Glioma-induced alterations in excitatory neurons are reversed by mTOR inhibition.

Gliomas are aggressive neoplasms that diffusely infiltrate the brain and cause neurological symptoms, including cognitive deficits and seizures. Increased mTOR signaling has been implicated in glioma-induced neuronal hyperexcitability, but the molecular and functional consequences have not been identified. Here, we show three types of changes in tumor-associated neurons: (1) downregulation of transcripts encoding excitatory and inhibitory postsynaptic proteins and dendritic spine development and upregulation of cytoskeletal transcripts via neuron-specific profiling of ribosome-bound mRNA, (2) marked decreases in dendritic spine density via light and electron microscopy, and (3) progressive functional alterations leading to neuronal hyperexcitability via in vivo calcium imaging.

From Sheep to Sling: Pediatric Injuries Due to Rodeo Mutton Bustin'.

Background: Mutton Bustin' was developed as a safer alternative to rough stock rodeo events such as bull riding to allow kids to participate in the rodeo. Children hold on to the bareback of a running sheep until they fall, competing to see who can ride the longest. While reports of injuries due to other rodeo events are well described in the literature, there are no reports of Mutton Bustin'-associated injuries.

Obturator Neurectomy for the Treatment of Adductor Spasticity: A Novel Technique and Case Series.

Background The management of adductor spasticity and long-term sequelae for cerebral palsy (CP) patients is complex. Hip displacement is a common consequence of CP, and obturator neurectomy (ON) is a potentially underutilized procedure to address the underlying adductor spasticity. The aim of this study is to describe the operational technique of ON and highlight the potential efficacy of ON in reducing spasticity, as well as pain, hip, and functional outcomes in these patients.

Mycophenolate Mofetil Appears Effective for the Treatment of Patients With Refractory Crohn's Disease.

Background: Medically refractory Crohn's disease (CD) is associated with a high risk of complications. Mycophenolate mofetil (MMF), a small molecule immunosuppressant, has limited data in patients with CD, and objective endoscopic response to MMF has not been reported.

Aims: We evaluated the safety and clinical, endoscopic, and biochemical effectiveness of off-label MMF for refractory CD as monotherapy or in combination with a biologic in patients with CD.

Resistance to spindle inhibitors in glioblastoma depends on STAT3 and therapy induced senescence.

While mitotic spindle inhibitors specifically kill proliferating tumor cells without the toxicities of microtubule poisons, resistance has limited their clinical utility. Treating glioblastomas with the spindle inhibitors ispinesib, alisertib, or volasertib creates a subpopulation of therapy induced senescent cells that resist these drugs by relying upon the anti-apoptotic and metabolic effects of activated STAT3. Furthermore, these senescent cells expand the repertoire of cells resistant to these drugs by secreting an array of factors, including TGFβ, which induce proliferating cells to exit mitosis and become quiescent-a state that also resists spindle inhibitors.

Resistance to Spindle Inhibitors in Glioblastoma Depends on STAT3 and Therapy Induced Senescence.

Unlabelled: While mitotic spindle inhibitors specifically kill proliferating tumor cells without the toxicities of microtubule poisons, resistance has limited their clinical utility. Treating glioblastomas with the spindle inhibitors ispinesib, alisertib, or volasertib creates a subpopulation of therapy induced senescent cells that resist these drugs by relying upon the anti-apoptotic and metabolic effects of activated STAT3. Furthermore, these senescent cells expand the repertoire of cells resistant to these drugs by secreting an array of factors, including TGFβ, which induce proliferating cells to exit mitosis and become quiescent-a state that also resists spindle inhibitors.

Ipsilateral Supracondylar and Medial Epicondyle Humerus Fractures in Pediatric Patients: A Retrospective Analysis of Incidence, Epidemiology, Treatment, and Outcomes.

Background: Pediatric supracondylar humerus (SCH; AO/OTA13-M/3.1) and medial epicondyle fractures (AO/OTA13u-M/7.1) are common.

MT-125 Inhibits Non-Muscle Myosin IIA and IIB, Synergizes with Oncogenic Kinase Inhibitors, and Prolongs Survival in Glioblastoma.

Unlabelled: We have identified a NMIIA and IIB-specific small molecule inhibitor, MT-125, and have studied its effects in GBM. MT-125 has high brain penetrance and retention and an excellent safety profile; blocks GBM invasion and cytokinesis, consistent with the known roles of NMII; and prolongs survival as a single agent in murine GBM models. MT-125 increases signaling along both the PDGFR- and MAPK-driven pathways through a mechanism that involves the upregulation of reactive oxygen species, and it synergizes with FDA-approved PDGFR and mTOR inhibitors .

Evaluating Chat Generative Pre-trained Transformer Responses to Common Pediatric In-toeing Questions.

Objective: Chat generative pre-trained transformer (ChatGPT) has garnered attention in health care for its potential to reshape patient interactions. As patients increasingly rely on artificial intelligence platforms, concerns about information accuracy arise. In-toeing, a common lower extremity variation, often leads to pediatric orthopaedic referrals despite observation being the primary treatment.

Multiplexed single-cell lineage tracing of mitotic kinesin inhibitor resistance in glioblastoma.

Glioblastoma (GBM) is a deadly brain tumor, and the kinesin motor KIF11 is an attractive therapeutic target with roles in proliferation and invasion. Resistance to KIF11 inhibitors, which has mainly been studied in animal models, presents significant challenges. We use lineage-tracing barcodes and single-cell RNA sequencing to analyze resistance in patient-derived GBM neurospheres treated with ispinesib, a potent KIF11 inhibitor.

NCCN Guidelines® Insights: Prostate Cancer, Version 3.2024.

The NCCN Guidelines for Prostate Cancer include recommendations for staging and risk assessment after a prostate cancer diagnosis and for the care of patients with localized, regional, recurrent, and metastatic disease. These NCCN Guidelines Insights summarize the panel's discussions for the 2024 update to the guidelines with regard to initial risk stratification, initial management of very-low-risk disease, and the treatment of nonmetastatic recurrence.

How Reliable Is the Measurement of the Lateral Center Edge Angle on Scoliosis Radiographs for Detecting Acetabular Dysplasia?

Purpose: Hip dysplasia reportedly occurs in up to 12% of the general population and may be higher in patients with adolescent idiopathic scoliosis (AIS). When using lateral center edge angle (LCEA) measurements to help identify hip dysplasia, it is uncertain if this measurement can be performed reliably on scoliosis radiographs due to parallax. The purpose of this study is to evaluate the reliability of measuring LCEA on scoliosis radiographs compared with standard pelvis radiographs.

Clinical impact of diagnostic image-guided injections for musculoskeletal pain work-up in adolescent and adult patients at a children's hospital: initial results.

Objective: To assess the clinical impact of diagnostic musculoskeletal (MSK) injections on treatment decision-making in adolescent and adult patients at a children's hospital.

Materials And Methods: Retrospective study in patients who underwent diagnostic MSK injections by fluoroscopy or ultrasound (US) between 8/2020 and 3/2023 at a children's hospital. Patients received ropivacaine and triamcinolone acetonide at pain site, reporting quantitative FACES pain score prior to, immediately following, and 2-3 days following injection.

Revealing the hidden biodiversity of Antarctic and the Magellanic Sub-Antarctic Ecoregion: A comprehensive study of aquatic invertebrates from the BASE Project.

Background: Antarctica, its outlying archipelagoes and the Magellanic Subantarctic (MSA) ecoregion are amongst the last true wilderness areas remaining on the planet. Therefore, the publication, citation and peer review of their biodiversity data are essential. The new Millennium Institute Biodiversity of Antarctic and Subantarctic Ecosystems (BASE), a Chilean scientific initiative funded by the National Agency of Research and Innovation, contributes 770 new records of aquatic invertebrates as a point of reference for present-day biodiversity research at these latitudes.

Laevilacunaria (Mollusca, Gastropoda) in the Southern Ocean: A comprehensive occurrence dataset.

Background: The present dataset is a compilation of georeferenced occurrences of the littorinid genus Powell, 1951 (Mollusca, Gastropoda) in the Southern Ocean. Occurrence data were obtained from field expeditions (Antarctic and sub-Antarctic sampling) between 2015 and 2022, together with a review of published literature including records from 1887 to 2022. Three species have been recorded from the Southern Ocean: , and .

From the Operating Room to the Laboratory: Role of the Neuroscience Tissue Biorepository in the Clinical, Translational, and Basic Science Research Pipeline.

Objective: To establish a neurologic disorder-driven biospecimen repository to bridge the operating room with the basic science laboratory and to generate a feedback cycle of increased institutional and national collaborations, federal funding, and human clinical trials.

Methods: Patients were prospectively enrolled from April 2017 to July 2022. Tissue, blood, cerebrospinal fluid, bone marrow aspirate, and adipose tissue were collected whenever surgically safe.

Glioma-Induced Alterations in Excitatory Neurons are Reversed by mTOR Inhibition.

Gliomas are highly aggressive brain tumors characterized by poor prognosis and composed of diffusely infiltrating tumor cells that intermingle with non-neoplastic cells in the tumor microenvironment, including neurons. Neurons are increasingly appreciated as important reactive components of the glioma microenvironment, due to their role in causing hallmark glioma symptoms, such as cognitive deficits and seizures, as well as their potential ability to drive glioma progression. Separately, mTOR signaling has been shown to have pleiotropic effects in the brain tumor microenvironment, including regulation of neuronal hyperexcitability.

Musculoskeletal injections for palliative treatment of neuromuscular hip dysplasia patients: how I do it.

This review describes our institution's standardized technique as well as potential pitfalls for therapeutic steroid injections in children with symptomatic neuromuscular hip dysplasia. Symptomatic, painful neuromuscular hip dysplasia can dramatically affect quality of life. Steroid injections are used to identify the source of perceived pain, temporarily treat pain while awaiting surgical intervention, or for therapeutic management for nonoperative hip joints.

Awake Craniotomy Program Implementation.

Importance: Implementing multidisciplinary teams for treatment of complex brain tumors needing awake craniotomies is associated with significant costs. To date, there is a paucity of analysis on the cost utility of introducing advanced multidisciplinary standardized teams to enable awake craniotomies.

Objective: To assess the cost utility of introducing a standardized program of awake craniotomies.

A novel mechanoeffector role of fibroblast S100A4 in myofibroblast transdifferentiation and fibrosis.

Fibroblast to myofibroblast transdifferentiation mediates numerous fibrotic disorders, such as idiopathic pulmonary fibrosis (IPF). We have previously demonstrated that non-muscle myosin II (NMII) is activated in response to fibrotic lung extracellular matrix, thereby mediating myofibroblast transdifferentiation. NMII-A is known to interact with the calcium-binding protein S100A4, but the mechanism by which S100A4 regulates fibrotic disorders is unclear.

Fate of acetabular dysplasia after closed and open reduction of hips in children with developmental hip dislocation.

Acetabular underdevelopment (acetabular dysplasia) is a common finding in children with hip dislocation, and residual acetabular dysplasia can remain after hip reduction. Residual dysplasia leads to unsatisfactory long-term outcomes and osteoarthritis. Dynamics of acetabular dysplasia [measured as Acetabular Index (AI)] in a pediatric cohort that underwent open (OR) or closed reduction are reported.

Prostate Cancer, Version 4.2023, NCCN Clinical Practice Guidelines in Oncology.

The NCCN Guidelines for Prostate Cancer provide a framework on which to base decisions regarding the workup of patients with prostate cancer, risk stratification and management of localized disease, post-treatment monitoring, and treatment of recurrence and advanced disease. The Guidelines sections included in this article focus on the management of metastatic castration-sensitive disease, nonmetastatic castration-resistant prostate cancer (CRPC), and metastatic CRPC (mCRPC). Androgen deprivation therapy (ADT) with treatment intensification is strongly recommended for patients with metastatic castration-sensitive prostate cancer.

Preclinical In-Vivo Safety and Toxicokinetics of D-PLEX100 in an Abdominal Surgery Incision Model in Juvenile Miniature Swine.

D-PLEX100 (D-PLEX) is a novel product candidate made of a polymer-lipid-based matrix (PLEX platform) which contains doxycycline that is being released at a constant rate for 30 days. D-PLEX was developed to prevent surgical site infections, which are a major global health challenge. Previous studies have shown its safety in adult humans, adult swine, and adult rabbits.

Stakeholder Reflections on Implementing the National Institutes of Health's Policy on Single Institutional Review Boards.

The National Institutes of Health (NIH) requires use of a single institutional review board (sIRB) for multisite, nonexempt, NIH-funded research with human participants. The Clinical Trials Transformation Initiative (CTTI) conducted in-depth interviews with 34 stakeholders at two universities and in research administration leadership positions at multiple institutions about their experiences implementing the sIRB model, focusing on the NIH policy's goals soon after the policy was enacted. While some stakeholders suggested that using an sIRB has streamlined and reduced inefficiencies associated with the local IRB model, more stakeholders indicated that the sIRB model has not simplified the ethics review process and instead created new inefficiencies due to unclear roles and responsibilities for staff and institutions; a lack of systems and processes for implementing the sIRB model, including communication systems; and increased workloads.