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Brain Sci., Volume 7, Issue 11 (November 2017)

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Research

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Open AccessArticle Mental Health Literacy Content for Children of Parents with a Mental Illness: Thematic Analysis of a Literature Review
Brain Sci. 2017, 7(11), 141; doi:10.3390/brainsci7110141
Received: 1 August 2017 / Revised: 15 October 2017 / Accepted: 16 October 2017 / Published: 26 October 2017
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Abstract
Millions of children have a parent with a mental illness (COPMI). These children are at higher risk of acquiring behavioural, developmental and emotional difficulties. Most children, including COPMI, have low levels of mental health literacy (MHL), meaning they do not have accurate, non-stigmatized
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Millions of children have a parent with a mental illness (COPMI). These children are at higher risk of acquiring behavioural, developmental and emotional difficulties. Most children, including COPMI, have low levels of mental health literacy (MHL), meaning they do not have accurate, non-stigmatized information. There is limited knowledge about what kind of MHL content should be delivered to children. The aim of this exploratory study is to identify the knowledge content needed for general population children and COPMI to increase their MHL. A second aim is to explore content for emerging children’s MHL scales. Researchers created and analyzed a literature review database. Thematic analysis yielded five main mental health knowledge themes for children: (1) attaining an overview of mental illness and recovery; (2) reducing mental health stigma; (3) building developmental resiliencies; (4) increasing help-seeking capacities; and (5) identifying risk factors for mental illness. COPMI appeared to need the same kind of MHL knowledge content, but with extra family-contextual content such as dealing with stigma experiences, managing stress, and communicating about parental mental illness. There is a need for MHL programs, validated scales, and research on what works for prevention and early intervention with COPMI children. Full article
(This article belongs to the Special Issue Mental Illness in Children)
Open AccessCommunication 4SC-202 as a Potential Treatment for the Pediatric Brain Tumor Medulloblastoma
Brain Sci. 2017, 7(11), 147; doi:10.3390/brainsci7110147
Received: 31 August 2017 / Revised: 20 October 2017 / Accepted: 23 October 2017 / Published: 3 November 2017
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Abstract
This project involves an examination of the effect of the small molecule inhibitor 4SC-202 on the growth of the pediatric brain cancer medulloblastoma. The small molecule inhibitor 4SC-202 significantly inhibits the viability of the pediatric desmoplastic cerebellar human medulloblastoma cell line DAOY, with
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This project involves an examination of the effect of the small molecule inhibitor 4SC-202 on the growth of the pediatric brain cancer medulloblastoma. The small molecule inhibitor 4SC-202 significantly inhibits the viability of the pediatric desmoplastic cerebellar human medulloblastoma cell line DAOY, with an IC50 = 58.1 nM, but does not affect the viability of noncancerous neural stem cells (NSC). 4SC-202 exposure inhibits hedgehog expression in the DAOY cell line. Furthermore, microarray analysis of human medulloblastoma patient tumors indicate significant upregulation of key targets in the Hedgehog signaling pathway and Protein Tyrosine Kinase (PTK7). Full article
(This article belongs to the Special Issue Advances in Adult and Pediatric Brain Tumor Management)
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Open AccessArticle Adolescent Alcohol Drinking Renders Adult Drinking BLA-Dependent: BLA Hyper-Activity as Contributor to Comorbid Alcohol Use Disorder and Anxiety Disorders
Brain Sci. 2017, 7(11), 151; doi:10.3390/brainsci7110151
Received: 30 August 2017 / Revised: 31 October 2017 / Accepted: 10 November 2017 / Published: 14 November 2017
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Abstract
Adolescent alcohol drinking increases the risk for alcohol-use disorder in adulthood. Yet, the changes in adult neural function resulting from adolescent alcohol drinking remain poorly understood. We hypothesized that adolescent alcohol drinking alters basolateral amygdala (BLA) function, making alcohol drinking BLA-dependent in adulthood.
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Adolescent alcohol drinking increases the risk for alcohol-use disorder in adulthood. Yet, the changes in adult neural function resulting from adolescent alcohol drinking remain poorly understood. We hypothesized that adolescent alcohol drinking alters basolateral amygdala (BLA) function, making alcohol drinking BLA-dependent in adulthood. Male, Long Evans rats were given voluntary, intermittent access to alcohol (20% ethanol) or a bitter, isocaloric control solution, across adolescence. Half of the rats in each group received neurotoxic BLA lesions. In adulthood, all rats were given voluntary, intermittent access to alcohol. BLA lesions reduced adult alcohol drinking in rats receiving adolescent access to alcohol, but not in rats receiving adolescent access to the control solution. The effect of the BLA lesion was most apparent in high alcohol drinking adolescent rats. The BLA is essential for fear learning and is hyper-active in anxiety disorders. The results are consistent with adolescent heavy alcohol drinking inducing BLA hyper-activity, providing a neural mechanism for comorbid alcohol use disorder and anxiety disorders. Full article
(This article belongs to the Special Issue Alcohol Induced Central Nervous System Damage)
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Open AccessArticle Salivary Oxytocin Concentration Changes during a Group Drumming Intervention for Maltreated School Children
Brain Sci. 2017, 7(11), 152; doi:10.3390/brainsci7110152
Received: 25 July 2017 / Revised: 9 November 2017 / Accepted: 13 November 2017 / Published: 16 November 2017
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Abstract
Many emotionally-disturbed children who have been maltreated and are legally separated from their parents or primary caregivers live in group homes and receive compulsory education. Such institutions provide various special intervention programs. Taiko-ensou, a Japanese style of group drumming, is one such program
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Many emotionally-disturbed children who have been maltreated and are legally separated from their parents or primary caregivers live in group homes and receive compulsory education. Such institutions provide various special intervention programs. Taiko-ensou, a Japanese style of group drumming, is one such program because playing drums in a group may improve children’s emotional well-being. However, evidence for its efficacy has not been well established at the biological level. In this study, we measured salivary levels of oxytocin (OT), a neuropeptide associated with social memory and communication, in three conditions (recital, practice, and free sessions) in four classes of school-aged children. Following the sessions, OT concentrations showed changes in various degrees and directions (no change, increases, or decreases). The mean OT concentration changes after each session increased, ranging from 112% to 165%. Plasma OT concentrations were equally sensitive to drum playing in school-aged boys and girls. However, the difference between practice and free play sessions was only significant among elementary school boys aged 8–12 years. The results suggest that younger boys are most responsive to this type of educational music intervention. Full article
(This article belongs to the Special Issue Mental Illness in Children)
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Open AccessArticle Hyperplanar Morphological Clustering of a Hippocampus by Using Volumetric Computerized Tomography in Early Alzheimer’s Disease
Brain Sci. 2017, 7(11), 155; doi:10.3390/brainsci7110155
Received: 25 September 2017 / Revised: 14 November 2017 / Accepted: 17 November 2017 / Published: 21 November 2017
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Abstract
Background: On diagnosing Alzheimer’s disease (AD), most existing imaging-based schemes have relied on analyzing the hippocampus and its peripheral structures. Recent studies have confirmed that volumetric variations are one of the primary indicators in differentiating symptomatic AD from healthy aging. In this
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Background: On diagnosing Alzheimer’s disease (AD), most existing imaging-based schemes have relied on analyzing the hippocampus and its peripheral structures. Recent studies have confirmed that volumetric variations are one of the primary indicators in differentiating symptomatic AD from healthy aging. In this study, we focused on deriving discriminative shape-based parameters that could effectively identify early AD from volumetric computerized tomography (VCT) delineation, which was previously almost intangible. Methods: Participants were 63 volunteers of Thai nationality, whose ages were between 40 and 90 years old. Thirty subjects (age 68.51 ± 5.5) were diagnosed with early AD, by using Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria and the National Institute of Neurological and Communicative Disorders and the Stroke and the Alzheimer’s disease and Related Disorders Association (NINCDS-ADRDA) criteria, while the remaining 33 were in the healthy control group (age 67.93 ± 5.5). The structural imaging study was conducted by using VCT. Three uninformed readers were asked to draw left and right hippocampal outlines on a coronal section. The resultant shapes were aligned and then analyzed with statistical shape analysis to obtain the first few dominant variational parameters, residing in hyperplanes. A supervised machine learning, i.e., support vector machine (SVM) was then employed to elucidate the proposed scheme. Results: Provided trivial delineations, relatively as low as 5 to 7 implicit model parameters could be extracted and used as discriminants. Clinical verification showed that the model could differentiate early AD from aging, with high sensitivity, specificity, accuracy and F-measure of 0.970, 0.968, 0.983 and 0.983, respectively, with no apparent effect of left-right asymmetry. Thanks to a less laborious task required, yet high discriminating capability, the proposed scheme is expected to be applicable in a typical clinical setting, equipped with only a moderate-specs VCT. Full article
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Review

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Open AccessReview Self-Injury in Autism Spectrum Disorder and Intellectual Disability: Exploring the Role of Reactivity to Pain and Sensory Input
Brain Sci. 2017, 7(11), 140; doi:10.3390/brainsci7110140
Received: 18 September 2017 / Revised: 11 October 2017 / Accepted: 23 October 2017 / Published: 26 October 2017
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Abstract
This paper provides information about the prevalence and topography of self-injurious behavior in children and adults with autism spectrum disorder and intellectual disability. Dominant models regarding the etiology of self-injury in this population are reviewed, with a focus on the role of reactivity
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This paper provides information about the prevalence and topography of self-injurious behavior in children and adults with autism spectrum disorder and intellectual disability. Dominant models regarding the etiology of self-injury in this population are reviewed, with a focus on the role of reactivity to pain and sensory input. Neuroimaging studies are presented and suggestions are offered for future research. Full article
(This article belongs to the Special Issue Autism Spectrum Disorder: From Etio-Pathology to Treatment)
Open AccessReview Biomarkers Associated with the Outcome of Traumatic Brain Injury Patients
Brain Sci. 2017, 7(11), 142; doi:10.3390/brainsci7110142
Received: 29 August 2017 / Revised: 24 September 2017 / Accepted: 20 October 2017 / Published: 27 October 2017
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Abstract
This review focuses on biomarkers associated with the outcome of traumatic brain injury (TBI) patients, such as caspase-3; total antioxidant capacity; melatonin; S100B protein; glial fibrillary acidic protein (GFAP); glutamate; lactate; brain-derived neurotrophic factor (BDNF); substance P; neuron-specific enolase (NSE); ubiquitin carboxy-terminal hydrolase
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This review focuses on biomarkers associated with the outcome of traumatic brain injury (TBI) patients, such as caspase-3; total antioxidant capacity; melatonin; S100B protein; glial fibrillary acidic protein (GFAP); glutamate; lactate; brain-derived neurotrophic factor (BDNF); substance P; neuron-specific enolase (NSE); ubiquitin carboxy-terminal hydrolase L-1 (UCH-L1); tau; decanoic acid; and octanoic acid. Full article
Open AccessReview Intellectual Functioning in Offspring of Parents with Bipolar Disorder: A Review of the Literature
Brain Sci. 2017, 7(11), 143; doi:10.3390/brainsci7110143
Received: 12 September 2017 / Revised: 12 October 2017 / Accepted: 20 October 2017 / Published: 28 October 2017
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Abstract
Impaired intellectual functioning is an important risk factor for the emergence of severe mental illness. Unlike many other forms of mental disorder however, the association between bipolar disorder and intellectual deficits is unclear. In this narrative review, we examine the current evidence on
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Impaired intellectual functioning is an important risk factor for the emergence of severe mental illness. Unlike many other forms of mental disorder however, the association between bipolar disorder and intellectual deficits is unclear. In this narrative review, we examine the current evidence on intellectual functioning in children and adolescents at risk for developing bipolar disorder. The results are based on 18 independent, peer-reviewed publications from 1980 to 2017 that met criteria for this study. The findings yielded no consistent evidence of lower or higher intellectual quotient (IQ) in offspring of parents diagnosed with bipolar disorder. Some tentative evidence was found for lower performance IQ in offspring of bipolar parents as compared to controls. It is recommended that future research examine variability in intellectual functioning and potential moderators. These findings demonstrate the need to examine how intellectual functioning unfolds across development given the potential role of IQ as a marker of vulnerability or resilience in youth at high risk for affective disorders. Full article
(This article belongs to the Special Issue Neurological Research of Bipolar Disorder)
Open AccessFeature PaperReview Bipolar Disorder and Immune Dysfunction: Epidemiological Findings, Proposed Pathophysiology and Clinical Implications
Brain Sci. 2017, 7(11), 144; doi:10.3390/brainsci7110144
Received: 13 October 2017 / Revised: 25 October 2017 / Accepted: 27 October 2017 / Published: 30 October 2017
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Abstract
Bipolar disorder (BD) is strongly associated with immune dysfunction. Replicated epidemiological studies have demonstrated that BD has high rates of inflammatory medical comorbidities, including autoimmune disorders, chronic infections, cardiovascular disease and metabolic disorders. Cytokine studies have demonstrated that BD is associated with chronic
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Bipolar disorder (BD) is strongly associated with immune dysfunction. Replicated epidemiological studies have demonstrated that BD has high rates of inflammatory medical comorbidities, including autoimmune disorders, chronic infections, cardiovascular disease and metabolic disorders. Cytokine studies have demonstrated that BD is associated with chronic low-grade inflammation with further increases in pro-inflammatory cytokine levels during mood episodes. Several mechanisms have been identified to explain the bidirectional relationship between BD and immune dysfunction. Key mechanisms include cytokine-induced monoamine changes, increased oxidative stress, pathological microglial over-activation, hypothalamic-pituitary-adrenal (HPA) axis over-activation, alterations of the microbiome-gut-brain axis and sleep-related immune changes. The inflammatory-mood pathway presents several potential novel targets in the treatment of BD. Several proof-of-concept clinical trials have shown a positive effect of anti-inflammatory agents in the treatment of BD; however, further research is needed to determine the clinical utility of these treatments. Immune dysfunction is likely to only play a role in a subset of BD patients and as such, future clinical trials should also strive to identify which specific group(s) of BD patients may benefit from anti-inflammatory treatments. Full article
(This article belongs to the Special Issue Neurological Research of Bipolar Disorder)
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Open AccessReview Role of Immunological Memory Cells as a Therapeutic Target in Multiple Sclerosis
Brain Sci. 2017, 7(11), 148; doi:10.3390/brainsci7110148
Received: 31 August 2017 / Revised: 31 October 2017 / Accepted: 2 November 2017 / Published: 7 November 2017
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Abstract
Pharmacological targeting of memory cells is an attractive treatment strategy in various autoimmune diseases, such as psoriasis and rheumatoid arthritis. Multiple sclerosis is the most common inflammatory disorder of the central nervous system, characterized by focal immune cell infiltration, activation of microglia and
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Pharmacological targeting of memory cells is an attractive treatment strategy in various autoimmune diseases, such as psoriasis and rheumatoid arthritis. Multiple sclerosis is the most common inflammatory disorder of the central nervous system, characterized by focal immune cell infiltration, activation of microglia and astrocytes, along with progressive damage to myelin sheaths, axons, and neurons. The current review begins with the identification of memory cell types in the previous literature and a recent description of the modulation of these cell types in T, B, and resident memory cells in the presence of different clinically approved multiple sclerosis drugs. Overall, this review paper tries to determine the potential of memory cells to act as a target for the current or newly-developed drugs. Full article
(This article belongs to the Special Issue Pathophysiology and Imaging Diagnosis of Demyelinating Disorders)
Open AccessReview Is High Folic Acid Intake a Risk Factor for Autism?—A Review
Brain Sci. 2017, 7(11), 149; doi:10.3390/brainsci7110149
Received: 14 September 2017 / Revised: 2 November 2017 / Accepted: 6 November 2017 / Published: 10 November 2017
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Abstract
Folate is required for metabolic processes and neural development. Insuring its adequate levels for pregnant women through supplementation of grain-based foods with synthetic folic acid (FA) in order to prevent neural tube defects has been an ongoing public health initiative. However, because women
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Folate is required for metabolic processes and neural development. Insuring its adequate levels for pregnant women through supplementation of grain-based foods with synthetic folic acid (FA) in order to prevent neural tube defects has been an ongoing public health initiative. However, because women are advised to take multivitamins containing FA before and throughout pregnancy, the supplementation together with natural dietary folates has led to a demographic with high and rising serum levels of unmetabolized FA. This raises concerns about the detrimental effects of high serum synthetic FA, including a rise in risk for autism spectrum disorder (ASD). Some recent studies have reported a protective effect of FA fortification against ASD, but others have concluded there is an increased risk for ASD and other negative neurocognitive development outcomes. These issues are accompanied by further health questions concerning high, unmetabolized FA levels in serum. In this review, we outline the reasons excess FA supplementation is a concern and review the history and effects of supplementation. We then examine the effects of FA on neuronal development from tissue culture experiments, review recent advances in understanding of metabolic functional blocks in causing ASD and treatment for these with alternative forms such as folinic acid, and finally summarize the conflicting epidemiological findings regarding ASD. Based on the evidence evaluated, we conclude that caution regarding over supplementing is warranted. Full article
(This article belongs to the Special Issue Autism Spectrum Disorder: From Etio-Pathology to Treatment)
Open AccessReview Digital Platforms in the Assessment and Monitoring of Patients with Bipolar Disorder
Brain Sci. 2017, 7(11), 150; doi:10.3390/brainsci7110150
Received: 19 July 2017 / Revised: 24 October 2017 / Accepted: 6 November 2017 / Published: 12 November 2017
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Abstract
This paper aims to review the application of digital platforms in the assessment and monitoring of patients with Bipolar Disorder (BPD). We will detail the current clinical criteria for the diagnosis of BPD and the tools available for patient assessment in the clinic
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This paper aims to review the application of digital platforms in the assessment and monitoring of patients with Bipolar Disorder (BPD). We will detail the current clinical criteria for the diagnosis of BPD and the tools available for patient assessment in the clinic setting. We will go on to highlight the difficulties in the assessment and monitoring of BPD patients in the clinical context. Finally, we will elaborate upon the impact that diital platforms have made, and have the potential to make, on healthcare, mental health, and specifically the management of BPD, before going on to evaluate the benefits and drawbacks of the use of such technology. Full article
(This article belongs to the Special Issue Neurological Research of Bipolar Disorder)
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Open AccessReview Please Wait, Processing: A Selective Literature Review of the Neurological Understanding of Emotional Processing in ASD and Its Potential Contribution to Neuroeducation
Brain Sci. 2017, 7(11), 153; doi:10.3390/brainsci7110153
Received: 28 September 2017 / Revised: 1 November 2017 / Accepted: 13 November 2017 / Published: 17 November 2017
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Abstract
Autism spectrum disorder (ASD) and its corresponding conditions have been investigated from a multitude of perspectives resulting in varying understandings of its origin, its outplay, its prognosis, and potential methods of intervention and education for individuals with the disorder. One area that has
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Autism spectrum disorder (ASD) and its corresponding conditions have been investigated from a multitude of perspectives resulting in varying understandings of its origin, its outplay, its prognosis, and potential methods of intervention and education for individuals with the disorder. One area that has contributed significantly to providing a different type of understanding is that of neuroscience, and specifically neuroimaging. This paper will offer a selective literature review of research that investigates the role of emotional processing in ASD, and how a deepening of this line of understanding can be used to inform more comprehensive educational practices. Full article
(This article belongs to the Special Issue Autism Spectrum Disorder: From Etio-Pathology to Treatment)
Open AccessReview Systematic Review of Epigenetic Effects of Pharmacological Agents for Bipolar Disorders
Brain Sci. 2017, 7(11), 154; doi:10.3390/brainsci7110154
Received: 15 October 2017 / Revised: 6 November 2017 / Accepted: 16 November 2017 / Published: 18 November 2017
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Abstract
Epigenetic effects of medications are an evolving field of medicine, and can change the landscape of drug development. The aim of this paper is to systematically review the literature of the relationship between common medications used for treatment of bipolar disorders and epigenetic
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Epigenetic effects of medications are an evolving field of medicine, and can change the landscape of drug development. The aim of this paper is to systematically review the literature of the relationship between common medications used for treatment of bipolar disorders and epigenetic modifications. MedLine/PubMed searches were performed based on pre-specified inclusion criteria from inception to November 2017. Six animal and human studies met the inclusion criteria. These studies examined the epigenetic changes in the main classes of medications that are used in bipolar disorders, namely mood stabilizers and antipsychotics. Although these initial studies have small to moderate sample size, they generally suggest an evolving and accumulating evidence of epigenetic changes that are associated with several of the medications that are used in bipolar I and II disorders. In this manuscript, we describe the specific epigenetic changes that are associated with the medications studied. Of the studies reviewed, five of the six studies revealed epigenetic changes associated with the use of mood stabilizers or antipsychotic medications. This review contributes to future research directions. Further understanding of the complexities of the epigenome and the untangling of the effects and contributions of disease states versus medications is crucial for the future of drug design and the development of new therapeutics. Epigenetic therapeutics hold great promise for complex disease treatment and personalized interventions, including psychiatric diseases. Full article
(This article belongs to the Special Issue Neurological Research of Bipolar Disorder)
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Other

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Open AccessAddendum Addendum: Shinozuka, K. et al. Stem Cell Transplantation for Neuroprotection in Stroke. Brain Sci. 2013, 3, 239–261
Brain Sci. 2017, 7(11), 145; doi:10.3390/brainsci7110145
Received: 28 October 2017 / Revised: 30 October 2017 / Accepted: 30 October 2017 / Published: 31 October 2017
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Abstract
It has been brought to our attention that the Acknowledgement section is missing in our published paper [1], and therefore we would like to add it as follows[...] Full article
(This article belongs to the Special Issue Neuroprotection against Ischemic Brain Injury)
Open AccessConcept Paper Promoting Mental Health in Unaccompanied Refugee Minors: Recommendations for Primary Support Programs
Brain Sci. 2017, 7(11), 146; doi:10.3390/brainsci7110146
Received: 1 August 2017 / Revised: 9 October 2017 / Accepted: 18 October 2017 / Published: 1 November 2017
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Abstract
During the last years, the number of refugees around the world increased to about 22.5 million. The mental health of refugees, especially of unaccompanied minors (70% between the ages of 16 and 18 years) who have been exposed to traumatic events (e.g., war),
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During the last years, the number of refugees around the world increased to about 22.5 million. The mental health of refugees, especially of unaccompanied minors (70% between the ages of 16 and 18 years) who have been exposed to traumatic events (e.g., war), is generally impaired with symptoms of post-traumatic stress disorder, depression, and anxiety. Several studies revealed (1) a huge variation among the prevalence rates of these mental problems, and (2) that post-migration stressors (e.g., language barriers, cultural differences) might be at least as detrimental to mental health as the traumatic events in pre- and peri-flight. As psychotherapy is a limited resource that should be reserved for severe cases and as language trainings are often publicly offered for refugees, we recommend focusing on intercultural competence, emotion regulation, and goal setting and goal striving in primary support programs: Intercultural competence fosters adaptation by giving knowledge about cultural differences in values and norms. Emotion regulation regarding empathy, positive reappraisal, and cultural differences in emotion expression fosters both adaptation and mental health. Finally, supporting unaccompanied refugee minors in their goal setting and goal striving is necessary, as they carry many unrealistic wishes and unattainable goals, which can be threatening to their mental health. Building on these three psychological processes, we provide recommendations for primary support programs for unaccompanied refugee minors that are aged 16 to 18 years. Full article
(This article belongs to the Special Issue Mental Illness in Children)
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