Development and implementation of an herbal and natural product elective in undergraduate medical education

<p>Abstract</p> <p>Background</p> <p>Medical students have consistently expressed interest in learning about alternative healing modalities, especially herbal and natural products. To fill this void in medical education at our institution, a novel elective was developed and implemented for fourth year medical students. This herbal/natural product course uses guest lecturers, classroom presentations, and active learning mechanisms that include experiential rotations, case-based learning, and team-based learning to increase student knowledge of herbal/natural product safety and efficacy.</p> <p>Methods</p> <p>Knowledge outcomes were evaluated via administration of a pre- and post-course test (paired student <it>t</it>-test). End-of-course evaluations (Likert-type questions and narrative responses) were used to assess student opinion of knowledge and skills imparted by the elective and overall course content (mean, standard deviation).</p> <p>Results</p> <p>Over three academic years, 23 students have enrolled in this elective. More than 60% of participants have been female and nearly half of the students (43%) have pursued residencies in primary care. Completion of the course significantly increased student knowledge of common herbal/natural product mechanisms, uses, adverse effects, and drug-interactions as determined by a pre- and post-course knowledge assessment (45% ± 10% versus 78% ± 6%; p < 0.0001). The course was highly rated by enrollees (overall course quality, 4.6 of 5.0 ± 0.48) who appreciated the variety of activities to which they were exposed and the open classroom discussions that resulted. While students tended to view some alternative medical systems with skepticism, they still believed it was valuable to learn what these modalities encompass.</p> <p>Conclusions</p> <p>Development and implementation of a herbal/natural product elective that engages undergraduate medical students through active learning mechanisms and critical analysis of the literature has proven effective in increasing knowledge outcomes and is deemed to be a valuable curricular addition by student participants. In the future, it will be of interest to explore mechanisms for expanding the course to reach a larger number of students within the time, financial, and logistical constraints that currently exist.</p

The Early Clinical Features of Dengue in Adults: Challenges for Early Clinical Diagnosis

Dengue infection in adults has become increasingly common throughout the world. As most of the clinical features of dengue have been described in children, we undertook a prospective study to determine the early symptoms and signs of dengue in adults. We show here that, overall, dengue cases presented with high rates of symptoms listed in the WHO 1997 or 2009 classification schemes for probable dengue fever thus resulting in high sensitivities of these schemes when applied for early diagnosis. However, symptoms such as myalgia, arthralgia, retro-orbital pain and mucosal bleeding were less frequently reported in older adults. This trend resulted in reduced sensitivity of the WHO classification schemes in older adults even though they showed increased risks of hospitalization and severe dengue. Instead, we suggest that older adults who present with fever and leukopenia should be tested for dengue, even in the absence of other symptoms. This could be useful for early clinical diagnosis in older adults so that they can be monitored and treated for severe dengue, which is especially important when an antiviral drug becomes available

Syndecan-1 Regulates Vasculat Smooth Muscle Cell Phenotype

Objective: We examined the role of syndecan-1 in modulating the phenotype of vascular smooth muscle cells in the context of endogenous inflammatory factors and altered microenvironments that occur in disease or injury-induced vascular remodeling. Methods and Results: Vascular smooth muscle cells (vSMCs) display a continuum of phenotypes that can be altered during vascular remodeling. While the syndecans have emerged as powerful and complex regulators of cell function, their role in controlling vSMC phenotype is unknown. Here, we isolated vSMCs from wild type (WT) and syndecan-1 knockout (S1KO) mice. Gene expression and western blotting studies indicated decreased levels of α-smooth muscle actin (α-SMA), calponin, and other vSMC-specific differentiation markers in S1KO relative to WT cells. The spread area of the S1KO cells was found to be greater than WT cells, with a corresponding increase in focal adhesion formation, Src phosphorylation, and alterations in actin cytoskeletal arrangement. In addition, S1KO led to increased S6RP phosphorylation and decreased AKT and PKC-α phosphorylation. To examine whether these changes were present in vivo, isolated aortae from aged WT and S1KO mice were stained for calponin. Consistent with our in-vitro findings, the WT mice aortae stained higher for calponin relative to S1KO. When exposed to the inflammatory cytokine TNF-α, WT vSMCs had an 80% reduction in syndecan-1 expression. Further, with TNF-α, S1KO vSMCs produced increased pro-inflammatory cytokines relative to WT. Finally, inhibition of interactions between syndecan-1 and integrins αvβ3 and αvβ5 using the inhibitory peptide synstatin appeared to have similar effects on vSMCs as knocking out syndecan-1, with decreased expression of vSMC differentiation markers and increased expression of inflammatory cytokines, receptors, and osteopontin. Conclusions: Taken together, our results support that syndecan-1 promotes vSMC differentiation and quiescence. Thus, the presence of syndecan-1 would have a protective effect against vSMC dedifferentiation and this activity is linked to interactions with integrins αvβ3 and αvβ5.This study was supported by the American Heart Association (10SDG2630139) and the National Institutes of Health (1DP2OD008716-01). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Biomedical EngineeringEmail: [email protected] (SC), Email: [email protected] (AB

Inhibition of the interactions of syndecan-1 with integrins αvβ3 and αvβ5 was inhibited with the synstatin and gene or protein expression was measured after 48 hours.

<p>(A–C) Decreased expression of vSMC-specific differentiation markers; (D–F) Increased expression of inflammatory cytokine, MCP-1, and, adhesion receptors, ICAM-1 and VCAM-1.</p

Western blotting analysis of intracellular signaling pathways in WT and S1KO vascular smooth muscle cells (vSMCs).

<p>For all western blots, cell lysates were obtained from vSMCs that were treated with 1% FBS, heparin or with heparin and TGF-β1 for 48 hours prior to cell lysis. (A) Western blotting for phospho-S6RP and total S6RP. (B) Immunoblotting analyses for phosphorylated PKC-α and total PKC-α. (C) Western blotting indicated reduced phospho-AKT in S1KO vSMCs versus WT vSMCs in heparin and heparin/TGF-β1 treated cells. In all quantification analyses, expression levels of the target protein for S1KO vSMCs were normalized to those for WT vSMCs treated with control culture medium. *Statistically significant difference with WT group under similar culture conditions (p<0.05).</p

Treatment of vascular smooth muscle cells (vSMCs) with TNF-α alters expression of syndecan-1 (sdc-1) and the absence of syndecan-1 in syndecan-1 knockout (S1KO) increases the expression of inflammatory cytokines by vSMCs.

<p>The cells were treated with 20/mL TNF-α for 48 hours. (A) Treatment of WT mouse cells with TNF-α reduces gene expression of sdc-1. (B) Baseline expression of IL-6 was lower in S1KO vSMCs but higher after stimulation with TNF-α. (C) Higher MCP-1 gene expression in S1KO vSMCs relative to WT vSMCs after stimulation with TNF-α. *Statistically significant difference with WT cell group under similar culture conditions. †Statistically significant difference with non-TNF-α treated WT cell group. ‡Statistically significant difference with non-TNF-α treated S1KO cell group.</p

Syndecan-1 knockout increases vSMC proliferation and induces a more spread adherent cell morphology.

<p>(A) Cell proliferation measured using an MTS assay demonstrated faster growth in syndecan-1 knockout (S1KO) vSMCs versus wild type (WT) vSMCs. (B) DNA synthesis in S1KO and WT cell lines, as indicated by the BrdU index. (C) Altered morphology of S1KO vSMCs when subjected to changes in the biochemical environment, specifically control (1% FBS), medium containing 30 µg/mL heparin, and medium containing 30 µg/mL heparin and 5 ng/mL TGF-β1. (D) Cell area after spreading was smaller for WT vSMCs in comparison to S1KO vSMCs. (E) Shape factor determinations indicated that S1KO vSMCs were more circular than WT vSMCs. (F) Elliptical form factor (EFF) determinations indicated that S1KO vSMCs were shorter and wider than their WT counterparts. Scale bar is 100 µm. *Statistically significant difference with WT group under similar culture conditions (p<0.05).</p

Measurement of protein levels of α-SMA and calponin in cultured vSMCs confirmed the upregulation of α-SMA and calponin in WT vSMCs.

<p>(A, C) Western blotting for α-SMA and calponin in WT and S1KO cells after 48 hours of the shown treatments. (B, D) Immunostaining for α-SMA and calponin demonstrated higher expression in WT vSMCs versus S1KO vSMCs. Scale bars are 100 microns in length. *Statistically significant difference with WT group under similar culture conditions (p<0.05).</p