Road traffic noise exposure and its impact on health: evidence from animal and human studies-chronic stress, inflammation, and oxidative stress as key components of the complex downstream pathway underlying noise-induced non-auditory health effects.

In heavily urbanized world saturated with environmental pollutants, road traffic noise stands out as a significant factor contributing to widespread public health issues. It contributes in the development of a diverse range of non-communicable diseases, such as cardiovascular diseases, metabolic dysregulation, cognitive impairment, and neurodegenerative disorders. Although the exact mechanisms behind these non-auditory health effects remain unclear, the noise reaction model centres on the stress response to noise. When exposed to noise, the body activates the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, leading to the secretion of stress hormones like catecholamines and cortisol. Prolonged exposure to noise-induced stress results in chronic inflammation and oxidative stress. This review underscores the role of inflammation and oxidative stress in the progression of noise-induced vascular dysfunction, disruption of the circadian rhythm, accelerated aging, neuroinflammation, and changes in microbiome. Additionally, our focus is on understanding the interconnected nature of these health outcomes: These interconnected factors create a cascade effect, contributing to the accumulation of multiple risk factors that ultimately lead to severe adverse health effects.

Hair cortisol determinants in 11-year-old children: Environmental, social and individual factors.

INTRODUCTION: Children's exposure to chronic stress is associated with several health problems. Measuring hair cortisol concentration is particularly useful for studying chronic stress but much is unknown about hair cortisol determinants in children and adolescents, and previous research has often not considered the simultaneous exposure of multiple variables. This research is focused on investigating the relationship between environmental, social and individual factors with hair cortisol concentration in children. METHODS: The data used in this study are from the INMA prospective epidemiological cohort study. The assessment of chronic stress was made on the basis of hair samples taken at the age of 11 years in the INMA-Gipuzkoa cohort (n = 346). A metamodel summarizing the hypothesized relationships among environmental, social and individual factors and hair cortisol concentration was constructed based on previous literature. Structural Equation Modelling was performed to examine the relationships among the variables. RESULTS: In the general model higher behavioural problems were associated with higher cortisol levels and an inverse relationship between environmental noise and cortisol levels was observed, explaining 5 % of the variance in HCC. Once stratified by sex these associations were only hold in boys, while no significant effect of any of the study variables was related with cortisol levels in girls. Importantly, maternal stress was positively related to behavioural difficulties in children. Finally, higher traffic-related air pollution and lower exposure to neighborhood greenness were related to higher environmental noise. DISCUSSION: This study highlights that simultaneous exposure to different environmental, social and individual characteristics may determine the concentration of hair cortisol. More research is needed and future studies should include this complex view to better understanding of hair cortisol determinants in children.

Chronic defeat stress induces monoamine level dysregulation in the prefrontal cortex but not in the hippocampus of OF1 male mice.

Chronic social stress can increase susceptibility to chronic diseases such as depression. One of the most used models to study the physiological mechanisms and behavioral outcomes of this type of stress is chronic defeat stress (CDS) in male mice. OF1 male mice were subjected to a stress period lasting 18 days. During that time, non-stressed animals were housed in groups. The cluster analysis of the behavioral profile displayed during the first social interaction divided subjects into two groups: active/aggressive (AA) and passive/reactive (PR). The day after the end of the stress period, the following behavioral analyses were performed: the sucrose preference test (SPT) on day 19, the open field test (OFT) on day 20, and the forced swim test (FST) on day 21. Immediately after completing the last test, animals were weighed, and blood samples were obtained. Then, they were sacrificed, and their prefrontal cortices and hippocampi were removed and stored to analyze monoamine levels. Stressed animals displayed anhedonia, and solely the PR mice continued to show higher levels of immobility in the OFT and FST. All stressed animals, regardless of the coping strategy, presented higher plasma corticosterone levels. In addition, stressed mice showed lower levels of tyrosine, dopamine, DOPAC, MHPG, kynurenine, kynurenic acid, and 5-HIAA levels but higher serotonin levels in the prefrontal cortex, not in the hippocampus. In conclusion, our results show that CSD induces differences in monoamine levels between brain areas, and these differences did not respond to the coping strategy adopted.

Do Hormone Levels Influence Bullying during Childhood and Adolescence? A Systematic Review of the Literature.

(1) Background: Bullying is one of the most common forms of aggressive behavior during childhood and adolescence. Some decades ago, researchers began exploring the basis of peer victimization from a biological perspective. Specifically, the Hypothalamic-Pituitary-Adrenal (HPA) and Hypothalamic-Pituitary-Gonadal (HPG) axes have been studied in relation to status-relevant behaviors, such as bullying. (2) Methods: We conducted a systematic review following the PRISMA guide and registered the review protocol at PROSPERO (CRD42023494738). We searched for relevant studies in PubMed, Psycinfo, Scopus, and Web of Science, and assessed them using the Robins E-tool. (3) Results: Our search yielded 152 studies, of which 33 were included in the review. These studies explored the association between testosterone and cortisol levels with bullying behavior, finding diverse results. Most of the studies were rated as having a low risk of bias. (4) Conclusions: This study not only enhances our understanding of bullying, but also provides guidance for the development of prevention and management programs for it. In the future, researchers should continue exploring the joint effects of different hormones on the HPA and HPG axis, using a broader set of biomarkers.

Sleep problems at ages 8-9 and ADHD symptoms at ages 10-11: evidence in three cohorts from INMA study.

Sleep problems and attention deficit hyperactivity disorder (ADHD) are interrelated during childhood and preadolescence. The objective of this work is assessing if sleep problems at ages 8-9 represent an alarm sign for presenting ADHD problems at ages 10-11 in three cohorts from INMA Study. Participants were 1244 children from Gipuzkoa, Sabadell, and Valencia cohorts. Sleep problems were assessed (ages 8-9) with the sleep items of the Child's Behaviour Checklist (CBCL), and ADHD problems were collected through the Conner's Parent Rating Scales-Revised: Short Form (CPRS-R:S) (age 10-11). Minimally and fully adjusted negative binomial models were fitted for each CPRS-R:S scale. Linearity of the relationship was assessed with generalized additive models (cubic smoothing splines with 2, 3, and 4 knots). For sensitivity analyses, children with previous symptoms, those born preterm and small for gestational age, and cases with extreme values, were excluded. Sleep problems presented IRR (95% CI) of 1.14 (1.10-1.19), 1.20 (1.14-1.26), 1.18 (1.11-1.25), and 1.18 (1.13-1.23) for opposition, inattention, hyperactivity, and ADHD scales, respectively. Fully adjusted models slightly decreased the IRR, but the association remained similar and significant. Sensitivity analyses showed similar results to fully adjusted models with only hyperactivity shown a slight decrease on significance (p = 0.051) when ADHD cases at age 9 were excluded.   Conclusion: Sleep problems are an alarm sign for later neurodevelopment problems such as ADHD. Healthcare systems could take advantage implementing policies to pay special attention on the sleep habits and sleep hygiene. This could contribute to add evidence to public health programmes such as the Healthy Child Programme.

The role of sociability in social instability stress: Behavioral, neuroendocrine and monoaminergic effects.

Extensive literature has reported a link between social stress and mental health. In this complex relationship, individual strategies for coping with social stress are thought to have a possible modulating effect, with sociability being a key factor. Despite the higher incidence of affective disorders in females and sex-related neurochemical differences, female populations have been understudied. The aim of the present study was, therefore, to analyze the behavioral, neuroendocrine, and neurochemical effects of stress in female OF1 mice, paying special attention to social connectedness (female mice with high vs low sociability). To this end, subjects were exposed to the Chronic Social Instability Stress (CSIS) model for four weeks. Although female mice exposed to CSIS had increased arousal, there was no evidence of depressive-like behavior. Neither did exposure to CSIS affect corticosterone levels, although it did increase the MR/GR ratio by decreasing GR expression. Female mice exposed to CSIS had higher noradrenaline and dopamine levels in the hippocampus and striatum respectively, with a lower monoaminergic turnover, resulting in an increased arousal. CSIS increased serotonin levels in both the hippocampus and striatum. Similarly, CSIS was found to reduce kynurenic acid, 3-HK, and IDO and iNOS enzyme levels in the hippocampus. Interestingly, the observed decrease in IDO synthesis and the increased serotonin and dopamine levels in the striatum were only found in subjects with high sociability. These highly sociable female mice also had significantly lower levels of noradrenaline in the striatum after CSIS application. Overall, our model has produced neuroendocrine and neurochemical but not behavioral changes, so it has not allowed us to study sociability in depth. Therefore, a model that induces both molecular and behavioral phenotypes should be applied to determine the role of sociability.

Individualized Housing Modifies the Immune-Endocrine System in CD1 Adult Male Mice.

In the last years, different research groups have made considerable efforts to improve the care and use of animals in research. Mice (Mus musculus) are the most widely used animal species in research in the European Union and are sociable and hierarchical creatures. During experiments, researchers tend to individualize males, but no consideration is given to whether this social isolation causes them stress. The aim of this study was, therefore, to explore whether 4 weeks of social isolation could induce changes in different physiological parameters in adult Crl:CD1(ICR) (CD1) males, which may interfere with experimental results. Body weight, blood cells, and fecal corticosterone metabolites levels were the analyzed parameters. Blood and fecal samples were collected at weeks 1 and 4 of the experimental procedure. Four weeks of single housing produced a significant time-dependent decrease in monocytes and granulocytes. Fecal corticosterone metabolite levels were higher in single-housed mice after 1 week and then normalized after 4 weeks of isolation. Body weight, red blood cells, and platelets remained unchanged in both groups during this period. We can, therefore, conclude that social isolation affects some immune and endocrine parameters, and that this should be taken into account in the interpretation of research data.

Refinement in the European Union: A Systematic Review.

Refining experiments and housing conditions so as to cause the minimum possible pain and distress is one of the three principles (3Rs) on which Directive 2010/63/EU is based. In this systematic review, we aimed to identify and summarize published advances in the refinement protocols made by European Union-based research groups from 2011 to 2021, and to determine whether or not said research was supported by European or national grants. We included 48 articles, the majority of which were related to improvements in experimental procedures (37/77.1%) for mice (26/54.2%) and were written by research groups belonging to universities (36/57.1%) and from the United Kingdom (21/33.9%). More than two thirds (35/72.9%) of the studies received financial support, 26 (mostly British) at a national level and 8 at a European level. Our results indicated a clear willingness among the scientific community to improve the welfare of laboratory animals, as although funding was not always available or was not specifically granted for this purpose, studies were published nonetheless. However, in addition to institutional support based on legislation, more financial support is needed. We believe that more progress would have been made in refinement during these years if there had been more specific financial support available at both the national and European Union levels since our data suggest that countries investing in refinement have the greatest productivity in successfully publishing refinements.

Environmental Noise Exposure and Sleep Habits among Children in a Cohort from Northern Spain.

Environmental noise is considered the second most serious environmental risk factor in Europe. However, little evidence exists regarding its impact on health and sleep in children, and the results are inconclusive. In this study, we aim to analyse the effect of environmental noise exposure on 11-year-old children's sleep habits. Data were collected from 377 participants in the INMA-Gipuzkoa (INfancia y Medio Ambiente) cohort project using both parent-reported and actigraphic sleep measures. The results revealed that 60% of children have a day-evening-night environmental noise exposure (Lden) of above 55 dB, which is defined as a "high noise level". No differences in noise exposure were observed between different socioeconomic groups. However, no effect of environmental noise was found on sleep variables. The paper highlights the importance of studying how environmental noise may affect children's sleep.

Professional quality of life among Spanish veterinarians.

Background: In Spain, the perceived professional quality of life among veterinarians has not been explored. Methods: Veterinarians were invited to complete an online questionnaire in which they answered the Professional Quality of Life scale, the Medical Outcomes Study Social Support Survey and the Warwick-Edinburgh Mental Well-Being Scale. Participants were asked whether they were receiving psychological therapy or were taking anxiolytics, hypnotics or antidepressant medication. Alcohol consumption was measured using the Alcohol Use Disorders Identification Test and nicotine dependence was assessed using the Fagerström test; participants were asked whether they took illegal drugs. Results: The study sample comprised a total of 602 veterinarians, most of whom reported average levels of compassion satisfaction, secondary stress trauma and burnout. Emotional support and mental wellbeing influenced participants' professional quality of life. The percentage of veterinarians in psychological therapy and/or taking anxiolytics was higher than in the general population. Conclusions: A considerable number of clinical veterinarians in Spain may be suffering from work-related stress. Our study identifies salary, emotional support and mental wellbeing as important factors that affect the professional quality of life. Interventions to improve veterinary clinicians' professional quality of life should therefore focus on these factors.

Chronic social instability stress down-regulates IL-10 and up-regulates CX3CR1 in tumor-bearing and non-tumor-bearing female mice.

Extensive literature has reported a link between stress and tumor progression, and between both of these factors and mental health. Despite the higher incidence of affective disorders in females and the neurochemical differences according to sex, female populations have been understudied. The aim of this study was therefore to analyze the effect of stress on tumor development in female OF1 mice. For this purpose, subjects were inoculated with B16F10 melanoma cells and exposed to the Chronic Social Instability Stress (CSIS) model. Behavioral, neurochemical and neuroendocrine parameters were analyzed. Female mice exposed to CSIS exhibited reduced body weight and increased arousal, but there was no evidence of depressive behavior or anxiety. Exposure to CSIS did not affect either corticosterone levels or tumor development, although it did provoke an imbalance in cerebral inflammatory cytokines, decreasing IL-10 expression (IL-6/IL-10 and TNF-α/IL-10); chemokines, increasing CX3CR1 expression (CX3CL1/CX3CR1); and glucocorticoid receptors, decreasing GR expression (MR/GR). In contrast, tumor development did not alter body weight and, although it did alter behavior, it did so to a much lesser extent. Tumor inoculation did not affect corticosterone levels, but increased the MR/GR ratio in the hippocampus and provoked an imbalance in cerebral inflammatory cytokines and chemokines, although differently from stress. These results underscore the need for experimental approaches that allow us to take sex differences into account when exploring this issue, since these results appear to indicate that the female response to stress is mediated by mechanisms different from those often proposed in relation to male mice.

The Moderating Role of Surgency, Behavioral Inhibition, Negative Emotionality and Effortful Control in the Relationship between Parenting Style and Children's Reactive and Proactive Aggression.

The principal aim of this study is to explore the moderating role of temperament in the relationship between parenting style and the reactive and proactive aggressive behavior of 8-year-old children. The participants are 279 children (154 boys and 125 girls). To measure reactive and proactive aggression, children completed the reactive and proactive questionnaire (RPQ). Child temperament and parenting styles were evaluated by both parents using the temperament in middle childhood questionnaire (TMCQ) and the parenting styles and dimensions questionnaire (PSDQ). The results revealed that boys with high surgency levels and authoritarian fathers displayed more reactive aggression, whereas behaviorally inhibited boys with mothers who scored low for authoritarian parenting displayed less reactive aggression. Finally, girls with high levels of effortful control and mothers who scored low for authoritative parenting displayed more proactive aggression. The results highlight the value of studying the moderating role of temperament in the relationship between children's aggressive behavior and both mothers' and fathers' parenting styles, and underscores the importance of doing so separately for boys and girls.

Professional Quality of Life in Research Involving Laboratory Animals.

Many workers contribute to the success of animal welfare and study outcomes in biomedical research. However, the professional quality of life (ProQoL) of those who work with laboratory animals has not been explored in Spain. To this end, we adapted the ProQoL scale to the Spanish population working with laboratory animals. Participants were contacted by email and asked to complete an anonymous on-line questionnaire. The study comprised a total of 498 participants, 12.4% welfare officers/veterinarians, 19.5% caretaker/technicians, 13.9% principal investigators, 20.7% investigators, 13.6% research technicians, and 19.9% PhD students. The adapted scale revealed very good reliability and internal validity, providing information about two different subscales, compassion satisfaction and compassion fatigue. Animal-facility personnel showed higher total ProQoL and compassion-satisfaction scores than researchers; PhD students showed the lowest scores. Thus, our results indicate that job category is a contributing factor in perceived professional quality of life. We observed that compassion satisfaction is negatively associated with the perceived animal stress/pain. Participants reporting poorer compassion satisfaction also reported lower social-support scores. Overall, our ProQoL scale is a useful tool for analyzing the professional quality of life in the Spanish population, and may help to design future interventions to improve workplace wellbeing in Spain and other Spanish-speaking populations.

Anxiety and depression after breast cancer: The predictive role of monoamine levels.

PURPOSE: Despite the fact that the prevalence of anxiety and depression in breast cancer survivors is higher than in the general female population, the psychobiological substrate of this phenomenon has yet to be elucidated. We aimed to examine the predictive role of peripheral dopamine (DA), noradrenaline (NA), serotonin (5-HT) and kynurenine (KYN) in anxiety and depression among breast cancer survivors. METHOD: We evaluated 107 women using the Hospital Anxiety and Depression Scale, and monoamine levels were analyzed via high-performance liquid chromatography. RESULTS: High KYN levels predicted both disorders, while low NA and DA predicted anxiety and depressive symptoms, respectively. A negative conditional effect of 5-HT was found for anxiety and depression among younger women only, while being both middle-aged and younger influenced the negative conditional effect of DA on depression. CONCLUSION: Monoamine variations may render breast cancer survivors more vulnerable to anxiety and depression, with young women being especially vulnerable to the detrimental effect of low DA and 5-HT. Assessing subclinical psychobiological markers allows mental health nurses to identify vulnerable survivors prior to the onset of anxiety and depression, and to adjust nursing interventions accordingly.

Venlafaxine reduces the striatal il6/il10 ratio and increases hippocampal GR expression in female mice subjected to chronic social instability stress.

Women are twice as likely as men to develop depression and antidepressant treatment is more frequent in females. Moreover, neuroinflammatory changes related to affective disorders differ in accordance with sex. Despite this evidence, female populations have been largely omitted from preclinical experiments studying antidepressants. The aim of this work is to analyze the potential restorative effect of venlafaxine on an animal model of depression. Female CD1 mice were subjected to chronic social instability (CSI) stress for 7 weeks, and were administered venlafaxine during the last 3 weeks of the stress period. Behavioral and physiological parameters were then analyzed. Stressed mice showed a decreased sucrose preference and increased whisking behavior, and had a lower body weight, higher plasma corticosterone levels and increased hypothalamic GR expression. They also had lower levels of 5-HT, 5-HIAA and NA and a higher KYN/TRYP ratio in the hippocampus. Moreover, CSI increased striatal IL-6 mRNA expression levels. Venlafaxine treatment reduced the striatal IL-6/IL-10 ratio and increased hippocampal GR expression, although it did not reverse stress-induced behavioral changes. In conclusion, seven weeks of exposure to CSI produced depressive-like alterations in female mice. The venlafaxine treatment regimen was found to have a modest anti-inflammatory effect in the striatum and increased hippocampal GR mRNA, although it failed to redress stress-induced behavioral disturbances.

Distress, proinflammatory cytokines and self-esteem as predictors of quality of life in breast cancer survivors.

OBJECTIVE: To examine the extent to which anxiety and depressive symptoms, self-esteem and proinflammatory cytokines interact to significantly predict quality of life in breast cancer survivors. METHODS: Cross-sectional data were collected from 134 breast cancer survivors. Hospital Anxiety and Depression Scale, Rosenberg Self-Esteem Scale and Quality of Life in Adult Cancer Survivors questionnaire, which includes the generic quality of life (QOL) and the quality of life related to cancer (QOLRC) subscales, were administered. Plasma IL-6 and TNF-α levels were measured using ELISA kits. Moderation analyses were performed to study the influence of psychobiological variables on quality of life. RESULTS: Anxiety and depressive symptoms, TNF-α predicted QOL scores, and both medium and high levels of TNF-α influenced the negative conditional effect of depressive symptoms on QOL. Anxiety symptoms and TNF-α was associated with QOLRC scores, and lower self-esteem predicted poorer QOLRC when women had high levels of TNF-α. CONCLUSIONS: These results highlight the booster effect of TNF-α for poorer quality of life in breast cancer survivors, both alone and in combination with depressive symptoms or low self-esteem. The study provides a framework for assessing subclinical markers, identifying vulnerable survivors and implementing psychological strategies to improve quality of life.

Behavioral coping strategies predict tumor development and behavioral impairment after chronic social stress in mice.

The aims of this study were to identify behavioral strategies to cope with social defeat, evaluate their impact on tumor development and analyze the contributions of both to changes in physiology and behavior produced by chronic defeat stress. For this purpose, OF1 mice were inoculated with B16F10 melanoma cells and subjected to 18 days of repeated defeat stress in the presence of a resident selected for consistent levels of aggression. Combined cluster and discriminant analyses of behavior that manifested during the first social interaction identified three types of behavioral profiles: active/aggressive (AA), passive/reactive (PR) and an intermediate active/non-aggressive (ANA) profile. Animals that showed a PR coping strategy developed more pulmonary metastases at the end of the social stress period than animals in other groups. The ANA but not AA group also showed higher tumor metastases than non-stressed subjects. In addition, the ANA group differed from the other groups because it displayed the highest corticosterone levels after the first interaction. Chronic stress reduced sucrose consumption, which indicates anhedonia, in all the stressed groups. However, the PR subjects exhibited a longer immobility time and swam for less time than other subjects in the forced swim test (FST), and they travelled a shorter distance in the open field test (OFT). In this test, the ANA group also travelled smaller distances than the non-stressed group, but the difference was more moderate. In contrast, tumor development but not stress increased behaviors associated with anxiety in the OFT (e.g., time in the center) in all tumor-bearing subjects. In summary, although the effects of social stress and tumor development on behavior were rather moderate, the results indicate the importance of behavioral coping strategies in modulating the effects of chronic stress on health.

Active and Passive Coping Strategies: Comparing Psychological Distress, Cortisol, and Proinflammatory Cytokine Levels in Breast Cancer Survivors.

BACKGROUND: Breast cancer survivors can experience psychological distress, such as anxiety and depression, long after treatment has ended, and the development of such negative affective states has been related to the coping strategy used. OBJECTIVES: This pilot study aims to determine whether different coping strategies are associated with differences in psychological distress, cortisol, and tumor necrosis factor alpha (TNF-a) levels in breast cancer survivors. METHODS: 54 breast cancer survivors completed the Stress Coping Questionnaire and the Hospital Anxiety and Depression Scale and provided a blood sample for cortisol and proinflammatory cytokine measures. FINDINGS: Passive coping strategies were associated with higher psychological distress, cortisol, and TNF-a levels. The passive group had more avoidance and negative self-targeting and less positive reappraisal and focusing on a problem's solution.

Aggressive Behavior in School-aged Children: Clusters based on Anger, Empathy and Testosterone and Cortisol Measures.

The aim of this piece of research was to study the existence of clusters based on anger, empathy and cortisol and testosterone measures associated with aggressive behavior in school-aged children. The sample group comprised 139 eight-year-old children (80 boys and 59 girls). Aggressive behavior was measured using the Direct and Indirect Aggression Scale. Both psychological and biological variables were used to determine psychobiological profiles. The psychological variables considered were trait anger, measured using the State-Trait Anger Expression Inventory for Children and Adolescents, and empathy, measured using the Empathy Quotient-Child Version. Testosterone and cortisol concentrations were measured through saliva samples and analyzed using an ELISA (Enzyme-linked immunosorbent assay). A Cluster Analysis revealed three clusters which were clearly different as regards their psychological and biological characteristics. The analysis of variance (ANOVA) revealed that the cluster characterized by having higher anger levels, lower empathy levels and higher testosterone and cortisol levels was more aggressive than the other two (p < .0001, η2 = .19). The results indicate that studying psychological and biological variables together may help establish differentiated aggression patterns among children.

Aggressive behavior in school-aged children: clusters based on anger, empathy and testosterone and cortisol measures

The aim of this piece of research was to study the existence of clusters based on anger, empathy and cortisol and testosterone measures associated with aggressive behavior in school-aged children. The sample group comprised 139 eight-year-old children (80 boys and 59 girls). Aggressive behavior was measured using the Direct and Indirect Aggression Scale. Both psychological and biological variables were used to determine psychobiological profiles. The psychological variables considered were trait anger, measured using the State-Trait Anger Expression Inventory for Children and Adolescents, and empathy, measured using the Empathy Quotient-Child Version. Testosterone and cortisol concentrations were measured through saliva samples and analyzed using an ELISA (Enzyme-linked immunosorbent assay). A Cluster Analysis revealed three clusters which were clearly different as regards their psychological and biological characteristics. The analysis of variance (ANOVA) revealed that the cluster characterized by having higher anger levels, lower empathy levels and higher testosterone and cortisol levels was more aggressive than the other two (p < .0001, η2 = .19). The results indicate that studying psychological and biological variables together may help establish differentiated aggression patterns among children

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