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.

Background/Aims: Lactase deficiency, which has many similarities with small intestinal bacterial overgrowth (SIBO), causes various gastrointestinal symptoms. We estimate the prevalence of SIBO in patients with intestinal symptoms from dairy products and investigate the association between lactase deficiency (LD) and SIBO. Methods: This prospective study included patients with functional intestinal symptoms from dairy product indigestion. A questionnaire on gastrointestinal symptoms, a hydrogen (H 2 )-methane glucose breath test (GBT) for SIBO, and lactose intolerance quick test (LQT) for LD using upper gastrointestinal endoscopy were performed. Results: A total of 88 patients, 29 (33.0%) with severe and 36 (40.9%) with mild LD were included. Sixteen patients (18.2%) were GBT positive. Patients with LQT negativity indicating severe LD showed a higher positivity to GBT or GBT (H 2 ) than the historic controls (27.6% vs 6.7%, P = 0.032). There was no difference in the items on the symptom questionnaire according to the presence of LD or SIBO, except for higher symptom scores for urgency in GBT-positive patients. There were more LQT-negative patients in the GBT (H 2 )-positive group than in the other groups (27.6% vs 10.2%, P = 0.036). Moreover, only GBT (H 2 )-positivity was significantly associated with a higher risk of LQT negativity in multivariate analysis (OR, 4.19; P = 0.029). Conclusions SIBO producing H 2is common in patients with severe LD suspected lactose intolerance. SIBO may be a new therapeutic target for managing intestinal symptoms in patients with lactose intolerance.

Various probiotic strains have been reported to affect emotional behavior. However, the underlying mechanisms by which specific probiotic strains change brain function are not clearly understood. Here, we report that extracellular vesicles derived from Lactobacillus paracasei (Lpc-EV) have an ability to produce genome-wide changes against glucocorticoid (GC)-induced transcriptional responses in HT22 hippocampal neuronal cells. Genome-wide analysis using microarray assay followed by Rank-Rank Hypergeometric Overlap (RRHO) method leads to identify the top 20%-ranked 1,754 genes up- or down-regulated following GC treatment and their altered expressions are reversed by Lpc-EV in HT22 cells. Serial k-means clustering combined with Gene Ontology enrichment analyses indicate that the identified genes can be grouped into multiple functional clusters that contain functional modules of “responses to stress or steroid hormones”, “histone modification”, and “regulating MAPK signaling pathways”. While all the selected genes respond to GC and Lpc-EV at certain levels, the present study focuses on the clusters that contain Mkp-1, Fkbp5, and Mecp2, the genes characterized to respond to GC and Lpc-EV in opposite directions in HT22 cells. A translational study indicates that the expression levels of Mkp-1, Fkbp5, and Mecp2 are changed in the hippocampus of mice exposed to chronic stress in the same directions as those following GC treatment in HT22 cells, whereas Lpc-EV treatment restored stress-induced changes of those factors, and alleviated stress-induced depressive-like behavior. These results suggest that Lpc-EV cargo contains bioactive components that directly induce genome-wide transcriptional responses against GC-induced transcriptional and behavioral changes.

Background and Objectives: To analyze mapping changes in dynamic range (DR) and neural response threshold (NRT) as prognostic factors for cochlear implant (CI). To analyze whether postoperative speech perception performance could be predicted using DR change and initial NRT. Subjects and Methods: The speech comprehension data of 33 patients with CI were retrospectively analyzed after 1, 3, 6, and 12 months of device use. All subjects were adult, postlingually hearing-impaired, and Cochlear Nucleus CI users. Speech perception performance was evaluated using aided pure tone audiometry, consonant, vowel, one-word, two-word, and sentence tests. Results: The averages of initial NRT and DR changes were 197.8±25.9 CU (104–236) and 22.2±18.4 CU (-15–79), respectively. The initial DR was 40.8±16.6 CU. The postoperative DR was 50.3±16.4 CU at 3 months, 58±12.3 CU at 6 months, and 62.9±10.4 CU at 12 months. A gradual increase of DR was observed during the first year of CI. Compared with the initial DR, significant increases in DR were observed at 3 (p<0.05), 6 (p<0.001), and 12 (p<0.001) months. Compared with initial speech performance outcomes, a significant gain in all performance outcomes was achieved at 12 months (p<0.001). Conclusions Patients with low NRT after CI surgery could initially set DR to a wider range and had better final speech perception outcomes. Conversely, patients with high NRT after CI surgery had to set up a gradual increase in DR while adjusting the T-C level, and the final speech perception outcomes were worse. DR and NRT, the main CI mapping variables, can help predict prognosis related to speech perception outcomes after CI surgery. In conclusion, the post-CI speech perception is better with a lower initial NRT, wider final DR, or younger age.

Although patellofemoral arthritis is a common and debilitating orthopedic disorder, its treatment varies and remains controversial. This review aims to provide an overview of the current understanding of the pathophysiology of patellofemoral arthritis, as well as its various diagnostic and treatment options.Current Concepts: The pathophysiology of patellofemoral arthritis includes lower limb malalignment, trochlear and/or patellar dysplasia, patellar instability, trauma, and obesity. The disorder is characterized by chronic anterior knee pain aggravated by flexion of the knee joint. A critical imaging study of the Merchant and lateral knee radiographs may show the progression of patellofemoral arthritis and dysplasia of the patellofemoral joints. Non-pharmacologic treatment options for patellofemoral arthritis include patient education, self-management, exercise, weight loss, taping, bracing, and orthotics. Pharmacologic agents (non-steroidal anti-inflammatory drugs, acetaminophen, oral narcotics, and duloxetine) and intra-articular injection therapies (glucocorticoids, hyaluronic acid, platelet-rich plasma, and other regenerative therapies) can be helpful for symptom relief in patients with patellofemoral arthritis. The surgical treatment can begin with lateral retinacular release to realign and decompress the patellofemoral joint. If failure in the improvement of symptoms is noted, a tibial tubercle osteotomy can be considered in young and active patients. While the early design and technique of patellofemoral arthroplasty were less than encouraging, more recent implant design and surgical techniques have demonstrated robust results.Discussion and Conclusion: Patellofemoral arthritis is a unique entity compared with tibiofemoral arthritis marked by distinct epidemiology, biomechanics, and risk factors and treatment options. It is essential to understand its pathophysiology and ensure proper treatment options.

BACKGROUND: Inflammatory bowel disease (IBD) is an incurable disease that negatively influences the quality of life of patients. Current and emerging therapies target proinflammatory cytokines and/or receptors to downregulate proinflammatory responses, but insufficient remission requires other therapeutic agents. Herein, we report that the synthetic antiinflammatory peptide 15 (SAP15) is capable of cell penetration and anti-inflammatory activity in human macrophages. METHODS: SAP15 was labeled with fluorescence and administered to human leukemia monocytic cells (THP-1) cells for cell penetration analysis. Using biolayer interferometry analysis, the binding affinity of SAP15 with histone deacetylase 5 (HDAC5) was measured. SAP15-treated THP-1 cells were analyzed by protein phosphorylation assay, flow cytometry, and enzyme-linked immunosorbent assay (ELISA). In addition, in vivo analysis of the therapeutic effect on IBD was observed in a dextran sulfate sodium (DSS)-induced model. Samples from SAP15-treated mice were analyzed at both the macroscopic and microscopic levels using ELISA, myeloperoxidase (MPO) assays, and histological evaluations. RESULTS: SAP15 was internalized within the cytosol and nucleus of THP-1 cells and bound to the HDAC5 protein. SAP15-treated macrophages were assessed for protein phosphorylation and showed inhibited phosphorylation of HDAC5 and other immune-related proteins, which led to increased M2-like macrophage markers and decreased M1-like macrophage markers and tumor necrosis factor-a and interleukin-6 cytokine levels. The SAP15 treatment on IBD model showed significant recovery of colon length. Further histological analysis of colon demonstrated the therapeutic effect of SAP15 on mucosal layer. Moreover, proinflammatory cytokine levels and MPO activity from the plasma show that SAP15 is effective in reduced proinflammatory responses. CONCLUSION These findings suggest that SAP15 is a novel peptide with a novel cell-penetrating peptide with antiinflammatory property that can be used as a therapeutic agent for IBD and other inflammatory diseases.