Biological, diagnostic and therapeutic implications of exosomes in glioma.

Despite therapeutic advances, overall survival in glioblastoma is dismal. To optimize progress, a more detailed understanding of glioma's molecular, cellular, and intercellular pathophysiology is needed. Recent investigation has revealed a vital role for exosomes in inter-cellular signaling, tumor cell support, and regulation of the tumor microenvironment. Exosomes carry miRNAs, lncRNAs, mRNAs, proteins, immune regulatory molecules, nucleic acids, and lipids; however, the composition of exosome cargo is variable depending on the cell of origin. Specific exosomal miRNA contents such as miR-21, miR-301a, miR-151a, miR-148a, and miR-5096 are altered in high-grade glioma. Unique proteomic, genomic, and miRNA signatures of tumor exosomes have been associated with disease pathobiology, temozolomide resistance, immunosuppression, and tumor proliferation. Exosomes hold promise for tissue diagnostic glioma diagnosis and monitoring response to therapy. This review summarizes the current understanding of exosomes, their crucial role in glioma pathology, and future directions for their use in diagnosis and treatment. METHODS: The MEDLINE/PubMed database was reviewed for papers written in English and publication dates of 1981-2023, using the search string "Exosome", "Extracellular vesicles", "Glioma", "Exosomes in glioma".

Effect of a single one-hour teaching session about environmental pollutants and climate change on the understanding and behavioral choices of adolescents: The BREATHE pilot randomized controlled trial.

BACKGROUND: Despite the wealth of scientific information on the health effects of air pollution, the adult public's lifestyle continues to be largely detrimental towards the environment. OBJECTIVE: The purpose of the study was to determine whether a short interactive teaching session on air pollution could shift reported behavioral choices of adolescents towards environmentally friendlier options. METHODS: We performed a pilot randomized control trial in which eighth-grade students were randomized to receive a one-hour script-based teaching on either the effects of air pollution on lung health (intervention group) or the role of vaccination in public health (active control group). The enrolled students completed a survey (15 multiple-choice questions; five targeting understanding (score range 5 to 20); ten targeting behavioral choices (score range 10 to 38) newly designed for this study to evaluate their understanding and predict their future behavior towards air pollution immediately before, immediately after, and one month after the teaching sessions. RESULTS: Seventy-seven students (age = 13.5±0.6 years; 50.4% female; median annual family income = $25K-$50K with 70.1% <$50K; 39 assigned to intervention group) were enrolled in the study. The teaching sessions did not result in any significant change in the participants' understanding domain scores in either the intervention or the control groups. However, the intervention (air pollution) teaching session resulted in a statistically significant increase in behavior domain score from baseline to immediately post-teaching, which continued to be present at one-month follow-up (mean ± standard deviation of score change immediately after = 1.7±3.3; score change 1-month after = 2.5±3.2; P<0.001; minimally important difference = 1.0). DISCUSSION: This pilot study highlights the potential of a short one-time teaching session in promoting environmentally friendly behavior choices among adolescents.

Investigation into the vascular contributors to dementia and the associated treatments.

As the average lifespan has increased, memory disorders have become a more pressing public health concern. However, dementia in the elderly population is often neglected in light of other health priorities. Therefore, expanding the knowledge surrounding the pathology of dementia will allow more informed decision-making regarding treatment within elderly and older adult populations. An important emerging avenue in dementia research is understanding the vascular contributors to dementia. This review summarizes potential causes of vascular cognitive impairment like stroke, microinfarction, hypertension, atherosclerosis, blood-brain-barrier dysfunction, and cerebral amyloid angiopathy. Also, this review address treatments that target these vascular impairments that also show promising results in reducing patient's risk for and experience of dementia.

Nutritional Support Following Traumatic Brain Injury: A Comprehensive Review.

Traumatic brain injury (TBI) can contribute to extensive dysbiosis of the gastrointestinal system, leading to worsened outcomes. The importance of nutrition in recovery is underappreciated but highly important. In this focused review, we discuss the timing of nutritional interventions with supporting data. We highlight routes of administration that are important given the extent of injury often seen in TBI. The increased energy demands can be met through these approaches. Furthermore, patients need increased vitamins, minerals, and supplements. These interventions are constantly being refined. The current standards are reviewed with an emphasis on evidence-based practices.

Muscimol inactivation of dorsal striatum in young and aged male rats does not affect paired associates learning performance.

Improving cognitive health for older adults requires understanding the neurobiology of age-related cognitive decline and the mechanisms underlying preserved cognition in old age. During spatial learning tasks, aged humans and rodents shift navigation preferences in favor of a stimulus-response learning strategy. This has been hypothesized to result from competitive interactions of the caudate nucleus/dorsal striatum (DS) memory system with the hippocampus (HPC)-dependent spatial/allocentric memory system. In support of this hypothesis, a recent study reported that inactivation of the DS in aged rodents rescued HPC-dependent spatial learning on a T-maze (Gardner, Gold, & Korol, 2020). Currently, it is unclear whether a shift from HPC-dependent to DS-dependent behavior also contributes to age-related cognitive decline outside of spatial learning and memory. To test the hypothesis that inactivation of the DS can restore age-related cognitive function outside of spatial behavior, the present study bilaterally inactivated the DS of young (n = 8) and aged (n = 7) rats during visuospatial paired associates learning (PAL). This study found that inactivation of the DS did not alter PAL performance in young or aged rats, but did alter a positive control, DS-dependent spatial navigation task. This observation suggests that elevated DS activity does not play a role in the decline of HPC-dependent PAL performance in aged male rats. Given the persistent tendencies of aged rodents toward DS-dependent learning, it will be worthwhile to explore further the coordination dynamics between the HPC and DS that may contribute to age-related cognitive decline. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Surgical Management of Brain Tumors with Focused Ultrasound.

Focused ultrasound is a novel technique for the treatment of aggressive brain tumors that uses both mechanical and thermal mechanisms. This non-invasive technique can allow for both the thermal ablation of inoperable tumors and the delivery of chemotherapy and immunotherapy while minimizing the risk of infection and shortening the time to recovery. With recent advances, focused ultrasound has been increasingly effective for larger tumors without the need for a craniotomy and can be used with minimal surrounding soft tissue damage. Treatment efficacy is dependent on multiple variables, including blood-brain barrier permeability, patient anatomical features, and tumor-specific features. Currently, many clinical trials are currently underway for the treatment of non-neoplastic cranial pathologies and other non-cranial malignancies. In this article, we review the current state of surgical management of brain tumors using focused ultrasound.

Research on the Damage of the Central Nervous System Lymphoma to the Nervous System.

Management of central nervous system (CNS) lymphoma requires multidisciplinary care. The disease can manifest in the context of immunocompromised states or in the context of chronic infections. Nervous system damage from this lymphoma has highly variable presentation that is dependent on the location of the tumor lesions. Damage from disease progression can lead to lasting neurologic deficits and even death. However, some lesions are a consequence of radiation-induced neurotoxicity. This review discusses the sources of and consequences of brain damage due to tumor damage and the associated effect of clinical therapies. We discuss workup, management, and treatments. These include chemotherapy and radiation techniques. We discuss potential complications and avoidance strategies. The review will serve as a user-friendly resource for clinicians.

Paired associates learning is disrupted after unilateral parietal lobe controlled cortical impact in rats: A trial-by-trial behavioral analysis.

Approximately 60-70 million people suffer from traumatic brain injury (TBI) each year. Animal models continue to be paramount in understanding mechanisms of cellular dysfunction and testing new treatments for TBI. Enhancing the translational potential of novel interventions therefore necessitates testing pre-clinical intervention strategies with clinically relevant cognitive assays. This study used a unilateral parietal lobe controlled cortical impact (CCI) model of TBI and tested rats on a touchscreen-based Paired Associates Learning (PAL) task, which is part of the Cambridge Neuropsychological Test Automated Battery. In humans, the PAL task has been used to assess cognitive deficits in the ability to form stimulus-location associations in a multitude of disease states, including TBI. Although the use of PAL in animal models could be important for understanding the clinical severity of cognitive impairment post-injury and throughout intervention, to date, the extent to which a rat model of TBI produces deficits in PAL task performance has not yet been reported. This study details the behavioral consequences of the CCI injury model with a Trial-by-Trial analysis of PAL performance that enables behavioral strategy use to be inferred. Following behavior, the extent of the injury was quantified with histology and staining for the presence of glial fibrillary acid protein and ionized calcium-binding adapter molecule 1. Rats that received unilateral CCI were impaired on the PAL task and showed more aberrant response-driven behavior. The magnitude of PAL impairment was also correlated with Iba1 staining in the thalamus. These observations suggest that PAL could be useful for pre-clinical assessments of novel interventions for treating TBI.

Proteinopathies and Neurotrauma: Update on Degenerative Cascades.

Neurotrauma, especially repetitive neurotrauma, is associated with the development of progressive neurodegeneration leading to chronic traumatic encephalopathy (CTE). Exposure to neurotrauma regularly occurs during sports and military service, often not requiring medical care. However, exposure to severe and/or repeated sub-clinical neurotrauma has been shown cause physical and psychological disability, leading to reduce life expectancy. Misfolding of proteins, or proteinopathy, is a pathological hallmark of CTE, in which chronic injury leads to local and diffuse protein aggregates. These aggregates are an overlapping feature of many neurodegenerative diseases such as CTE, Alzheimer's Disease, Parkinsons disease. Neurotrauma is also a significant risk factor for the development of these diseases, however the mechanism's underlying this association are not well understood. While phosphorylated tau aggregates are the primary feature of CTE, amyloid-beta, Transactive response DNA-binding protein 43 (TDP-43), and alpha-synuclein (αSyn) are also well documented. Aberrant misfolding of these proteins has been shown to disrupt brain homeostasis leading to neurodegeneration in a disease dependent manor. In CTE, the interaction between proteinopathies and their associated neurodegeneration is a current area of study. Here we provide an update on current literature surrounding the prevalence, characteristics, and pathogenesis of proteinopathies in CTE.

Headache persisting after aneurysmal subarachnoid hemorrhage: A narrative review of pathophysiology and therapeutic strategies.

OBJECTIVE: This narrative review of the literature concerns persistent headache attributed to past non-traumatic subarachnoid hemorrhage (SAH), based off demographic and clinical features, what are pathophysiologic mechanisms by which these headaches occur, which medical and interventional treatments have the most evidence for pain alleviation, and what pre-clinical evidence is there for emerging treatments for these patients. BACKGROUND: Following initial stabilization and treatment of spontaneous SAH, most commonly due to aneurysmal rupture, headache in the immediate inpatient setting and persisting after discharge are an important cause of morbidity. These headaches often receive heterogenous treatment of uncertain efficacy, and the risk factors and pathophysiology of their development has received little study. METHODS: A narrative review of current literature discussing post-SAH headache was conducted using a literature search in PubMed with search term combinations including "post subarachnoid hemorrhage pain", "subarachnoid hemorrhage headache", and "post subarachnoid hemorrhage headache". Clinical studies mentioning headache after SAH and/or treatment in the abstract/title were included through March, 2022. RESULTS AND CONCLUSION: Post-SAH headaches are shown to decrease quality of life, have a multi-modal pathophysiology in their occurrence, and only a select few medications (reviewed herein) have been demonstrated to have efficacy in alleviation of these headaches, while also harboring possible risks including vasospasm and re-bleeding. An effective treatment paradigm of these headaches will include trials of evidence-based therapeutics, rapid reduction of opioid medications if not effective, and consideration of multi-modal pain control strategies including nerve blocks.

Low-Pressure Hydrocephalus in Spontaneous Angiogram-Negative Subarachnoid Hemorrhage Following COVID-19 Infection.

A preliminary report warned that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could have neuro-invasive potential as it was observed that some patients showed neurologic symptoms such as headache, nausea, and vomiting. Following early speculation there have been reports of neurologic manifestations involving both the central nervous system and peripheral nervous system including reports that coronavirus disease 2019 (COVID-19) may increase the risk of acute ischemic stroke. Here we present a patient with recent COVID-19 infection who experienced low-pressure hydrocephalus requiring high-output cerebrospinal fluid (CSF) diversion following spontaneous angiogram-negative subarachnoid hemorrhage. We hypothesize that patients who are either currently or who have recently been infected with SARS-CoV-2 may have altered ventricular compliance and/or altered CSF hydrodynamics from mechanisms that are not yet understood but potentially related to previously described pathophysiologic mechanisms of the virus and associated inflammatory reaction.

Recurrent pancreatitis in the setting of gallbladder agenesis, ansa pancreatica, Santorinicoele and eventual intraductal papillary mucinous neoplasia (IPMN).

Gallbladder agenesis is a rare condition. Patients with gallbladder agenesis can present with biliary type symptoms and rarely pancreatitis. We present the case of a 35-year-old gentleman who was admitted and treated for recurrent pancreatitis on a background of gallbladder agenesis, ansa pancreatica and Santorinicoele. He has had several admissions with pancreatitis and has had multiple imaging modalities during these admissions which we delineate. We discuss this rare anatomical variant and describe the course and management of his illness leading up to his eventual diagnosis of intraductal papillary neoplasia (IPMN).

Primary pain generator identification by CT-SPECT in patients with degenerative spinal disease.

OBJECTIVE: Axial spinal pain generators are difficult to identify using current diagnostic modalities. Merging CT with SPECT (CT-SPECT) scans allows for accurate identification of areas with increased osteoblastic activity, which may reflect pain generators. In this study, the authors aimed to evaluate the degree of pain improvement in patients who underwent surgery, addressing primary pain generators identified by CT-SPECT. METHODS: The authors retrospectively reviewed all patients with chronic axial spine pain who underwent diagnostic CT-SPECT at their institution and analyzed pain improvement in those who underwent surgical treatment in order to determine whether CT-SPECT correctly identified the primary pain generator. RESULTS: A total of 315 patients underwent diagnostic CT-SPECT between January 2014 and August 2018. Forty-eight patients underwent either cervical or lumbar fusion; there were 26 women (16 cervical, 10 lumbar) and 22 men (9 cervical, 13 lumbar). The overall axial spinal pain, as assessed through self-reporting of visual analog scale scores at 6 months postoperatively, improved from 9.04 ± 1.4 to 4.34 ± 2.3 (p = 0.026), with cervical fusion patients improving from 8.8 ± 1.8 to 3.92 ± 2.2 (p = 0.019) and lumbar fusion patients improving from 9.35 ± 0.7 to 4.87 ± 2.3 (p = 0.008). CONCLUSIONS: CT-SPECT may offer a diagnostic advantage over current imaging modalities in identifying the primary pain generator in patients with axial spinal pain.

Traumatic cervical spine injury during sexual activity.

Sexual activity is unlikely to result in spinal injuries. We present the first case of a cervical fracture-subluxation and spinal cord injury following sexual activity. This 31-year-old female presented to the emergency room with neck pain and quadriparesis, following sexual activity in an extreme position. Imaging revealed a hyperflexion cervical fracture-subluxation injury, requiring reduction by traction, followed by circumferential surgical fixation. At 6 months postoperatively, she reported baseline return of function. This case demonstrates that sex-induced spinal injuries are possible and may require urgent surgical treatment.

The theory of planned behavior and helmet use among college students.

OBJECTIVES: To assess undergraduate helmet use attitudes and behaviors in accordance with the theory of planned behavior (TPB). We predicted helmet wearers and nonwearers would differ on our subscales. METHODS: Participants (N=414, 69% female, 84% white) completed a survey. RESULTS: Principal component analysis and reliability analysis guided the creation of subscales. Group differences were detected on 9 of 10 subscales: F(18,788) = 10.721, P=.001, eta(2) = .187. Few ethnicity and sex differences were detected. CONCLUSIONS: This study supports the validity of the TPB in predicting college student helmet use and offers a new scale for future research purposes.