Differential Diagnosis of OKC and SBC on Panoramic Radiographs: Leveraging Deep Learning Algorithms.

This study aims to determine whether it can distinguish odontogenic keratocyst (OKC) and simple bone cyst (SBC) based solely on preoperative panoramic radiographs through a deep learning algorithm. (1) Methods: We conducted a retrospective analysis of patient data from January 2018 to December 2022 at Pusan National University Dental Hospital. This study included 63 cases of OKC confirmed by histological examination after surgical excision and 125 cases of SBC that underwent surgical curettage. All panoramic radiographs were obtained utilizing the Proline XC system (Planmeca Co., Helsinki, Finland), which already had diagnostic data on them. The panoramic images were cut into 299 × 299 cropped sizes and divided into 80% training and 20% validation data sets for 5-fold cross-validation. Inception-ResNet-V2 system was adopted to train for OKC and SBC discrimination. (2) Results: The classification network for diagnostic performance evaluation achieved 0.829 accuracy, 0.800 precision, 0.615 recall, and a 0.695 F1 score. (4) Conclusions: The deep learning algorithm demonstrated notable accuracy in distinguishing OKC from SBC, facilitated by CAM visualization. This progress is expected to become an essential resource for clinicians, improving diagnostic and treatment outcomes.

Effect of Surgeon-Performed Thoracic Paravertebral Block on Postoperative Pain in Adolescent Idiopathic Scoliosis Surgery: A Prospective Randomized Controlled Trial.

Posterior spinal fusion for adolescent idiopathic scoliosis (AIS) causes severe postoperative pain. Thoracic paravertebral block (PVB) provides excellent analgesia during various surgeries. We examined the effects of PVB on postoperative analgesia in children undergoing AIS surgery. In this study, 32 children scheduled for AIS surgery were randomly assigned to receive either PVB (PVB group) or no block (control group). The PVB group underwent surgeon-performed PVB with 0.5 mL/kg of adrenalized 0.2% ropivacaine on each side. The primary outcome was the pain score at rest at 6 h postoperatively. Secondary outcomes included pain scores both at rest and during movement and analgesic use for 48 h postoperatively. The postoperative resting pain scores at 6 h were comparable between the control and PVB groups (5.2 ± 2.0 and 5.1 ± 1.8, respectively), with no significant differences. However, at 1 h postoperatively, the control group showed significantly higher resting and mean moving pain scores than the PVB group (p < 0.05). The pain scores at other time points and analgesic use were comparable between the groups. Initial benefits of surgeon-performed bilateral PVB were observed but diminished at 6 h postoperatively. Future research using various anesthetics is needed to extend the effects of PVB.

Continuous Superior Trunk Block versus Single-Shot Superior Trunk Block with Intravenous Dexmedetomidine for Postoperative Analgesia in Arthroscopic Shoulder Surgery: A Prospective Randomized Controlled Trial.

Background/Objectives: Intravenous dexmedetomidine (DEX) can increase the analgesia duration of peripheral nerve block; however, its effect in combination with superior trunk block (STB) remains unclear. We examined whether combining single-shot STB (SSTB) with intravenous DEX would provide noninferior postoperative analgesia comparable to that provided by continuous STB (CSTB). Methods: Ninety-two patients scheduled for elective arthroscopic rotator cuff repair were enrolled in this prospective randomized trial. Patients were randomly assigned to the CSTB or SSTB + DEX group. Postoperatively, each CSTB group patient received 15 mL of 0.5% ropivacaine and a continuous 0.2% ropivacaine infusion. Each SSTB group patient received a 15 mL postoperative bolus injection of 0.5% ropivacaine. DEX was administered at 2 mcg/kg for 30 min post anesthesia, then maintained at 0.5 mcg/kg/h till surgery ended. Pain scores were investigated every 12 h for 48 h post operation, with evaluation of rebound pain incidence and opioid consumption. Results: The SSTB + DEX group had significantly higher median pain scores at 12 h post operation (resting pain, 8.0 vs. 3.0; movement pain, 8.0 vs. 5.0) and a higher incidence of rebound pain (56% vs. 20%) than the CSTB group. However, no significant between-group differences were observed in pain scores postoperatively at 24, 36, or 48 h. The CSTB group required less opioids and fewer rescue analgesics within 12-24 h post operation than the SSTB + DEX group. Conclusions: Compared with CSTB, SSTB + DEX required additional adjuvant or multimodal analgesics to reduce the risk and intensity of postoperative rebound pain in patients who underwent arthroscopic rotator cuff repair.

Minimum 19-Year Clinical Results and Patient Satisfaction After Total Knee Arthroplasty.

BACKGROUND: Long-term (minimum 19-year) outcome data on clinical results and patient satisfaction after posterior-stabilized total knee arthroplasties (TKAs) are missing in the literature. The purpose of the study was to evaluate the clinical and radiographic results as well as patient satisfaction at a mean of 21.2 years after posterior-stabilized TKAs. METHODS: This study included 756 patients (1,350 knees) who had undergone TKAs. There were 96 men and 660 women (mean age, 58 years; range, 40 to 84). The mean follow-up was 21.2 years (range, 19 to 23). At each follow-up visit, the patients were assessed radiographically and clinically. Furthermore, patient satisfaction was determined. RESULTS: The Knee Society total, pain, function, and deformity scores were 42, 18, 33, and 5 points, respectively, at the final follow-up. The mean Western Ontario and McMaster Universities Arthritis Index score was 25 points at the final follow-up. With revision or aseptic loosening as the end point, the 23-year intimated survival for the implant was 96% (95% confidence interval, 91 to 100%). The overall patient satisfaction score at the final follow-up was 83.3 points (range, 81 to 86). Patient satisfaction scores with regard to pain, housework, recreation, and surgery were 84, 81, 82, and 86 points, respectively. CONCLUSIONS: The findings of the present, mean 21-year follow-up clinical study suggest excellent results with regard to the revision rates and survivorship of the posterior-stabilized total knee implants. However, consistent with the literature, we found that about 80% of patients expressed overall satisfaction with their primary TKAs. About 8% of patients were either somewhat or very dissatisfied with the procedure.

Jagged1 intracellular domain/SMAD3 complex transcriptionally regulates TWIST1 to drive glioma invasion.

Jagged1 (JAG1) is a Notch ligand that correlates with tumor progression. Not limited to its function as a ligand, JAG1 can be cleaved, and its intracellular domain translocates to the nucleus, where it functions as a transcriptional cofactor. Previously, we showed that JAG1 intracellular domain (JICD1) forms a protein complex with DDX17/SMAD3/TGIF2. However, the molecular mechanisms underlying JICD1-mediated tumor aggressiveness remains unclear. Here, we demonstrate that JICD1 enhances the invasive phenotypes of glioblastoma cells by transcriptionally activating epithelial-to-mesenchymal transition (EMT)-related genes, especially TWIST1. The inhibition of TWIST1 reduced JICD1-driven tumor aggressiveness. Although SMAD3 is an important component of transforming growth factor (TGF)-ß signaling, the JICD1/SMAD3 transcriptional complex was shown to govern brain tumor invasion independent of TGF-ß signaling. Moreover, JICD1-TWIST1-MMP2 and MMP9 axes were significantly correlated with clinical outcome of glioblastoma patients. Collectively, we identified the JICD1/SMAD3-TWIST1 axis as a novel inducer of invasive phenotypes in cancer cells.

Trends in the treatment of fibromyalgia in South Korea between 2011 and 2018: a retrospective analysis of cross-sectional health insurance data.

OBJECTIVES: Fibromyalgia treatment trends vary globally; however, the trend in South Korea has not been investigated yet. This study aimed to analyse the fibromyalgia treatment trends in South Korea. DESIGN: Retrospective, observational study using serial cross-sectional data. SETTING: The National Patient Samples of the Korean Health Insurance Review & Assessment Service from 2011 to 2018 were used. PARTICIPANTS: A total of 31 059 patients with fibromyalgia were included in this study. The basic characteristics of the patients were stratified by sex, age and comorbidity. A patient was considered to have a condition if it was recorded as a principal diagnosis at least once in a year. PRIMARY AND SECONDARY OUTCOME MEASURES: Trends in the types of medical visits and prescribed treatments were investigated and the values are presented as rates per 100 patients. The types of pharmacological treatment were presented according to the existing clinical guidelines. Additionally, combination prescription trends and associated characteristics were investigated. RESULTS: Of the patients, 66.2% were female. Visits to internal medicine departments showed the most significant increase (2011: 11.34; 2018: 21.99; p<0.001). Non-pharmacological treatment rates declined (physical therapy 2011: 18.11; 2018: 13.69; p<0.001, acupuncture 2011: 52.03; 2018: 30.83; p<0.001). Prescription rates increased for analgesics, relaxants, antiepileptics and antidepressants. Non-steroidal anti-inflammatory drug prescriptions had the highest increase (2011: 27.65; 2018: 40.02; p<0.001). Serotonin-norepinephrine reuptake inhibitor prescriptions showed significant growth (2011: 2.4; 2018: 8.05; p<0.001). Prescription durations were generally longer for women (p<0.001), with higher rate increases in this group. Combinations of ≥3 medication classes increased (2011: 8.2; 2018: 9.64; p=0.041). Women were more likely to receive combination prescriptions (crude OR 1.47 (95% CI 1.29 to 1.68), adjusted 1.18 (95% CI 1.03 to 1.36)). CONCLUSIONS: Our findings provide basic reference data for the development and application of national guidelines for fibromyalgia.

Annexin A2 Stabilizes Oncogenic JAG1 Intracellular Domain by Inhibiting Proteasomal Degradation in Glioblastoma Cells.

Glioblastoma (GBM) is the most lethal brain cancer, causing inevitable deaths of patients owing to frequent relapses of cancer stem cells (CSCs). The significance of the NOTCH signaling pathway in CSCs has been well recognized; however, there is no NOTCH-selective treatment applicable to patients with GBM. We recently reported that Jagged1 (JAG1), a NOTCH ligand, drives a NOTCH receptor-independent signaling pathway via JAG1 intracellular domain (JICD1) as a crucial signal that renders CSC properties. Therefore, mechanisms regulating the JICD1 signaling pathway should be elucidated to further develop a selective therapeutic regimen. Here, we identified annexin A2 (ANXA2) as an essential modulator to stabilize intrinsically disordered JICD1. The binding of ANXA2 to JICD1 prevents the proteasomal degradation of JICD1 by heat shock protein-70/90 and carboxy-terminus of Hsc70 interacting protein E3 ligase. Furthermore, JICD1-driven propagation and tumor aggressiveness were inhibited by ANXA2 knockdown. Taken together, our findings show that ANXA2 maintains the function of the NOTCH receptor-independent JICD1 signaling pathway by stabilizing JICD1, and the targeted suppression of JICD1-driven CSC properties can be achieved by blocking its interaction with ANXA2.

Feasibility of an implantable bioreactor for renal cell therapy using silicon nanopore membranes.

The definitive treatment for end-stage renal disease is kidney transplantation, which remains limited by organ availability and post-transplant complications. Alternatively, an implantable bioartificial kidney could address both problems while enhancing the quality and length of patient life. An implantable bioartificial kidney requires a bioreactor containing renal cells to replicate key native cell functions, such as water and solute reabsorption, and metabolic and endocrinologic functions. Here, we report a proof-of-concept implantable bioreactor containing silicon nanopore membranes to offer a level of immunoprotection to human renal epithelial cells. After implantation into pigs without systemic anticoagulation or immunosuppression therapy for 7 days, we show that cells maintain >90% viability and functionality, with normal or elevated transporter gene expression and vitamin D activation. Despite implantation into a xenograft model, we find that cells exhibit minimal damage, and recipient cytokine levels are not suggestive of hyperacute rejection. These initial data confirm the potential feasibility of an implantable bioreactor for renal cell therapy utilizing silicon nanopore membranes.

Lidocaine intensifies the anti-osteogenic effect on inflammation-induced human dental pulp stem cells via mitogen-activated protein kinase inhibition.

Background/purpose: Human dental pulp stem cells (hDPSCs) are an emerging source of mesenchymal stem cells (MSCs) for bone tissue regeneration and engineering. In bone regeneration using transplanted MSCs, the extracellular environment or co-injected drugs can affect their success or failure. In this study, we investigated the effects and signaling mechanisms of lidocaine on osteogenic differentiation of hDPSCs after inducing inflammatory conditions with lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-α). Materials and methods: To investigate the effect of lidocaine on the osteogenic differentiation of LPS/TNF-α-treated hDPSCs, alkaline phosphatase (ALP) and Alizarin red S (ARS) staining were conducted. The expression of osteogenesis-related genes was assessed using quantitative real-time polymerase chain reaction and western blotting. The expression of mitogen-activated protein kinases was analyzed to evaluate the effect of lidocaine on osteogenic differentiation of LPS/TNF-α-treated hDPSCs. Results: Various concentrations of lidocaine (0.05, 0.2, and 1 mM) further decreased ALP and ARS staining of LPS/TNF-α-treated hDPSCs. Similarly, the mRNA and protein expression of osteogenesis-related genes was suppressed via lidocaine treatment in LPS/TNF-α-treated hDPSCs. Lidocaine treatment downregulated the protein expression of p-ERK and p-JNK in LPS/TNF-α-treated hDPSCs. Conclusion: Lidocaine intensified the inhibition of osteogenic differentiation on inflammation-induced hDPSCs by inhibiting the ERK and JNK signaling pathways. This in vitro study suggested that lidocaine may have an inhibitory effect on bone regeneration.

Comparison of postoperative nausea and vomiting between Remimazolam and Propofol in Patients undergoing oral and maxillofacial surgery: a prospective Randomized Controlled Trial.

BACKGROUND: Remimazolam is a recently approved, ultra-short-acting benzodiazepine. However, few studies have investigated remimazolam in relation to postoperative nausea and vomiting (PONV). This study aimed to compare the effects of remimazolam and propofol on PONV in patients undergoing oral and maxillofacial surgery. METHODS: Patients (n = 206) aged 19-65 years who were scheduled for oral and maxillofacial surgery were randomized into two groups, the remimazolam (R) and propofol group (P). In the R group (n = 94), remimazolam was used to induce anesthesia at 12 mg/kg/h and to maintain anesthesia at 1-2 mg/kg/h. In the P group (n = 95), anesthesia was induced and maintained with propofol (target effect-site concentration: 3-5 µg/ml). In both groups, remifentanil was administered at a target effect-site concentration of 2.5-4 ng/ml. The primary outcome was the overall incidence of PONV during the first 24 h after surgery. Secondary outcomes included the severity of nausea, use of rescue antiemetics, severity of postoperative pain, use of rescue analgesia, and quality of recovery. RESULTS: The incidence of PONV during the first 24 h after surgery was 11.7% and 10.5% in the R group and P group, respectively, and there was no significant difference in the severity of nausea (P > 0.05). Ten patients in the R group and ten patients in the P group required rescue antiemetics during the first 24 h after surgery (P = 0.98). No inter-group differences were observed in terms of postoperative pain score, use of rescue analgesia, and quality of recovery (P > 0.05). CONCLUSIONS: In this study, remimazolam did not increase the incidence and severity of PONV compared with propofol. TRIAL REGISTRATION: KCT0006965, Clinical Research Information Service (CRIS), Republic of Korea. Registration date: 26/01/2022.

Generation of a novel monoclonal antibody against inflammatory biomarker S100A8 using hybridoma technology.

OBJECTIVES: S100A8 is highly expressed in several inflammatory and oncological conditions. To address the current lack of a reliable and sensitive detection method for S100A8, we generated a monoclonal antibody with a high binding affinity to human S100A8 to enable early disease diagnosis. RESULTS: A soluble recombinant S100A8 protein with a high yield and purity was produced using Escherichia coli. Next, mice were immunized with recombinant S100A8 to obtain anti-human S100A8 monoclonal antibodies using hybridoma technology. Lastly, the high binding activity of the antibody was confirmed and its sequence was identified. CONCLUSIONS: This method, including the production of antigens and antibodies, will be useful for the generation of hybridoma cell lines that produce anti-S100A8 monoclonal antibodies. Moreover, the sequence information of the antibody can be used to develop a recombinant antibody for use in various research and clinical applications.

Lidocaine inhibits osteogenic differentiation of human dental pulp stem cells in vitro.

OBJECTIVE: Lidocaine is an amide local anaesthetic commonly used for pain control, however, few studies have investigated the effect of lidocaine on the osteogenic differentiation of human dental pulp stem cells (HDPSCs). The present study aimed to determine the effect of lidocaine on HDPSC viability and osteogenic differentiation. METHODS: HDPSCs were incubated with 0, 0.05, 0.2, 0.5, and 1 mM lidocaine for 24, 48 and 72 h, after which, MTT assays were performed. HDPSCs cultured with the above lidocaine concentrations and osteogenic differentiation medium for 7 and 14 days were stained for alkaline phosphatase (ALP). Protein and mRNA levels of relevant osteogenic factors (bone morphogenetic protein-2 [BMP-2] and runt-related transcription factor 2 [RUNX2]) were examined using western blotting and real-time reverse-transcription polymerase chain reaction, respectively. RESULTS: Lidocaine did not affect the viability of HDPSCs, however, lidocaine reduced ALP activity in HDPSCs. Levels of ALP, BMP-2, and RUNX2 mRNA were reduced with lidocaine, and levels of BMP-2 and RUNX2 proteins were decreased, versus controls. CONCLUSIONS: Lidocaine inhibits osteogenic differentiation markers in HDPSCs in vitro, even at low concentrations, without cytotoxicity. This study suggests that lidocaine may inhibit osteogenic differentiation in HDPSC-mediated regenerative medicine, including pulp regeneration and repair.

Exploring the Knowledge Structure of Patient Safety in Nursing Using a Keyword Network Analysis.

Patient safety is a critical and long-standing issue in nursing research. The purposes of this study were to explore the knowledge structure of patient safety and to provide a direction for future research by offering new perspectives and a theoretical clarification of patient safety in nursing. Keyword network analysis was performed by extracting keywords from abstracts of 6072 published articles. To reflect nursing perspectives, focus group interviews were conducted and Kim's typology consisting of four domains was used as the framework of analysis. Visualized knowledge structure showed avoiding medication error and preventing pressure ulcers or falls remain important topics within this research field. The distribution of core keywords as per four domains was in the following order: practice, client, environment, and client-nurse domain. Within the client domain, patients' harm-related core keywords were limited to physical harm. The detailed knowledge structure consisted of five themes: patient, preventable patient harm, practice, error, and environment. It comprised risk assessment for patients' characteristics and environmental elements surrounding patient and nursing practice, and risk management using information as knowledge-based nursing practice. Regarding further research, we suggest a multidimensional approach to patient harm, and the utilization of the client-nurse relationship and information systems as strategies for patient safety.

Minimum 30-Year Results of Bilaterally Implanted Cemented and Cementless Total Hip Arthroplasty in Patients Younger Than 50 Years.

BACKGROUND: The rate of failure of cemented and cementless total hip arthroplasty (THA) in younger patients is higher than that in elderly patients. The purpose of this study is to document the long-term clinical results of THA with the so-called third-generation cementing and the results of second-generation cementless THA in patients <50 years of age. METHODS: This study included 106 patients who had had bilateral THA with a cemented stem in one hip and a cementless stem in the other. There were 78 men and 28 women. Their mean age was 47 years (range, 21-49). The average follow-up duration was 31 years (range, 30-32.5). RESULTS: There were similar mean Harris Hip Scores (90 versus 91 points) between the groups at the final follow-up. Forty-six acetabular components (43%) in the cemented group and 48 acetabular components (45%) in the cementless group were revised. Five femoral components (5%) in the cemented group and 4 femoral components (4%) in the cementless group were revised. Survivorship of the acetabular component at 30.8 years was similar in both groups (57% in the cemented group versus 55% in the cementless group). Survivorship of the femoral component at 30.8 years was also similar in both groups (95% in the cemented group versus 96% in the cementless group). CONCLUSION: Long-term fixation of the cemented or cementless femoral stem was outstanding. There was a high rate of the acetabular component revision due to conventional polyethylene wear and periacetabular osteolysis in both hybrid and fully cementless THA groups.

Long-Term Results (Minimum of 20 Years) of a Pure Proximal-Loading Metaphyseal-Fitting Anatomic Cementless Stem Without Distal Stem Fixation in Hip Arthroplasty.

BACKGROUND: There are no reported results for more than 20 years of a pure proximal-loading anatomic cementless femoral stem without diaphyseal stem fixation. The purpose of this study was to evaluate the long-term (minimum 20 years) clinical results, bone remodeling, revision rate, and survivorship of these implants in patients aged less than 60 years. METHODS: We included 523 patients (657 hips), including 319 men and 204 women. The mean body mass index was 26.7 (range, 23-29 kg/m2). The mean age of patients at index surgery was 55 years (range, 20-59 years). The Harris Hip Score, the Western Ontario and McMaster Universities Osteoarthritis Index, and the University of California, Los Angeles activity score were recorded preoperatively and at each follow-up. Mean follow-up was 23.5 years (range, 20-27 years). RESULTS: The Harris Hip Score at the final follow-up was a mean 93 points (range, 70-100 points). The Western Ontario and McMaster Universities Osteoarthritis Index and University of California, Los Angeles activity scores at the final follow-up were 16 and 7.6 points, respectively. Five femoral components (0.8%) and 13 acetabular components (2.0%) were revised. All cases in the current series had grade 2 stress shielding; no hips had grade 3 or 4 stress shielding. Kaplan-Meier survivorship of the implants at 23.5 years was 98.0% (95% confidence interval 92%-100%) for the acetabular component and 99.2% (95% confidence interval 93%-100%) for the femoral component. CONCLUSION: A pure proximal-loading metaphyseal-fitting anatomic cementless stem with alumina-on-alumina ceramic bearing couples functioned well, with no osteolysis or mild stress-shielding at an average 23.5-year follow-up.

The oncogenic JAG1 intracellular domain is a transcriptional cofactor that acts in concert with DDX17/SMAD3/TGIF2.

Jagged1 (JAG1) is a Notch ligand that contact-dependently activates Notch receptors and regulates cancer progression. The JAG1 intracellular domain (JICD1) is generated from JAG1, like formation of the NOTCH1 intracellular domain (NICD1); however, the role of JICD1 in tumorigenicity has not been comprehensively elucidated. Here we show that JICD1 induces astrocytes to acquire several cancer stem cell properties, including tumor formation, invasiveness, stemness, and resistance to anticancer therapy. The transcriptome, chromatin immunoprecipitation sequencing (ChIP-seq), and proteomics analyses show that JICD1 increases SOX2 expression by forming a transcriptional complex with DDX17, SMAD3, and TGIF2. JICD1-driven tumorigenicity is directly regulated by SOX2. Our results demonstrate that, like NICD1, JICD1 acts as a transcriptional cofactor in formation of the DDX17/SMAD3/TGIF2 transcriptional complex, leading to oncogenic transformation.

A rapid ELISA for the detection of matrix metallopeptidase 9 using a recombinant Fab-type antibody.

Matrix metalloproteinase 9 (MMP9) contributes to several aspects of inflammation and cancer pathology, including invasion, metastasis, and angiogenesis. In this study, we expressed a recombinant fragment antigen-binding (Fab)-type anti-MMP9 antibody in Escherichia coli with high purity within five days and confirmed the nanomolar order of antigen-binding efficiency of the recombinant Fab. Moreover, we optimized the experimental time for performing enzyme-linked immunosorbent assay (ELISA), and decreased the reaction time from the conventional 20.5 h to 3.5 h. The rapid and sensitive MMP9 detection system developed in this study can be applied to a range of applications, including the diagnosis of diseases with MMP9 overexpression including inflammatory and cancer-related diseases.

Efficacy and safety evaluation of adjuvant auricular acupuncture for smoking cessation: A study protocol of randomized, assessor-blinded, pragmatic pilot trial.

BACKGROUND: Smoking negatively impacts public health. There are several treatments to quit smoking, and nicotine replacement treatment (NRT) reportedly doubles the smoking cessation rate, with some limitations. Acupuncture is an alternative option with proven effects on smoking cessation. However, there has been no definite report that indicates the efficacy and safety of auricular acupuncture (AA) combined with NRT on smoking cessation. METHODS: This is a randomized, assessor-blind, and pragmatic pilot study. We will recruit 40 participants who want to stop smoking and randomly allocate them into an NRT group and an NRT + AA group with a 1:1 ratio. Participants will receive NRT for 4 weeks and the NRT + AA group will receive additional AA treatment with 5 AA points (Shenmen (TF4), lung (CO14), throat (TF3), inner nose (TG4), and endocrine (CO18)) twice a week for 4 weeks. Follow-up will be conducted 1 and 3 months after intervention completion. The primary outcome will be tobacco consumption and abstinence rate determined by calculating the rate of change in cigarette use and a urine test. Secondary outcomes will be the quality of life (EuroQol-5D and visual analogue scale), nicotine dependence (Fagerstrom test for nicotine dependence), nicotine withdrawal (Minnesota nicotine withdrawal scale), physical effects, satisfaction, and safety measurement (adverse events). RESULTS: We will investigate the efficacy and safety of AA combined with NRT treatment for smoking cessation. CONCLUSION: Our study will provide additional clinical evidence for AA as an adjuvant treatment for smoking cessation. TRIAL REGISTRATION NUMBER: Clinical Research Information Service (registration number: KCT0007212).

Propofol protects against lipopolysaccharide-induced inflammatory response in human amnion-derived WISH cells.

Background: Nonobstetric surgery is sometimes required during pregnancy, and neck abscess or facial bone fracture surgery cannot be postponed in pregnant women. However, dental surgery can be stressful and can cause inflammation, and the inflammatory response is a well-known major cause of preterm labor. Propofol is an intravenous anesthetic commonly used for general anesthesia and sedation. Studies investigating the effect of propofol on human amnion are rare. The current study investigated the effects of propofol on lipopolysaccharide (LPS)-induced inflammatory responses in human amnion-derived WISH cells. Methods: WISH cells were exposed to LPS for 24 h and co-treated with various concentrations of propofol (0.01-1 µg/ml). Cell viability was measured using the MTT assay. Nitric oxide (NO) production was analyzed using a microassay based on the Griess reaction. The protein expression of cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE 2), p38, and phospho-p38 was analyzed using western blotting. Results: Propofol did not affect the viability and NO production of WISH cells. Co-treatment with LPS and propofol reduced COX-2 and PGE2 protein expression and inhibited p38 phosphorylation in WISH cells. Conclusion: Propofol does not affect the viability of WISH cells and inhibits LPS-induced expression of inflammatory factors. The inhibitory effect of propofol on inflammatory factor expression is likely mediated by the inhibition of p38 activation.

Subpial delivery of adeno-associated virus 9-synapsin-caveolin-1 (AAV9-SynCav1) preserves motor neuron and neuromuscular junction morphology, motor function, delays disease onset, and extends survival in hSOD1G93A mice.

Elevating neuroprotective proteins using adeno-associated virus (AAV)-mediated gene delivery shows great promise in combating devastating neurodegenerative diseases. Amyotrophic lateral sclerosis (ALS) is one such disease resulting from loss of upper and lower motor neurons (MNs) with 90-95% of cases sporadic (SALS) in nature. Due to the unknown etiology of SALS, interventions that afford neuronal protection and preservation are urgently needed. Caveolin-1 (Cav-1), a membrane/lipid rafts (MLRs) scaffolding and neuroprotective protein, and MLR-associated signaling components are decreased in degenerating neurons in postmortem human brains. We previously showed that, when crossing our SynCav1 transgenic mouse (TG) with the mutant human superoxide dismutase 1 (hSOD1G93A) mouse model of ALS, the double transgenic mouse (SynCav1 TG/hSOD1G93A) exhibited better motor function and longer survival. The objective of the current study was to test whether neuron-targeted Cav-1 upregulation in the spinal cord using AAV9-SynCav1 could improve motor function and extend longevity in mutant humanized mouse and rat (hSOD1G93A) models of familial (F)ALS. Methods: Motor function was assessed by voluntary running wheel (RW) in mice and forelimb grip strength (GS) and motor evoked potentials (MEP) in rats. Immunofluorescence (IF) microscopy for choline acetyltransferase (ChAT) was used to assess MN morphology. Neuromuscular junctions (NMJs) were measured by bungarotoxin-a (Btx-a) and synaptophysin IF. Body weight (BW) was measured weekly, and the survival curve was determined by Kaplan-Meier analysis. Results: Following subpial gene delivery to the lumbar spinal cord, male and female hSOD1G93A mice treated with SynCav1 exhibited delayed disease onset, greater running-wheel performance, preserved spinal alpha-motor neuron morphology and NMJ integrity, and 10% increased longevity, independent of affecting expression of the mutant hSOD1G93A protein. Cervical subpial SynCav1 delivery to hSOD1G93A rats preserved forelimb GS and MEPs in the brachial and gastrocnemius muscles. Conclusion: In summary, subpial delivery of SynCav1 protects and preserves spinal motor neurons, and extends longevity in a familial mouse model of ALS without reducing the toxic monogenic component. Furthermore, subpial SynCav1 delivery preserved neuromuscular function in a rat model of FALS. The latter findings strongly indicate the therapeutic applicability of SynCav1 to treat ALS attributed to monogenic (FALS) and potentially in sporadic cases (i.e., SALS).