Vascular function is dynamically regulated and dependent on a bevy of cell types and factors that work in concert across the vasculature. The vasoactive eicosanoid, 20-Hydroxyeicosatetraenoic acid (20-HETE) is a key player in this system influencing the sensitivity of the vasculature to constrictor stimuli, regulating endothelial function, and influencing the renin angiotensin system (RAS), as well as being a driver of vascular remodeling independent of blood pressure elevations. Several of these bioactions are accomplished through the ligand-receptor pairing between 20-HETE and its high-affinity receptor, GPR75. This 20-HETE axis is at the root of various vascular pathologies and processes including ischemia induced angiogenesis, arteriogenesis, septic shock, hypertension, atherosclerosis, myocardial infarction and cardiometabolic diseases including diabetes and insulin resistance. Pharmacologically, several preclinical tools have been developed to disrupt the 20-HETE axis including 20-HETE synthesis inhibitors (DDMS and HET0016), synthetic 20-HETE agonist analogues (20-5,14-HEDE and 20-5,14-HEDGE) and 20-HETE receptor blockers (AAA and 20-SOLA). Systemic or cell-specific therapeutic targeting of the 20-HETE-GPR75 axis continues to be an invaluable approach as studies examine the molecular underpinnings activated by 20-HETE under various physiological settings. In particular, the development and characterization of 20-HETE receptor blockers look to be a promising new class of compounds that can provide a considerable benefit to patients suffering from these cardiovascular pathologies.

BACKGROUND: Lesions involving the cavernous sinus (CS) represent some of the most challenging pathologies of the skull base owing to the dense traversing and sur-rounding neurovasculature. Extradural exposure and preparation of this region, whether as initial preparation for a combined intra-extradural approach or as the main avenue of surgical exposure, can enlarge surgical corri-dors and minimize the need for brain retraction in this very confined space. We provide a detailed assessment of the entry corridors to the CS that are available within each approach, the surgical exposure and freedom provided by each of these corridors, and demonstrate how extradural and intradural preparation of these corridors can be used to widen the available working space and facilitate surgery. -METHODS: Pterional, frontotemporal-orbital, fronto-temporal-orbitozygomatic, frontotemporal-zygomatic, peril-abyrinthine transtentorial, and endoscopic transnasal transsphenoidal approaches were performed on cadaveric heads to access the perisellar and CS regions. Periclinoid maneuvers (extradural cutting of the meningo-orbital band, anterior clinoidectomy, unroofing of the optic canal, opening of the superior orbital fissure, displacement of the extra-annular structures, opening of the annulus of Zinn, and interdural dissection), pericavernous maneuvers (intradural cutting of the distal dural ring, mobilization of the supraclinoid internal carotid artery, opening of the oculomotor porus, and mobilization of cranial nerve (CN) III), peritrigeminal extensions (extradural mobilization of CN V2 [maxillary] and/or V3 [mandibular]), and other sur-gical maneuvers were performed and evaluated. The CS was divided into 8 anatomical compartments and 9 entry corridors were described, and exposure and freedom were assessed accordingly. -RESULTS: Intradurally, the standard unextended pter-ional, frontotemporal-orbital, and frontotemporal orbitozy-gomatic transsylvian approaches provided access solely to the parasellar entry corridor into the superior wall of the CS. Expanding these approaches with extradural peri-clinoid maneuvers allowed for subsequent application of the intradural pericavernous maneuvers and enlargement of the parasellar corridor and exposure of the carotid cave. Extradurally, the frontotemporal-orbital approach could be expanded via application of periclinoid maneuvers, which provided access to the anterior portions of the main lateral wall entry corridors. The frontotemporal-orbitozygomatic approach could also be expanded with periclinoid ma-neuvers to provide extradural access to all 6 lateral wall entry corridors. The extradural frontotemporal-zygomatic approach only provided exposure following interdural dissection, which allowed for access to the inferolateral entry corridors into the lateral wall. Extradural peri-trigeminal extension in the frontotemporal-orbitozygomatic and frontotemporal-zygomatic approaches allows for enlargement of the supramaxillary and pre-and post -mandibular corridors. The perilabyrinthine approach to the posterior wall was enlarged with opening of Dorello's canal and the endoscopic transnasal transsphenoidal approach was enlarged with opening of the optic canal. -CONCLUSIONS: Targeted extradural preparation opti-mizes exposure and significantly improves access to deep-seated targets by enhancing surgical maneuverability through the unlocking of neurovascular structures and widening of surgical corridors without the need for addi-tional brain retraction.

Background: Developing and maintaining a three-dimensional working knowledge of neuroanatomy is an essential skill in neurosurgery. However, conventional 2D head, neck, and neuroanatomy education is typically characterized by the separate rote learning of constituent tissues and often fails to provide learners with a contextual understanding of the relationships between these highly complex and interconnected structures. This can pose a significant challenge to medical students entering neurosurgery who lack a topographic understanding of intracranial anatomy. Methods: We report on the design and efficacy of a novel 6-part 3D surgical neuroanatomy pilot elective for medical students that utilized a navigation-based pedagogical technique with the goal of providing students with a framework for developing a 3D mental map of the skull base, neurovasculature, ventricular system, and associated brain regions. Students took on the perspective of physically traveling along the paths of key structures with a 360-degree view of surrounding anatomy such that they could appreciate the integration and relative spatial relationships of the varying tissues within the cranium. Mental navigation exercises and pre- and post-course surveys were used to assess students' baseline and learned familiarity with the different anatomical regions covered. Results: At the conclusion of the course, all students were able to successfully complete all of the multifaceted mental navigation exercises. Post-course survey data indicated that respondents perceived significant increases in their knowledge of cranial nerves; anterior, middle, and posterior skull base anatomy; anterior and posterior cranial circulation; and the ventricular system. Conclusion: 3D navigation-based fly-through instruction is a novel and effective technique for teaching complex anatomy and can provide learners with the foundational skills for developing and maintaining a 3D mental map of intracranial anatomy.

20‐Hydroxyeicosatetraenoic acid (20‐HETE) and its receptor (20HR), GPR75 (Gq), exhibit diverse bioactions that promote the activation of pro‐hypertensive, ‐diabetic and ‐obesity signals. The pharmacological properties associated with analogues that target GPR75 remain unclear. The screening of 20‐HETE and synthetic 20‐HETE analogues using changes of intracellular calcium (iCa2+) in the endothelial cell line, EA.hy926, as a measure of 20HR activation, revealed that the compounds 20‐HETE (10 nM), sodium 20‐hydroxyeicosa‐5Z,14Z‐dienoate (20‐5,14‐HEDE) (10 nM) and sodium 14‐((6‐hydroxyhexyl)oxy)tetradec‐5(Z)‐enoate (5Z‐HOTE) (10 nM) promote significant and comparable elevations in iCa2+. In EA.hy926 cells, 20‐HETE elicited a half‐maximal effective concentrations (EC50) with respect to iCa2+ of 1.228 e‐9 M while 20‐5,14‐HEDE’s EC50 was 6.908 e‐10 M. The water‐soluble derivative of 20‐5,14‐HEDE, SOLAGO, exhibited a marked and leftward shift in the dose‐response with an EC50 of 2.702 e‐10 M. Interestingly, sodium 19(R)‐ and 19(S)‐hydroxyeicosa‐5(Z),14(Z)‐dienoate, analogues of 19(R)‐HETE, an endogenous 20HR blocker (20HRB), demonstrated partial agonist activity; elevating iCa2+to 1.6‐ and 2‐fold over baseline vehicle treatment, respectively. With respect to 20HR blockers, the water‐soluble 20HRBs 2,5,8,11,14,17‐hexaoxanonadecan‐19‐yl 20‐hydroxyeicosa‐6(Z),15(Z)‐dienoate (20‐SOLA) and N‐disodium succinate‐20‐hydroxyeicosa‐6(Z),15(Z)‐diencarboxamide (AAA) displayed potent half‐maximal inhibitory concentrations (IC50s) of 8.059 e‐10 and 5.356 e‐10 M, respectively. The 19(R)‐HETE analogue sodium (19(R)‐hydroxyeicosa‐5(Z),14(Z)‐dienoyl)glycinate (19(R)‐HEDGE) also demonstrated a strong yet less potent IC50 response of 6.715 e‐9 M. Further studies are necessary to better understand the structure‐function relationships between 20HR agonists, partial agonists, and receptor blockers. These data would allow for the development of novel 20HRBs for the treatment of various pathologies associated with elevations in 20‐HETE including hypertension, cancer, diabetes, and obesity.

Suturing and knot tying are essential skills and a mainstay of medical education, however, there remains a lack of detailed literature on effective methods for teaching new learners.1,2 Over the previous decade of teaching suturing, our team of surgical educators, led by an experienced academic neurosurgeon, has noticed a typical pattern of errors made by new learners, characterized by rigidity and a narrow working area, that result in wasted motions, pulling out the tail of the suture, and loosely tied knots. To combat this, we developed a novel teaching technique using the Chicken Dance that emphasizes visuospatial awareness and the importance of the elbows in knot tying while allowing students to learn the fundamental motions in an unconstricted space. Students are divided into small instructor-led groups, spaced 1 meter apart and positioned perpendicular to the wound. The suture needle is advanced through each end of the wound using a needle driver and forceps, with supination of the wrist, and the suture is pulled leaving a 2–3 cm tail. The needle is removed from the driver, the forceps are palmed, and the long end of the suture is grasped by the non-dominant hand, securing the needle. The Chicken Dance technique is then taught using the following steps. 1. Starting Position: Start by imitating chicken wings—abduct the arm at the shoulder to bring the elbows to 75–90° and flex the elbow to bring the wrists to the sternum while holding the suture with the non-dominant hand behind the needle driver in the dominant hand (Figure 1A). Place the hands approximately 10 cm in front of the chest and at least 10 cm above the wound to maximize the working area. 2. Wing Flapping: With the suture held behind the needle driver, begin the wrapping of the suture around the driver by flapping your “chicken wings”—moving both elbows superiorly from the starting position (Figure 1B-C) and then inferiorly below the starting position (Figure 1C), wrapping the suture around the driver once. Repeat to wrap the suture around the driver a second time (Figure 1D-E), keeping both wrists relatively still and each arm moving in concert so that one arm is not moving more than the other. The flapping motion of the elbows results in the suture wrapping around the needle driver without creating tension on the suture. 3. First Square Knot: Once the suture is wrapped around the needle driver, supinate the dominant hand to prevent the suture from slipping off and grasp the tip of the tail with the driver (Figure 1F). The non-dominant hand is then extended to pull the suture off the driver and create and tighten a knot (Figure 1G). This is performed with minimal movement of the driver to prevent elongation of the tail during tightening. Perpendicular force should then be applied using both hands. 4. Additional Throws: Repeat steps 1–4 with one wrap of the suture around the needle driver, alternating the direction of the wrap with each throw of the knot until the desired number of throws is reached, ensuring a tight square knot (Figure 1B-C, F-G). Cut the suture leaving the desired tail length. As students become more proficient, the working area can be narrowed and these same motions can be translated to the wrists and later the fingers for micro-suturing. By training students from the elbows down, the Chicken Dance Technique helps establish a simple technical foundation from which more advanced skills can be developed. This technique was designed to stimulate situational awareness of oneself and one’s working area as well as the positions of the suture, needle driver, and needle. Flapping of the elbows helps to reduce tension and tunnel vision while demonstrating efficiency of movement and maximizing available workspace.

BACKGROUND: Anatomical variations of the course of the internal carotid artery (ICA) may complicate surgical clipping of posterior communicating artery (PCoA) aneurysms by narrowing the retrocarotid window. We evaluated the efficacy of the periclinoid surgical maneuvers for expanding the retrocarotid window and analyzed computed tomography angiography (CTA) data from patients with PCoA aneurysms to define parameters for low-coursing ICAs. METHODS: Using cadaveric specimens, standard pterional craniotomies were fashioned and extradural or intradural periclinoid surgical maneuvers-cutting of the meningo-orbital band, anterior clinoidectomy, and cutting of the distal dural ring (DDR)-were performed, and their relative advantages for expanding the retrocarotid window were assessed. Additionally, preoperative CTA data from 24 patients with PCoA aneurysms used to calculate the angles of the ICA relative to the skull base. RESULTS: Periclinoid maneuvers, especially the anterior clinoidectomy, provided additional exposure of the retrocarotid space. Cutting of the DDR allowed for partial mobilization of the ICA and widened the retrocarotid surgical window, enhancing maneuverability. The anterior clinoidectomy with cutting of the DDR allowed for enhanced exposure of the medial, middle, and posterolateral aspects of the retrocarotid space. Cutting the anterior petroclinoid fold and mobilizing cranial nerve III provided wide exposure of the lateral aspect of retrocarotid space. CONCLUSION: When clipping PCoA aneurysms in the presence of normal-coursing ICAs (approximately >= 30 degrees ICA angle), a standard pterional craniotomy with anterior clinoidectomy and cutting of the DDR allows for substantial expansion of the retrocarotid window.