Miracle-dz/UniFAR-FTUs huggingface dataset:
Twelve tips for developing an integrated curriculum

Background: Integration of curriculum is meant to make the teaching/learning activities meaningful; however, the interpretation of ‘integration’ varies in different institutions and among individuals. Many medical schools find it hard to change their existing curriculum or develop a new integrated curriculum mainly because of lack of will, infrastructure and understanding the process of change. Aim: Drawn from experience, these 12 tips relating to staff development, establishing working groups, organizing the teaching/learning materials under themes and developing some innovative teaching/learning and assessment strategies, are the techniques that a teaching institution can use to change the existing curriculum to an integrated one or develop a new curriculum. Conclusion: Knowing about the different levels of integration and steps for developing an integrated curriculum can make it easier to integrate an existing curriculum or develop a new one.
Opposing Impact of B Cell–Intrinsic TLR7 and TLR9 Signals on Autoantibody Repertoire and Systemic Inflammation

Systemic lupus erythematosus is a multisystem autoimmune disease characterized by autoantibodies targeting nucleic acid–associated Ags. The endosomal TLRs TLR7 and TLR9 are critical for generation of Abs targeting RNA- or DNA-associated Ags, respectively. In murine lupus models, deletion of TLR7 limits autoimmune inflammation, whereas deletion of TLR9 exacerbates disease. Whether B cell or myeloid TLR7/TLR9 signaling is responsible for these effects has not been fully addressed. In this study, we use a chimeric strategy to evaluate the effect of B cell–intrinsic deletion of TLR7 versus TLR9 in parallel lupus models. We demonstrate that B cell–intrinsic TLR7 deletion prevents RNA-associated Ab formation, decreases production of class-switched Abs targeting nonnuclear Ags, and limits systemic autoimmunity. In contrast, B cell–intrinsic TLR9 deletion results in decreased DNA-reactive Ab, but increased Abs targeting a broad range of systemic autoantigens. Further, we demonstrate that B cell–intrinsic TLR9 deletion results in increased systemic inflammation and immune complex glomerulonephritis, despite intact TLR signaling within the myeloid compartment. These data stress the critical importance of dysregulated B cell–intrinsic TLR signaling in the pathogenesis of systemic lupus erythematosus.
IL-17A Influences Essential Functions of the Monocyte/Macrophage Lineage and Is Involved in Advanced Murine and Human Atherosclerosis

Atherosclerosis is a chronic inflammatory disease. Lesion progression is primarily mediated by cells of the monocyte/macrophage lineage. IL-17A is a proinflammatory cytokine, which modulates immune cell trafficking and is involved inflammation in (auto)immune and infectious diseases. But the role of IL-17A still remains controversial. In the current study, we investigated effects of IL-17A on advanced murine and human atherosclerosis, the common disease phenotype in clinical care. The 26-wk-old apolipoprotein E–deficient mice were fed a standard chow diet and treated either with IL-17A mAb (n = 15) or irrelevant Ig (n = 10) for 16 wk. Furthermore, essential mechanisms of IL-17A in atherogenesis were studied in vitro. Inhibition of IL-17A markedly prevented atherosclerotic lesion progression (p = 0.001) by reducing inflammatory burden and cellular infiltration (p = 0.01) and improved lesion stability (p = 0.01). In vitro experiments showed that IL-17A plays a role in chemoattractance, monocyte adhesion, and sensitization of APCs toward pathogen-derived TLR4 ligands. Also, IL-17A induced a unique transcriptome pattern in monocyte-derived macrophages distinct from known macrophage types. Stimulation of human carotid plaque tissue ex vivo with IL-17A induced a proinflammatory milieu and upregulation of molecules expressed by the IL-17A–induced macrophage subtype. In this study, we show that functional blockade of IL-17A prevents atherosclerotic lesion progression and induces plaque stabilization in advanced lesions in apolipoprotein E–deficient mice. The underlying mechanisms involve reduced inflammation and distinct effects of IL-17A on monocyte/macrophage lineage. In addition, translational experiments underline the relevance for the human system.
Patterns of distress in US medical students

Background: How multiple forms of psychological distress coexist in individual medical students has not been formally studied. Aim: To explore the prevalence of various forms of distress in medical students and their relationship to recent suicidal ideation or serious thoughts of dropping out of school. Methods: All medical students at seven US schools were surveyed with standardized instruments to evaluate burnout, depression, stress, mental quality of life (QOL), physical QOL, and fatigue. Additional items explored recent suicidal ideation and serious thoughts of dropping out of medical school. Results: Nearly all (1846/2246, 82%) of medical students had at least one form of distress with 1066 (58%) having ≥3 forms of distress. A dose-response relationship was found between the number of manifestations of distress and recent suicidal ideation or serious thoughts of dropping out. For example, students with 2, 4, or 6 forms of distress were 5, 15, and 24 fold, respectively, more likely to have suicidal ideation than students with no forms of distress assessed. All forms of distress were independently associated with suicidal ideation or serious thoughts of dropping out on multivariable analysis. Conclusions: Most medical students experience ≥1 manifestation of distress with many experiencing multiple forms of distress simultaneously. The more forms of distress experienced the greater the risk for suicidal ideation and thoughts of dropping out of medical school.
HIV-1 Single-Stranded RNA Induces CXCL13 Secretion in Human Monocytes via TLR7 Activation and Plasmacytoid Dendritic Cell–Derived Type I IFN

Elevated levels of the chemokine CXCL13 have been observed in the plasma of chronically HIV-1–infected subjects and have been correlated with plasma viremia, which in turn has been linked to progressive dysregulation of humoral responses. In this study we sought to identify mechanisms of CXCL13 induction in response to HIV-1 infection. Plasma levels of CXCL13 in HIV-1–infected antiretroviral therapy–naive subjects correlated with viral load and were higher compared with antiretroviral therapy–treated HIV-1–infected and HIV-1–uninfected subjects. To elucidate the relationship between HIV-1 viremia and CXCL13 plasma levels, PBMCs from uninfected donors were stimulated with HIV-1 infectious virions, HIV-1 ssRNA, TLR 7 and 8 agonists, or IFN-α. The cellular sources of CXCL13 were determined by intracellular cytokine staining of cell populations. CXCL13 was produced by monocytes after stimulation with TLR 7 and 8 ligands or HIV-1–derived ssRNA. CXCL13 production by monocytes required TLR7 activation of plasmacytoid dendritic cells and secretion of type I IFN. IFN-α alone was sufficient to induce CXCL13 expression in human monocytes. In sum, we identified a novel mechanism of HIV-1–induced CXCL13 secretion—one caused by TLR7 induction of type I IFN by plasmacytoid dendritic cells and subsequent IFN stimulation of monocytes. Our findings are relevant in understanding how HIV-1 infection leads to immune dysregulation and provide the opportunity to develop and test potential therapeutic interventions.
The Ventriloscope® as an innovative tool for assessing clinical examination skills: Appraisal of a novel method of simulating auscultatory findings

Background: Simulation is increasingly used as a teaching tool and in assessment. The Ventriloscope® (VS) is a new auscultation simulator. This modified stethoscope allows pre-recorded sounds (activated wirelessly) to be integrated with a simulated patient (SP, professional actor). Aims: This study explores the instrument's potential for overcoming limitations of current objective structured clinical examination (OSCE) assessment by increasing validity while retaining reliability. Methods: After training SPs to synchronise the device with their breathing (recreating abnormal signs), we evaluated the VS during a third year undergraduate medical student OSCE. Students (n = 385), examiners (n = 19) and SPs (n = 10) completed post-exam questionnaires which were analysed using a coding framework. OSCE performance data were analysed using Stata 10. Results: When ‘compared to their usual stethoscope’ 40% of students found no difference in using the VS; 69% found it easier to identify sounds; 68% found examination with the VS very or fairly realistic when ‘compared to examining a real patient’. Examination scores were comparable with other OSCE stations. Conclusions: The VS reliably provided consistent ‘abnormal’ auscultatory signs within an OSCE framework. Using a VS may increase OSCE validity, allowing examiners to assess students' application of knowledge in a realistically simulated setting. The VS can help bridge the gap between simulation and real patients.
Eliminación de la tuberculosis, un vecindario por vez

OBJETIVOS: Evaluamos una estrategia para la prevencion de la tuberculosis en las comunidades mas afectadas por esta enfermedad. METODOS: En 1996, trazamos un mapa de los casos de tuberculosis notificados (1985-1995) y de las personas con reaccion positiva a la prueba de la tuberculina (1993-1995) en el condado de Smith, Texas, Estados Unidos de America. Definimos los dos conglomerados de mayor tamano y densidad, identificando los dos vecindarios con mayor incidencia (180 manzanas y 3 153 residentes). Tras una preparacion intensiva de la comunidad, personal sanitario capacitado ofrecio a todos los residentes, de vivienda en vivienda, la posibilidad de hacerse la prueba de la tuberculina, a menos que estuviera contraindicado. A las personas con resultados positivos en esta prueba se las acompano a un consultorio movil para realizarles ahi radiografias, una evaluacion clinica y, segun fuera pertinente, proceder con el tratamiento preventivo con isoniazida. Para evaluar las repercusiones a largo plazo, trazamos un mapa de todos los casos de tuberculosis que se registraron en el condado de Smith durante el periodo equivalente despues del proyecto. RESULTADOS: De las 2 258 personas que cumplian los requisitos para participar, 1 291 (57,1%) se sometieron a la prueba de la tuberculina, 229 (17,7%) presentaron resultados positivos en dicha prueba y 147 fueron tratadas. De 1996 al 2006, no se registro ningun caso de tuberculosis en ninguno de los vecindarios del proyecto, a diferencia de lo ocurrido en el decenio anterior a la intervencion y en el resto del condado de Smith, donde aparecieron continuamente casos de tuberculosis. CONCLUSIONES: Dirigirse a los vecindarios con una incidencia alta para realizar el tamizaje activo en la comunidad y aplicar tratamiento preventivo con isoniazida puede acelerar la eliminacion de la tuberculosis en los Estados Unidos.
IL-2/Anti–IL-2 Antibody Complex Treatment Inhibits the Development but Not the Progression of Herpetic Stromal Keratitis

The IL-2/anti–IL-2 Ab immunocomplex has recently been shown to expand the naturally occurring pool of CD4+Foxp3+ regulatory T cells (Tregs). In this study, we show that administration of the IL-2/anti–IL-2 Ab immunocomplex to C57BL/6 mice, prior to corneal HSV-1 infection, significantly increased the pool of Foxp3+ Tregs when measured at early time points postinfection. Increased numbers of Foxp3+ Tregs on days 2 and 4 postinfection resulted in a marked reduction in the development of severe herpetic stromal keratitis (HSK). When compared with corneas from the control group, corneas from the immunocomplex-treated group showed a significant reduction in the amount of infectious virus on day 2 but not on day 4 postinfection. Reduced viral load was associated with a 2-fold increase in NK cell numbers in corneas from the immunocomplex-treated group of mice. Moreover, a dramatic reduction in the influx of CD4 T cells in inflamed corneas was determined on days 7 and 16 postinfection in the immunocomplex-treated group of infected mice. Immunocomplex treatment given on days 5, 6, and 7 postinfection significantly increased Foxp3+ Tregs in draining lymph nodes and in the spleen but failed to reduce the severity of HSK. In terms of the influx of CD4 T cells and granulocytes into inflamed corneas, no significant differences were noted between both groups of mice on day 16 postinfection. Our findings demonstrate that increasing Foxp3+ Tregs early but not late postinfection in secondary lymphoid tissues is more efficacious in controlling the severity of HSK.
Effect of feedback from standardized patients on medical students’ performance and perceptions of the neurological examination

Background: Feedback can have a powerful influence on the performance of learners, and has traditionally been provided by faculty. Aim: This study set out to explore whether feedback from a standardized patient (SP) can improve students’ performance of the neurological examination. Methods: A randomized controlled design was used with final year medical students. The control group did not receive any feedback. The intervention groups received either written feedback or a combination of written and verbal feedback. A written test was given prior to the intervention to assess comparability of the three groups. Pretest and post-test scores on the neurological examination were compared. Attitudinal questionnaires were administered at the time of the posttest, and 6 months later. Results: Students receiving feedback from the SPs had significantly greater scores on the posttest than the control group. In the intervention groups, students receiving both verbal and written feedback scored significantly higher than those who received only written feedback. More positive perceptions of learning outcomes and the value of SP feedback were noted in the intervention groups. Conclusion: SP feedback was associated with a significant increase in student scores on the neurological examination, as well as more favorable perceptions of the experience.
Social accountability in medical education – An Australian rural and remote perspective

Australia's medical education system is undergoing a socially motivated transformation focused on improving access to medical care for rural and remote communities. A rural and remote backbone of Rural Clinical Schools (RCS), University Departments of Rural Health, regional medical schools, and the postgraduate college, ACRRM, have enabled community responsive innovation and partnerships with rural health services that once would have been difficult to imagine. This article argues that this transformation is succeeding because of the passionate leadership of rural medical and community leaders, government seed funding to encourage rural medicine as an academic discipline, rigorous research and consultation that underpinned each step of the innovation pathway, and a political campaign to invest in rural medical education as a form of rural social capital.
Student experiences of creating and sharing material in online learning

Background: User-generated content in an online environment has significant implications in both education and health. Instead of a model of knowledge being something transferred from the expert to the student or to the patient, Web 2.0 technologies offer the hope of making learning, and healthcare delivery, a more collaborative and participative process. However, some evidence suggests that this supposed democratisation of production is not entirely democratic and, in an educational context, many students are uncomfortable about sharing material they create with their peers. Aim: To understand students’ affective and other experiences of generating content to be shared online with peers (e.g. in online discussions). Methods: Online interviews, face-to-face focus groups and further methods with two student groups in medical education, one undergraduate and one postgraduate. Results: Students were broadly positive about creating and sharing material online, but were also quite anxious about doing so. Many practical issues, including around course design, student workload and assessment pressures, were barriers to students creating and sharing material. Group size is also important, with self-sustaining activity less likely in small groups. Conclusion: Successfully introducing user-generated content into medical education requires attention to practical details and an awareness of the student anxiety that can arise.
HSV-2 Immediate-Early Protein US1 Inhibits IFN-β Production by Suppressing Association of IRF-3 with IFN-β Promoter

HSV-2 is the major cause of genital herpes, and its infection increases the risk of HIV-1 acquisition and transmission. After initial infection, HSV-2 can establish latency within the nervous system and thus maintains lifelong infection in humans. It has been suggested that HSV-2 can inhibit type I IFN signaling, but the underlying mechanism has yet to be determined. In this study, we demonstrate that productive HSV-2 infection suppresses Sendai virus (SeV) or polyinosinic-polycytidylic acid-induced IFN-β production. We further reveal that US1, an immediate-early protein of HSV-2, contributes to such suppression, showing that US1 inhibits IFN-β promoter activity and IFN-β production at both mRNA and protein levels, whereas US1 knockout significantly impairs such capability in the context of HSV-2 infection. US1 directly interacts with DNA binding domain of IRF-3, and such interaction suppresses the association of nuclear IRF-3 with the IRF-3 responsive domain of IFN-β promoter, resulting in the suppression of IFN-β promoter activation. Additional studies demonstrate that the 217–414 aa domain of US1 is critical for the suppression of IFN-β production. Our results indicate that HSV-2 US1 downmodulates IFN-β production by suppressing the association of IRF-3 with the IRF-3 responsive domain of IFN-β promoter. Our findings highlight the significance of HSV-2 US1 in inhibiting IFN-β production and provide insights into the molecular mechanism by which HSV-2 evades the host innate immunity, representing an unconventional strategy exploited by a dsDNA virus to interrupt type I IFN signaling pathway.
Myocardial infarction, heart failure and sympathetic nervous system activity: new pharmacological approaches that affect neurohumoral activation

Background: Myocardial infarction (MI) is a leading cause of death among adults and MI survivors have increased risk of developing heart failure. MI is accompanied by acute sympathetic nervous system activation, which becomes persistent in heart failure patients. Objective: We establish whether current and investigated therapies affect sympathetic activation after MI and in heart failure patients. Methods: We reviewed the literature on the mechanisms of sympathetic nervous system activation and effects of standard and investigated treatments on adrenergic activation after MI and in heart failure patients. Results/conclusion: Angioplasty and β-blockers result in a decrease of adrenergic activation after acute MI; in heart failure patients, medications that affect renin–angiotensin–aldosterone system modulate sympathetic activation. Endothelin receptors agonists, adenosine receptors antagonists, arginin vasopressin antagonists, cardiac myosin activators, natriuretic peptide analogues, vasopeptide inhibitors, renin inhibitors, tyrosine kinase inhibitors and dopamine receptors inhibitors were tested in heart failure settings. They target better management of neurohumoral activation.
SAP-Regulated T Cell–APC Adhesion and Ligation-Dependent and -Independent Ly108–CD3ζ Interactions

The germinal center response requires cooperation between Ag-specific T and B lymphocytes, which takes the form of long-lasting cell–cell conjugation in vivo. Signaling lymphocytic activation molecule (SLAM)–associated protein (SAP) is required for stable cognate T–B cell conjugation, whereas SLAM family transmembrane (TM) receptor Ly108 may negatively regulate this process. We show that, other than phosphotyrosine-binding, SAP does not harbor motifs that recruit additional signaling intermediates to stabilize T–B adhesion. Ly108 dampens T cell adhesion to not only Ag-presenting B cells, but also dendritic cells by inhibiting CD3ζ phosphorylation through two levels of regulated Ly108–CD3ζ interactions. Constitutively associated with Src homology 2 domain–containing tyrosine phosphatase-1 even in SAP-competent cells, Ly108 is codistributed with the CD3 complex within a length scale of 100–200 nm on quiescent cells and can reduce CD3ζ phosphorylation in the absence of overt TCR stimulation or Ly108 ligation. When Ly108 is engaged in trans during cell–cell interactions, Ly108–CD3ζ interactions are promoted in a manner that uniquely depends on Ly108 TM domain, leading to more efficient CD3ζ dephosphorylation. Whereas replacement of the Ly108 TM domain still allows the constitutive, colocalization-dependent inhibition of CD3ζ phosphorylation, it abrogates the ligation-dependent Ly108–CD3ζ interactions and CD3ζ dephosphorylation, and it abolishes the suppression on Ag-triggered T–B adhesion. These results offer new insights into how SAP and Ly108 antagonistically modulate the strength of proximal TCR signaling and thereby control cognate T cell–APC interactions.
Phytochemical Analysis of Cynanchum callialatum through GCMS and LCMS

Medicinal plants are still important source for drug discovery. Herbal medicines have gained importance in recent years because of their efficacy and cost effectiveness. The objective of the present study is to investigate the phytochemical present in the Cynanchum callialatum. The phytochemical analysis was done by preliminary phytochemical test for secondary metabolites, GCMS for volatile constituents and LCMS for nonvolatile constituents. The phytochemical test confirms the presents of alkaloids, flavonoids, terpenoids, tanins etc. The GCMS analysis shows the presents of 52 compounds in which some have medicinal value. The LCMS analysis shows the presents of compounds in which most of them have the medicinal properties. The present study on Cynanchum callialatum reveals the presence of various phytochemical constituents like Betulinic acid, Lupeol, Germacrone and Longiverbenone. Cynanchum callialatum may be a potential source for anticancer, antiHIV, antiinflammatory, antimicrobial drug discovery.