Mitochondrial uridine insertion/deletion RNA editing, catalyzed by a multiprotein complex (editosome), is essential for gene expression in trypanosomes and Leishmania parasites. As this process is ...absent in the human host, a drug targeting this mechanism promises high selectivity and reduced toxicity. Here, we successfully miniaturized our FRET-based full-round RNA editing assay, which replicates the complete RNA editing process, adapting it into a 1536-well format. Leveraging this assay, we screened over 100,000 compounds against purified editosomes derived from Trypanosoma brucei, identifying seven confirmed primary hits. We sourced and evaluated various analogs to enhance the inhibitory and parasiticidal effects of these primary hits. In combination with secondary assays, our compounds marked inhibition of essential catalytic activities, including the RNA editing ligase and interactions of editosome proteins. Although the primary hits did not exhibit any growth inhibitory effect on parasites, we describe eight analog compounds capable of effectively killing T. brucei and/or Leishmania donovani parasites within a low micromolar concentration. Whether parasite killing is - at least in part - due to inhibition of RNA editing in vivo remains to be assessed. Our findings introduce novel molecular scaffolds with the potential for broad antitrypanosomal effects.
Successful hotel branding requires the management of both external and internal branding. External branding has been widely studied to understand how hotel brands connect with customers; however, ...internal branding targets internal employees, and the practice is not well understood by hoteliers. For that reason, this study proposes a framework for implementing internal branding in hotel organizations. We analyzed an internal branding project for three consecutive years using a participatory action study. The findings of this study support a six dimensions framework for implementing internal branding strategies: (1) corporate support; (2) leadership of managers; (3) reciprocal learning; (4) being proactive at the personal level; (5) characteristics of departments; and (6) performance evaluation. In the proposed framework, we applied a combined social identity and social exchange approach to identify how these approaches function in different paths which contributes new theoretical insights to the understanding of internal branding.
Summary
Obesity is a chronic disease with a significant and growing impact on Canadians. The “Awareness, Care and Treatment In Obesity MaNagement” (ACTION) Study investigated perceptions, attitudes ...and perceived barriers to obesity management among Canadian people with obesity (PwO), healthcare providers (HCPs) and employers. In this study adult PwO (body mass index ≥30 kg/m2, based on self‐reported height/weight), HCPs (physicians and allied HCPs managing PwO) and employers (≥20 employees; offering health insurance), completed online surveys between 3 August and 11 October 2017 in a cross‐sectional design. Survey respondents (N = 2545) included 2000 PwO, 395 HCPs and 150 employers. Obesity was viewed as a “chronic medical condition” by most PwO (60%), HCPs (94%) and employers (71%) and deemed to have a large impact on overall health (74%, 78%, 81%, respectively). Many PwO (74%) believed weight management was their own responsibility. While PwO (55%) reportedly knew how to manage their weight, only 10% reported maintaining ≥10% weight reduction for >1 year. Despite low success rates, the most commonly reported effective long‐term weight loss methods tried and/or recommended were “improvements in eating habits” (PwO 38%; HCP 63%) and “being more active” (PwO 39%; HCP 54%). PwO and HCPs reported very different perceptions of the quality and content of their interaction during obesity management discussions. These findings highlight the communication gaps and misunderstanding between PwO, HCPs and employers. This underscores the importance of, and need for, evidence‐based management of obesity and a collaborative approach and understanding of the complex nature of this chronic disease.
Cancer can be a major cause of poverty. This may be due either to the costs of treating and managing the illness as well as its impact upon people's ability to work. This is a concern that ...particularly affects countries that lack comprehensive social health insurance systems and other types of social safety nets. The ACTION study is a longitudinal cohort study of 10,000 hospital patients with a first time diagnosis of cancer. It aims to assess the impact of cancer on the economic circumstances of patients and their households, patients' quality of life, costs of treatment and survival. Patients will be followed throughout the first year after their cancer diagnosis, with interviews conducted at baseline (after diagnosis), three and 12 months. A cross-section of public and private hospitals as well as cancer centers across eight member countries of the Association of Southeast Asian Nations (ASEAN) will invite patients to participate. The primary outcome is incidence of financial catastrophe following treatment for cancer, defined as out-of-pocket health care expenditure at 12 months exceeding 30% of household income. Secondary outcomes include illness induced poverty, quality of life, psychological distress, economic hardship, survival and disease status. The findings can raise awareness of the extent of the cancer problem in South East Asia and its breadth in terms of its implications for households and the communities in which cancer patients live, identify priorities for further research and catalyze political action to put in place effective cancer control policies.
ACTION, a 24-week, prospective, randomized, parallel-group, double-blind study in patients with severe Alzheimer's disease (AD), demonstrated significant efficacy of 13.3 mg/24 h versus 4.6 mg/24 h ...rivastigmine patch on the Severe Impairment Battery (SIB) and Alzheimer's Disease Cooperative Study-Activities of Daily Living scale-Severe Impairment Version (ADCS-ADL-SIV). Overall, 61% of the study population received at least 1 dose of concomitant memantine, regardless of dose or duration. This retrospective analysis investigated the effects of concomitant memantine on the efficacy, safety and tolerability of 13.3 mg/24 h versus 4.6 mg/24 h rivastigmine patch.
Patients were stratified according to whether or not they received at least one dose of concomitant memantine during the double-blind phase. Changes from baseline on the SIB and ADCS-ADL-SIV were compared using analysis of covariance (ANCOVA) with treatment, pooled center, memantine usage and treatment-by-memantine as factors, and baseline as a covariate. Safety and tolerability were assessed.
Memantine-treated patients were younger than those not receiving memantine (mean 75.9 and 78.8 years, respectively), with a lower screening Mini-Mental State Examination (8.6 and 9.2, respectively). ANCOVA confirmed there was no significant interaction (p>0.1) between study treatment and memantine use on the SIB or ADCS-ADL-SIV. The incidence of adverse events was: 71.4%, 13.3 mg/24 h patch with memantine; 79.7%, 13.3 mg/24 h patch alone; 74.7%, 4.6 mg/24 h patch with memantine; and 71.1%, 4.6 mg/24 h patch alone.
These data suggest benefit of 13.3 mg/24 h versus 4.6 mg/24 h rivastigmine patch, regardless of concomitant memantine use. The incidence of adverse events with highdose patch was similar in memantine-treated patients and those not receiving memantine.
Background: Control over automatic tendencies is often compromised in challenging situations when people fall back on automatic defensive reactions, such as freeze-fight-flight responses. ...Stress-induced lack of control over automatic defensive responses constitutes a problem endemic to high-risk professions, such as the police. Difficulties controlling automatic defensive responses may not only impair split-second decisions under threat, but also increase the risk for and persistence of posttraumatic stress disorder (PTSD) symptoms. However, the significance of these automatic defensive responses in the development and maintenance of trauma-related symptoms remains unclear due to a shortage of large-scale prospective studies.
Objective: The 'Police-in-Action' study is conducted to investigate the role of automatic defensive responses in the development and maintenance of PTSD symptomatology after trauma exposure.
Methods: In this prospective study, 340 police recruits from the Dutch Police Academy are tested before (wave 1; pre-exposure) and after (wave 2; post-exposure) their first emergency aid experiences as police officers. The two waves of data assessment are separated by approximately 15 months. To control for unspecific time effects, a well-matched control group of civilians (n = 85) is also tested twice, approximately 15 months apart, but without being frequently exposed to potentially traumatic events. Main outcomes are associations between (changes in) behavioural, psychophysiological, endocrine and neural markers of automatic defensive responses and development of trauma-related symptoms after trauma exposure in police recruits.
Discussion: This prospective study in a large group of primary responders enables us to distinguish predisposing from acquired neurobiological abnormalities in automatic defensive responses, associated with the development of trauma-related symptoms. Identifying neurobiological correlates of (vulnerability for) trauma-related psychopathology may greatly improve screening for individuals at risk for developing PTSD symptomatology and offer valuable targets for (early preventive) interventions for PTSD.
From theoretical analysis to practical teaching tools, an indispensable guide for educators seeking to link feminist theory and activism to their teaching. Included are web sites, videos, recommended ...texts, and additional course outlines.
이 연구의 목적은 블랜디드 러닝의 실천적 모형을 개발하고 체육교육 현장에 적용함으로써 이를 경험한 학생의 관점에서 블랜디드 러닝의 경험적 의미를 이해하고 그 가치를 탐색하는 것이다. 연구 참여자는 I광역시 소재 B중학교 3학년 학생 412명이며, 참여 관찰자료, 서술적 관찰자료, 면담자료, 심층면접자료, 현장노트, 웹문서, 최종 결과물 등의 자료를 모으고 ...분석하였다. 이 연구를 위해 질적 연구방법이 적용되었고, 구체적으로 실행연구를 수행하였으며 반성적 실천의 자기 순환 과정을 거쳤다. 자료 분석 결과, 연구 참여자의 블랜디드 러닝에 대한 경험과 그 의미는 긍정적 상호작용, 자기 주도적 학습, 긍정적 정서, 학습의 효율성이라는 4개의 주제로 범주화되었다. 이 연구의 결과는 향후 블랜디드 러닝을 운영하는데 기초 자료로 활용될 수 있으며, 앞으로 블랜디드 러닝이 나아갈 방향과 프로그램 개발에 시사점을 제시하였다.
The purpose of this study was to understand the experiential meaning of Blended Learning in students` perspective and look for the value by developing the model of Blended Learning and applying it to the field of PE. The participants consist of 412 students in third grade of B middle school in I city, and the study was conducted by gathering and analyzing participant observation data, interview data, focus group interview data, field notes, web documents, and final reports. Qualitative approach was applied for the study, and an action study was conducted in concrete and the self-circulation process of reflective practice was gone through. In the result of the study, the participants` experiential meaning of Blended Learning was categorized into four themes: positive interaction, self-regulated learning, positive emotion, and efficiency of learning. The result of this study can be used as a basic data to manage Blended Learning and there are implications for the future direction of Blended Learning and program development.
Enterprise resource planning (ERP) is involving diverse and complicated knowledge, such like specialized knowledge, workflow, and procedures. This complex and tremendous information caused students ...and users hard to learn ERP system quickly. Despite some scholars had investigated and researched on the issue, but its results are quite conceptual to assist ERP learner. Therefore, this research based on action research perspective to develop the optimized learning stage, which contains 4 dimensions, 6 processes, 13 forms, and 38 critical success factors. This stage accurately indicates the process, problem, situation in learning, and even confirms the rationality and value of the research result. This research result not only connecting scholar theory and practical workflow, but providing clear learning mechanism, application value, and decision guide for educators in front-line. The learning stage is able to assist ERP user and students to learn ERP effectively, and improve ERP effect in business.
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