Potential mechanisms for osteopathic manipulative treatment to alleviate migraine-like pain in female rats.

Introduction: Migraines are the leading cause of disability in the United States, and the use of non-pharmaceutical treatments like osteopathic manipulative treatment (OMT) has shown promise. Despite its potential, the lack of mechanistic understanding has hindered widespread adoption. This study aims to investigate the efficacy of OMT in treating acute migraines and unravel its underlying mechanisms of action. Methods: Female rats were subjected to a "two-hit" approach to induce migraine-like pain. This involved bilateral injections of Complete Freund's Adjuvant (CFA) into the trapezius muscle (1st hit) followed by exposure to Umbellulone, a human migraine trigger, on Day 6 post-CFA (2nd hit). Soft tissue and articulatory techniques were applied to the cervical region for acute abortive or repeated prophylactic treatment. Cutaneous allodynia and trigeminal system activation were assessed through behavioral tests and immunohistochemical staining. Results: Following Umbellulone inhalation, CFA-primed rats exhibited periorbital and hind paw allodynia. Immediate application of OMT after Umbellulone inhalation as an abortive treatment partially alleviated cutaneous allodynia. With OMT applied thrice as a prophylactic measure, complete suppression of tactile hypersensitivity was observed. Prophylactic OMT also prevented the increase of c-fos signals in the trigeminal nucleus caudalis and the elevation of calcitonin gene-related peptide expression in trigeminal ganglia induced by CFA and Umbellulone exposure at 2 h post-inhalation. Discussion: These findings provide mechanistic insights into OMT's migraine-relief potential and underscore its viability as a non-pharmacological avenue for managing migraines.

Consensus and Equipose in the Management of Military Trainee Femoral Neck Stress Fractures: A Survey of Military Surgeons.

BACKGROUND: Femoral neck stress fractures (FNSFs) are a unique injury pattern not commonly treated in the civilian trauma population; however, it is particularly high with military trainees engaged in basic combat training. To date, no study has surveyed a population of military orthopedic surgeons on treatment preferences for military service members (SMs) with FNSF. QUESTIONS: We aim to evaluate the extent of clinical equipoise that exists in the management of these injuries, hypothesizing that there would be consensus in the factors dictating surgical and non-surgical intervention for FNSF. PATIENTS AND METHODS: A 27-question survey was created and sent to U.S. military orthopedic surgeon members of the Society of Military Orthopaedic Surgeons. The survey was designed in order to gather the experience among surgeons in treating FNSF and identifying variables that play a role in the treatment algorithm for these patients. In addition, seven detailed, clinical vignettes were presented to further inquire on surgeon treatment preferences. Binomial distribution analysis was used to evaluate for common trends within the surgeon's treatment preferences. RESULTS: Seventy orthopedic surgeons completed the survey, the majority of whom were on active duty status in the U.S. Military (82.86%) and having under 5 years of experience (61.43%). Majority of surgeons elected for a multiple screw construct (92.86%), however the orientation of the multiple screws was dependent on whether the fracture was open or closed. Management for compression-sided FNSF involving ≥50% of the femoral neck width, tension-sided FNSF, and stress fractures demonstrating fracture line progression had consensus for operative management. Respondents agreed upon prophylactic fixation of the contralateral hip if the following factors were involved: Complete fracture (98.57%), compression-sided fracture line >75% (88.57%), compression-sided fracture line >50-75% with hip effusion (88.57%), contralateral tension-sided fracture (87.14%), and compression-sided fracture line >50-75% (84.29%). An FNSF < 50% on the contralateral femoral neck or a hip effusion was indeterminate in surgeons indicating need for prophylactic fixation. Majority of surgeons (77.1%) utilized restricted toe-touch weight-bearing for postoperative mobility restrictions. CONCLUSIONS: Consensus exists for surgical and non-surgical management of FNSF by U.S. military orthopedic surgeons, despite the preponderance of surgeons reporting a low annual volume of FNSF cases treated. However, there are certain aspects in the operative and non-operative management of FNSF that are unanimously adhered to. Specifically, our results demonstrate that there is no clear indication on the management of FNSF when an associated hip effusion is involved. Additionally, the indications for surgically treating contralateral FNSF are unclear. LEVEL OF EVIDENCE: IV.

In Situ Liquid Cell Transmission Electron Microscopy Study of Studtite Particle Formation and Growth via Electron Beam Radiolysis.

This study presents in situ observations of studtite (UO2O2(H2O)2·2H2O) crystal growth utilizing liquid phase transmission electron microscopy (LP-TEM). Studtite was precipitated from a uranyl nitrate hexahydrate solution using hydrogen peroxide formed by the radiolysis of water in the TEM electron beam. The hydrogen peroxide (H2O2) concentration, directly controlled by the electron beam current, was varied to create local environments of low and high concentrations to compare the impact of the supersaturation ratio on the nucleation and growth mechanisms of studtite particles. The subsequent growth mechanisms were observed in real time by TEM and scanning TEM imaging. After the initial precipitation reaction, a post-mortem TEM analysis was performed on the samples to obtain high-resolution TEM images and selected area electron diffraction patterns to investigate crystallinity as well as energy-dispersive X-ray spectroscopy spectra to ensure that studtite was produced. The results reveal that studtite particles form through various mechanisms based on the concentration ratio of uranyl to H2O2 and that studtite is initially produced through an amorphous intermediary prior to formation of the crystalline material commonly reported in the literature.

TRPC Channels Activated by G Protein-Coupled Receptors Drive Ca2+ Dysregulation Leading to Secondary Brain Injury in the Mouse Model.

Canonical transient receptor potential (TRPC) non-selective cation channels, particularly those assembled with TRPC3, TRPC6, and TRPC7 subunits, are coupled to Gαq-type G protein-coupled receptors for the major classes of excitatory neurotransmitters. Sustained activation of this TRPC channel-based pathophysiological signaling hub in neurons and glia likely contributes to prodigious excitotoxicity-driven secondary brain injury expansion. This was investigated in mouse models with selective Trpc gene knockout (KO). In adult cerebellar brain slices, application of glutamate and the class I metabotropic glutamate receptor agonist (S)-3,5-dihydroxyphenylglycine to Purkinje neurons expressing the GCaMP5g Ca2+ reporter demonstrated that the majority of the Ca2+ loading in the molecular layer dendritic arbors was attributable to the TRPC3 effector channels (Trpc3KO compared with wildtype (WT)). This Ca2+ dysregulation was associated with glutamate excitotoxicity causing progressive disruption of the Purkinje cell dendrites (significantly abated in a GAD67-GFP-Trpc3KO reporter brain slice model). Contribution of the Gαq-coupled TRPC channels to secondary brain injury was evaluated in a dual photothrombotic focal ischemic injury model targeting cerebellar and cerebral cortex regions, comparing day 4 post-injury in WT mice, Trpc3KO, and Trpc1/3/6/7 quadruple knockout (TrpcQKO), with immediate 2-h (primary) brain injury. Neuroprotection to secondary brain injury was afforded in both brain regions by Trpc3KO and TrpcQKO models, with the TrpcQKO showing greatest neuroprotection. These findings demonstrate the contribution of the Gαq-coupled TRPC effector mechanism to excitotoxicity-based secondary brain injury expansion, which is a primary driver for mortality and morbidity in stroke, traumatic brain injury, and epilepsy.

Management Considerations for Unicompartmental Osteoarthritis in Athletic Populations: A Review of the Literature.

Unicompartmental osteoarthritis in the young athlete poses a challenge for both patients and providers. Coronal plane malalignment is frequently a concomitant finding that adds to the complexity of management. Military surgeons are presented unique challenges, in that they must consider optimal joint-preservation methods while returning patients to a high-demand occupational function. Management options range from lifestyle changes to surgical interventions. We present a concise review of the available literature on this subject, with a specific focus on indications and outcomes within the military and young athletic population.