Deprivation Effect Research Articles

Attention enhances short-term monocular deprivation effect.

Patching one eye of an adult human for a few hours has been found to promote the dominance of the patched eye, which is called short-term monocular deprivation effect. Interestingly, recent work has reported that prolonged eye-specific attention can also cause a shift of ocular dominance toward the unattended eye though visual inputs during adaptation are balanced across the eyes. Considering that patching blocks all input information from one eye, attention is presumably deployed to the opposite eye. Therefore, the short-term monocular deprivation effect might be, in part, mediated by eye-specific attentional modulation. Yet this question remains largely unanswered. To address this issue, here we asked participants to perform an attentive tracking task with one eye patched. During the tracking, participants were presented with both target gratings (attended stimuli) and distractor gratings (unattended stimuli) that were distinct from each other in fundamental visual features. Before and after one hour of tracking, they completed a binocular rivalry task to measure perceptual ocular dominance. A larger shift of ocular dominance toward the deprived eye was observed when the binocular rivalry testing gratings shared features with the target gratings during the tracking compared to when they shared features with the distractor gratings. This result, for the first time, suggests that attention can boost the strength of the short-term monocular deprivation effect. Therefore, the present study sheds new light on the role of attention in ocular dominance plasticity.

Income inequality and healthcare utilization of the older adults-based on a study in three provinces and six cities in China.

The objective of this study is to gain a more nuanced understanding of the specific impact of income inequality on the utilization of healthcare services for older adults. Additionally, the study aims to elucidate the moderating and mediating roles of public transfer income and psychological health in this context. A systematic examination of the impact of income inequality on healthcare utilization among older adults was conducted through field questionnaire surveys in six cities across three major geographical regions (West, Central, and East). The analysis employed baseline regression, as well as mediating and moderating effect tests. First, there is a negative relationship between income inequality and the use of therapeutic healthcare services (β1 = -0.484, P < 0.01) and preventive healthcare services (β2 = -0.576, P < 0.01) by older adults. This relationship is more pronounced in the low- and medium-income groups as well as in the western region. The mediating effect of psychological state is significant (β3 = -0.331, P < 0.05, β4 = -0.331, P < 0.05). Public transfer income plays a significant role in regulation. The moderating effect of public transfer income on therapeutic services was more significant in low-income groups (β5 = 0.821, P < 0.01). The moderating effect of public transfer income on preventive services was more significant in middle-income groups (β6 = 0.833, P < 0.01). The study clearly demonstrates a significant negative correlation between income inequality and the utilization of healthcare services by older adults. Furthermore, the study reveals that this relationship is particularly pronounced among older adults in low- and medium-income and Western regions. This detailed analysis of regional and income level heterogeneity is of particular value in this field of research. Secondly, this study attempts to integrate the two pivotal dimensions of public transfer income and psychological state for the first time, elucidating their moderating and mediating roles in this relationship. The findings indicate that public transfer income serves as a moderating factor, exerting a notable "reordering effect" on income inequality and resulting in a "deprivation effect." Such factors may impede the utilization of medical services, potentially influencing the psychological state of older adults.

Negligible contribution of adaptation of ocular opponency neurons to the effect of short-term monocular deprivation.

Modeling work on binocular rivalry has described how ocular opponency neurons represent interocular conflict. These neurons have recently been considered to mediate an ocular dominance shift to the eye that has viewed a backward movie for long during which time the other eye is presented with a regular movie. Unlike typical short-term monocular deprivation, the visual inputs are comparable across eyes in that "dichoptic-backward-movie" paradigm. Therefore, it remains unclear whether the ocular opponency neurons are also responsible for the short-term monocular deprivation effect which is prevalently explained by the homeostatic compensation theory. We designed two experiments from distinct perspectives to investigate this question. In Experiment 1, we mitigated the imbalance in the activity of opponency neurons between the two eyes during monocular deprivation by presenting video stimuli alternately. In Experiment 2, we directly evaluated the response of opponency neurons before and after monocular deprivation using SSVEP techniques. Consistent with each other, both experiments failed to provide reliable evidence supporting the involvement of ocular opponency neurons in the short-term monocular deprivation effect. Our results suggest that ocular opponency neurons may not play an essential role in the short-term monocular deprivation effect, potentially due to interference from the homeostatic plasticity mechanism.

Material Hardship, Labor Market Characteristics and Substantiated Child Maltreatment: A Bayesian Spatiotemporal Analysis

Child maltreatment is a critical public health problem whose structural underpinnings underscore the need to move prevention efforts from individual-level risk factors to social policy. Despite previous studies exploring the evolution of child maltreatment risk in socially vulnerable contexts, little is known about how neighborhood level material deprivation and job market characteristics, beyond the employment context, impact substantiated maltreatment risk. The present analysis integrates multiple streams of data to explore the complexity of child maltreatment in the most populous county in New Mexico as a case-study. A geospatial model was used to produce posterior risk estimates and exceedance probabilities of substantiated child maltreatment derived from administrative records controlling for financial strength, economic inequality and hardship, educational attainment, housing and food insecurity and labor market characteristics. Findings showed that over the nine-year study period, the average relative risk of child maltreatment increased substantially, however, there was substantial regional and temporal heterogeneity. More specifically, substantiated child maltreatment risk became more highly concentrated into the most deprived 20% of neighborhoods over time. The results showed a very strong area deprivation effect such that: (1) the risk of maltreatment in the most deprived 20% of neighborhoods on financial strength was 130.78% higher compared to the least deprived 20% of neighborhoods; and (2) maltreatment rates in the bottom 20% of neighborhoods on economic inequality and hardship were 40.52% higher compared to the least deprived 20% of neighborhoods. Finally, substantiated child maltreatment was significantly associated with multiple labor market characteristics including commuting times to work, origin–destination job flows, and mode of transportation to work. From a policy perspective, the results of this study support structural interventions aimed at reducing neighborhood-level material hardship and labor market disadvantage as avenues to support parents so that children and families can thrive.

Age-period-cohort analysis of mortality and its association with deprivation in Hungary, 2007-2021

Abstract Background Severe spatial inequalities in health and its determinants are a well-known and long-standing phenomenon in Central-Eastern European countries, including Hungary. The aim of our study was to perform an age-period-cohort (APC) analysis to provide information on mortality trends and their association with deprivation in Hungary using the latest available data for the period 2007-2021. Methods The extended APC model, allowing estimation of mortality risk considering deprivation, time, age, and cohort effects and their interactions, was used to analyse the trajectories of several outcome variables along complex dimensions. Model fitting and inference were carried out by using Bayesian computation with INLA methodology. Results Mortality risk was the lowest in the 5-9 year age group and increased with age. Between 2007-19, the mortality risk showed a decreasing trend, which returned to the 2007 level by 2020-21 due to the COVID-19 pandemic. Considering the birth cohort effect, the mortality risk peaked in the 1953-57 cohort, then decreased until the 1972-76 cohort, followed by a steady state, and then decreased from the 1988-92 cohort onwards. Deprivation was positively associated with higher mortality risk. The interaction of deprivation and period effect on mortality risk showed a steeper increasing trend for deprived groups for 2020-21. In terms of the interaction of deprivation and cohort effect, the risk of mortality in the most deprived group was higher than the national risk for all birth cohorts. The risk increased until the 1967-71 cohort, then decreased until the 1992-96 cohort, and then again showed an increasing trend. The risk of mortality for the least deprived population was lower than the national average risk, while the opposite difference could be observed for the most deprived group. Conclusions Deprivation was associated with higher mortality risk, COVID-related mortality and cohort effect during the study period. Key messages • The COVID epidemic-associated increase in mortality affected groups of different deprivation status to varying degree. • Different cohort effects were found behind the mortality risk in different deprivation groups.

Acamprosate reduces ethanol intake in the rat by a combined action of different drug components

Alcohol misuse accounts for a sizeable proportion of the global burden of disease, and Campral® (acamprosate; calcium-bis-(N-acetylhomotaurinate)) is widely used as relapse prevention therapy. The mechanism underlying its effect has in some studies been attributed to the calcium moiety and not to the N-acetylhomotaurine part of the compound. We recently suggested that the dopamine elevating effect of acamprosate is mediated both by N-acetylhomotaurine and calcium in a glycine receptor dependent manner. Here we aimed to explore, by means of in vivo microdialysis, if our previous study using local administration was functionally relevant and if systemic administration of the sodium salt of N-acetylhomotaurine (sodium acamprosate; 200 mg/kg, i.p.) enhanced the effects of calcium chloride (CaCl2; 73.5 mg/kg, i.p.) on nucleus accumbens (nAc) dopamine and/or taurine levels in male Wistar rats. In addition, we investigated the impact of regular acamprosate and the combination of CaCl2 and N-acetylhomotaurine on the alcohol deprivation effect (ADE). Finally, we assessed if N-acetylhomotaurine potentiates the ethanol-intake reducing effect of CaCl2 in a two-bottle choice voluntary ethanol consumption model followed by an ADE paradigm. Systemic administration of regular acamprosate, sodium acamprosate and CaCl2 all trended to increase nAc dopamine whereas the combination of CaCl2 and sodium acamprosate produced a significant increase. Sodium acamprosate elevated extracellular taurine levels without additional effects of CaCl2. Ethanol intake was significantly reduced by systemic administration of CaCl2 without additional effects of the combination of CaCl2 and sodium acamprosate. Both acamprosate and CaCl2 combined with sodium acamprosate blocked the ADE following acute treatment. The data presented suggest that CaCl2 and N-acetylhomotaurine act in concert on a neurochemical level, but calcium appears to have the predominant effect on ethanol intake.

The neighborhood deprivation gradient and child physical abuse and neglect: A Bayesian spatial model

BackgroundChild abuse and neglect is a public health priority due to its long-term maladaptive consequences. No study in the USA has assessed the nature and magnitude of the social deprivation effect on substantiated child maltreatment risk. ObjectivesTo examine linear and non-linear relationships between area level deprivation and the log-risk of both substantiated physical abuse and neglect while accounting for spatial and heterogeneous random effects. MethodsSubstantiated child maltreatment and population data (2008–2015) were aggregated to neighborhoods in Bernalillo County, New Mexico. The contribution of area level deprivation to the geographical variation in the log-risks of substantiated child physical abuse and neglect was modeled using Bayesian spatial regression. ResultsForty-three percent and 46.4 % of the 153 neighborhoods recorded greater risk for either substantiated physical abuse or neglect compared to the county average. The most deprived 20 % of neighborhoods had 71 % and 72 % more cases of substantiated physical abuse and neglect, respectively, than would be expected if the substantiations were randomly distributed throughout the county. Area level deprivation explained 47 % of the variation in substantiated physical abuse and 51 % of the variation in substantiated neglect after controlling for both spatial autocorrelation and heterogeneity. ConclusionsImplications from this study can be used to quantify disparities in substantiated child maltreatment attributed to regional differences in social deprivation and to identify priority areas for intervention.

The GlyT1-inhibitor Org 24598 facilitates the alcohol deprivation abolishing and dopamine elevating effects of bupropion + varenicline in rats

Alcohol Use Disorder (AUD) is a relapsing brain disorder that involves perturbations of brain dopamine (DA) systems, and combined treatment with varenicline + bupropion produces additive effects on accumbal DA output and abolishes the alcohol deprivation effect (ADE) in rats. Also, direct and indirect glycine receptor (GlyR) agonists raise basal DA, attenuate alcohol-induced DA release in the nucleus Accumbens (nAc) and reduce alcohol consumption in rats. This study in rats examines whether the GlyT1-inhibitor Org 24598, an indirect GlyR agonist, enhances the ADE-reducing and DA elevating action of the combined administration of varenicline + bupropion in lower doses than previously applied. Effects on voluntary alcohol consumption, the ADE and extracellular levels of glycine and DA in nAc were examined following treatment with Org 24598 6 and 9 mg/kg i.p., bupropion 3.75 mg/kg i.p. and varenicline 1.5 mg/kg s.c., in monotherapy or combined, using a two-bottle, free-choice alcohol consumption paradigm with an ADE paradigm, and in vivo microdialysis in male Wistar rats. Notably, all treatment regimens appeared to abolish the ADE but only the effect produced by the triple combination (Org24598 + varenicline + bupropion) was significant compared to vehicle. Hence, addition of Org 24598 may enhance the ADE-reducing action of varenicline + bupropion and appears to allow for a dose reduction of bupropion. Treatment with Org 24598 raised accumbal glycine levels but did not significantly alter DA output in monotherapy. Varenicline + bupropion produced a substantial elevation in accumbal DA output that was slightly enhanced following addition of Org 24598. Conceivably, the blockade of the ADE is achieved by the triple combination enhancing accumbal DA transmission in complementary ways, thereby alleviating a hypothesized hypodopaminergia and negative reinforcement to drink. Ultimately, combining an indirect or direct GlyR agonist with varenicline + bupropion may constitute a new pharmacological treatment principle for AUD, although further refinement in dosing and evaluation of other glycinergic compounds are warranted.

Mutual Information between EDA and EEG in Multiple Cognitive Tasks and Sleep Deprivation Conditions.

Sleep deprivation, a widespread phenomenon that affects one-third of normal American adults, induces adverse changes in physical and cognitive performance, which in turn increases the occurrence of accidents. Sleep deprivation is known to increase resting blood pressure and decrease muscle sympathetic nerve activity. Monitoring changes in the interplay between the central and autonomic sympathetic nervous system can be a potential indicator of human's readiness to perform tasks that involve a certain level of cognitive load (e.g., driving). The electroencephalogram (EEG) is the standard to assess the brain's activity. The electrodermal activity (EDA) is a reflection of the general state of arousal regulated by the activation of the sympathetic nervous system through sweat gland stimulation. In this work, we calculated the mutual information between EDA and EEG recordings in order to consider linear and non-linear interactions and provide an insight of the relationship between brain activity and peripheral autonomic sympathetic activity. We analyzed EEG and EDA data from ten participants performing four cognitive tasks every two hours during 24 h (12 trials). We decomposed EEG data into delta, theta, alpha, beta, and gamma spectral components, and EDA into tonic and phasic components. The results demonstrate high values of mutual information between the EDA and delta component of EEG, mainly in working memory tasks. Additionally, we found an increase in the theta component of EEG in the presence of fatigue caused by sleep deprivation, the alpha component in tasks demanding inhibition and attention, and the delta component in working memory tasks. In terms of the location of brain activity, most of the tasks report high mutual information in frontal regions in the initial trials, with a trend to decrease and become uniform for all the nine analyzed EEG channels as a consequence of the sleep deprivation effect. Our results evidence the interplay between central and sympathetic nervous activity and can be used to mitigate the consequences of sleep deprivation.

Short-term monocular pattern deprivation reduces the internal additive noise of the visual system.

Previous studies have shown that short-term monocular pattern deprivation can shift perceptual dominance in favor of the deprived eye. However, little is known about the effect of monocular pattern deprivation on contrast sensitivity (CS) and its corresponding mechanisms. Here, contrast sensitivity function (CSF) in the nondominant eye of normal subjects was evaluated before and after 150 min of monocular pattern deprivation. To obtain a CSF with high precision and efficiency before deprivation effect washout, a quick CSF (qCSF) method was used to assess CS over a wide range of spatial frequencies and at two external noise levels. We found that (1) monocular pattern deprivation effectively improved the CS of the deprived eye with larger effect on high spatial frequencies, (2) CS improvement only occurred when external noise was absent and its amount was spatial frequency dependent, and (3) a perceptual template model (PTM) revealed that decreased internal additive noise accounted for the mechanism of the monocular pattern derivation effect. These findings help us better understand the features of short-term monocular pattern deprivation and shed light on the treatment of amblyopia.

Sex- and age-specific effects on the development of addiction and compulsive-like drinking in rats

BackgroundBiological factors are known to influence disease trajectories and treatment effectiveness in alcohol addiction and preclinical and clinical evidence suggests that sex is an important factor influencing disease dynamics in alcohol dependence. Another critical factor is age at first intoxicating drink, which has been identified as a risk factor for later alcohol binging. Preclinical research allows prospective monitoring of rodents throughout the lifespan, providing very detailed information that cannot be acquired in humans. Lifetime monitoring in rodents can be conducted under highly controlled conditions, during which one can systematically introduce multiple biological and environmental factors that impact behaviors of interest.MethodsHere, we used the alcohol deprivation effect (ADE) rat model of alcohol addiction in a computerized drinkometer system, acquiring high-resolution data to study changes over the course of addictive behavior as well as compulsive-like drinking in cohorts of adolescent vs. adult as well as male vs. female rats.ResultsFemale rats drank more alcohol than male rats during the whole experiment, drinking much more weak alcohol (5%) and similar amounts of stronger alcohol solutions (10%, 20%); female rats also consumed more alcohol than male rats during quinine taste adulteration. Increased consumption in females compared to males was driven by larger access sizes of alcohol. Differences in circadian patterns of movement were observed between groups. Early age of onset of drinking (postnatal day 40) in male rats had surprisingly little impact on the development of drinking behavior and compulsivity (quinine taste adulteration) when compared to rats that started drinking during early adulthood (postnatal day 72).ConclusionsOur results suggest that there are sex-specific drinking patterns, not only in terms of total amount consumed, but specifically in terms of solution preference and access size. These findings provide a better understanding of sex and age factors involved in the development of drinking behavior, and can inform the preclinical development of models of addiction, drug development and exploration of options for new treatments.

Stroke severity mediates the effect of socioeconomic disadvantage on poor outcomes among patients with intracerebral hemorrhage.

Socioeconomic deprivation drives poor functional outcomes after intracerebral hemorrhage (ICH). Stroke severity and background cerebral small vessel disease (CSVD) burden have each been linked to socioeconomic status and independently contribute to worse outcomes after ICH, providing distinct, plausible pathways for the effects of deprivation. We investigate whether admission stroke severity or cerebral small vessel disease (CSVD) mediates the effect of socioeconomic deprivation on 90-day functional outcomes. Electronic medical record data, including demographics, treatments, comorbidities, and physiological data, were analyzed. CSVD burden was graded from 0 to 4, with severe CSVD categorized as ≥3. High deprivation was assessed for patients in the top 30% of state-level area deprivation index scores. Severe disability or death was defined as a 90-day modified Rankin Scale score of 4-6. Stroke severity (NIH stroke scale (NIHSS)) was classified as: none (0), minor (1-4), moderate (5-15), moderate-severe (16-20), and severe (21+). Univariate and multivariate associations with severe disability or death were determined, with mediation evaluated through structural equation modelling. A total of 677 patients were included (46.8% female; 43.9% White, 27.0% Black, 20.7% Hispanic, 6.1% Asian, 2.4% Other). In univariable modelling, high deprivation (odds ratio: 1.54; 95% confidence interval: [1.06-2.23]; p = 0.024), severe CSVD (2.14 [1.42-3.21]; p < 0.001), moderate (8.03 [2.76-17.15]; p < 0.001), moderate-severe (32.79 [11.52-93.29]; p < 0.001), and severe stroke (104.19 [37.66-288.12]; p < 0.001) were associated with severe disability or death. In multivariable modelling, severe CSVD (3.42 [1.75-6.69]; p < 0.001) and moderate (5.84 [2.27-15.01], p < 0.001), moderate-severe (27.59 [7.34-103.69], p < 0.001), and severe stroke (36.41 [9.90-133.85]; p < 0.001) independently increased odds of severe disability or death; high deprivation did not. Stroke severity mediated 94.1% of deprivation's effect on severe disability or death (p = 0.005), while CSVD accounted for 4.9% (p = 0.524). CSVD contributed to poor functional outcome independent of socioeconomic deprivation, while stroke severity mediated the effects of deprivation. Improving awareness and trust among disadvantaged communities may reduce admission stroke severity and improve outcomes.

Psilocybin prevents reinstatement of alcohol seeking by disrupting the reconsolidation of alcohol-related memories.

For most psychiatric conditions, including alcohol use disorder (AUD), FDA-approved pharmacological treatments are limited and their efficacy is restricted to only certain subgroups of patients. Scientific interest in the potential of psychedelic drugs has dramatically increased because of clinical preliminary evidence of efficacy in treating various psychiatric disorders. One of the most promising compounds belonging to this class of molecules is psilocybin. Here, to elucidate the therapeutic potential and treatment modalities of this drug, we investigated the effect of psilocybin on alcohol drinking and seeking in genetically selected Marchigian Sardinian alcohol-preferring (msP) rats, a well validated animal model of AUD characterized by excessive drinking and seeking. Using male and female msP rats, we tested the effect of psilocybin on home cage voluntary alcohol consumption. We also tested the effect of the drug on the alcohol deprivation effect (ADE) model of relapse and on cue-induced reinstatement of alcohol seeking after a period of abstinence. Finally, we evaluated if psilocybin may disrupt the reconsolidation process of alcohol-related memory. Psilocybin did not reduce alcohol consumption, nor it prevented increased alcohol drinking after a period of forced abstinence and cue-induced reinstatement of alcohol-seeking. Noteworthy, in a memory retrieval-reconsolidation paradigm, psilocybin markedly attenuated resumption of alcohol seeking. Altogether these data suggest that, despite psilocybin does not affect alcohol drinking and relapse, it may be highly effective if used to block the reconsolidation process of alcohol-related memories. This opens to the possibility of using this psychedelic drug in clinical settings in which AUD patients undergo procedures to recall the memory of alcohol and are then treated with psilocybin during the memory reconsolidation phase.

Intermittent-access operant alcohol self-administration promotes binge-like drinking and drinking despite negative consequences in male and female heterogeneous stock rats

The study of Alcohol Use Disorders (AUD) in preclinical models is hampered by difficulty in training rodents to voluntarily consume high levels of alcohol. The intermittency of alcohol access/exposure is well known to modulate alcohol consumption (e.g., alcohol deprivation effect, intermittent-access two-bottle-choice) and recently, intermittent access operant self-administration procedures have been used to produce more intense and binge-like self-administration of intravenous psychostimulant and opioid drugs. In the present study, we sought to systematically manipulate the intermittency of operant self-administered alcohol access to determine the feasibility of promoting more intensified, binge-like alcohol consumption. To this end, 24 male and 23 female NIH Heterogeneous Stock rats were trained to self-administer 10% w/v ethanol, before being split into three different-access groups. Short Access (ShA) rats continued receiving 30-min training sessions, Long Access (LgA) rats received 16-h sessions, and Intermittent Access (IntA) rats received 16-h sessions, wherein the hourly alcohol-access periods were shortened over sessions, down to 2 min. IntA rats demonstrated an increasingly binge-like pattern of alcohol drinking in response to restriction of alcohol access, while ShA and LgA rats maintained stable intake. All groups were tested on orthogonal measures of alcohol-seeking and quinine-punished alcohol drinking. The IntA rats displayed the most punishment-resistant drinking. In a separate experiment, we replicated our main finding, that intermittent access promotes a more binge-like pattern of alcohol self-administration using 8 male and 8 female Wistar rats. In conclusion, intermittent access to self-administered alcohol promotes more intensified self-administration. This approach may be useful in developing preclinical models of binge-like alcohol consumption in AUD.

Competition and game-playing: The academic returns and mental health costs of private tutoring

Given the intense academic competition in China, we ask the question of whether the academic returns to private tutoring come at the expense of students’ mental health. This topic involves the investigation and analysis of the dual effect of private tutoring. By using China Education Panel Survey data for 2014 and 2015, this study consistently finds that although investing time in private tutoring can boost academic achievement, it has a significant negative impact on students’ mental health. With an increase in average time spent and proportional participation in tutoring at the class level, the positive effect of the time invested in after-school tutoring on academic performance continues to weaken while the negative impact on mental health is gradually enhanced for a given individual. The main triggers for the worsening of mental health are the weakening of the social comparison effect as well as the enhancement of the role stress effect and the sleep deprivation effect.

N-Acetylcysteine normalizes brain oxidative stress and neuroinflammation observed after protracted ethanol abstinence: a preclinical study in long-term ethanol-experienced male rats

RationaleUsing a preclinical model based on the Alcohol Deprivation Effect (ADE), we have reported that N-Acetylcysteine (NAC) can prevent the relapse-like drinking behaviour in long-term ethanol-experienced male rats.ObjectivesTo investigate if chronic ethanol intake and protracted abstinence affect several glutamate transporters and whether NAC, administered during the withdrawal period, could restore the ethanol-induced brain potential dysfunctions. Furthermore, the antioxidant and anti-inflammatory effects of NAC during abstinence in rats under the ADE paradigm were also explored.MethodsThe expression of GLT1, GLAST and xCT in nucleus accumbens (Nacc) and dorsal striatum (DS) of male Wistar was analysed after water and chronic ethanol intake. We used the model based on the ADE within another cohort of male Wistar rats. During the fourth abstinence period, rats were treated for 9 days with vehicle or NAC (60, 100 mg/kg; s.c.). The effects of NAC treatment on (i) glutamate transporters expression in the Nacc and DS, (ii) the oxidative status in the hippocampus (Hip) and amygdala (AMG) and (iii) some neuroinflammatory markers in prefrontal cortex (PFC) were tested.ResultsNAC chronic administration during protracted abstinence restored oxidative stress markers (GSSG and GGSH/GSH) in the Hip. Furthermore, NAC was able to normalize some neuroinflammation markers in PFC without normalizing the observed downregulation of GLT1 and GLAST in Nacc.ConclusionsNAC restores brain oxidative stress and neuroinflammation that we previously observed after protracted ethanol abstinence in long-term ethanol-experienced male rats. This NAC effect could be a plausible mechanism for its anti-relapse effect. Also, brain oxidative stress and neuroinflammation could represent and identify plausible targets for searching new anti-relapse pharmacotherapies.

Role of mammography accessibility, deprivation and spatial effect in breast cancer screening participation in France: an observational ecological study

BackgroundThe detection of cancer in its early latent stages can improve patients’ chances of recovery and thereby reduce the overall burden of the disease. Our objectives were to investigate factors (geographic accessibility and deprivation level) affecting mammography screening participation variation and to determine how much geographic variation in participation rates can be explained by spillover effects between adjacent areas, while controlling for covariates.MethodsMammography screening participation rates between 2015 and 2016 were calculated by census blocks (CB), for women aged 50–74 years, residing in Lyon metropolitan area. Global spatial autocorrelation tests were applied to identify the geographic variation of participation. Spatial regression models were used to incorporate spatial structure to estimate associations between mammography participation rate and the combined effect (geographic accessibility and deprivation level) adjusting for modes of travel and social cohesion.ResultsThe mammography participation rate was found to have a statistically significant and positive spatial correlation. The participation rate of one CB was significantly and positively associated with the participation rates of neighbouring CB. The participation was 53.2% in residential and rural areas and 46.6% in urban areas, p < 0.001. Using Spatial Lag models, whereas the population living in most deprived CBs have statistically significantly lower mammography participation rates than lower deprived ones, significant interaction demonstrates that the relation differs according to the degree of urbanization.ConclusionsThis study makes an important methodological contribution in measuring geographical access and understanding better the combined effect of deprivation and the degree of urbanization on mammography participation and other contextual factors that affect the decision of using mammography screening services -which is a critical component of healthcare planning and equity.

MGlu2 mechanism-based interventions to treat alcohol relapse.

Recently we identified a deficiency in metabotropic glutamate receptor 2 (mGlu2) function in the corticoaccumbal pathway, as a common pathological mechanism underlying alcohol-seeking and relapse behavior. Based on this mechanism, we hypothesized that mGlu2/3 agonists and mGlu2 positive allosteric modulators (PAMs) may be effective in reducing relapse-like behavior. Two mGlu2/3 agonists, LY379268 and LY354740 (a structural analog of LY379268 six-fold more potent in activating mGlu2 over mGluR3), were tested in a well-established rat model of relapse, the alcohol deprivation effect (ADE) with repeated deprivation phases. Since these agonists do not readily discriminate between contributions of mGlu2 and mGluR3, we also tested LY487379, a highly specific PAM that potentiates the effect of glutamate on the mGlu2 with less specificity on other mGlu receptor subtypes. Both LY379268 and LY354740 significantly and dose-dependently reduced the expression of the ADE. No significant changes in water intake, body weight and locomotor activity were observed. Importantly, repeated administration of mGlu2/3 agonist did not lead to tolerance development. mGlu2 PAM LY487379 treatment significantly reduced expression of the ADE in both male and female rats. Combination treatment of mGlu2/3 agonist and PAM had similar effect on relapse-like drinking to that seen in mGlu2/3 agonist treatment alone. Together with other preclinical data showing that PAMs can reduce alcohol-seeking behavior we conclude that mGlu2 PAMs should be considered for clinical trials in alcohol-dependent patients.

Plasma tau, NfL, GFAP and UCHL1 as candidate biomarkers of alcohol withdrawal-associated brain damage: A pilot study.

In this translational study, we investigated the plasma tau protein, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCHL1), which are established biomarkers of neurological injury, as predictive biomarkers of alcohol withdrawal-associated brain toxicity. In the clinical study, patients with severe alcohol use disorder (AUD) on D1 of hospitalization for alcohol cessation (AC) (N = 36) were compared to severe AUD patients with at least 3 months of abstinence (N = 16). Overall, patients were 40 men (76.9%), aged 49.8 years [SD ±9.9]. Tau, NfL, GFAP and UCHL1 levels were measured using SIMOA and analysed with a quasipoisson regression model adjusted for age and sex. The NfL level was higher in the AC group (p = 0.013). In the AC group, the tau (p = 0.021) and UCHL1 (p = 0.021) levels were positively associated with the dose of diazepam per weight, and the tau (p = 0.045), NfL (p = 4.9 × 10-3 ) and UCHL1 (p = 0.036) levels were higher in the presence of signs of Wernicke's encephalopathy (n = 9). In the preclinical study, NfL and GFAP levels were assessed in the alcohol deprivation effect (ADE) procedure (N = 17) and control Wistar rats (N = 15). Furthermore, ADE rats were prospectively assessed: after 24 h (T1) and 3 weeks of AC (T2) (paired-samples Wilcoxon and Mann-Whitney tests). The NfL level was higher in the ADE model than in the control rats at both T1 and T2 (p = 0.033 and p = 1.3 × 10-3 ) and higher at T2 than at T1 (p = 0.040). Plasma tau, NfL and UCHL1 are potential biomarkers of brain suffering during alcohol withdrawal.

N-acetylcysteine improves impulse control and attenuates relapse-like alcohol intake in long-term drinking rats

Increasing evidence suggests that individuals with alcohol use disorder (AUD) present with a disrupted glutamatergic system that underlies core components of addictive disorders, including drug relapse and low impulse control. N-acetylcysteine (NAC) is a cystine prodrug that has been found to promote glutamate homeostasis and drug abstinence. However, no studies to date have evaluated NAC’s effect on impulsivity in substance use disorders. Here we determined whether NAC would decrease alcohol-intake behaviors, in addition to improving impulse control, in long-term alcohol drinking male Wistar-Han rats. Before the start of the experiments, all rats were exposed to long-term intermittent access to 20% ethanol for at least seven weeks. Next, in different groups of rats, the effect of NAC (60 and/or 90 mg/kg) was evaluated on (i) voluntary alcohol drinking using a two-bottle free choice paradigm, (ii) the motivation to self-administer alcohol under a progressive ratio schedule of reinforcement, and (iii) relapse-like drinking using the alcohol deprivation effect model. Finally, (iv) NAC’s effect on impulse control was evaluated using the five-choice serial reaction time task. Results showed that NAC administration at 90 mg/kg significantly reduced relapse-like drinking and improved impulse control. In contrast, NAC had no effect on levels of alcohol drinking or motivation to drink alcohol. In conclusion, our findings continue to support the use of NAC as an adjuvant treatment for the maintenance of abstinence in AUD. Moreover, we provide evidence for NAC’s efficacy in improving impulse control following drinking, which warrants further investigation in substance use settings.