Antagonistic roles of canonical and Alternative-RPA in disease-associated tandem CAG repeat instability.

Expansions of repeat DNA tracts cause >70 diseases, and ongoing expansions in brains exacerbate disease. During expansion mutations, single-stranded DNAs (ssDNAs) form slipped-DNAs. We find the ssDNA-binding complexes canonical replication protein A (RPA1, RPA2, and RPA3) and Alternative-RPA (RPA1, RPA3, and primate-specific RPA4) are upregulated in Huntington disease and spinocerebellar ataxia type 1 (SCA1) patient brains. Protein interactomes of RPA and Alt-RPA reveal unique and shared partners, including modifiers of CAG instability and disease presentation. RPA enhances in vitro melting, FAN1 excision, and repair of slipped-CAGs and protects against CAG expansions in human cells. RPA overexpression in SCA1 mouse brains ablates expansions, coincident with decreased ATXN1 aggregation, reduced brain DNA damage, improved neuron morphology, and rescued motor phenotypes. In contrast, Alt-RPA inhibits melting, FAN1 excision, and repair of slipped-CAGs and promotes CAG expansions. These findings suggest a functional interplay between the two RPAs where Alt-RPA may antagonistically offset RPA's suppression of disease-associated repeat expansions, which may extend to other DNA processes.

Clonally expanded CD8 T cells characterize amyotrophic lateral sclerosis-4.

Amyotrophic lateral sclerosis (ALS) is a heterogenous neurodegenerative disorder that affects motor neurons and voluntary muscle control1. ALS heterogeneity includes the age of manifestation, the rate of progression and the anatomical sites of symptom onset. Disease-causing mutations in specific genes have been identified and define different subtypes of ALS1. Although several ALS-associated genes have been shown to affect immune functions2, whether specific immune features account for ALS heterogeneity is poorly understood. Amyotrophic lateral sclerosis-4 (ALS4) is characterized by juvenile onset and slow progression3. Patients with ALS4 show motor difficulties by the time that they are in their thirties, and most of them require devices to assist with walking by their fifties. ALS4 is caused by mutations in the senataxin gene (SETX). Here, using Setx knock-in mice that carry the ALS4-causative L389S mutation, we describe an immunological signature that consists of clonally expanded, terminally differentiated effector memory (TEMRA) CD8 T cells in the central nervous system and the blood of knock-in mice. Increased frequencies of antigen-specific CD8 T cells in knock-in mice mirror the progression of motor neuron disease and correlate with anti-glioma immunity. Furthermore, bone marrow transplantation experiments indicate that the immune system has a key role in ALS4 neurodegeneration. In patients with ALS4, clonally expanded TEMRA CD8 T cells circulate in the peripheral blood. Our results provide evidence of an antigen-specific CD8 T cell response in ALS4, which could be used to unravel disease mechanisms and as a potential biomarker of disease state.

On the proportion of patients who experience a prodrome prior to psychosis onset: A systematic review and meta-analysis.

BACKGROUND: Preventing or delaying the onset of psychosis requires identification of those at risk for developing psychosis. For predictive purposes, the prodrome - a constellation of symptoms which may occur before the onset of psychosis - has been increasingly recognized as having utility. However, it is unclear what proportion of patients experience a prodrome or how this varies based on the multiple definitions used. METHODS: We conducted a systematic review and meta-analysis of studies of patients with psychosis with the objective of determining the proportion of patients who experienced a prodrome prior to psychosis onset. Inclusion criteria included a consistent prodrome definition and reporting the proportion of patients who experienced a prodrome. We excluded studies of only patients with a prodrome or solely substance-induced psychosis, qualitative studies without prevalence data, conference abstracts, and case reports/case series. We searched Ovid MEDLINE, Embase (Ovid), APA PsycInfo (Ovid), Web of Science Core Collection (Clarivate), Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, APA PsycBooks (Ovid), ProQuest Dissertation & Thesis, on March 3, 2021. Studies were assessed for quality using the Critical Appraisal Checklist for Prevalence Studies. Narrative synthesis and proportion meta-analysis were used to estimate prodrome prevalence. I2 and predictive interval were used to assess heterogeneity. Subgroup analyses were used to probe sources of heterogeneity. (PROSPERO ID: CRD42021239797). RESULTS: Seventy-one articles were included, representing 13,774 patients. Studies varied significantly in terms of methodology and prodrome definition used. The random effects proportion meta-analysis estimate for prodrome prevalence was 78.3% (95% CI = 72.8-83.2); heterogeneity was high (I2 97.98% [95% CI = 97.71-98.22]); and the prediction interval was wide (95% PI = 0.411-0.936). There were no meaningful differences in prevalence between grouped prodrome definitions, and subgroup analyses failed to reveal a consistent source of heterogeneity. CONCLUSIONS: This is the first meta-analysis on the prevalence of a prodrome prior to the onset of first episode psychosis. The majority of patients (78.3%) were found to have experienced a prodrome prior to psychosis onset. However, findings are highly heterogenous across study and no definitive source of heterogeneity was found despite extensive subgroup analyses. As most studies were retrospective in nature, recall bias likely affects these results. While the large majority of patients with psychosis experience a prodrome in some form, it is unclear if the remainder of patients experience no prodrome, or if ascertainment methods employed in the studies were not sensitive to their experiences. Given widespread investment in indicated prevention of psychosis through prospective identification and intervention during the prodrome, a resolution of this question as well as a consensus definition of the prodrome is much needed in order to effectively direct and organize services, and may be accomplished through novel, densely sampled and phenotyped prospective cohort studies that aim for representative sampling across multiple settings.

Different learning aberrations relate to delusion-like beliefs with different contents.

The prediction error account of delusions has had success. However, its explanation of delusions with different contents has been lacking. Persecutory delusions and paranoia are the common unfounded beliefs that others have harmful intentions towards us. Other delusions include believing that one's thoughts or actions are under external control, or that events in the world have specific personal meaning. We compare learning on two different cognitive tasks, probabilistic reversal learning (PRL) and Kamin blocking, that have relationships to paranoid and non-paranoid delusion-like beliefs, respectively. We find that Clinical High-Risk status alone does not result in different behavioral results on the PRL task but that an individual's level of paranoia is associated with excessive switching behavior. During the Kamin blocking task, paranoid individuals learned inappropriately about the blocked cue. However, they also had decreased learning about the control cue, suggesting more general learning impairments. Non-paranoid delusion-like belief conviction (but not paranoia) was associated with aberrant learning about the blocked cue but intact learning about the control cue, suggesting specific impairments in learning related to cue combination. We fit task-specific computational models separately to behavioral data to explore how latent parameters vary within individuals between tasks, and how they can explain symptom-specific effects. We find that paranoia is associated with low learning rates on the PRL task as well as the blocking task. Non-paranoid delusion-like belief conviction was instead related to parameters controlling the degree and direction of similarity between cue updating during simultaneous cue presentation. These results suggest that paranoia and other delusion-like beliefs involve dissociable deficits in learning and belief updating, which - given the transdiagnostic status of paranoia - may have differential utility in predicting psychosis.

Barriers and solutions to the adoption of translational tools for computational psychiatry.

Computational psychiatry is a field aimed at developing formal models of information processing in the human brain, and how alterations in this processing can lead to clinical phenomena. There has been significant progress in the development of tasks and how to model them, presenting an opportunity to incorporate computational psychiatry methodologies into large- scale research projects or into clinical practice. In this viewpoint, we explore some of the barriers to incorporation of computational psychiatry tasks and models into wider mainstream research directions. These barriers include the time required for participants to complete tasks, test-retest reliability, limited ecological validity, as well as practical concerns, such as lack of computational expertise and the expense and large sample sizes traditionally required to validate tasks and models. We then discuss solutions, such as the redesigning of tasks with a view toward feasibility, and the integration of tasks into more ecologically valid and standardized game platforms that can be more easily disseminated. Finally, we provide an example of how one task, the conditioned hallucinations task, might be translated into such a game. It is our hope that interest in the creation of more accessible and feasible computational tasks will help computational methods make more positive impacts on research as well as, eventually, clinical practice.

Accelerated cortical thinning precedes and predicts conversion to psychosis: The NAPLS3 longitudinal study of youth at clinical high-risk.

Progressive grey matter loss has been demonstrated among clinical high-risk (CHR) individuals who convert to psychosis, but it is unknown whether these changes occur prior to psychosis onset. Identifying illness-related neurobiological mechanisms that occur prior to conversion is essential for targeted early intervention. Among participants in the third wave of the North American Prodrome Longitudinal Study (NAPLS3), this report investigated if steeper cortical thinning was observable prior to psychosis onset among CHR individuals who ultimately converted (CHR-C) and assessed the shortest possible time interval in which rates of cortical thinning differ between CHR-C, CHR non-converters (CHR-NC), and health controls (HC). 338 CHR-NC, 42 CHR-C, and 62 HC participants (age 19.3±4.2, 44.8% female, 52.5% racial/ethnic minority) completed up to 5 MRI scans across 8 months. Accelerated thinning among CHR-C compared to CHR-NC and HC was observed in multiple prefrontal, temporal, and parietal cortical regions. CHR-NC also exhibited accelerated cortical thinning compared to HC in several of these areas. Greater percent decrease in cortical thickness was observed among CHR-C compared to other groups across 2.9±1.8 months, on average, in several cortical areas. ROC analyses discriminating CHR-C from CHR-NC by percent thickness change in a left hemisphere region of interest, scanner, age, age2, and sex had an AUC of 0.74, with model predictive power driven primarily by percent thickness change. Findings indicate that accelerated cortical thinning precedes psychosis onset and differentiates CHR-C from CHR-NC and HC across short time intervals. Mechanisms underlying cortical thinning may provide novel treatment targets prior to psychosis onset.

Non-catalytic Roles for XPG with BRCA1 and BRCA2 in Homologous Recombination and Genome Stability.

XPG is a structure-specific endonuclease required for nucleotide excision repair, and incision-defective XPG mutations cause the skin cancer-prone syndrome xeroderma pigmentosum. Truncating mutations instead cause the neurodevelopmental progeroid disorder Cockayne syndrome, but little is known about how XPG loss results in this devastating disease. We identify XPG as a partner of BRCA1 and BRCA2 in maintaining genomic stability through homologous recombination (HRR). XPG depletion causes DNA double-strand breaks, chromosomal abnormalities, cell-cycle delays, defective HRR, inability to overcome replication fork stalling, and replication stress. XPG directly interacts with BRCA2, RAD51, and PALB2, and XPG depletion reduces their chromatin binding and subsequent RAD51 foci formation. Upstream in HRR, XPG interacts directly with BRCA1. Its depletion causes BRCA1 hyper-phosphorylation and persistent chromatin binding. These unexpected findings establish XPG as an HRR protein with important roles in genome stability and suggest how XPG defects produce severe clinical consequences including cancer and accelerated aging.

Preservation of the heart in ancient Egyptian mummies: A computed tomography investigation with focus on the myocardium.

The ancient Egyptians considered the heart to be the most important organ. The belief that the heart remained in the body is widespread in the archeological and paleopathological literature. The purpose of this study was to perform an overview of the preserved intrathoracic structures and thoracic and abdominal cavity filling, and to determine the prevalence and computed tomography (CT) characteristics of the myocardium in the preserved hearts of ancient Egyptian mummies. Whole-body CT examinations of 45 ancient Egyptian mummies (23 mummies from the Ägyptisches Museum und Papyrussammlung, Berlin, Germany, and 22 mummies from the Museo Egizio, Turin, Italy) were systematically assessed for preserved intrathoracic soft tissues including various anatomical components of the heart (pericardium, interventricular septum, four chambers, myocardium, valves). Additionally, evidence of evisceration and cavity filling was documented. In cases with identifiable myocardium, quantitative (measurements of thickness and density) and qualitative (description of the structure) assessment of the myocardial tissue was carried out. Heart structure was identified in 28 mummies (62%). In 33 mummies, CT findings demonstrated evisceration, with subsequent cavity filling in all but one case. Preserved myocardium was identified in nine mummies (five male, four female) as a mostly homogeneous, shrunken structure. The posterior wall of the myocardium had a mean maximum thickness of 3.6 mm (range 1.4-6.6 mm) and a mean minimum thickness of 1.0 mm (range 0.5-1.7 mm). The mean Hounsfield units (HU) of the myocardium at the posterior wall was 61 (range, 185-305). There was a strong correlation between the HU of the posterior wall of the myocardium and the mean HU of the muscles at the dorsal humerus (R = 0.77; p = 0.02). In two cases, there were postmortem changes in the myocardium, most probably due to insect infestation. To our knowledge, this is the first study to investigate the myocardium systematically on CT scans of ancient Egyptian mummies. Strong correlations between the densities of the myocardium and skeletal muscle indicated similar postmortem changes of the respective musculature during the mummification process within individual mummies. The distinct postmortem shrinking of the myocardium and the collapse of the left ventriclular cavity in several cases did not allow for paleopathological diagnoses such as myocardial scarring.

One-Pot Synthesis of Affordable Redox-Responsive Drug Delivery System Based on Trithiocyanuric Acid Nanoparticles.

Redox-responsive drug delivery systems present a promising avenue for drug delivery due to their ability to leverage the unique redox environment within tumor cells. In this work, we describe a facile and cost-effective one-pot synthesis method for a redox-responsive delivery system based on novel trithiocyanuric acid (TTCA) nanoparticles (NPs). We conduct a thorough investigation of the impact of various synthesis parameters on the morphology, stability, and loading capacity of these NPs. The great drug delivery potential of the system is further demonstrated in vitro and in vivo by using doxorubicin as a model drug. The developed TTCA-PEG NPs show great drug delivery efficiency with minimal toxicity on their own both in vivo and in vitro. The simplicity of this synthesis, along with the promising characteristics of TTCA-PEG NPs, paves the way for new opportunities in the further development of redox-responsive drug delivery systems based on TTCA.

Revisiting Glutamate Excitotoxicity in Amyotrophic Lateral Sclerosis and Age-Related Neurodegeneration.

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disorder. While there are five FDA-approved drugs for treating this disease, each has only modest benefits. To design new and more effective therapies for ALS, particularly for sporadic ALS of unknown and diverse etiologies, we must identify key, convergent mechanisms of disease pathogenesis. This review focuses on the origin and effects of glutamate-mediated excitotoxicity in ALS (the cortical hyperexcitability hypothesis), in which increased glutamatergic signaling causes motor neurons to become hyperexcitable and eventually die. We characterize both primary and secondary contributions to excitotoxicity, referring to processes taking place at the synapse and within the cell, respectively. 'Primary pathways' include upregulation of calcium-permeable AMPA receptors, dysfunction of the EAAT2 astrocytic glutamate transporter, increased release of glutamate from the presynaptic terminal, and reduced inhibition by cortical interneurons-all of which have been observed in ALS patients and model systems. 'Secondary pathways' include changes to mitochondrial morphology and function, increased production of reactive oxygen species, and endoplasmic reticulum (ER) stress. By identifying key targets in the excitotoxicity cascade, we emphasize the importance of this pathway in the pathogenesis of ALS and suggest that intervening in this pathway could be effective for developing therapies for this disease.

Wilderness Medical Society Clinical Practice Guidelines for Prevention and Management of Avalanche and Nonavalanche Snow Burial Accidents: 2024 Update.

To provide guidance to the general public, clinicians, and avalanche professionals about best practices, the Wilderness Medical Society convened an expert panel to revise the evidence-based guidelines for the prevention, rescue, and resuscitation of avalanche and nonavalanche snow burial victims. The original panel authored the Wilderness Medical Society Practice Guidelines for Prevention and Management of Avalanche and Nonavalanche Snow Burial Accidents in 2017. A second panel was convened to update these guidelines and make recommendations based on quality of supporting evidence.

Wilderness Medical Society Clinical Practice Guidelines for the Treatment of Acute Pain in Austere Environments: 2024 Update.

The Wilderness Medical Society (WMS) convened an expert panel to develop evidence-based guidelines for the management of pain in austere environments. Recommendations are graded based on the quality of supporting evidence as defined by criteria put forth by the American College of Chest Physicians. This is an update of the 2014 version of the "WMS Practice Guidelines for the Treatment of Acute Pain in Remote Environments" published in Wilderness & Environmental Medicine 2014; 25:41-49.

Surgical Safety Does Not Happen By Accident: Learning From Perioperative Near Miss Case Studies.

Adverse surgical events cause negative patient health outcomes and harm that can often overshadow the safe and effective patient care provided daily by nurses as members of interprofessional healthcare teams. Near misses occur far more frequently than adverse events and are less visible to nurse leaders because patient harm is avoided due to chance, prevention, or mitigation. However, near misses have comparable root causes to adverse events and exhibit the same underlying patterns of failure. Reviewing near misses provides nurses with learning opportunities to identify patient care weaknesses and build appropriate solutions to enhance care. As the operating room is one of the most complex work settings in healthcare, identifying potential weaknesses or sources for errors is vital to reduce healthcare-associated risks for patients and staff. The purpose of this manuscript is to educate, inform, and stimulate critical thinking by discussing perioperative near miss case studies and the underlying factors that lead to errors. Our authors discuss 15 near miss case studies occurring across the perioperative patient experience of care and discuss barriers to near miss reporting. Nurse leaders can use our case studies to stimulate discussion among perioperative and perianesthesia nurses in their hospitals to inform comprehensive risk reduction programs.

The reliability and validity of the revised Green et al. paranoid thoughts scale in individuals at clinical high-risk for psychosis.

INTRODUCTION: Paranoia is a common and impairing psychosis symptom, which exists along a severity continuum that extends into the general population. Individuals at clinical high-risk for psychosis (CHR) frequently experience paranoia and this may elevate their risk for developing full psychosis. Nonetheless, limited work has examined the efficient measurement of paranoia in CHR individuals. The present study aimed to validate an often-used self-report measure, the revised green paranoid thoughts scale (RGPTS), in this critical population. METHOD: Participants were CHR individuals (n = 103), mixed clinical controls (n = 80), and healthy controls (n = 71) who completed self-report and interview measures. Confirmatory factor analysis (CFA), psychometric indices, group differences, and relations to external measures were used to evaluate the reliability and validity of the RGPTS. RESULTS: CFA replicated a two-factor structure for the RGPTS and the associated reference and persecution scales were reliable. CHR individuals scored significantly higher on both reference and persecution, relative to both healthy (ds = 1.03, 0.86) and clinical controls (ds = 0.64, 0.73). In CHR participants, correlations between reference and persecution and external measures were smaller than expected, though showed evidence of discriminant validity (e.g., interviewer-rated paranoia, r = 0.24). When examined in the full sample, correlation magnitude was larger and follow-up analyses indicated that reference related most specifically to paranoia (ß = 0.32), whereas persecution uniquely related to poor social functioning (ß = -0.29). CONCLUSION: These results demonstrate the reliability and validity of the RGPTS, though its scales related more weakly to severity in CHR individuals. The RGPTS may be useful in future work aiming to develop symptom-specific models of emerging paranoia in CHR individuals.

Autophagy gene haploinsufficiency drives chromosome instability, increases migration, and promotes early ovarian tumors.

Autophagy, particularly with BECN1, has paradoxically been highlighted as tumor promoting in Ras-driven cancers, but potentially tumor suppressing in breast and ovarian cancers. However, studying the specific role of BECN1 at the genetic level is complicated due to its genomic proximity to BRCA1 on both human (chromosome 17) and murine (chromosome 11) genomes. In human breast and ovarian cancers, the monoallelic deletion of these genes is often co-occurring. To investigate the potential tumor suppressor roles of two of the most commonly deleted autophagy genes in ovarian cancer, BECN1 and MAP1LC3B were knocked-down in atypical (BECN1+/+ and MAP1LC3B+/+) ovarian cancer cells. Ultra-performance liquid chromatography mass-spectrometry metabolomics revealed reduced levels of acetyl-CoA which corresponded with elevated levels of glycerophospholipids and sphingolipids. Migration rates of ovarian cancer cells were increased upon autophagy gene knockdown. Genomic instability was increased, resulting in copy-number alteration patterns which mimicked high grade serous ovarian cancer. We further investigated the causal role of Becn1 haploinsufficiency for oncogenesis in a MISIIR SV40 large T antigen driven spontaneous ovarian cancer mouse model. Tumors were evident earlier among the Becn1+/- mice, and this correlated with an increase in copy-number alterations per chromosome in the Becn1+/- tumors. The results support monoallelic loss of BECN1 as permissive for tumor initiation and potentiating for genomic instability in ovarian cancer.

Labeling and Tracking of Individual Human Mesenchymal Stromal Cells Using Photoconvertible Fluorescent Microcapsules.

The behavior and migration of human mesenchymal stromal cells (hMSCs) are focal points of research in the biomedical field. One of the major aspects is potential therapy using hMCS, but at present, the safety of their use is still controversial owing to limited data on changes that occur with hMSCs in the long term. Fluorescent photoconvertible proteins are intensively used today as "gold standard" to mark the individual cells and study single-cell interactions, migration processes, and the formation of pure lines. A crucial disadvantage of this method is the need for genetic modification of the primary culture, which casts doubt on the possibility of exploring the resulting clones in personalized medicine. Here we present a new approach for labeling and tracking hMSCs without genetic modification based on the application of cell-internalizable photoconvertible polyelectrolyte microcapsules (size: 2.6 ± 0.5 µm). These capsules were loaded with rhodamine B, and after thermal treatment, exhibited fluorescent photoconversion properties. Photoconvertible capsules demonstrated low cytotoxicity, did not affect the immunophenotype of the hMSCs, and maintained a high level of fluorescent signal for at least seven days. The developed approach was tested for cell tracking for four days and made it possible to trace the destiny of daughter cells without the need for additional labeling.

Targeted Therapy for Glomerulonephritis Using Arterial Delivery of Encapsulated Etanercept.

Complex immunosuppressive therapy is prescribed in medical practice to patients with glomerulonephritis to help them overcome symptoms and prevent chronic renal failure. Such an approach requires long-term systemic administration of strong medications, which causes severe side effects. This work shows the efficiency of polymer capsule accumulation (2.8 ± 0.4 µm) containing labeled etanercept (100 µg per dose) in the kidneys of mice. The comparison of injection into the renal artery and tail vein shows the significant superiority of the intra-arterial administration strategy. The etanercept retention rate of 18% and 8% ID in kidneys was found 1 min and 1 h after injection, respectively. The capsules were predominantly localized in the glomeruli after injection in mice using a model of acute glomerulonephritis. Histological analysis confirmed a significant therapeutic effect only in animals with intra-arterial administration of microcapsules with etanercept. The proposed strategy combines endovascular surgery and the use of polymer microcapsules containing a high molecular weight drug that can be successfully applied to treat a wide range of kidney diseases associated with glomerular pathology.

The Effect of Flame-Retardant Additives DDM-DOPO and Graphene on Flame Propagation over Glass-Fiber-Reinforced Epoxy Resin under the Influence of External Thermal Radiation.

The flammability of various materials used in industry is an important issue in the modern world. This work is devoted to the study of the effect of flame retardants, graphene and DDM-DOPO (9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide-4,4'-diamino-diphenyl methane), on the flammability of glass-fiber-reinforced epoxy resin (GFRER). Samples were made without additives and with additives of fire retardants: graphene and DDM-DOPO in various proportions. To study the flammability of the samples, standard flammability tests were carried out, such as thermogravimetric analysis, the limiting oxygen index (LOI) test, and cone calorimetry. In addition, in order to test the effectiveness of fire retardants under real fire conditions, for the first time, the thermal structure of downward flame propagation over GFRER composites was measured using thin thermocouples. For the first time, the measured thermal structure of the flame was compared with the results of numerical simulations of flame propagation over GFRER.

Overcoming the blood-brain barrier for the therapy of malignant brain tumor: current status and prospects of drug delivery approaches.

Besides the broad development of nanotechnological approaches for cancer diagnosis and therapy, currently, there is no significant progress in the treatment of different types of brain tumors. Therapeutic molecules crossing the blood-brain barrier (BBB) and reaching an appropriate targeting ability remain the key challenges. Many invasive and non-invasive methods, and various types of nanocarriers and their hybrids have been widely explored for brain tumor treatment. However, unfortunately, no crucial clinical translations were observed to date. In particular, chemotherapy and surgery remain the main methods for the therapy of brain tumors. Exploring the mechanisms of the BBB penetration in detail and investigating advanced drug delivery platforms are the key factors that could bring us closer to understanding the development of effective therapy against brain tumors. In this review, we discuss the most relevant aspects of the BBB penetration mechanisms, observing both invasive and non-invasive methods of drug delivery. We also review the recent progress in the development of functional drug delivery platforms, from viruses to cell-based vehicles, for brain tumor therapy. The destructive potential of chemotherapeutic drugs delivered to the brain tumor is also considered. This review then summarizes the existing challenges and future prospects in the use of drug delivery platforms for the treatment of brain tumors.