Synaptic effects of xenon on NMDA receptor-mediated response in rat spinal neuron.

To investigate the precise mechanism of xenon (Xe), pharmacologically isolated AMPA/KA and NMDA receptor-mediated spontaneous (s) and evoked (e) excitatory postsynaptic currents (s/eEPSCAMPA/KA and s/eEPSCNMDA) were recorded from mechanically isolated single spinal sacral dorsal commissural nucleus (SDCN) neurons attached with glutamatergic nerve endings (boutons) using conventional whole-cell patch-clamp technique. We analysed kinetic properties of both s/eEPSCAMPA/KA and s/eEPSCNMDA by focal single- and/or paired-pulse electrical stimulation to compare them. The s/eEPSCNMDA showed smaller amplitude, slower rise time, and slower 1/e decay time constant (τDecay) than those of s/eEPSCAMPA/KA. We previously examined how Xe modulates s/eEPSCAMPA/KA, therefore, examined the effects on s/eEPSCNMDA in the present study. Xe decreased the frequency and amplitude of sEPSCNMDA, and decreased the amplitude but increased the failure rate and paired-pulse ratio of eEPSCNMDA without affecting their τDecay. It was concluded that Xe might suppress NMDA receptor-mediated synaptic transmission via both presynaptic and postsynaptic mechanisms.

Epidural, Inadvertent Subdural, and Combined Epidural-Subdural Anesthesia in Lumbar Spine Surgery: A Retrospective Analysis.

This study aimed to categorize contrast media images associated with epidural, subdural, and combined epidural-subdural anesthesia in patients who had undergone fluoroscopy-guided epidural anesthesia using contrast media combined with monitored anesthesia care (MAC) targeted at deep sedation, incorporating capnography over 5 years. Additionally, a correlation was established between the anesthetic effects and radiographic findings according to the categorized imaging appearances. This study included 628 patients who underwent endoscopic, open, or fusion surgery under epidural anesthesia at Nanoori Hospital in Gangnam between March 2018 and September 2023. Fluoroscopy-guided epidural anesthesia using contrast media combined with MAC and capnography was used. The dataset included detailed radiographic imaging, nursing, and anesthesia records. Distinct patterns of anesthesia administration were observed, with 49%, 19.6%, and 31% of patients receiving epidural, subdural, and combined epidural-subdural anesthesia, respectively. The incidence and duration of motor block were significantly different among the three groups. Additionally, subdural anesthesia displayed a higher incidence of motor block and a prolonged motor deficit duration than epidural anesthesia. Fluoroscopic guidance using a contrast medium for epidural and subdural anesthesia ensures precise space identification and prevents serious anesthetic complications. Our findings suggest the potential to achieve stable anesthesia, particularly using subdural and combined epidural-subdural anesthesia.

Comparison of En Masse Repair versus Separate Double-Layer Repair for Delaminated Rotator Cuff Tears: A Systematic Review and Meta-Analysis.

BACKGROUND: Delamination of cuff tendons has a negative impact on outcomes following arthroscopic rotator cuff repair (RCR). The purpose of this study is to compare en masse repair (EMR) and separate double-layer repair (SDLR) for delaminated rotator cuff tears. METHODS: A systematic literature search was conducted on major databases (MEDLINE/PubMed, EMBASE, Cochrane Library, and Scopus) until 1 June 2023. Comparative studies with a minimum 24-month follow-up of patients undergoing arthroscopic RCR for delaminated tears were included. The outcomes assessed retear rates and functional outcomes. RESULTS: Five eligible studies involving 325 cases were analyzed. The meta-analysis showed no significant difference in retear rates between SDLR and EMR for delaminated tears (OR = 0.73, 95% CI: 0.35-1.49). However, the meta-analysis demonstrated a significant intergroup difference in favor of the SDLR for the total Constant score (SMD = 0.68, 95% CI: 0.35 to 1.02), SST score (SMD = 0.37, 95% CI: 0.02 to 0.71), and postoperative range of abduction (SMD = 0.34, 95% CI: 0.03 to 0.64). CONCLUSION: The evidence suggests that the SDLR in arthroscopic RCR for delaminated rotator cuff tears leads to improved short-term functional outcomes and range of motion compared to EMR. However, there is no significant difference in retear risk between the two approaches.

Sarcopenia as the Mobility Phenotype of Aging: Clinical Implications.

Sarcopenia, which is characterized by an age-related decline in muscle mass and function, poses significant challenges to geriatric care. Its definition has evolved from muscle-specific criteria to include muscle mass, muscle function, and physical performance, recognizing sarcopenia as a physical frailty. Sarcopenia is associated with adverse outcomes, including mortality, falls, fractures, cognitive decline, and admission to long-term care facilities. Neuromechanical factors, protein-energy balance, and muscle protein synthesis-breakdown mechanisms contribute to its pathophysiology. The identification of sarcopenia involves screening tests and a comprehensive assessment of muscle mass, strength, and physical function. Clinical approaches aligned with the principles of comprehensive geriatric assessment prioritize patient-centered care. This assessment aids in identifying issues related to activities of daily living, cognition, mood, nutrition, and social support, alongside other aspects. The general approach to factors underlying muscle loss and functional decline in patients with sarcopenia includes managing chronic diseases and evaluating administered medications, with interventions including exercise and nutrition, as well as evolving pharmacological options. Ongoing research targeting pathways, such as myostatin-activin and exercise mimetics, holds promise for pharmacological interventions. In summary, sarcopenia requires a multifaceted approach, acknowledging its complex etiology and tailoring interventions to individual patient needs.

Frailty is not an independent risk factor for worse clinical outcomes in lumbar spinal surgery: a prospective cohort study.

PURPOSE: Recently, many studies revealed that frailty affects unfavorably on postoperative outcomes in lumbar spinal diseases. This study aimed to investigate the relationship between frailty and clinical outcomes while identifying risk factors associated with worse clinical outcomes following lumbar spinal surgery. METHODS: From March 2019 to February 2021, we prospectively enrolled eligible patients with degenerative lumbar spinal diseases requiring surgery. Frailty was assessed preoperatively. To identify the impact of frailty on lumbar spinal diseases, clinical outcomes, which were measured with patient-reported outcomes (PROs) and postoperative complications, were compared according to the frailty. PROs were assessed preoperatively and one year postoperatively. In addition, risk factors for preoperative and postoperative worse clinical outcomes were investigated. RESULTS: PROs were constantly lower in the frail group than in the non-frail group before and after surgery, and the change of PROs between before and after surgery and postoperative complications were not different between the groups. In addition, frailty was a persistent risk factor for postoperative worse clinical outcome before and after surgery in lumbar spinal surgery. CONCLUSION: Frailty persistently affects the clinical outcome negatively before and after surgery in lumbar spinal surgery. However, as the change of the clinical outcome is not different between the frail group and the non-frail group, it is difficult to interpret whether the frail patients are vulnerable to the surgery. In conclusion, frailty is not an independent risk factor for worse clinical outcome in lumbar spinal surgery.

Serratus Anterior Plane Block: A Better Modality of Pain Control after Pectus Excavatum Repair.

Background: Postoperative pain management following minimally invasive repair of pectus excavatum (MIRPE) remains a critical concern due to severe post-procedural pain. Promising results have been reported for cryoanalgesia following MIRPE; however, its invasiveness, single-lung ventilation, and additional instrumentation requirements remain obstacles. Serratus anterior plane block (SAPB) is a regional block technique capable of covering the anterior chest wall at the T2-9 levels, which are affected by MIRPE. We hypothesized that SAPB would be a superior alternative pain control modality that reduces postoperative pain more effectively than conventional methods. Methods: We conducted a retrospective study of patients who underwent MIRPE between March 2022 and August 2023. The efficacy of pain control was compared between group N (conventional pain management, n=24) and group S (SAPB, n=26). Group N received intravenous patient-controlled analgesia (IV-PCA) and subcutaneous local anesthetic infusion. Group S received bilateral continuous SAPB with 0.3% ropivacaine after a bilateral bolus injection of 30 mL of 0.25% ropivacaine with baseline IV-PCA. Pain levels were evaluated using a Visual Analog Scale (VAS) at 1, 3, 6, 12, 24, 48, and 72 hours postoperatively and total intravenous rescue analgesic consumption by morphine milligram equivalents (MME). Results: Mean VAS scores were significantly lower in group S than in group N throughout the 72-hour postoperative period (p<0.01). Group S showed significantly lower MME at postoperative 72 hours (group N: 108.53, group S: 16.61; p<0.01). Conclusion: SAPB improved immediate postoperative pain control in both the resting and dynamic states and reduced opioid consumption compared to conventional management.

Smartphone application-based rehabilitation in patients with chronic respiratory and cardiovascular diseases.

Rehabilitation improves symptoms, quality of life, and survival in patients with chronic respiratory or cardiovascular disease. We evaluated smartphone application-based rehabilitation programs for patients with chronic respiratory or cardiovascular diseases. This was a single-center prospective single arm study. Participants underwent smartphone application-based pulmonary or cardiac rehabilitation for 12 weeks. A total of 93 participants were recruited, and 75 visited after rehabilitation. Their median age was 67.0 (interquartile range, 60.0-70.8) years, and 60 (80.0%) were men. For patients with chronic respiratory disease (n = 41), VO2peak (median 13.7 to 15.4 ml/kg/min, P = 0.049), chronic obstructive pulmonary disease assessment test (median 14 to 6, P < 0.001), Euro-QoL 5-Dimension 5-Level (EQ-5D-5L) index (median 0.795 to 0.862, P = 0.001), and Health-related Quality of Life Instrument with 8 Items (HINT-8) index (median 0.784 to 0.855, P < 0.001) were significantly improved. For patients with chronic cardiovascular disease (n = 34), VO2peak (median 21.8 to 23.3, P = 0.007), EQ-5D-5L index (median 0.871 to 1.000, P = 0.037), and HINT-8 index (median 0.890 to 0.903, P < 0.001) were significantly improved. The smartphone application-based rehabilitation program improved exercise capacity and quality of life in patients with chronic respiratory or cardiovascular disease.Trial registration: https://clinicaltrials.gov/ct2/show/NCT05383950 (20/05/2022).

Outcomes of Superior Capsular Reconstruction Using the Long Head of the Biceps Tendon in Large to Massive Rotator Cuff Tears: A Meta-Analysis and Systematic Review.

(1) Background: Addressing large to massive rotator cuff tears (LMRCTs) poses complex challenges. This systematic review investigated outcomes of superior capsular reconstruction (SCR) with the long head of the biceps tendon (LHBT) compared to conventional rotator cuff repair (RCR) for LMRCTs. (2) Methods: A systematic search across the MEDLINE/PubMed, EMBASE, Cochrane Library, and Scopus databases until 1 October 2023 identified studies that directly compared SCR with LHBT with conventional RCR in patients with LMRCTs and included a minimum of a 12-month follow-up period. The assessed outcome measures encompassed retear rates, functional outcomes, range of motion (ROM), and acromiohumeral interval (AHI). Risk of bias assessment was conducted via the Robins-I tool. (3) Results: In six studies with 456 cases (210 SCR using LHBT and 246 using RCR), SCR with LHBT significantly reduced retear rates (OR = 0.21; 95% CI, 0.12-0.36; p < 0.01; I2 = 0%). Furthermore, SCR with LHBT showed significant improvement in range of forward flexion (SMD 0.32, 95% CI: 0.09-0.55, p < 0.01, I2 = 39%) and AHI (SMD 0.61, 95% CI: 0.31-0.92, p < 0.01, I2 = 0%) postoperatively. (4) Conclusion: SCR with LHBT is a safe and effective treatment for LMRCTs, reducing retear rates, maintaining greater postoperative AHI, and improving ROM compared to conventional RCR. Additional high-quality interventional studies are needed to confirm these results.

Effect of Bone Marrow Stimulation on Arthroscopic Rotator Cuff Repair: A Systematic Review and Meta-analysis.

Background: Arthroscopic rotator cuff repair (RCR) is a common orthopaedic procedure, but it has a high rate of retears that can negatively affect the functional outcomes. Bone marrow stimulation (BMS) has been suggested as an additional treatment to improve the outcomes of RCR. Purpose: To compare the effectiveness of the BMS procedure during RCR with conventional RCR. Study Design: Systematic review; Level of evidence, 2. Methods: A systematic literature search was conducted in MEDLINE/PubMed, Embase, Cochrane Library, and Scopus, on March 1, 2023, for studies comparing postoperative retear rates and functional outcomes between patients who underwent primary arthroscopic RCR with and without the BMS procedure. Only level 1 and 2 randomized controlled trials with a minimum 12-month follow-up were included. The primary outcomes were retear rates and functional outcomes as measured by the Constant; American Shoulder and Elbow Surgeons (ASES); and University of California, Los Angeles (UCLA) scores and by postoperative range of motion. Subgroup analyses were performed based on repair technique (single-row repair vs double-row or suture-bridge repair). The standardized mean difference (SMD) and odds ratio (OR) were utilized to synthesize continuous and dichotomous outcomes, respectively. Homogeneity was evaluated using the chi-square test and I2 statistic. Results: The literature search yielded 661 articles, of which 6 studies (522 patients; 261 with BMS, 261 without BMS) met the eligibility criteria. The combined analysis showed no significant decrease in retear rates with the utilization of the BMS procedure during RCR (OR, 0.60; 95% CI, 0.35 to 1.03; P = .07; I2 = 24%). There was no significant intergroup difference in functional outcomes (Constant score: SMD, 0.13; 95% CI, -0.04 to 0.31; P = .13; I2 = 0%; ASES score: SMD, 0.04; 95% CI, -0.20 to 0.28; P = .73; I2 = 0%; UCLA score: SMD, -0.13; 95% CI, -0.50 to 0.23; P = .47; I2 = 0%). Subgroup analyses revealed no significant differences in postoperative retear risk or total Constant score according to the repair technique. Conclusion: Based on the available evidence, this systematic review did not find a significant benefit of the BMS procedure at the footprint during arthroscopic RCR compared with conventional RCR in terms of retear rates and functional outcomes at short-term follow-up.

Advantages of laparoscopy in gynecologic surgery in elderly patients.

OBJECTIVE: Geriatric patients requiring gynecological surgery is increasing worldwide. However, older patients are at higher risk of postoperative morbidity and mortality, particularly cardiopulmonary complications. Laparoscopic surgery is widely used as a minimally invasive method for reducing postoperative morbidities. We compared the outcomes of open and laparoscopic gynecologic surgeries in patients older than 55 years. METHODS: We included patients aged >55 years who underwent gynecological surgery at a single tertiary center between 2010 and 2020, excluding vaginal or ovarian cancer surgeries were excluded. Surgical outcomes were compared between the open surgery and laparoscopic groups, with age cutoff was set at 65 years for optimal discriminative power. We performed linear or logistic regression analyses to compare the surgical outcomes according to age and operation type. RESULTS: Among 2,983 patients, 28.6% underwent open surgery and 71.4% underwent laparoscopic surgery. Perioperative outcomes of laparoscopic surgery were better than those of open surgery in all groups. In both the open and laparoscopic surgery groups, the older patients showed worse overall surgical outcomes. However, age-related differences in perioperative outcomes were less severe in the laparoscopic group. In the linear regression analysis, the differences in estimated blood loss, transfusion, and hospital stay between the age groups were smaller in the laparoscopy group. Similar restuls were observed in cancer-only and benign-only cohorts. CONCLUSION: Although the surgical outcomes were worse in the older patients, the difference between age groups was smaller for laparoscopic surgery. Laparoscopic surgery offers more advantages and safety in patients aged >65 years.

Circulating lumican as a potential biomarker for osteosarcopenia in older adults.

In vitro and animal experiments demonstrated that lumican exerts anabolic effects on bone and muscle by stimulating osteoblastogenesis, suppressing osteoclastogenesis and increasing myogenesis. However, the relationship between circulating lumican and musculoskeletal phenotypes in humans remains unclear. We aimed to analyze the relationship between serum lumican levels and osteosarcopenia in older adults. Blood samples were collected from 134 participants (age: 65 years and older) who underwent comprehensive assessment of bone and muscle phenotypes. Osteoporosis and sarcopenia were diagnosed based on World Health Organization and Asian consensus guidelines, respectively. Osteosarcopenia was defined as the simultaneous presence of osteoporosis and sarcopenia. After adjusting for sex, age, and body mass index, older adults with osteosarcopenia had 20.2 % lower serum lumican levels than those without (P = 0.010). The odds ratio (OR) for osteosarcopenia per standard deviation decrease in serum lumican level was 4.17 (P = 0.003). Consistently, higher serum lumican levels were correlated with higher bone mass at all measured sites (P = 0.004 to 0.045) and higher grip strength (P = 0.023). Furthermore, participants in the lowest tertile (T1) had 7.56-fold higher OR for osteosarcopenia (P = 0.024) than those in the highest lumican tertile (T3). In conclusion, these findings clinically validate previous experimental data showing the musculoskeletal protective effects of lumican and suggest that blood lumican levels could be used as a potential biomarker to assess the risk of not only osteosarcopenia but also osteoporosis or sarcopenia in older adults.

Narrative Review of Uniportal Posterior Endoscopic Cervical Foraminotomy.

Cervical radiculopathy is a common and disabling cervical condition characterized by symptoms including axial neck pain, radicular pain, weakness, and numbness in one or both arms. Common causes include herniated discs and foraminal stenosis, often accompanied by varying degrees of degenerative disc disease and uncovertebral joint hypertrophy. In the treatment of cervical radiculopathy, there is an increasing preference for posterior foraminotomy over anterior cervical discectomy and fusion due to the avoidance of fusion-related complications. As endoscopic spine surgery techniques continue to evolve, there is a rising interest in posterior endoscopic cervical foraminotomy and posterior endoscopic cervical discectomy as effective treatments for cervical radiculopathy. Because these procedures can performed through a single subcentimeter incision with minimal soft tissue damage, they can often be carried out as ambulatory procedures. In this narrative review, we examined current literature addressing the indications, surgical techniques, outcomes, and potential complications associated with posterior cervical endoscopic approaches.

Phenotype validation of the Korean working group on sarcopenia guideline.

BACKGROUND: This study aimed to validate the proposed Korean Working Group on Sarcopenia (KWGS) guideline, which introduces the concept of functional sarcopenia, in older Korean adults. METHODS: Data from the Aging Study of Pyeongchang Rural Area, a longitudinal cohort of community-dwelling older adults, were utilized to compare frailty status and institutionalization-free survival among participants according to sarcopenia status. Based on the KWGS guideline, severe sarcopenia was defined as low muscle mass and strength with slow gait speed; sarcopenia (not severe) was defined as low muscle mass with low muscle strength or slow gait speed; and functional sarcopenia was defined as low muscle strength and slow gait speed without low muscle mass. RESULTS: Among the 1302 participants, 329 (25.3 %) had severe sarcopenia, 147 (11.3 %) had sarcopenia (not severe), and 277 (21.3 %) had functional sarcopenia. Frailty was significantly greater in participants with any phenotype of sarcopenia than in those without sarcopenia. Additionally, participants with functional sarcopenia were frailer than those with sarcopenia (not severe). Furthermore, the rates of institutionalization and mortality were higher in participants with any phenotype of sarcopenia than in those without sarcopenia. There was no statistical difference between the rates of sarcopenia (not severe) and those with functional sarcopenia. These findings remained consistent after adjusting for age and sex. CONCLUSIONS: Each phenotype according to the KWGS guideline was associated with significantly greater frailty and increased risk of institutionalization and mortality. Functional sarcopenia was associated with greater frailty and had comparable prognosis with sarcopenia (not severe).

Functional modulation of lysophosphatidic acid type 2 G-protein coupled receptor facilitates alveolar bone formation.

Lipid biosynthesis is recently studied its functions in a range of cellular physiology including differentiation and regeneration. However, it still remains to be elucidated in its precise function. To reveal this, we evaluated the roles of lysophosphatidic acid (LPA) signaling in alveolar bone formation using the LPA type 2 receptor (LPAR2) antagonist AMG-35 (Amgen Compound 35) using tooth loss without periodontal disease model which would be caused by trauma and usually requires a dental implant to restore masticatory function. In this study, in vitro cell culture experiments in osteoblasts and periodontal ligament fibroblasts revealed cell type-specific responses, with AMG-35 modulating osteogenic differentiation in osteoblasts in vitro. To confirm the in vivo results, we employed a mouse model of tooth loss without periodontal disease. Five to 10 days after tooth extraction, AMG-35 facilitated bone formation in the tooth root socket as measured by immunohistochemistry for differentiation markers KI67, Osteocalcin, Periostin, RUNX2, transforming growth factor beta 1 (TGF-ß1) and SMAD2/3. The increased expression and the localization of these proteins suggest that AMG-35 elicits osteoblast differentiation through TGF-ß1 and SMAD2/3 signaling. These results indicate that LPAR2/TGF-ß1/SMAD2/3 represents a new signaling pathway in alveolar bone formation and that local application of AMG-35 in traumatic tooth loss can be used to facilitate bone regeneration and healing for further clinical treatment.

ALiGN: Attention based Line Guided Network for Vertebral Comprssion Fracture Detection.

Vertebral Compression Fracture (VCF) is one of the common fractures, especially for elderlies. As it affects postural deformation that may cause secondary disorders in the respiratory or digestive system if not treated in time, diagnosis of VCF is crucial. Using deep learning model based detection technology in diagnosis can reduce the workload of healthcare workers and misdiagnosis. Hence in this work, we propose ALiGN, a compression fracture detection model in the lumbar vertebra based on a deep convolutional neural network (CNN). Specifically, we take the location of each vertebral body into account via a feature pyramid network with an attention mechanism. Our proposed model outperforms the earlier works with a sensitivity 0.9729, specificity 0.9914, and mAP 0.7882.

Adverse Effect of the Duration of Antibiotic Use Prior to Immune Checkpoint Inhibitors on the Overall Survival of Patients with Recurrent Gynecologic Malignancies.

PURPOSE: Antibiotic use preceding immune checkpoint inhibitor (ICI) treatment has been associated with a decreased efficacy of ICI in solid tumors. In this study, we evaluated the effect of antibiotic use before ICI therapy on oncological outcomes. METHODS: We examined patients with recurrent gynecologic malignancies at two academic institutions. The clinical data, including antibiotic use within 60 days of ICI initiation, type of antibiotics, reasons for antibiotic use, body mass index, tumor site, chemotherapy-free interval, prior history of radiotherapy, disease control rate (DCR), and overall survival (OS), were assessed. RESULTS: Of 215 patients, 22.9% (n = 47) received antibiotics before ICI treatment. The most common cancer was ovarian (52.1%, n = 112), followed by cervical (24.7%, n = 53) and endometrial (16.7%, n = 36). When we divided the cohort based on antibiotic use before ICIs, there were no significant differences in the DCR and baseline characteristics between the two groups. On multivariate analyses, the variables associated with poor OS were previous use of antibiotics for a cumulative duration of >14 days (HR 2.286, 95% CI 1.210-4.318; p = 0.011); Eastern Cooperative Oncology Group 2 or 3 (HR 4.677, 95% CI 2.497-8.762; p < 0.001); and chemotherapy-free interval of <6 months (HR 2.007, 95% CI 1.055-3.819; p = 0.034). CONCLUSION: Prior use of antibiotics for a cumulative duration of >14 days was associated with reduced survival in recurrent gynecologic malignancies.

Ibuprofen modulates tetrodotoxin-resistant persistent Na+ currents at acidic pH in rat trigeminal ganglion neurons.

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to relieve various symptoms such as headache, arthralgia, and dental pain. While the primary mechanism of NSAID-based pain relief is the inhibition of cyclooxygenase-2, several NSAIDs also modulate other molecular targets related to nociceptive transmission such as voltage-gated Na+ channels. In the present study, we examined the effects of NSAIDs on persistent Na+ current (INaP) mediated by tetrodotoxin-resistant (TTX-R) Na+ channels in small-to medium-sized trigeminal ganglion neurons using a whole-cell patch-clamp technique. At clinically relevant concentrations, all propionic acid derivatives tested (ibuprofen, naproxen, fenoprofen, and flurbiprofen) preferentially inhibited the TTX-R INaP. The inhibition was more potent at acidic extracellular pH (pH 6.5) than at normal pH (pH 7.4). Other NSAIDs, such as ketorolac, piroxicam, and aspirin, had a negligible effect on the TTX-R INaP. Ibuprofen both accelerated the onset of inactivation and retarded the recovery from inactivation of TTX-R Na+ channels at acidic extracellular pH. However, all NSAIDs tested in this study had minor effects on voltage-gated K+ currents, as well as hyperpolarization-activated and cyclic nucleotide-gated cation currents, at both acidic and normal extracellular pH. Under current-clamp conditions, ibuprofen decreased the number of action potentials elicited by depolarizing current stimuli at acidic (pH 6.5) extracellular pH. Considering that extracellular pH falls as low as 5.5 in inflamed tissues, TTX-R INaP inhibition could be a mechanism by which ibuprofen and propionic acid derivative NSAIDs modulate inflammatory pain.

Comparison of Prophylactic Effects between Localized Biomimetic Minocycline and Systematic Amoxicillin on Implants Placed Immediately in Infected Sockets.

This study evaluated the prophylactic effect of localized biomimetic minocycline and systemic amoxicillin on immediate implant placement at infected extraction sites. Twelve mongrels with six implants each were randomly assigned to five groups: uninfected negative control (Group N); infected with oral complex bacteria (Group P); infected and treated with amoxicillin one hour before implant placement (Group A); infected and treated with minocycline during implant placement (Group B); and infected and treated with amoxicillin one hour before implant placement and with minocycline during implant placement (Group C). Radiographic bone level, gingival index (GI), probing depth (PD), papillary bleeding index (PBI), and removal torque (RT) were recorded. There was no significant difference between Groups A, B, and C for bone loss. Group A showed the highest RT, the lowest PBI, and significantly lower GI and PD values than Group P. Group B exhibited significantly higher RT value than Group N and significantly smaller PD value than Group P at 6 w postoperatively. Localized minocycline could improve implant success by reducing bone loss and increasing RT and systemic amoxicillin could maintain the stability of the peri-implant soft tissue. However, combined use of these two antibiotics did not augment the prophylactic effect.

Periodontitis promotes bacterial extracellular vesicle-induced neuroinflammation in the brain and trigeminal ganglion.

Gram-negative bacteria derived extracellular vesicles (EVs), also known as outer membrane vesicles, have attracted significant attention due to their pathogenic roles in various inflammatory diseases. We recently demonstrated that EVs secreted by the periodontopathogen Aggregatibacter actinomycetemcomitans (Aa) can cross the blood-brain barrier (BBB) and that their extracellular RNA cargo can promote the secretion of proinflammatory cytokines, such as IL-6 and TNF-α, in the brain. To gain more insight into the relationship between periodontal disease (PD) and neuroinflammatory diseases, we investigated the effect of Aa EVs in a mouse model of ligature-induced PD. When EVs were administered through intragingival injection or EV-soaked gel, proinflammatory cytokines were strongly induced in the brains of PD mice. The use of TLR (Toll-like receptor)-reporter cell lines and MyD88 knockout mice confirmed that the increased release of cytokines was triggered by Aa EVs via TLR4 and TLR8 signaling pathways and their downstream MyD88 pathway. Furthermore, the injection of EVs through the epidermis and gingiva resulted in the direct retrograde transfer of Aa EVs from axon terminals to the cell bodies of trigeminal ganglion (TG) neurons and the subsequent activation of TG neurons. We also found that the Aa EVs changed the action potential of TG neurons. These findings suggest that EVs derived from periodontopathogens such as Aa might be involved in pathogenic pathways for neuroinflammatory diseases, neuropathic pain, and other systemic inflammatory symptoms as a comorbidity of periodontitis.