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      Clinical impact of melatonin on breast cancer patients undergoing chemotherapy; effects on cognition, sleep and depressive symptoms: A randomized, double-blind, placebo-controlled trial

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          Abstract

          This randomized, double-blinded, placebo-controlled trial tested the hypothesis that 20mg of melatonin before and during the first cycle of adjuvant chemotherapy for breast cancer (ACBC) reduced the side effects associated with cognitive impairment. We evaluated the effects of melatonin on cognition, depressive symptoms and sleep quality, and whether these effects were related to serum levels of Brain Derived Neurotrophic Factor (BDNF) and its receptor, tropomyosin kinase B (TrkB). Thirty-six women were randomly assigned to receive melatonin or placebo for 10 days. To evaluate cognitive performance, we used the Trail-Making-Test Parts A and B (A-B), Rey Auditory-Verbal Learning Test (RAVLT), Controlled Oral Word Association Test (COWAT) and an inhibitory task type Go / No-Go. Our results revealed that melatonin improved executive function on TMT scores, enhanced episodic memory (immediate and delayed) and recognition on RAVLT, and increased verbal fluency in the orthographic COWAT. The TMT-A-B(A-B) were negatively correlated with baseline levels of TrkB and BDNF, respectively. At the end of treatment, changes in TrkB and BDNF were inversely associated with depressive symptoms and sleep quality, but not with the TMT scores. These results suggest a neuroprotective effect of melatonin to counteract the adverse effects of ACBC on cognitive function, sleep quality and depressive symptoms.

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          Psychometric properties of the Beck Depression Inventory-II: a comprehensive review

          Objective: To review the psychometric properties of the Beck Depression Inventory-II (BDI-II) as a self-report measure of depression in a variety of settings and populations. Methods: Relevant studies of the BDI-II were retrieved through a search of electronic databases, a hand search, and contact with authors. Retained studies (k = 118) were allocated into three groups: non-clinical, psychiatric/institutionalized, and medical samples. Results: The internal consistency was described as around 0.9 and the retest reliability ranged from 0.73 to 0.96. The correlation between BDI-II and the Beck Depression Inventory (BDI-I) was high and substantial overlap with measures of depression and anxiety was reported. The criterion-based validity showed good sensitivity and specificity for detecting depression in comparison to the adopted gold standard. However, the cutoff score to screen for depression varied according to the type of sample. Factor analysis showed a robust dimension of general depression composed by two constructs: cognitive-affective and somatic-vegetative. Conclusions: The BDI-II is a relevant psychometric instrument, showing high reliability, capacity to discriminate between depressed and non-depressed subjects, and improved concurrent, content, and structural validity. Based on available psychometric evidence, the BDI-II can be viewed as a cost-effective questionnaire for measuring the severity of depression, with broad applicability for research and clinical practice worldwide.
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            Global connectivity of prefrontal cortex predicts cognitive control and intelligence.

            Control of thought and behavior is fundamental to human intelligence. Evidence suggests a frontoparietal brain network implements such cognitive control across diverse contexts. We identify a mechanism--global connectivity--by which components of this network might coordinate control of other networks. A lateral prefrontal cortex (LPFC) region's activity was found to predict performance in a high control demand working memory task and also to exhibit high global connectivity. Critically, global connectivity in this LPFC region, involving connections both within and outside the frontoparietal network, showed a highly selective relationship with individual differences in fluid intelligence. These findings suggest LPFC is a global hub with a brainwide influence that facilitates the ability to implement control processes central to human intelligence.
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              Inflammation: The Common Pathway of Stress-Related Diseases

              While modernization has dramatically increased lifespan, it has also witnessed that the nature of stress has changed dramatically. Chronic stress result failures of homeostasis thus lead to various diseases such as atherosclerosis, non-alcoholic fatty liver disease (NAFLD) and depression. However, while 75%–90% of human diseases is related to the activation of stress system, the common pathways between stress exposure and pathophysiological processes underlying disease is still debatable. Chronic inflammation is an essential component of chronic diseases. Additionally, accumulating evidence suggested that excessive inflammation plays critical roles in the pathophysiology of the stress-related diseases, yet the basis for this connection is not fully understood. Here we discuss the role of inflammation in stress-induced diseases and suggest a common pathway for stress-related diseases that is based on chronic mild inflammation. This framework highlights the fundamental impact of inflammation mechanisms and provides a new perspective on the prevention and treatment of stress-related diseases.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: InvestigationRole: MethodologyRole: SupervisionRole: Writing – original draft
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: InvestigationRole: Methodology
                Role: Data curationRole: MethodologyRole: Validation
                Role: Data curationRole: MethodologyRole: Writing – original draft
                Role: ConceptualizationRole: Methodology
                Role: ConceptualizationRole: ResourcesRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: VisualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                17 April 2020
                2020
                : 15
                : 4
                : e0231379
                Affiliations
                [1 ] Department of Pharmacology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
                [2 ] School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
                [3 ] La Salle University Center, Canoas, RS, Brazil
                [4 ] Division of Breast Surgery, Hospital de Clinicas de Porto Alegre (HCPA), Post-graduate Program in Gynecology and Obstetrics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
                [5 ] Pharmacology Department, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
                [6 ] Spaulding Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA, United States of America
                [7 ] Pain and Palliative Care Service, Hospital de Clínicas de Porto Alegre (HCPA), Department of Surgery, School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
                Betsi Cadwaladr University Health Board, UNITED KINGDOM
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Article
                PONE-D-19-21207
                10.1371/journal.pone.0231379
                7164654
                32302347
                48bcc3f5-98f0-410b-97e6-18446e9a2c47
                © 2020 Palmer et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 6 August 2019
                : 22 March 2020
                Page count
                Figures: 3, Tables: 5, Pages: 24
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100002322, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior;
                Award ID: 1509885/2013
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100003593, Conselho Nacional de Desenvolvimento Científico e Tecnológico;
                Award ID: 302345/2011-6
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100003593, Conselho Nacional de Desenvolvimento Científico e Tecnológico;
                Award ID: 301256/2013-6
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100004809, Financiadora de Estudos e Projetos;
                Award ID: 1245/13
                Award Recipient :
                Funded by: Research Incentive Funding (FIPE/HCPA)
                Award ID: 14-0701
                Funded by: funder-id http://dx.doi.org/10.13039/501100004263, Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul;
                Award Recipient :
                The present research was funded via the following Brazilian agencies: (i) Committee for the Development of Higher Education Personnel (CAPES) (PNPD Grant no. 1509885 MZ). (ii) National Council for Scientific and Technological Development [(CNPq (Research grant: IT 302345/2011-6 and WC 30 1256/ 201 3-6)]. (iii) Hospital de Clínicas de Porto Alegre (HCPA) Research Incentive Funding (FIPE: 14-0701). (iv) Foundation for Research of the State of Rio Grande do Sul (FAPERGS). (v) Studies and Projects Financing Agency (FINEP: 1245/13). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Biochemistry
                Hormones
                Melatonin
                Biology and Life Sciences
                Physiology
                Physiological Processes
                Sleep
                Medicine and Health Sciences
                Physiology
                Physiological Processes
                Sleep
                Biology and Life Sciences
                Neuroscience
                Cognitive Science
                Cognition
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                Cellular Neuroscience
                Neuronal Plasticity
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                Mental Health and Psychiatry
                Mood Disorders
                Depression
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                Cognitive Science
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                Cognitive Neurology
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                Cognitive Neuroscience
                Cognitive Neurology
                Medicine and Health Sciences
                Neurology
                Cognitive Neurology
                Biology and Life Sciences
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                Cognitive Science
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                Cognitive Neurology
                Cognitive Impairment
                Biology and Life Sciences
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                Cognitive Neuroscience
                Cognitive Neurology
                Cognitive Impairment
                Medicine and Health Sciences
                Neurology
                Cognitive Neurology
                Cognitive Impairment
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Breast Tumors
                Breast Cancer
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