Project description:Interferon-stimulated gene product 15 (ISG15) is a key component of host responses to microbial infection. Despite having been known for four decades, grasping the functions and features of ISG15 has been a slow and elusive process. Substantial work over the past two decades has greatly enhanced this understanding, revealing the complex and variable nature of this protein. This has unveiled multiple mechanisms of action that are only now beginning to be understood. In addition, it has uncovered diversity not only between how ISG15 affects different pathogens but also between the function and structure of ISG15 itself between different host species. Here we review the complexity of ISG15 within the context of viral infection, focusing primarily on its antiviral function and the mechanisms viruses employ to thwart its effects. We highlight what is known regarding the impact of ISG15 sequence and structural diversity on these interactions and discuss the aspects presenting the next frontier toward elucidating a more complete picture of ISG15 function.
Project description:Each microbe has the ability to produce a wide variety of sugar structures that includes some combination of glycolipids, glycoproteins, exopolysaccharides and oligosaccharides. For example, bacteria may synthesize lipooligosaccharides or lipopolysaccharides, teichoic and lipoteichoic acids, N- and O-linked glycoproteins, capsular polysaccharides, exopolysaccharides, poly-N-acetylglycosamine polymers, peptidoglycans, osmoregulated periplasmic glucans, trehalose or glycogen, just to name a few of the more broadly distributed carbohydrates that have been studied. The composition of many of these glycans are typically dissimilar from those described in eukaryotes, both in the seemingly endless repertoire of sugars that microbes are capable of synthesizing, and in the unique modifications that are attached to the carbohydrate residues. Furthermore, strain-to-strain differences in the carbohydrate building blocks used to create these glycoconjugates are the norm, and many strains possess additional mechanisms for turning on and off transferases that add specific monosaccharides and/or modifications, exponentially contributing to the structural heterogeneity observed by a single isolate, and preventing any structural generalization at the species level. In the past, a greater proportion of research effort was directed toward characterizing human pathogens rather than commensals or environmental isolates, and historically, the focus was on microbes that were simple to grow in large quantities and straightforward to genetically manipulate. These studies have revealed the complexity that exists among individual strains and have formed a foundation to better understand how other microbes, hosts and environments further transform the glycan composition of a single isolate. These studies also motivate researchers to further explore microbial glycan diversity, particularly as more sensitive analytical instruments and methods are developed to examine microbial populations in situ rather than in large scale from an enriched nutrient flask. This review emphasizes many of these points using the common foodborne pathogen Campylobacter jejuni as the model microbe.
Project description:Abstract Many older adults express a lack of confidence in using technology and this can become a barrier to participating in technology heavy research. This presentation will introduce the face-to-face digital communication, electronic medication adherence tracking, and online recruitment technology used in the I-CONECT study (ClinicalTrials.gov: NCT02871921). In particular, we will demonstrate how the project has simplified enterprise video conferencing for in-home use, removed obstacles related to remote hardware troubleshooting, and further discuss how it has been received by older adults who have participated thus far. Finally we will cover particular hurdles related to I-CONECT (e.g., targeting social isolated older adults, aiming to recruit 50% of participants being African American older subjects living in the Detroit Metropolitan area). Our experience indicates that such high tech gerontological research is feasible given a creative and solution-focused research approaches and multi-disciplinary team.
Project description:Artificial intelligence (AI) driven by machine learning (ML) algorithms is a branch in computer science that is rapidly gaining popularity within the healthcare sector. Recent regulatory approvals of AI-driven companion diagnostics and other products are glimmers of a future in which these tools could play a key role by defining the way medicine will be practiced. Educating the next generation of medical professionals with the right ML techniques will enable them to become part of this emerging data science revolution.
Project description:ObjectivesInternationally, public health strategies encourage health care professionals to deliver opportunistic behaviour change interventions. The present study: (1) examines the barriers and enablers to delivering interventions during routine consultations, and (2) provides recommendations for the design of interventions to increase delivery of opportunistic behaviour change interventions.DesignQualitative interview study.MethodsTwenty-eight semi-structured interviews were conducted with patient-facing health care professionals. The Behaviour Change Wheel informed a framework analysis in which findings were mapped onto the Theoretical Domains Framework (TDF). Intervention functions and behaviour change techniques (BCTs) targeting each TDF domain were identified.ResultsHealth care professionals understood the importance of opportunistic behaviour change interventions (beliefs about consequences), but were sceptical about their capabilities to facilitate behaviour change with patients (beliefs about capabilities). Some clinicians were unwilling to discuss behaviours perceived as unrelated to the patient's visit (social/professional role and identity). Discipline-specific tasks were prioritized, and delivering interventions was perceived as psychologically burdensome. One-to-one contact was favoured over busy hospital settings (environmental context and resources). Seven intervention functions (training, restriction, environmental restructuring, enablement, education, persuasion, and modelling) and eight BCT groupings (antecedents, associations, comparison of outcomes, covert learning, feedback and monitoring, natural consequences, reward and threat, and self-belief) were identified.ConclusionsAcross disciplines, health care professionals see the value of opportunistic behaviour change interventions. Barriers related to workload, the clinical environment, competence, and perceptions of the health care professional role must be addressed, using appropriate intervention functions and BCTs, in order to support health care professionals to increase the delivery of interventions in routine practice. Statement of contribution What is already known on this subject? Brief, opportunistic interventions can be a cost effective way of addressing population health problems. Public health policies compel health care professionals to deliver behaviour change interventions opportunistically. Health care professionals do not always deliver interventions opportunistically during routine medical consultations; however the barriers and enablers are currently unclear. What does this study add? This is the first study to examine cross-disciplinary barriers and enablers to delivering opportunistic behaviour change interventions. Across diverse professional groups, working in different medical professions, participants saw the value of delivering opportunistic behaviour change interventions. Targeting key theoretical domains that are shared across professional groups may be useful for increasing the delivery of opportunistic behaviour change interventions.
Project description:IntroductionHistology teaching in India and in other developing countries has not changed much over the past decades and has not joined the global movement of using virtual microscopy (VM). Many factors may have contributed to this academic inertia-including curricular requirements for traditional microscopy (TM) skills, assessments that are heavily based on TM, and unfamiliarity with modern technology among faculty, as well as infrastructural shortcomings. This study is aimed at overcoming these roadblocks by using a blended approach combining VM with TM in a tradition-centered curricular setting.MethodsFor validation of this approach, the authors conducted a non-randomized controlled trial with a crossover design on first year medical students at the Government Medical College, Thiruvananthapuram, India. Examination scores and responses of a student group taught with VM as an adjunct to TM were compared with a student group taught with TM only.ResultsThe test group had significantly better results when compared to the control group for knowledge-based tests (p = 0.012; analysis of co-variance) and for an unannounced visual-based test conducted 1 month later (p = 0.001; Mann-Whitney U test). Feedback collected from students showed highly favorable responses to the use of VM for teaching histology.ConclusionThis study should encourage Indian medical colleges and schools in other developing countries to start using VM as a supplementary approach for their histology education programs. Furthermore, as the Medical Council of India recommends the introduction of new competency-based integrated curriculum in India starting in 2019, the use of VM may facilitate more effective learning in the new scenario.Trial registrationCTRI/2018/04/012928.
Project description:Objective: In order to evaluate the quality of postgraduate medical education in Germany, we examined how the learning of theoretical and practical competencies is conceptualized and how the learning process takes place in real terms. The training conditions, as perceived by medical residents, are compared with the learning objectives, as stated by the Federal Chamber of Physicians in its regulation on postgraduate education. The analysis is based on the data of the "KarMed" study (abbreviation of "career progression and career breaks among physicians during postgraduate education"), a multicentre cohort study of medical school graduates from seven universities who arre followed until they receive their licenses as specialist physicians. The study was conducted by the Institute of Primary Medical Care of the University Medical Center Hamburg-Eppendorf starting in 2008. Methodology: The KarMed study is based on annual, standardized surveys of the population described above. 48% responded in the initial survey (n=1012) and 85% or more in each of the following surveys. Descriptive statistics and logistical regressions were used for analysis. Gender-specific analyses were performed where possible in order to highlight the differences in the professional objectives and workloads between female and male physicians. Results: The study shows that both the practical and the theoretical components of postgraduate medical education in Germany are insufficient. There is a lack of a curriculum with precise learning objectives and descriptions of the corresponding educational settings. In fact, the act of learning is identical to daily clinical work. There is no structuring of the work process with regard to learning; for example, documentation procedures and feedback discussions are prescribed but largely omitted. Evidence-based medicine is not a systematic part of the training, nor is the evaluation of residents' progress. The summative final oral examination pretends that the necessary specialist competencies can be evaluated within 30 minutes. Many factors indicate that female doctors, especially those with children, have fewer learning opportunities than male doctors. Conclusion: The quality of postgraduate medical education in Germany has become inadequate, especially in an international comparison. The deficits are well known. The responsible institutions are called upon to implement sustainable reforms in the sense of postgraduate education that is structured according to educational principles and whose quality is assured.
Project description:Triple-negative breast cancer (TNBC) is a pathological term used to identify invasive breast cancers that lack expression of estrogen and progesterone receptors and do not have pathologic overexpression of the HER2 receptor or harbor ERBB2 gene amplification. TNBC includes a collection of multiple distinct disease entities based upon genomic, transcriptomic and phenotypic characterization. Despite improved clinical outcomes with the development of novel therapeutics, TNBC still yields the worst prognosis among all clinical subtypes of breast cancer. We will systematically review evidence of the genomic evolution of TNBC, as well as potential mechanisms of disease progression and treatment resistance, defined in part by advances in next-generation DNA sequencing technology (including single cell sequencing), providing a new perspective on treatment strategies, and promise to reveal new potential therapeutic targets. Moreover, we review novel therapies aimed at homologous recombination deficiency, PI3 kinase/AKT/PTEN pathway activation, androgen receptor blockade, immune checkpoint inhibition, as well as antibody-drug conjugates engaging novel cell surface targets, including recent progress in pre-clinical and clinical studies which further validate the role of targeted therapies in TNBC. Despite major advances in treatment for TNBC, including FDA approval of 2 PARP inhibitors for metastatic TNBC, the crossing of the superiority boundary in a phase 3, placebo-controlled study of adjuvant olaparib in early-stage patients with germline BRCA-mutated high-risk HER2-negative early breast cancer, the FDA approval of 2 PD-(L)1 checkpoint antibodies for metastatic TNBC, and the FDA approval of the first antibody drug conjugate for TNBC, significant challenges remain. For example, despite the dawn of immunotherapy in metastatic TNBC, durable responses are limited to a small subset of patients, definitive biomarkers for patient selection are lacking, and the Oncology Drug Advisory Committee to the FDA has recently voted against approval of an anti-PD-1 checkpoint antibody high risk early-stage TNBC in the neoadjuvant setting. Also, despite early positive randomized phase 2 studies of AKT inhibition in metastatic TNBC, a recent phase 3 registration trial failed to validate earlier phase 2 data. Finally, we note that level one evidence for clinical efficacy of androgen receptor blockade in TNBC is still lacking. To meet these and other challenges, we will catalogue the ongoing exponential increase in interest in basic, translational, and clinical research to develop new treatment paradigms for TNBC.
Project description:Background As COVID-19 has been declared as a pandemic disease by the WHO on March 11th, 2020, the global incidence of COVID-19 disease increased dramatically. In response to the COVID-19 situation, Jordan announced the emergency state on the 19th of March, followed by the curfew on 21 March. All educational institutions have been closed as well as educational activities including clinical medical education have been suspended on the 15th of March. As a result, Distance E-learning emerged as a new method of teaching to maintain the continuity of medical education during the COVID-19 pandemic related closure of educational institutions. Distance E-Learning is defined as using computer technology to deliver training, including technology-supported learning either online, offline, or both. Before this period, distance learning was not considered in Jordanian universities as a modality for education. This study aims to explore the situation of distance E-learning among medical students during their clinical years and to identify possible challenges, limitations, satisfaction as well as perspectives for this approach to learning. Methods This cross-sectional study is based on a questionnaire that was designed and delivered to medical students in their clinical years. For this study, the estimated sample size (n =?588) is derived from the online Raosoft sample size calculator. Results A total of 652 students have completed the questionnaire, among them, 538 students (82.5%) have participated in distance learning in their medical schools amid COVID-19 pandemic. The overall satisfaction rate in medical distance learning was 26.8%, and it was significantly higher in students with previous experience in distance learning in their medical schools as well as when instructors were actively participating in learning sessions, using multimedia and devoting adequate time for their sessions. The delivery of educational material using synchronous live streaming sessions represented the major modality of teaching and Internet streaming quality and coverage was the main challenge that was reported by 69.1% of students. Conclusion With advances in technologies and social media, distance learning is a new and rapidly growing approach for undergraduate, postgraduate, and health care providers. It may represent an optimal solution to maintain learning processes in exceptional and emergency situations such as COVID-19 pandemic. Technical and infrastructural resources reported as a major challenge for implementing distance learning, so understanding technological, financial, institutional, educators, and student barriers are essential for the successful implementation of distance learning in medical education.
Project description:Medical schools have been making efforts to develop their own problem-based learning (PBL) approaches based on their educational conditions, human resources and existing curriculum structures. This study aimed to explore a new framework by integrating the essential features of PBL and coaching psychology applicable to the undergraduate medical education context.A participatory research design was employed. Four educational psychology researchers, eight undergraduate medical school students and two accredited PBL tutors participated in a four-month research programme. Data were collected through participatory observation, focus groups, semi-structured interviews, workshop documents and feedback surveys and then subjected to thematic content analysis. The triangulation of sources and member checking were used to ensure the credibility and trustworthiness of the research process.Five themes emerged from the analysis: current experience of PBL curriculum; the roles of and relationships between tutors and students; student group dynamics; development of self-directed learning; and coaching in PBL facilitation. On the basis of this empirical data, a systematic model of PBL and coaching psychology was developed.The findings highlighted that coaching psychology could be incorporated into the facilitation system in PBL. The integrated framework of PBL and coaching psychology in undergraduate medical education has the potential to promote the development of the learning goals of cultivating clinical reasoning ability, lifelong learning capacities and medical humanity. Challenges, benefits and future directions for implementing the framework are discussed in this paper.