Exploration of the integration of microbiology and immunology emerging topics into undergraduate medical education.

Purpose: Medical school educators face challenges determining which new and emerging topics to incorporate into medical school curricula, and how to do so. A study was conducted to gain a better understanding of the integration of emerging topics related to microbiology and immunology in the undergraduate medical curriculum (UME).

Methods: An anonymous survey with 17 questions was emailed to medical school faculty who teach immunology and/or microbiology through the DR-Ed listserv, the American Society for Microbiology (ASM) Connect listserv, and attendees of the Association of Medical School Microbiology and Immunology Chairs (AMSMIC) Educational Strategies Workshop.

A Virtual Patient Encounter to Promote Integration in a Preclinical Case-Based Learning Session.

In medical education, virtual patients increase the realism of learning in a safe environment. We added an integrated learning event using a virtual patient to integrate patient history taking into a preclinical basic science course. Herein, we describe the process and our overall satisfaction with the virtual patient encounter.

Use of the Team-Based Learning Readiness Assessment Test as a Low-Stakes Weekly Summative Assessment to Promote Spaced and Retrieval-Based Learning.

Spaced learning and retrieval-based learning are two powerful learning tools that have repeatedly been shown to be effective learning strategies. Team-Based Learning (TBL) is a collaborative learning and teaching approach that is evidence-based and promotes active learning. To combine these learning strategies, we designed a TBL-centered preclinical curriculum that uses the readiness assurance test (RAT) as a low-stakes weekly summative assessment to promote spaced learning and retrieval-based learning.

Effectiveness of instructor-guided independent learning in comparison to traditional didactic lecture in the preclinical medical curriculum: A retrospective cohort study.

To create time for learner-centered forms of active learning in the classroom, didactic lectures are being replaced with instructor-guided independent learning (IGIL) assignments that students complete on their own outside of the formal educational setting. The effectiveness of IGIL assignments in supporting learning across the preclinical medical curriculum when applied to all learners in the same class of students has not been examined. Further, we have examined this performance across three class cohorts.

HIV/AIDS: A Case-Based Learning Module for First-Year Medical Students.

In medical and healthcare-related education, case-based learning (CBL) is a teaching strategy that uses clinical cases to engage students in active learning using course concepts to solve important problems. Here we describe the design and implementation of a CBL module to teach first year medical students about the human immunodeficiency virus (HIV), acute retroviral syndrome, clinical progression to acquired immunodeficiency syndrome, HIV diagnostics, assays used to assess stage of disease and response to antiretroviral treatment, and highly active antiretroviral therapy. A team of basic science and clinical faculty in the disciplines of microbiology, immunology, infection prevention and control, clinical medicine, pharmacology, and medical ethics collaboratively designed the CBL module.

The phorbol 12-myristate-13-acetate differentiation protocol is critical to the interaction of THP-1 macrophages with Salmonella Typhimurium.

THP-1 cells differentiated with phorbol 12-myristate 13-acetate (PMA) are widely used as a model for function and biology of human macrophages. However, the conditions used for differentiation, particularly the concentration of PMA and the duration of treatment, vary widely. Here we compare several differentiation conditions and compare the ability of THP-1 macrophages to interact with the facultative intracellular pathogen Salmonella enterica serovar Typhimurium.

Salmonella Meningitis Associated with Monocyte Infiltration in Mice.

In the current study, we examined the ability of Salmonella enterica serovar Typhimurium to infect the central nervous system and cause meningitis following the natural route of infection in mice. C57BL/6J mice are extremely susceptible to systemic infection by Salmonella Typhimurium because of loss-of-function mutations in Nramp1 (SLC11A1), a phagosomal membrane protein that controls iron export from vacuoles and inhibits Salmonella growth in macrophages. Therefore, we assessed the ability of Salmonella to disseminate to the central nervous system (CNS) after oral infection in C57BL/6J mice expressing either wild-type (resistant) or mutant (susceptible) alleles of Nramp1.

Blood vascular abnormalities in Rasa1(R780Q) knockin mice: implications for the pathogenesis of capillary malformation-arteriovenous malformation.

Capillary malformation-arteriovenous malformation (CM-AVM) is an autosomal dominant blood vascular (BV) disorder characterized by CM and fast flow BV lesions. Inactivating mutations of the RASA1 gene are the cause of CM-AVM in most cases. RASA1 is a GTPase-activating protein that acts as a negative regulator of the Ras small GTP-binding protein.

Mitochondrial ROS potentiates indirect activation of the AIM2 inflammasome.

Activation of the inflammasome is important for the detection and clearance of cytosolic pathogens. In contrast to avirulent Francisella novicida (Fn), infection with virulent Francisella tularensis ssp tularensis does not trigger activation of the host AIM2 inflammasome. Here we show that differential activation of AIM2 following Francisella infection is due to sensitivity of each isolate to reactive oxygen species (ROS).

Virulent Francisella tularensis destabilize host mRNA to rapidly suppress inflammation.

Highly virulent bacterial pathogens have evolved rapid means to suppress host inflammatory responses by unknown mechanisms. Here, we use virulent Francisella tularensis, the cause of lethal tularemia in humans, as a model to elucidate these mechanisms. We show that following infection of murine macrophages F.

Nonreceptor tyrosine phosphatase Shp2 promotes adipogenesis through inhibition of p38 MAP kinase.

The molecular mechanism underlying adipogenesis and the physiological functions of adipose tissue are not fully understood. We describe here a unique mouse model of severe lipodystrophy. Ablation of Ptpn11/Shp2 in adipocytes, mediated by aP2-Cre, led to premature death, lack of white fat, low blood pressure, compensatory erythrocytosis, and hepatic steatosis in Shp2(fat-/-) mice.

IFN-β mediates suppression of IL-12p40 in human dendritic cells following infection with virulent Francisella tularensis.

Active suppression of inflammation is a strategy used by many viral and bacterial pathogens, including virulent strains of the bacterium Francisella tularensis, to enable colonization and infection in susceptible hosts. In this study, we demonstrated that virulent F. tularensis strain SchuS4 selectively inhibits production of IL-12p40 in primary human cells via induction of IFN-β.

Development of severe skeletal defects in induced SHP-2-deficient adult mice: a model of skeletal malformation in humans with SHP-2 mutations.

SHP-2 (encoded by PTPN11) is a ubiquitously expressed protein tyrosine phosphatase required for signal transduction by multiple different cell surface receptors. Humans with germline SHP-2 mutations develop Noonan syndrome or LEOPARD syndrome, which are characterized by cardiovascular, neurological and skeletal abnormalities. To study how SHP-2 regulates tissue homeostasis in normal adults, we used a conditional SHP-2 mouse mutant in which loss of expression of SHP-2 was induced in multiple tissues in response to drug administration.

The FERM and PDZ domain-containing protein tyrosine phosphatases, PTPN4 and PTPN3, are both dispensable for T cell receptor signal transduction.

PTPN3 and PTPN4 are two closely-related non-receptor protein tyrosine phosphatases (PTP) that, in addition to a PTP domain, contain FERM (Band 4.1, Ezrin, Radixin, and Moesin) and PDZ (PSD-95, Dlg, ZO-1) domains. Both PTP have been implicated as negative-regulators of early signal transduction through the T cell antigen receptor (TCR), acting to dephosphorylate the TCRzeta chain, a component of the TCR complex.

Generation of mice with a conditional allele of the p120 Ras GTPase-activating protein.

p120 Ras GTPase-activating protein (RasGAP) encoded by the rasa1 gene in mice is a prototypical member of the RasGAP family of proteins involved in negative-regulation of the p21 Ras proto-oncogene. RasGAP has been implicated in signal transduction through a number of cell surface receptors. In humans, inactivating mutations in the coding region of the RASA1 gene cause capillary malformation arteriovenous malformation.

Normal TCR signal transduction in mice that lack catalytically active PTPN3 protein tyrosine phosphatase.

PTPN3 (PTPH1) is a cytoskeletal protein tyrosine phosphatase that has been implicated as a negative regulator of early TCR signal transduction and T cell activation. To determine whether PTPN3 functions as a physiological negative regulator of TCR signaling in primary T cells, we generated gene-trapped and gene-targeted mouse strains that lack expression of catalytically active PTPN3. PTPN3 phosphatase-negative mice were born in expected Mendelian ratios and exhibited normal growth and development.