriction (P = 0.02) following blue-light stimulation.ConclusionsChromatic pupillometry following 1- and 20-minute dark adaptation is an effective tool for screening NHPs for achromatopsia.Translational relevanceRapid identification of NHPs with IRDs will provide animal research models to advance research and treatment of achromatopia in humans.

BackgroundLow intensity, transcranial focused ultrasound (tFUS) is a re-emerging brain stimulation technique with the unique capability of reaching deep brain structures non-invasively.Objective/hypothesisWe sought to demonstrate that tFUS can selectively and accurately target and modulate deep brain structures in humans important for emotional functioning as well as learning and memory. We hypothesized that tFUS would result in significant longitudinal changes in perfusion in the targeted brain region as well as selective modulation of BOLD activity and BOLD-based functional connectivity of the target region.MethodsIn this study, we collected MRI before, simultaneously during, and after tFUS of two deep brain structures on different days in sixteen healthy adults each serving as their own control. Using longitudinal arterial spin labeling (ASL) MRI and simultaneous blood oxygen level dependent (BOLD) functional MRI, we found changes in cerebral perfusion, regional brain activity and functional connectivity specific to the targeted regions of the amygdala and entorhinal cortex (ErC).ResultstFUS selectively increased perfusion in the targeted brain region and not in the contralateral homolog or either bilateral control region. Additionally, tFUS directly affected BOLD activity in a target specific fashion without engaging auditory cortex in any analysis. Finally, tFUS resulted in selective modulation of the targeted functional network connectivity.ConclusionWe demonstrate that tFUS can selectively modulate perfusion, neural activity and connectivity in deep brain structures and connected networks. Lack of auditory cortex findings suggests that the mechanism of tFUS action is not due to auditory or acoustic startle response but rather a direct neuromodulatory process. Our findings suggest that tFUS has the potential for future application as a novel therapy in a wide range of neurological and psychiatric disorders associated with subcortical pathology.

This study investigated whether abnormal peak inversion spontaneous potentials (PISPs) recorded at resting myofascial trigger points (MTrPs) stem from the discharge of muscle spindles. Forty-eight male Sprague-Dawley rats were randomly divided into six groups. Five groups underwent MTrP modeling intervention, whereas one group did not receive intervention and was duly designated as the blank control. After model construction, five rat models were randomly subjected to ramp-and-hold stretch tests, succinylcholine injection, eperisone hydrochloride injection, saline injection, and blank drug intervention. By contrast, the rats in the blank control group were subjected to ramp-and-hold stretch tests as a control. Frequencies and amplitudes of PISPs were recorded pre- and post-interventions and compared with those of the blank group. Stretch tests showed that the depolarization time and amplitude of PISPs ranged from 0.4 ms to 0.9 ms and from 80 uV to 140 μV, respectively. However, no PISPs were observed in the control rats. The frequency of PISPs in the ramp and hold phases and the first second after the hold phase was higher than that before stretching (p < 0.01). Succinylcholine and eperisone exerted excitatory and inhibitory effects on PISPs, respectively. In the group injected with 0.9% saline, no considerable differences of the PISPs were observed during the entire observation period. In conclusion, PISPs recorded at resting MTrPs are closely related to muscle spindles. The formation of MTrPs may be an important factor that regulate dysfunctional muscle spindles. [ABSTRACT FROM AUTHOR]

Background and Aims: Maxillofacial surgeries, including procedures to the face, oral cavity, jaw, and head and neck, are common in adults . However, they impose a risk of adverse cardiac events (ACEs). While ACEs are well understood for other non‑cardiac surgeries, there is a paucity of data about maxillofacial surgeries. This systematic review and meta‑analysis report the incidence and presentation of perioperative ACEs during maxillofacial surgery. Methods: We included primary studies that reported on perioperative ACEs in adults. To standardise reporting, ACEs were categorised as 1. heart rate and rhythm disturbances, 2. blood pressure disturbances, 3. ischaemic heart disease and 4. heart failure and other complications. The primary outcome was ACE presentation and incidence during the perioperative period. Secondary outcomes included the surgical outcome according to the Clavien–Dindo classification and trigeminocardiac reflex involvement. STATA version 17.0 and MetaProp were used to delineate proportion as effect size with a 95% confidence interval (CI). Results: Twelve studies (34,227 patients) were included. The incidence of perioperative ACEs was 2.58% (95% CI 1.70, 3.45, I 2 = 96.17%, P = 0.001). Heart rate and rhythm disturbances resulted in the greatest incidence at 3.84% among the four categories. Most commonly, these ACEs resulted in intensive care unit admission (i.e. Clavien–Dindo score of 4). Conclusion: Despite an incidence of 2.58%, ACEs can disproportionately impact surgical outcomes. Future research should include large‑scale prospective studies that may provide a better understanding of the contributory factors and long‑term effects of ACEs in patients during maxillofacial surgery. [ABSTRACT FROM AUTHOR]

Eslicarbazepine acetate (ESL) is a third-generation antiepileptic drug indicated as monotherapy for adults with newly diagnosed epilepsy and as adjunctive therapy for the treatment of partial seizures. Our aim was to assess the effectiveness and safety of both acute and repeated ESL administration against reflex audiogenic seizures, as shown by the Genetic Audiogenic Seizures Hamster from Salamanca (GASH/Sal). Animals were subject to the intraperitoneal administration of ESL, applying doses of 100, 150 and 200 mg/kg for the acute study, whereas a daily dose of 100 mg/kg was selected for the subchronic study, which lasted 14 days. In both studies, the anticonvulsant effect of the therapy was evaluated using neuroethological methods. To assess the safety of the treatment, behavioral tests were performed, hematological and biochemical liver profiles were obtained, and body weight was monitored. In addition, the ESL levels in blood were measured after the acute administration of a 200 mg/kg dose. Treatment with ESL caused a reduction in seizure severity. No statistically significant differences were detected between the selected doses or between the acute or repeated administration of the drug. To summarize, the intraperitoneal administration of ESL is safe and shows an anticonvulsant effect in the GASH/Sal. [ABSTRACT FROM AUTHOR]

Introduction and Hypothesis: Involuntary pelvic floor muscle (PFM) contractions are thought to occur during an increase in intra-abdominal pressure (IAP). Although no studies have assessed their presence in women with normal pelvic floor (PF) function, existing literature links the absence of involuntary PFM contractions to various PF dysfunctions. This study rectifies this lacuna by evaluating involuntary PFM contractions during IAP in healthy nulliparous women with no PF dysfunction, using visual observation and vaginal palpation. Results were compared with the literature and the IUGA/ICS Terminology Reports. Methods: Nulliparous (n=149) women performed three sets of three maximal coughs. Visual observation and vaginal palpation were conducted in the standing and supine positions. The women were not instructed to contract their PFMs. Occurrence rates were calculated for each assessment method and position; differences between positions were analyzed using the Chi-squared test. Results: Rates of occurrence of involuntary PFM contraction were low across both assessments and positions (5–17%). Significant differences were found between standing (5%) and supine (15%) positions for visual observation, but not vaginal palpation (15%, 17% respectively). Occurrence rates also differed compared with the literature and terminology reports. Conclusions: Contrary to clinical expectations, rates of occurrence of involuntary PFM contraction among our cohort of nulliparous women were extremely low. Digital palpation results showed high agreement with the terminology reports, but only partial agreement was observed for the visual observation results. Our study underscores the need for more research aimed at defining normal involuntary PF functions, a review of our understanding of involuntary PFM contractions, and better standardized guidelines for involuntary PFM assessment methods. [ABSTRACT FROM AUTHOR]

Noninvasive spinal stimulation has been increasingly used in research on motor control and neurorehabilitation. Despite advances in percutaneous electrical stimulation techniques, magnetic stimulation is not as commonly used as electrical stimulation. Therefore, it is still under discussion what neuronal elements are activated by magnetic stimulation of the human spinal cord. In this study, we demonstrated that transvertebral magnetic stimulation (TVMS) induced transsynaptic activation of spinal motoneuron pools in the lumbar cord. In healthy humans, paired-pulse TVMS was given over an intervertebral space between the L1-L2 vertebrae with an interpulse interval of 100 ms, and the stimulus-evoked electromyographic (EMG) responses were recorded in the lower limb muscles. The results show that the evoked EMG responses after the 2nd pulse were clearly suppressed compared with the widespread responses evoked after the 1st pulse in the muscles of the lower extremity, indicating that the transsynaptic activation of spinal motoneurons by the 2nd pulse was suppressed by the effects produced by the 1st pulse. The inconsistent modulation of response suppression to stimulus intensity across individuals suggests that the TVMS-evoked EMG responses are composed of the compound potentials mediated by the direct activation of motor axons and the transsynaptic activation of motoneuron pools through sensory afferents and that the recruitment order of those fibers by TVMS may be nonhomogeneous across individuals. • This study aimed to determine which neuronal elements are activated by transvertebral magnetic stimulation (TVMS) in humans. • Paired-pulse TVMS induced suppression of the muscle response after the 2nd stimulation. • TVMS induced transsynaptic activation of spinal motoneuron pools. [ABSTRACT FROM AUTHOR]

Abstract Background Spinal cord injuries (SCI) lead to functional alteration with important consequences such as motor and sensory disorders. The repair strategies developed to date remain ineffective. The adipose tissue-derived stromal vascular fraction (SVF) is composed of a cocktail of cells with trophic, pro-angiogenic and immunomodulatory effects. Numerous therapeutic benefits were shown for tissue reconstitution, peripheral neuropathy and for the improvement of neurodegenerative diseases. Here, the therapeutic efficacy of SVF on sensorimotor recovery after an acute thoracic spinal cord contusion in adult rats was determined. Method Male Sprague Dawley rats (n = 45) were divided into 3 groups: SHAM (without SCI and treatment), NaCl (animals with a spinal lesion and receiving a saline injection through the dura mater) and SVF (animals with a spinal lesion and receiving a fraction of fat removed from adipocytes through the dura mater). Some animals were sacrificed 14 days after the start of the experiment to determine the inflammatory reaction by measuring the interleukin-1β, interleukin-6 and Tumor Necrosis Factor-α in the lesion area. Other animals were followed once a week for 12 weeks to assess functional recovery (postural and locomotor activities, sensorimotor coordination). At the end of this period, spinal reflexivity (rate-dependent depression of the H-reflex) and physiological adjustments (ventilatory response to metabosensitive muscle activation following muscle fatigue) were measured with electrophysiological tools. Results Compared to non-treated animals, results indicated that the SVF reduced the endogenous inflammation and increased the behavioral recovery in treated animals. Moreover, H-reflex depression and ventilatory adjustments to muscle fatigue were found to be comparable between SHAM and SVF groups. Conclusion Our results highlight the effectiveness of SVF and its high therapeutic potential to improve sensorimotor functions and to restore the segmental sensorimotor loop and the communication between supra- and sub-lesional spinal cord regions after traumatic contusion. Graphical Abstract

Background and Aims: Maxillofacial surgeries, including procedures to the face, oral cavity, jaw, and head and neck, are common in adults . However, they impose a risk of adverse cardiac events (ACEs). While ACEs are well understood for other non-cardiac surgeries, there is a paucity of data about maxillofacial surgeries. This systematic review and meta-analysis report the incidence and presentation of perioperative ACEs during maxillofacial surgery. Methods: We included primary studies that reported on perioperative ACEs in adults. To standardise reporting, ACEs were categorised as 1. heart rate and rhythm disturbances, 2. blood pressure disturbances, 3. ischaemic heart disease and 4. heart failure and other complications. The primary outcome was ACE presentation and incidence during the perioperative period. Secondary outcomes included the surgical outcome according to the Clavien–Dindo classification and trigeminocardiac reflex involvement. STATA version 17.0 and MetaProp were used to delineate proportion as effect size with a 95% confidence interval (CI). Results: Twelve studies (34,227 patients) were included. The incidence of perioperative ACEs was 2.58% (95% CI 1.70, 3.45, I2 = 96.17%, P = 0.001). Heart rate and rhythm disturbances resulted in the greatest incidence at 3.84% among the four categories. Most commonly, these ACEs resulted in intensive care unit admission (i.e. Clavien–Dindo score of 4). Conclusion: Despite an incidence of 2.58%, ACEs can disproportionately impact surgical outcomes. Future research should include large-scale prospective studies that may provide a better understanding of the contributory factors and long-term effects of ACEs in patients during maxillofacial surgery.

PURPOSE: Resting heart rate variability (HRV) is an important biomarker linking mental health to cardiovascular outcomes. However, resting HRV is also impaired in autonomic neuropathy, a common and underdiagnosed complication of common medical conditions which is detected by testing autonomic reflexes. We sought to describe the relationship between autonomic reflex abnormalities and resting HRV, taking into consideration medical comorbidities and demographic variables. METHODS: Participants (n = 209) underwent a standardized autonomic reflex screen which was summarized as the Composite Autonomic Severity Score (CASS) and included measures of reflexive HRV, e.g., heart rate with deep breathing (HRDB). Resting HRV measures were: pNN50 (percentage of NN intervals that differ by > 50 ms) and cvRMSSD (adjusted root mean square of successive differences). RESULTS: In univariate analyses, lower resting HRV was associated with: older age, higher CASS, neuropathy on examination, hypertension, diabetes, chronic obstructive pulmonary disease, chronic kidney disease, and psychiatric disease. Adaptive regression spline analysis revealed that HRDB explained 27% of the variability in resting HRV for participants with values of HRDB in the normal range. Outside this range, there was no linear relationship because: (1) when HRDB was low (indicating autonomic neuropathy), resting HRV was also low with low variance; and (2) when HRDB was high, the variance in resting HRV was high. In multivariate models, only HRDB was significantly independently associated with cvRMSSD and pNN50. CONCLUSION: Subclinical autonomic neuropathy, as evidenced by low HRDB and other autonomic reflexes, should be considered as a potential confounder of resting HRV in research involving medically and demographically diverse populations.

Background: Spinal cord injuries (SCI) lead to functional alteration with important consequences such as motor and sensory disorders. The repair strategies developed to date remain ineffective. The adipose tissue-derived stromal vascular fraction (SVF) is composed of a cocktail of cells with trophic, pro-angiogenic and immunomodulatory effects. Numerous therapeutic benefits were shown for tissue reconstitution, peripheral neuropathy and for the improvement of neurodegenerative diseases. Here, the therapeutic efficacy of SVF on sensorimotor recovery after an acute thoracic spinal cord contusion in adult rats was determined. Method: Male Sprague Dawley rats (n = 45) were divided into 3 groups: SHAM (without SCI and treatment), NaCl (animals with a spinal lesion and receiving a saline injection through the dura mater) and SVF (animals with a spinal lesion and receiving a fraction of fat removed from adipocytes through the dura mater). Some animals were sacrificed 14 days after the start of the experiment to determine the inflammatory reaction by measuring the interleukin-1β, interleukin-6 and Tumor Necrosis Factor-α in the lesion area. Other animals were followed once a week for 12 weeks to assess functional recovery (postural and locomotor activities, sensorimotor coordination). At the end of this period, spinal reflexivity (rate-dependent depression of the H-reflex) and physiological adjustments (ventilatory response to metabosensitive muscle activation following muscle fatigue) were measured with electrophysiological tools. Results: Compared to non-treated animals, results indicated that the SVF reduced the endogenous inflammation and increased the behavioral recovery in treated animals. Moreover, H-reflex depression and ventilatory adjustments to muscle fatigue were found to be comparable between SHAM and SVF groups. Conclusion: Our results highlight the effectiveness of SVF and its high therapeutic potential to improve sensorimotor functions and to restore the segmental sensorimotor loop and the communication between supra- and sub-lesional spinal cord regions after traumatic contusion. [ABSTRACT FROM AUTHOR]

Traumatic spinal cord injuries (SCIs) often result in sensory, motor, and vegetative function loss below the injury site. Although preclinical results have been promising, significant solutions for SCI patients have not been achieved through translating repair strategies to clinical trials. In this study, we investigated the effective potential of mechanically activated lipoaspirated adipose tissue when transplanted into the epicenter of a thoracic spinal contusion. Male Sprague Dawley rats were divided into three experimental groups: SHAM (uninjured and untreated), NaCl (spinal cord contusion with NaCl application), and AF (spinal cord contusion with transplanted activated human fat). Pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) were measured to assess endogenous inflammation levels 14 days after injury. Sensorimotor recovery was monitored weekly for 12 weeks, and gait and electrophysiological analyses were performed at the end of this observational period. The results indicated that AF reduced endogenous inflammation post-SCI and there was a significant improvement in sensorimotor recovery. Moreover, activated adipose tissue also reinstated the segmental sensorimotor loop and the communication between supra- and sub-lesional spinal cord regions. This investigation highlights the efficacy of activated adipose tissue grafting in acute SCI, suggesting it is a promising therapeutic approach for spinal cord repair after traumatic contusion in humans. [ABSTRACT FROM AUTHOR]

Copyright of Acta Linguistica Lithuanica is the property of Institute of the Lithuanian Language and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: This systematic review aimed to summarize how oral contraceptives (OC) affect resting autonomic function and the autonomic response to a variety of physiological stressors. Methods: A search strategy was created to retrieve citations investigating physiological responses comparing OC users to non-users (NOC) in response to autonomic reflex activation. Results: A total of 6148 citations were identified across databases from inception to June 2, 2022, and 3870 citations were screened at the abstract level after deduplication. Then, 133 texts were assessed at full-text level, and only 40 studies met eligibility requirements. Included citations were grouped by the aspect of autonomic function assessed, including autonomic reflex (i.e., baroreflex, chemoreflex, mechanoreflex, metaboreflex, and venoarterial reflex), or indicators (i.e., heart rate variability, pulse wave velocity, and sympathetic electrodermal activity), and physiological stressors that may alter autonomic function (i.e., auditory, exercise, mental or orthostatic stress, altitude, cold pressor test, sweat test, and vasodilatory infusions). Conclusion: OC influence the physiological responses to chemoreflex, mechanoreflex, and metaboreflex activation. In terms of autonomic indices and physiological stressors, there are more inconsistencies within the OC literature, which may be due to estrogen dosage within the OC formulation (i.e., heart rate variability) or the intensity of the stressor (exercise intensity/duration or orthostatic stress). Further research is required to elucidate the effects of OC on these aspects of autonomic function because of the relatively small amount of available research. Furthermore, researchers should more clearly define or stratify OC use by duration, dose, and/or hormone cycling to further elucidate the effects of OC. [ABSTRACT FROM AUTHOR]

Copyright of Mexican Journal of Behavioral Analysis / Revista Mexicana de Análisis de la Conducta is the property of Sociedad Mexicana de Analisis de la Conducta and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Acta Comportamentalia is the property of Instituto de Psicologia y Educacion de la Universidad Veracruzana and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Intraoperative targeting of the analgesic effect still lacks an optimal solution. Opioids are currently the main drug used to achieve antinociception, and although underdosing can lead to an increased stress response, overdose can also lead to undesirable adverse effects. To better understand how to achieve the optimal analgesic effect of opioids, we studied the influence of remifentanil on the pupillary reflex dilation (PRD) and its relationship with the reflex movement response to a standardized noxious stimulus. The main objective was to generate population pharmacodynamic models relating remifentanil predicted concentrations to movement and to pupillary dilation during general anesthesia. A total of 78 patients undergoing gynecological surgery under general anesthesia were recruited for the study. PRD and movement response to a tetanic stimulus were measured multiple times before and after surgery. We used nonlinear mixed effects modeling to generate a population pharmacodynamic model to describe both the time profiles of PRD and movement responses to noxious stimulation. Our model demonstrated that movement and PRD are equally depressed by remifentanil. Using the developed model, we changed the intensity of stimulation and simulated remifentanil predicted concentrations maximizing the probability of absence of movement response. An estimated effect site concentration of 2 ng/ml of remifentanil was found to inhibit movement to a tetanic stimulation with a probability of 81%.

Co-occurring posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) is common and particularly associated with elevation of hyperarousal compared to PTSD alone. Treatment options are limited. Oxytocin regulates physiological stress response. Intranasal oxytocin administration has demonstrated potential in reducing symptoms of both PTSD and AUD. This study addresses a gap in the literature by investigating effects of intranasal oxytocin on startle reactivity, an important potential marker of both PTSD and AUD symptomatology. This is a randomized, double-blind, placebo-controlled, within- and between-participant, crossover, dose-ranging study examining the effects of a single administration of oxytocin 20 IU versus 40 IU versus placebo on psychophysiological responses to a common laboratory fear-potentiated acoustic startle paradigm in participants with PTSD-AUD (n = 47) and controls (n = 37) under three different levels of threat. Contrary to our hypothesis, for the PTSD-AUD group, oxytocin 20 IU had no effect on startle reactivity, while oxytocin 40 IU increased measures of startle reactivity. Additionally, for PTSD-AUD only, ambiguous versus low threat was associated with an elevated skin conductance response. For controls only, oxytocin 20 IU versus placebo was associated with reduced startle reactivity.

Fibroblast growth factor binding protein 3 (Fgfbp3) have been known to be crucial for the process of neural proliferation, differentiation, migration, and adhesion. However, the specific role and the molecular mechanisms of fgfbp3 in regulating the development of motor neurons remain unclear. In this study, we have investigated the function of fgfbp3 in morphogenesis and regeneration of motor neuron in zebrafish. Firstly, we found that fgfbp3 was localized in the motor neurons and loss of fgfbp3 caused the significant decrease of the length and branching number of the motor neuron axons, which could be partially rescued by fgfbp3 mRNA injection. Moreover, the fgfbp3 knockdown (KD) embryos demonstrated similar defects of motor neurons as identified in fgfbp3 knockout (KO) embryos. Furthermore, we revealed that the locomotion and startle response of fgfbp3 KO embryos were significantly restricted, which were partially rescued by the fgfbp3 overexpression. In addition, fgfbp3 KO remarkably compromised axonal regeneration of motor neurons after injury. Lastly, the malformation of motor neurons in fgfbp3 KO embryos was rescued by overexpressing drd1b or neurod6a, respectively, which were screened by transcriptome sequencing. Taken together, our results provide strong cellular and molecular evidence that fgfbp3 is crucial for the axonal morphogenesis and regeneration of motor neurons in zebrafish.

Angelman syndrome (AS) is a rare genetic neurodevelopmental disorder characterized by intellectual disabilities, motor and balance deficits, impaired communication, and a happy, excitable demeanor with frequent laughter. We sought to elucidate a preclinical outcome measure in male and female rats that addressed communication abnormalities of AS and other neurodevelopmental disorders in which communication is atypical and/or lack of speech is a core feature. We discovered, and herein report for the first time, excessive laughter-like 50 kHz ultrasonic emissions in the Ube3amat-/pat+ rat model of AS, which suggests an excitable, playful demeanor and elevated positive affect, similar to the demeanor of individuals with AS. Also in line with the AS phenotype, Ube3amat-/pat+ rats demonstrated aberrant social interactions with a novel partner, distinctive gait abnormalities, impaired cognition, an underlying LTP deficit, and profound reductions in brain volume. These unique, robust phenotypes provide advantages compared with currently available mouse models and will be highly valuable as outcome measures in the evaluation of therapies for AS.SIGNIFICANCE STATEMENT Angelman syndrome (AS) is a severe neurogenetic disorder for which there is no cure, despite decades of research using mouse models. This study used a recently developed rat model of AS to delineate disease-relevant outcome measures to facilitate therapeutic development. We found the rat to be a strong model of AS, offering several advantages over mouse models by exhibiting numerous AS-relevant phenotypes, including overabundant laughter-like vocalizations, reduced hippocampal LTP, and volumetric anomalies across the brain. These findings are unconfounded by detrimental motor abilities and background strain, issues plaguing mouse models. This rat model represents an important advancement in the field of AS, and the outcome metrics reported herein will be central to the therapeutic pipeline.

Introduction. One of the additional instrumental methods for diagnosing pudendal neuropathy is needle electroneuromyography (ENMG) of the bulbocavernosus reflex (BCR). The accumulated data on ENMG BCR in patients with primary chronic pelvic pain syndrome (CPPS) are insufficient due to the specificity of the procedure and its performance only in expert centres that specialise in the treatment of pelvic pain. Therefore, a study to investigate the features of ENMG BCR in patients with CPPS is of increased interest.Objective. To assess the representativeness and informativeness of the ENMG BCR technique in patients with CPPS and to identify factors influencing changes in the main parameters of the BCR M-response such as latency, amplitude, and duration.Materials & methods. Retrospective cohort study, which included 75 data from patients with (CPPS) who underwent needle-guided ENMG recording of BCR. Subjective complaints of patients were recorded using validated questionnaires: visual analogue scale (VAS) and chronic prostatitis and male pelvic pain syndrome symptom scale index (NIH-CPSI). Basic ENMG parameters such as the amplitude, latency, and duration of the M-responses were recorded.Results. We found statistically significant correlations between the duration and height of the M response of the patients (r = 0.31, p = 0.03) and their body weight (r = 0.34, p = 0.02). Anthropometric data did not correlate with amplitude and latency. Significant excess latency above 45 ms was observed, confirming nerve tissue destruction, in 11 (55%) women and 24 (44%) men. Although there were no statistically significant differences in any of the M-response parameters between men and women, there was a tendency for an increase in response amplitude in men and an increase in BCR latency time in women.Conclusion. The results of our study show that the duration of the M-response of BCR can correlate positively with the anthropometric data of the patient. At the same time, the mean latency and amplitude of the response are independent of anthropometric data, and the difference between them may be more determined by sex differences.

Background Neurological opportunistic infections cause significant morbidity and mortality in people with human immunodeficiency virus (HIV) but are difficult to diagnose. Methods One hundred forty people with HIV with acute neurological symptoms from Iquitos, Peru, were evaluated for cerebral toxoplasmosis with quantitative polymerase chain reaction (qPCR) of cerebrospinal fluid (CSF) and for cryptococcal meningitis with cryptococcal antigen test (CrAg) in serum or CSF. Differences between groups were assessed with standard statistical methods. A subset of samples was evaluated by metagenomic next-generation sequencing (mNGS) of CSF to compare standard diagnostics and identify additional diagnoses. Results Twenty-seven participants were diagnosed with cerebral toxoplasmosis by qPCR and 13 with cryptococcal meningitis by CrAg. Compared to participants without cerebral toxoplasmosis, abnormal Glasgow Coma Scale score (P =.05), unilateral focal motor signs (P =.01), positive Babinski reflex (P =.01), and multiple lesions on head computed tomography (CT) (P =.002) were associated with cerebral toxoplasmosis. Photophobia (P =.03) and absence of lesions on head CT (P =.02) were associated with cryptococcal meningitis. mNGS of 42 samples identified 8 cases of cerebral toxoplasmosis, 7 cases of cryptococcal meningitis, 5 possible cases of tuberculous meningitis, and incidental detections of hepatitis B virus (n = 1) and pegivirus (n = 1). mNGS had a positive percentage agreement of 71% and a negative percentage agreement of 91% with qPCR for T gondii. mNGS had a sensitivity of 78% and specificity of 100% for Cryptococcus diagnosis. Conclusions An infection was diagnosed by any method in only 34% of participants, demonstrating the challenges of diagnosing neurological opportunistic infections in this population and highlighting the need for broader, more sensitive diagnostic tests for central nervous system infections. [ABSTRACT FROM AUTHOR]

Background: Chewing and licking are primarily activated by central pattern generator (CPG) neuronal circuits in the brainstem and when activated trigger repetitive rhythmic orofacial movements such as chewing, licking and swallowing. These CPGs are reported to modulate orofacial reflex responses in functions such as chewing. Objective: This study explored the modulation of reflex responses in the anterior and posterior bellies (ant‐Dig and post‐Dig, respectively) of the digastric muscle evoked by low‐intensity trigeminal stimulation in conscious rats. Methods: The ant‐Dig and post‐Dig reflexes were evoked by using low‐intensity electrical stimulation applied to either the right or left inferior alveolar nerve. Peak‐to‐peak amplitudes and onset latencies were measured. Results: No difference was observed between threshold and onset latency for evoking ant‐Dig and post‐Dig reflexes, suggesting that the latter was also evoked disynaptically. The peak‐to‐peak amplitude of both reflexes was significantly reduced during chewing, licking and swallowing as compared to resting period and was lowest during the jaw‐closing phase of chewing and licking. Onset latency was significantly largest during the jaw‐closing phase. Inhibitory level was similar between the ant‐Dig and post‐Dig reflex responses and between the ipsilateral and contralateral sides. Conclusion: These results suggest that both the ant‐Dig and post‐Dig reflex responses were significantly inhibited, probably due to CPG activation during feeding behaviours to maintain coordination of jaw and hyoid movements and hence ensure smooth feeding mechanics. [ABSTRACT FROM AUTHOR]

Background Many people who have a positive hepatitis C virus (HCV) antibody (Ab) test never receive a confirmatory HCV RNA viral load (VL) test. Reflex VL testing may help address this problem. We undertook a systematic review to evaluate the effectiveness of reflex VL testing compared with standard nonreflex approaches on outcomes across the HCV care cascade. Methods We searched 4 databases for studies that examined laboratory-based reflex or clinic-based reflex VL testing approaches, with or without a nonreflex comparator, and had data on the uptake of HCV RNA VL test and treatment initiation and turnaround time between Ab and VL testing. Both laboratory- and clinic-based reflex VL testing involve only a single clinic visit. Summary estimates were calculated using random-effects meta-analyses. Results Fifty-one studies were included (32 laboratory-based and 19 clinic-based reflex VL testing). Laboratory-based reflex VL testing increased HCV VL test uptake versus nonreflex testing (RR: 1.35; 95% CI: 1.16–1.58) and may improve linkage to care among people with a positive HCV RNA test (RR: 1.47; 95% CI:.81–2.67) and HCV treatment initiation (RR: 1.03; 95% CI:.46–2.32). The median time between Ab and VL test was <1 day for all laboratory-based reflex studies and 0–5 days for 13 clinic-based reflex testing. Conclusions Laboratory-based and clinic-based HCV reflex VL testing increased uptake and reduced time to HCV VL testing and may increase HCV linkage to care. The World Health Organization now recommends reflex VL testing as an additional strategy to promote access to HCV VL testing and treatment. Clinical Trials Registration PROSPERO CRD42021283822. [ABSTRACT FROM AUTHOR]

The forces applied during a spinal manipulation produce a neuromuscular response in the paraspinal muscles. A systematic evaluation of the factors involved in producing this muscle activity provides a clinical insight. The purpose of this study is to quantify the effect of treatment factors (manipulation sequence and manipulation site) and response factors (muscle layer, muscle location, and muscle side) on the neuromuscular response to spinal manipulation. The surface and indwelling electromyographies of 8 muscle sites were recorded during lumbar side-lying manipulations in 20 asymptomatic participants. The effects of the factors on the number of muscle responses and the muscle activity onset delays were compared using mixed-model linear regressions, effect sizes, and equivalence testing. The treatment factors did not reveal statistical differences between the manipulation sequences (first or second) or manipulation sites (L3 or SI) in the number of muscle responses (p = 0.11, p = 0.28, respectively), or in muscle activity onset delays (p = 0.35 p = 0.35, respectively). There were significantly shorter muscle activity onset delays in the multifidi compared to the superficial muscles (p = 0.02). A small effect size of side (d = 0.44) was observed with significantly greater number of responses (p = 0.02) and shorter muscle activity onset delays (p < 0.001) in the muscles on the left side compared to the right. The location, layer, and side of the neuromuscular responses revealed trends of decreasing muscle response rates and increasing muscle activity onset delays as the distance from the manipulation site increased. These results build on the body of work suggesting that the specificity of manipulation site may not play a role in the neuromuscular response to spinal manipulation—at least within the lumbar spine. In addition, these results demonstrate that multiple manipulations performed in similar areas (L3 and S1) do not change the response significantly, as well as contribute to the clinical understanding that the muscle response rate is higher and with a shorter delay, the closer it is to the manipulation. [ABSTRACT FROM AUTHOR]

When a muscle is stretched, sensory feedback not only causes reflexes but also leads to a depolarization of sensory afferents throughout the spinal cord (primary afferent depolarization, PAD), readying the whole limb for further disturbances. This sensoryevoked PAD is thought to be mediated by a trisynaptic circuit, where sensory input activates first-order excitatory neurons that activate GABAergic neurons that in turn activate GABAA receptors on afferents to cause PAD, though the identity of these firstorder neurons is unclear. Here, we show that these first-order neurons include propriospinal V3 neurons, as they receive extensive sensory input and in turn innervate GABAergic neurons that cause PAD, because optogenetic activation or inhibition of V3 neurons in mice mimics or inhibits sensory-evoked PAD, respectively. Furthermore, persistent inward sodium currents intrinsic to V3 neurons prolong their activity, explaining the prolonged duration of PAD. Also, local optogenetic activation of V3 neurons at one segment causes PAD in other segments, due to the long propriospinal tracts of these neurons, helping to explain the radiating nature of PAD. This in turn facilitates monosynaptic reflex transmission to motoneurons across the spinal cord. In addition, V3 neurons directly innervate proprioceptive afferents (including Ia), causing a glutamate receptor-mediated PAD (glutamate PAD). Finally, increasing the spinal cord excitability with either GABAA receptor blockers or chronic spinal cord injury causes an increase in the glutamate PAD. Overall, we show the V3 neuron has a prominent role in modulating sensory transmission, in addition to its previously described role in locomotion. NEW & NOTEWORTHY Locomotor-related propriospinal neurons depolarize sensory axons throughout the spinal cord by either direct glutamatergic axoaxonic contacts or indirect innervation of GABAergic neurons that themselves form axoaxonic contacts on sensory axons. This depolarization (PAD) increases sensory transmission to motoneurons throughout the spinal cord, readying the sensorimotor system for external disturbances. The glutamate-mediated PAD is particularly adaptable, increasing with either an acute block of GABA receptors or chronic spinal cord injury, suggesting a role in motor recovery. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to examine the effects of orally administered metoprolol on the frequency and severity of pain caused by rocuronium injection in patients who started to use and were currently using oral metoprolol for any reason such as ischemic heart disease, hypertension, and arrhythmias. Methods: Patients were evaluated in four groups. Group M: patients currently using metoprolol and who did not receive lidocaine before the application of rocuronium. Group ML: patients currently using metoprolol and who received lidocaine before rocuronium application. Group L: patients currently not using metoprolol and received lidocaine before rocuronium application. Group C: patients currently not using metoprolol and who did not receive lidocaine before rocuronium application. Following the induction of general anesthesia with thiopental sodium, a researcher blind to the groups observed the pain during rocuronium injection based on the following scale: (1) no reaction, (2) movement only in the ankle, (3) movement or withdrawal only in the arm (shoulder and ankle), and (4) diffuse reaction (movement or withdrawal in more than one extremity, coughing and holding breath). Results: Two hundred patients with 50 in each of four groups were included. The incidence of pain was statistically significantly lower in Group ML compared to Groups M and C (p = 0.001). The correlations between pain caused by rocuronium injection and duration of metoprolol usage and the time since the last dose were not statistically significant (for all, p > 0.05). Conclusions: Oral metoprolol combined with lidocaine reduced pain and withdrawal reflex caused by rocuronium injection. No significant difference was observed between the last dose and the duration of metoprolol usage. [ABSTRACT FROM AUTHOR]