Maximum Constriction Research Articles

Rivaroxaban improves vascular response in LPS-induced acute inflammation in experimental models.

Rivaroxaban (RVX) was suggested to possess anti-inflammatory and vascular tone modulatory effects. The goal of this study was to investigate whether RVX impacts lipopolysaccharide (LPS)-induced acute vascular inflammatory response. Male rats were treated with 5 mg/kg RVX (oral gavage) followed by 10 mg/kg LPS i.p injection. Circulating levels of IL-6, MCP-1, VCAM-1, and ICAM-1 were measured in plasma 6 and 24 hours after LPS injection, while isolated aorta was used for gene expression analysis, immunohistochemistry, and vascular tone evaluation. RVX pre-treatment significantly reduced LPS mediated increase after 6h and 24h for IL-6 (4.4±2.2 and 2.8±1.7 fold), MCP-1 (1.4±1.5 and 1.3±1.4 fold) VCAM-1 (1.8±2.0 and 1.7±2.1 fold). A similar trend was observed in the aorta for iNOS (5.5±3.3 and 3.3±1.9 folds reduction, P<0.01 and P<0.001, respectively), VCAM-1 (1.3±1.2 and 1.4±1.3 fold reduction, P<0.05), and MCP-1 (3.9±2.2 and 1.9±1.6 fold reduction, P<0.01). Moreover, RVX pre-treatment, improved LPS-induced PE contractile dysfunction in aortic rings (Control vs LPS, Emax reduction = 35.4 and 31.19%, P<0.001; Control vs LPS+RVX, Emax reduction = 10.83 and 11.48%, P>0.05, respectively), resulting in 24.5% and 19.7% change in maximal constriction in LPS and LPS+RVX respectively. These data indicate that RVX pre-treatment attenuates LPS-induced acute vascular inflammation and contractile dysfunction.

Pupillary light reflex in ethambutol-induced optic neuropathy

We evaluated changes in the pupillary light reflex (PLR) of ethambutol (EMB)-induced optic neuropathy and analyzed the correlations between PLR parameters and other structural changes in EMB-induced optic neuropathy. This retrospective, observational, case–control study involved thirty-two eyes of 17 patients with EMB-induced optic neuropathy (EON group), sixty eyes of 60 patients without EMB-induced optic neuropathy (non-EON group) while taking ethambutol, and forty-five eyes of 45 normal controls. PLR was measured by digital pupillometry. The clinical characteristics, optical coherence tomography measurements and PLR parameters including pupil diameter, constriction latency, constriction ratio/velocity, and dilation velocity were noted. The differences in PLR measurements were compared among the three groups. Correlations between PLR parameters and other structural parameters in EMB-induced optic neuropathy were evaluated. The pupillary constriction ratio, constriction and dilation velocities were significantly reduced in the EON group compared to the non-EON group and controls (all P < 0.05). In EMB-induced optic neuropathy, average outer macular ganglion cell layer (mGCL) thickness showed a significant correlation with the pupillary constriction ratio (ß = 4.14, P = 0.003) and maximal constriction velocity (ß = 1.08, P < 0.001). This study confirmed that pupillary constriction and dilation velocities were significantly decreased in patients with EMB-induced optic neuropathy, compared to normal controls. Digital pupillometry may be a useful tool in the evaluation of EMB-induced optic neuropathy.

The pupillary light reflex as a point-of-care test for suicide risk: Preliminary results

The pupillary light reflex (PLR) reflects physiologic arousal, and a potential point-of-care biomarker of suicide risk. We collected data from 9 healthy controls, 6 non-suicidal depressed patients, 7 with prior suicide attempts but not presently suicidal, and 8 depressed patients who were actively suicidal. The pupillary maximum constriction velocity (MCV) was similar between the non-suicidal depressed patients and healthy controls (the “Never suicidal” group). Patients with prior attempt resembled the patients expressing active suicidal ideation (the “Ever suicidal” group). MCV was a significant predictor within a logistic regression model of participants who were “Ever suicidal” versus “Never suicidal”.

Dynamic Pupillometry in Type 2 Diabetes: Pupillary Autonomic Dysfunction and the Severity of Diabetic Retinopathy.

PurposeAutonomic dysfunction may precede the microvascular changes that characterise diabetic retinopathy. The aim of this pilot study was to measure and compare pupillometry indices in type 2 diabetes (T2DM) patients – with and without diabetic retinopathy – and in healthy, age-matched controls.MethodsTwo hundred and eleven participants with T2DM aged 45–80 years were recruited from Dunedin Hospital Eye Department, Dunedin, New Zealand. They were categorised into three groups – no, mild/moderate, or severe diabetic retinopathy. Seventy age-matched, diabetes screen negative control participants were recruited from the Dunedin city community. Dynamic pupillometry was performed using an infrared pupillometer. The main outcome measures were maximum constriction velocity, average constriction velocity, absolute constriction amplitude, relative reflex amplitude, average dilation velocity and 75% re-dilation (recovery) time. Outcome measures were compared between study groups using the Kruskal–Wallis nonparametric test (with Dunn’s multiple comparison post-test).ResultsPupillary parasympathetic function differed between groups. Maximum constriction velocity (p <0.001) and average constriction velocity (p <0.001) were slower, and absolute constriction amplitude (p <0.001) and relative reflex amplitude (p <0.05) were lower in the three diabetes groups compared with controls. There were no significant differences in pupillary sympathetic function between the four groups for re-dilation time, but the diabetes groups had significantly slower average dilation velocity times.ConclusionPupillary light reflex is significantly impaired with diabetic retinal neuropathy, before clinically observable signs of diabetic retinopathy. Dynamic pupillometry may be a cheap, clinically relevant test, but sensitivity and specificity need to be determined before utilising as a screening tool for diabetic retinopathy.

Concussion Alters Dynamic Pupillary Light Responses in Children.

To investigate the impact of concussion on pupillary function in children by examining pupillometric parameters and assessing for differences in children reporting photosensitivity. Retrospective chart review was performed of pediatric patients referred for visual symptoms after concussion from 2017 to 2018 seen in a single academic outpatient clinic. Pupillometry data of 92 patients were included. Outcomes were compared to normative pediatric data from the same institution by 2-sample t tests. The association between photosensitivity and each outcome was assessed by use of linear mixed models with photosensitivity as a fixed effect and random patient effect. Outcomes of 181 eyes in 92 concussion patients were averaged by patient and compared to normative values in scotopic conditions. Concussion patients had an average age of 13.8 ± 2.64 years. Average constriction velocity (P = .0008), maximum constriction velocity (P = .0012), and average dilation velocity (P = .0034) were faster in concussion patients, whereas 75% recovery times (P = .0027) was increased. Photosensitivity did not significantly affect measured pupillary responses. Dynamic pupillary responses may be increased in pediatric concussion. Pupillometry may provide insight into the complex pathophysiological changes underlying pediatric concussion.

The Pupillary Response of the Common Octopus (Octopus vulgaris).

Cephalopods have very conspicuous eyes that are often compared to fish eyes. However, in contrast to many fish, the eyes of cephalopods possess mobile pupils. To increase the knowledge of pupillary and thus visual function in cephalopods, the dynamics of the pupil of one of the model species among cephalopods, the common octopus (Octopus vulgaris), was determined in this study. We measured pupillary area as a function of ambient luminance to document the light and dark reaction of the octopus eye. The results show that weak light (<1 cd/m2) is enough to cause a pupil constriction in octopus, and that the pupil reacts fast to changing light conditions. The t50-value defined as the time required for achieving half-maximum constriction ranged from 0.45 to 1.29 s and maximal constriction from 10 to 20% of the fully dilated pupil area, depending on the experimental condition. Axial light had a stronger influence on pupil shape than light from above, which hints at a shadow effect of the horizontal slit pupil. We observed substantial variation of the pupil area under all light conditions indicating that light-independent factors such as arousal or the need to camouflage the eye affect pupil dilation/constriction. In conclusion, the documentation of pupil dynamics provides evidence that the pupil of octopus is adapted to low ambient light levels. Nevertheless it can quickly adapt to and thus function under brighter illumination and in a very inhomogeneous light environment, an ability mediated by the dynamic pupil in combination with previously described additional processes of light/dark adaptation in octopus.

Abstract P066: Purinergic Receptor Function In The Middle Cerebral Artery From Clopidogrel-treated Rabbits

Arterial thrombosis is the leading cause of death in the developed world and hypertensive patients are at an increased risk. Dual antiplatelet therapy, consisting of low-dose aspirin in combination with a P2Y 12 antagonist, is the most common preventative treatment for arterial thrombosis. Clopidogrel, a P2Y 12 antagonist, is associated with cerebral microbleeds and intracerebral hemorrhages. We have previously reported in rabbits that clopidogrel (3mg/kg) induces bleeding at lower doses than required to inhibit platelet aggregation, making it unlikely that the clopidogrel-mediated bleeding events are the result of platelet inhibition. I hypothesized that clopidogrel was acting on other purinergic receptors to impair artery function due to the structural similarity of the metabolites of clopidogrel. Purinergic receptors, P2Y 1 , P2Y 2 , P2Y 4 and P2Y 6 , are expressed in the endothelium of cerebral vessels. The purpose of this study was to determine the effects of clopidogrel on vascular function in response to activation of P2Y 1 , P2Y 2 , P2Y 4 and P2Y 6 . The middle cerebral artery (MCA) was used as it is the site most common for cerebrovascular events. New Zealand white rabbits (n=3) were treated for 3 days with vehicle or clopidogrel (3mg/kg/day) prior to MCA isolation. Myogenic tone was allowed to develop before assessing the response of the MCA to increasing concentrations (10 -9 -10 -5 M) of specific purinergic receptor agonists P2Y 1 : MRS 2365; P2Y 2 : MRS 2768; P2Y 4 : MRS 4062; P2Y 6 : MRS 2693. If myogenic tone was not generated the MCA was preconstricted with 10 -6 M serotonin. Response was analyzed by two-way ANOVA and compared to vehicle using Dunnett’s post-test. In all cases, p &lt; 0.05 denote statistical significance. Constriction was calculated as a percent change from baseline. Stimulation with the P2Y 4 agonist resulted in a mean maximal constriction of 28.95% (28.95 of 100) for vehicle and 52.72% (52.72 of 100) for 3mg/kg clopidogrel. There was no significant difference upon stimulation with the P2Y 1 , P2Y 2 , or P2Y 6 agonists compared to vehicle. These data suggest that clopidogrel has vascular effects on the P2Y 4 receptor expressed in the MCA and may explain the cerebral bleeding side effects observed.

Effects of Narrowband Light on Choroidal Thickness and the Pupil.

PurposeTo determine the effects of narrowband light exposure on choroidal thickness and the pupil response in humans.MethodsTwenty subjects, ages 21 to 43 years, underwent 1 hour of exposure to broadband, short wavelength “blue,” or long wavelength “red” light, or darkness. Choroidal thickness, imaged with spectral domain optical coherence tomography, axial length, determined from biometry, and rod/cone- and intrinsically photosensitive retinal ganglion cell-driven pupil responses were measured before and after exposure. Pupil stimuli were six 1 second alternating red (651 nm) and blue (456 nm) stimuli, 60 seconds apart. Pupil metrics included maximum constriction and the 6 second post-illumination pupil response (PIPR).ResultsCompared with before exposure, the choroid significantly thinned after broadband light, red light, and dark exposure (all P < 0.05), but not after blue light exposure (P = 0.39). The maximum constriction to 1 second red stimuli significantly decreased after all light exposures (all P < 0.001), but increased after dark exposure (P = 0.02), compared with before exposure. Maximum constriction and 6-second PIPR to 1 second blue stimuli significantly decreased after all light exposures compared with before exposure (all P < 0.005), with no change after dark exposure (P > 0.05). There were no differences in axial length change or 6-second PIPR to red stimuli between exposures.ConclusionsNarrowband blue and red light exposure induced differential changes in choroidal thickness. Maximum constriction, a function of rod/cone activity, and the intrinsically photosensitive retinal ganglion cell-mediated PIPR were attenuated after all light exposures. Findings demonstrate differing effects of short-term narrowband light and dark exposure on the choroid, rod/cone activity, and intrinsically photosensitive retinal ganglion cells.

Acoustic characteristics of American English liquids /ɹ/, /l/, /ɹl/ produced by Korean L2 adults.

This study examined the acoustic characteristics of American English liquids /ɹ/, /l/, and /ɹl/ produced by 14 adult learners of English (L2) and 13 native speakers of English. Several temporal and spectral measures were examined, including a novel measure to describe the relative timing of the maximum constriction during liquid production. The results indicated that L2 speakers rely more on duration contrasts to distinguish the three liquids than spectral contrasts. Reduced spectral differences among the liquids in L2 speakers are discussed concerning the influence of the native language of L2 speakers.

Chromatic Pupil Campimetry Reveals Functional Defects in Exudative Age-Related Macular Degeneration with Differences Related to Disease Activity.

PurposeThe purpose of this study was to use chromatic pupil campimetry (CPC) for an objective evaluation of local retinal function in exudative age-related macular degeneration (AMD) and to assess disease activity.MethodsGaze-controlled CPC was performed in 19 subjects with optical coherence tomography–confirmed exudative AMD (75 ± 4 years; 11 women) and the results compared with those of an age-matched control group (n = 11; 72 ± 6 years; 8 women). Local retinal function was evaluated by measuring pupil responses to 3° red stimuli (60 cd/m2, 1 second) at 41 positions covering 30° of the central visual field on a dim blue background (test duration 6 minutes). Primary outcome parameters were relative maximal pupil constriction amplitude (% from baseline) and latency to constriction onset.ResultsPupil constriction amplitudes were significantly reduced in the macular region, and especially in the fovea in AMD (16% ± 4.7%; mean ± standard deviation), compared with the control group (24% ± 6%; P = 0.00036). Receiver operating characteristic values were 0.84 for the constriction amplitude in the fovea, and 0.9 for the steepness angle between periphery and center. Mean latency to constriction onset in the fovea in AMD was significantly longer (333 ± 53 ms; normals 273 ± 59 ms, P = 0.0072), and particularly in the active compared with the inactive status of exudative AMD (P = 0.01).ConclusionsCPC detected functional changes in exudative AMD with high sensitivity. Time dynamics of active exudative AMD differed from disease inactivity.Translational RelevanceWith the combination of short recording time, objectiveness of the measurement and gaze-correction for fixation problems, this method presents a suitable complement to the currently used clinical functional tests of the macula.

A Cross-Sectional, Quantitative Videofluoroscopic Analysis of Swallowing Physiology and Function in Individuals With Amyotrophic Lateral Sclerosis.

PurposeTo date, research characterizing swallowing changes in individuals with amyotrophic lateral sclerosis (ALS) has primarily relied on subjective descriptions. Thus, the degree to which swallowing physiology is altered in ALS, and relationships between such alterations and swallow safety and/or efficiency are not well characterized. This study provides a quantitative representation of swallow physiology, safety, and efficiency in a sample of individuals with ALS, to estimate the degree of difference in comparison to published healthy reference data and identify parameters that pose risk to swallow safety and efficiency. Secondary analyses explored the therapeutic effect of thickened liquids on swallowing safety and efficiency.MethodNineteen adults with a diagnosis of probable-definite ALS (El-Escorial Criteria–Revised) underwent a videofluoroscopic swallowing study, involving up to 15 sips of barium liquid (20% w/v), ranging in thickness from thin to extremely thick. Blinded frame-by-frame videofluoroscopy analysis yielded the following measures: Penetration–Aspiration Scale, number of swallows per bolus, amount of pharyngeal residue, degree of laryngeal vestibule closure (LVC), time-to-LVC, duration of LVC (LVCdur), pharyngeal area at maximum constriction, diameter of upper esophageal sphincter opening, and duration of UES opening (UESOdur). Measures of swallow physiology obtained from thin liquid trials were compared against published healthy reference data using unpaired t tests, chi-squared tests, and Cohen’s d effect sizes (adjusted p < .008). Preliminary relationships between parameters of swallowing physiology, safety, and efficiency were explored using nonparametric Cochrane’s Q, Friedman’s test, and generalized estimating equations (p < .05).ResultsCompared to healthy reference data, this sample of individuals with ALS displayed a higher proportion of swallows with partial or incomplete LVC (24% vs. < 1%), increased time-to-LVC (d = 1.09), reduced UESwidth (d = 0.59), enlarged pharyngeal area at maximum constriction, prolonged LVCdur (d = 0.64), and prolonged UESOdur (d = 1.34). Unsafe swallowing (i.e., PAS ≥ 3) occurred more frequently when LVC was partial/incomplete or time-to-LVC was prolonged. Pharyngeal residue was associated with larger pharyngeal areas at maximum constriction. Unsafe swallowing occurred less frequently with extremely thick liquids, compared to thin liquids. No significant differences in pharyngeal residue were observed based on liquid thickness.ConclusionsQuantitative videofluoroscopic measurements revealed moderate-to-large differences in swallow physiology between this sample of individuals with ALS and healthy reference data. Increased time-to-LVC, noncomplete LVC, and enlarged pharyngeal area at maximum constriction were associated with impaired swallow safety or efficiency. Thickened liquids may mitigate the risk of acute episodes of aspiration in individuals with ALS. Further work is needed to corroborate these preliminary findings and explore how swallowing profiles evolve throughout disease progression.

The Effect of Preterm Birth and Recurrent Laryngeal Nerve Lesion on Palatopharyngeal Arch Function During Feeding

Feeding in infant mammals requires the precise coordination of multiple oropharyngeal structures, including the palatopharyngeal arch. During a typical swallow, the activity of the palatopharyngeus muscle produces constriction of the arches and lowers the soft palate, which may be responsible for flipping of the epiglottis to cover the airway. Most research on the role of the palatopharyngeal arches in swallowing has been limited to pharyngeal manometry, which provides insight into the relative pressures in the oropharynx during swallowing. Studies using manometry in preterm infants, or in those with iatrogenic sequelae such as recurrent laryngeal nerve (RLN) damage, suggest differences in function, but not on how the structures in the oropharynx move to contribute to those changes in function. In this study, we assessed palatopharyngeal arch kinematics during feeding by using our validated infant pig model to determine the impact of birth status (preterm versus term), lesion status (lesioned RLN versus intact) and their interaction on feeding performance. We placed tantalum radio‐opaque beads into relevant anatomical structures of 16 infant pigs, including the palatopharyngeal arches, the tongue, the hard and soft palate, and the nose. We recorded feeding at both seven and 17 days postnatal via biplanar high‐speed videofluoroscopy (100fps) across a total of 584 swallows. Using XMALab, we tracked the three‐dimensional movement of the arches relative to a rigid body comprised of the markers in the hard palate and the nose. We then used custom MATLAB code to calculate the three‐dimensional excursion of the arches during a swallow, as well as the timing of constriction initiation, and the point of maximal constriction during a swallow. We found that preterm infants had more variable arch excursion than term infants, and RLN lesion increased excursion for both term and preterm infants although there were minimal differences in arch excursion within an age between term and preterm infants. Term infants also reached maximal arch constriction later than preterm infants, most likely due to their larger arch excursion and larger bolus volume. Lesion infants, both term and preterm, also had delayed maximal arch constriction during swallows, although day 17 term lesion infants reached maximal constriction earlier than term day 17 infants. Lesion resulted in delayed initiation of arch constriction, which did not change with age, although older term infants exhibited later arch constriction initiation than older preterm infants. Our results show that preterm birth and RLN lesion have distinct yet pervasive effects on infant feeding. Altered feeding performance in these neurologically compromised infants may be due in part to changes in the activity of the palatopharyngeal arches.Support or Funding InformationNIH R01HD088561

Static Muscle Stretching Enhances Vascular Responsiveness of the Tibial Nutrient Artery

The magnitude of bone formation and remodeling is linked to both the magnitude of strain placed on the bone and the perfusion of bone. We have previously shown that daily static stretching of the ankle flexor muscles in aged rats results in increased blood flow to the stretched muscles and to the proximal tibial metaphasis during walking exercise. The purpose of this study was to determine the effects of daily static muscle stretching on vasoreactivity of the nutrient artery that perfuses the proximal tibial metaphasis. Static stretching of ankle flexor muscles was performed in aged male Fischer 344 rats (20 months) by placement of a dorsiflexion splint on the left ankle for 30 min/day, 5d/wk for 4wks. The right hindlimb served as a contralateral control (unstretched) limb. After the 4 wk stretching intervention, the tibial nutrient artery was isolated from both the stretched and unstretched limb. Vasoconstrictor responses to the adrenergic agonist, phenylephrine (10‐9‐10‐4M) and vasodilatory responses to acetylcholine (10‐9‐10‐4M) and Dea‐NONO‐ate (10‐9‐10‐4M) were evaluated. Vasoconstrictor responses to phenylephrine were significantly increased in the tibial nutrient artery from the stretched limb as compared to those from the unstretched limb (maximal constriction, stretched limb = 54±4%, maximal constriction, unstretched limb = 42±6%; P&lt;0.05 stretched vs. unstretched). Endothelium‐dependent vasodilation to acetylcholine was also significantly increased in the tibial nutrient artery from the stretched limb (maximal dilation = 62±5%) as compared to the unstretched limb (maximal dilation = 41±5%); P&lt;0.01, stretched vs. unstretched). Endothelium‐independent dilation to the NO donor, Dea‐NONO‐ate was not different in the tibial nutrient arteries from the stretched and unstretched limbs. These data indicate that static muscle stretching alters the reactivity of both the smooth muscle and the endothelium of the tibial nutrient artery, leading to enhanced vasoconstrictor and vasodilatory responsiveness of the artery. This enhancement of vascular function in the nutrient artery may contribute to increased perfusion of the tibia during walking exercise following 4 weeks of daily static stretching.Support or Funding InformationSupported By: NIH R15AG055029

The use Of Pupillary Light Reflex in Concussed Athletes

Background:Despite advancements, concussion diagnosis remains reliant on subjective symptom report and clinical assessments. Visual deficits and autonomic dysfunction have been described following concussion. Testing of the pupillary light reflex (PLR) is a simple, portable, non-invasive, and objective means of quantifying pupillary function.Purpose:The aim of this study was to objectively evaluate pupillary responses to a light stimulus in concussed adolescent athletes and to determine whether clinical assessments correlated with PLR responses after a diagnosed concussion when compared to pre-injury responses.Methods:In this prospective cohort study, PLR and clinical measures [PCSI and/or SCAT symptom scales, near point of convergence (NPC) and accommodation amplitude (AA) of both eyes] were assessed in 93 (45 female), non-concussed adolescent athletes (ages 14-18) during their pre-season. PLR was obtained in response to a brief white light stimulus using a hand-held pupillometer. During each assessment, three monocular trials were performed in each eye alternatively, with subsequent averaged responses for each eye. Seven athletes (ages 14-17) sustained a concussion and had post-injury assessments of PLR and clinical measures completed longitudinally through recovery.Results:All seven concussed athletes completed PLR and clinical assessments at least once post-injury (mean initial day of evaluation = 6 days post injury). Six out of the seven concussed athletes demonstrated an increase in steady state diameter of 24% (median 18%), minimum pupil diameter of 17% (median 11%) and a maximum constriction velocity of 28% (median 33%) following concussion which decreased over the course of recovery, returning to pre-injury or below pre-injury measurements. Six of seven of the concussed athletes completed NPC and AA assessments at both pre-season and post-injury timepoints. In contrast to the PLR findings, both NPC and AA measures were normal at post-injury assessments. Reported symptom scores improved throughout recovery, correlating with PLR response recovery, with both returning to pre-injury measurements.Conclusion:Pupil responsivity was found to be significantly enhanced after concussion compared to pre-injury measurements, waning over time during recovery, following a similar trajectory as symptom burden. NPC and AA, which have autonomic contributions and are clinical measures, were normal pre- and post-injury and did not differentiate the concussed state from the uninjured state in our series. Our preliminary results demonstrate that dynamic PLR responses may detect acute autonomic deficits that are not evident via clinical assessments. Further investigation of its potential utility as sensitive and objective biomarker in concussion diagnosis, management and sports clearance is warranted.

Effects of stimulus size, eccentricity, luminance, and attention on pupillary light response examined by concentric stimulus

Previous studies show that the amplitude of pupillary light response (PLR) depends on the corneal flux density (CFD), which is the product of stimulus area by luminance. However, the contribution of CFD has been investigated only when the stimulus was centered on the fovea, whereas perceived luminance to pupillary response would reduce with stimulus eccentricity. Additionally, it has been shown recently that attentional state modulates pupillary response. In this study, we aimed to clarify the complete mechanisms of PLR by manipulating the stimulus size, eccentricity, luminance, and the participants’ attentional states. We focused on four indices to examine PLR, that is, pupillary latency (PL), maximum constriction velocity (MCV), maximum constriction (MC), and mean pupil change (MPC). Results showed that PL was a function of CFD, whereas MCV, MC, and MPC were functions of both CFD and stimulus eccentricity. Furthermore, the magnitude of effect due to stimulus eccentricity for MCV and MC was different from that for MPC. These results provided new evidence that the different processing systems in PLR existed.

Is There a Correlation Between Airway Volume and Maximum Constriction Area Location in Different Dentofacial Deformities?

The purpose of the present study was to correlate the airway volume and maximum constriction area (MCA) with the type of dentofacial deformity in patients who required orthognathic surgery. The present retrospective cohort study included orthognathic surgery patients selected from the private practice of one of us. The selected cases were stratified into 5 different groups according to the clinical and cephalometric diagnosis of their dentofacial deformity. The preoperative airway volume and anatomic location of the MCA were calculated using the airway tool of the Dolphin Imaging software module (Dolphin Imaging and Management Solutions, Chatsworth, CA) and correlated with the diagnosed dentofacial deformity. Differences in the pretreatment airway volumes and MCA location were compared among the deformities. The MCA location was more often the nasopharynx for maxillary deficiency and the oropharynx for mandibular deficiency deformities. The nasopharynx volume was significantly smaller statistically (P<.005) for maxillary deficiency plus mandibular excess compared with mandibular deficiency. The hypopharynx volume was significantly smaller statistically (P<.005) for vertical maxillary excess plus mandibular deficiency than for both maxillary deficiency and maxillary deficiency plus mandibular excess. No statistically significant difference was found among the different deformity groups in relation to the mean airway volume (P>.005). The location of the airway MCA seems to have a strong correlation with the horizontal position of the maxilla and mandible. The MCA in maxillary deficiencies (isolated or combined) was in the nasopharynx, and the MCA in mandibular deficiencies (isolated or combined) was in the oropharynx. Clinicians should consider these anatomic findings when planning the location and magnitude of orthognathic surgery movements to optimize the outcomes.

Establishing a normative database for quantitative pupillometry in the pediatric population

BackgroundPupillary evaluation is a crucial element of physical exams. Noting size, reactivity, and consensual response is critical in assessing for optic nerve dysfunction. We aim to establish normative data for scotopic pupillary size and function in the pediatric population in a clinical setting.MethodsPupillometry was obtained prospectively for consecutive, normal patients < 18 years old being evaluated by Lurie Children’s Ophthalmology. Quantitative data included maximum (MAX) and minimum (MIN) diameters, constriction percentage (CON), latency (LAT), average (ACV) and maximum (MCV) constriction velocities, average dilation velocity (ADV), and 75% recovery time (T75). Iris color was noted as light, intermediate, or dark.Results196 eyes of 101 participants (42.6% male, ages 1–17 years, average age 10.3 years) were analyzed. Mean MAX was 6.6 mm (5.1–8.1 mm 95% CI); MIN was 4.7 mm (3.1–6.1 mm 95% CI); CON was 30% (17–42 95% CI); LAT was 230 milliseconds (160–300 ms 95% CI); ACV was 3.70 mm/sec (2.21–5.18 mm/sec 95% CI); and ADV was 0.88 mm/sec (0.38–1.38 mm/sec 95% CI). Age had a positive correlation with MAX, MIN, and CON. 84.2 and 95.8% of participants showed resting pupil asymmetry of ≤0.5 mm and ≤ 1.0 mm, respectively.ConclusionsQuantitative pupillometry can be a useful tool for screening pediatric patients. We sought to establish normative data in this group. We found males to have significantly greater MCV and CON than females (p < 0.05). Also, age had a positive correlation with MAX, MIN, and CON.

Microvascular function and oxidative stress in adult individuals with early onset of cardiovascular disease

The current study aims to investigate retinal vascular function and its relationship with systemic anti-oxidative defence capacity in normal individuals versus those with early hypertensive changes according to the current ESC/ESH guidelines. Retinal microvascular function was assessed in 201 participants by means of dynamic retinal vessel analysis. Blood pressure, lipid panel, oxidized (GSH) & reduced glutathione (GSSG) were also evaluated for each participant. Individuals classed as grade 1 hypertension demonstrated higher retinal arterial baseline diameter fluctuation (p = 0.0012), maximum dilation percentage (p = 0.0007), time to maximum constriction (p = 0.0003) and lower arterial constriction slope (p = 0.0131). Individuals classed as high normal and grade 1 hypertension also demonstrated higher time to maximum dilation than individuals classed as optimal or normal. GSH levels correlated negatively with SBP, DBP and MBP values in all participants (p = 0.0010; p = 0.0350 and p = 0.0050) as well as with MBP values in high normal and grade 1 hypertension (p = 0.0290). The levels of GSSG correlated positively with SBP, DBP and MBP values in all participants (p = 0.0410; p = 0.0330 and, p = 0.0220). Our results point to the fact that microvascular alterations can be identifiable at BP values still considered within normal values and go in parallel with the changes observed in the level of oxidative stress.

Pupillary light responses in type 1 and type 2 diabetics with and without retinopathy.

We assessed the function of rod/cones and melanopsin in type 1 (T1DM) and type 2 diabetes mellitus (T2DM) with and without non-proliferative diabetic retinopathy (NPDR). We performed pupillometry on 22 healthy controls and four diabetic groups: 12 T1DM patients without NPDR and 12 with moderate NPDR, and 16 T2DM patients without NPDR and 12 with moderate NPDR. Monocular stimulations of 20seconds with red (λ=633nm) and blue light (λ=463nm) at ~15log quanta/cm2 /second were performed. The primary outcome was the melanopsin-mediated late redilation phase of postillumination pupillary light response (PIPRL ate ) to blue light. The secondary outcomes were the mixed rod/cone and melanopsin responses, that is maximal pupil constriction and the early redilation phase of PIPR (PIPRE arly ). Late redilation phase of PIPR (PIPRL ate ) to blue and red light stimuli was not significantly different between healthy control and the four diabetic groups (n.s.). The maximal pupil contractions to blue light stimulus were significantly reduced in T1DM patients as well as in T2DM patients with NPDR (p≤0.02), whereas for red light stimuli, the maximal pupil constriction was only reduced in T2DM with NPDR (p<0.01). Early redilation phase of PIPR (PIPRE arly ) to blue and red light stimuli was not significantly different between healthy controls and diabetic patients (n.s.). Neither the PIPRE arly nor the PIPRL ate was significantly reduced in diabetics with or without NPDR compared to healthy controls. The reduced maximal pupil constrictions in diabetics with NPDR indicate decreased mixed rod/cone and melanopsin responses.

Acepromazine and Chlorpromazine as Pharmaceutical-grade Alternatives to Chlorprothixene for Pupillary Light Reflex Imaging in Mice.

Studies of visual responses in isoflurane-anesthetized mice often use the sedative chlorprothixene to decrease the amount of isoflurane used because excessive isoflurane could adversely affect light-evoked responses. However, data are not available to justify the use of this nonpharmaceutical-grade chemical. The current study tested whether pharmaceutical-grade sedatives would be appropriate alternatives for imaging pupillary light reflexes. Male 15-wk-old mice were injected intraperitoneally with 1 mg/kg chlorprothixene, 5 mg/kg acepromazine, 10 mg/kg chlorpromazine, or saline. After anesthetic induction, anesthesia maintenance used 0.5% and 1% isoflurane for sedative- and saline-injected mice, respectively. A photostimulus (16.0 log photons cm-2 s-1; 470 nm) was presented to the right eye for 20 min, during which the left eye was imaged for consensual pupillary constriction and involuntary pupil drift. Time to immobilization, loss of righting reflex, physiologic parameters, gain of righting reflex, and degree of recovery were assessed also. The sedative groups were statistically indistinguishable for all measures. By contrast, pupillary drift occurred far more often in saline-treated mice than in the sedative groups. Furthermore, saline-treated mice took longer to reach maximal pupil constriction than all sedative groups and had lower heart rates compared with chlorpromazine- and chlorprothixene-sedated mice. Full recovery (as defined by purposeful movement, response to tactile stimuli, and full alertness) was not regularly achieved in any sedative group. In conclusion, at the doses tested, acepromazine and chlorpromazine are suitable pharmaceutical-grade alternatives to chlorprothixene for pupil imaging and conceivably other in vivo photoresponse measurements; however, given the lack of full recovery, lower dosages should be investigated further for use in survival procedures.