Appendage regeneration requires IMPDH2 and creates a sensitized environment for enzyme filament formation.

Regeneration of lost tissue requires biosynthesis of metabolites needed for cell proliferation and growth. Among these are the critical purine nucleotides ATP and GTP. The abundance and balance of these purines is regulated by inosine monophosphate dehydrogenase 2 (IMPDH2), which catalyzes the committing step of GTP synthesis.

Adeno-associated virus delivered CXCL9 sensitizes glioblastoma to anti-PD-1 immune checkpoint blockade.

There are numerous mechanisms by which glioblastoma cells evade immunological detection, underscoring the need for strategic combinatorial treatments to achieve appreciable therapeutic effects. However, developing combination therapies is difficult due to dose-limiting toxicities, blood-brain-barrier, and suppressive tumor microenvironment. Glioblastoma is notoriously devoid of lymphocytes driven in part by a paucity of lymphocyte trafficking factors necessary to prompt their recruitment and activation.

Identification of Fasnall as a therapeutically effective Complex I inhibitor.

Proliferating cancer cells actively utilize anabolic processes for biomass production, including biosynthesis of amino acids, nucleotides, and fatty acids. The key enzyme of the fatty acid biosynthesis pathway, fatty acid synthase (FASN), is widely recognized as a promising therapeutic target in cancer and other health conditions. Here, we establish a metabolic signature of FASN inhibition using a panel of pharmacological inhibitors (GSK2194069, TVB-2640, TVB-3166, C75, cerulenin, and Fasnall).

Imaging of congenital anomalies and defects of the skull base and calvarium.

Congenital anomalies and defects of the skull base and calvarium encompass a broad and complex spectrum of pathologies. The clinical presentation is highly variable, and these anomalies may be discovered incidentally in asymptomatic individuals. Radiological assessment plays a pivotal role in precisely characterizing these abnormalities, facilitating the diagnostic process, and assisting in any preoperative preparation.

Protocol for tail vein injection in Xenopus tropicalis tadpoles.

Functional studies in post-embryonic Xenopus tadpoles are challenging because embryonic perturbations often lead to developmental consequences, such as lethality. Here, we describe a high-throughput protocol for tail vein injection to introduce fluorescent tracers into tadpoles, which we have previously used to effectively inject morpholinos and molecular antagonists. We describe steps for safely positioning tadpoles onto agarose double-coated plates, draining media, injecting into the ventral tail vein, rehydrating plates, and sorting tadpoles by fluorescence with minimal injury for high-throughput experiments.

Mitochondrial leak metabolism induces the Spemann-Mangold Organizer via Hif-1α in Xenopus.

An instructive role for metabolism in embryonic patterning is emerging, although a role for mitochondria is poorly defined. We demonstrate that mitochondrial oxidative metabolism establishes the embryonic patterning center, the Spemann-Mangold Organizer, via hypoxia-inducible factor 1α (Hif-1α) in Xenopus. Hypoxia or decoupling ATP production from oxygen consumption expands the Organizer by activating Hif-1α.

Can Anterior Osteophyte Fractures Be Distinguished From Fracture Mimics in the Subaxial Cervical Spine? A Retrospective Analysis Evaluating Reported Fractures With Clinical Management Correlation.

Objective: This study aimed to retrospectively distinguish true- from false-positive fractures of anterior subaxial cervical osteophytes, which were reported on noncontrast computed tomography reports, and to correlate the imaging findings with patient symptoms and analyze the downstream impact on management of both true and false positive fractures.

Methods: A total of 127 patients had computed tomography reports of anterior osteophyte fractures. Radiology reports and imaging studies were evaluated to distinguish true fractures from fracture mimics.

Radiologic utility of the Gehweiler and AO spine classification systems for C1 Trauma: A retrospective review from a Level I trauma center.

Objective: The purpose of our study was to identify adult trauma patients with an acute C1 burst fracture, evaluate for concomitant transverse atlantal ligament (TAL) injury, and apply the modified Gehweiler and AO spine classification systems to determine the utility of these classification systems in accurately defining C1 trauma.

Materials And Methods: Adult trauma patients with an acute C1 fracture were identified retrospectively using Nuance mPower software. The C1 fracture was described based on whether the fracture involved the anterior arch, posterior arch, lateral mass, medial tubercle, and/or transverse process.

Is Contrast-Enhanced Computed Tomography Redundant for Suspected Intracranial Infection in the Emergency Setting?

Objective: There are currently no guidelines for when to use intravenous contrast with head computed tomography (CT) when there is suspected acute intracranial infection. The purpose of our study was to determine the proportion of cases with enhancing findings on CT that also have conspicuous correlating associated findings on noncontrast CT, which would have on their own merited further evaluation with magnetic resonance imaging, the criterion standard for evaluating central nervous system pathology.

Methods: A retrospective keyword search of the history and clinical information fields in radiology reports for CT examinations of the head without and with contrast from the period January 1, 2004, to October 31, 2021 was performed.

Interrelationship Between Craniocervical Dissociation Spectrum Injuries and Atlantoaxial Instability on Trauma Cervical MRI Examinations.

Background and purpose Craniocervical dissociation injuries encompass a spectrum of osteoligamentous injuries between the skull base and C1-C2 that may be treated via prolonged external immobilization versus occipital cervical fusion depending on the risk of persistent craniocervical instability. However, the presence of atlantoaxial instability (AAI) at C1-C2, as determined by transverse atlantal ligament (TAL) integrity with or without a C1 fracture, may guide the neurosurgical management of craniocervical dissociation spectrum injuries (CDSI) since it implies an overall greater degree of instability at the craniocervical junction (CCJ). Materials and methods Adult trauma patients who suffered a transverse atlantal ligament injury on cervical magnetic resonance imaging (MRI) were identified retrospectively.

SPARSH electronic sub-health centers (e-SHCs) - A model of nurse-run SHCs supported by general practitioners through telemedicine.

Background: The primary health care services in India suffer from inconsistent availability of providers, lack of quality, poor availability of medicines and diagnostics, and a poorly functioning referral linkage. A multi-pronged approach is required to address these issues.

Methods: We describe here a model of electronic sub-health centers (e-SHCs) managed by trained nurses supported by a general practitioner over telemedicine.

Chromatin accessibility analysis reveals distinct functions for HDAC and EZH2 activities in early appendage regeneration.

Xenopus tropicalis tadpoles have the capacity for scarless regeneration of appendages including the limb and tail. Following injury, transcriptional programs must be activated and inactivated with high spatial and temporal resolution to result in a properly patterned appendage. Functional studies have established that histone-modifying enzymes that act to close chromatin are required for regeneration, but the genomic regions sensitive to these activities are not fully established.

Elevated pentose phosphate pathway flux supports appendage regeneration.

A fundamental step in regeneration is rapid growth to replace lost tissue. Cells must generate sufficient lipids, nucleotides, and proteins to fuel rapid cell division. To define metabolic pathways underlying regenerative growth, we undertake a multimodal investigation of metabolic reprogramming in Xenopus tropicalis appendage regeneration.

Imaging Review of the Endoscopic Operative Corridor for Clivus Lesions.

Traditional transcranial approaches for lesions involving the clivus, in particular skull base chordoma have several disadvantages for midline skull base lesions as compared to the endoscopic endonasal approach (EEA), such as higher morbidity and lesser extent of resection. These disadvantages led to the development of endoscopic skull-base approaches to access pathology that involves the anterior cranial fossa, central skull base, and lower skull base lesions. In particular, lesions of the clivus are well suited for EEA.

Appropriateness of Cervical Magnetic Resonance Imaging in the Evaluation and Management of C1 Jefferson Fractures.

Background: Traditionally, C1 fractures have been designated as stable or unstable based on the inherent integrity of the transverse altantal ligament. The purpose of our study was to identify adult trauma patients with C1 fractures on cervical computed tomography and evaluate whether C1-C2 alignment differed in patients with and without an associated transverse atlantal ligament injury on follow-up cervical magnetic resonance imaging.

Methods: Adult trauma patients who suffered a C1 fracture were identified retrospectively.

The incidence of brainstem toxicity following high-dose conformal proton therapy for adult skull-base malignancies.

Background: Dose escalation for skull-based malignancies often presents risks to critical adjacent neural structures, including the brainstem. We report the incidence of brainstem toxicity following fractionated high-dose conformal proton therapy and associated dosimetric parameters.

Material And Methods: We performed a single-institution review of patients with skull-base chordoma or chondrosarcoma who were treated with proton therapy between February 2007 and January 2020 on a prospective outcomes-tracking protocol.

Gradient expectations: Revisiting Charles Manning Child's theory of metabolic regionalisation in developmental patterning and regeneration.

Charles Manning Child introduced one of several early models to explain how an organism can both establish and re-establish positional identity during embryogenesis and regeneration. In his gradient theory model, tissues along an axis exhibit graded levels of metabolic activity demonstrated through their differential susceptibility to metabolic inhibitors. While Child's work was difficult to place in a mechanistic framework in his own time, technological advances and recent discoveries in both embryos and regenerating organisms make his early work on redox signalling as a positional cue newly pertinent.

Hif1α and Wnt are required for posterior gene expression during Xenopus tropicalis tail regeneration.

Regeneration of complex tissues is initiated by an injury-induced stress response, eventually leading to activation of developmental signaling pathways such as Wnt signaling. How early injury cues are interpreted and coupled to activation of these developmental signals and their targets is not well understood. Here, we show that Hif1α, a stress induced transcription factor, is required for tail regeneration in Xenopus tropicalis.

Imaging of dental infections.

Dental infections are a common presentation in the emergency department (ED). To help guide clinical management for these infections, the radiologist must be familiar with the anatomy of the oral cavity and neighboring structures, the range of appearance of dental infections, and the routes along which they may spread. Computed tomography (CT) is often performed when severe dental infections are suspected.