Methods: Patients undergoing primary, elective 1–3 level ACDF for radiculopathy at a single academic center between 2015 and 2021 were identified retrospectively. Cervical FS was evaluated using axial T2-weighted MRI images via a validated grading scale. The maximum degree of stenosis was used for multilevel disease. Motor symptoms were classified using encounters at their final preoperative and first postoperative visits, with examinations ≤3/5 indicating weakness. PROMs were obtained preoperatively and at 1-year follow-up. Bivariate analysis was used to compare outcomes based on stenosis severity, followed by multivariable analysis. Results: This study included 354 patients, 157 with moderate stenosis and 197 with severe stenosis. Overall, 58 patients (16.4%) presented with upper extremity weakness ≤3/5. A similar number of patients in both groups presented with baseline motor weakness (13.5% vs. 16.55, p =0.431). Postoperatively, 97.1% and 87.0% of patients with severe and moderate FS, respectively, experienced full motor recovery (p =0.134). At 1-year, patients with severe neuroforaminal stenosis presented with significantly worse 12-item Short Form Survey Physical Component Score (PCS-12) (33.3 vs. 37.3, p =0.049) but demonstrated a greater magnitude of improvement (Δ PCS-12: 5.43 vs. 0.87, p =0.048). Worse stenosis was independently associated with greater ΔPCS-12 at 1-year (β =5.59, p =0.022). Conclusions Patients with severe FS presented with worse preoperative physical health. While ACDF improved outcomes and conferred similar motor recovery in all patients, those with severe FS reported much better improvement in physical function.

Purpose: Medical schools have faced various challenges in preparing their clinical students for the frontlines of a pandemic. This study investigated medical students’ satisfaction with their institutions during the coronavirus disease 2019 (COVID-19) pandemic with the intention of guiding educators in future public health crises. Methods: In this cross-sectional study surveying students in clinical rotations, the primary outcome was overall satisfaction regarding medical schools’ responses to the pandemic, and the four secondary outcomes were school communication, exposure to COVID-19, availability of personal protective equipment, and access to COVID-19 testing. Results: The survey was distributed to ten medical schools, of which 430 students responded for a response rate of 13.0%. While most students were satisfied (61.9%, n=266) with their schools’ response, more than one in five (21.9%, n=94) were dissatisfied. Among the four secondary outcomes, communication with students was most predictive of overall satisfaction. Conclusion In future crises, schools can best improve student satisfaction by prioritizing timely communication.

BACKGROUND: Acne vulgaris is a disease of the pilosebaceous unit characterized by increased sebum production, hyperkeratinization, and immune responses to Propionibacterium acnes (PA). Here, we explore a possible mechanism by which a lipid receptor, G2A, regulates immune responses to a commensal bacterium. OBJECTIVE: To elucidate the inflammatory properties of G2A in monocytes in response to PA stimulation. Furthermore, our study sought to investigate pathways by which lipids modulate immune responses in response to PA. METHODS: Our studies focused on monocytes collected from human peripheral blood mononuclear cells, the monocytic cell line THP-1, and a lab strain of PA. Our studies involved the use of enzyme-linked immunosorbent, Western blot, reverse transcription polymerase chain reaction, small interfering RNA (siRNA), and microarray analysis of human acne lesions in the measurements of inflammatory markers. RESULTS: G2A gene expression is higher in acne lesions compared to normal skin and is inducible by the acne therapeutic, 13-cis-retinoic acid. In vitro, PA induces both the Toll-like receptor 2-dependent expression of G2A as well as the production of the G2A ligand, 9-hydroxyoctadecadienoic acid, from human monocytes. G2A gene knockdown through siRNA enhances PA stimulation of interleukin (IL)-6, IL-8, and IL-1β possibly through increased activation of the ERK1/2 MAP kinase and nuclear factor kappa B p65 pathways. CONCLUSION: G2A may play a role in quelling inflammatory cytokine response to PA, revealing G2A as a potential attenuator of inflammatory response in a disease associated with a commensal bacterium.
Acne Vulgaris ; Blotting, Western ; Cell Line ; Cytokines* ; Gene Expression ; Gene Knockdown Techniques ; Humans* ; In Vitro Techniques ; Interleukin-8 ; Interleukins ; Isotretinoin ; Microarray Analysis ; Monocytes* ; NF-kappa B ; Phosphotransferases ; Polymerase Chain Reaction ; Propionibacterium acnes* ; Propionibacterium* ; Reverse Transcription ; RNA, Small Interfering ; Sebum ; Skin ; Toll-Like Receptors

BACKGROUND: Phenol and alcohol have been used to ablate nerves to treat pain but are not specific for nerves and can damage surrounding soft tissue. Lidocaine at concentrations > 8% injected intrathecal in the animal model has been shown to be neurotoxic. Tests the hypothesis that 10% lidocaine is neurolytic after a peri-neural blockade in an ex vivo experiment on the canine sciatic nerve. METHODS: Under ultrasound, one canine sciatic nerve was injected peri-neurally with 10 cc saline and another with 10 cc of 10% lidocaine. After 20 minutes, the sciatic nerve was dissected with gross inspection. A 3 cm segment was excised and preserved in 10% buffered formalin fixative solution. Both samples underwent progressive dehydration and infusion of paraffin after which they were placed on paraffin blocks. The sections were cut at 4 µm and stained with hemoxylin and eosin. Microscopic review was performed by a pathologist from Henry Ford Hospital who was blinded to which experimental group each sample was in. RESULTS: The lidocaine injected nerve demonstrated loss of gross architecture on visual inspection while the saline injected nerve did not. No gross changes were seen in the surrounding soft tissue seen in either group. The lidocaine injected sample showed basophilic degeneration with marked cytoplasmic vacuolation in the nerve fibers with separation of individual fibers and endoneurial edema. The saline injected sample showed normal neural tissue. CONCLUSIONS: Ten percent lidocaine causes rapid neurolytic changes with ultrasound guided peri-neural injection. The study was limited by only a single nerve being tested with acute exposure.
Basophils ; Cytoplasm ; Dehydration ; Edema ; Eosine Yellowish-(YS) ; Formaldehyde ; Lidocaine* ; Models, Animal ; Nerve Fibers ; Paraffin ; Phenol ; Pilot Projects* ; Sciatic Nerve* ; Ultrasonography*

BACKGROUND: Expression of hepatic cholesterol 7alpha-hydroxylase (CYP7A1) is negatively regulated by orphan nuclear receptor small heterodimer partner (SHP). In this study, we aimed to find whether thyroid hormone regulates SHP expression by modulating the transcriptional activities of liver receptor homolog-1 (LRH-1). METHODS: We injected thyroid hormone (triiodothyronine, T3) to C57BL/6J wild type. RNA was isolated from mouse liver and used for microarray analysis and quantitative real-time polymerase chain reaction (PCR). Human hepatoma cell and primary hepatocytes from mouse liver were used to confirm the effect of T3 in vitro. Promoter assay and electrophoretic mobility-shift assay (EMSA) were also performed using human hepatoma cell line RESULTS: Initial microarray results indicated that SHP expression is markedly decreased in livers of T3 treated mice. We confirmed that T3 repressed SHP expression in the liver of mice as well as in mouse primary hepatocytes and human hepatoma cells by real-time PCR analysis. LRH-1 increased the promoter activity of SHP; however, this increased activity was markedly decreased after thyroid hormone receptor beta/retinoid X receptor alpha/T3 administration. EMSA revealed that T3 inhibits specific LRH-1 DNA binding. CONCLUSION: We found that thyroid hormone regulates the expression of SHP mRNA through interference with the transcription factor, LRH-1.
Animals ; Bile Acids and Salts ; Carcinoma, Hepatocellular ; Cell Line ; Child ; Child, Orphaned ; Cholesterol ; Cholesterol 7-alpha-Hydroxylase ; DNA ; Hepatocytes ; Humans ; Liver* ; Mice ; Microarray Analysis ; Real-Time Polymerase Chain Reaction ; Receptors, Thyroid Hormone ; RNA ; RNA, Messenger* ; Thyroid Gland* ; Thyroid Hormones ; Transcription Factors

BACKGROUNDWe previously demonstrated that the aqueous extract of the Schizandra chinensis fruit (AESC) ameliorated Cd-induced depletion of monoamine neurotransmitters in the brain through antioxidant activity. In the present study, we investigated the effect of AESC on anxiety-like behavior and the levels of norepinephrine and 3-methoxy-4-hydroxy-phenylglycol (a metabolite of norepinephrine) in different brain regions during ethanol withdrawal in rats.

METHODSMale Sprague-Dawley rats were treated with 3 g/kg of ethanol (20%, w/v) or saline by daily intraperitoneal injection for 28 days followed by three days of withdrawal. During withdrawal, rats were given AESC (100 mg × kg(-1)× d(-1) or 300 mg × kg(-1)× d(-1), P.O.) once a day for three days. Thirty minutes after the final dose of AESC, the anxiogenic response was evaluated using an elevated plus maze, and the plasma corticosterone levels were examined by radioimmunoassay. Meanwhile, the concentrations of norepinephrine and 3-methoxy-4-hydroxy-phenylglycol in the hypothalamic paraventricular nucleus and hippocampus were also measured by high performance liquid chromatography.

RESULTSRats undergoing ethanol withdrawal exhibited substantial anxiety-like behavior, which was characterized by both the decrease in time spent in the open arms of the elevated plus maze and the increased level of corticosterone secretion, which were greatly attenuated by doses of AESC in a dose-dependent manner. The high performance liquid chromatography analysis revealed that ethanol withdrawal significantly increased norepinephrine and 3-methoxy-4-hydroxy-phenylglycol levels in the hypothalamic paraventricular nucleus, while not significantly altering them in the hippocampus. Similar to the results from the elevated plus maze test, the AESC significantly inhibited the elevation of norepinephrine and its metabolite in the hypothalamic paraventricular nucleus in a dose-dependent manner.

CONCLUSIONSThese results suggest that AESC attenuates anxiety-like behavior induced by ethanol withdrawal through modulation of the hypothalamic norepinephrine system in the brain.

Animals ; Anxiety ; drug therapy ; etiology ; Behavior, Animal ; drug effects ; Ethanol ; adverse effects ; Fruit ; chemistry ; Male ; Plant Extracts ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Schisandra ; chemistry ; Substance Withdrawal Syndrome ; drug therapy

This review deals with the characteristics of various inflammatory mediators identified in the middle ear during otitis media and in cholesteatoma. The role of each inflammatory mediator in the pathogenesis of otitis media and cholesteatoma has been discussed. Further, the relation of each inflammatory mediator to the pathophysiology of the middle and inner ear along with its mechanisms of pathological change has been described. The mechanisms of hearing loss including sensorineural hearing loss (SNHL) as a sequela of otitis media are also discussed. The passage of inflammatory mediators through the round window membrane into the scala tympani is indicated. In an experimental animal model, an application of cytokines and lipopolysaccharide (LPS), a bacterial toxin, on the round window membrane induced sensorineural hearing loss as identified through auditory brainstem response threshold shifts. An increase in permeability of the blood-labyrinth barrier (BLB) was observed following application of these inflammatory mediators and LPS. The leakage of the blood components into the lateral wall of the cochlea through an increase in BLB permeability appears to be related to the sensorineural hearing loss by hindering K+ recycling through the lateral wall disrupting the ion homeostasis of the endolymph. Further studies on the roles of various inflammatory mediators and bacterial toxins in inducing the sensorineumral hearing loss in otitis media should be pursued.
Bacterial Toxins ; Chemokines ; Cholesteatoma ; Cochlea ; Cytokines ; Ear, Inner ; Ear, Middle ; Endolymph ; Evoked Potentials, Auditory, Brain Stem ; Hearing Loss ; Hearing Loss, Sensorineural ; Homeostasis ; Membranes ; Models, Animal ; Otitis ; Otitis Media ; Permeability ; Recycling ; Scala Tympani