Exploring students' [pre-pandemic] use and the impact of commercial-off-the-shelf learning platforms on students' national licensing exam performance: A focused review - BEME Guide No. 72.

BACKGROUND: Commercial-off-the-shelf learning platforms developed for medical education (herein referred to as MedED-COTS) have emerged as a resource used by a majority of medical students to prepare for licensing examinations. As MedED-COTS proliferate and include more functions and features, there is a need for an up-to-date review to inform medical educators on (a) students' use of MedED-COTS outside the formal medical school curriculum, (b) the integration of MedED-COTS into the formal curriculum, and (c) the potential effects of MedED-COTS usage on students' national licensing exam scores in the USA. METHODS: Due to the limited number of studies published on either the use or integration of MedED-COTS, a focused review of literature was conducted to guide future research and practice. Data extraction and quality appraisal were conducted independently by three reviewers; with disagreements resolved by a fourth reviewer. A narrative synthesis was completed to answer research questions, contextualize results, and identify trends and issues in the findings reported by the studies included in the review. RESULTS: Results revealed consistent positive correlations between students' use of question banks and their licensing exam performance. The limited number of integration studies, combined with a number of methodological issues, makes it impossible to isolate specific effects or associations of integrated commercial resources on standardized test or course outcomes. However, consistent positive correlations, along with students' pervasive use and strong theoretical foundations explaining the results, provide evidence for integrating MedED-COTS into medical school curricula and highlight the need for further research. CONCLUSIONS: Based on findings, we conclude that students use exam preparation materials broadly and they have a positive impact on exam results; the literature on integration of MedED-COTS into formal curriculum and the use by students of resources outside of exam preparation is scant.

COVID-19 Trends and Forecast in the Eastern Mediterranean Region With a Particular Focus on Pakistan.

First reported in China, the coronavirus responsible for coronavirus disease 2019 (COVID-19) has spread to 213 countries and territories around the world as of April 26, 2020. This study was designed to explore COVID-19 trends in the Eastern Mediterranean Region (EMR), with a particular focus on Pakistan. Daily reports and updates from the Ministry of National Health Services Regulations and Coordination COVID-19 Pakistan and the European Centre for Disease Prevention and Control were collected and study-specific data were extracted and analyzed. Our analysis revealed that, as of April 26, 2020, a total of 22 countries and territories in the EMR have reported COVID-19 cases. Iran had the highest number of cases (89,329) followed by Saudi Arabia (16,299), Pakistan (12,723), and the United Arab Emirates (9,813). Egypt (7.1%), Iran (6.3%), and Iraq (4.9%) had high case fatality rates; Lebanon (3.4%) and Pakistan (2.1%) had moderate case fatality rates; Saudi Arabia and the United Arab Emirates had low case fatality rates of 0.8% and 0.7%, respectively. Iran (76.3%) and Iraq (69.4 %) had the highest recovery rate followed by Pakistan (22.5%), the United Arab Emirates (19.2%), and Saudi Arabia (13.6%). If the current trend continues, based on the susceptible, infected, recovered (SIR) epidemiological model, we predict that EMR countries might experience a surge in the number of COVID-19 cases, resulting in as many as 2.12 million cases in Iran, 0.58 million in Saudi Arabia, and 0.51 million in Pakistan by June 20, 2020. Pakistan is the most populated country in the EMR and was the third most-affected country in terms of the number of cases with moderate case fatality and recovery rates. We predict that Pakistan's weak healthcare system would not be able to sustain care if there is an explosive increase in the number of cases due to insufficient and inconsistent disease prevention and control policies. The best strategy for mitigating the COVID-19 pandemic is to strictly follow recommendations based on epidemiological principles.

How Postbaccalaureate Career Changer and Traditional Medical Students Differ Academically.

OBJECTIVE: This retrospective descriptive study compared the academic performance of postbaccalaureate career changer students with that of traditional students during the classroom-based, science-dominated early years of medical school. Earlier studies documented the eventual success of nontraditional medical students, although we found little information specific to the medical school performance of career changers. Our objective was to determine whether postbaccalaureate career changer medical students perform differently from traditionally prepared medical students in the science-dominated early years of medical school classroom education. METHODS: This study analyzed the admission data and academic performance of medical students at the University of Central Florida College of Medicine across 8 years (N = 630). Differences in performance were assessed using examination grades from the first 2 years of medical school, and US Medical Licensing Examination (USMLE) Step 1 and Step 2 scores. RESULTS: Statistically significant differences were found between traditional and career changer students for all science modules in year 1, and 4 of the 5 modules in year 2. Traditional students performed better on USMLE Step 1. Significant differences between the groups disappeared by USMLE Step 2. CONCLUSIONS: Career changer medical students show a small, persistent academic lag in the first 2 years of medical school and on USMLE Step 1 scores. By USMLE Step 2 the difference disappears. Similar undergraduate grade point averages and Medical College Admission Test scores suggest that science exposure, not ability may explain these differences. An unexpected finding is the number of career changer students is not increasing proportional to the proliferation of postbaccalaureate programs in the United States. This study may benefit student advisors and residency directors, and, it is hoped, provide reassurance to career changer students.

Developing a tool for observing group critical thinking skills in first-year medical students: a pilot study using physiology-based, high-fidelity patient simulations.

Most assessments of physiology in medical school use multiple choice tests that may not provide information about a student's critical thinking (CT) process. There are limited performance assessments, but high-fidelity patient simulations (HFPS) may be a feasible platform. The purpose of this pilot study was to determine whether a group's CT process could be observed over a series of HFPS. An instrument [Critical Thinking Skills Rating Instrument CTSRI)] was designed with the IDEAS framework. Fifteen groups of students participated in three HFPS that consisted of a basic knowledge quiz and introduction, HFPS session, and debriefing. HFPS were video recorded, and two raters reviewed and scored all HFPS encounters with the CTSRI independently. Interrater analysis suggested good reliability. There was a correlation between basic knowledge scores and three of the six observations on the CTSRI providing support for construct validity. The median CT ratings significantly increased for all observations between the groups' first and last simulation. However, there were still large percentages of video ratings that indicated students needed substantial prompting during the HFPS. The data from this pilot study suggest that it is feasible to observe CT skills in HFPS using the CTSRI. Based on the findings from this study, we strongly recommend that first-year medical students be competent in basic knowledge of the relevant physiology of the HFPS before participating, to minimize the risk of a poor learning experience.

Knockdown of aberrantly expressed nuclear localized decorin attenuates tumour angiogenesis related mediators in oral cancer progression model in vitro.

BACKGROUND: Oral cancer accounts for roughly 3% of cancer cases in the world with about 350,000 newly reported cases annually and a 5-year survival rate of only 50%. Majority of oral cancers are squamous cell carcinomas that originate in the oral mucosal epithelial linings. We have previously shown that in human malignant squamous cells carcinoma (SCC-25) as well as in dysplastic oral keratinocytes (DOK), a small leucine-rich multifunctional proteoglycan decorin is aberrantly expressed and localized in the nucleus where it interacts with nuclear epidermal growth factor receptor (EGFR). Post-transcriptional silencing of nuclear decorin significantly reduced IL-8 and IL8-dependent migration and invasion in these dysplastic and malignant oral epithelia. The objective of this study was to further examine the effects of nuclear decorin silencing on angiogenesis and angiogenesis related mediators in this oral cancer progression cell line model. METHODS: We have used multiplex PCR, western blotting, and in vitro endothelial tube formation assay to study angiogenesis and related pathways in nuclear decorin silenced (stable knockdown) DOK and SCC-25 cells. RESULTS: Nuclear decorin knockdown resulted in significant down regulation of IL-8 expression, however IL-10, and TGF-ß expression was not affected in either DOK or SCC25 cells as measured by multiplex RT PCR. IL-8 receptor CXCR 1 and 2 expression was slightly lower in nuclear decorin silenced cells indicating a contributing mechanism in previously shown reduced IL-8 mediated migration and invasion phenotype in these cells. IL-8 is known to induce Matrix metalloproteinase 9 (MMP9) which not only plays a role in tumour migration and invasion but also induces angiogenic switch. We found MMP9 to be significantly reduced in nuclear decorin silenced dysplastic and malignant oral epithelia. Other potent angiogenic mediators, VEGF189 and ANG-1 were either significantly reduced or completely abrogated in these cells. Angiogenesis as measured by endothelial tube-like formations of HUVEC cells was reduced by almost 50 percent when HUVECs were incubated in the presence of conditioned medium form nuclear decorin silenced dysplastic and malignant cell lines as compared to respective controls. CONCLUSIONS: Together these results indicate that aberrantly expressed nuclear localized decorin strongly influences angiogenic potential of dysplastic and malignant oral epithelial cells.

A role for aberrantly expressed nuclear localized decorin in migration and invasion of dysplastic and malignant oral epithelial cells.

BACKGROUND: Oral cancer is the sixth most common malignancy worldwide with a mortality rate that is higher than many other cancers. Death usually occurs as a result of local invasion and regional lymph node metastases. Decorin is a multifunctional proteoglycan of the extracellular matrix that affects the biology of various types of cancer. Previously; we have shown that decorin is aberrantly expressed in the nucleus in human dysplastic oral keratinocytes (DOK) and malignant squamous cells carcinoma (SCC-25) and human biopsy tissues. In this study, we examined the role of nuclear decorin in oral cancer progression. MATERIALS AND METHODS: We have used a post-transcriptional gene silencing (RNA interference) approach to stably knockdown nuclear decorin gene expression in DOK and SCC-25 cells using a specific shRNA plasmid and a combination of immunological and molecular techniques to study nuclear decorin function in these oral epithelial cell lines. RESULTS: More than 80% decorin silencing/knockdown was achieved as confirmed by real time PCR and western blot analysis in both DOK and SCC-25 cells. This RNA interference-mediated knockdown of nuclear decorin expression resulted in significantly reduced invasion and migration in these cell lines as measured by Matrigel™ coated and uncoated Trans well chamber assays respectively. Decorin silencing also resulted in reduced IL-8 mRNA and proteins levels in these cell lines. Culturing decorin silenced DOK and SCC-25 cells, with recombinant human IL-8 or IL-8 containing conditioned medium from respective un-transfected cells for 24 h prior to migration and invasion experiments, resulted in the salvation of reduced migration and invasion phenotype. Furthermore, we found that nuclear localized decorin interacts with EGFR in the nuclear fractions of both DOK and SCC-25 cells. Interestingly, EGFR (trans) activation has previously been shown to be involved in IL-8 production in various epithelia. CONCLUSIONS: Taken together, our results indicate that nuclear localized decorin plays an important role in migration and invasion of oral cancer cells and thus may present as a novel potential target for the treatment of oral cancer.

What's new in asthma pathophysiology and immunopathology?

Research on asthma pathophysiology over the past decade has expanded the complex repertoire involved in the pathophysiology of asthma to include inflammatory, immune and structural cells, as well as a wide range of mediators. Studies have identified a role for connective and other mesenchymal tissues involved in airway remodeling. Recent findings have implicated the innate immune response in asthma and have revealed interesting patterns of interaction between the innate and adaptive immune response and the associated complex chronic inflammatory reaction. New immune cell populations have also been added to this repertoire, including Tregs, natural killer T cells and Th17 cells. The role of the eosinophil, a prominent pathological feature in most asthma phenotypes, has also been expanding to include roles such as tissue modifiers and immune regulators via a number of fascinating and hitherto unexplored mechanistic pathways. In addition, new and significant roles have been proposed for airway smooth muscle cells, fibroblasts, epithelial and endothelial cells. Tissue remodeling is now considered an integral element of asthma pathophysiology. Finally, an intricate network of mediators, released from both immune and inflammatory cells, including thymus stromal lymphopoietin and matrix metalloproteinases, have added to the complex milieu of asthma immunity and inflammation. These findings have implications for therapy and the search for novel strategies towards better disease management. Sadly, and perhaps due to the complex nature of asthma, advances in therapeutic discoveries and developments have been limited. Thus, understanding the precise roles played by the numerous dramatis personae in this odyssey, both individually and collectively within the context of asthma pathophysiology, continues to pose new challenges. It is clear that the next stage in this saga is to embark on studies that transcend reductionist approaches to involve system analysis of the complex and multiple variables involved in asthma, including the need to narrow down the phenotypes of this condition based on careful analysis of the organs (lung and airways), cells, mediators and other factors involved in bronchial asthma.

Role of phosphoinositide 3-kinase p110 delta in TLR4- and TLR9-mediated B cell cytokine production and differentiation.

Phosphoinositide 3-kinase (PI3K) enzymes play key roles in signaling via antigen receptors and cytokine receptors and isoform-selective PI3K inhibitors are being evaluated as targets for treatment of allergic and inflammatory diseases. The specific roles of PI3K isoforms in TLR-mediated activation of lymphocytes have not been defined. In this study we assess the role of p110 delta PI3K in TLR4, TLR9, or TLR4+TLR9-mediated B cell responses. Utilizing both p110 delta-mutant mice and p110 delta-specific inhibitor IC87114, we find that signaling via p110 delta is required for optimal B cell proliferation, but is not required for TLR-mediated B cell differentiation into plasma cells or Ig isotype switch. However PI3K blockade led to increased frequencies of IgG1 and IgE expressing cells, and partially reversed ability of CpG to inhibit IgG1 and IgE. Examination of B cell cytokine production revealed that p110 delta blockade markedly reduced IL-6 and IL-10 production. In contrast, p110 delta signaling was clearly not required for IL-12 production, with p110 delta-mutant B cells in fact showing enhanced IL-12 p70 production. TLR4- and TLR9-ligands act in synergy to drive IL-6 and IL-10 production, but not IL-12, and this additive effect is independent of p110 delta signaling. Together, these results indicate that PI3K delta functions in influencing the type of B cell cytokine production and differentiation response induced by TLR-ligands.

Interleukin-1beta does not contribute to genetic strain-based differences in iNOS expression and activity in chicken macrophages.

The expression of IL-1beta and inducible nitric oxide synthase (iNOS) from iNOS hypo (GB2, B(6)B(6)) and hyper (K-strain, B(15)B(15)) responder chickens was examined. Compared to GB2, macrophages from K-strain expressed higher iNOS mRNA as quantitated by reverse transcriptase polymerase (RT-PCR) chain reaction after stimulation with 1 microgram/ml of Escherichia coli (E. coli) lipopolysaccharide (LPS). On the contrary, IL-1beta mRNA expression was comparable between K and GB2 macrophages at 3h post-LPS stimulation but persisted up to 9h only in GB2 macrophages. The LPS-inducible interleukin-1 (IL-1) surface receptor expression, measured by flow cytometry, was higher in GB2 than on K-strain macrophages. Blocking of IL-1 receptor by the anti-IL-1 receptor antibody reduced the LPS-mediated iNOS expression by 50% as quantified by competitive RT-PCR. Furthermore, iNOS activity (nitrite) was also reduced to 50%. However, this magnitude of inhibition was similar in both K and GB2 macrophages. While these observations suggest that IL-1beta is involved in mediating LPS-induced iNOS expression and activity, the differential response of GB1 and K-strain macrophages in terms of LPS-induced iNOS expression and activity is unlikely to be modulated by IL-1beta.