Recent studies have shown an increased abundance of Sphingomonas paucimobilis, an aerobic, Gram-negative bacterium with a distinctive cell envelope rich in glycosphingolipids, within the gut microbiome of individuals with Alzheimer Disease (AD). However, the fact that S. paucimobilis is a well-known pathogen associated with nosocomial infections presents a significant challenge in investigating whether its presence in the gut microbiome is detrimental or beneficial, particularly in the context of AD. This study examines the impact of S. paucimobilis-derived extracellular vesicles (Spa-EV) on Aβ-induced pathology in cellular and animal models of AD. Microarray analysis reveals that Spa-EV treatment modulates Aβ42-induced alterations in gene expression in both HT22 neuronal cells and BV2 microglia cells. Among the genes significantly affected by SpaEV, notable examples include Bdnf, Nt3/4, and Trkb, which are key players of neurotrophic signaling; Pgc1α, an upstream regulator of mitochondrial biogenesis; Mecp2 and Sirt1, epigenetic factors that regulate numerous gene expressions; and Il1β, Tnfα, and Nfκb-p65, which are associated with neuroinflammation. Remarkably, Spa-EV effectively reverses Aβ42-induced alteration in the expression of these genes through the upregulation of Mecp2. Furthermore, administration of Spa-EV in Tg-APP/PS1 mice restores the reduced expression of neurotrophic factors, Pgc1α, MeCP2, and Sirt1, while suppressing the increased expression of proinflammatory genes in the brain. Our results indicate that Spa-EV has the potential to reverse Aβ-induced dysregulation of gene expression in neuronal and microglial cells. These alterations encompass those essential for neurotrophic signaling and neuronal plasticity, mitochondrial function, and the regulation of inflammatory processes.

Recent studies have shown an increased abundance of Sphingomonas paucimobilis, an aerobic, Gram-negative bacterium with a distinctive cell envelope rich in glycosphingolipids, within the gut microbiome of individuals with Alzheimer Disease (AD). However, the fact that S. paucimobilis is a well-known pathogen associated with nosocomial infections presents a significant challenge in investigating whether its presence in the gut microbiome is detrimental or beneficial, particularly in the context of AD. This study examines the impact of S. paucimobilis-derived extracellular vesicles (Spa-EV) on Aβ-induced pathology in cellular and animal models of AD. Microarray analysis reveals that Spa-EV treatment modulates Aβ42-induced alterations in gene expression in both HT22 neuronal cells and BV2 microglia cells. Among the genes significantly affected by SpaEV, notable examples include Bdnf, Nt3/4, and Trkb, which are key players of neurotrophic signaling; Pgc1α, an upstream regulator of mitochondrial biogenesis; Mecp2 and Sirt1, epigenetic factors that regulate numerous gene expressions; and Il1β, Tnfα, and Nfκb-p65, which are associated with neuroinflammation. Remarkably, Spa-EV effectively reverses Aβ42-induced alteration in the expression of these genes through the upregulation of Mecp2. Furthermore, administration of Spa-EV in Tg-APP/PS1 mice restores the reduced expression of neurotrophic factors, Pgc1α, MeCP2, and Sirt1, while suppressing the increased expression of proinflammatory genes in the brain. Our results indicate that Spa-EV has the potential to reverse Aβ-induced dysregulation of gene expression in neuronal and microglial cells. These alterations encompass those essential for neurotrophic signaling and neuronal plasticity, mitochondrial function, and the regulation of inflammatory processes.

Recent studies have shown an increased abundance of Sphingomonas paucimobilis, an aerobic, Gram-negative bacterium with a distinctive cell envelope rich in glycosphingolipids, within the gut microbiome of individuals with Alzheimer Disease (AD). However, the fact that S. paucimobilis is a well-known pathogen associated with nosocomial infections presents a significant challenge in investigating whether its presence in the gut microbiome is detrimental or beneficial, particularly in the context of AD. This study examines the impact of S. paucimobilis-derived extracellular vesicles (Spa-EV) on Aβ-induced pathology in cellular and animal models of AD. Microarray analysis reveals that Spa-EV treatment modulates Aβ42-induced alterations in gene expression in both HT22 neuronal cells and BV2 microglia cells. Among the genes significantly affected by SpaEV, notable examples include Bdnf, Nt3/4, and Trkb, which are key players of neurotrophic signaling; Pgc1α, an upstream regulator of mitochondrial biogenesis; Mecp2 and Sirt1, epigenetic factors that regulate numerous gene expressions; and Il1β, Tnfα, and Nfκb-p65, which are associated with neuroinflammation. Remarkably, Spa-EV effectively reverses Aβ42-induced alteration in the expression of these genes through the upregulation of Mecp2. Furthermore, administration of Spa-EV in Tg-APP/PS1 mice restores the reduced expression of neurotrophic factors, Pgc1α, MeCP2, and Sirt1, while suppressing the increased expression of proinflammatory genes in the brain. Our results indicate that Spa-EV has the potential to reverse Aβ-induced dysregulation of gene expression in neuronal and microglial cells. These alterations encompass those essential for neurotrophic signaling and neuronal plasticity, mitochondrial function, and the regulation of inflammatory processes.

Recent studies have shown an increased abundance of Sphingomonas paucimobilis, an aerobic, Gram-negative bacterium with a distinctive cell envelope rich in glycosphingolipids, within the gut microbiome of individuals with Alzheimer Disease (AD). However, the fact that S. paucimobilis is a well-known pathogen associated with nosocomial infections presents a significant challenge in investigating whether its presence in the gut microbiome is detrimental or beneficial, particularly in the context of AD. This study examines the impact of S. paucimobilis-derived extracellular vesicles (Spa-EV) on Aβ-induced pathology in cellular and animal models of AD. Microarray analysis reveals that Spa-EV treatment modulates Aβ42-induced alterations in gene expression in both HT22 neuronal cells and BV2 microglia cells. Among the genes significantly affected by SpaEV, notable examples include Bdnf, Nt3/4, and Trkb, which are key players of neurotrophic signaling; Pgc1α, an upstream regulator of mitochondrial biogenesis; Mecp2 and Sirt1, epigenetic factors that regulate numerous gene expressions; and Il1β, Tnfα, and Nfκb-p65, which are associated with neuroinflammation. Remarkably, Spa-EV effectively reverses Aβ42-induced alteration in the expression of these genes through the upregulation of Mecp2. Furthermore, administration of Spa-EV in Tg-APP/PS1 mice restores the reduced expression of neurotrophic factors, Pgc1α, MeCP2, and Sirt1, while suppressing the increased expression of proinflammatory genes in the brain. Our results indicate that Spa-EV has the potential to reverse Aβ-induced dysregulation of gene expression in neuronal and microglial cells. These alterations encompass those essential for neurotrophic signaling and neuronal plasticity, mitochondrial function, and the regulation of inflammatory processes.

Objective: To assess whether local anesthetic infiltration could minimize the carotid baroreceptor reflex (CBR) which has an incidence after carotid artery stenting (CAS) that varies from 29% to 51%. Methods: This retrospective single-center study included 51 patients (mean age, 70.47 years) who underwent CAS for carotid stenosis. The groups included patients who underwent CAS for asymptomatic ischemic stroke (n=41) or symptomatic disease (n=10). Preprocedural percutaneous lidocaine injections (PPLIs) were administered to 70.6% and 5.9% of patients who underwent elective CAS and emergency CAS, respectively. Results: Among patients who received PPLIs, the mean degree of stenosis was 80.5% (95% confidence interval [CI]: ±10.74, 51–98%). The mean distance from the common carotid artery bifurcation to the most stenotic lesion (CSD) was 8.3 mm (95% CI: ±0.97, 6.3–10.2 mm); the mean angle between the internal carotid artery and common carotid artery (CCA) trunk (IAG) was 65.6° (95% CI: ±2.39, 61–70°). Among patients who did not receive PPLIs, the mean degree of stenosis was 84.0% (95% CI: ±8.96, 70–99%). The mean CSD was 5.9 mm (95% CI: ±1.83, 1.9–9.9 mm); the mean IAG was 60.4° (95% CI: ±4.41, 51–70°). The procedure time was longer in the PPLI group than in the no PPLI group (28.19 [n=39] vs. 18.88 [n=12] days) (P=0.057); the length of intensive care unit stay was shorter in the PPLI group (20.01 [n=36] vs. 28.10 [n=5] days) (P=0.132). Conclusions Targeted PPLI administration to the carotid bulb decreased aberrant heart rates and blood pressure changes induced by carotid stent deployment and balloon inflation. As CBR sensitivity increases with decreasing distance to the stenotic lesion from the CCA bifurcation, PPLIs may help stabilize patients during procedures for stenotic lesions closer to the CCA.

Progressive epidural hematoma is a form of acute epidural hematoma that graduallyexpands from a small initial hematoma; in cases that are clinically aggravated dueto the presence of a mental illness or neurological condition, patients should be surgicallytreated for evacuation of the hematoma, but poorer outcomes are expected ifthe patient has several medical co-morbidities for surgery. We experienced two casesof progressive epidural hematoma which were successfully managed by endovasculartreatment: an 85-year-old male with medical co-morbidities and a 51-year-oldfemale with a poor-grade subarachnoid hemorrhage resulting from the rupture of adissecting aneurysm of the vertebral artery. In both cases, a middle meningeal arteryembolization was performed and contrast leakage was observed and controlled usingcerebral angiography, halting the progression of their epidural hematomas. Thus,endovascular embolization of a middle meningeal artery may play a useful role in salvagetherapy in certain complicated situations that limit treatment of the hematomaby surgical evacuation.

Striatal-enriched protein tyrosine phosphatase (STEP) is abundantly expressed in the striatum, which strongly expresses dopamine and opioid receptors and mediates the effects of many drugs of abuse. However, little is known about the role of STEP in opioid receptor function. In the present study, we generated STEP-targeted mice carrying a nonsense mutation (C230X) in the kinase interaction domain of STEP by screening the N-ethyl-N-nitrosourea (ENU)-driven mutant mouse genomic DNA library and subsequent in vitro fertilization. It was confirmed that the C230X nonsense mutation completely abolished functional STEP protein expression in the brain. STEP(C230X−/−) mice showed attenuated acute morphine-induced psychomotor activity and withdrawal symptoms, whereas morphine-induced analgesia, tolerance and reward behaviors were unaffected. STEP(C230X−/−) mice displayed reduced hyperlocomotion in response to intrastriatal injection of the μ-opioid receptor agonist DAMGO, but the behavioral responses to δ- and κ-opioid receptor agonists remained intact. These results suggest that STEP has a key role in the regulation of psychomotor action and physical dependency to morphine. These data suggest that STEP inhibition may be a critical target for the treatment of withdrawal symptoms associated with morphine.
Analgesia* ; Animals ; Brain ; Codon, Nonsense ; Dopamine ; Enkephalin, Ala(2)-MePhe(4)-Gly(5)- ; Ethylnitrosourea ; Fertilization in Vitro ; Gene Library ; Mass Screening ; Mice ; Morphine* ; Phosphotransferases ; Protein Tyrosine Phosphatases ; Receptors, Opioid ; Reward* ; Street Drugs ; Substance Withdrawal Syndrome*

Compression of the airway is relatively common in pediatric patients, although it is often an unrecognized complication of congenital cardiac and aortic arch anomalies. Aortopexy has been established as a surgical treatment for tracheobronchial obstruction associated with vascular anomaly, aortic arch anomaly, esophageal atresia, and tracheoesophageal fistula. The tissue-to-tissue arch repair technique could result in severe airway complication such as compression of the left main bronchus which was not a problem before the correction. We report three cases of corrective open heart surgery monitored by intraoperative bronchoscopy performed during prebypass, and performed immediately before weaning from bypass, to evaluate tracheobronchial obstruction caused by congenital, complex cardiac anomalies in the operating room.
Airway Obstruction* ; Aorta, Thoracic ; Aortic Coarctation ; Bronchi ; Bronchoscopy* ; Esophageal Atresia ; Humans ; Operating Rooms ; Thoracic Surgery ; Tracheoesophageal Fistula ; Weaning

Ethanol sclerotherapy for the treatment of low-flow vascular malformations can cause catastrophic cardiopulmonary complications, including pulmonary embolism and pulmonary hypertension, that can result in right heart failure and fatal arrhythmias, leading to death. We here report a case of abrupt cardiovascular collapse that developed immediately following ethanol sclerotherapy in 31-year-old female patient who had a large arteriovenous malformation in her leg. Anesthesiologists should be aware of the fatal cardiopulmonary complications that are associated with ethanol sclerotherapy and consider the use of invasive hemodynamic monitoring, such as pulmonary artery pressure monitoring, when large doses of ethanol are required.
Adult ; Arrhythmias, Cardiac ; Arteriovenous Malformations ; Ethanol* ; Female ; Heart Arrest ; Heart Failure* ; Hemodynamics ; Humans ; Hypertension, Pulmonary ; Leg ; Pulmonary Artery ; Pulmonary Embolism ; Sclerotherapy* ; Vascular Malformations

The anticholinesterase pyridostigmine is usually used as a reversal agent of non-depolarizing muscle relaxants in general anesthesia. Most adverse muscarinic effects of anticholinesterases are controlled by anticholinergics; however, there is still a potential for fatal cardiac complications. We report a case of cardiac arrest associated with coronary vasospasm that developed during emergence from general anesthesia in a 61-year-old male patient undergoing uvulopalatopharyngoplasty with preoperatively undiagnosed coronary vasospastic angina. Anticholinesterases should be administered with caution for neuromuscular blockade reversal, especially in patients with coronary vasospastic angina.
Anesthesia, General ; Cholinergic Agents ; Cholinergic Antagonists ; Cholinesterase Inhibitors ; Coronary Vasospasm ; Heart Arrest* ; Humans ; Male ; Middle Aged ; Muscle Relaxation* ; Neuromuscular Blockade ; Neuromuscular Nondepolarizing Agents ; Pyridostigmine Bromide*