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Spike-mediated entry of SARS-CoV-2 into human airway epithelial cells is an attractive therapeutic target for COVID-19. In addition to protein receptors, the SARS-CoV-2 spike (S) protein also interacts with heparan sulfate, a negatively charged glycosaminoglycan (GAG) attached to certain membrane proteins on the cell surface. This interaction facilitates the engagement of spike with a downstream receptor to promote viral entry. Here, we show that Mitoxantrone, an FDA-approved topoisomerase inhibitor, targets a spike-GAG complex to compromise the fusogenic function of spike in viral entry. As a single agent, Mitoxantrone inhibits the infection of an authentic SARS-CoV-2 strain in a cell-based model and in human lung EpiAirway 3D tissues. Gene expression profiling supports the plasma membrane as a major target of Mitoxantrone but also underscores an undesired activity targeting nucleosome dynamics. We propose that Mitoxantrone analogs bearing similar GAG-binding activities but with reduced affinity for DNA topoisomerase may offer an alternative therapy to overcome breakthrough infections in the post-vaccine era.
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Purpose@#Physicians' awareness of their cancer patients' unmet needs is an essential element for providing effective treatment. This study investigated the accuracy of physicians' awareness of breast cancer survivors' unmet needs in Korea. @*Methods@#A cross-sectional interview survey was performed among 106 physicians and 320 Korean breast cancer survivors. The Comprehensive Needs Assessment Tool was administered to physicians and cancer survivors after obtaining their written informed consent to participate. Data were analyzed using t-test, analysis of variance, and multiple regression analysis. @*Results@#The level of unmet needs was highest in the hospital service domain (mean ± standard deviation: 2.19 ± 0.82), and the top-ranked unmet need item was “wished my doctor to be easy, specific, and honest in his/her explanation” (2.44 ± 0.93). Higher unmet needs were correlated with the presence of a genetic counseling clinic. They were not associated with age, sex, marital status, religion, department, working period, type of institution, number of staff, and number of operations. In multiple regression analysis, the presence of a genetic counseling clinic was associated with a higher level of recognition for psychological problems, social support, hospital service, and information and education needs. Physicians overestimated breast cancer survivors' unmet needs in all domains, compared to their selfreported unmet needs. The discordance in the perceived unmet needs was highest in the ‘family/personal relationship problems’ domain. @*Conclusions@#Physicians who treat Korean breast cancer survivors rated the level of unmet needs of breast cancer survivors as highest in the hospital service domain. The presence of a genetic counseling clinic in physicians' institutions was associated with a higher perception of survivors' unmet needs. Physicians overestimated the level of unmet needs in Korean breast cancer survivors. Efforts to reduce these discordances are needed to implement optimal survivorship care.
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Purpose@#As the survival rates of cancer patients have been increasing due to early diagnosis and technological advances in treatment, their caregiver burden has also emerged as an important issue. In view of this situation, this study aims to investigate the unmet needs and quality of life of caregivers of Korean breast cancer survivors. @*Methods@#A multicenter cross-sectional interview survey was performed among 160 caregivers of Korean breast cancer survivors. Caregivers who gave written informed consent to participate completed the Comprehensive Needs Assessment Tool for Cancer Caregivers and EuroQol-5 Dimensions. @*Results@#The mean age of the caregivers was 46.4 years, 44.4% (71 of 160) were spouses of patients, and 52.5% (84 of 160) were personally taking care of cancer survivors. Unmet needs were highest in the ‘healthcare staff’ domain and the item with the highest level of unmet needs was ‘needed information about the current status of the patient’s illness and its future courses.’ Poorer quality of life was closely related to higher levels of unmet needs. In multiple regression analysis, older age, employment, the presence of religion, and higher levels of stress and despair in daily life were associated with higher levels of unmet needs. @*Conclusion@#The most prevalent unmet need in Korean breast cancer caregivers was found in the ‘healthcare staff’ domain, and their quality of life was closely related to unmet needs. Therefore, healthcare staff is required to make efforts to accurately identify breast cancer caregivers vulnerable in terms of unmet needs and address their unmet needs.
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Purpose@#Physicians' awareness of their cancer patients' unmet needs is an essential element for providing effective treatment. This study investigated the accuracy of physicians' awareness of breast cancer survivors' unmet needs in Korea. @*Methods@#A cross-sectional interview survey was performed among 106 physicians and 320 Korean breast cancer survivors. The Comprehensive Needs Assessment Tool was administered to physicians and cancer survivors after obtaining their written informed consent to participate. Data were analyzed using t-test, analysis of variance, and multiple regression analysis. @*Results@#The level of unmet needs was highest in the hospital service domain (mean ± standard deviation: 2.19 ± 0.82), and the top-ranked unmet need item was “wished my doctor to be easy, specific, and honest in his/her explanation” (2.44 ± 0.93). Higher unmet needs were correlated with the presence of a genetic counseling clinic. They were not associated with age, sex, marital status, religion, department, working period, type of institution, number of staff, and number of operations. In multiple regression analysis, the presence of a genetic counseling clinic was associated with a higher level of recognition for psychological problems, social support, hospital service, and information and education needs. Physicians overestimated breast cancer survivors' unmet needs in all domains, compared to their selfreported unmet needs. The discordance in the perceived unmet needs was highest in the ‘family/personal relationship problems’ domain. @*Conclusions@#Physicians who treat Korean breast cancer survivors rated the level of unmet needs of breast cancer survivors as highest in the hospital service domain. The presence of a genetic counseling clinic in physicians' institutions was associated with a higher perception of survivors' unmet needs. Physicians overestimated the level of unmet needs in Korean breast cancer survivors. Efforts to reduce these discordances are needed to implement optimal survivorship care.
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Purpose@#As the survival rates of cancer patients have been increasing due to early diagnosis and technological advances in treatment, their caregiver burden has also emerged as an important issue. In view of this situation, this study aims to investigate the unmet needs and quality of life of caregivers of Korean breast cancer survivors. @*Methods@#A multicenter cross-sectional interview survey was performed among 160 caregivers of Korean breast cancer survivors. Caregivers who gave written informed consent to participate completed the Comprehensive Needs Assessment Tool for Cancer Caregivers and EuroQol-5 Dimensions. @*Results@#The mean age of the caregivers was 46.4 years, 44.4% (71 of 160) were spouses of patients, and 52.5% (84 of 160) were personally taking care of cancer survivors. Unmet needs were highest in the ‘healthcare staff’ domain and the item with the highest level of unmet needs was ‘needed information about the current status of the patient’s illness and its future courses.’ Poorer quality of life was closely related to higher levels of unmet needs. In multiple regression analysis, older age, employment, the presence of religion, and higher levels of stress and despair in daily life were associated with higher levels of unmet needs. @*Conclusion@#The most prevalent unmet need in Korean breast cancer caregivers was found in the ‘healthcare staff’ domain, and their quality of life was closely related to unmet needs. Therefore, healthcare staff is required to make efforts to accurately identify breast cancer caregivers vulnerable in terms of unmet needs and address their unmet needs.
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The cell entry of SARS-CoV-2 has emerged as an attractive drug repurposing target for COVID-19. Here we combine genetics and chemical perturbation to demonstrate that ACE2-mediated entry of SARS-CoV and CoV-2 requires the cell surface heparan sulfate (HS) as an assisting cofactor: ablation of genes involved in HS biosynthesis or incubating cells with a HS mimetic both inhibit Spike-mediated viral entry. We show that heparin/HS binds to Spike directly, facilitates the attachment of viral particles to the cell surface to promote cell entry. We screened approved drugs and identified two classes of inhibitors that act via distinct mechanisms to target this entry pathway. Among the drugs characterized, Mitoxantrone is a potent HS inhibitor, while Sunitinib and BNTX disrupt the actin network to indirectly abrogate HS-assisted viral entry. We further show that drugs of the two classes can be combined to generate a synergized activity against SARS-CoV-2-induced cytopathic effect. Altogether, our study establishes HS as an attachment factor that assists SARS coronavirus cell entry, and reveals drugs capable of targeting this important step in the viral life cycle.
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This study aimed to evaluate the relationship of sweet taste perception with overweight and obesity among workers in some industrial areas. Participants were 63 workers (mean age: 57.8±7.8 years), who were divided into three subgroups based on sweet taste evaluation using a sweet taste assessment tool provided by Ministry of Food and Drug Safety: unsweet group (n=25), medium sweet group (n=27), and sweet group (n=11). There was no significant difference in body mass index (BMI), and any work-related variables among the three groups; however, the difference between subjective perception and objective perception for sweet tastes is statistically different. We also found slight or fair agreement between subjective and objective sweet taste perception of the subjects (weighted kappa value 0.34~0.43). The present study provided measuring objective sweet taste perception may be useful for assessing the risk of high sugar consumption and for improving undesirable dietary behaviors, and management of non-communicable disease among workers.
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BACKGROUND: The intraarticular (IA) injection has become popular for the management of the osteoarthritic knee without an effusion. The success rate of IA injection would be better if it was able to be visually confirmed. We hypothesized that an anterolateral approach, which targets the synovial membrane of the lateral condyle using ultrasound, would provide an equivalent alternative to the anterolateral approach, targeting the synovial membrane of the medial condyle for IA injection of the knee. METHODS: A total of 96 knees with osteoarthritis were randomized placed into the two groups, which were group I (anterolateral approach to the medial condyle) and group II (anterolateral approach to the lateral condyle). The primary outcome was to compare the success rate of the two methods of IA injection. The required length of the needle for injection was also measured and compared. Pain intensity was assessed using the Numeric Rating Scale in order to evaluate the success of injection. RESULTS: There were no significant differences in the success rate between both groups. The success rate of group I and group II were 87.8% (95%, CI 78.7–97.0) and 91.5% (95%, CI 83.6–99.5), respectively (P = 0.549). The needle depth was 5.0 ± 0.8 (3.0 to 6.1 cm) in group I, and 3.0 ± 0.8 (1.5 to 5 cm) in group II (P < 0.001). CONCLUSIONS: The anterolateral approach to the lateral femoral condyle, using ultrasound, is an alternative method to the approach targeting the medial femoral condyle, using shorter needle.
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Humanos , Epífises , Injeções Intra-Articulares , Articulação do Joelho , Joelho , Métodos , Agulhas , Osteoartrite , Membrana Sinovial , UltrassonografiaRESUMO
PURPOSE: Follow-up after primary treatment for breast cancer is an important component of survivor care and various international guidelines exist for the surveillance. However, little is known about current actual practice patterns of physicians whether they adhere to or deviate from recommended guidelines. The aim of this study was to determine how physicians follow-up their patients after primary treatment for breast cancer in Korea. METHODS: A questionnaire survey with 34 questions in 4 categories was e-mailed to the members of Korean Breast Cancer Society from November to December 2013. Respondents were asked how they use follow-up modalities after primary treatment of breast cancer and we compared the survey results with present guidelines. RESULTS: Of the 129 respondents, 123 (95.3%) were breast surgeons. The most important consideration in follow-up was tumor stage. History taking, physical examinations, and mammography were conducted in similar frequency recommended by other guidelines while breast ultrasonography was performed more often. The advanced imaging studies such as CT, MRI, and bone scan, which had been recommended to be conducted only if necessary, were also examined more frequently. Regular screenings for secondary malignancy were performed in 38 respondents (29.5%). Five years later after primary treatment, almost the whole respondents (94.6%) themselves monitored their patients. CONCLUSION: A majority of respondents have been performed more intensive follow-up modalities in comparison with present guidelines and less frequently screenings for secondary malignancy. For optimal follow-up of breast cancer survivors, tailored delivery system should be considered.
