Anterior and Posterior Oral Cavity Responsive Neurons Are Differentially Distributed Among Parabrachial Subnuclei in Rat

1997 ◽  
Vol 78 (2) ◽  
pp. 920-938 ◽  
Author(s):  
Christopher B. Halsell ◽  
Susan P. Travers
Keyword(s):  
Oral Cavity ◽  
Taste Receptor ◽  
Hierarchical Cluster ◽  
Response Rates ◽  
Differential Sensitivity ◽  
Response Profiles ◽  
To Receive ◽  
Gustatory Neurons ◽  
Comparable Population ◽  
Stimulation Of

Halsell, Christopher B. and Susan P. Travers. Anterior and posterior oral cavity responsive neurons are differentially distributed among parabrachial subnuclei in rat. J. Neurophysiol. 78: 920–938, 1997. The responses of single parabrachial nucleus (PBN) neurons were recorded extracellularly to characterize their sensitivity to stimulation of individual gustatory receptor subpopulations (G neurons, n = 75) or mechanical stimulation of defined oral regions (M neurons, n = 54) then localized to morphologically defined PBN subdivisions. Convergence from separate oral regions onto single neurons occurred frequently for both G and M neurons, but converging influences were more potent when they arose from nearby locations confined to the anterior (AO) or posterior oral cavity (PO). A greater number of G neurons responded optimally to stimulation of AO than to PO receptor subpopulations, and these AO-best G neurons had higher spontaneous and evoked response rates but were less likely to receive convergent input than PO-best G neurons. In contrast, proportions, response rates, and convergence patterns of AO- and PO-best M neurons were more comparable. The differential sensitivity of taste receptor subpopulations was reflected in PBN responses. AO stimulation with NaCl elicited larger responses than PO stimulation; the converse was true for QHCl stimulation. Within the AO, NaCl elicited a larger response when applied to the anterior tongue than to the nasoincisor duct. Hierarchical cluster analysis of chemosensitive response profiles suggested two groups of PBN G neurons. One group was composed of neurons optimally responsive to NaCl (N cluster); the other to HCl (H cluster). Most N- and H-cluster neurons were AO-best. Although they were more heterogenous, all but one of the remaining G neurons were unique in responding best or second-best to quinine and so were designated as quinine sensitive (Q+). Twice as many Q+ neurons were PO- compared with AO-best. M neurons were scattered across PBN subdivisions, but G neurons were concentrated in two pairs of subdivisions. The central medial and ventral lateral subdivisions contained both G and M neurons but were dominated by AO-best N-cluster G neurons. The distribution of G neurons in these subdivisions appeared similar to distributions in most previous studies of PBN gustatory neurons. In contrast to earlier studies, however, the external medial and external lateral-inner subdivisions also contained G neurons, intermingled with a comparable population of M neurons. Unlike cells in the central medial and ventral lateral subnuclei, nearly every neuron in the external subnuclei was PO best, and only one was an N-cluster cell. In conclusion, the present study supports a functional distinction between sensory input from the AO and PO at the pontine level, which may represent an organizing principle throughout the gustatory neuraxis. Furthermore, two morphologically distinct pontine regions containing orosensory neurons are described.

Organization of orosensory responses in the nucleus of the solitary tract of rat

1995 ◽  
Vol 73 (6) ◽  
pp. 2144-2162 ◽  
Author(s):  
S. P. Travers ◽  
R. Norgren
Keyword(s):  
Receptive Field ◽  
Oral Cavity ◽  
Mechanical Stimulation ◽  
Taste Receptor ◽  
Taste Bud ◽  
Solitary Tract ◽  
Topographic Organization ◽  
Gustatory Stimulation ◽  
Two Populations ◽  
Stimulation Of

1. The receptive field and topographic organization of single orosensory neurons located throughout the rostral division of the nucleus of the solitary tract (rNST) was studied by determining their responsiveness to gustatory stimulation of the entire oral cavity and to gustatory and mechanical stimulation of restricted oral regions. The rNST contained roughly equal numbers of two distinct populations of orosensory neurons, one responsive exclusively to oral mechanical stimulation (M neurons), the other to gustatory stimulation (G neurons). Some G neurons also responded to oral somatosensory stimuli, but usually less vigorously than to gustatory stimuli. The distribution of these two populations of rNST neurons was topographically organized: G neurons were centered anteriorly and medially to M neurons. 2. Eight of 44 G neurons responded only when the whole oral cavity was stimulated, but the remaining 36 cells responded to circumscribed stimulation of taste buds on the anterior tongue (AT), foliate papillae of the posterior tongue, nasoincisor ducts, retromolar mucosa (RM), or soft palate (SP). Overall, AT and SP stimulation were the most effective, and RM stimulation the least effective, for activating nucleus of the solitary tract (NST) G neurons. 3. Approximately half of the G neurons for which a receptive field could be defined (N = 36) responded to stimulation of a single taste receptor subpopulation, but the remaining neurons received convergent input from two or more taste bud groups. The receptive field configurations for convergent G neurons were orderly: convergence occurred preferentially between receptor subpopulations either within the anterior oral cavity (AO) or the posterior oral cavity (PO). An AO-PO distinction also was reflected in the topographic organization of gustatory responses. The mean location of neurons responding optimally to AO gustatory stimulation was more anterior in the NST, and also tended to be more lateral and ventral than the location of neurons that responded optimally to PO stimulation. 4. Forty-four rNST M neurons responded to innocuous mechanical stimulation of restricted areas of the tongue, palate, buccal mucosa, or periodontium. Stimulation of the hard palate and circumvallate papilla were most effective, whereas periodontal stimulation was least effective for activating these cells. 5. A majority (32 of 44) of rNST M neurons responded to stimulation of more than one of the oral sites tested.(ABSTRACT TRUNCATED AT 400 WORDS)

Amiloride Blocks Acid Responses in NaCl-Best Gustatory Neurons of the Hamster Solitary Nucleus

1998 ◽  
Vol 80 (3) ◽  
pp. 1362-1372 ◽  
Author(s):  
John D. Boughter ◽  
David V. Smith
Keyword(s):  
Citric Acid ◽  
Taste Receptor ◽  
Nerve Fibers ◽  
Chorda Tympani ◽  
Chorda Tympani Nerve ◽  
Receptor Cells ◽  
Biophysical Studies ◽  
Taste Receptor Cells ◽  
To Receive ◽  
Gustatory Neurons

Boughter, John D., Jr. and David V. Smith. Amiloride blocks acid responses in NaCl-best gustatory neurons of the hamster solitary nucleus. J. Neurophysiol. 80: 1362–1372, 1998. Biophysical studies of isolated taste receptor cells show that one mechanism of Na+ salt transduction involves the inward movement of Na+ through amiloride-blockable ion channels on the apical receptor cell membrane, which leads to a direct depolarization. Hamster taste receptor cells with amiloride-blockable Na+ responses also show an amiloride-sensitive H+ current. Thus one mechanism for the transduction of acid taste involves the amiloride-sensitive channel. We investigated the effects of amiloride on responses to acids in neurons of the nucleus of the solitary tract (NST) of the hamster. The responses of 47 NST neurons were recorded extracellularly while the anterior tongue was stimulated with solutions representing the four taste qualities (NaCl, sucrose, HCl, quinine), which were used to characterize each cell on the basis of its best stimulus. The effects of amiloride on responses to 10 mM HCl, 10 mM citric acid, 100 mM NaCl, and 100 mM sucrose were then investigated. Stimuli were presented alone for 30 s (control trials) and also presented for 10 s, followed by a mixture of the stimulus with 10 μM amiloride for 10 s, followed by the stimulus alone again for 10 s (amiloride trials). The effects of amiloride were assessed by comparing the responses of cells with the stimulus + amiloride with that of the stimulus alone. In neurons classified as NaCl-best, amiloride reversibly blocked responses to NaCl, HCl, and citric acid. In HCl-best neurons, amiloride had no effect on responses to any of these stimuli. In sucrose-best neurons, amiloride blocked the response to NaCl but not to sucrose or to either acid. These results support the hypothesis that acids are transduced by at least two different receptor mechanisms in the hamster, amiloride sensitive and amiloride insensitive. At the NST, these inputs are tightly maintained in two separate populations of neurons. Sucrose-best neurons, which show amiloride effects on NaCl but not acids, appear to receive converging inputs from both amiloride-sensitive (N-best) and amiloride-insensitive (H-best) chorda tympani nerve fibers.

Activity in the Hypothalamus, Amygdala, and Cortex Generates Bilateral and Convergent Modulation of Pontine Gustatory Neurons

2004 ◽  
Vol 91 (3) ◽  
pp. 1143-1157 ◽  
Author(s):  
Robert F. Lundy ◽  
Ralph Norgren
Keyword(s):  
Citric Acid ◽  
Hypothalamic Stimulation ◽  
Central Nucleus ◽  
Parabrachial Nucleus ◽  
Stimulus Response ◽  
Sodium Appetite ◽  
Response Profiles ◽  
Chemical Selectivity ◽  
Gustatory Neurons ◽  
Stimulation Of

Evidence suggests that centrifugal modulation of brain stem gustatory cells might play a role in the elaboration of complex taste-guided behaviors like conditioned taste aversion and sodium appetite. We previously showed that activity in one forebrain area, the central nucleus of the amygdala (CeA), increased the chemical selectivity of taste cells in the parabrachial nucleus (PBN). The present study investigates how activity in 2 other similarly interconnected forebrain sites, the lateral hypothalamus (LH) and gustatory cortex (GC), might influence PBN gustatory processing in rats. The potential convergence of descending inputs from these sites, as well as the CeA, was also evaluated. After anesthesia (35 mg/kg Nembutal ip), 70 PBN gustatory neurons were tested before, during, and after electrical stimulation of these forebrain sites, while responding to 0.3 M sucrose, 0.1 M NaCl, 0.01 M citric acid, and 0.003 M QHCl. Although each forebrain site modulated taste-evoked responses, more PBN neurons were influenced by stimulation of the GC (67%) and CeA (73%) than of the LH (48%). Activation of cortex (71%) and amygdala (85%) most often produced inhibition, whereas inhibition and excitation occurred equally often during hypothalamic stimulation. Of the neurons tested for convergence ( n = 60), 88% were influenced by ≥1 of the 3 sites. Twenty were modulated by stimulation at all 3 sites and another 17 by 2 of the 3 sites. The net effect of centrifugal modulation was to sharpen the across-stimulus response profiles of PBN cells, particular with regard to the NaCl- and citric acid-best cells.

scholarly journals OP0173 IMMUNOMODULATION CO-THERAPY WITH PEGLOTICASE: DATABASE TRENDS 2014-2019

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 108.2-108
Author(s):  
B. Lamoreaux ◽  
M. Francis-Sedlak ◽  
K. Svensson ◽  
R. Holt
Keyword(s):  
Case Series ◽  
Standard Of Care ◽  
Response Rates ◽  
Therapeutic Benefit ◽  
Azathioprine Therapy ◽  
Claims Database ◽  
Immunomodulating Therapy ◽  
Therapeutic Benefits ◽  
To Receive ◽  
Medical Claims Database

Background:Pegloticase is a PEGylated biologic therapy for patients with uncontrolled gout who have not improved on or could not tolerate conventional urate-lowering therapies.1All biologics have the ability to engender anti-drug antibodies (ADAs) and it is known that some patients given pegloticase develop ADAs that cause them to stop treatment prior to recieving a complete course of therapy.2-3In other rheumatic autoimmune diseases, DMARDs such as methotrexate or azathioprine are used as standard of care to prevent the development of ADAs to biologics. These DMARDs often allow patients to remain on biologic therapies longer and recieve the full therapeutic benefits while minimizing adverse events.4While pegloticase has been used traditionally as monotherapy, recent case series have demonstrated the therapeutic benefit of immunomodulator co-administration, allowing more patients to receive a full course of pegloticase therapy.5-6Little has been published on how widespread this practice is and whether it has changed over time.Objectives:To examine medical claims database from 2014-2019 for trends in immunomodulating therapies being co-prescribed with pegloticase.Methods:An IQVIA claims database (November 2014 to October 2019) representing 1.3 billion claims, covering 30 million patients diagnosed with gout or CKD, was utilized to search for patients who had received pegloticase. Patients who had recieved pegloticase were classified as having been on an immunomodulating co-therapy if they were prescribed methotrexate or azathioprine within 60 days before or after initiation of their first pegloticase infusion.Results:We found relatively steady low rates of immunomodulation co-therapy with pegloticase from 2014 through 2018 ranging from 1% in 2016 to 4% in 2018 (Figure 1). In 2019 however, the proportion of pegloticase patients that were co-treated with methotrexate or azathioprine therapy increased to 15%. Most patients were started on immunomodulating therapy 20 days before to 10 days after initiation of pegloticase. Methotrexate was the more frequently used immunomodulaton co-therapy as compared to azathioprine.Conclusion:We found evidence of a relatively dramatic increasing initiation of immunomodulation therapy with pegloticase beginning soon after a November 2018 presentation of a case series which demonstrated improved response rates of pegloticase when co-administered with methotrexate. These data indicate that clinicians began to more frequently employ a strategy of DMARD co-treatment with pegloticase in 2019 to improve response rates to this important gout medicine.References:[1]Sundy JS, et al.JAMA2011;306:711-20.[2]Abeles AM.Arthritis Research & Therapy2014, 16:112[3]Strand V, et al.BioDrugs2017; 31:299–316.[4]Krieckaert CL, et al.Arthritis Res Ther2010;12:217.[5]Botson J and Peterson J.Ann Rheum Dis.2019; 78: A1289.[6]Bessen SY, et al.Semin Arthritis Rheum.2019;49:56-61.Disclosure of Interests:Brian LaMoreaux Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, Megan Francis-Sedlak Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, Karl Svensson Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, Robert Holt Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics

Differential Gurmarin Suppression of Sweet Taste Responses in Rat Solitary Nucleus Neurons

2003 ◽  
Vol 90 (2) ◽  
pp. 911-923 ◽  
Author(s):  
Christian H. Lemon ◽  
Toshiaki Imoto ◽  
David V. Smith
Keyword(s):  
Cluster Analysis ◽  
Sucrose Concentration ◽  
Hierarchical Cluster ◽  
Initial Response ◽  
Sweet Taste ◽  
Induced Response ◽  
Response Suppression ◽  
Response Profiles ◽  
Neuronal Type ◽  
Concentration Series

We examined the effect of the sweet transduction blocker gurmarin on taste responses recorded from neurons in the rat solitary nucleus (NST) to determine how gurmarin sensitivity is distributed across neuronal type. Initially, responses evoked by washing the anterior tongue and palate with 0.5 M sucrose, 0.1 M NaCl, 0.01 M HCl, and 0.01 M quinine-HCl were recorded from 35 neurons. For some cells, responses to a sucrose concentration series (0.01–1.0 M) or an array of sweet-tasting compounds were also measured. Gurmarin (10 μg/ml, 2–4 ml) was then applied to the tongue and palate. Stimuli were reapplied after 10–15 min. Neurons were segregated into groups based on similarities among their initial response profiles using hierarchical cluster analysis (HCA). Results indicated that sucrose responses recorded from neurons representative of each HCA-defined class were suppressed by gurmarin. However, a disproportionate percentage of cells in each group displayed sucrose responses that were substantially attenuated after gurmarin treatment. Postgurmarin sucrose responses recorded from neurons that composed 57% of class S, 40% of class N, and 33% of class H were suppressed by ≥50% relative to control. On average, attenuation was statistically significant only in class S and N neurons. Although the magnitude of gurmarin-induced response suppression did not differ across sucrose concentration, responses to different sweet-tasting compounds were differentially affected. Responses to NaCl, HCl, or quinine were not suppressed by gurmarin. Results suggest that information from gurmarin-sensitive and -insensitive receptor processes converges onto single NST neurons.

Sodium-deficient diet reduces gustatory activity in the nucleus of the solitary tract of behaving rats

1995 ◽  
Vol 269 (3) ◽  
pp. R647-R661 ◽  
Author(s):  
K. Nakamura ◽  
R. Norgren
Keyword(s):  
Citric Acid ◽  
Dietary Sodium ◽  
Solitary Tract ◽  
Deficient Diet ◽  
Dietary Condition ◽  
Response Profiles ◽  
The Mean ◽  
Response To Water ◽  
Gustatory Neurons ◽  
General Reduction

The activity of single taste neurons was recorded from the nucleus of the solitary tract before (n = 41) and after (n = 58) awake, behaving rats were switched to a sodium-free diet. During sodium deprivation, the spontaneous activity of the neurons increased (142%), but responses to water and sapid stimuli decreased. For all neurons in the sample, the mean response to water decreased to 72% of its predeprivation level, NaCl dropped to 53%, sucrose to 41%, citric acid to 68%, and quinine HCl to 84%. Despite the drop in magnitude, the response profiles of the taste neurons were not changed by the dietary condition. In the Na-replete state, 61% of the activity elicited by NaCl occurred in NaCl-best cells and 33% in sucrose-best neurons. In the depleted state, these values were 60 and 26%, respectively. Nevertheless, at the highest concentrations tested, deprivation did alter the relative responsiveness of the gustatory neurons to sucrose and NaCl in specific categories of neurons. Compared with acute preparations, dietary sodium deprivation in awake, behaving rats produced a more general reduction in the gustatory responses of neurons in the nucleus of the solitary tract. The largest reductions in elicited activity occurred for the "best stimulus" of a particular neuron, thus leading to smaller differences in response magnitude across stimuli, particularly at the highest concentrations tested.

Gustatory neural coding in the monkey cortex: stimulus quality

1991 ◽  
Vol 66 (4) ◽  
pp. 1156-1165 ◽  
Author(s):  
V. L. Smith-Swintosky ◽  
C. R. Plata-Salaman ◽  
T. R. Scott
Keyword(s):  
Cortical Neurons ◽  
Neural Coding ◽  
Monosodium Glutamate ◽  
Stimulus Array ◽  
Cortical Region ◽  
Stimulus Similarity ◽  
Somatosensory Stimulation ◽  
Wide Range ◽  
Response Profiles ◽  
Stimulation Of

1. Extracellular action potentials were recorded from 50 single neurons in the insular-opercular cortex of two alert cynomolgus monkeys during gustatory stimulation of the tongue and palate. 2. Sixteen stimuli, including salts, sugars, acids, alkaloids, monosodium glutamate, and aspartame, were chosen to represent a wide range of taste qualities. Concentrations were selected to elicit a moderate gustatory response, as determined by reference to previous electrophysiological data or to the human psychophysical literature. 3. The cortical region over which taste-evoked activity could be recorded included the frontal operculum and anterior insula, an area of approximately 75 mm3. Taste-responsive cells constituted 50 (2.7%) of the 1,863 neurons tested. Nongustatory cells responded to mouth movement (20.7%), somatosensory stimulation of the tongue (9.6%), stimulus approach or anticipation (1.7%), and tongue extension (0.6%). The sensitivities of 64.6% of these cortical neurons could not be identified by our stimulation techniques. 4. Taste cells had low spontaneous activity levels (3.7 +/- 3.0 spikes/s, mean +/- SD) and showed little inhibition. They were moderately broadly tuned, with a mean entropy coefficient of 0.76 +/- 0.17. Excitatory responses were typically not robust. 5. Hierarchical cluster analysis was used to determine whether neurons could be divided into discrete types, as defined by their response profiles to the entire stimulus array. There was an apparent division of response profiles into four general categories, with primary sensitivities to sodium (n = 18), glucose (n = 15), quinine (n = 12), and acid (n = 5). However, these categories were not statistically independent. Therefore the notion of functionally distinct neuron types was not supported by an analysis of the distribution of response profiles. It was the case, however, that neurons in the sodium category could be distinguished from other neurons by their relative specificity. 6. The similarity among the taste qualities represented by this stimulus array was assessed by calculating correlations between the activity profiles they elicited from these 50 neurons. The results generally confirmed expectations derived from human psychophysical studies. In a multidimensional representation of stimulus similarity, there were groups that contained acids, sodium salts, and chemicals that humans label bitter and sweet. 7. The small proportion of insular-opercular neurons that are taste sensitive and the low discharge rates that taste stimuli are able to evoke from them suggest a wider role for this cortical area than just gustatory coding.(ABSTRACT TRUNCATED AT 400 WORDS)

Fronto-striatal network activation leads to less fatigue in multiple sclerosis

2017 ◽  
Vol 24 (9) ◽  
pp. 1174-1182 ◽  
Author(s):  
Ekaterina Dobryakova ◽  
Hanneke E Hulst ◽  
Angela Spirou ◽  
Nancy D Chiaravalloti ◽  
Helen M Genova ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Goal Attainment ◽  
Functional Neuroimaging ◽  
Network Activation ◽  
Healthy Control ◽  
Neuroimaging Study ◽  
To Receive ◽  
Monetary Gain ◽  
Healthy Participants ◽  
Stimulation Of

Background: The fronto-striatal network has been implicated in both fatigue, a common multiple sclerosis (MS) symptom, and goal attainment, which has been shown to reduce fatigue in healthy individuals. Objectives: To investigate whether stimulation of the fronto-striatal network through goal attainment (potential monetary gain) leads to fatigue reduction in MS and healthy control (HC) participants. Methods: In all, 14 healthy and 19 MS participants performed a gambling task during functional magnetic resonance imaging (fMRI). Participants were presented with an opportunity to receive monetary reward during the outcome condition of the task but not during the no outcome condition. Self-reported fatigue measures were obtained after each condition and outside of the scanner. Structural alterations were also examined. Results: A significant decrease in fatigue was observed after the outcome condition compared to the no outcome condition in both groups. Significantly greater activation was observed in the ventral striatum in association with the outcome condition compared to the no outcome condition in both groups. Ventromedial prefrontal cortex showed significantly greater activation during the no outcome condition compared to the outcome condition with greater difference between conditions in the HC group. Conclusion: This is the first functional neuroimaging study showing that stimulation of the fronto-striatal network through goal attainment leads to decreased on-task fatigue in MS and healthy participants.

Concept of neuron types in gustation in the rat

1979 ◽  
Vol 42 (5) ◽  
pp. 1390-1409 ◽  
Author(s):  
D. C. Woolston ◽  
R. P. Erickson
Keyword(s):  
Dimensional Space ◽  
Correlation Coefficients ◽  
Hierarchical Cluster ◽  
Scaling Analysis ◽  
Peripheral Neurons ◽  
Neuron Response ◽  
The Matrix ◽  
Formal Taxonomy ◽  
Response Profiles ◽  
Mathematical Techniques

1. In taste neurophysiology, from Pfaffmann's (49, 50) pioneering work until the present, the possibility of types of neurons corresponding in some sense with the "primary" taste qualities of Henning (33) has been entertained: recently types of gustatory neurons in peripheral nerves have been established according to which of the four classical stimuli is the "best stimulus." However, considerable variation occurs in the response profiles within neurons classified as belonging to the same type. The purpose of this research is to determine, using mathematical techniques where appropriate, if the within-type variation is spurious or, instead, indicates the absence of a typology of taste neurons. The data used were counts of the spike discharges of 50 individual taste neurons in the nucleus of the solitary tract of the rat, evoked by 32 diverse chemical stimuli. 2. Using as input the matrix of Pearson r correlation coefficients calculated for the responses of all pairings of neurons to all stimuli, multidimensional scaling analysis revealed a two-dimensional space in which no clear groupings of neurons occurred. 3. In a hierarchical cluster analysis of the neuron response profile similarities, no evidence of grouping was found, suggesting a more-or-less continuous variation among neurons. 4. When the organization of the 32 stimuli utilized was studied by the same techniques, no clear evidence for stimulus types was found, although the possibility of two stimulus types--"sweet" and "nonsweet"--was raised. 5. Construction of a joint neuron-stimulus space supported a spatial model of taste neuron-stimulus interaction, while analysis of the number and pattern of high correlations among neurons--even after allowance for attenuation due to measurement error--failed to support the notion of types of taste neurons with identical response profiles. 6. Aspects of the logical role of types of neurons in gustatory coding were discussed, and the results and methods of the present investigation were related to classification schemes for neurons in general. Suggestions for a formal taxonomy of neurons were given. 7. It should be emphasized that the present study and conclusions are of second-order, CNS neurons, whereas the studies advocating the presence of neurons types were of peripheral neurons. Taken together, the implication to be drawn from these studies is that if neural types do exist in peripheral taste nerves, the typology is lost at the first synapse and is thus unavailable to the CNS for coding purposes, at least in the rat.

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