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What is the central question of this study? We assessed the test-retest variability of respiratory chemoreflex characterization by Duffin's modified rebreathing method and explored whether signal averaging of repeated trials improves confidence in parameter estimation. What is the main finding and its importance? Modified rebreathing is a reproducible method to characterize responses of central and peripheral respiratory chemoreflexes. Signal averaging of multiple repeated tests minimizes within- and between-test variability, improves the confidence of chemoreflex characterization and reduces the minimal change in parameters required to establish an effect. Future experiments that apply this method might benefit from signal averaging to improve its discriminatory effect.We assessed the test-retest variability of central and peripheral respiratory chemoreflex characterization by Duffin's modified rebreathing method and explored whether signal averaging of repeated trials improves confidence in parameter estimation. Over four laboratory visits, 13 participants (mean ± SD age, 25 ± 5 years) performed six repetitions of modified rebreathing in isoxic-hypoxic conditions [end-tidal

The mechanisms of pain perception in individuals with masochistic behaviour (MB) remain poorly documented. We hypothesized that MB is associated with context-specific changes in descending pain modulation.We compared the effects of four standardized sets of images with positive (erotic), negative (mutilations), masochistic or neutral emotional valences on the RIII nociceptive reflex evoked by electrical stimulation of the sural nerve and recorded on the ipsilateral biceps femoris in 15 controls and 15 men routinely engaging in MB. We systematically assessed the RIII reflex threshold and recruitment curves (up to the tolerance threshold), thermal (heat and cold) pain thresholds measured on the upper and lower limbs and responses to the pain sensitivity questionnaire, to compare basal pain perception between our two groups of participants. We also assessed anxiety, depression, empathy, alexithymia, high sensation seeking and catastrophizing, to investigate their potential influence on the emotional modulation of pain.Thermal pain thresholds, RIII reflex recruitment curves, and responses to the psychological and pain sensitivity questionnaires were similar in the two groups. Neutral, positive and negative images modulated the RIII reflex similarly in the two groups. By contrast, masochistic images induced a significant (p lt; 0.01) decrease in RIII reflex responses in subjects with MB, whereas it tended to increase these responses in control subjects.Our data suggest that psychological profile, basal pain sensitivity and the emotional modulation of pain are normal in individuals with MB but that these subjects selectively engage descending pain inhibition in the masochistic context.Decrease pain perception related to masochistic behaviours is associated with specific activation of descending pain inhibition.

The efferent branches of the splanchnic sympathetic nerves that enhance interleukin-10 (IL-10) and suppress tumour necrosis factor-α (TNF) levels in the reflex response to systemic immune challenge were investigated in anaesthetized, ventilated rats. Plasma levels of TNF and IL-10 were measured 90 min after intravenous lipopolysaccharide (LPS, 60 µg/kg). Splanchnic nerve section, ganglionic blockade with pentolinium tartrate or β

Sometimes it is necessary to use sedatives or even general anaesthetics to examine animals with spinal cord injuries. These drugs may affect spinal reflexes, alter the outcome of neurological examinations, and make it difficult to diagnose location of the lesion.The aim of this study was to evaluate the effects of five pre-anaesthetic and anaesthetic agents commonly used in clinics on spinal reflexes in dogs.Ten native adult dogs were participated in three groups. In all groups, the dogs were premedicated with medetomidine and midazolam; then, in the first group, ketamine, in the second group, propofol and in the third group, isoflurane were used for induction of anaesthesia. The spinal reflexes were evaluated before injection, 15 min after medetomidine, 20 min after midazolam, and at 15, 30, 45 and 60 min after induction of anaesthesia.Medetomidine did not reduce monosynaptic reflexes (patellar and cranial tibial reflexes) but increased them while it had no effect on the polysynaptic limb withdrawal reflexes. Midazolam had no effect on the spinal reflexes; Ketamine did not affect the patellar, cranial tibial and extensor carpi radialis reflexes, but reduced polysynaptic pain-related reflexes; and propofol and isoflurane abolished the all spinal reflexes.Medetomidine, midazolam and ketamine have no effect on reducing monosynaptic reflexes (patellar and cranial tibial reflexes) and may be used for neurological examination of restless animals in the clinic. Propofol and isoflurane eliminated all spinal reflex responses and are not suitable for neurological examinations.

As suggested by this article, considerable advances in clinical management and research have taken place during the past 20 years. Although mechanisms underlying the pain syndrome CRPS I and CRPS II remain far from one's understanding, glimpses of the pathophysiology are beginning to take shape. There is now strong evidence that these syndromes exemplify a complex neurologic disease involving the brain at several integrated levels. The changes that occur in CRPS I patients involve somatosensory, sympathetic, and somatomotor systems. The diagnostic criteria have helped to focus on aspects of these foregoing systems and whereas there is no specific laboratory test for CRPS, enough is now known about the pathophysiology to use the following tests: quantitative sensory testing (QST), autonomic testing that include quantitative sudomotor axon reflex test (QSART) for sweating abnormalities, the cold pressor test in conjunction with thermographic imaging to observe the vasoconstrictor response, and laser Doppler flowmetry to monitor background vasomotor control. Recognition of a motor disorder requires accurate documentation and may be a component of the diagnostic criteria in the future. Until a better understanding of mechanistic overtones that would help to put in place mechanism-based therapeutic strategies, current management is built around a rehabilitation model. For this to be successful, as described in the foregoing pages, different non-interventional and interventional modalities are applied in a time-restricted manner to facilitate those modalities that favor progress in the treatment algorithm. As has been described, it is important when using physiotherapeutic maneuvers to minimize joint movement in the affected region to reduce the mechanorecpetor barrage and its increase in perceived pain to encourage and maintain a patient's compliance with their rehabilitation. Finally, of greater significance is the understanding that sympatholysis per se is not a "diagnostic" test for CRPS, but rather a useful procedure that may facilitate treatment for pain that is sympathetically maintained.

Reflex seizures are consistently evoked by a specific afferent stimulus or by patient activity. Patients experiencing reflex seizures when playing a game on a mobile phone are rarely reported. We describe a boy with reflex seizures after prolonged exposure to the game, Cut the rope, on his mobile phone. The video-EEG documented electroclinical events characterized by distal myoclonic jerks of the upper limbs, in combination with irregular, diffuse spike-and-wave and polyspike-and-wave discharges on EEG, followed by a tonic-clonic seizure. Playing video games on mobile phones may potentially induce reflex seizures, similar to other commonly used platforms such as docking stations connected to video screens.

This study aimed to assess the physiological response of patients with anorexia nervosa (AN) to different types of silhouettes using pupillometry.We measured the pupil psychosensory reflex (PSR) of 42 patients with AN and 35 healthy controls in response to standardised body silhouettes and to pictures of their own silhouettes digitally modified to represent different body mass indices (BMI). Perceptual distortion and body dissatisfaction were assessed using Anamorphic Micro Software©. Twenty-three of the recruited patients were tested up to four times during an inpatient treatment programme to assess the impact of weight gain.PSR correlated with the subjective rating of emotional arousal in controls but not in patients. Own silhouettes and standardised silhouettes triggered a different pupil response both in patients with AN and in controls. With pictures of their own silhouettes, pupil response to underweight stimuli differed from pupil response to normal weight or overweight stimuli in both groups. Weight gain was associated with an increase in PSR, an improvement of ideal BMI and a decrease of body dissatisfaction, but no change in perceptual distortion.Our findings support the idea that pupillometry could be a useful tool to assess the physiological state of patients with AN.

Understanding the contribution of the autonomic nervous system to cerebral blood flow (CBF) control is challenging, and interpretations are unclear. The identification of calcium channels and adrenoreceptors within cerebral vessels has led to common misconceptions that the function of these receptors and actions mirror those of the peripheral vasculature. This review outlines the fundamental differences and complex actions of cerebral autonomic activation compared to the peripheral circulation. Anatomical differences, including the closed nature of the cerebrovasculature, and differential adrenoreceptor subtypes, density, distribution and sensitivity, provide evidence that measures on peripheral sympathetic nerve activity cannot be extrapolated to the cerebrovasculature. Cerebral sympathetic nerve activity seems to act opposingly to the peripheral circulation, mediated at least in part by changes in intracranial pressure and cerebral blood volume. Additionally, heterogeneity in cerebral adrenoreceptor distribution highlights regional-specific autonomic regulation of CBF. Compensatory chemo- and autoregulatory responses throughout the cerebral circulation, and interactions with parasympathetic nerve activity are unique features to the cerebral circulation. This crosstalk between sympathetic and parasympathetic reflexes acts to ensure adequate perfusion of CBF to rising and falling perfusion pressures, optimising delivery of oxygen and nutrients to the brain, whilst attempting to maintain blood volume and intracranial pressure. Herein, we highlight the distinct similarities and differences between autonomic control of cerebral and peripheral blood flow, and the regional specificity of sympathetic and parasympathetic regulation within the cerebrovasculature. Future research directions are outlined with the goal to further our understanding of autonomic control of CBF in humans. This article is protected by copyright. All rights reserved.

A 10-year-old 466 kg mustang gelding presented to an equine referral hospital for surgical repair of nasal, frontal and lacrimal bone fractures from an unknown trauma. Surgical repair was performed under general anaesthesia, including a right-sided maxillary regional anaesthetic block with mepivacaine hydrochloride. Progressive hyperkalaemia was documented perianaesthetically (T-3 mins; 134 mins after induction; potassium 6.4 mmol/L (ref 3.5-5.1 mmol/L). Perianaesthetic bradycardia was attributed to alpha -2 agonist infusion administration, and other characteristic ECG changes (flattened P waves, narrow T waves of increased amplitude, prolonged QRS complex) were not documented. Asystole occurred 137 min after induction of anaesthesia; however, a review of the available literature suggests the degree of hyperkalaemia documented was unlikely to be the primary cause of asystole but may have been a contributing factor. It is hypothesised that a trigeminocardiac reflex was the primary contributory factor to asystole in the described case, and may represent a maxillomandibulocardiac reflex that has not been previously described in the horse.

BACKGROUND AND PURPOSE Lasmiditan is a novel selective 5-HT1F receptor agonist, recently approved for acute treatment of migraine. 5-HT1F receptors are widely expressed in the CNS and trigeminovascular system. Here, we have explored the therapeutic effects of 5-HT1F receptor activation in preclinical models of migraine and cluster headache. EXPERIMENTAL APPROACH Electrical stimulation of the dura mater or the superior salivatory nucleus in anaesthetised rats evoked trigeminovascular or trigeminal-autonomic reflex activation at the level of the trigeminocervical complex. Additionally, cranial autonomic manifestations in response to trigeminal-autonomic reflex activation were measured, via anterior choroidal blood flow alterations. These responses were then challenged with lasmiditan. We explored the tissue distribution of mRNA for 5-HT1F receptors in human post-mortem tissue and of several 5-HT1 receptor subtypes in specific tissue beds. KEY RESULTS Lasmiditan dose-dependently reduced trigeminovascular activation in a preclinical model of migraine. Lasmiditan also reduced superior salivatory nucleus-evoked activation of the trigeminal-autonomic reflex, but had no effect on cranial autonomic activation. mRNA profiling in human tissue showed expression of the 5-HT1F receptor in several structures relevant for migraine and cluster headache. CONCLUSION AND IMPLICATIONS Our data suggest that lasmiditan acts, at least in part, as an anti-migraine agent by reducing trigeminovascular activation. Furthermore, our results highlight a clear action for lasmiditan in a preclinical model of cluster headache. Given the proven translational efficacy of this model, our data support the potential utility of lasmiditan as a therapeutic option for the acute treatment of cluster headache attacks.

OBJECTIVE To describe acute cerebral compression caused by an epidural hematoma (EDH) in a dog with cryptococcal infection. CASE SUMMARY An 18-month-old neutered male Neapolitan Mastiff was found comatose with no preceding clinical signs apart from a mild forelimb lameness. A CT scan of the head revealed a lesion within the right caudal nasal cavity that traversed the cribriform plate in addition to a right epidural lesion resulting in compression of the right cerebrum. Assessment of brain death was made based on the presence of coma, apnea, and absence of brain stem reflexes and included assessment of the vestibulo-ocular reflex. Postmortem identified a large EDH causing marked compression of the right frontal lobe. A nasal biopsy cultured Cryptococcus gattii. NEW OR UNIQUE INFORMATION PROVIDED EDH formation in a dog secondary to cryptococcosis has not been previously reported. This is also the first time a caloric vestibulo-ocular reflex assessment has been reported in a dog.

BACKGROUND AND PURPOSE The purpose of this study was to determine the role of NaV 1.7 in action potential conduction in C-fibres in the bronchial branches of the human vagus nerve. EXPERIMENTAL APPROACH Bronchial branches of the vagus nerve were dissected from human donor tissue. The C-wave of the electrically evoked compound action potential was quantified in the absence and presence of increasing concentrations of the selective NaV 1.7 blocking drugs, PF-05089771 and ST-2262, as well as the NaV 1.1, 1.2, and 1.3 blocking drug ICA121-431. The efficacy and potency of these inhibitors were compared to the standard NaV 1 blocker, tetrodotoxin. We then compared the relative potencies of the NaV 1 blockers in inhibiting the C-wave of the compound action potential, with their ability to inhibit parasympathetic cholinergic contraction of human isolated bronchi, a response previously shown to be strictly dependent on NaV 1.7 channels. KEY RESULTS The selective NaV 1.7 blockers inhibited the C-wave of the compound action potential with potencies similar to that observed in the NaV 1.7 bronchial contractions assay. Using rt-PCR, we noted that NaV 1.7 mRNA was strongly expressed and transported down the vagus nerve bundles. CONCLUSIONS AND IMPLICATIONS NaV 1.7 blockers can prevent action potential conduction in the majority of vagal C-fibres arising from human bronchi. Blockers of NaV 1.7 channels may therefore have value in inhibiting the responses to excessive airway C-fibre activation in inflammatory airway disease, responses that include coughing as well as reflex bronchoconstriction and secretions.

INTRODUCTION/AIMS Motion artifact signals (MASs) created by the relative movement of intramuscular wire electrodes are an indicator of the mechanical stimulus arrival time to the muscle belly. This study proposes a method that uses wire electrodes as an intramuscular mechanosensor to determine the stretch reflex (SR) latency without lag time. METHODS Gastrocnemius SR was induced by tendon tap, heel tap, and forefoot tap. The MASs recorded by intramuscular wire electrodes were extracted from background electromyographic activity using the spike-triggered averaging technique. Simultaneous recordings were obtained from multiple sites to validate the MAS technique. RESULTS Using intramuscular wire electrodes, the MASs were successfully determined and extracted for all stimulus sites. In the records from the rectus femoris, MASs were also successfully extracted; thus, the reflex latency could be calculated. DISCUSSION Wire electrodes can be used as an intramuscular mechanosensor to determine the mechanical stimulus arrival time to the muscle belly.

Background We aim to determine the clinical utility of reflex coagulation investigations (RCI) for prolonged lupus insensitive activated partial thromboplastin time (aPTT) at our institution. Methods We retrospectively reviewed all potential RCI (lupus insensitive aPTT of ≥32s) from April 2014 to June 2019. Our diagnostic algorithm requires completion of RCI only if samples had no interfering medications to explain a prolonged aPTT and were either from a preoperative sample or from a patient presenting with unexplained bleeding. Appropriate RCI samples undergo further investigations with one-stage factor activity testing for factors 8(FVIII), 9(FIX), and 11(FXI) reflexively. Data were obtained through electronic medical records to capture clinical characteristics, laboratory findings, prophylactic hemostatic replacement, and bleeding outcomes. Results Three thousand and three hundreds seventeen samples from 2940 distinct patients were considered as potential RCI during the study period. 263/3317 (8%) samples had RCI completed. Of those, 55/263 (21%) had abnormal factor testing, with the majority from preoperative setting (43/55; 78%). 5/43 (12%) patients were referred to hematology for preoperative evaluation. 5/43 patients received preoperative hemostatic support. A total of 5 patients (5/43) developed postop bleeding. Six patients (6/55) had RCI for unexplained bleeding, and five patients (83%) had a newly identified clinically significant bleeding disorder. Conclusion Reflex coagulation investigations benefited patients presenting with unexplained bleeding as this expedited the diagnosis and management of clinically significant bleeding disorders. RCI for preoperative evaluation infrequently led to additional hemostatic support/referral to hematology. The lack of additional workup for an abnormal factor activity level suggests laboratory alert fatigue as a potential contributory factor.

BACKGROUND Axo-axonic contacts onto central terminals of primary afferents modulate sensory inputs to the spinal cord. These contacts produce primary afferent depolarization (PAD), which serves as a mechanism for presynaptic inhibition, and also produce dorsal root reflexes (DRRs), which may regulate the excitability of peripheral terminals and second order neurons. We aimed to identify changes in these responses as a consequence of peripheral inflammation. METHODS In vitro spinal cord recordings of spontaneous activities in dorsal and ventral roots were performed in control mice and following paw inflammation. We also used pharmacological assays to define the neurotransmitter systems implicated in such responses. RESULTS Paw inflammation increased the frequency and amplitude of spontaneous dorsal root depolarizations, the occurrence of DRRs and the amplitude of ventral roots depolarizations. PAD was classified in two different patterns based on their relation to ventral activity: time-locked and independent events. Both patterns increased in amplitude after paw inflammation, and independent events also increased in frequency. The circuits that were responsible for this activity implicated both glutamatergic and GABAergic transmission. Adrenergic modulation differentially affected both types of PAD, and this modulation changed after paw inflammation. CONCLUSIONS Our findings suggest the existence of independent spinal circuits at the origin of PAD and DRRs. Inflammation modulates these circuits differentially, unveiling varied mechanisms of spinal sensitization. This in vitro approach provides an isolated model for the study of the mechanisms of central sensitization and for the performance of pharmacological assays with the purpose of identifying and testing novel antinociceptive targets. SIGNIFICANCE Spinal circuits modulate activity of primary afferents acting on central terminals. Under in vitro conditions, dorsal roots show spontaneous activity in the form of depolarizations and action potentials. Our findings are consistent with the existence of several independent generator circuits. Experimental paw inflammation reduced mechanical withdrawal threshold and significantly increased the spontaneous activity of dorsal roots, which may be secondary to an enhanced output of spinal generators. This can be considered as a novel sign of central sensitization.

PURA syndrome is a distinct form of developmental encephalopathy, characterized by early-onset hypotonia, severe developmental delay, intellectual disability, epilepsy and respiratory and gastrointestinal disorders. We report a child with PURA syndrome, harbouring a previously described mutation, whose phenotype included two peculiar aspects: (1) hypokinetic-rigid syndrome, which was part of the clinical presentation from an early stage of the disease, and (2) reflex seizures, consisting of a series of spasms. We provide detailed clinical description and video recordings demonstrating both these aspects that are newly described in PURA syndrome. The early clinical features described here may therefore be included in the complex phenotype associated with PURA gene mutations and may help in the early diagnosis of patients. Furthermore, PURA syndrome should be considered in the differential diagnosis of early-onset bradykinetic rigid syndromes.

The association of musicogenic epilepsy (ME) with antibodies against glutamic decarboxylase (GAD) supports autoimmune workups for these patients. No appropriate treatment has been established for ME; therefore, immunotherapy should be considered for patients who become drug‐resistant. The connection between neurological manifestations and antibodies against GAD, a rate‐limiting enzyme that helps create the inhibitory neurotransmitter gamma‐aminobutyric acid, has been well established. Furthermore, a strong correlation has been found between ME and the temporal lobe. However, its connection with anti‐GAD antibodies is still unclear. This paper reports on a 50‐year‐old right‐handed female who has had ME symptoms for 14 years and been found to be anti‐GAD antibody–positive. Therefore, we will elaborate on the relation between ME and anti‐GAD antibodies.

AIMS Detrusor underactivity (DU) is an understudied health concern with inadequate clinical management. The pathophysiology of DU is unclear, and current therapies fail to improve symptoms. The current studies characterized voiding function and contractility of bladder and urethral tissues in a novel rat model of DU. METHODS Female obese prone (OP) and obese resistant (OR) rats were fed a 60 kcal% fat diet at 8 weeks old. A subset of rats (n = 4/strain) underwent uroflowmetry biweekly for 18 weeks in metabolic cages. At 40-56 weeks old, rats (n = 9-10/strain) underwent instrumented cystometry under urethane anesthesia. Following cystometry, bladder and urethral tissues (n = 8-9/strain) were harvested for in vitro assessments of contractility in response to carbachol, electric field stimulation, atropine, alpha, beta-methylene ATP, and caffeine. RESULTS OP rats exhibited increased urinary frequency (p = 0.0031), decreased voided volume (p = 0.0093), and urine flow rate (p = 0.0064) compared to OR rats during uroflowmetry. Bethanechol (10 mg/kg) did not alter uroflowmetry parameters. During cystometry, OP rats exhibited decreased bladder emptying efficiency (p

Objectives/hypothesis To develop a method for threshold estimation of the laryngeal adductor reflex (LAR) response using Cheung-Bearelly monofilaments. Study design Cross-sectional. Methods Twenty-two healthy adults (12 men, 10 women) were tested for LAR response outcome using 30 mm 5-0 and 4-0 nylon monofilaments. Tactile stimuli were delivered to the aryepiglottic (AE) fold and medial pyriform sinus (MPS). Dichotomous classifier features and performance (area under the curve (AUC)), the LAR response outcome agreement and disagreement matrix, and test-retest reliability were examined. From those data, a test protocol that would minimize patient burden to estimate the LAR triggering threshold was formulated. Results Classifier performance of 5-0 monofilament stimulation of the AE fold (sensitivity = 0.63, specificity = 0.63, PPV = 0.74, NPV = 0.25) and MPS (sensitivity = 0.45, specificity = 0.77, PPV = 0.74, NPV = 0.23,) was slightly below that of 4-0 monofilament stimulation of the AE fold (sensitivity = 0.82, specificity = 0.50, PPV = 0.82, NPV = 0.50) and MPS (sensitivity = 0.84, specificity = 0.64, PPV = 0.90, NPV = 0.56), based on AUC. LAR response outcome agreement for 5-0 and 4-0 stimulations was high (93%) for 5-0 positive response, but low (29%) for 5-0 negative response. Aesthesiometer test-retest reliability for LAR response outcome was excellent (Cronbach's alpha = 0.97). Conclusions Threshold estimation of the LAR response may be operationalized by adopting a decision tree protocol. For negative LAR response to initial 5-0 monofilament stimulation and positive response to subsequent 4-0 monofilament stimulation, the higher threshold is confirmed. Positive LAR response to 5-0 or 4-0 monofilament stimulation is expected in over 90% of asymptomatic adults. Negative LAR response to 4-0 monofilament stimulation identifies patients at risk for laryngopharyngeal hyposensitivity. Level of evidence 3b Laryngoscope, 2021.

Aim To examine outcomes in women following cervical screening detection of oncogenic human papillomavirus (HPV), with reflex cytology showing possible high-grade squamous intraepithelial lesion (pHSIL). Materials and methods A retrospective observational study of 523 women seen in the Royal Women's Hospital Colposcopy Clinic from 1 January 2018 to 31 July 2020. Results Two hundred eighty-two (53.9%) women had histology-confirmed HSIL, encompassing CIN2 or worse (CIN2+), including seven cancers (1.3%) and two adenocarcinoma in situ (AIS) (0.4%). In 81.2% (229/282) of women with CIN2+, this was detected on cervical biopsy at initial colposcopy, with another 8.9% (25/282) of CIN2+ detected at cervical excision following initial colposcopy and the remaining 9.9% (28/282) at follow-up colposcopy thereafter. When discordant cervical biopsy results were discussed at multidisciplinary meeting (MDM), 66.7% of women with pHSIL cytology upgraded to definite HSIL were found to have CIN2+, but only 20.8% when pHSIL cytology was retained and none when downgraded to low-grade (LSIL) or normal. No significant difference was found in the proportion of CIN2+ based on patient age above or below 40, HPV16 and/or 18 versus non 16/18, or whether discordant findings were reviewed at MDM. Conclusions We propose a pathway for management of women with positive oncogenic HPV and reflex pHSIL cytology. MDM review is recommended when CIN2+ is not identified on cervical biopsy at initial colposcopy. Conservative management is safe with low risk of CIN2+ when LBC prediction of pHSIL is confirmed or downgraded at MDM with no high-grade change on colposcopy or repeat cytology.

The study of cardiovascular function with galvanic vestibular stimulation has provided evidence on the neural structures that are involved in the vestibulo-autonomic reflex. This study determined if the effect on heart rate using galvanic vestibular stimulation persists after provoking a sympathetic response and if this response differs when using unilateral or transmastoid (bilateral) stimulation. We analysed heart rate and heart rate variability using unilateral and transmastoid galvanic vestibular stimulation combined with cardiovascular reflex evoked by postural change in 24 healthy human subjects. Three electrode configurations were selected for unilateral stimulation considering the anatomical location of each semicircular canal. We compared recordings performed in seated and standing positions, and with unilateral and transmastoid stimulation. With subjects seated, a significant transient decrease in heart rate was observed with unilateral stimulation. With transmastoid stimulation, heart rate decreased in both seated and standing positions. Average intervals between normal heartbeats recorded with stimulation resemble parasympathetic cardiac function induced by auricular vagal nerve stimulation. Our results indicate that unilateral stimulation does not eliminate the natural heart rate increase caused by orthostatic hypotension. In contrast, transmastoid stimulation provoked a transient reduction in heart rate, even when subjects were standing. These responses should be considered while performing experiments with galvanic vestibular stimulation and subsequent effects in cardiac regulation mechanisms.

OBJECTIVES/HYPOTHESIS Tinnitus can develop due to, or be aggravated by, stress in a rat model. To investigate stress as a possible causal factor in the development of tinnitus, we designed an animal study that included tinnitus behavior and excitatory/inhibitory neurotransmitter expression after noise exposure as well as restraint stress. STUDY DESIGN An experimental animal study. METHODS Wistar rats were grouped according to single or double exposure to noise and restraint stress. The noise exposure (NE) group was subjected to 110 dB sound pressure level (SPL) of 16 kHz narrow-band noise (NBN) for 1 hour, and the restraint stress (RS) group was restrained for 1 hour with or without noise exposure. Gap prepulse inhibition of the acoustic startle (GPIAS) reflex was measured at an NBN of 16 kHz to investigate tinnitus development. Various immunohistopathologic and molecular biologic studies were undertaken to evaluate possible mechanisms of tinnitus development after noise and/or restraint stress. RESULTS The RS-only group showed a reduced GPIAS response, which is a reliable sign of tinnitus development. In the double-stimulus groups, more tinnitus-development signs of reduced GPIAS responses were observed. The expression of γ-aminobutyric acid A receptor α1 (GABAAR α1) in the hippocampus decreased in the NE│RS group. Increased N-methyl-d-aspartate receptor1 intensities in the NE│RS group and decreased GABAAR α1 intensities in the RS and NE│RS groups were observed in the CA3 region of the hippocampus. CONCLUSIONS Tinnitus appeared to develop after stress alone in this animal study. An imbalance in excitatory and inhibitory neurotransmitters in the hippocampus may be related to the development of tinnitus after acute NE and/or stress. LEVEL OF EVIDENCE NA Laryngoscope, 131:2332-2340, 2021.

Key points We examined the influence of cutaneous feedback from the heel and metatarsal regions of the foot sole on the soleus stretch reflex pathway during standing. We found that heel electrical stimuli suppressed and metatarsal stimuli enhanced the soleus vibration response. Follow-up experiments indicated that the interaction between foot sole cutaneous feedback and the soleus vibration response was likely not mediated by presynaptic inhibition and was contingent upon a modulation at the ⍺-motoneuron pool level. The spatially organized interaction between cutaneous feedback from the foot sole and the soleus vibration response provides information about how somatosensory information is combined to appropriately respond to perturbations during standing. Abstract Cutaneous feedback from the foot sole provides balance-relevant information and has the potential to interact with spinal reflex pathways. In this study, we examined how cutaneous feedback from the foot sole (heel and metatarsals) influenced the soleus response to proprioceptive stimuli during standing. We delivered noisy vibration (10-115 Hz) to the right Achilles tendon while we intermittently applied electrical pulse trains (five 1-ms pulses at 200 Hz, every 0.8-1.0 s) to the skin under either the heel or the metatarsals of the ipsilateral foot sole. We analysed time-dependent (referenced to cutaneous stimuli) coherence and cross-correlations between the vibration acceleration and rectified soleus EMG. Vibration-EMG coherence was observed across a bandwidth of ∼10-80 Hz, and coherence was suppressed by heel but enhanced by metatarsal cutaneous stimuli. Cross-correlations showed soleus EMG was correlated with the vibration (∼40 ms lag) and cross-correlations were also suppressed by heel (from 104-155 ms) but enhanced by metatarsal (from 76-128 ms) stimuli. To examine the neural mechanisms mediating this reflex interaction, we conducted two further experiments to probe potential contributions from (1) presynaptic inhibition, and (2) modulations at the ⍺- and γ-motoneuron pools. Results suggest the cutaneous interactions with the stretch reflex pathway required a modulation at the ⍺-motoneuron pool and were likely not mediated by presynaptic inhibition. These findings demonstrate that foot sole cutaneous information functionally tunes the stretch reflex pathway during the control of upright posture and balance.

Key points During exercise, bradykinin (BK), a muscle metabolite in ischaemic muscles, exaggerates autonomic responses to activation of muscle afferent nerves in peripheral artery disease (PAD). We examined whether BK inhibits activity of KV 4 channels in muscle afferent neurons of PAD rats induced by femoral artery occlusion. We demonstrated that: 1) femoral occlusion attenuates KV 4 currents in dorsal root ganglion (DRG) neurons innervating the hindlimb muscles and decreases the threshold of action potential firing; 2) BK has a greater inhibitory effect on KV 4 currents in muscle DRG neurons of PAD rats; and 3) expression of KV 4.3 is downregulated in DRGs of PAD rats and inhibition of KV 4.3 significantly decreases activity of KV 4 currents in muscle DRG neurons. Femoral artery occlusion-induced limb ischaemia and/or ischaemia-induced metabolites (i.e. BK) inhibit activity of KV 4 channels in muscle afferent neurons and this is likely involved in the exaggerated exercise pressor reflex in PAD. Abstract Muscle afferent nerve-activated reflex sympathetic nervous and blood pressure responses are exaggerated during exercise in patients with peripheral artery diseases (PAD) and in PAD rats induced by femoral artery occlusion. However, the precise signalling pathways and molecular mediators responsible for these abnormal autonomic responses in PAD are poorly understood. A-type voltage-gated K+ (KV ) channels are quintessential regulators of cellular excitability in the various tissues. Among KV channels, KV 4 (i.e. KV 4.1 and KV 4.3) in primary sensory neurons mainly participate in physiological functions in regulation of mechanical and chemical sensation. However, little is known about the role of KV 4 in regulating neuronal activity in muscle afferent neurons of PAD. In addition, bradykinin (BK) is considered as a muscle metabolite contributing to the exaggerated exercise pressor reflex in PAD rats with femoral artery occlusion. Our data demonstrated that: 1) KV 4 currents are attenuated in dorsal root ganglion (DRG) neurons innervating the hindlimb muscles of PAD rats, along with a decreasing threshold of action potential firing; 2) KV 4 currents are inhibited by application of BK onto muscle DRG neurons of PAD rats to a greater degree; and 3) expression of KV 4.3 is downregulated in the DRGs of PAD rats and KV 4.3 channel is a major contributor to the activity of KV 4 currents in muscle DRG neurons. In conclusion, data suggest that femoral artery occlusion-induced limb ischaemia and/or ischaemia-induced metabolites (i.e. BK) inhibit the activity of KV 4 channels in muscle afferent neurons likely leading to the exaggerated exercise pressor reflex observed in PAD.

Esophageal distal baseline impedance (DBI) is an indicator of mucosal integrity; lower values suggest increased permeability. Aims were to characterize the (1) effect of DBI category (900 Ω, 900-2000 Ω, and 2000 Ω) on sensory-motor characteristics of mid-esophageal provocation-induced motility reflexes, and (2) clinical outcomes among high-risk human infants evaluated for gastroesophageal reflux disease. Symptomatic infants (N = 49, 41 ± 3 weeks postmenstrual age) underwent pH-impedance testing to characterize acid reflux index (ARI) and DBI, and pharyngo-esophageal manometry to examine upper esophageal sphincter (UES), peristaltic, and lower esophageal sphincter (LES) functions. Sensory-motor response characteristics included response threshold (ml), occurrence (%), latency (s), duration (s), and magnitude (mmHg) upon mid-esophageal stimulations (0.1-2.0 ml of air, water, and apple juice). Motility and clinical outcomes were compared among DBI groups. In infants with DBI900 Ω and 900-2000 Ω (vs.2000 Ω): (a) Long-term feeding milestones did not differ (p 0.05); (b) complete peristaltic propagation decreased in 900-2000 Ω (p 0.05), polymorphic waveforms increased in900 Ω and 900-2000 Ω (p 0.05); (c) media effects were noted with liquids (vs. air) wherein UES and esophageal contractility were prolonged in900 Ω and 900-2000 Ω (p 0.05), and esophageal sensitivity heightened for900 Ω with water and for 900-2000 Ω with air (both p 0.05). ARI was not correlated with DBI in infants with chronic lung disease (r = 0.05, p = 0.82). We conclude that pharyngo-esophageal motility sensory-motor characteristics in infants are modified by DBI category. These preliminary findings pave-the-way for further physiological testing in convalescing high-risk infants to ascertain potential mechanisms of airway-digestive reflex interactions and symptom generation, which may lead to targeted therapies.

Non-invasive techniques are scarce with which human (motor) cortical mechanisms can be investigated. In a series of previous experiments, we have applied an advanced form of conditioning technique with transcranial magnetic stimulation (TMS) and peripheral nerve stimulation by which excitability changes at the laminar level in the primary motor cortex can be estimated. This method builds on the assumption that the first of subsequent corticospinal waves from TMS which is assessed with H-reflexes (called early facilitation) results from indirect excitation of corticospinal neurons in motor cortex (I-wave) and not direct excitation of corticospinal axons (D-wave). So far, we have not provided strong experimental evidence that this is actually the case. In the present study, we therefore compared temporal differences of the early facilitation between transcranial magnetic and electrical stimulation (TES). TES is known to excite the axons of corticospinal neurons. TES in our study caused a temporal shift of the early facilitation of H-reflexes in all subjects compared to TMS, which indicates that the early facilitation with TMS is indeed produced by an I-wave. Additionally, we investigated temporal shifts of the early facilitation with different TMS intensities and two TMS coils. It has long been known that TMS with higher intensities can induce a D-wave. Accordingly, we found that TMS with an intensity of 150 % of resting motor threshold compared to 130 %/110 % results in a temporal shift of the early facilitation, indicating the presence of a D-wave. This effect was dependent on the coil type.

Background Primary human papillomavirus (HPV) screening was introduced in Australia in December 2017. Aims Outcomes for women after positive HPV in their cervical screening test (CST). Materials and methods A retrospective observational study of 4458 women seen at the Royal Women's Hospital Colposcopy Clinic from 1 January 2018 to 31 July 2020. Results HPV16/18 was positive (considered higher-risk CST) in 42.2% of women in the study, 16.6% with reflex possible with high-grade squamous intraepithelial lesions (pHSIL) or worse and 54.9% with normal cytology. There were 24.8% of women with positive HPV16/18 who had histological confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+), 10.3% CIN2+ (including six cancers) among women with reflex negative cytology and 87.7% CIN2+ among women with reflex HSIL cytology. In women with positive HPV (not 16/18), CIN2+ was found in 60.2% with reflex pHSIL or worse cytology (higher risk) and 10.2% with reflex low-grade SIL (LSIL) or normal cytology (intermediate risk). Median waiting time to colposcopy with the intermediate-risk group went up to 181 days. Our colposcopists were able to achieve a positive predictive value (PPV) for CIN2+ of 69.9%, higher than 57.8% PPV in the National Cervical Screening Program (NCSP) 2020 monitoring report. Women with type 3 transformation zone on colposcopy could be followed up with CST if no HSIL was suspected on screening or at colposcopy as their risk of CIN2+ was only 2.5%. Conclusions Our findings support direct referral to colposcopy for women with higher-risk CST, with all cancers confined to this group. The NCSP recommendation to refer for colposcopy only after three intermediate-risk CST will need monitoring with the LSIL triage group.

Neural circuits underlying reflex and rhythmic behaviours in molluscs can be understood at the level of single identified neurons. Using these systems, the most important advances have been made in the understanding of the cellular and molecular basis of learning and memory. Keywords: molluscs; nervous systems; neurons; behaviour; learning

Arousal from sleep in response to CO2 is a life-preserving reflex that enhances ventilatory drive and facilitates behavioural adaptations to restore eupnoeic breathing. Recurrent activation of the CO2 -arousal reflex is associated with sleep disruption in obstructive sleep apnoea. In this review we examine the role of chemoreceptors in the carotid bodies, the retrotrapezoid nucleus and serotonergic neurons in the dorsal raphe in the CO2 -arousal reflex. We also provide an overview of the supra-medullary structures that mediate CO2 -induced arousal. We propose a framework for the CO2 -arousal reflex in which the activity of the chemoreceptors converges in the parabrachial nucleus to trigger cortical arousal.

The aim of the study was to describe the electroclinical features of visual sensitivity in patients with familial cortical myoclonic tremor and epilepsy. We searched the EEG database using the terms "familial cortical myoclonic tremor and epilepsy" and "visual sensitivity" over a seven-year period from March 2013 to April 2020 in the Xijing hospital, Xi'an, China. The inclusion criteria were demonstrable electroclinical visual sensitivity in the form of eye-opening sensitivity, eye-closure sensitivity, eyes-closed sensitivity and photosensitivity. Clinical, EEG and imaging records of patients were screened, and subsequently, detailed analysis of their data was undertaken. We enrolled six patients with visual sensitivity, five of whom suffered with rare generalized tonic-clonic seizures. Neuroimaging was negative in all cases. All patients demonstrated photosensitivity; eye-opening sensitivity associated with cortical myoclonic in one patient, eyes-closed sensitivity associated with cortical myoclonic tremor status in three patients, and eye-closure sensitivity in two patients. At the last follow-up visit, cortical myoclonic tremor and epilepsy in all patients was well controlled with first-line treatment. Visual sensitivity is therefore likely to be an important reflex trait in some patients with familial cortical myoclonic tremor and epilepsy, and should be routinely evaluated in order to better define the electroclinical features in FCMTE syndrome. [Published with video sequences].

The purpose of this study was to investigate changes in muscle spindle sensitivity with early and late soleus reflex responses via tendon taps and transcranial magnetic stimulation, respectively, after an acute bout of prolonged static plantar flexor muscle stretching. Seventeen healthy males were tested before and after 5 min (5 × 60-s stretches) of passive static stretching of the plantar flexor muscles. Maximal voluntary isometric torque and M wave-normalized triceps surae muscle surface electromyographic activity were recorded. Both soleus tendon reflexes, evoked by percussion of the Achilles tendon during rest and transcranial magnetic stimulation-evoked soleus late responses during submaximal isometric dorsiflexion were also quantified. Significant decreases in maximal voluntary isometric plantar flexion torque (-19.2 ± 13.6%, p = .002) and soleus electromyographic activity (-20.1 ± 11.4%, p .001) were observed immediately after stretching, and these changes were highly correlated (r = 0.76, p .001). No changes were observed in tendon reflex amplitude or latency or peak muscle twitch torque (p .05). Significant reductions in soleus late response amplitudes (-46.9 ± 36.0%, p = .002) were detected, although these changes were not correlated with changes in maximal electromyographic activity, torque or tendon reflex amplitudes. No changes in soleus late response latency were detected. In conclusion, impaired neural drive was implicated in the stretch-induced force loss; however, no evidence was found that this loss was related to changes in muscle spindle sensitivity. We hypothesize that the decrease in soleus late response indicates a stretch-induced reduction in a polysynaptic postural reflex rather than spindle reflex sensitivity.

Background The reflex zone stimulation technique (RST) activates complex motor responses and has a positive impact on the locomotor system. This technique may also indirectly affect breathing; however, the use of this technique as adjunct of the treatment of cystic fibrosis (CF) has not yet been characterised. Methods We performed a randomised controlled single-centre interventional trial to evaluate the short-term effects of RST on lung function in 21 paediatric CF patients with normal baseline spirometry. The effect of 30 min of RST was compared to that of sham therapy in a crossover design. The interventions were performed in random order and planned 6 months apart. The primary outcome was a change in global ventilation inhomogeneity after intervention, assessed by lung clearance index (LCI2.5 ) derived from a nitrogen multiple breath washout test. Secondary outcomes included changes in regional ventilation inhomogeneity (indices of acinar [Sacin*Vt] and conductive airway [Scond*Vt] inhomogeneity) and spirometry parameters (inspiratory capacity, forced vital capacity, and forced expiratory volume in 1 s). Trunk deformity was assessed by physiotherapists at study entry. Results After the RST intervention, the LCI2.5 (p = .004) and Scond*Vt (p = .009) decreased significantly, while inspiratory capacity increased (p = .012). In the sham-therapy group, none of the parameters changed significantly. Trunk deformity was seen in 76.5% of all patients, and 92.9% of those with trunk deformity showed a decrease in LCI2.5 after RST. Conclusion RST has multiple positive short-term effects on lung function, especially in CF patients with trunk deformities.

NEW FINDINGS What is the central question of this study? Auditory stimulation produces a response in different physiological systems: cardiac, peripheral blood flow, electrodermal, cortical and peripheral haemodynamic responses and auditory event-related potentials. Do all these subsystems covary when responding to auditory stimulation, suggesting a unified locus of control, or do they not covary, suggesting independent loci of control for these physiological responses? What is the main finding and its importance? Auditory sensory gating reached a fixed level of neural activity independently of the intensity of auditory stimulation. The use of multivariate techniques revealed the presence of different regulatory mechanisms for the different physiologically recorded signals. ABSTRACT We studied the effects of an increasing amplitude of auditory stimulation on a variety of autonomic and CNS responses and their possible interdependence. The subjects were stimulated with an increasing amplitude of auditory tones while the auditory event-related potentials (ERPs), the cortical and extracerebral functional near-infrared spectroscopy (fNIRS) signal of standard and short separation channel recordings, the peripheral pulse measured by photoplethysmography, heart rate and electrodermal responses were recorded. Trials with eight tones of equal amplitude were presented. The results showed a parallel increase of activity in ERPs, fNIRS and peripheral responses with the increase in intensity of auditory stimulation. The ERPs, measured as peak-to-peak N1-P2, showed an increase in amplitude with auditory stimulation and a high attenuation from the first presentation with respect to the second to eighth presentations. Peripheral signals and standard and short channel fNIRS responses showed a decrease in amplitude in the high-intensity auditory stimulation conditions. Principal components analysis showed independent sources of variance for the recorded signals, suggesting independent control of the recorded physiological responses. The present results suggest a complex response associated to the increase of auditory stimulation with a fixed amplitude for ERPs, and a decrease in the peripheral and cortical haemodynamic response, possibly mediated by activation of the sympathetic nervous system, constituting a defensive reflex to excessive auditory stimulation.

Objectives Both detrusor underactivity (DU) and bladder outlet obstruction are the common causes of chronic urinary retention. Some novel treatment approaches focus on modulating micturition reflex and external urethral sphincter (EUS) function. This study used electrophysiologic (EP) studies to investigate the micturition reflex and EUS conditions of chronic urinary retention patients. Methods Sixty patients with urodynamic DU and chronic urinary retention were studied using (1) bulbocavernous reflex (BCR) by electric stimulation, (2) electromyography (EMG) of the EUS, and (3) nerve conduction velocity (NCV) studies of the pudendal nerve. The EP findings were analyzed in DU patients with different etiologies. Results The BCR was positive in 41.7% of patients. In EMG studies, denervation, reinnervation, and reduced recruitment of the EUS were observed in 21.7%, 71.7%, and 88.3% patients, respectively. Decreased amplitude of pudendal nerve conduction in NCV studies was noted in 73.3% of patients. Patients with sacral neuropathy had a lower BCR positive rate (p = 0.001), a nonsignificant but higher denervation rate (p = 0.059) in EMG studies, and a higher rate of decreased amplitude in NCV (p = 0.011) than those without sacral neuropathy. Excluding patients with sacral neuropathy or diabetes mellitus, a high percentage of neurologic deficits was still detected in EP studies. Conclusions Chronic urinary retention patients with urodynamic DU not only have bladder dysfunction, but also potential neuropathy in the sacral reflexes, pudendal nerve, or urethral sphincter innervation. The neurologic deficits explored in EP studies may affect the decision-making around the therapy to restore the voiding function in DU.

Objective To test the hypothesis that death with physiological parallels to human cases of sudden unexpected death in epilepsy (SUDEP) can be induced in seizing rats by ictal activation of oxygen-conserving reflexes (OCRs). Methods Urethane-anesthetized female Long-Evans rats were implanted with electrodes for electrocardiography (ECG), electrocorticography (ECoG), and respiratory thermocouple; venous and arterial cannulas; and a laryngoscope guide and cannula or nasal cannula for activation of the laryngeal chemoreflex (LCR) or mammalian diving reflex (MDR), respectively. Kainic acid injection, either systemic or into the ventral hippocampus, induced prolonged acute seizures. Results Reflex challenges during seizures caused sudden death in 18 of 20 rats-all MDR rats (10) and all but two LCR rats (8) failed to recover from ictal activation of OCRs and died within minutes of the reflexes. By comparison, 4 of 4 control (ie, nonseizing) rats recovered from 64 induced diving reflexes (16 per rat), and 4 of 4 controls recovered from 64 induced chemoreflexes (16 per rat). Multiple measures were consistent with reports of human SUDEP. Terminal central apnea preceded terminal asystole in all cases. Heart and respiratory rate fluctuations that paralleled those seen in human SUDEP occurred during OCR-induced sudden death, and mean arterial pressure (MAP) was predictive of death, showing a 17 or 15 mm Hg drop (MDR and LCR, respectively) in the 20 s window centered on the time of brain death. OCR activation was never fatal in nonseizing rats. Significance These results present a method of inducing sudden death in two seizure models that show pathophysiology consistent with that observed in human cases of SUDEP. This proposed mechanism directly informs previous findings by our group and others in the field; provides a repeatable, inducible animal model for the study of sudden death; and offers a potential explanation for observations made in cases of human SUDEP.

Objective To evaluate the efficacy of three different carrier screening workflows designed to identify couples at risk for having offspring with autosomal recessive conditions. Methods Partner testing compliance, unnecessary testing, turnaround time, and ability to identify at‐risk couples (ARCs) were measured across all three screening strategies (sequential, tandem, or tandem reflex). Results A total of 314,100 individuals who underwent carrier screening were analyzed. Sequential, tandem, and tandem reflex screening yielded compliance frequencies of 25.8%, 100%, and 95.9%, respectively. Among 14,595 couples tested in tandem, 42.2% of females were screen‐negative, resulting in unnecessary testing of the male partner. In contrast, less than 1% of tandem reflex couples included unnecessary male testing. The median turnaround times were 29.2 days (sequential), 8 days (tandem), and 13.3 days (tandem reflex). The proportion of ARCs detected per total number of individual screens were 0.5% for sequential testing and 1.3% for both tandem and tandem reflex testing. Conclusion The tandem reflex strategy simplifies a potentially complex clinical scenario by providing a mechanism by which providers can maximize partner compliance and the detection of at‐risk couples while minimizing workflow burden and unnecessary testing and is more efficacious than both sequential and tandem screening strategies., Highlights What's already known about this topic? Studies have explored barriers to carrier screening and follow up partner testing to identify at‐risk couples. However, to date, no one has explored the efficacy of different carrier screening workflows. What does this study add? This study highlights how providers could maximize the utility of carrier screening in identifying at‐risk couples based on the screening strategy utilized.

It is well known that mechanically stimulating the perineal region potently facilitates hindlimb locomotion and weight support in mammals with a spinal transection (spinal mammals). However, how perineal stimulation mediates this excitatory effect is poorly understood. We evaluated the effect of mechanically stimulating (vibration or pinch) the perineal region on ipsilateral (9-14 ms onset) and contralateral (14-18 ms onset) short-latency cutaneous reflex responses evoked by electrically stimulating the superficial peroneal or distal tibial nerve in seven adult spinal cats where hindlimb movement was restrained. Cutaneous reflexes were evoked before, during, and after mechanical stimulation of the perineal region. We found that vibration or pinch of the perineal region effectively triggered rhythmic activity, ipsilateral and contralateral to nerve stimulation. When electrically stimulating nerves, adding perineal stimulation modulated rhythmic activity by decreasing cycle and burst durations and by increasing the amplitude of flexors and extensors. Perineal stimulation also disrupted the timing of the ipsilateral rhythm, which had been entrained by nerve stimulation. Mechanically stimulating the perineal region decreased ipsilateral and contralateral short-latency reflex responses evoked by cutaneous inputs, a phenomenon we observed in muscles crossing different joints and located in different limbs. The results suggest that the excitatory effect of perineal stimulation on locomotion and weight support is mediated by increasing the excitability of central pattern-generating circuitry and not by increasing excitatory inputs from cutaneous afferents of the foot. Our results are consistent with a state-dependent modulation of reflexes by spinal interneuronal circuits.

Reflex anuria is a rare cause of acute renal failure, which may occur following ureteric manipulation or painful stimuli to adjacent organs during pelvic surgery. This condition, relatively unfamiliar to the general gynecologist, should be considered even when no obvious cause of anatomical obstruction is found. We present a case of reflex anuria in a 28-year-old woman for two large intramural fibroids. Evaluation did not reveal any organic obstruction of the urinary tract. Bilateral ureteric stenting and other supportive measures resulted in diuresis and improvement of renal function. Stents were removed after 10 days and patient was discharged on the 15th postoperative day with normal renal parameters. Intrarenal arteriolar spasm or ureteric spasm following pelvic manipulation can cause reflex anuria and should be considered in the differential diagnosis of acute renal failure in cases following pelvic surgery.

Made available in DSpace on 2021-06-25T10:50:25Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-03-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) The most commonly used technique to study the barostatic regulation of blood pressure in ectothermic vertebrates consists of determining the heart rate response to pharmacological manipulations of blood pressure, the so-called “Oxford method.” Although well established, the Oxford method has some important limitations, such as induction of hypervolemia in small animals and undesired effects of vasoactive drugs on central and peripheral baroreflex components. As an alternative, the sequence method, which consists in the computerized evaluation of naturally-occurring baroreflex adjustments of heart rate without the need for pharmacological administrations, was developed to study baroreflexes. In the present study, we compare this sequence method with the Oxford technique in two teleost species with different life styles, and we assess the optimal software configuration for the employment of the sequence method in fish. Calculation of baroreflex gain through the sequence method was adequate and reliable when the software was configured to search for baroreflex sequences with a minimum length of three cardiac cycles with a delay of one cardiac cycle between fluctuations in mean ventral aortic blood pressure and reflex changes in pulse interval. When properly configured, the sequence and the Oxford methods yielded similar determinations of the baroreflex gain in fish. Department of Physiology University of São Paulo (USP) Department of Zoology and Botany São Paulo State University (UNESP) National Institute of Science and Technology in Comparative Physiology (INCT—FAPESP/CNPq) Section for Zoophysiology, Department of Bioscience Aarhus University (AU) Aquaculture Center (CAUNESP) São Paulo State University (UNESP) Department of Zoology and Botany São Paulo State University (UNESP) Aquaculture Center (CAUNESP) São Paulo State University (UNESP) CAPES: 001 CNPq: 08/57712-4 FAPESP: 08/57712-4 FAPESP: 16/17572-5 CAPES: 88881.133009/2016-01 CAPES: 88881.133760/2016-01

A persistent basal tone in the internal anal sphincter (IAS) is essential for keeping the anal canal closed and fecal continence. Its inhibition via the rectoanal inhibitory reflex (RAIR) is required for successful defecation. However, cellular signals underlying the IAS basal tone remain enigmatic. Here we report the origin and molecular mechanisms of calcium signals that control the IAS basal tone, using a combination approach including a novel IAS slice preparation that retains cell arrangement and architecture as in vivo, 2-photon imaging, and cell-specific gene-modified mice. We found that IAS smooth muscle cells generate two forms of contractions (i.e., phasic and sustained contraction) and Ca(2+) signals (i.e., synchronized Ca(2+) oscillations (SCaOs) and asynchronized Ca(2+) oscillations (ACaOs)) that last for hours. RyRs, TMEM16A, L-type Ca(2+) channels, and gap junctions are required for SCaOs, which account for phasic contraction and 75% of sustained contraction. Nevertheless, only RyRs are required for ACaOs, which contribute 25% of sustained contraction. Nitric oxide, the primary neurotransmitter mediating the RAIR, blocks both types of Ca(2+) signals, leading to IAS’s full relaxation. Our results show that the oscillating nature of Ca(2+) signals generates and maintains the basal tone without causing cytotoxicity to IAS. Our study provides insight into fecal continence and normal defecation.

Saccades are often directed toward a stimulus that provides useful information for observers to navigate the visual world. The quality of visual signals of a stimulus is influenced by global luminance, and the pupil constricts or dilates after a luminance increase or decrease, respectively, to optimize visual signals for further information processing. Although luminance level changes regularly in the real environment, saccades are mostly studied in the luminance-unchanged setup. Whether pupillary responses triggered by global luminance changes modulate saccadic behavior are yet to be explored. Through varying background luminance level in an interleaved pro- and anti-saccade paradigm, we investigated the modulation of pupillary luminance responses on the generation of reflexive and voluntary saccades. Subjects were instructed to either automatically look at the peripheral stimulus (pro-saccade) or to suppress the automatic response and voluntarily look in the opposite direction from the stimulus (anti-saccade). Level of background luminance was increased (light), decreased (dark), or unchanged (control) during the instructed fixation period. Saccade reaction time distributions of correct pro- and anti-saccades in the light and dark conditions were differed significantly from those in the control condition. Moreover, the luminance condition modulated saccade kinematics, showing reduced performances in the light condition than in the control condition, particularly in pro-saccades. Modeling results further suggested that both pupil diameter and pupil size derivative significantly modulated saccade behavior, though effect sizes were small and mainly mediated by intersubject differences. Together, our results demonstrated the influence of pupillary luminance responses on the generation of pro- and anti-saccades.