Therapeutic Potential of Combined Herbal Medicine and Electroacupuncture in Mild Cognitive Impairment Through Cytokine Modulation: An Observational Study.

Purpose: We aimed to investigate the efficacy of a combined herbal formula and electroacupuncture (EA) for mild cognitive impairment (MCI), a neurodegenerative disease leading to dementia, and its underlying mechanisms of action. Patients and Methods: This was a prospective open-label observational pilot study at Daejeon Korean Medicine Hospital of Daejeon University in South Korea from March 2022 to March 2023. We included six Korean patients (50% male) aged ≥ 45 years and < 85 years with MCI, a clinical dementia rating score of 0.5, and a Montreal Cognitive Assessment-Korea (MoCA-K) score ≤ 22. The exclusion criterion was impaired cognitive function. Patients received combined therapy, including a herbal formula and EA, for 12-24 weeks. We prescribed the herbal formulas Gamiguibi-tang, Yukmijihwang-tang, and Banhasasim-tang to the patients for at least 70% of the treatment period, in combination with EA. Moreover, we investigated changes in cognitive and cognition-related symptoms and cytokine expression in the blood following combined traditional medicine therapy. At baseline and after 12 and 24 weeks, we administered the MoCA-K and cognitive-related questionnaires. We analyzed network pharmacology to reflect the herbal formula intervention mechanism comprehensively. Results: The median score [interquartile range] of MoCA-K at baseline was 19.5 [16.0, 22.0], which improved significantly (24.5 [24.0, 26.0], p < 0.01) over 24 weeks following combined therapy. We obtained no significant conclusion regarding cytokine changes due to the small sample size. In network pharmacology, we analyzed the brain, head, heart, peripheral nerves, peripheral nervous system, and pancreas as the enriched organs from the common targets of the three herbal formulas. Conclusion: Combined herbal medicine and EA improved cognitive function in patients with MCI. We assume the underlying mechanism of herbal formulas to be antioxidative and anti-inflammatory changes in cytokine expression. Combined traditional medicine has potential therapeutic application in preventing MCI progression to dementia.

This was a single-centered study focusing on the therapeutic effect of combined herbal medicine and electroacupuncture in patients with mild cognitive impairment, including a small number of participants, a relatively long treatment intervention of 12 weeks, and a follow-up assessment of 24 weeks. The intervention was a combination of a herbal formula and electroacupuncture treatment customized for each participant. The blood cytokine analyses of the participants were compared with the network analysis of the predicted target organs and pathways for the herbal formulas administered. Because each participant was not given the exact same intervention, we were unable to identify the specific treatment that produced the predicted effect. The observational study design of the study limited the ability to accurately assess causation between intervention and outcome. However, combined traditional medicine has potential therapeutic application in preventing mild cognitive impairment progression to dementia.

Cytotoxic rhamnolipid micelles drive acute virulence in Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an opportunistic human pathogen that has developed multi- or even pan-drug resistance toward most frontline and last resort antibiotics, leading to increasing frequency of infections and deaths among hospitalized patients, especially those with compromised immune systems. Further complicating treatment, P. aeruginosa produces numerous virulence factors that contribute to host tissue damage and immune evasion, promoting bacterial colonization and pathogenesis. In this study, we demonstrate the importance of rhamnolipid production in host-pathogen interactions. Secreted rhamnolipids form micelles that exhibited highly acute toxicity toward murine macrophages, rupturing the plasma membrane and causing organellar membrane damage within minutes of exposure. While rhamnolipid micelles (RMs) were particularly toxic to macrophages, they also caused membrane damage in human lung epithelial cells, red blood cells, Gram-positive bacteria, and even noncellular models like giant plasma membrane vesicles. Most importantly, rhamnolipid production strongly correlated with P. aeruginosa virulence against murine macrophages in various panels of clinical isolates. Altogether, our findings suggest that rhamnolipid micelles are highly cytotoxic virulence factors that drive acute cellular damage and immune evasion during P. aeruginosa infections.

In vitro lung epithelial cell model reveals novel roles for Pseudomonas aeruginosa siderophores.

The multidrug-resistant pathogen Pseudomonas aeruginosa is a common nosocomial respiratory pathogen that continues to threaten the lives of patients with mechanical ventilation in intensive care units and those with underlying comorbidities such as cystic fibrosis or chronic obstructive pulmonary disease. For over 20 years, studies have repeatedly demonstrated that the major siderophore pyoverdine is an important virulence factor for P. aeruginosa in invertebrate and mammalian hosts in vivo. Despite its physiological significance, an in vitro, mammalian cell culture model that can be used to characterize the impact and molecular mechanisms of pyoverdine-mediated virulence has only been developed very recently. In this study, we adapt a previously-established, murine macrophage-based model to use human bronchial epithelial (16HBE) cells. We demonstrate that conditioned medium from P. aeruginosa induced rapid 16HBE cell death through the pyoverdine-dependent secretion of cytotoxic rhamnolipids. Genetic or chemical disruption of pyoverdine biosynthesis decreased rhamnolipid production and mitigated cell death. Consistent with these observations, chemical depletion of lipids or genetic disruption of rhamnolipid biosynthesis abrogated the toxicity of the conditioned medium. Furthermore, we also examine the effects of exposure to purified pyoverdine on 16HBE cells. While pyoverdine accumulated within cells, it was largely sequestered within early endosomes, resulting in minimal cytotoxicity. More membrane-permeable iron chelators, such as the siderophore pyochelin, decreased epithelial cell viability and upregulated several pro-inflammatory genes. However, pyoverdine potentiated these iron chelators in activating pro-inflammatory pathways. Altogether, these findings suggest that the siderophores pyoverdine and pyochelin play distinct roles in virulence during acute P. aeruginosa lung infection. IMPORTANCE: Multidrug-resistant Pseudomonas aeruginosa is a versatile bacterium that frequently causes lung infections. This pathogen is life-threatening to mechanically-ventilated patients in intensive care units and is a debilitating burden for individuals with cystic fibrosis. However, the role of P. aeruginosa virulence factors and their regulation during infection are not fully understood. Previous murine lung infection studies have demonstrated that the production of siderophores (e.g., pyoverdine and pyochelin) is necessary for full P. aeruginosa virulence. In this report, we provide further mechanistic insight into this phenomenon. We characterize distinct and novel ways these siderophores contribute to virulence using an in vitro human lung epithelial cell culture model.

Mortality Risk Scoring System in Patients after Bleeding from Cancers in the Upper Gastrointestinal Tract.

Background/Aims: : Risk scoring systems for upper gastrointestinal (UGI) bleeding have not been well validated for tumor bleeding. This study aimed to identify risk factors for mortality in patients with UGI cancer bleeding and to develop a predictive model. Methods: : Consecutive patients with UGI cancers who underwent esophagogastroduodenoscopy for suspected bleeding were retrospectively included. Patient characteristics, endoscopic findings and 30-day mortality were assessed. A predictive model was made based on risk factors for mortality using logistic regression, and the area under the curve (AUC) of this model was calculated. It was then compared with other risk scoring systems. Results: : In a total of 264 patients, 193 had tumor bleeding. Among them, 108 (56.0%), 76 (39.4%), and nine (4.7%) patients received conservative treatment, endoscopic therapy, and non-endoscopic hemostasis, respectively. Rebleeding occurred in 23 (21.3%), 26 (34.2%), and one (11.1%) patient(s), respectively. Our new model is composed of altered mental status, renal failure, rebleeding, age older than 65 years, and low serum albumin (all p<0.05). This model predicted 30-day mortality with an AUC of 0.79 (95% confidence interval, 0.72 to 0.86), which was significantly higher than AUCs of the Glasgow-Blatchford score, Rockall, and AIMS65 score (AUC=0.61, 0.64, and 0.69, respectively, all p<0.05). Conclusions: : Our new scoring system provides a better prediction of 30-day mortality than existing scoring systems in patients with UGI cancer bleeding. This new scoring system can be used to predict and prepare these patients who are known to have high mortality.

CTM and QFD analysis: Framework for fintech adoption priority in commercial banks.

As financial technology (fintech) is developing rapidly, many commercial banks experience difficulty deciding what kind of fintech to primarily focus on when managing their business. Owing to limited resources and assets, there is a practical need for guidelines for banks' investments in fintech. This study provides a systemic procedure to identify promising fintech groups and their investment priorities. We propose a QFD-based decision support framework for banks by considering both aspects of the emerging fintech push identified using patent topic modeling and the market pull of banking services obtained from a survey of the literature and experts. An empirical application of the proposed QFD framework to major South Korean banks shows that transaction support technology, secure transactions, and trading platforms are the three most important fintech categories. The QFD results are utilized to guide individual banks for further investment strategies such as mergers and acquisitions, strategic partnerships, and spin-off operations. The proposed framework can be generalized and applied to other financial service firms.

Cytotoxic rhamnolipid micelles drive acute virulence in Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an opportunistic human pathogen that has developed multi- or even pan-drug resistance towards most frontline and last resort antibiotics, leading to increasing infections and deaths among hospitalized patients, especially those with compromised immune systems. Further complicating treatment, P. aeruginosa produces numerous virulence factors that contribute to host tissue damage and immune evasion, promoting bacterial colonization and pathogenesis. In this study, we demonstrate the importance of rhamnolipid production in host-pathogen interactions. Secreted rhamnolipids form micelles that exhibited highly acute toxicity towards murine macrophages, rupturing the plasma membrane and causing organellar membrane damage within minutes of exposure. While rhamnolipid micelles (RMs) were particularly toxic to macrophages, they also caused membrane damage in human lung epithelial cells, red blood cells, Gram-positive bacteria, and even non-cellular models like giant plasma membrane vesicles. Most importantly, rhamnolipid production strongly correlated to P. aeruginosa virulence against murine macrophages in various panels of clinical isolates. Altogether, our findings suggest that rhamnolipid micelles are highly cytotoxic virulence factors that drive acute cellular damage and immune evasion during P. aeruginosa infections.

Impact of Autoimmune Gastritis on Occurrence of Metachronous Gastric Neoplasms after Endoscopic Resection for Gastric Neoplasms.

Gastric cancer is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. Autoimmune gastritis (AIG) is characterized by antibody production against the gastric parietal cells, reducing the number of functional parietal cells. It is also associated with an increased susceptibility to gastric neuroendocrine tumors and gastric cancer. Endoscopic resection (ER) is an effective treatment for early gastric cancer; however, metachronous gastric neoplasms (MGN) can develop. This study aimed to evaluate the clinical effect of AIG on the occurrence of MGN after ER for gastric neoplasms. We retrospectively analyzed patients who underwent ER for gastric neoplasms. Patients with multiple lesions, recurrent lesions, or a history of partial gastrectomy were excluded. The presence of AIG was determined using anti-parietal cell antibody (APCA) testing. Follow-up endoscopy and metachronous tumor occurrence rates were compared between the AIG and non-AIG groups. Of the 569 patients, 282 underwent APCA testing and 20 (7.1%) were diagnosed with AIG. The incidence of MGN was significantly higher in the AIG group than in the non-AIG group (45.0% vs. 18.3%); however, the MGN occurrence pattern was similar between the two groups. Multivariate analysis revealed that AIG (HR 3.32, 95% CI 1.55-7.10, p = 0.002) and a higher body mass index (HR 1.16, 95% CI 1.06-1.27, p = 0.002) were independent factors significantly associated with the occurrence of MGN. Patients with AIG have a higher risk of metachronous lesion occurrence after ER for gastric neoplasms. Positive results of APCA testing have independent clinical implications for predicting MGN. Proper monitoring and management are essential for early detection and treatment of recurrent lesions in patients with AIG.

MWCNT-Coated Glass Fabric/Phenol Composite Heating Panel Fabricated by Resin Infusion Process.

MWCNTs (multiwalled carbon nanotubes) were applied to fiber-reinforced composite materials with phenolic resin having flame retardance for the composite heating panels of railroad vehicles. Instead of dispersing MWCNTs in the matrix, the surface of a pristine plain-weave glass fiber fabric was coated with MWCNTs through a series of dip-coating and drying processes, followed by the resin infusion of the phenolic resin to make the composite heating panel. Before and after the resin infusion process, low percolation thresholds of 0.00216 wt%MWCNT (weight percent of MWCNTs) and 0.001 wt%MWCNT, respectively, were achieved, as were very high electrical conductivities of 47.5 S/m at 0.210 wt%MWCNT and 26.7 S/m at 0.116 wt%, respectively. The low threshold and high conductivity can be attributed to the formation of electrical pathways directly onto the glass fabrics. It was confirmed that mechanical properties such as modulus, strength, and maximum strain were at the same level as those of the pristine glass fabric composite. The heating performance with temperature uniformity, as well as the electrical and mechanical properties, indicates that the resin-infused glass fabric composite having MWCNTs directly coated onto the fabric surface can be a solution for lightweight structural composite heating panels for railway vehicles.

Promoting Science Literacy and Awareness across the Globe: the Role of Scientists as Science Ambassadors.

Science literacy has many personal and societal benefits that allows for better informed decision-making. Although the importance of science literacy is recognized globally, there are many challenges associated with its promotion. Scientists are more frequently engaging with nonscientific audiences through public outreach activities and with increasing support from institutions and professional societies. This is especially true regarding microbiologists and other related professionals since the start of the global 2019 coronavirus disease pandemic heightened the need to convey novel and rapidly evolving scientific information to lay audiences. The means by which professionals engage with these audiences affect the efficacy of the relay of scientific information. One method of engagement is the "ambassador approach," which aims to establish dialogue among different groups of people and scientists. In this perspective article, we discuss this approach, highlighting activities for the promotion of science literacy organized by the American Society for Microbiology Ambassador Program and similar programs of other scientific societies. We discuss the benefits and challenges of implementing an ambassador approach, propose potential improvements that could be made to existing programs promoting science literacy, and ultimately advocate for increased implementation of science ambassador programs.

Efficacy and safety of a combination of emotional freedom technique with acupuncture versus acupuncture alone to treat psychiatric symptoms in Parkinson's disease: A protocol for a randomized, assessor-blind, parallel-group clinical trial.

BACKGROUND: Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases in world. As some psychiatric symptoms degrade the quality of life of patients with PD, a novel alternative non-pharmacological treatment is required. Acupuncture appears to be an effective and safe treatment for PD. The emotional freedom technique (EFT) is a type of psychological therapy that alleviates psychiatric symptoms by stimulating acupoints. In this study, we will compare the efficacy and safety of a combination of the EFT and acupuncture and acupuncture alone. METHODS: This study is a randomized, assessor-blind, parallel-group clinical trial. Eighty participants will be equally divided into experimental and control groups. Each participant will receive a total of 24 interventions over 12 weeks. The experimental group will receive EFT combined with acupuncture and the control group will receive acupuncture alone. The primary outcome is the change in the Beck Depression Inventory score from baseline to 12 weeks, and the secondary outcomes include change in the following variables: Beck Depression Inventory, Parkinson's disease sleep scale, State-Trait Anxiety Inventory, the Korean version of the Fatigue, Resistance, Ambulation, Illnesses, and Loss of weight questionnaire scale, and unified Parkinson's disease rating scale III and exercises. DISCUSSION: Acupuncture is a safe and effective treatment for motor and nonmotor symptoms in PD, and EFT appears to be safe and effective for a variety of psychiatric symptoms. In this study, we will investigate the potential of EFT combined with acupuncture to improve psychiatric symptoms in PD.

Paradoxical massive pulmonary thromboembolism in a postpartum woman with factor VII deficiency with bleeding tendency: A case report.

RATIONALE: Factor VII (FVII) deficiency is an inherited bleeding disorder, and women with FVII deficiency are at risk of gynecological bleeding and postpartum hemorrhage. There have been no reports of pulmonary embolism in a postpartum woman with FVII deficiency as of yet. We report a case of postpartum massive pulmonary embolism with FVII deficiency. PATIENT CONCERNS: A 32-year-old woman visited the hospital with premature rupture of membranes at 24 weeks and 4 days of gestation. She was diagnosed with FVII deficiency in an additional blood test after her laboratory results at admission included an increased prothrombin time and international normalized ratio abnormalities. After 12 days of pregnancy maintenance treatment, an emergency cesarean delivery was performed due to uncontrolled preterm labor. The day after the operation, she suffered a sudden loss of consciousness and cardiac arrest, and after she received 1 cycle of cardiopulmonary resuscitation, she was moved to the intensive care unit. DIAGNOSES: She was diagnosed with massive pulmonary thromboembolism with heart failure by chest enhanced computed tomography, C-echo, and angiography. INTERVENTIONS: She was successfully treated with the early application of extracorporeal membrane oxygenation, catheter-guided thrombectomy, and anticoagulants. OUTCOMES: There were no major sequelae over 2 months of follow-up. LESSONS: FVII deficiency does not protect against thrombosis. Due to the high thrombotic risk after childbirth, the risk of thrombosis should be recognized, and thromboprophylaxis should be considered if additional obstetric thrombotic risk factors are present.

Prognostic value of soluble PD-L1 and exosomal PD-L1 in advanced gastric cancer patients receiving systemic chemotherapy.

The prognostic role of soluble PD-L1 (sPD-L1) and exosomal PD-L1 (exoPD-L1) in patients with gastric cancer (GC) receiving systemic chemotherapy remains unelucidated. Thus, we examined their prognostic significance in patients with advanced GC. Blood samples were obtained from 99 patients with advanced GC receiving first-line chemotherapy. Serum-derived exosomes were isolated by centrifugation and polymer precipitation. The correlation between serum-derived exoPD-L1, plasma sPD-L1, immune-related markers, and circulating immune cells was evaluated. Patients were divided into two groups according to pretreatment sPD-L1 and exoPD-L1 levels: low sPD-L1 and high sPD-L1 groups, low exoPD-L1 and high exoPD-L1 groups. Patients with low sPD-L1 level before treatment (< 9.32 pg/mL) showed significantly better overall survival (OS) and progression-free survival (PFS) than those with high sPD-L1 level (≥ 9.32 pg/mL). The low exoPD-L1 group (< 10.21 pg/mL) showed a tendency of longer PFS than the high exoPD-L1 group (≥ 10.21 pg/mL). Pretreatment sPD-L1 was an independent prognostic factor for OS in multivariate analysis. exoPD-L1 was associated with systemic inflammation markers, immunomodulatory cytokines, and T cells, while sPD-L1 was associated with tumor markers. Pretreatment plasma-derived sPD-L1 level could be used as a prognostic marker for patients receiving cytotoxic chemotherapy. Serum-derived exoPD-L1 may reflect the immunosuppressive state of patients with advanced GC.

Bangpungtongsung-san for patients with major depressive disorder: study protocol for a randomized controlled phase II clinical trial.

BACKGROUND: Bangpungtongsung-san (BTS) is a representative herbal medicine that has been widely used for patients with obesity in east Asian countries. Various preclinical studies have demonstrated the anti-depressive effect of BTS granules in various animal models of depression. This phase II trial aimed to explore the efficacy and safety of BTS in human patients with depression. METHODS: A total of 126 patients diagnosed with major depressive disorder and who are not underweight (body mass index ≥ 18.5 kg/m2) will be enrolled in this study. Eligible participants will be randomly allocated into three groups: the high-dose BTS, low-dose BTS, and placebo groups in a 1:1:1 ratio. BTS or placebo granules will be orally administered twice a day for 8 weeks. The BTS and placebo granules will be made to have identical color, scent, and shape, and participants and investigators will be blinded to the allocation. The primary efficacy endpoint is the change from baseline of the 17-item Hamilton Depression Rating Scale total score at 8 weeks. The superiority of the high- and low-dose BTS granules to the placebo granules will be tested. DISCUSSION: The results of this clinical trial will provide evidence on the efficacy and safety of BTS for patients with major depressive disorder. This study will be conducted in accordance with ethical and regulatory guidelines, and the results will be submitted and published in international peer-reviewed journals. TRIAL REGISTRATION: CRIS registration Number: KCT0007571; registered on 2022/07/26 ( https://cris.nih.go.kr/cris/search/detailSearch.do/23192 ).

Independent Heating Performances in the Sub-Zero Environment of MWCNT/PDMS Composite with Low Electron-Tunneling Energy.

The structural stability of various structures (railroads, bridges, buildings, etc.) is lowered due to freezing because of the decreasing outside temperature in winter. To prevent damage from freezing, a technology for de-icing has been developed using an electric-heating composite. For this purpose, a highly electrically conductive composite film with multi-wall carbon nanotubes (MWCNTs) uniformly dispersed in a polydimethylsiloxane (PDMS) matrix through a three-roll process was fabricated by shearing the MWCNT/PDMS paste, through a two-roll process. The electrical conductivity and the activation energy of the composite were 326.5 S/m and 8.0 meV at 5.82 Vol% of MWCNTs, respectively. The dependence of the electric-heating performance (heating rate and temperature change) on the applied voltage and environmental temperature (from -20 °C to 20 °C) was evaluated. The heating rate and effective-heat-transfer characteristics were observed to decrease as the applied voltage increased, while they showed the opposite tendency when the environmental temperature was at sub-zero temperatures. Nevertheless, the overall heating performance (heating rate and temperature change) was maintained with little significant difference in the considered external-temperature range. The unique heating behaviors can result from the low activation energy and the negative-temperature (T) coefficient of resistance (R) (NTCR, dR/dT < 0) of the MWCNT/PDMS composite.

Accuracy of administrative claim data for gastric adenoma after endoscopic resection.

BACKGROUND/AIMS: Administrative databases provide valuable information for large-cohort studies. This study aimed to evaluate the diagnostic accuracy of an administrative database for resected gastric adenomas. METHODS: Data of patients who underwent endoscopic resection for benign gastric lesions were collected from three hospitals. Gastric adenoma cases were identified in the hospital database using International Classification of Diseases (ICD) 10-codes. The non-adenoma group included patients without gastric adenoma codes. The diagnostic accuracy for gastric adenoma was analyzed based on the pathological reports of the resected specimen. RESULTS: Among 5,095 endoscopic resections with codes for benign gastric lesions, 3,909 patients were included in the analysis. Among them, 2,831 and 1,078 patients were allocated to the adenoma and non-adenoma groups, respectively. Regarding the overall diagnosis of gastric adenoma with ICD-10 codes, the sensitivity, specificity, positive predictive value, and negative predictive value were 98.7%, 88.5%, 95.2%, and 96.8%, respectively. There were no significant differences in these parameters between the tertiary and secondary centers. CONCLUSION: Administrative codes of gastric adenoma, according to ICD-10 codes, showed good accuracy and can serve as a useful tool to study prognosis of these patients in real-world data studies in the future.

Long-term clinical outcomes of gastric mucosa-associated lymphoid tissue lymphoma in real-world experience.

This long-term, retrospective, single-center study evaluated real-world clinical outcomes of gastric mucosa-associated lymphoid tissue (MALT) lymphoma using different therapeutic modalities and analyzed factors affecting survival outcomes and long-term prognosis. We enrolled 203 patients with pathologically confirmed low-grade gastric MALT lymphoma and examined their treatment responses. Helicobacter pylori eradication was performed in all patients with H. pylori infection (HPI) and localized stage gastric MALT lymphoma. All patients underwent pre-treatment and physical evaluations, with complete blood count, biochemistry panel, and staging workup. Among 144 HPI-positive patients with stage I or II1-2 disease who underwent H. pylori eradication, 112 (77.8%) achieved complete remission (CR). All HPI-negative patients who received first-line radiotherapy achieved CR (100%), but only 22 of 27 first-line chemotherapy-treated patients achieved CR (81.5%). Lesions in the proximal upper-third or in multiple locations and an invasion depth to the submucosa or deeper were associated with poor response to eradication, and HPI negativity was significantly correlated with poor progression-free survival. HPI eradication treatment should be the first-line treatment for patients with localized stage HPI-positive gastric MALT lymphoma. The "watch-and-wait" strategy should be adopted for delayed responders. We suggest radiotherapy for patients with a localized HPI-negative status or when eradication has failed.

In vitro Lung Epithelial Cell Model Reveals Novel Roles for Pseudomonas aeruginosa Siderophores.

Multidrug-resistant Pseudomonas aeruginosa is a common nosocomial respiratory pathogen that continues to threaten the lives of patients with mechanical ventilation in intensive care units and those with underlying comorbidities such as cystic fibrosis or chronic obstructive pulmonary disease. For over 20 years, studies have repeatedly demonstrated that the major siderophore pyoverdine is an important virulence factor for P. aeruginosa in invertebrate and mammalian hosts in vivo. Despite its physiological significance, an in vitro, mammalian cell culture model to characterize the impact and molecular mechanism of pyoverdine-mediated virulence has only been developed very recently. In this study, we adapt a previously-established, murine macrophage-based model for human bronchial epithelial cells (16HBE). We demonstrate that conditioned medium from P. aeruginosa induced rapid 16HBE cell death through the pyoverdine-dependent secretion of cytotoxic rhamnolipids. Genetic or chemical disruption of pyoverdine biosynthesis decreased rhamnolipid production and mitigated cell death. Consistent with these observations, chemical depletion of lipid factors or genetic disruption of rhamnolipid biosynthesis was sufficient to abrogate conditioned medium toxicity. Furthermore, we also examine the effects of purified pyoverdine exposure on 16HBE cells. While pyoverdine accumulated within cells, the siderophore was largely sequestered within early endosomes, showing minimal cytotoxicity. More membrane-permeable iron chelators, such as the siderophore pyochelin, decreased epithelial cell viability and upregulated several proinflammatory genes. However, pyoverdine potentiated these iron chelators in activating proinflammatory pathways. Altogether, these findings suggest that the siderophores pyoverdine and pyochelin play distinct roles in virulence during acute P. aeruginosa lung infection.

Collagenous Gastoduodenitis in the Form of a Gastric Ulcer.

Collagenous gastroduodenitis is a rare gastrointestinal disease diagnosed histologically by subepithelial collagen deposition in the lamina propria. Its clinical presentation is diverse. The authors encountered a 17-year-old female patient who complained of epigastric pain. Endoscopy revealed several deep ulcers in the gastric body. The gastric mucosa around the ulcer showed diffuse fine nodularity in the shape of cobblestones with open-type atrophy. The duodenal mucosa showed nodular lesions similar to those of the gastric mucosa. The gastric ulcer healed completely with proton pump inhibitor treatment. The patient was followed up, showing no remarkable mucosal change of stomach or duodenum for several years. Collagenous gastroduodenitis was diagnosed by repeated histologic examinations. This paper reports a rare case of chronic collagen gastritis with deep gastric ulcer and its long-term clinical progress.

Combined high NEDD9 expression and E-cadherin loss correlate with poor clinical outcome in gastric cancer.

BACKGROUND AND AIM: Neural precursor cell expressed developmentally downregulated 9 (NEDD9) is a member of the Cas family. Previous studies have revealed that NEDD9 coordinates the focal adhesion kinase and Src signaling cascades that are involved in integrin-dependent adhesion and migration, invasion, cell apoptosis and life cycle, and survival, which may play a role in epithelial-mesenchymal transformation. The aim of this study was to analyze the expression of NEDD9 and E-cadherin in gastric cancer (GC) and evaluate their clinical significance. METHODS: NEDD9 and E-cadherin expression was analyzed with immunohistochemistry using tissue microarray technique in 435 GC patients who underwent gastrectomy. The NEDD9 expression level was defined by the combination score, which was determined by multiplying the staining intensity score and the proportion score (≥5; NEDD9-high, <5; NEDD9-low). E-cadherin loss was defined as a total loss of staining. The clinicopathologic parameters, overall survival, and disease-free survival rates were analyzed according to the NEDD9 and E-cadherin expression status. RESULTS: The combined NEDD9 and E-cadherin expression status correlated with lymphatic invasion (P = 0.001), vascular invasion (P = 0.020), and T stage (P = 0.001). Combined high NEDD9 expression and loss of E-cadherin expression status had a worse overall survival rate (P < 0.001) and served as a poor prognostic factor (Hazard ratio 2.49, 95% CI 1.25-5, P = 0.01). CONCLUSIONS: Immunohistochemical staining for NEDD9 and E-cadherin may function as a candidate prognostic marker for gastric cancer in everyday practice, especially when applied in combination.

An ergonomic comfort workspace analysis of master manipulator for robotic laparoscopic surgery with motion scaled teleoperation system.

BACKGROUND: In robotic surgery, a surgeon controls a surgical robot through a master manipulator in motion scaled teleoperation environment. However, there are no clear criteria for the master's workspace. METHODS: From the user experiment, we proposed an Ergonomic Comfort Workspace considering ergonomics and performed a verification experiment using the actual surgeons' dataset. RESULTS: From the user experiment, with comfortable posture, there was no significant difference (p-value < 0.05) between the master workspace when the task space is increased, and the workspace is defined as an ergonomic comfort workspace. Using the JIGSAWS dataset, elementary surgical tasks using surgical robots, verify the effectiveness of the ergonomic comfort workspace (ECW). It was confirmed that more than 95% of surgical task data were almost included in the ECW. CONCLUSIONS: The proposed ECW of the master for robotic laparoscopic surgery enables surgeons to perform surgery with high comfort and precision.