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ABSTRACTObjective:The study aimed to evaluate the improvement of patient knowledge of warfarin use, satisfaction with pharmacists, and the quality of international normalized ratio (INR) control after the implementation of an anticoagulant clinic (ACC) service.Methods:This was a prospective single-group pre- and post-comparison study. Patients who were at least 20 years of age and participated in a pharmacist-managed ACC service were enrolled from February 2012 to September 2015. Each participant completed a self-administered questionnaire before and after the ACC service to evaluate changes in warfarin knowledge. Another questionnaire was distributed after the ACC to evaluate participants’ satisfaction with the pharmacist service in the ACC. The INR levels before and after the ACC intervention were obtained to calculate the proportion of time spent in the therapeutic INR range (time in therapeutic range, TTR). Paired t-tests were used to compare changes in participants’ knowledge related to warfarin use. Multiple linear regressions were performed to explore the predictors associated with the participants’ knowledge scores and TTR after the ACC intervention.Results:One hundred and forty-eight participants were enrolled in this study. A significant improvement (31.5%,p<0.001) in the knowledge of warfarin use was observed at the end of the ACC intervention. The interaction between warfarin and food was the most confusing factor for participants in warfarin use. More than 95% of the participants perceived a positive value of the pharmacist-managed ACC service. However, the consultation fee was the least satisfactory of the ACC service. The average TTR increased from 51.0±34.3% to 78.6±24.5% (p<0.001) after the ACC service was implemented. Participants’ education levels and baseline knowledge scores were significant determinants associated with the knowledge improvement in the appropriate warfarin use (p<0.001).Conclusions:A pharmacist-managed ACC improved patient knowledge of warfarin use and INR control, and led to high satisfaction with the pharmacist service in the ACC in Taiwan. Pharmacists should focus on patients with lower education levels to facilitate their understanding of the appropriate warfarin use for better health outcomes.

This study aims to: (1) assess learner demographics of Introduction to Dental Medicine (IDM), an early Massive Open Online Course (MOOC) developed for the Coursera platform and (2) analyze course enrollment to determine worldwide interest in accessible, high‐quality dental education. The authors review the development and organization of IDM and present learner statistics to critically evaluate learner traits and course engagement for IDM. IDM has been available since June 15, 2015, and as of March 1, 2020, gained 90,374 visitors, of whom 16,739 have enrolled and demonstrate continued monthly and daily engagement. Learners represent all age groups and genders and include participants of all educational and employment backgrounds, reflecting broad interest in dental knowledge. They originate from 6 continents with the largest percentages of learners from countries including the United States, Egypt, India, and the United Kingdom. IDM learners have provided positive feedback, rating the course 4.8/5 stars and often providing individual accounts of the benefit of their experiences. IDM presented an opportunity to learn general dental concepts. The course served to increase familiarity in the field for all learners, including health professionals, patients, and anyone with an interest in the subject. It also served as preparation for or to expand education in dental, medical, and allied health professions. High learner engagement with wide global distribution demonstrated interest in dental education worldwide.

The coronavirus disease 2019 (COVID‐19) pandemic presented unprecedented challenges and interruptions to education at all levels. As many across the world were required to stay at home, virtual educational resources were developed and relied upon to provide all levels and subjects of instruction. Introduction to Dental Medicine, a massive open online course in dentistry, experienced an increase in enrollment during the start of the pandemic and learners displayed a positive reception to the information provided. Introduction to Dental Medicine was particularly well positioned as a resource during the pandemic given its availability, established nature, and the wide accessibility of course material. As disruptions to normal activities continue, this and other virtual educational methods may continue to play a central role in education and exposure to dentistry.

This paper describes a facile and tunable method, performed at room temperature and amenable to mass-production, for the preparation of nitrogen-doped graphene sheets using in situelectrochemical cathodic plasma exfoliation of a graphite/melamine composite. The plasma generated at the submerged surface of the graphite/melamine composite electrode not only exfoliated the graphite granules into graphene sheets but also induced the doping of nitrogen atoms. The sizes and morphologies of the graphene sheets, comprising four to five layers of graphene, were confirmed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Tuning the concentration of melamine in the graphite/melamine composites led to different levels of nitrogen-doping in the graphene sheets; the stability of the nitrogen-doped graphene sheets was investigated in various harsh environments. Furthermore, the use of the 4.63 at% nitrogen-doped graphene sheets as anode materials resulted in lithium-ion batteries displaying excellent performance, with a capacity of 488 mA h g−1at 100 mA g−1after 100 cycles that was better than that of the device incorporating pristine graphene sheets (344 mA h g−1at 100 mA g−1after 100 cycles). This method is a new and tunable approach for producing massive amounts of nitrogen-doped graphene sheets from graphite powder at room temperature.

ABSTRACTMycobacterium aviumsubsp. paratuberculosiscauses Johne's disease, an enteric infection in cattle and other ruminants, greatly afflicting the dairy industry worldwide. Once inside the cell, M. aviumsubsp. paratuberculosisis known to survive harsh microenvironments, especially those inside activated macrophages. To improve our understanding of M. aviumsubsp. paratuberculosispathogenesis, we examined phagosome maturation associated with transcriptional responses of M. aviumsubsp. paratuberculosisduring macrophage infection. Monitoring cellular markers, only live M. aviumsubsp. paratuberculosisbacilli were able to prevent phagosome maturation and reduce its acidification. On the transcriptional level, over 300 M. aviumsubsp. paratuberculosisgenes were significantly and differentially regulated in both naive and IFN-?-activated macrophages. These genes include the sigma factor H (sigH) that was shown to be important for M. aviumsubsp. paratuberculosissurvival inside gamma interferon (IFN-?)-activated bovine macrophages. Interestingly, an sigH-knockout mutant showed increased sensitivity to a sustained level of thiol-specific oxidative stress. Large-scale RNA sequence analysis revealed that a large number of genes belong to the sigHregulon, especially following diamide stress. Genes involved in oxidative stress and virulence were among the induced genes in the sigHregulon with a putative consensus sequence for SigH binding that was recognized in a subset of these genes (n= 30), suggesting direct regulation by SigH. Finally, mice infections showed a significant attenuation of the ?sigHmutant compared to its parental strain, suggesting a role for sigHin M. aviumsubsp. paratuberculosisvirulence. Such analysis could identify potential targets for further testing as vaccine candidates against Johne's disease.

The electron-emission properties of nitrogen-induced (N-induced) localized defects in InAsN/GaAs quantum dots (QDs) are investigated in detail by capacitance--voltage ($C$--$V$) profiling and bias-dependent deep-level transient spectroscopy (DLTS). The incorporation of nitrogen (N) into InAs QDs is shown to produce localized defects near QDs and threading-dislocation-related defects in the top GaAs layer. The threading dislocation is associated with an electron-emission energy of approximately 0.648 eV and emission from the sample surface toward the QDs. The electron-emission energy from the QDs associated with the localized defects increases from 0.19 to 0.36 eV, indicating that both types of defect near QDs have low electron emission energies. Therefore, the change in emission energy is attributable to the defects across the QD interface where a band offset exists. The $C$--$V$ profile at 300 K shows extended carrier depletion near the QDs. As ac frequency increases, an electron-emission peak emerges at the QDs; this peak is followed by another prominent peak, suggesting that the localized defect that is responsible for this latter peak has an energy below the QD electron ground state. On the basis of a $C$--$V$ profile simulation, this defect is located at the QD at the observed emission energy below the GaAs conduction band, 360 meV. A comparison with InAsN QD and strain relaxation InAs QD samples reveals that the localized defect arises from a nitrogen alloy fluctuation in the QD. The energy location of this defect reveals a possibility that incorporated N is associated with a particular mode.

Infection with Mycobacterium avium subsp. paratuberculosis causes Johne's disease in cattle and is a serious problem for the dairy industry worldwide. Development of models to mimic aspects of Johne's disease remains an elusive goal because of the chronic nature of the disease. In this report, we describe a surgical approach employed to characterize the very early stages of infection of calves with M. avium subsp. paratuberculosis. To our surprise, strains of M. avium subsp. paratuberculosis were able to traverse the intestinal tissues within 1 h of infection in order to colonize distant organs, such as the liver and lymph nodes. Both the ileum and the mesenteric lymph nodes were persistently infected for months following intestinal deposition of M. avium subsp. paratuberculosis despite a lack of fecal shedding of mycobacteria. During the first 9 months of infection, humoral immune responses were not detected. Nonetheless, using flow cytometric analysis, we detected a significant change in the cells participating in the inflammatory responses of infected calves compared to cells in a control animal. Additionally, the levels of cytokines detected in both the ileum and the lymph nodes indicated that there were TH1-type-associated cellular responses but not TH2-type-associated humoral responses. Finally, surgical inoculation of a wild-type strain and a mutant M. avium subsp. paratuberculosis strain (with an inactivated gcpE gene) demonstrated the ability of the model which we developed to differentiate between the wild-type strain and a mutant strain of M. avium subsp. paratuberculosis deficient in tissue colonization and invasion. Overall, novel insights into the early stages of Johne's disease were obtained, and a practical model of mycobacterial invasiveness was developed. A similar approach can be used for other enteric bacteria.

ABSTRACTInfection with Mycobacterium aviumsubsp. paratuberculosiscauses Johne's disease in cattle and is a serious problem for the dairy industry worldwide. Development of models to mimic aspects of Johne's disease remains an elusive goal because of the chronic nature of the disease. In this report, we describe a surgical approach employed to characterize the very early stages of infection of calves with M. aviumsubsp. paratuberculosis. To our surprise, strains of M. aviumsubsp. paratuberculosiswere able to traverse the intestinal tissues within 1 h of infection in order to colonize distant organs, such as the liver and lymph nodes. Both the ileum and the mesenteric lymph nodes were persistently infected for months following intestinal deposition of M. aviumsubsp. paratuberculosisdespite a lack of fecal shedding of mycobacteria. During the first 9 months of infection, humoral immune responses were not detected. Nonetheless, using flow cytometric analysis, we detected a significant change in the cells participating in the inflammatory responses of infected calves compared to cells in a control animal. Additionally, the levels of cytokines detected in both the ileum and the lymph nodes indicated that there were TH1-type-associated cellular responses but not TH2-type-associated humoral responses. Finally, surgical inoculation of a wild-type strain and a mutant M. aviumsubsp. paratuberculosisstrain (with an inactivated gcpEgene) demonstrated the ability of the model which we developed to differentiate between the wild-type strain and a mutant strain of M. aviumsubsp. paratuberculosisdeficient in tissue colonization and invasion. Overall, novel insights into the early stages of Johne's disease were obtained, and a practical model of mycobacterial invasiveness was developed. A similar approach can be used for other enteric bacteria.

ABSTRACTJohne's disease, caused by Mycobacterium paratuberculosisinfection, is a worldwide problem for the dairy industry and has a possible involvement in Crohn's disease in humans. To identify virulence determinants of this economically important pathogen, a library of 5,060 transposon mutants was constructed using Tn5367insertion mutagenesis, followed by large-scale sequencing to identify disrupted genes. In this report, 1,150 mutants were analyzed and 970 unique insertion sites were identified. Sequence analysis of the disrupted genes indicated that the insertion of Tn5367was more prevalent in genomic regions with G+C content (50.5 to 60.5%) lower than the average G+C content (69.3%) of the rest of the genome. Phenotypic screening of the library identified disruptions of genes involved in iron, tryptophan, or mycolic acid metabolic pathways that displayed unique growth characteristics. Bioinformatic analysis of disrupted genes identified a list of potential virulence determinants for further testing with animals. Mouse infection studies showed a significant decrease in tissue colonization by mutants with a disruption in the gcpE, pstA, kdpC, papA2, impA, umaA1, or fabG2_2gene. Attenuation phenotypes were tissue specific (e.g., for the umaA1mutant) as well as time specific (e.g., for the impAmutant), suggesting that those genes may be involved in different virulence mechanisms. The identified potential virulence determinants represent novel functional classes that could be necessary for mycobacterial survival during infection and could provide suitable targets for vaccine and drug development against Johne's and Crohn's diseases.