Cadherin-6 is a novel mediator for the migration of mesenchymal stem cells to glioblastoma cells in response to stromal cell-derived factor-1.

Glioblastoma recruits various nontransformed cells from distant tissues. Although bone marrow-derived mesenchymal stem cells (MSCs) have been observed migrating to glioblastoma, the underlying mechanism driving MSC migration toward glioblastoma remains unclear. Tumor vascularity is critical in the context of recurrent glioblastoma and is closely linked to the expression of stromal cell-derived factor-1 (SDF-1). We demonstrated that cadherin-6 mediated MSC migration both toward SDF-1 and toward glioblastoma cells. Cadherin-6 knockdown resulted in the downregulation of MSCs capacity to migrate in response to SDF-1. Furthermore, MSCs with cadherin-6 knockdown exhibited impaired migration in response to conditioned media derived from glioblastoma cell lines (U87 and U373) expressing SDF-1, thus simulating the glioblastoma microenvironment. Moreover, MSCs enhanced the vasculogenic capacity of U87 cells without increasing the proliferation, cancer stem cell characteristics, or migration of U87. These results suggest that the current strategy of utilizing MSCs as carriers for antiglioblastoma drugs requires careful examination. Furthermore, cadherin-6 may represent a novel potential target for controlling the recruitment of MSCs toward glioblastoma.

Automatic recognition of second language speech-in-noise.

Measuring how well human listeners recognize speech under varying environmental conditions (speech intelligibility) is a challenge for theoretical, technological, and clinical approaches to speech communication. The current gold standard-human transcription-is time- and resource-intensive. Recent advances in automatic speech recognition (ASR) systems raise the possibility of automating intelligibility measurement. This study tested 4 state-of-the-art ASR systems with second language speech-in-noise and found that one, whisper, performed at or above human listener accuracy. However, the content of whisper's responses diverged substantially from human responses, especially at lower signal-to-noise ratios, suggesting both opportunities and limitations for ASR--based speech intelligibility modeling.

Development of service standards and manpower calculation criteria for hospital clinical pharmacies in South Korea: a survey-based study.

BACKGROUND: After the revision of the Korean Pharmaceutical Affairs Act, the certification of specialized pharmacists is scheduled to be legally recognized in 2023. Considering that the specialized pharmacist certification was developed based on the working model of hospital clinical pharmacists, it is necessary to establish standards for clinical pharmacists in hospitals and to calculate appropriate manpower. Through this study, we aim to establish practical standards for clinical pharmacists and propose a method for calculating staffing levels based on an investigation of actual workloads. METHODS: This survey-based study consisted of two phases. In the first phase, a literature review was conducted to establish standards for clinical pharmacy services, and tasks in relevant literature were classified to identify clinical pharmacy service tasks that are applicable to the practice of Korean hospitals. Additionally, a preliminary survey was conducted to investigate the essential tasks. In the second phase of the investigation, a multicenter survey was conducted targeting pharmacists in facilities with more than 1,000 beds to explore their perceptions and actual workloads related to tasks. RESULTS: According to the standards for clinical pharmacists in Korea, clinical pharmacy services consist of a total of 23 tasks, of which 16 have been identified as essential tasks. Essential tasks accounted for 93% of the total tasks in clinical pharmacy services. The average full-time equivalent (FTE) through workload calculation was 2.5 ± 1.9 for each field, while the FTE allocated to actual practice was 2.1 ± 1.6. The distribution of each type of clinical pharmacy service was as follows: 77% for medication therapy management, 13% for medication education, 8% for multidisciplinary team activities, and 3% for medication use evaluation. CONCLUSION: This study identified essential tasks common to clinical pharmacy services across different healthcare institutions. However, the FTE of clinical pharmacists in actual practice was insufficient compared to the required amount. In order to establish and expand clinical pharmacy services in a hospital, it is necessary to ensure an adequate workforce for essential tasks.

Breast Tumor Cell-Stimulated Bone Marrow-Derived Mesenchymal Stem Cells Promote the Sprouting Capacity of Endothelial Cells by Promoting VEGF Expression, Mediated in Part through HIF-1α Increase.

Breast tumor cells recruit bone marrow-derived mesenchymal stem cells (BM-MSCs) and alter their cellular characteristics to establish a tumor microenvironment. BM-MSCs enhance tumor angiogenesis through various mechanisms. We investigated the mechanisms by which BM-MSCs promote angiogenesis in response to breast tumor. Conditioned media from MDA-MB-231 (MDA CM) and MCF7 (MCF7 CM) breast tumor cells were used to mimic breast tumor conditions. An in vitro spheroid sprouting assay using human umbilical vein endothelial cells (HUVECs) was conducted to assess the angiogenesis-stimulating potential of BM-MSCs in response to breast tumors. The ROS inhibitor N-acetylcysteine (NAC) and JAK inhibitor ruxolitinib attenuated increased HIF-1α in BM-MSCs in response to MDA CM and MCF7 CM. HIF-1α knockdown or HIF-1ß only partially downregulated VEGF expression and, therefore, the sprouting capacity of HUVECs in response to conditioned media from BM-MSCs treated with MDA CM or MCF7 CM. Inactivation of the VEGF receptor using sorafenib completely inhibited the HUVECs' sprouting. Our results suggest that increased HIF-1α expression under normoxia in BM-MSCs in response to breast tumor cells is mediated by ROS and JAK/Stat3, and that both HIF-1α-dependent and -independent mechanisms increase VEGF expression in BM-MSCs to promote the angiogenic sprouting capacity of endothelial cells in a VEGF-dependent manner.

Localizing category-related information in speech with multi-scale analyses.

Measurements of the physical outputs of speech-vocal tract geometry and acoustic energy-are high-dimensional, but linguistic theories posit a low-dimensional set of categories such as phonemes and phrase types. How can it be determined when and where in high-dimensional articulatory and acoustic signals there is information related to theoretical categories? For a variety of reasons, it is problematic to directly quantify mutual information between hypothesized categories and signals. To address this issue, a multi-scale analysis method is proposed for localizing category-related information in an ensemble of speech signals using machine learning algorithms. By analyzing how classification accuracy on unseen data varies as the temporal extent of training input is systematically restricted, inferences can be drawn regarding the temporal distribution of category-related information. The method can also be used to investigate redundancy between subsets of signal dimensions. Two types of theoretical categories are examined in this paper: phonemic/gestural categories and syntactic relative clause categories. Moreover, two different machine learning algorithms were examined: linear discriminant analysis and neural networks with long short-term memory units. Both algorithms detected category-related information earlier and later in signals than would be expected given standard theoretical assumptions about when linguistic categories should influence speech. The neural network algorithm was able to identify category-related information to a greater extent than the discriminant analyses.

Veno-arterial extracorporeal membrane oxygenation for severe fever with thrombocytopenia syndrome with fulminant myocarditis: a case report.

BACKGROUND: The clinical spectrum of severe fever with thrombocytopenia syndrome (SFTS) is wide, which can range from fever to multiple organ failure. Conservative therapy plays a key role in the treatment of SFTS. However, severe cases of SFTS, such as fulminant myocarditis, may require mechanical hemodynamic support. CASE PRESENTATION: This report presents a case of a 59-year old woman diagnosed with SFTS by reverse-transcription polymerase chain reaction. The patient had no initial symptoms of cardiac involvement and rapidly developed hemodynamic instability 3 days after hospitalization. She suffered from chest pain and had elevated cardiac enzymes. In the absence of atrio-ventricular conduction abnormalities, left ventricular dysfunction, and coronary artery abnormalities by coronary angiography, she was diagnosed with fulminant myocarditis. At that time, her pulse rate nearly dropped to 0 bpm and she developed near complete akinesia of the heart despite vasopressor administration. Veno-arterial extracorporeal membrane oxygenation (ECMO) was initiated with other supportive measures and she fully recovered after 21 days. CONCLUSIONS: This case indicates that SFTS can cause fulminant myocarditis even without evidence of cardiac involvement at presentation. When symptoms and/or signs of acute heart failure develop in patients with SFTS, myocarditis should be suspected and the patient should be promptly evaluated. Additionally, mechanical hemodynamic support like ECMO can be a lifesaving tool in the treatment of fulminant myocarditis.

Air and Environmental Contamination Caused by COVID-19 Patients: a Multi-Center Study.

BACKGROUND: The purpose of this study was to determine the extent of air and surface contamination of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in four health care facilities with hospitalized coronavirus disease 2019 (COVID-19) patients. METHODS: We investigated air and environmental contamination in the rooms of eight COVID-19 patients in four hospitals. Some patients were in negative-pressure rooms, and others were not. None had undergone aerosol-generating procedures. On days 0, 3, 5, and 7 of hospitalization, the surfaces in the rooms and anterooms were swabbed, and air samples were collected 2 m from the patient and from the anterooms. RESULTS: All 52 air samples were negative for SARS-CoV-2 RNA. Widespread surface contamination of SARS-CoV-2 RNA was observed. In total, 89 of 320 (27%) environmental surface samples were positive for SARS-CoV-2 RNA. Surface contamination of SARS-CoV-2 RNA was common in rooms without surface disinfection and in rooms sprayed with disinfectant twice a day. However, SARS-CoV-2 RNA was not detected in a room cleaned with disinfectant wipes on a regular basis. CONCLUSION: Our data suggest that remote (> 2 m) airborne transmission of SARS-CoV-2 from hospitalized COVID-19 patients is uncommon when aerosol-generating procedures have not been performed. Surface contamination was widespread, except in a room routinely cleaned with disinfectant wipes.

Minimal Resection of Jejuna Dieulafoy's Lesion Using an Intraoperative Fluoroscopic Localization of the Metallic Coils Used in Angiography.

Dieulafoy's lesions of the Jejunum are extremely rare. Therefore, localization of lesions is very difficult due to their small size and tendency of occasional bleeding. However, it is important to mention the location of the Dieulafoy's lesions to prevent excessive intestinal resections or, even worse, resection of the normal intestine. We report a case of preoperative localization of a Dieulafoy's lesion embolized by a metallic coil that allows a surgeon to accurately identify the bleeding, permitting a minimally invasive surgical treatment. A 25-year-old man presented with massive hematochezia. There was no definite bleeding focus on the upper gastrointestinal endoscopy and colonoscopy. An angiography found a persistent extravasation of the contrast media at the end of straight artery of the mid-jejunal branch, around the terminal ileum, embolized with metallic coils immediately. The combination of embolized metallic coils and intraoperative fluoroscopy allowed accurate identification and minimal laparotomy. Consequently, a highly selective and minimal resection of the jejunum containing the dieulafoy lesion was possible without any postoperative complications.

The role of second-look endoscopy in endoscopic submucosal dissection for early gastric cancer.

BACKGROUND/AIMS: Delayed bleeding is a major complication of endoscopic submucosal dissection. Second-look endoscopy is routinely performed in most hospitals to reduce the possibility of delayed bleeding without solid evidence to support this practice. The aim of this study was to evaluate whether second-look endoscopy prevents delayed bleeding, and to verify clinicopathological features of delayed bleeding in order to identify lesions that may benefit from a second-look endoscopy. MATERIALS AND METHODS: We investigated 392 lesions in 388 patients who underwent endoscopic submucosal dissection for early gastric cancer from January 2006 to July 2011. Clinically evident bleeding from mucosal defects 24 hours after endoscopic submucosal dissection was considered delayed bleeding. Data including characteristics of patients, lesions, and procedures were reviewed. Furthermore, the rate of delayed bleeding before and after second-look endoscopy, performed within three days of endoscopic submucosal dissection, was investigated to determine the utility of second-look endoscopy. RESULTS: Delayed bleeding was evident in 12 of 392 lesions (3,1%), all of which achieved endoscopic hemostasis. The only significant factor predicting delayed bleeding was a resected specimen size of over 40 mm (OR=6,200, 95% CI=1,912 - 20,108). Delayed bleeding occurred more frequently prior to the second-look endoscopy (p=0,022). CONCLUSIONS: In our endoscopic submucosal dissection data about early gastric cancer, it is too early to conclude that second-look endoscopy is not a valuable procedure, and second-look endoscopy may be useful for preventing post-endoscopic submucosal dissection bleeding, especially in resected specimens greater than 40 mm in size.

[Benzoxazole derivative B-98 ameliorates dextran sulfate sodium-induced acute murine colitis and the change of T cell profiles in acute murine colitis model].

BACKGROUND/AIMS: The unique role of enzyme 5-lipoxygenase (5-LO) in the production of leukotrienes makes it a therapeutic target for inflammatory bowel disease (IBD). The aim of this study was to evaluate the effects of B-98, a newly synthesized benzoxazole derivatives and a novel 5-LO inhibitor, in a mouse model of IBD induced by dextran sulfate sodium (DSS). METHODS: C57BL/6 mice were randomly assigned to four groups: normal control, DSS colitis (DSS+saline), low dose B-98 (DSS＋B-98 20 mg/kg) and high dose B-98 (DSS＋B-98 100 mg/kg). B-98 was administered with 3% DSS intraperitoneally. The severity of the colitis was assessed via the disease activity index (DAI), colon length, and histopathologic grading. The production of inflammatory cytokines interleukin (IL)-6 was determined by RT-PCR. Th cells were examined for the proportion of Th1 cell, Th2 cell, Th9 cell, Th17 cell and Treg cell using intracellular cytometry. RESULTS: The B-98 group showed lower DAI, less shortening of the colon length and lower histopathologic grading compared with the DSS colitis group (p<0.01). The expression of IL-6 in colonic tissue was significantly lower in the B-98 groups than the DSS colitis group (p<0.05). The cellular profiles revealed that the Th1, Th9 and Th17 cells were increased in the DSS colitis group compared to the B-98 group (p<0.05). CONCLUSIONS: Our results suggest that acute intestinal inflammation is reduced in the group treated with B-98 by Th1, Th9 and Th17 involved cellular immunity.

Diabetes and oral health: the importance of oral health-related behavior.

PURPOSE: The objective of this study was to explore oral health-related behavior, how patients with diabetes differ from patients not diagnosed with diabetes in their oral health and whether oral health-related behavior moderates the oral health status of patients with diabetes. METHODS: Survey and chart review data were collected from 448 patients (52% male, 48% female, average age: 57 years) of which 77 were diagnosed with diabetes (17%). RESULTS: Patients with diabetes had a higher percentage of teeth with mobility than those not diagnosed with diabetes (14% vs. 8%, p=0.023), as well as gingival recession (16% vs. 12%, p=0.035) and more teeth with recession in the esthetic zone (1.17 vs. 0.88, p=0.046). They also had more decayed, missing and filled surfaces due to caries (101 vs. 82, p<0.001) and more missing teeth due to caries (11 vs. 7, p<0.001). Patients with diabetes brushed and flossed less frequently. Patients with diabetes who did not brush regularly had poorer periodontal health (percentage of teeth with probing depth of <4 mm: 82% vs. 60%, p=0.039, 4 to 6 mm: 34% vs. 17%, p=0.059) and more caries (percentage of decayed teeth: 32% vs. 15%, p=0.033) than regularly brushing patients with diabetes. CONCLUSION: Educating patients with diabetes about the importance of good oral self care needs to become a priority for their oral health care providers.

Vascular administration of adenoviral vector soaked in absorbable gelatin sponge particles (GSP) prolongs the transgene expression in hepatocytes.

Transcatheter hepatic arterial chemoembolization using emulsions composed of anticancer agents and gelatin sponges (GS) has been an efficient and safe palliative treatment for inoperable hepatocellular carcinoma (HCC). We employed catheter-mediated left hepatic arterial embolization (CHAE) to increase transduction efficiency of adenoviral vector in canine hepatocytes. The emulsion was prepared by mixing pieces of GSP and adenoviral vectors expressing recombinant beta-galactosidase (Ad.LacZ) or human hepatocyte growth factor (Ad.hHGF). After the left hepatic artery was catheterized under angiography, CHAE with Ad.LacZ or Ad.hHGF was performed. Livers were removed and stained for LacZ activity on day 7. The expression pattern of LacZ staining was either scarce or patchy around the central hilum of the hepatic artery, or was homogeneously distributed in whole lobes, depending on whether large or small pieces of GSP were used. Hematological and serum biochemical changes during CHAE exhibited only a few effects. The chronological measurement of serum HGF concentration showed that the duration of transgene expression was greater after CHAE with Ad.hHGF. A similar pattern of transgene expression was observed in a rat model after hepatic arterial embolization with differential doses of Ad.hHGF soaked in GSP. These results suggest that hepatic arterial embolization by transcatheter mediated infusion with a mixture of adenovirus-GSP could be used for human HCC.