Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Editorial

Editorial (Thematic Issue: Crosstalk Between the Nervous and the Immune Systems in Health and Sickness)

Author(s): Monica De la Fuente

Volume 20, Issue 29, 2014

Page: [4605 - 4607] Pages: 3

DOI: 10.2174/1381612820666140130213734

Abstract

Today it is recognized that the regulatory systems namely nervous, endocrine and immune systems, do not function independently but are intimately linked, constituting a psychoneuroimmunoendocrine system. The communication between these physiological systems, is the basis of the maintenance of homeostasis and therefore of health. Each of these homeostatic systems is complex and more so, the interactions between them. Currently, there is abundant work that confirms this bidirectional communication, which depends on the following facts: A) The cells of each of the three systems can express receptors for the mediators of the others, namely cytokines, hormones and neurotransmitters; B) Immune, nervous and endocrine products coexist in lymphoid, endocrine and neural tissue; C) Endocrine and neural mediators can affect the immune system; and D) Immune mediators can affect endocrine and neural functions. These bidirectional communications may happen in long or short loops. With respect to the long loops, the effect of mediators of nervous and endocrine systems on the immune cells was possibly the easiest aspect to understand, since both primary and secondary immune organs, are innervated and irrigated. It was more difficult to accept that immune mediators, such as cytokines, can arrive to the brain. In fact, mediators produced by peripheral immune cells reach the Central Nervous System (CNS), and the leukocytes even being able, in specific situations, to pass through the blood-brain barrier. Nevertheless, the CNS can show an immune response using its resident cells such as glial cells, ependymal cells or neurons. At the level of short-loop interactions, the capacity of production of typical neurotransmitters and hormones by immune cells, as well as of cytokines by nervous and endocrine cells, was also difficult to accept, not only at peripheral level, but also in the brain. Currently, the improved knowledge of this communication between homeostatic systems constitutes the scientific basis, which allows us to understand many facts of everyday life. Thus, it is well known that situations of emotional stress or anxiety are accompanied by a greater vulnerability to conditions ranging from infectious processes to cancer or autoimmune diseases, agreeing with the concept that the immune system is impaired. By contrast, pleasant emotions and a “positive outlook” on life help us to overcome immune system-related diseases and enjoy better overall health. Conversely, it has been shown that immune system changes, such as those found in infectious processes, alter the functions of the nervous system, which could lead, if those changes are not well controlled, to psychotic disorders and neural diseases. Thus, we must take into consideration that health is the result of the appropriate functioning of homeostatic systems as well as the perfect balance of mediators produced by them. When one of these mediators is overproduced or released in lower amounts than those necessary, the pathology appears. Any process is good or bad for health depending on the context, the amount of mediators, the period of time in which it is developing, etc. For example, inflammation is essential for survival since it serves to eliminate dangerous intrinsic and extrinsic factors and mediates tissue repair. However, this process requires a tight control exerted by anti-inflammatory cytokines. When the inflammation is uncontrolled many pathologies occur. In the current issue 15 different aspects of this psychoneuroimmunoendocrine communication will be presented by experts in the field, bringing together the most recent and novel studies available. Moreover, on reading several reviews in this issue some new physiological, pathological and therapeutic ideas will be discussed opening our mind to new ways of understanding health and sickness. It is possible that the response to stress situations, which are an integral part of daily life, is one of the best examples to understand the communication between the homeostatic systems. The stress response is essential for survival and when this is not adequate, due to bad crosstalk between the three regulatory systems, health can be compromised leading to the development of a pathology. In the article of Cruces et al. [1] the effects of stress, and especially psychological stress, on the nervous, endocrine and immune systems are covered. Moreover, social isolation, an important cause of psychological stress, provokes a deterioration of the psychoneuroimmunoendocrine system and thus may increase morbidity and mortality. In fact, this increase has been commonly observed in individuals following the death of their partner. Nevertheless, these deleterious effects depend on the individual’s reaction, for example whether the subject shows anxiety or not, in this stress situation. Maternal deprivation, a model of isolation in the early stages of life, is another example of the effects of stress disrupting the communication between the homeostatic systems. As another concrete example of how a psychological stress situation affects the neuroimmunoendocrine communication the study of Palermo- Neto and Alves [2] deals with the effects produced by cohabitation with a sick partner. Since this subject has not been sufficiently studied in caregivers of sick persons, and the results obtained in rodent models appear to be similar to those in humans, the authors propose a rodent model, which permits a deeper study of the mechanisms involved in the response to this psychological stress. A very interesting subject, which is not frequently considered in physiological studies, is the circadian system, which could be a relevant part of the homeostatic complex that represents the neuroimmunoendocrine system. In fact, this system shows circadian as well as circannual or seasonal variations in most of its variables. The aging process is another biological rhythm. With aging, an impairment of the homeostatic systems occurs and an alteration in the control of circadian and circannual rhythms has been demonstrated. This regulation of the homeostatic systems, especially that of the immune system, by biological rhythms as well as its age-related dysregulation, which compromise the quality of life of individuals, is covered by Maté et al. [3]. In this review it is shown how several immune function parameters, which are good markers of health and of the rate of aging, change not only with age (immunosenescence) but also throughout the day and year. Thus, the immune functions during the early afternoon show values more similar to those of older subjects than during the morning. In addition, in winter, especially in the case of mature men and women, the immune cell function show the most significant impairment. The role of immunomodulatory hormones, such as melatonin, in the regulation of biological rhythms and their involvement in the aging process is noteworthy. Furthermore, the evidence of regulation of the circadian system by the immune system and its disturbance with aging, is also mentioned, highlighting the importance of proinflammatory cytokines in this complex cross-talk. In addition to age, in some diseases the biological rhythms can be impaired. This and the use of chronotherapy are other relevant aspects encompassed in this review. To understand the mechanisms underlying the impairment of homeostatic systems it is necessary to know how oxidative stress and inflammatory stress are involved. In the review by Vida et al. [4] this subject is covered, highlighting the oxidative-inflammatory stress in the regulatory systems, which occurs with aging and anxiety, two very related situations. In fact, in a model of premature aging in mice, in which animals show a poor response to stress and high levels of anxiety, an oxidative stress in their immune cells and tissues occurs, as well as a premature immunosenescence and a shorter life expectancy. This model supports the hypothesis that anxiety can be a situation of chronic oxidative stress and inflammation, especially in brain and immune cells, and this accelerates the rate of aging. Nitric oxide (NO) is a significant molecule involved in oxidative stress. NO can be transformed into highly reactive and harmful molecules producing an impairment of the bio-molecules (DNA, lipids or proteins), altering their function. Thus, NO shows an important role in many pathological processes, but also in many physiological functions, including those of a mediator of blood vessel dilation, neurotransmitter, neuromodulator and inductor of mitochondrial biogenesis. The dual action of NO and its role in homeostasis, especially in the nervous and immune systems, is reviewed by Rocha et al. [5]. As mentioned above, an aspect of neuroimmunoendocrine communication, is the production by immune organs of molecules with hormonal functions. In the review by Reggiani et al. [6], the physiological and therapeutic roles of thymulin, a thymic hormone, are covered. Moreover, studies that show how the production and secretion of thymulin is strongly influenced by the neuroendocrine system are mentioned. These represent examples of how mediators of the nervous and endocrine systems can affect immune organs. The endocannabinoid system constitutes a relevant example of molecules produced by both brain and immune cells. This system has as its main function the maintenance of body homeostasis. The role of this in the hypothalamic-pituitary axes in their responses to inflammation and infection has been extensively reviewed by De Laurentiis et al. [7]. These authors also covered the potential pharmacological therapies based on the manipulation of the components of this endocannabinoid system, which could provide novel treatments for many disorders. More information on the cannabinoid system as well as its role in inflammation as a neuro-protective system, is shown in the review by Hernangómez et al., [8]. These authors demonstrate the importance of innate immunity response within the CNS and the role that this response plays, when it is uncontrolled (with macrophages and microglia as important participants), in the development and expansion of autoimmune and neurodegenerative diseases. Primary examples of these are multiple sclerosis (MS) and Alzheimer's disease (AD). In the regulatory mechanisms involved in the control of this CNS innate immunity, the neuroimmune regulatory proteins (NIReg) are relevant. Concretely, in this review the role of CD200 and its receptor CD200R, in silencing and reshaping an adverse innate immune response, is emphasized. Thus, CD200-CD200R as an anti-inflammatory and neuroprotective pair in MS, is highlighted. In addition, the role of CD200-CD200R in aging brain and in Alzheimer´s disease (AD) is reviewed. Moreover, the possibility that endocannabinoids can be used as therapeutic targets for promoting CD200-CD200R interaction is proposed for the above mentioned diseases. Alzheimer´s disease (AD) is widely considered in the review by Gimenez-Llort et al. [9]. This disease can be better understood in the context of the aging of the neuroimmunoendocrine system. These authors show evidence of the relevance of the disruption of the cross-talk between the cells of the homeostatic systems and their mediators from the prodromal stages of AD, when cognitive function still seems apparently normal. This disruption contributes to the onset of disease, and to know this, may help us to understand its biological mechanisms and to find behavioral and immunological biomarkers for the prodromic phases. Moreover, the use of lifestyle strategies such as physical exercise, environmental enrichment and nutrition to improve the nervous and immune functions in animal models for this disease is highlighted in the review. As previously stated, all the homeostatic system mediators have to be present in the appropriate amount and their production and release must take place with a perfectly controlled spatial and temporal pattern. As an example of this Besedovsky and Del Rey [10] show what happens with IL-1, the pro-inflammatory cytokine most studied in the context of nervous-immune communication. Among the different physiological effects of this cytokine, its role in re-setting glucose homeostasis, in the peripheral and brain levels, is emphasized in this review. The authors mention the capacity of IL-1 to deviate glucose to immune cells during inflammatory and infectious diseases as one of the bases of metabolic control produced by the immune system. Several mechanisms are involved in the deviation of the physiological functions of IL-1 to pathology. Thus, depending on the amount of this cytokine, physiological or diabetogenic effects are produced. The role of bacterial infections and the possible aberrant activation of the inflammatory response and the consequent disease are covered in the following reviews. Burdet et al. [11] review the case of pregnant women, and how maternal infections and inflammation can produce premature labor. How bacteria invade the uterine capacity, which is normally a sterile environment, is a very interesting subject. This, and the reasons why different species of bacteria vary in their capacity to induce inflammation and preterm birth, are covered in this review as well as possible therapeutic interventions. The review by Rettori et al. [12] shows periodontitis as another chronic inflammatory complex problem caused by microorganisms. This disease, characterized by the progressive destruction of the tooth and its support leading to tooth loss, has a possible impact on general health, and the balance of the host neuro-immuno-endocrine responses is altered. The possible link between periodontitis and diabetes, cardiovascular diseases, strokes and metabolic syndromes, all sharing a common denominator that is inflammation and oxidative stress, is covered. In addition, the negative effects of stress on this disease, the effects of oxytocin in modulating the individual response to stress, and the participation of components and functions of the endocannabinoid system with anti-inflammatory actions on gingiva, are also mentioned. As another concrete example of the involvement of the reciprocal interactions between the neuroendocrine and immune systems in a pathological situation, Hauk et al. [13] review an inflammatory disorder, the Sjögren syndrome (SS), in which a progressive loss of salivary and lacrimal gland secretions occurs. The effects of the neurotransmitter vaso intestinal peptide (VIP) and its receptor (VPAC) using a model of SS, non obese diabetic (NOD) mice, showing the physiopathological mechanisms of this disease, are mentioned in this review. The microbiota present in the gut and the gut-brain-immune system axis are extensively dealt with by Martín-Villa [14]. In this context, the author explains the etiology of two major inflammatory bowel diseases such as Crohn´s disease and ulcerative colitis. Recent data suggest that these diseases are an exaggerated mucosal immune response to microbiota present in the gut, in which T lymphocytes play a crucial role in the pathogenic events leading to tissue damage. These diseases are the result of psychological trauma, stress or depression, acting on genetically predisposed individuals. Thus, these diseases are an example of how emotional stress could increase epithelial permeability, modify the gut microbiota composition and activate pre-sensitized T lymphocytes, showing the link between emotions, microbiota and immune functions. Following the relevant role of micro-organisms, especially those in gut, the last review of this issue by Montiel-Castro et al. [15] deals with a very novel and interesting subject such as the effect of the microbiota-gut-brain axis on social interactions. The first part of the article describes concepts of behavior and nervous system function. This is followed by how different neurological processes are the base of socialdecision making and how the regulation of different aspects of animal behavior is carried out. Finally, the authors suggest the involvement of microbiota in the social interactions of each individual. The idea that microbiota are our closet partners interacting with gut immune and nervous systems, and these with the central nervous system, and how these microbiota can modify our behavior is a new field in psychoneuroimmunoendocrinology. The collection of articles in this issue of CPD allows the reader to bring their knowledge of psychoneuroimmunoendocrinology up to date. This is a novel field of research not frequently found in scientific publications. Moreover, it should be stated that any pharmaceutical intervention designed to improve health will affect the three regulatory systems and their communication. Thus, the contributions to this issue highlighting original aspects of this field could lead to a better understanding of our prospects of health.

Next »

© 2025 Bentham Science Publishers | Privacy Policy
Request history8.2.27PHP Version487msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[03:01:55] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
  • warninglog[03:01:55] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[03:01:55] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • Booting (115ms)time
  • Application (371ms)time
  • 1 x Application (76.29%)
    371ms
    1 x Booting (23.71%)
    115ms
    13 templates were rendered
    • articlearticle.blade.php#?blade
    • includes.article_top_bannerarticle_top_banner.blade.php#?blade
    • export_citation_formexport_citation_form.blade.php#?blade
    • includes.article_bottom_bannerarticle_bottom_banner.blade.php#?blade
    • includes.inc_related_journalsinc_related_journals.blade.php#?blade
    • includes.inc_related_ebooksinc_related_ebooks.blade.php#?blade
    • includes.journal_rightmenujournal_rightmenu.blade.php#?blade
    • includes.journal_right_bannerjournal_right_banner.blade.php#?blade
    • layouts.appapp.blade.php#?blade
    • layouts._login_access_login_access.blade.php#?blade
    • layouts._header_header.blade.php#?blade
    • layouts._main_menu_main_menu.blade.php#?blade
    • layouts._footer_menu_footer_menu.blade.php#?blade
    uri
    GET article/{article_id}/{param?}
    middleware
    web, check_user_access
    controller
    App\Http\Controllers\ArticleController@GetArticleDetails
    namespace
    App\Http\Controllers
    where
    as
    article
    file
    app/Http/Controllers/ArticleController.php:1974-2510
    32 statements were executed, 4 of which were duplicates, 28 unique. Show only duplicated286ms
    • Connection Establishedalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 9. middleware::check_user_access:24
      • 10. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 11. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address (ip_address,visitor_agent,visitor_count, created_on,updated_on) VALUES ('59142255','',1,1739847715,1739847715) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1739847715
      7.07msalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 11. middleware::check_user_access:24
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address_detail (ip_address,visitor_url,visitor_count, created_on,updated_on) VALUES ('59142255','/article/58927',1,1739847715,1739847715)
      190μsalphaeurekaselec_live_10_06_2022UserAccessCheck.php#27
      Backtrace
      • 11. middleware::check_user_access:27
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_trail WHERE to_ip >= 59142255 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59142255) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_corporate WHERE to_ip >= 59142255 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59142255) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_token WHERE to_ip >= 59142255 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59142255) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_trail WHERE to_ip >= 59142255 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59142255) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_corporate WHERE to_ip >= 59142255 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59142255) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_token WHERE to_ip >= 59142255 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59142255) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 59142255 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59142255) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 59142255 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59142255) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 59142255 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59142255) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 59142255 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59142255) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 59142255 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59142255) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 59142255 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59142255) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 59142255 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59142255) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 59142255 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59142255) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 59142255 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59142255) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 59142255 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59142255) limit 1
      17.39msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 59142255
      • 1: 59142255
      • 2: 59142255
      • 3: 59142255
      • 4: 59142255
      • 5: 59142255
      • 6: 59142255
      • 7: 59142255
      • 8: 59142255
      • 9: 59142255
      • 10: 59142255
      • 11: 59142255
      • 12: 59142255
      • 13: 59142255
      • 14: 59142255
      • 15: 59142255
      Backtrace
      • 14. app/Models/UserAccess/UserAccess.php:784
      • 15. middleware::check_user_access:114
      • 16. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 18. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
    • SELECT at.type_name, p.copyright, p.publisher_location,m.month,y.year, a.publish_on, a.nid article_nid,a.article_id, a.pmid, a.issue_id, a.title, a.abstract,a.podcast,a.altmetric_score,a.altmetric_url,a.kudos_url, a.page_count, a.first_page, a.elocator, a.last_page, i.publication_date, a.file_name, a.file_path, a.doi, a.is_epub,a.epub_type, a.volume_id, a.is_uploaded, a.editor_choice, a.is_epub, j.image_file_name, a.article_no, a.art_type AS article_type, a.supplementary_filename,a.html_filename,a.prc_filename,a.epub_filename, a.graph_abs_lg_filename, a.graph_abs_sm_filename, a.oa_image_lg_filename, a.oa_image_sm_filename, j.journal_banner,a.animated_abstract,a.erratum_in,a.erratum_for, (CASE WHEN a.issue_id =0 THEN j.epub_price ELSE j.price END) AS sell_price, j.epub_price, j.nid AS jour_nid, j.title AS journal_title, j.issn, j.eissn,j.journal_id, j.subtitle AS jour_subtitle, v.volume_id,v.volume_name AS volume, v.year_id, i.title AS issue, i.month_id ,i.type issue_type, j.subtitle,j.formerly_title, ac.subtitle AS epub_title,a.crossmark_enabled,a.text_mining_urls,a.license_urls,a.created, a.receivedate, a.revisedate, a.acceptdate,js.js_title FROM article a LEFT JOIN article_section ac ON a.is_epub = ac.art_sec_id LEFT JOIN journal_section js ON a.js_id = js.js_id LEFT JOIN article_type at ON a.art_type = at.art_type_id LEFT JOIN issue i ON a.issue_id = i.issue_id LEFT JOIN month m ON m.id = i.month_id LEFT JOIN volume v ON v.volume_id = a.volume_id INNER JOIN year y ON y.id = v.year_id INNER JOIN journal j ON j.journal_id = a.journal_id INNER JOIN publisher p ON p.publisher_id = j.publisher_id WHERE a.article_id=58927
      1msalphaeurekaselec_live_10_06_2022Article.php#408
      Backtrace
      • 11. app/Models/Article.php:408
      • 12. app/Http/Controllers/ArticleController.php:2515
      • 13. app/Http/Controllers/ArticleController.php:2035
      • 14. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 15. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `journal` where `journal_id` = 29 limit 1
      820μsalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 29
      Backtrace
      • 14. app/Models/Journal.php:64
      • 15. app/Http/Controllers/ArticleController.php:2516
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=29) and sj.journal_id!=29 group by `j`.`nid`) as `aggregate_table`
      1.43msalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 16. app/Models/Subject.php:200
      • 17. app/Http/Controllers/ArticleController.php:2517
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=29) and sj.journal_id!=29 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      870μsalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 14. app/Models/Subject.php:200
      • 15. app/Http/Controllers/ArticleController.php:2517
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=29) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      1.57msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 16. app/Models/Subject.php:220
      • 17. app/Http/Controllers/ArticleController.php:2518
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=29) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      1.49msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 14. app/Models/Subject.php:220
      • 15. app/Http/Controllers/ArticleController.php:2518
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `keywords` where `article_id` = '58927'
      1.14msalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 58927
      Backtrace
      • 13. app/Models/Keywords.php:43
      • 14. app/Http/Controllers/ArticleController.php:2519
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `article_citation` where `article_id` = '58927'
      220μsalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 58927
      Backtrace
      • 13. app/Models/Article.php:1570
      • 14. app/Http/Controllers/ArticleController.php:2520
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select CONCAT_WS(' ',au.first_name, ' ', ifnull(au.initials,''), ' ', au.last_name) as authors, CONCAT(au.last_name, IFNULL(CONCAT(' ', au.initials), ''), ' ', au.first_name) AS authorsRIS, CONCAT_WS(' ',au.last_name, ' ', ifnull(au.initials,''), ' ', au.first_name) as authorsCiteAs, CONCAT_WS(' ',au.first_name, IFNULL(CONCAT(' ', au.initials), ''), IFNULL(CONCAT(' ', au.last_name), '')) as authorsmodal , `au`.*, `af`.`ror_id`, `af`.`institution`, `af`.`department`, `af`.`country`, `af`.`city`, `af`.`address`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.institution,','),''), ifnull(concat(af.department,','),''), ifnull(concat(af.address,','),''), ifnull(concat(af.city,','),''), ifnull(concat(af.country,','),''), ifnull(concat(af.postal_code,','),''), ifnull(concat(af.phone,','),''), ifnull(concat(af.fax,','),''))) SEPARATOR '|')) as `author_affiliation`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.web_view,','),''))) SEPARATOR '|')) as `web_view` from `author` as `au` left join `author_affiliation` as `af` on `au`.`author_id` = `af`.`author_id` where `au`.`article_id` = '58927' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      1.71msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 58927
      Backtrace
      • 13. app/Models/Author.php:86
      • 14. app/Http/Controllers/ArticleController.php:2533
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      280μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2535
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `subtitle` from `journal` where `continues_publication_journal` = 1
      670μsalphaeurekaselec_live_10_06_2022Article.php#1960
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/Article.php:1960
      • 14. app/Http/Controllers/ArticleController.php:2062
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • Select j.subtitle, v.volume_id as volume_id,v.year_id,y.year as year,v.volume_name, v.total_no_of_issues, i.issue_id as issue_id,i.title as issue, i.publication_date as issue_pub_date from journal j join volume v on j.journal_id = v.journal_id join issue i on v.volume_id = i.volume_id join article a on a.issue_id = i.issue_id join year y on v.year_id = y.id where j.journal_id = 29 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      62.34msalphaeurekaselec_live_10_06_2022Issue.php#298
      Backtrace
      • 11. app/Models/Issue.php:298
      • 12. app/Http/Controllers/ArticleController.php:2068
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 1 and a.journal_id = 29 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      63.75msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2070
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 4 and a.journal_id = 29 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      65.28msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2071
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select pdf, html, epub, prc from `article_metrics` where `article_id` = 58927 limit 1
      830μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 58927
      Backtrace
      • 14. app/Models/Article.php:744
      • 15. app/Http/Controllers/ArticleController.php:2091
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from content_by_diseases where content_id = 58927 and content_type = 'article' order by status desc limit 1
      1.69msalphaeurekaselec_live_10_06_2022Article.php#751
      Backtrace
      • 11. app/Models/Article.php:751
      • 12. app/Http/Controllers/ArticleController.php:2094
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid article_nid,a.title article_title,j.title journal_title from content_by_diseases cd inner join article a on a.article_id=cd.content_id inner join journal j on j.journal_id=a.journal_id where cd.pid = 16 and cd.sub_disease_id = 434 and content_id!=58927 and cd.content_type = 'article' order by rand() limit 20
      46.62msalphaeurekaselec_live_10_06_2022Article.php#769
      Backtrace
      • 11. app/Models/Article.php:769
      • 12. app/Http/Controllers/ArticleController.php:2098
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `node_meta` where `nid` = 120079 limit 1
      380μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 120079
      Backtrace
      • 14. app/Models/Meta.php:30
      • 15. app/Http/Controllers/ArticleController.php:2101
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      330μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2108
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `tbl_ht_submission` as `h` where `h`.`subtitle` = 'CPD' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      480μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CPD
      Backtrace
      • 13. app/Models/Article.php:2025
      • 14. app/Http/Controllers/ArticleController.php:2112
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '58927' and content_type = 'a' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      530μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2186
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `first_page` < '4605' and is_uploaded = 1 and issue_id = 5845 order by cast(first_page as SIGNED) desc limit 1
      580μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 4605
      Backtrace
      • 14. app/Models/Article.php:1819
      • 15. app/Http/Controllers/ArticleController.php:2470
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `last_page` > '4607' and is_uploaded = 1 and issue_id = 5845 order by cast(first_page as SIGNED) asc limit 1
      470μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 4607
      Backtrace
      • 14. app/Models/Article.php:1831
      • 15. app/Http/Controllers/ArticleController.php:2472
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `language_id` from `multilanguage` where `short_code` = 'en'
      180μsalphaeurekaselec_live_10_06_2022ArticleController.php#2497
      Bindings
      • 0: en
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2497
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `source_lang_label`, `target_lang_label` from `multilanguage_labels` where `target_lang_id` = 1
      340μsalphaeurekaselec_live_10_06_2022MultiLanguage.php#23
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/MultiLanguage.php:23
      • 14. app/Http/Controllers/ArticleController.php:2498
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `id` from `multilanguage_article` where `article_id` = 58927 limit 1
      2.59msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 58927
      Backtrace
      • 16. app/Http/Controllers/ArticleController.php:2506
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 29 and `b`.`banner_from_date` <= 1739847715 and `b`.`banner_to_date` >= 1739847715 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.53msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 29
      • 3: 1739847715
      • 4: 1739847715
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 29 and `b`.`banner_from_date` <= 1739847715 and `b`.`banner_to_date` >= 1739847715 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.49msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 29
      • 3: 1739847715
      • 4: 1739847715
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='fe936a4f458d9b7bdf85e32f83992b0e'
      300μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\MultiLanguage
    1MultiLanguage.php#?
        _token
        Vc8GA7pCYVRYTewlg42B9oJ8jH3uiHIoLpljeaDO
        uc_cart_id
        fe936a4f458d9b7bdf85e32f83992b0e
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/58927" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/58927
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:8 [ "accept-encoding" => array:1 [ 0 => "gzip, deflate" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] "connection" => array:1 [ 0 => "keep-alive" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] ]
        request_cookies
        []
        
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Tue, 18 Feb 2025 03:01:55 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6InNTTUVYbWptckYvNjNQOXdPTFplakE9PSIsInZhbHVlIjoiY3VsaklHQlFyYlF6c3drR1NCTDUrU213aTJuQWhWODJpVmJUT3NUVWl0RGxRQzg0OUV2TkVRdDc0bXg5ZU8xdk16THZnQkEvelRSeGdJMGUvM0cyUGxrS0hsRWhIRDFpc2VJRVp1Y1VlOVk0RnVTYlVMYjhxeVZ2SW0zTVVOcWciLCJtYWMiOiJmOGM1NjVjOGRjNDdiMmE1ZWE5N2UxNWZmODBjZWE5MDAzNzU5YzRiM2EyOGY3MWJkNDU5ZDFlYjhiYmRjODBkIiwidGFnIjoiIn0%3D; expires=Thu, 20 Feb 2025 15:01:55 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6InNTTUVYbWptckYvNjNQOXdPTFplakE9PSIsInZhbHVlIjoiY3VsaklHQlFyYlF6c3drR1NCTDUrU213aTJuQWhWODJpVmJUT3NUVWl0RGxRQzg0OUV2TkVRdDc0bXg5ZU8xdk16THZnQ" 1 => "alphaeurekaselectnet_session=eyJpdiI6IjBGdTBoN2ZhRlNvOWFMdXFmRjlmYXc9PSIsInZhbHVlIjoiVHZTcWpTZndNSVg3T1FwMU4vUFhUVklHQ1B1bEtRTFVmM3F3cTVGZ1pSSXdVY0JkY1U4c3Fxd1RSRlFOTnpOSGlFZ1M1SEphZzNTWGNUbnRCVjYwRUdXcE9PRU8vbXVWcGQrTURPa0lVSDZmdllDc0N4Q3IwQ2JMK2x2VWNWQjYiLCJtYWMiOiI1ZjUzNThmYWNhNWFjN2M1NjkwOWZiMDRhMDc3MjM2MDI1YTE0MTJhM2QzY2ViM2Y1ZTcxM2Y2NDcwOTgwNzdhIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6IjBGdTBoN2ZhRlNvOWFMdXFmRjlmYXc9PSIsInZhbHVlIjoiVHZTcWpTZndNSVg3T1FwMU4vUFhUVklHQ1B1bEtRTFVmM3F3cTVGZ1pSSXdVY0JkY1U4c3Fxd1R" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6InNTTUVYbWptckYvNjNQOXdPTFplakE9PSIsInZhbHVlIjoiY3VsaklHQlFyYlF6c3drR1NCTDUrU213aTJuQWhWODJpVmJUT3NUVWl0RGxRQzg0OUV2TkVRdDc0bXg5ZU8xdk16THZnQkEvelRSeGdJMGUvM0cyUGxrS0hsRWhIRDFpc2VJRVp1Y1VlOVk0RnVTYlVMYjhxeVZ2SW0zTVVOcWciLCJtYWMiOiJmOGM1NjVjOGRjNDdiMmE1ZWE5N2UxNWZmODBjZWE5MDAzNzU5YzRiM2EyOGY3MWJkNDU5ZDFlYjhiYmRjODBkIiwidGFnIjoiIn0%3D; expires=Thu, 20-Feb-2025 15:01:55 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6InNTTUVYbWptckYvNjNQOXdPTFplakE9PSIsInZhbHVlIjoiY3VsaklHQlFyYlF6c3drR1NCTDUrU213aTJuQWhWODJpVmJUT3NUVWl0RGxRQzg0OUV2TkVRdDc0bXg5ZU8xdk16THZnQ" 1 => "alphaeurekaselectnet_session=eyJpdiI6IjBGdTBoN2ZhRlNvOWFMdXFmRjlmYXc9PSIsInZhbHVlIjoiVHZTcWpTZndNSVg3T1FwMU4vUFhUVklHQ1B1bEtRTFVmM3F3cTVGZ1pSSXdVY0JkY1U4c3Fxd1RSRlFOTnpOSGlFZ1M1SEphZzNTWGNUbnRCVjYwRUdXcE9PRU8vbXVWcGQrTURPa0lVSDZmdllDc0N4Q3IwQ2JMK2x2VWNWQjYiLCJtYWMiOiI1ZjUzNThmYWNhNWFjN2M1NjkwOWZiMDRhMDc3MjM2MDI1YTE0MTJhM2QzY2ViM2Y1ZTcxM2Y2NDcwOTgwNzdhIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6IjBGdTBoN2ZhRlNvOWFMdXFmRjlmYXc9PSIsInZhbHVlIjoiVHZTcWpTZndNSVg3T1FwMU4vUFhUVklHQ1B1bEtRTFVmM3F3cTVGZ1pSSXdVY0JkY1U4c3Fxd1R" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "Vc8GA7pCYVRYTewlg42B9oJ8jH3uiHIoLpljeaDO" "uc_cart_id" => "fe936a4f458d9b7bdf85e32f83992b0e" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/article/58927" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-18 03:01:55GET/article/58927313321