Cultural assimilation of adult Syrian refugees in Lebanon: Effect modification by religiosity and sex on the relation between cultural adversities and common mental health disorders.

OBJECTIVE: In this study, we aimed to explore the prevalence and determinants of common mental health disorders (CMHDs, posttraumatic stress disorder [PTSD], depression, and anxiety) in Syrian refugees in Lebanon. Specifically, we examined how the associations between cultural adversities (discrimination, unemployment, and separation from family) and CMHDs are modified by levels of religiosity and sex. METHOD: Between March and June 2017, a cross-sectional study was conducted targeting adult Arab Syrian refugees residing in Beirut and Southern Lebanon. Eligibility criteria comprised being a United Nations High Commissioner for Refugees-registered Syrian refugee residing in Lebanon, 18 years and older, and having no history of mental disorder or physical disability. A total of 191 refugees agreed to participate and complete a battery of six questionnaires. Exposures were measured using a sociodemographic questionnaire, the Postmigration Living Difficulties Checklist, the Harvard Trauma Questionnaire, and the Belief into Action Scale, while outcomes were measured using the Posttraumatic Stress Disorder Checklist for DSM-5 and the Depression and Anxiety Scale-21 Items. RESULTS: Half (50.3%) of our sample had high PTSD risk, 73.8% had high depression risk, and 73.8% had high anxiety risk. Stratified analysis revealed religiosity and sex to be effect modifiers of the associations between cultural adversities and CMHDs. Specifically, cultural adversities were only significantly associated with CMHDs in the low religiosity stratum and males. Only unemployment was a significant risk factor for PTSD in both males (OR = 4.53, 95% CI [1.44, 14.27]) and females (OR = 2.77, 95% CI [1.14, 6.74]). CONCLUSIONS: Religiosity and sex are effect modifiers of the associations between cultural adversities and CMHDs. Religious and spiritual interventions in mental health care should be adopted in refugee settings. Moreover, there is an urgent need for capacity-building initiatives addressing social determinants of mental health among Syrian refugees in Lebanon. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Orexins/Hypocretins: Gatekeepers of Social Interaction and Motivation.

Ever since the discovery of the brain's orexin/hypocretin system, most research was directed toward unveiling its contribution to the normal functioning of individuals. The investigation of reward-seeking behaviors then gained a lot of attention once the distribution of orexinergic neurons was revealed. Here, we discuss findings on the involvement of orexins in social interaction, a natural reward type. While some studies have succeeded in defining the relationship between orexin and social interaction, the controversy regarding its nature (direct or inverse relation) raises questions about what aspects have been overlooked until now. Upon examining the literature, we identified a research gap concerning conditions influencing the impact of orexins on social behavior expression. In this review, we introduce a number of factors (e.g., stress, orexin's source) that must be considered while studying the role of orexins in social interaction. Furthermore, we refer to published research to investigate the stage at which orexins affect social interaction and we highlight the nucleus accumbens (NAc) shell's role in social interaction and other rewarding behaviors. Finally, the underlying orexin molecular pathway influencing social motivation in particular illnesses is proposed. We conclude that orexin's impact on social interaction is multifactorial and depends on specific conditions available at a time.

The Radboud dysarthria assessment: validity and reliability of the Arabic version.

PURPOSE: To cross-culturally adapt and validate the Radboud Dysarthria Assessment (RDA) and the speech component of the Radboud Oral Motor inventory for Parkinson's disease (ROMP-speech) into the Arabic language among Lebanese subjects with dysarthria. MATERIALS AND METHODS: This study included 50 participants with dysarthria. The Arabic versions of the RDA (A-RDA) and the ROMP-speech (A-ROMP-speech) were administered in addition to the Arabic Speech Intelligibility test, the Lebanese Voice Handicap Index-10 (VHI-10lb) and semantic verbal fluency tasks. The maximum performance tasks were analyzed using the Praat software. The A-RDA qualitative recording form and the A-ROMP-speech were assessed for construct validity and internal consistency. The convergent validity of the maximum performance tasks, the severity scale, and the A-ROMP-speech were evaluated. RESULTS: Exploratory factor analysis of the qualitative recording form extracted 3 factors explaining 82.973% of the total variance, and it demonstrated high internal consistency (α = 0.912). The maximum performance tasks of the RDA correlated significantly with the corresponding Praat scores. The severity scale and the A-ROMP-speech correlated fairly to strongly with the Arabic Speech Intelligibility test (rs=-0.695 and -0.736, p < 0.001) and the VHI-10lb (r = 0.539 and 0.640, p < 0.001). CONCLUSION: The A-RDA and the A-ROMP-speech are valid and reliable dysarthria tools among Lebanese subjects.

The present study cross-culturally adapts and validates a dysarthria assessment tool in the Arab culture.The Arabic Radboud Dysarthria Assessment (A-RDA) and the speech component of the Arabic Radboud Oral Motor inventory for Parkinson's disease-speech component (A-ROMP-speech) are valid and reliable measures to be used among Lebanese individuals with dysarthria.The use of the A-RDA and the A-ROMP-speech will contribute to better therapeutic outcomes and will lead to a common language among speech and language therapists.

Evaluation of the accuracy of new modalities in the assessment and classification of lumbar lordosis: A comparison to Cobb's angle measurement.

Background: Because of the association of lumbar lordosis with some clinical conditions such as low back pain, the chiropractic field has emphasized the significance of evaluating the lumbar lordotic status, by measuring Cobb's angle, regarded as the radiological gold standard, for the assessment of lumbar lordosis, on lateral radiographs. However, research has shown that this technique has some considerable drawbacks, mostly in terms of low accuracy and high variability between clinicians when compared with other radiological modalities. The main objective was to compare the diagnostic accuracy of newly established radiological measurements with one of Cobb's angle methods, for the characterization of lumbar lordosis status in a sample of Lebanese patients aged 15 and above. Material and methods: This retrospective single-center study consisted of measuring Cobb's L1-S1 and Cobb's L1-L5 angles, along with the novel established measurements which are the derivative and the normalized surface area, on 134 lateral radiographs of the lumbar spine of Lebanese patients aged fifteen years old and above, gotten from the Radiology department at Zahra'a's Hospital in Beirut, performed by two observers using MATLAB. Inter-rater agreement was assessed by calculating the Intra-class correlation coefficients. Spearman correlation was analyzed between both Cobb's angle methods and with the derivative and normalized area respectively. 54 patients of the sample were diagnosed by two radiologists, according to their LL status. ROC curve analysis was performed to compare the diagnostic accuracy of the four techniques used. Data were analyzed with IBM SPSS Statistics 23.0 (NY, USA); P < 0.05 was considered statistically significant. Results: According to the ROC curve analysis the new methods, which are the derivative and the normalized surface area, displayed lower diagnostic accuracy (AUCderivative = 0.818 and 0.677, AUCsurface area = 0.796 and 0.828) than Cobb's L1-L5 (AUCL1-L5 = 0.924 and 0.929 values) and L1-S1 (AUCL1-S1 = 0.971 and 0.955) angles, in the characterization of hypo and hyperlordotic patients, respectively, in our Lebanese sample consisting of patients aged 15 and above, because of their lower area under the curve's values compared to the traditional Cobb's techniques. The Cobb's L1-S1 has shown to have the highest diagnostic accuracy among the four methods to characterize normal patients from hypo and hyperlordotic ones, by referring to its highest area under the curve's values. However, the sensitivity of Cobb's L1-L5 angle in characterizing hyperlordotic patients was similar to the one of the normalized surface area with a value of 100%.Conclusion: among the four modalities, the new methods didn't show a better diagnostic accuracy compared to the traditional modalities. Cobb's L1-S1 displayed the highest diagnostic accuracy despite its drawbacks. Further prospective studies are needed to validate the cut-offs obtained for Cobb's L1-S1 angle in our sample.

Association between vitamin D deficiency and multiple sclerosis- MRI significance: A scoping review.

Background/Objective: Multiple Sclerosis is a common demyelinating disease of the central nervous system. Several studies suggested a link between vitamin D deficiency and multiple sclerosis disease activity, which can be evaluated by magnetic resonance imaging. Thereby, the main objective of the following scoping review is to summarize the magnetic resonance imaging findings assessing the probable effects of vitamin D on MS disease activity. Methodology: PRISMA checklist for systematic reviews and meta-analyses was employed to structure this review. Literature was searched for observational and clinical studies tackling the given matter using several search engines including PubMed, CORE, and Embase. Data was extracted in a systematic manner, and the articles meeting the inclusion criteria were quality-assessed by Jadad scale for randomized clinical trials (RCTs) and Newcastle-Ottawa scale for observational studies. Results: A total of 35 articles were included. Twenty-one (60%) studies noted a statistically significant association between vitamin D and Multiple Sclerosis MRI-detected disease activity. MRI-detected features involved lower contrast-enhancing T1 lesions, lower hyperintense T2 lesions, and a decrease in lesions volume. On the other hand, 40% (14 articles) of the articles did not detect any significant effect of vitamin D on Multiple Sclerosis disease activity. Due to the heterogeneity of the studies involved, meta-analysis was not employed in the given review. Discussion/conclusion: There was an abundance in the number of research studies investigating the relationship between vitamin D and Multiple Sclerosis while highlighting the significant role of MRI in assessing the activity of the disease. Numerous studies found that higher serum vitamin D levels are associated with decreased new active cortical and subcortical lesions and lower lesions volume. These findings highlight the importance of imaging modalities in the various aspects of neurological diseases and encourage further research to focus on the preventive effects of vitamin D on MS patients.

High fat diet exacerbates long-term metabolic, neuropathological, and behavioral derangements in an experimental mouse model of traumatic brain injury.

AIMS: Traumatic brain injury (TBI) constitutes a serious public health concern. Although TBI targets the brain, it can exert several systemic effects which can worsen the complications observed in TBI subjects. Currently, there is no FDA-approved therapy available for its treatment. Thus, there has been an increasing need to understand other factors that could modulate TBI outcomes. Among the factors involved are diet and lifestyle. High-fat diets (HFD), rich in saturated fat, have been associated with adverse effects on brain health. MAIN METHODS: To study this phenomenon, an experimental mouse model of open head injury, induced by the controlled cortical impact was used along with high-fat feeding to evaluate the impact of HFD on brain injury outcomes. Mice were fed HFD for a period of two months where several neurological, behavioral, and molecular outcomes were assessed to investigate the impact on chronic consequences of the injury 30 days post-TBI. KEY FINDINGS: Two months of HFD feeding, together with TBI, led to a notable metabolic, neurological, and behavioral impairment. HFD was associated with increased blood glucose and fat-to-lean ratio. Spatial learning and memory, as well as motor coordination, were all significantly impaired. Notably, HFD aggravated neuroinflammation, oxidative stress, and neurodegeneration. Also, cell proliferation post-TBI was repressed by HFD, which was accompanied by an increased lesion volume. SIGNIFICANCE: Our research indicated that chronic HFD feeding can worsen functional outcomes, predispose to neurodegeneration, and decrease brain recovery post-TBI. This sheds light on the clinical impact of HFD on TBI pathophysiology and rehabilitation as well.

Neuroanatomical regions associated with non-progressive dysarthria post-stroke: a systematic review.

BACKGROUND: Dysarthria is a common and persisting sequela to stroke. It can have a negative influence on psychological wellbeing, and quality of life. This systematic review aimed to describe and identify the neuroanatomical regions associated with non-progressive dysarthria following stroke. METHODS: A systematic search of PubMed, Ovid Medline, CINAHL, Cochrane, Scopus, and ScienceDirect was conducted to identify all relevant articles published in peer-reviewed journals up to December 2021. Following data extraction, the National Institutes of Health (NIH) quality assessment tools were used to evaluate the methodological quality of the included studies. RESULTS: Out of 2186 papers found in the literature related to dysarthria post-stroke, 24 met the inclusion criteria. Eligible articles assessed 1150 post-stroke subjects. Out of them, 420 subjects had dysarthria from isolated lesions. Regarding dysarthric subjects with ischemic strokes, 153 sustained supratentorial infarctions, while 267 had infratentorial infarctions. The majority had pontine infarctions (n = 142), followed by infarctions in the corona radiata (n = 104), and the cerebellum (n = 64). CONCLUSION: This systematic review is the first step toward establishing a neuroanatomical model of dysarthria throughout the whole brain. Our findings have many implications for clinical practice and provide a framework for implementing guidelines for early detection and management of dysarthria post-stroke.

STAT3 in medulloblastoma: a key transcriptional regulator and potential therapeutic target.

Medulloblastoma is the most common malignant brain tumor of childhood accounting for about 60% of all pediatric embryonal tumors. Despite improvements in the overall survival rate, this tumor still lacks an efficient, reliable, and less toxic therapeutic approach. Characterization of the molecular mechanisms involved in medulloblastoma initiation and progression is a crucial step for the development of effective therapies. Signal transducer and activator of transcription 3 is a convergence point for several signaling cascades that are implicated in medulloblastoma tumorigenesis. Accumulated evidence has revealed the pivotal role of signal transducer and activator of transcription 3 in medulloblastoma pathogenesis such as proliferation, survival, angiogenesis, and immunosuppression as well as maintenance, drug resistance, and recurrence. In this review, we focus on the role of signal transducer and activator of transcription 3 in medulloblastoma tumorigenesis and discuss the recent advances of signal transducer and activator of transcription 3 inhibition as a promising developed strategy for medulloblastoma therapy.

Immunohistochemical assessment of cannabinoid type-1 receptor (CB1R) and its correlation with clinicopathological parameters in glioma.

Background: Glioma is the most frequent primary brain tumor and one of the most aggressive forms of cancer. Recently, numerous studies have focused on cannabinoids as a new therapeutic approach due to their antineoplastic effects through activation of the cannabinoid receptors. This study aimed to investigate the immunohistochemical expression level of cannabinoid type-1 receptors (CB1R) in human glioma samples and evaluate its clinicopathologic significance. Materials and methods: We analyzed the expression of CB1R in 61 paraffin-embedded glioma and 4 normal brain tissues using automated immunohistochemical assay. CB1R expression was categorized into high versus low expression levels. Statistical analyses were performed to evaluate the association between CB1R and phosphorylated extracellular signal-related kinase (p-ERK) expression levels and the clinicopathologic features of glioma. Results: Our results showed that CB1R immunopositivity was seen in 59 of 61 cases (96.7%). CB1R was down-expressed in glioma compared to normal brain tissues. However, CB1R expression was not correlated with clinicopathological parameters except for p-ERK. Conclusion: Our findings indicate the down-expression of CB1R in glioma tissues when compared to non-cancerous brain tissues. This change in CB1R expression in gliomas should be further tested regardless of the clinicopathological findings to provide a therapeutic advantage in glioma patients.

Western and ketogenic diets in neurological disorders: can you tell the difference?

The prevalence of obesity tripled worldwide between 1975 and 2016, and it is projected that half of the US population will be overweight by 2030. The obesity pandemic is attributed, in part, to the increasing consumption of the high-fat, high-carbohydrate Western diet, which predisposes to the development of the metabolic syndrome and correlates with decreased cognitive performance. In contrast, the high-fat, low-carbohydrate ketogenic diet has potential therapeutic roles and has been used to manage intractable seizures since the early 1920s. The brain accounts for 25% of total body glucose metabolism and, as a result, is especially susceptible to changes in the types of nutrients consumed. Here, we discuss the principles of brain metabolism with a focus on the distinct effects of the Western and ketogenic diets on the progression of neurological diseases such as epilepsy, Parkinson's disease, Alzheimer's disease, and traumatic brain injury, highlighting the need to further explore the potential therapeutic effects of the ketogenic diet and the importance of standardizing dietary formulations to assure the reproducibility of clinical trials.

New insights into the role of fibroblast growth factors in Alzheimer's disease.

Alzheimer's disease (AD), acknowledged as the most common progressive neurodegenerative disorder, is the leading cause of dementia in the elderly. The characteristic pathologic hallmarks of AD-including the deposition of extracellular senile plaques (SP) formation, intracellular neurofibrillary tangles, and synaptic loss, along with prominent vascular dysfunction and cognitive impairment-have been observed in patients. Fibroblast growth factors (FGFs), originally characterized as angiogenic factors, are a large family of signaling molecules that are implicated in a wide range of biological functions in brain development, maintenance and repair, as well as in the pathogenesis of brain-related disorders including AD. Many studies have focused on the implication of FGFs in AD pathophysiology. In this review, we will provide a summary of recent findings regarding the role of FGFs and their receptors in the pathogenesis of AD, and discuss the possible opportunities for targeting these molecules as novel treatment strategies in AD.

Assessment of non-progressive dysarthria: practice and attitude of speech and language therapists in Lebanon.

BACKGROUND: Non-progressive dysarthria is an acquired motor speech disorder resulting from neurological diseases such as stroke and traumatic brain injury. The evidence base for the assessment of non-progressive dysarthria remains limited with professional practices relying mainly on therapists' clinical experience. Limited information on the assessment practices of Lebanese speech and language therapists (SLTs) is available. Such information is crucial for the development of adequate therapy services for clients with non-progressive dysarthria. This study aims to explore the assessment practices and attitudes of Lebanese SLTs working with adults with non-progressive dysarthria and to investigate their adherence to the framework of the World Health Organization's International Classification of Functioning, Disability and Health (ICF). METHODS: A cross-sectional study was conducted in Lebanon between March and May 2021. Data was collected through an online survey that included information on socio-demographic characteristics, practices, and attitudes of SLTs who assess adults with non-progressive dysarthria. RESULTS: A total of 50 Lebanese SLTs responded to the survey. The majority of SLTs (78%) assessed clients with non-progressive dysarthria across all ICF domains. SLTs reported dissatisfaction with the available assessment tools (64%) and reliance on informal tools (84%). In addition, 68% of the SLTs suggested the crucial need for the development of Arabic formal assessments that can quantitatively evaluate dysarthria and determine severity. The survey also showed that the respondents demonstrated a preference for the use of impairment-based tools. CONCLUSION: It can be concluded that the assessment practices of Lebanese SLTs, generally, follow the international trend and the recommended professional guidelines. Further research initiatives should be held to develop Arabic formal assessment tools for non-progressive dysarthria.

Biomarkers in Neuroblastoma: An Insight into Their Potential Diagnostic and Prognostic Utilities.

OPINION STATEMENT: Neuroblastoma (NB) is a heterogeneous solid tumor of the pediatric population that originates from neural crest cells and affects the developing sympathetic nervous system. It is the most common neuroblastic tumor accounting for approximately 10% of all childhood cancers and 10-15% of pediatric tumor mortalities. The outcomes range from spontaneous tumor regression in low-risk groups to metastasis and death even after multimodal therapy in high-risk groups. Hence, the detection of NB at an early stage improves outcomes and provides a better prognosis for patients. Early detection and prognosis of NB depend on specific molecules termed biomarkers which can be tissue-specific or circulating. Certain biomarkers are employed in the classification of NB into different groups to improve the treatment and prognosis, and others can be used as therapeutic targets. Therefore, novel biomarker discovery is essential for the early detection of NB, predicting the course of the disease, and developing new targeted treatment strategies. In this review, we aim to summarize the literature pertinent to some important biomarkers of NB and discuss the prognostic role of these biomarkers as well as their potential role in targeted therapy.

Immunosuppression in Medulloblastoma: Insights into Cancer Immunity and Immunotherapy.

OPINION STATEMENT: Medulloblastoma (MB) is the most common pediatric brain malignancy, with a 5-year overall survival (OS) rate of around 65%. The conventional MB treatment, comprising surgical resection followed by irradiation and adjuvant chemotherapy, often leads to impairment in normal body functions and poor quality of life, especially with the increased risk of recurrence and subsequent development of secondary malignancies. The development and progression of MB are facilitated by a variety of immune-evading mechanisms such as the secretion of immunosuppressive molecules, activation of immunosuppressive cells, inhibition of immune checkpoint molecules, impairment of adhesive molecules, downregulation of the major histocompatibility complex (MHC) molecules, protection against apoptosis, and activation of immunosuppressive pathways. Understanding the tumor-immune relationship in MB is crucial for effective development of immune-based therapeutic strategies. In this comprehensive review, we discuss the immunological aspect of the brain, focusing on the current knowledge tackling the mechanisms of MB immune suppression and evasion. We also highlight several key immunotherapeutic approaches developed to date for the treatment of MB.

Deciphering the roles of glycogen synthase kinase 3 (GSK3) in the treatment of autism spectrum disorder and related syndromes.

Autism spectrum disorder (ASD) is a complex and multifactorial neurodevelopmental disorder characterized by the presence of restricted interests and repetitive behaviors besides deficits in social communication. Syndromic ASD is a subset of ASD caused by underlying genetic disorders, most commonly Fragile X Syndrome (FXS) and Rett Syndrome (RTT). Various mutations and consequent malfunctions in core signaling pathways have been identified in ASD, including glycogen synthase kinase 3 (GSK3). A growing body of evidence suggests a key role of GSK3 dysregulation in the pathogenesis of ASD and its related disorders. Here, we provide a synopsis of the implication of GSK3 in ASD, FXS, and RTT as a promising therapeutic target for the treatment of ASD.

Characterization of Traumatic Brain Injury Research in the Middle East and North Africa Region: A Systematic Review.

OBJECTIVES: Traumatic brain injury (TBI) represents a major health concern worldwide with a large impact in the Middle East and North Africa (MENA) region as a consequence of protracted wars and conflicts that adversely affect the general population. Currently, systematic TBI studies in the MENA region are lacking, nonetheless they are immensely needed to enhance trauma management and increase survival rates among TBI patients. This systematic review aims to characterize TBI in the MENA region to guide future policy choices and research efforts and inform tailored guidelines capable of improving TBI management and patient treatment and outcome. Furthermore, it will serve as a road map to evaluate and assess knowledge of trauma impact on regional health systems that can be adopted by health-care providers to raise awareness and improve trauma care. METHODS: We conducted a comprehensive search strategy of several databases including MEDLINE/Ovid, PubMed, Embase, Scopus, CINAHL, Google Scholar, and the grey literature in accordance with the PROSPERO systematic review protocol CRD42017058952. Abstracts were screened, and selected eligible studies were reviewed independently by 2 reviewers. We collected demographics information along with TBI characteristics, mortality rates, and regional distribution. Data were extracted using REDCap and checked for accuracy. RESULTS: The search strategy yielded 23,385 citations; 147 studies met the eligibility criteria and were included in this review. Motor vehicle accident (MVA) was the leading cause of TBI (41%) in the MENA region, followed by the military- (15.6%) and fall- (8.8%) related TBI. Males predominantly suffer from TBI-related injuries (85%), with a high prevalence of MVA- and military-related TBI injuries. The TBI mortality rate was 12.9%. The leading causes of mortality were MVA (68%), military (20.5%), and assault (2.9%). The vast majority of reported TBI severity was mild (63.1%) compared to moderate (10.7%) and severe TBI (20.2%). Patients mainly underwent a Glasgow Coma Scale assessment (22.1%), followed by computed tomography scan (8.9%) and surgery (4.1%). CONCLUSIONS: Despite its clinical, social, and economic burden, the evidence of TBI research in the MENA region is scarce. Further research and high-quality epidemiological studies are urgently needed to gain a deep understanding of the TBI burden in the region, facilitate the allocation of adequate resources, implement effective preventive and intervention strategies and advise on the TBI patient management as reflective on the TBI patterns and modes.

Tideglusib attenuates growth of neuroblastoma cancer stem/progenitor cells in vitro and in vivo by specifically targeting GSK-3ß.

BACKGROUND: Neuroblastoma (NB) is the most frequently diagnosed extracranial solid tumor among the pediatric population. It is an embryonic tumor with high relapse rates pertaining to the presence of dormant slowly dividing cancer stem cells (CSC) within the tumor bulk that are responsible for therapy resistance. Therefore, there is a dire need to develop new therapeutic approaches that specifically target NB CSCs. Glycogen synthase kinase (GSK)-3ß is a serine/threonine kinase that represents a common signaling node at the intersection of many pathways implicated in NB CSCs. GSK-3ß sustains the survival and maintenance of CSCs and renders them insensitive to chemotherapeutic agents and radiation. METHODS: In our study, we aimed at evaluating the potential anti-tumor effect of Tideglusib (TDG), an irreversible GSK-3ß inhibitor drug, on three human NB cell lines, SK-N-SH, SH-SY5Y, and IMR-32. RESULTS: Our results showed that TDG significantly reduced cell proliferation, viability, and migration of the NB cells, in a dose- and time-dependent manner, and also significantly hindered the neurospheres formation eradicating the self-renewal ability of highly resistant CSCs. Besides, TDG potently reduced CD133 cancer stem cell marker expression in both SH-SY5Y cells and G1 spheres. Lastly, TDG inhibited NB tumor growth and progression in vivo. CONCLUSION: Collectively, we concluded that TDG could serve as an effective treatment capable of targeting the NB CSCs and hence overcoming therapy resistance. Yet, future studies are warranted to further investigate its potential role in NB and decipher the subcellular and molecular mechanisms underlying this role.

The potential use of tideglusib as an adjuvant radio-therapeutic treatment for glioblastoma multiforme cancer stem-like cells.

BACKGROUND: Glioblastoma multiforme (GBM), a stage IV astrocytoma, is the most common brain malignancy among adults. Conventional treatments of surgical resection followed by radio and/or chemotherapy fail to completely eradicate the tumor. Resistance to the currently available therapies is mainly attributed to a subpopulation of cancer stem cells (CSCs) present within the tumor bulk that self-renew leading to tumor relapse with time. Therefore, identification of characteristic markers specific to these cells is crucial for the development of targeted therapies. Glycogen synthase kinase 3 (GSK-3), a serine-threonine kinase, is deregulated in a wide range of diseases, including cancer. In GBM, GSK-3ß is overexpressed and its suppression in vitro has been shown to induce apoptosis of cancer cells. METHODS: In our study, we assessed the effect of GSK-3ß inhibition with Tideglusib (TDG), an irreversible non-ATP competitive inhibitor, using two human GBM cell lines, U-251 MG and U-118 MG. In addition, we combined TDG with radiotherapy to assess whether this inhibition enhances the effect of standard treatment. RESULTS: Our results showed that TDG significantly reduced cell proliferation, cell viability, and migration of both GBM cell lines in a dose- and time-dependent manner in vitro. Treatment with TDG alone and in combination with radiation significantly decreased the colony formation of U-251 MG cells and the sphere formation of both cell lines, by targeting and reducing their glioblastoma cancer stem-like cells (GSCs) population. Finally, cells treated with TDG showed an increased level of unrepaired radio-induced DNA damage and, thus, became sensitized toward radiation. CONCLUSIONS: In conclusion, TDG has proven its effectiveness in targeting the cancerous properties of GBM in vitro and may, hence, serve as a potential adjuvant radio-therapeutic agent to better target this deadly tumor.

Drug Repurposing in Medulloblastoma: Challenges and Recommendations.

OPINION STATEMENT: Medulloblastoma is the most frequently diagnosed primary malignant brain tumor among children. Currently available therapeutic strategies are based on surgical resection, chemotherapy, and/or radiotherapy. However, majority of patients quickly develop therapeutic resistance and are often left with long-term therapy-related side effects and sequelae. Therefore, there remains a dire need to develop more effective therapeutics to overcome the acquired resistance to currently available therapies. Unfortunately, the process of developing novel anti-neoplastic drugs from bench to bedside is highly time-consuming and very expensive. A wide range of drugs that are already in clinical use for treating non-cancerous diseases might commonly target tumor-associated signaling pathways as well and hence be of interest in treating different cancers. This is referred to as drug repurposing or repositioning. In medulloblastoma, drug repurposing has recently gained a remarkable interest as an alternative therapy to overcome therapy resistance, wherein existing non-tumor drugs are being tested for their potential anti-neoplastic effects outside the scope of their original use.