Rejected

Nonfreezing cold injury (NFCI) is caused by prolonged exposure to cold, usually wet conditions and represents a separate pathological entity from frostbite. The pathophysiology of NFCI is characterized by vasoconstriction and microcirculatory disturbance. Iloprost, a synthetic prostaglandin analogue with vasodilatory properties is a recognized adjuvant treatment in frostbite; however, its role in NFCI is unclear. We present a case of a 29-y-old man with severe NFCI to both forefeet after prolonged immersion in cold seawater. Initial treatment with passive rewarming, analgesia and aspirin was initiated. Infusion of iloprost was used within 24 h from presentation and was well tolerated. This resulted in reduced tissue loss compared to the apparent tissue damage documented during the initial assessment. Delayed surgical intervention allowed minor debridement and minor toe amputations, maintaining the patient's ability to ambulate. This case demonstrates the safe use of iloprost in acute NFCI and highlights the importance of delayed surgical intervention in patients presenting with severe NFCI.

Methylene blue (MB) mediated photodynamic therapy (PDT) is an emerging treatment for different kinds of skin lesions and ulcers. Our case report aims to assess its potential in treating diabetic foot ulcers, venous leg ulcers, and pressure ulcers. Patients presented with complex chronic wounds larger than 40 cm with low healing potential. Once a week, patients had an aqueous formulation of MB at a concentration of 10 mg/mL (1% w/v) applied topically on their wounds, which were then irradiated with a light-emitting diode (LED) light source (660 nm, 3.8 J/cm) with 9 mW/cm on tissue surface. Symptom improvement and recurrence rates were assessed with a long-term follow-up from 2018 to 2021. The results were satisfactory, with significant wound size reduction, and a decrease in aspects indicative of infection including odor, presence of exudates, and purulence. After methylene blue-mediated photodynamic therapy (MB-PDT), patients showed significantly reduced wound secretion, no signs of local reaction, and no adverse effects such as burning sensation, pain, itching, skin erythema, or general malaise.

Uterine mesenchymal lesions demonstrate various underlying genomic alterations involving MED12, JAZF1, YWHAE, BCOR, and ALK genes, among others. Recent publications describe a subset of high-grade endometrial stromal sarcoma lesions harboring BCORL1 gene aberrations including JAZF1::BCORL1. Herein, we present an unusual benign endomyometrial spindle cell lesion that defies classificatory efforts by demonstrating mixed histomorphologic and immunohistochemical features of endometrial stromal nodule, leiomyoma, and uterine inflammatory myofibroblastic tumor while harboring a JAZF1::BCORL1. The lesion was found in a 43-yr-old woman with pelvic pain and heavy menses as a 5.5 cm well-circumscribed ulcerated mass fungating from the cervical os. Microscopic examination revealed a polypoid, well-circumscribed, moderately cellular endomyometrial tumor composed by bland spindle cells haphazardly disposed within a slightly edematous stroma enriched by a delicate network of thin-walled vessels that were occasionally encircled by the tumor cells. Unequivocal evidence of tongue-like growth pattern into the myometrium, tumor-type necrosis or increased mitotic activity was not identified after sampling the entire lesion. The lesion showed patchy immunoreactivity for both smooth muscle actin-alpha and desmin while negative for CD10, HMB45, ALK (D5F3), and BCOR. An Archer FusionPlex panel assay demonstrated a fusion involving both exons 4 from the JAZF1 and BCORL1 genes. The JAZF1::BCORL1 has not, to the best of our knowledge, been previously reported in a benign/low-grade mesenchymal uterine lesion.

Pain management after foot and ankle surgery must surmount unique challenges that are not present in orthopaedic surgery performed on other parts of the body. However, disparate and inconsistent evidence makes it difficult to draw meaningful conclusions from individual studies.

The ability of drugs and therapeutic antibodies to reach central nervous system (CNS) targets is greatly diminished by the blood-brain barrier (BBB). Receptor-mediated transcytosis (RMT), which is responsible for the transport of natural protein ligands across the BBB, was identified as a way to increase drug delivery to the brain. In this study, we characterized IGF1R5, which is a single-domain antibody (sdAb) that binds to insulin-like growth factor-1 receptor (IGF1R) at the BBB, as a ligand that triggers RMT and could deliver cargo molecules that otherwise do not cross the BBB. Surface plasmon resonance binding analyses demonstrated the species cross-reactivity of IGF1R5 toward IGF1R from multiple species. To overcome the short serum half-life of sdAbs, we fused IGF1R5 to the human (hFc) or mouse Fc domain (mFc). IGF1R5 in both N- and C-terminal mFc fusion showed enhanced transmigration across a rat BBB model (SV-ARBEC) in vitro. Increased levels of hFc-IGF1R5 in the cerebrospinal fluid and vessel-depleted brain parenchyma fractions further confirmed the ability of IGF1R5 to cross the BBB in vivo. We next tested whether this carrier was able to ferry a pharmacologically active payload across the BBB by measuring the hypothermic and analgesic properties of neurotensin and galanin, respectively. The fusion of IGF1R5-hFc to neurotensin induced a dose-dependent reduction in the core temperature. The reversal of hyperalgesia by galanin that was chemically linked to IGF1R5-mFc was demonstrated using the Hargreaves model of inflammatory pain. Taken together, our results provided a proof of concept that appropriate antibodies, such as IGF1R5 against IGF1R, are suitable as RMT carriers for the delivery of therapeutic cargos for CNS applications.

(1) Background: Foster Kennedy syndrome (FKS) is an ophthalmological condition characterized by an insidious reduction in vision in one eye, accompanied by clinically significant papilledema in the fellow eye. The unilateral loss of vision and optic atrophy is due to compressive optic atrophy, which causes elevated intracranial pressure that leads to swelling in the fellow eye. The risk factors for FKS include the presence of mass lesions in radiographic imaging, female gender, and increased body mass index. Differential diagnoses of FKS include tumors and pseudotumor of the frontal lobe and cranial meninges. (2) Methods: We present two cases of FKS diagnosed in February 2021 and December 2021. (3) Results: A 52-year-old male with a history of poor vision in one eye after trauma complained of constant headache. Ocular examination revealed disc pallor in his right eye with disc edema in the contralateral eye. The patient was sent for computerized tomography (CT) and placed on oral prednisolone tablets. The CT scan confirmed the diagnosis of FKS. A 30-year-old female presented to the emergency department for poor vision in her left eye and headache on the left side. Medication included dexamethasone, chloramphenicol, timolol eyedrops, furosemide, and anti-oxidant tablets dispensed from a previous private eye clinic. Ophthalmoscopy showed disc pallor with 0.1 cupping and arteriolar attenuation in both eyes with macular hemorrhages in her left eye. Bilateral papilledema secondary to raised intracranial hyper-tension was suspected. CT scans showed an intracranial mass. (4) Conclusions: These two cases show the importance of ocular examination in the diagnosis of serious systemic conditions. A concise case history, extensive ocular workup, and cranial imaging with magnetic resonance imaging and/or CT scans are indicative of patients showing acute visual loss and retro-orbital pain, which can give rise to the diagnosis of sight-threatening, permanent and fatal conditions, such as FKS. Non-surgical treatments include oral steroidal therapy, radiotherapy, and chemotherapy; however, neurosurgery is normally required.

High-resolution spinal cord stimulation (HR-SCS) paddle can stimulate medial-dorsal columns and extend stimulation coverage to the laterally positioned spinal targets.

Fibromyalgia (FM), the most common cause of chronic musculoskeletal pain in the general public, lacks advanced therapeutic methodology and detailed bioinformation. However, acting as a newly developed and important transition metal carbide or carbonitride, the MoC nanozyme has provided a novel iatrotechnique with excellent bioactivity in a cell/animal model, which also exhibits potential prospects for future clinical applications. In addition, high-content and high-throughput integrated metabolomics (including aqueous metabolomics, lipidomics, and desorption electrospray ionization-mass spectrometry imaging) also specializes in qualitative and quantitative analysis of metabolic shifts at the molecular level. In this work, the FM-alleviation effect of MoC nanozyme was investigated through integrated metabolomics in a mouse model. An advanced platform combining gas chromatography-mass spectrometry, liquid chromatography-mass spectrometry and bioinformatics was utilized to study the variation in the mouse metabolome and lipidome. The results revealed that MoC treatment could effectively enhance energy metabolism-related biological events impaired by FM, leading to homeostasis of oxidative stress and energy metabolism toward the control levels. During this process, MoC facilitated the elimination of ROS in plasma and cells and the rehabilitation of mice from oxidative stress and mitochondrial dysfunction. It was believed that such an integrated metabolomics study on the FM-alleviation effect of MoC nanozyme could provide another excellent alternative to traditional MoC-based research with numerous pieces of bioinformation, further supporting research area innovation, material modification, and clinical application.

The aim of this study was to evaluate the postoperative analgesic and antioxidant effects of butorphanol given in the preoperative or early postoperative period. Twenty-seven healthy female dogs undergoing ovariohysterectomy were randomly divided into three groups as before surgery group (BSG, n = 7) received butorphanol 30 min before preanesthetic administration, after surgery group (ASG, n = 10) received butorphanol during the last skin suture and the control group (CG, n = 10) received no butorphanol. Pain was assessed with short form of the Glasgow composite pain scale (CMPS-SF). Serum concentration of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase activities (GPx) were quantified by spectrophotometric methods to assess oxidative stress status. The pain score increased rapidly at 1 h after surgery and then decreased gradually towards to 24 h in all groups. There was no statistical difference among the groups in terms of CMPS-SF scores (P > 0.05). Serum concentration of MDA was lower in ASG than in BSG and CG from 1 h to 24 h after surgery. Serum activity of GPx was higher in ASG than in BSG and CG from 2 h to 24 h (P < 0.05). Serum activity of SOD was higher in ASG than in BSG and CG from 1 h to 24 h after surgery (P < 0.05). Serum SOD activity at different time points in ASG did not differ compared to preoperative level though it decreased significantly from 1 h onwards both in CT and BSG. The results indicate that single butorphanol administration either before or after the operation might not provide sufficient analgesia, however, it seems that it has antioxidant potential and may protect tissues by reducing oxidative stress when administered early postoperative period following ovariohysterectomy.