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- Does the smell of alcohol make it harder to resist' The impact of
olfactory cues on inhibitory control and attentional bias-
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Abstract: Background It is well known that, owing to associative processing, olfactory cues can impact memory, emotion and behaviour. Research also points to a link between the smells of particular substances and craving. Yet, to date, little research has investigated how smell may impact other cognitive processes that are known to drive alcohol consumption. Aim To assess how exposure to alcohol-related (vodka) relative to neutral (citrus) olfactory cues impacts inhibitory control and attentional bias. Method Participants took part in a go/no-go (Study 1) and Stroop task (Study 2) while wearing masks that were pre-treated with vodka or citrus oil of equivalent intensity. Study 1 results Response error rates were higher in participants in the alcohol-related (versus neutral) olfactory condition, with no interaction between olfactory and visual cue. Study 2 results Responses to alcohol-related versus neutral words were similar, while performance appeared significantly impaired among participants wearing alcohol (relative to citrus) infused masks. Conclusion The smell of alcohol may impair signal detection performance on the go/no-go and Stroop task. As inhibitory control and attentional processes are known to be associated with decisions to drink or exercise restraint, these results may have implications for our understanding of alcohol consumption and for tailoring interventions.
PubDate: 2022-05-26
- Δ9-THC reduces reward-related brain activity in healthy adults
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Abstract: Rationale Greater availability of cannabis in the USA has raised concerns about adverse effects of the drug, including possible amotivational states. Lack of motivation may be assessed by examining acute effects of cannabinoids on reward processing. Objectives This study examined single doses of delta-9-tetrahydrocannabinol (∆9-THC; 7.5, 15 mg oral) in healthy adults using a version of the monetary incentive delay (MID) task adapted for electroencephalography (EEG; e-MID) in a within-subjects, double blind design. Methods Two phases of reward processing were examined: anticipation, which occurs with presentation of cues that indicate upcoming reward, punishment, or neutral conditions, and outcome, which occurs with feedback indicating hits or misses. During anticipation, we measured two event-related potential (ERP) components: the P300, which measures attention and motivation, and the LPP, which measures affective processing. During outcome processing, we measured P300 and LPP, as well as the RewP, which measures outcome evaluation. Results We found that ∆9-THC modulated outcome processing, but not reward anticipation. Specifically, both doses of ∆9-THC (7.5 and 15 mg) reduced RewP amplitudes after outcome feedback (hits and misses) relative to placebo. ∆9-THC (15 mg) also reduced P300 and LPP amplitudes following hits compared to misses, relative to both placebo and 7.5 mg ∆9-THC. Conclusions These findings suggest that ∆9-THC dampens responses to both reward and loss feedback, which may reflect an “amotivational” state. Future studies are needed to determine generalizability of this effect, such as its pharmacological specificity and its specificity to monetary vs other types of reward.
PubDate: 2022-05-25
- Editorial Expression of Concern: Histamine- and haloperidol-induced
catalepsy in aged mice: differential responsiveness to l-DOPA-
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PubDate: 2022-05-21
- Editorial Expression of Concern: Synergistic anticataleptic effect of
imipramine and nicotine in a rotenone-induced rat model-
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PubDate: 2022-05-21
- Editorial Expression of Concern: Anticataleptic activity of nicotine in
rats: involvement of the lateral entorhinal cortex-
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PubDate: 2022-05-21
- Editorial Expression of Concern: Somatostatin antagonist induces catalepsy
in the aged rat-
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PubDate: 2022-05-21
- Sex and drug differences in stress, craving and cortisol response to the
trier social stress task-
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Abstract: Rationale The hypothalamic–pituitary–adrenal (HPA) axis is a critical hormonal system involved in stress response. A number of studies have investigated the HPA axis response of drug-dependent individuals to stressors. Stress-induced vulnerabilities in the HPA axis may differ in response to chronic use of different substances, possibly leading to different target therapies. There has not been a direct comparison of HPA axis and subjective response between individuals with different types of substance use disorders following a laboratory stress intervention. Objectives The primary goal of the current study was to compare subjective and neuroendocrine response to the Trier Social Stress Task (TSST) across multiple primary types of substance use disorders and investigate differential response between males and females. Methods Four hundred participants were drawn from seven studies completed at the Medical University of South Carolina between 2011 and 2021. The TSST was utilized across studies and subjective and neuroendocrine responses measured following completion. Generalized linear mixed effects models and area under the response curve analysis were used to compare both substance type and sex differences. Results The study groups involving individuals with cocaine use disorder had blunted stress, craving and cortisol response following the TSST as compared to other substance use groups. Females in the cocaine groups reported higher subjective stress but lower cortisol than males. Conclusions The study results indicate that there may be differential effects of substances on the HPA axis, with cocaine using individuals exhibiting more blunting of the HPA axis response as compared to users of other substances.
PubDate: 2022-05-20
- PP2A-associated tau hyperphosphorylation was involved in sevoflurane
induced neonatal neurotoxicity-
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Abstract: Background The effects of sevoflurane anesthesia on childhood neurodevelopment and adult brain function have attracted increasing scientific attentions. However, the exact mechanisms underlying hyperphosphorylation of tau protein in sevoflurane induced abnormalities in central nervous system (CNS) development, particularly in the hippocampus, have not been fully determined. Methods We utilized molecular biological and behavioral approaches to compare the changes in cognitive function in mice exposed to repeated sevoflurane during the neonatal stage, and to assess whether PP2A-associated tau hyperphosphorylation is involved in sevoflurane induced neonatal neurotoxicity. Results We reported that mice anesthetized with repeated sevoflurane during the neonatal period caused cognitive dysfunction during the adulthood. More importantly, we found that hyperphosphorylation of tau protein and decreased level of protein phosphatase 2A (PP2A) were detected in the hippocampus of mice after neonatal exposure of sevoflurane. Meanwhile, GSK-3β activity was found to be increased with repeated sevoflurane exposure, but not for more than 2 weeks. Conclusion Our results suggest that PP2A-associated hyperphosphorylation of tau protein might contribute to sevoflurane induced developmental neurotoxicity. These findings could provide a theoretical basis for the safely usage of sevoflurane in pediatric surgeries, and offer a valuable reference and potential therapeutic targets for the development of neuroprotective drugs.
PubDate: 2022-05-17
- Development of pulsed intravenous nicotine infusions as a model for
inhaled nicotine in humans-
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Abstract: Rationale Although nicotine from cigarettes is delivered in puff-sized amounts, most preclinical and human intravenous (IV) nicotine studies have used bolus or continuous infusions. Objectives To determine the feasibility of a pulsed-nicotine infusion model in smokers. Methods Following overnight abstinence, 12 adult smokers underwent 5 laboratory sessions. Using a crossover design, in each session, participants were assigned to 1 of 5 conditions: (1) high/fast: 1.0 mg nicotine delivered over 5 pulsed-infusions, then 15 saline infusions; (2) high/slow: 1.0 mg nicotine delivered over 20 pulsed-infusions; (3) low/fast: 0.2 mg nicotine delivered over 5 pulsed-infusions, then 15 saline infusions; (4) low/slow: 0.2 mg nicotine delivered over 20 pulsed-infusions; and (5) placebo: Saline delivered over 20 pulsed-infusions. Subjective drug effects, urges to smoke, nicotine withdrawal, and cognitive performance were measured in each session. Results Both the high/fast and high/slow conditions were associated with greater “head rush” and “high” (p < 0.05). The high/fast condition also provided greater suppression of urges to smoke and nicotine withdrawal (p < 0.05), indexed by the Questionnaire of Urges to Smoke-Brief, and the Minnesota Nicotine Withdrawal Scale, respectively. The high/fast and high/slow conditions produced greater increases in heart rate (p < 0.01) than saline. Finally, there were no main effects of dosing conditions on cognitive performance, indexed by the continuous performance test. Conclusions These findings demonstrate the feasibility of pulsed-nicotine infusions to model nicotine delivery by smoking. This model could inform future studies testing novel smoking cessation therapies and tobacco regulatory studies testing the impact of nicotine reduction approaches.
PubDate: 2022-05-13
- Acute tryptophan depletion alters affective touch perception
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Abstract: Rationale Affiliative tactile interactions help regulate physiological arousal and confer resilience to acute and chronic stress. C-tactile afferents (CTs) are a population of unmyelinated, low threshold mechanosensitive cutaneous nerve fibres which respond optimally to a low force stimulus, moving at between 1 and 10 cm/s. As CT firing frequencies correlate positively with subjective ratings of touch pleasantness, they are hypothesised to form the first stage of encoding affiliative tactile interactions. Serotonin is a key modulator of social responses with known effects on bonding. Objectives The aim of the present study was to determine the effect of acutely lowering central serotonin levels on perceptions of CT-targeted affective touch. Methods In a double blind, placebo-controlled design, the effect of acute tryptophan depletion (ATD) on 25 female participants’ ratings of directly and vicariously experienced touch was investigated. Psychophysical techniques were used to deliver dynamic tactile stimuli; some velocities were targeted to optimally activate CTs (1–10 cm/s), whereas other, faster and slower strokes fell outside the CT optimal range. Discriminative tactile function, cold pain threshold and tolerance were also measured. Results ATD significantly increased pleasantness ratings of both directly and vicariously experienced affective touch, increasing discrimination of the specific hedonic value of CT targeted velocities. While ATD had no effect on either tactile or cold pain thresholds, there was a trend for reduced tolerance to cold pain. Conclusions These findings are consistent with previous reports that depletion of central serotonin levels modulates neural and behavioural responsiveness to appetitive sensory signals.
PubDate: 2022-05-12
- Glibenclamide alters serotonin and dopamine levels in the rat striatum and
hippocampus, reducing cognitive impairment-
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Abstract: Rationale Glibenclamide (GD) is a widely used medical drug; therefore, identifying the mechanisms underlying its pleiotropic effects in the central nervous system is urgent. Objectives The aim of this work was to determine the ability of GD to modulate serotonin (5-hydroxytryptamine, 5-HT) and dopamine (DA) transmission and to assess the dose-dependent effect of GD on cognitive function in rats during natural ageing. Methods In Experiment 1, rats received 10, 25, or 50 μg/kg GD intraperitoneally for 10 days. In Experiment 2, rats received 50 μg/kg GD intraperitoneally for 30 days. Spatial and working memory was assessed in the MWM and Y-maze tests, respectively. In both experiments, the levels of DA and 5-HT, their metabolites, and turnover rate were analysed by HPLC-ED in the rat hippocampus and striatum. Results Changes in DA and 5-HT levels occurred only with a dose of 50 μg/kg GD. Therefore, in the second experiment, we administered a dose of 50 μg/kg GD. At this dose, GD prevented the development of impairments in spatial and working memory. The hippocampal concentrations of DA and DOPAC decreased, and the striatal concentrations of DA, DOPAC, 5-HT, and 5-HIAA increased. Conclusion One of the possible mechanisms of the precognitive effect of GD is its ability to modulate monoamine transmission. Thus, in translating our results to humans, GD can be recommended as a prophylactic agent for natural ageing to reduce the risk of developing cognitive impairments.
PubDate: 2022-05-11
- Correction to: Psychedelics: Old trips, new destinations in
psychopharmacology research-
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PubDate: 2022-05-11
- Effects of alcohol hangover on attentional resources during a verbal
memory/psychomotor tracking dual attention task-
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Abstract: Background Alcohol hangover (AH) is associated with impaired attention and memory performance. However, whether this effect is related to reduced attentional resources remains unclear. Aims A dual-attention paradigm was employed to assess the effects of AH on attentional resources, delayed memory recognition, and the interaction between attentional load and AH. Mental effort and perceived performance during AH and control conditions were also assessed. Methods A seminaturalistic, crossover design was used. In total, 25 healthy social drinkers aged 18–35 years, visited the laboratory following a typical night out drinking (Hangover condition) and after alcohol abstinence (control) between 8:30 am and 12:30 pm, with conditions counterbalanced. Attentional load was manipulated via the presence (dual attention) or absence of psychomotor tracking during verbal memory encoding. Perceived mental effort and performance were measured using the NASA-TLX. Participants’ recollected alcohol consumption was used to compute estimated blood alcohol level (eBAC). Results Compared with the control visit, AH was associated with reduced recognition accuracy (particularly more false negatives), higher “tracking costs” (poorer accuracy) in the dual attention condition, increased ratings of “mental demand,” “effort,” and “frustration,” and lower ratings of task performance. There was also a significant main effect of attentional load with poorer recognition accuracy and response time in the dual attention condition. There were no significant interaction effects between hangover and attentional load. Conclusion These findings suggest that reduced attentional resources contribute to the cognitive deficits associated with AH including impaired memory consolidation. They further suggest that while hungover, participants are aware of these deficits but are unable to compensate.
PubDate: 2022-05-11
- Histamine H3 receptor antagonist, ciproxifan, alleviates cognition and
synaptic plasticity alterations in a valproic acid-induced animal model of
autism-
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Abstract: Rationale Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and cognitive behaviors. Histamine H3 receptor (H3R) antagonists are considered as therapeutic factors for treating cognitive impairments. Objectives The aim of the present study was to evaluate the effects of the H3R antagonist, ciproxifan (CPX), on cognition impairment especially, spatial learning memory, and synaptic plasticity in the CA1 region of the hippocampus in autistic rats. Methods Pregnant rats were injected with either valproic acid (VPA) (600 mg/kg, i.p.) or saline on an embryonic day 12.5 (E12.5). The effects of the H3R antagonist, ciproxifan (CPX) (1, 3 mg/kg, i.p.), were investigated on learning and memory in VPA-exposed rat pups and saline-exposed rat pups using Morris water maze (MWM) and social interaction tasks. The H2R antagonist, famotidine (FAM) (10, 20, 40 mg/kg, i.p.), was used to determine whether brain histaminergic neurotransmission exerted its procognitive effects through the H2R. In addition, synaptic reinforcement was evaluated by in vivo field potential recording. Results The results showed that VPA-exposed rat pups had significantly lower sociability and social memory performance compared to the saline rats. VPA-exposed rat pups exhibited learning and memory impairments in the MWM task. In addition, VPA caused suppression of long-term potentiation (LTP) in the CA1 area of the hippocampus. Our results demonstrated that CPX 3 mg/kg improved VPA-induced cognitive impairments and FAM 20 mg/kg attenuated cognitive behaviors as well as electrophysiological properties. Conclusions CPX 3 mg/kg improved VPA-induced impairments of LTP as well as learning and memory deficits through H2R.
PubDate: 2022-05-11
- Inactivation of the thalamic paraventricular nucleus promotes place
preference and sucrose seeking in male rats-
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Abstract: Rationale The experience of reward entails both positive affect and motivation. While the brain regions responsible for these distinct aspects of reward are dissociable from each other, the paraventricular nucleus of the thalamus (PVT) may play a role in both. Objectives To investigate the role of the PVT in both affect and motivation, and to identify neuropeptides that might mediate these effects. Methods Male rats were tested for conditioned place preference following temporary inactivation of the anterior or posterior PVT with local injections of the GABAB and GABAA agonists, baclofen + muscimol. They were tested for sucrose seeking under a fixed ratio 3 (FR3) schedule of reinforcement and after extinction, following injection into the posterior PVT of baclofen + muscimol or saline vehicle. Finally, quantitative real-time PCR was used to examine local neuropeptide gene expression following injection into the posterior PVT of baclofen + muscimol or saline vehicle. Results Conditioned place preference was induced by temporary inactivation of the posterior but not anterior PVT. While sucrose seeking under an FR3 schedule of reinforcement was unaffected by inactivation of the posterior PVT, reinstatement of sucrose seeking was promoted by posterior PVT inactivation. Local gene expression of pituitary adenylate cyclase–activating polypeptide (PACAP), but not enkephalin or neurotensin, was reduced following inactivation of the posterior PVT. Conclusions Temporary inactivation of the posterior PVT affects both affect and motivation as well as local gene expression of PACAP. These results suggest that the posterior PVT is one brain region that may participate in both major aspects of reward.
PubDate: 2022-05-07
- Spatial frequency processing and its modulation by emotional content in
severe alcohol use disorder-
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Abstract: Rationale Visuo-perceptive deficits in severe alcohol use disorder (SAUD) remain little understood, notably regarding the respective involvement of the two main human visual streams, i.e., magnocellular (MC) and parvocellular (PC) pathways, in these deficits. Besides, in healthy populations, low-level visual perception can adapt depending on the nature of visual cues, among which emotional features, but this MC and PC pathway adaptation to emotional content is unexplored in SAUD. Objectives To assess MC and PC functioning as well as their emotional modulations in SAUD. Methods We used sensitivity indices (d′) and repeated-measures analyses of variance to compare orientation judgments of Gabor patches sampled at various MC- and PC-related spatial frequencies in 35 individuals with SAUD and 38 matched healthy controls. We then explored how emotional content modulated performances by introducing neutral or fearful face cues immediately before the Gabor patches and added the type of cue in the analyses. Results SAUD patients showed a general reduction in sensitivity across all spatial frequencies, indicating impoverished processing of both coarse and fine-scale visual content. However, we observed selective impairments depending on facial cues: individuals with SAUD processed intermediate spatial frequencies less efficiently than healthy controls following neutral faces, whereas group differences emerged for the highest spatial frequencies following fearful faces. Altogether, SAUD was associated with mixed MC and PC deficits that may vary according to emotional content, in line with a flexible but suboptimal use of low-level visual content. Such subtle alterations could have implications for everyday life’s complex visual judgments.
PubDate: 2022-05-06
- An experimental medicine study of the effects of simvastatin on emotional
processing, reward learning, verbal memory, and inflammation in healthy
volunteers-
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Abstract: Rationale Clinical studies suggest that the highly lipophilic, anti-inflammatory molecule, simvastatin, might be an ideal candidate for drug repurposing in the treatment of depression. The neuropsychological effects of simvastatin are not known, but their ascertainment would have significant translational value about simvastatin’s influence on mood and cognition. Objectives We aimed to investigate the effects of simvastatin on a battery of psychological tests and inflammatory markers in healthy volunteers. Methods Fifty-three healthy subjects were randomly assigned to 7 days of either simvastatin (N = 27) or sucrose-based placebo (N = 26) given in a double-blind fashion. Then, participants were administered questionnaires measuring subjective rates of mood and anxiety, and a battery of tasks assessing emotional processing, reward learning, and verbal memory. Blood samples for C-reactive protein were also collected. Results Compared to placebo, participants on simvastatin showed a higher number of positively valenced intrusions in the emotional recall task (F1,51 = 4.99, p = 0.03), but also an increase in anxiety scores (F1,51 = 5.37, p = 0.02). An exploratory analysis of the females’ subgroup (N = 27) showed lower number of misclassifications as sad facial expression in the simvastatin arm (F1,25 = 6.60, p = 0.02). No further statistically significant changes could be observed on any of the other outcomes measured. Conclusions We found limited evidence that 7-day simvastatin use in healthy volunteer induces a positive emotional bias while also being associated with an increase in anxiety, potentially reflecting the early effects of antidepressants in clinical practice. Such effect might be more evident in female subjects. Different drug dosages, treatment lengths, and sample selection need consideration in further experimental medicine and clinical studies. Trial registration Clinicaltrials.gov: NCT04652089.
PubDate: 2022-05-05
- Do psychedelics change beliefs'
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Abstract: Abstract Renewed interest in psychedelics has reignited the debate about whether and how they change human beliefs. In both the clinical and social-cognitive domains, psychedelic consumption may be accompanied by profound, and sometimes lasting, belief changes. We review these changes and their possible underlying mechanisms. Rather than inducing de novo beliefs, we argue psychedelics may instead change the impact of affect and of others’ suggestions on how beliefs are imputed. Critically, we find that baseline beliefs (in the possible effects of psychedelics, for example) might color the acute effects of psychedelics as well as longer-term changes. If we are to harness the apparent potential of psychedelics in the clinic and for human flourishing more generally, these possibilities must be addressed empirically.
PubDate: 2022-05-04
- Alterations in gut microbiota affect behavioral and inflammatory responses
to methamphetamine in mice-
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Abstract: Rationale and objectives Methamphetamine (METH) is a highly addictive and widely abused drug that causes severe neuroinflammation in the human brain. The gut microbiota has a tremendous impact on the core symptoms of neuropsychiatric disorders via the microbiota-gut-brain (MGB) axis. However, it is not clear whether alterations in the gut microbiota are involved in METH exposure. Methods We established a mouse model with chronic, escalating doses of METH exposure. Intervene in gut microbiota with antibiotics to observe the changes of locomotor activity caused by METH exposure in mice. qPCR and 16S rRNA gene sequencing were used to analyze the gut microbiota profiles. In addition, we tested the levels of inflammatory factors in the nucleus accumbens (NAc), prefrontal cortex (mPFC), hippocampus (HIp), and spleen. Finally, short-chain fatty acids (SCFAs) were supplemented to determine the interaction between behavior changes and the structure of gut microbiota. Results In this research, METH increased the locomotor activity of mice, while antibiotics changed the effect. Antibiotics enhanced the expression of pro-inflammatory cytokines in mPFC, HIp, and spleen of METH-exposed mice. METH altered the gut microbiota of mice after antibiotic treatment, such as Butyricicoccus and Roseburia, which are related to butyrate metabolism. Supplementation with SCFAs changed the behavior of METH-exposed mice and decreased Parabacteroides and increased Lactobacillus in METH-exposed mice gut. Conclusions This research showed that antibiotics affected the behavior of METH-exposed mice and promoted inflammation. Our findings suggest that SCFAs might regulate METH-induced gut microbiota changes and behavior.
PubDate: 2022-05-03
- Effects of alcohol and task difficulty on visual tracking and
inattentional blindness-
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Abstract: Rationale Inattentional blindness (IB) describes the failure to notice salient but unexpected stimuli in one’s focal visual field. It typically occurs while performing a demanding task (e.g. tracking and counting basketball passes), which consumes attentional resources. Alcohol intoxication is also known to reduce attentional resources, thereby potentially increasing IB and disrupting task performance. Objectives To test the extent to which acute alcohol and task difficulty disrupt counting performance and increase the rate of IB across two experimental tasks. Methods To test the effects of alcohol consumption and task difficulty on IB, we used the Simons and Chabris (Percept 28:1059-1074, 1999) and Simons (2010) “gorilla in our midst” basketball clip in experiment 1 and abstract but analogous stimuli presented in a computerised alternative to that task in experiment 2. Results IB was associated with increased (counting) task difficulty but not alcohol consumption. However, counting accuracy was impaired by both alcohol and increased task difficulty, with the largest detriment being for alcohol participants who noticed the salient but unexpected stimulus. Conclusion The absence of alcohol effects on IB in both experiments was unexpected and warrants further investigation in a field vs lab study comparison and in combination with baseline cognitive measures to test for alcohol expectancy and task compensation effects.
PubDate: 2022-05-02
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